Simon Cherry

J Nucl Med. 2024 Aug 1:jnumed.123.267003. doi: 10.2967/jnumed.123.267003. Online ahead of print.

ABSTRACT

Immunotherapies, especially checkpoint inhibitors such as anti-programmed cell death protein 1 (anti-PD-1) antibodies, have transformed cancer treatment by enhancing the immune system's capability to target and kill cancer cells. However, predicting immunotherapy response remains challenging. ¹⁸F-arabinosyl guanine ([¹⁸F]F-AraG) is a molecular imaging tracer targeting activated T cells, which may facilitate therapy response assessment by noninvasive quantification of immune cell activity within the tumor microenvironment and elsewhere in the body. The aim of this study was to obtain preliminary data on total-body pharmacokinetics of [¹⁸F]F-AraG as a potential quantitative biomarker for immune response evaluation. Methods: The study consisted of 90-min total-body dynamic scans of 4 healthy subjects and 1 non-small cell lung cancer patient who was scanned before and after anti-PD-1 immunotherapy. Compartmental modeling with Akaike information criterion model selection was used to analyze tracer kinetics in various organs. Additionally, 7 subregions of the primary lung tumor and 4 mediastinal lymph nodes were analyzed. Practical identifiability analysis was performed to assess the reliability of kinetic parameter estimation. Correlations of the SUV_mean, the tissue-to-blood SUV ratio (SUVR), and the Logan plot slope (K _Logan) with the total volume of distribution (V _T) were calculated to identify potential surrogates for kinetic modeling. Results: Strong correlations were observed between K _Logan and SUVR with V _T, suggesting that they can be used as promising surrogates for V _T, especially in organs with a low blood-volume fraction. Moreover, practical identifiability analysis suggested that dynamic [¹⁸F]F-AraG PET scans could potentially be shortened to 60 min, while maintaining quantification accuracy for all organs of interest. The study suggests that although [¹⁸F]F-AraG SUV images can provide insights on immune cell distribution, kinetic modeling or graphical analysis methods may be required for accurate quantification of immune response after therapy. Although SUV_mean showed variable changes in different subregions of the tumor after therapy, the SUVR, K _Logan, and V _T showed consistent increasing trends in all analyzed subregions of the tumor with high practical identifiability. Conclusion: Our findings highlight the promise of [¹⁸F]F-AraG dynamic imaging as a noninvasive biomarker for quantifying the immune response to immunotherapy in cancer patients. Promising total-body kinetic modeling results also suggest potentially wider applications of the tracer in investigating the role of T cells in the immunopathogenesis of diseases.

PMID:39089813 | DOI:10.2967/jnumed.123.267003

medRxiv [Preprint]. 2024 Jul 27:2024.07.26.24311027. doi: 10.1101/2024.07.26.24311027.

ABSTRACT

Blood-brain barrier (BBB) disruption is involved in the pathogenesis and progression of many neurological and systemic diseases. Non-invasive assessment of BBB permeability in humans has mainly been performed with dynamic contrast-enhanced magnetic resonance imaging, evaluating the BBB as a structural barrier. Here, we developed a novel non-invasive positron emission tomography (PET) method in humans to measure the BBB permeability of molecular radiotracers that cross the BBB through different transport mechanisms. Our method uses high-temporal resolution dynamic imaging and kinetic modeling to jointly estimate cerebral blood flow and tracer-specific BBB transport rate from a single dynamic PET scan and measure the molecular permeability-surface area (PS) product of the radiotracer. We show our method can resolve BBB PS across three PET radiotracers with greatly differing permeabilities, measure reductions in BBB PS of ¹⁸F-fluorodeoxyglucose (FDG) in healthy aging, and demonstrate a possible brain-body association between decreased FDG BBB PS in patients with metabolic dysfunction-associated steatotic liver inflammation. Our method opens new directions to efficiently study the molecular permeability of the human BBB in vivo using the large catalogue of available molecular PET tracers.

PMID:39108503 | PMC:PMC11302722 | DOI:10.1101/2024.07.26.24311027

ArXiv [Preprint]. 2024 Jul 26:arXiv:2406.09720v2.

ABSTRACT

Standard Patlak plot is widely used to describe FDG kinetics for dynamic PET imaging. Whole-body Patlak parametric imaging remains constrained due to the need for a full-time input function. Here, we demonstrate the Relative Patlak (RP) plot, which eliminates the need for the early-time input function, for total-body parametric imaging and its application to clinical 20-min scan acquired in list-mode. We demonstrated that the RP intercept b' is equivalent to a ratio of standardized uptake value relative to the blood, while the RP slope Ki' is equal to the standard Patlak Ki multiplied by a global scaling factor for each subject. One challenge in applying RP to a short scan duration (20 min) is the high noise in parametric images. We applied a deep kernel method for noise reduction. Using the standard Patlak plot as the reference, the RP method was evaluated for lesion quantification, lesion-to-background contrast, and myocardial visualization in total-body parametric imaging with uEXPLORER in 22 human subjects who underwent a 1-h dynamic 18F-FDG scan. The RP method was also applied to the dynamic data regenerated from a clinical standard 20-min scan either at 1-h or 2-h post-injection for two cancer patients. We demonstrated that it is feasible to obtain high-quality parametric images from 20-min dynamic scans using the RP plot with a self-supervised deep-kernel noise reduction strategy. The RP Ki' highly correlated with Ki in lesions and major organs, demonstrating its quantitative potential across subjects. Compared to conventional SUVs, the Ki' images significantly improved lesion contrast and enabled visualization of the myocardium for potential cardiac assessment. The application of RP parametric imaging to two clinical scans also showed similar benefits. Total-body PET with the RP plot is feasible to generate parametric images from the dynamic data of a 20-min clinical scan.

PMID:39108297 | PMC:PMC11302668

Phys Med Biol. 2024 Aug 21. doi: 10.1088/1361-6560/ad7222. Online ahead of print.

ABSTRACT

OBJECTIVE: Penalty parameters in penalized likelihood positron emission tomography (PET) reconstruction are typically determined empirically. The cross-validation log-likelihood (CVLL) method has been introduced to optimize these parameters by maximizing a CVLL function, which assesses the likelihood of reconstructed images using one subset of a list-mode dataset based on another subset. This study aims to validate the efficacy of the CVLL method in whole-body imaging for cancer patients using a conventional clinical PET scanner.

APPROACH: Fifteen lung cancer patients were injected with 243.7±23.8 MBq of [18F]FDG and underwent a 22-minute PET scan on a Biograph mCT PET/CT scanner, starting at 60±5 minutes post-injection. The PET list-mode data were partitioned by subsampling without replacement, with 20 minutes used for image reconstruction using an in-house ordered subset expectation maximization algorithm and the remaining 2 minutes for cross-validation. Two penalty parameters, penalty strength β and Fair penalty function parameter δ, were subjected to optimization. Whole-body images were reconstructed, and CVLL values were computed across various penalty parameter combinations. The optimal image corresponding to the maximum CVLL value was selected by a grid search for each patient.

MAIN RESULTS: The δ value required to maximize the CVLL value was notably small (≤ 10-6 in this study). The influences of voxel size and scan duration on image optimization were investigated. A correlation analysis revealed a significant inverse relationship between optimal β and scan count level, with a correlation coefficient of -0.68 (p-value = 3.5×10-5). The optimal images selected by the CVLL method were compared with those chosen by two radiologists based on their diagnostic preferences. Differences were observed in the selection of optimal images.

SIGNIFICANCE: This study demonstrates the feasibility of incorporating the CVLL method into routine imaging protocols, potentially allowing for a wide range of combinations of injected radioactivity amounts and scan durations in modern PET imaging.

PMID:39168154 | DOI:10.1088/1361-6560/ad7222

J Nucl Med. 2024 Aug 1;65(8):1320-1326. doi: 10.2967/jnumed.124.267767.

ABSTRACT

The collaboration of Yale, the University of California, Davis, and United Imaging Healthcare has successfully developed the NeuroEXPLORER, a dedicated human brain PET imager with high spatial resolution, high sensitivity, and a built-in 3-dimensional camera for markerless continuous motion tracking. It has high depth-of-interaction and time-of-flight resolutions, along with a 52.4-cm transverse field of view (FOV) and an extended axial FOV (49.5 cm) to enhance sensitivity. Here, we present the physical characterization, performance evaluation, and first human images of the NeuroEXPLORER. Methods: Measurements of spatial resolution, sensitivity, count rate performance, energy and timing resolution, and image quality were performed adhering to the National Electrical Manufacturers Association (NEMA) NU 2-2018 standard. The system's performance was demonstrated through imaging studies of the Hoffman 3-dimensional brain phantom and the mini-Derenzo phantom. Initial ¹⁸F-FDG images from a healthy volunteer are presented. Results: With filtered backprojection reconstruction, the radial and tangential spatial resolutions (full width at half maximum) averaged 1.64, 2.06, and 2.51 mm, with axial resolutions of 2.73, 2.89, and 2.93 mm for radial offsets of 1, 10, and 20 cm, respectively. The average time-of-flight resolution was 236 ps, and the energy resolution was 10.5%. NEMA sensitivities were 46.0 and 47.6 kcps/MBq at the center and 10-cm offset, respectively. A sensitivity of 11.8% was achieved at the FOV center. The peak noise-equivalent count rate was 1.31 Mcps at 58.0 kBq/mL, and the scatter fraction at 5.3 kBq/mL was 36.5%. The maximum count rate error at the peak noise-equivalent count rate was less than 5%. At 3 iterations, the NEMA image-quality contrast recovery coefficients varied from 74.5% (10-mm sphere) to 92.6% (37-mm sphere), and background variability ranged from 3.1% to 1.4% at a contrast of 4.0:1. An example human brain ¹⁸F-FDG image exhibited very high resolution, capturing intricate details in the cortex and subcortical structures. Conclusion: The NeuroEXPLORER offers high sensitivity and high spatial resolution. With its long axial length, it also enables high-quality spinal cord imaging and image-derived input functions from the carotid arteries. These performance enhancements will substantially broaden the range of human brain PET paradigms, protocols, and thereby clinical research applications.

PMID:38871391 | PMC:PMC11294061 | DOI:10.2967/jnumed.124.267767

Igaku Butsuri. 2024;44(2):29-35. doi: 10.11323/jjmp.44.2_29.

ABSTRACT

This is an explanatory paper on Sun Il Kwon et al., Nat. Photon. 15: 914-918, 2021 and some parts of this manuscript are translated from the paper. Medical imaging modalities such as X-ray computed tomography, Magnetic resonance imaging, positron emission tomography (PET), and single photon emission computed tomography, require image reconstruction processes, consequently constraining them to form cylindrical shapes. However, among them, only PET can use additional information, so called time of flight, on an event-by-event basis. If coincidence time resolution (CTR) of PET detectors improved to 30 ps, which corresponds to spatial resolution of 4.5 mm, directly localizing electron-positron annihilation point is possible, allowing us to circumvent image reconstruction processes and free us from the geometric constraint. We call this concept direct positron emission imaging (dPEI). We have developed ultrafast radiation detectors by focusing on Cherenkov photon detection. Furthermore, the CTR of 32 ps being equivalent to 4.8 mm spatial resolution is achieved by combining deep learning-based signal processing with the detectors. In this article, we explain how we developed the detectors and demonstrated the first dPEI using different types of phantoms, how we will tackle limitations to be addressed to make the dPEI more practical, and how dPEI will emerge as an imaging modality in nuclear medicine.

PMID:38945880 | DOI:10.11323/jjmp.44.2_29

Neuroimage. 2024 Jun;293:120611. doi: 10.1016/j.neuroimage.2024.120611. Epub 2024 Apr 21.

ABSTRACT

Dynamic PET allows quantification of physiological parameters through tracer kinetic modeling. For dynamic imaging of brain or head and neck cancer on conventional PET scanners with a short axial field of view, the image-derived input function (ID-IF) from intracranial blood vessels such as the carotid artery (CA) suffers from severe partial volume effects. Alternatively, optimization-derived input function (OD-IF) by the simultaneous estimation (SIME) method does not rely on an ID-IF but derives the input function directly from the data. However, the optimization problem is often highly ill-posed. We proposed a new method that combines the ideas of OD-IF and ID-IF together through a kernel framework. While evaluation of such a method is challenging in human subjects, we used the uEXPLORER total-body PET system that covers major blood pools to provide a reference for validation.

METHODS: The conventional SIME approach estimates an input function using a joint estimation together with kinetic parameters by fitting time activity curves from multiple regions of interests (ROIs). The input function is commonly parameterized with a highly nonlinear model which is difficult to estimate. The proposed kernel SIME method exploits the CA ID-IF as a priori information via a kernel representation to stabilize the SIME approach. The unknown parameters are linear and thus easier to estimate. The proposed method was evaluated using ¹⁸F-fluorodeoxyglucose studies with both computer simulations and 20 human-subject scans acquired on the uEXPLORER scanner. The effect of the number of ROIs on kernel SIME was also explored.

RESULTS: The estimated OD-IF by kernel SIME showed a good match with the reference input function and provided more accurate estimation of kinetic parameters for both simulation and human-subject data. The kernel SIME led to the highest correlation coefficient (R = 0.97) and the lowest mean absolute error (MAE = 10.5 %) compared to using the CA ID-IF (R = 0.86, MAE = 108.2 %) and conventional SIME (R = 0.57, MAE = 78.7 %) in the human-subject evaluation. Adding more ROIs improved the overall performance of the kernel SIME method.

CONCLUSION: The proposed kernel SIME method shows promise to provide an accurate estimation of the blood input function and kinetic parameters for brain PET parametric imaging.

PMID:38643890 | PMC:PMC11251003 | DOI:10.1016/j.neuroimage.2024.120611

EJNMMI Res. 2024 Apr 16;14(1):39. doi: 10.1186/s13550-024-01104-7.

ABSTRACT

BACKGROUND: Kinetic modeling of ¹⁸F-florbetaben provides important quantification of brain amyloid deposition in research and clinical settings but its use is limited by the requirement of arterial blood data for quantitative PET. The total-body EXPLORER PET scanner supports the dynamic acquisition of a full human body simultaneously and permits noninvasive image-derived input functions (IDIFs) as an alternative to arterial blood sampling. This study quantified brain amyloid burden with kinetic modeling, leveraging dynamic ¹⁸F-florbetaben PET in aorta IDIFs and the brain in an elderly cohort.

METHODS: ¹⁸F-florbetaben dynamic PET imaging was performed on the EXPLORER system with tracer injection (300 MBq) in 3 individuals with Alzheimer's disease (AD), 3 with mild cognitive impairment, and 9 healthy controls. Image-derived input functions were extracted from the descending aorta with manual regions of interest based on the first 30 s after injection. Dynamic time-activity curves (TACs) for 110 min were fitted to the two-tissue compartment model (2TCM) using population-based metabolite corrected IDIFs to calculate total and specific distribution volumes (V_T, V_s) in key brain regions with early amyloid accumulation. Non-displaceable binding potential ([Formula: see text] was also calculated from the multi-reference tissue model (MRTM).

RESULTS: Amyloid-positive (AD) patients showed the highest V_T and V_S in anterior cingulate, posterior cingulate, and precuneus, consistent with [Formula: see text] analysis. [Formula: see text]and V_T from kinetic models were correlated (r² = 0.46, P < 2[Formula: see text] with a stronger positive correlation observed in amyloid-positive participants, indicating reliable model fits with the IDIFs. V_T from 2TCM was highly correlated ([Formula: see text]= 0.65, P < 2[Formula: see text]) with Logan graphical V_T estimation.

CONCLUSION: Non-invasive quantification of amyloid binding from total-body ¹⁸F-florbetaben PET data is feasible using aorta IDIFs with high agreement between kinetic distribution volume parameters compared to [Formula: see text]in amyloid-positive and amyloid-negative older individuals.

PMID:38625413 | PMC:PMC11021392 | DOI:10.1186/s13550-024-01104-7

J Nucl Med. 2024 Jul 1;65(7):1101-1106. doi: 10.2967/jnumed.124.267521.

ABSTRACT

Our aim was to define a lower limit of reduced injected activity in delayed [¹⁸F]FDG total-body (TB) PET/CT in pediatric oncology patients. Methods: In this single-center prospective study, children were scanned for 20 min with TB PET/CT, 120 min after intravenous administration of a 4.07 ± 0.49 MBq/kg dose of [¹⁸F]FDG. Five randomly subsampled low-count reconstructions were generated using ¼, ⅛, [Formula: see text], and [Formula: see text] of the counts in the full-dose list-mode reference standard acquisition (20 min), to simulate dose reduction. For the 2 lowest-count reconstructions, smoothing was applied. Background uptake was measured with volumes of interest placed on the ascending aorta, right liver lobe, and third lumbar vertebra body (L3). Tumor lesions were segmented using a 40% isocontour volume-of-interest approach. Signal-to-noise ratio, tumor-to-background ratio, and contrast-to-noise ratio were calculated. Three physicians identified malignant lesions independently and assessed the image quality using a 5-point Likert scale. Results: In total, 113 malignant lesions were identified in 18 patients, who met the inclusion criteria. Of these lesions, 87.6% were quantifiable. Liver SUV_mean did not change significantly, whereas a lower signal-to-noise ratio was observed in all low-count reconstructions compared with the reference standard (P < 0.0001) because of higher noise rates. Tumor uptake (SUV_max), tumor-to-background ratio, and total lesion count were significantly lower in the reconstructions with [Formula: see text] and [Formula: see text] of the counts of the reference standard (P < 0.001). Contrast-to-noise ratio and clinical image quality were significantly lower in all low-count reconstructions than with the reference standard. Conclusion: Dose reduction for delayed [¹⁸F]FDG TB PET/CT imaging in children is possible without loss of image quality or lesion conspicuity. However, our results indicate that to maintain comparable tumor uptake and lesion conspicuity, PET centers should not reduce the injected [¹⁸F]FDG activity below 0.5 MBq/kg when using TB PET/CT in pediatric imaging at 120 min after injection.

PMID:38664017 | PMC:PMC11218730 | DOI:10.2967/jnumed.124.267521

J Nucl Med. 2024 May 1;65(5):714-721. doi: 10.2967/jnumed.123.267036.

ABSTRACT

The lungs are supplied by both the pulmonary arteries carrying deoxygenated blood originating from the right ventricle and the bronchial arteries carrying oxygenated blood downstream from the left ventricle. However, this effect of dual blood supply has never been investigated using PET, partially because the temporal resolution of conventional dynamic PET scans is limited. The advent of PET scanners with a long axial field of view, such as the uEXPLORER total-body PET/CT system, permits dynamic imaging with high temporal resolution (HTR). In this work, we modeled the dual-blood input function (DBIF) and studied its impact on the kinetic quantification of normal lung tissue and lung tumors using HTR dynamic PET imaging. Methods: Thirteen healthy subjects and 6 cancer subjects with lung tumors underwent a dynamic ¹⁸F-FDG scan with the uEXPLORER for 1 h. Data were reconstructed into dynamic frames of 1 s in the early phase. Regional time-activity curves of lung tissue and tumors were analyzed using a 2-tissue compartmental model with 3 different input functions: the right ventricle input function, left ventricle input function, and proposed DBIF, all with time delay and dispersion corrections. These models were compared for time-activity curve fitting quality using the corrected Akaike information criterion and for differentiating lung tumors from lung tissue using the Mann-Whitney U test. Voxelwise multiparametric images by the DBIF model were further generated to verify the regional kinetic analysis. Results: The effect of dual blood supply was pronounced in the high-temporal-resolution time-activity curves of lung tumors. The DBIF model achieved better time-activity curve fitting than the other 2 single-input models according to the corrected Akaike information criterion. The estimated fraction of left ventricle input was low in normal lung tissue of healthy subjects but much higher in lung tumors (∼0.04 vs. ∼0.3, P < 0.0003). The DBIF model also showed better robustness in the difference in ¹⁸F-FDG net influx rate [Formula: see text] and delivery rate [Formula: see text] between lung tumors and normal lung tissue. Multiparametric imaging with the DBIF model further confirmed the differences in tracer kinetics between normal lung tissue and lung tumors. Conclusion: The effect of dual blood supply in the lungs was demonstrated using HTR dynamic imaging and compartmental modeling with the proposed DBIF model. The effect was small in lung tissue but nonnegligible in lung tumors. HTR dynamic imaging with total-body PET can offer a sensitive tool for investigating lung diseases.

PMID:38548347 | PMC:PMC11064825 | DOI:10.2967/jnumed.123.267036

Proc SPIE Int Soc Opt Eng. 2024 Feb;12463:124631F. doi: 10.1117/12.2654431. Epub 2023 Apr 7.

ABSTRACT

Dual-energy computed tomography (DECT) enables material decomposition for tissues and produces additional information for PET/CT imaging to potentially improve the characterization of diseases. PET-enabled DECT (PDECT) allows the generation of PET and DECT images simultaneously with a conventional PET/CT scanner without the need for a second x-ray CT scan. In PDECT, high-energy γ-ray CT (GCT) images at 511 keV are obtained from time-of-flight (TOF) PET data and are combined with the existing x-ray CT images to form DECT imaging. We have developed a kernel-based maximum-likelihood attenuation and activity (MLAA) method that uses x-ray CT images as a priori information for noise suppression. However, our previous studies focused on GCT image reconstruction at the PET image resolution which is coarser than the image resolution of the x-ray CT. In this work, we explored the feasibility of generating super-resolution GCT images at the corresponding CT resolution. The study was conducted using both phantom and patient scans acquired with the uEXPLORER total-body PET/CT system. GCT images at the PET resolution with a pixel size of 4.0 mm × 4.0 mm and at the CT resolution with a pixel size of 1.2 mm × 1.2 mm were reconstructed using both the standard MLAA and kernel MLAA methods. The results indicated that the GCT images at the CT resolution had sharper edges and revealed more structural details compared to the images reconstructed at the PET resolution. Furthermore, images from the kernel MLAA method showed substantially improved image quality compared to those obtained with the standard MLAA method.

PMID:38500666 | PMC:PMC10947795 | DOI:10.1117/12.2654431

ArXiv [Preprint]. 2024 Apr 12:arXiv:2402.02091v2.

ABSTRACT

X-ray computed tomography (CT) in PET/CT is commonly operated with a single energy, resulting in a limitation of lacking tissue composition information. Dual-energy (DE) spectral CT enables material decomposition by using two different x-ray energies and may be combined with PET for improved multimodality imaging, but would either require hardware upgrade or increase radiation dose due to the added second x-ray CT scan. Recently proposed PET-enabled DECT method allows dual-energy spectral imaging using a conventional PET/CT scanner without the need for a second x-ray CT scan. A gamma-ray CT (gCT) image at 511 keV can be generated from the existing time-of-flight PET data with the maximum-likelihood attenuation and activity (MLAA) approach and is then combined with the low-energy x-ray CT image to form dual-energy spectral imaging. To improve the image quality of gCT, a kernel MLAA method was further proposed by incorporating x-ray CT as a priori information. The concept of this PET-enabled DECT has been validated using simulation studies, but not yet with 3D real data. In this work, we developed a general open-source implementation for gCT reconstruction from PET data and use this implementation for the first real data validation with both a physical phantom study and a human subject study on a uEXPLORER total-body PET/CT system. These results have demonstrated the feasibility of this method for spectral imaging and material decomposition.

PMID:38351944 | PMC:PMC10862937

Phys Med Biol. 2024 Feb 16;69(4). doi: 10.1088/1361-6560/ad2230.

ABSTRACT

Objective.This study presents and evaluates a robust Monte Carlo-based scatter correction (SC) method for long axial field of view (FOV) and total-body positron emission tomography (PET) using the uEXPLORER total-body PET/CT scanner.Approach.Our algorithm utilizes the Monte Carlo (MC) tool SimSET to compute SC factors in between individual image reconstruction iterations within our in-house list-mode and time-of-flight-based image reconstruction framework. We also introduced a unique scatter scaling technique at the detector block-level for optimal estimation of the scatter contribution in each line of response. First image evaluations were derived from phantom data spanning the entire axial FOV along with image data from a human subject with a large body mass index. Data was evaluated based on qualitative inspections, and contrast recovery, background variability, residual scatter removal from cold regions, biases and axial uniformity were quantified and compared to non-scatter-corrected images.Main results.All reconstructed images demonstrated qualitative and quantitative improvements compared to non-scatter-corrected images: contrast recovery coefficients improved by up to 17.2% and background variability was reduced by up to 34.3%, and the residual lung error was between 1.26% and 2.08%. Low biases throughout the axial FOV indicate high quantitative accuracy and axial uniformity of the corrections. Up to 99% of residual activity in cold areas in the human subject was removed, and the reliability of the method was demonstrated in challenging body regions like in the proximity of a highly attenuating knee prosthesis.Significance.The MC SC method employed was demonstrated to be accurate and robust in TB-PET. The results of this study can serve as a benchmark for optimizing the quantitative performance of future SC techniques.

PMID:38266297 | DOI:10.1088/1361-6560/ad2230

Res Sq [Preprint]. 2023 Dec 27:rs.3.rs-3764930. doi: 10.21203/rs.3.rs-3764930/v1.

ABSTRACT

PURPOSE: Kinetic modeling of ¹⁸F-florbetaben provides important quantification of brain amyloid deposition in research and clinical settings but its use is limited by the requirement of arterial blood data for quantitative PET. The total-body EXPLORER PET scanner supports the dynamic acquisition of a full human body simultaneously and permits noninvasive image-derived input functions (IDIFs) as an alternative to arterial blood sampling. This study quantified brain amyloid burden with kinetic modeling, leveraging dynamic ¹⁸F-florbetaben PET in aorta IDIFs and the brain in an elderly cohort.

METHODS: ¹⁸F-florbetaben dynamic PET imaging was performed on the EXPLORER system with tracer injection (300 MBq) in 3 individuals with Alzheimer's disease (AD), 3 with mild cognitive impairment, and 9 healthy controls. Image-derived input functions were extracted from the descending aorta with manual regions of interest based on the first 30 seconds after injection. Dynamic time-activity curves (TACs) for 110 minutes were fitted to the two-tissue compartment model (2TCM) using population-based metabolite corrected IDIFs to calculate total and specific distribution volumes (V_T, V_s) in key brain regions with early amyloid accumulation. Non-displaceable binding potential (BP_ND) was also calculated from the multi-reference tissue model (MRTM).

RESULTS: Amyloid-positive (AD) patients showed the highest V_T and V_S in anterior cingulate, posterior cingulate, and precuneus, consistent with BP_ND analysis. BP_ND and V_T from kinetic models were correlated (r² = 0.46, P<2e^-16) with a stronger positive correlation observed in amyloid-positive participants, indicating reliable model fits with the IDIFs. V_T from 2TCM was highly correlated (r² = 0.65, P< 2e^-16) with Logan graphical V_T estimation.

CONCLUSION: Non-invasive quantification of amyloid binding from total-body ¹⁸F-florbetaben PET data is feasible using aorta IDIFs with high agreement between kinetic distribution volume parameters compared to BP_ND in amyloid-positive and negative older individuals.

PMID:38234716 | PMC:PMC10793501 | DOI:10.21203/rs.3.rs-3764930/v1

Proc IEEE Inst Electr Electron Eng. 2020 Jan;108(1):51-68. doi: 10.1109/JPROC.2019.2936809. Epub 2019 Sep 19.

ABSTRACT

Machine learning has found unique applications in nuclear medicine from photon detection to quantitative image reconstruction. While there have been impressive strides in detector development for time-of-flight positron emission tomography, most detectors still make use of simple signal processing methods to extract the time and position information from the detector signals. Now with the availability of fast waveform digitizers, machine learning techniques have been applied to estimate the position and arrival time of high-energy photons. In quantitative image reconstruction, machine learning has been used to estimate various corrections factors, including scattered events and attenuation images, as well as to reduce statistical noise in reconstructed images. Here machine learning either provides a faster alternative to an existing time-consuming computation, such as in the case of scatter estimation, or creates a data-driven approach to map an implicitly defined function, such as in the case of estimating the attenuation map for PET/MR scans. In this article, we will review the abovementioned applications of machine learning in nuclear medicine.

PMID:38045770 | PMC:PMC10691821 | DOI:10.1109/JPROC.2019.2936809

Methods Mol Biol. 2024;2729:371-389. doi: 10.1007/978-1-0716-3499-8_21.

ABSTRACT

The world's first total-body PET/CT system has been in routine clinical and research use at UC Davis since 2019. The uEXPLORER total-body PET scanner has been designed with an axial field-of-view long enough to completely encompass most human subjects (194 cm or 76 inches long), allowing for a 15-68-fold gain in the PET signal collection efficiency over conventional PET scanners. A high-sensitivity PET scanner that can image the entire subject with a single bed position comes with new benefits and challenges to consider for efficient and practical use. In this chapter, we discuss the common clinical and research imaging protocols implemented at our institution, along with the appropriate technical and practical considerations of total-body PET imaging.

PMID:38006507 | DOI:10.1007/978-1-0716-3499-8_21

Phys Med Biol. 2023 Oct 26;68(21):10.1088/1361-6560/ad00fa. doi: 10.1088/1361-6560/ad00fa.

ABSTRACT

Objective.Contrast recovery coefficient (CRC) is essential for image quality (IQ) assessment in positron emission tomography (PET), typically measured according to the National Electrical Manufacturers Association (NEMA) NU 2 standard. This study quantifies systematic uncertainties of the CRC measurement by a numerical investigation of the effects from scanner-independent parameters like voxel size, region-of-interest (ROI) misplacement, and sphere position on the underlying image grid.Approach.CRC measurements with 2D and 3D ROIs were performed on computer-generated images of a NEMA IQ-like phantom, using voxel sizes of 1-4 mm for sphere diameters of 5-40 mm-first in absence of noise and blurring, then with simulated spatial resolution and image noise with varying noise levels. The systematic uncertainties of the CRC measurement were quantified from above variations of scanner-independent parameters. Subsampled experimental images of a NEMA IQ phantom were additionally used to investigate the impact of ROI misplacement at different noise levels.Main results.In absence of noise and blurring, systematic uncertainties were up to 28.8% and 31.0% with 2D and 3D ROIs, respectively, for the 10 mm sphere, with the highest impact from ROI misplacement. In all cases, smaller spheres showed higher uncertainties with larger voxels. Contrary to prior assumptions, the use of 3D ROIs did not exhibit less susceptibility for parameter changes. Experimental and computer-generated images both demonstrated considerable variations on individual CRC measurements when background coefficient-of-variation exceeded 20%, despite negligible effects on mean CRC.Significance.This study underscores the effect of scanner-independent parameters on reliability, reproducibility, and comparability of CRC measurements. Our findings highlight the trade-off between the benefits of smaller voxel sizes and noise-induced CRC fluctuations, which is not considered in the current version of the NEMA IQ standards. The results furthermore warrant adjustments to the standard to accommodate the advances in sensitivity and spatial resolution of current-generation PET scanners.

PMID:37802064 | PMC:PMC10798005 | DOI:10.1088/1361-6560/ad00fa

medRxiv [Preprint]. 2023 Nov 1:2023.09.22.23295860. doi: 10.1101/2023.09.22.23295860.

ABSTRACT

Immunotherapies, especially the checkpoint inhibitors such as anti-PD-1 antibodies, have transformed cancer treatment by enhancing immune system's capability to target and kill cancer cells. However, predicting immunotherapy response remains challenging. ¹⁸F-AraG is a molecular imaging tracer targeting activated T cells, which may facilitate therapy response assessment by non-invasive quantification of immune cell activity within tumor microenvironment and elsewhere in the body. The aim of this study was to obtain preliminary data on total-body pharmacokinetics of ¹⁸F-AraG, as a potential quantitative biomarker for immune response evaluation.

METHODS: The study consisted of 90-min total-body dynamic scans of four healthy subjects and one non-small cell lung cancer (NSCLC) patient, scanned before and after anti-PD-1 immunotherapy. Compartmental modeling with Akaike information criterion model selection were employed to analyze tracer kinetics in various organs. Additionally, seven sub-regions of the primary lung tumor and four mediastinal lymph nodes were analyzed. Practical identifiability analysis was performed to assess reliability of kinetic parameter estimation. Correlations of SUVmean, SUVR (tissue-to-blood ratio), and Logan plot slope KLogan with total volume-of-distribution VT were calculated to identify potential surrogates for kinetic modeling.

RESULTS: Strong correlations were observed between KLogan and SUVR values with VT, suggesting that they can be used as promising surrogates for VT, especially in organs with low blood-volume fraction. Moreover, the practical identifiability analysis suggests that the dynamic ¹⁸F-AraG PET scans could potentially be shortened to 60 minutes, while maintaining quantification accuracy for all organs-of-interest. The study suggests that although ¹⁸F-AraG SUV images can provide insights on immune cell distribution, kinetic modeling or graphical analysis methods may be required for accurate quantification of immune response post-therapy. While SUVmean showed variable changes in different sub-regions of the tumor post-therapy, the SUVR, KLogan, and VT showed consistent increasing trends in all analyzed sub-regions of the tumor with high practical identifiability.

CONCLUSION: Our findings highlight the promise of ¹⁸F-AraG dynamic imaging as a non-invasive biomarker for quantifying the immune response to immunotherapy in cancer patients. The promising total-body kinetic modeling results also suggest potentially wider applications of the tracer in investigating the role of T cells in the immunopathogenesis of diseases.

PMID:37790461 | PMC:PMC10543042 | DOI:10.1101/2023.09.22.23295860

Sci Adv. 2023 Oct 13;9(41):eadh7968. doi: 10.1126/sciadv.adh7968. Epub 2023 Oct 12.

ABSTRACT

With most of the T cells residing in the tissue, not the blood, developing noninvasive methods for in vivo quantification of their biodistribution and kinetics is important for studying their role in immune response and memory. This study presents the first use of dynamic positron emission tomography (PET) and kinetic modeling for in vivo measurement of CD8⁺ T cell biodistribution in humans. A ⁸⁹Zr-labeled CD8-targeted minibody (⁸⁹Zr-Df-Crefmirlimab) was used with total-body PET in healthy individuals (N = 3) and coronavirus disease 2019 (COVID-19) convalescent patients (N = 5). Kinetic modeling results aligned with T cell-trafficking effects expected in lymphoid organs. Tissue-to-blood ratios from the first 7 hours of imaging were higher in bone marrow of COVID-19 convalescent patients compared to controls, with an increasing trend between 2 and 6 months after infection, consistent with modeled net influx rates and peripheral blood flow cytometry analysis. These results provide a promising platform for using dynamic PET to study the total-body immune response and memory.

PMID:37824612 | PMC:PMC10569706 | DOI:10.1126/sciadv.adh7968

JACC Cardiovasc Imaging. 2023 Oct;16(10):1335-1347. doi: 10.1016/j.jcmg.2023.06.022. Epub 2023 Sep 6.

ABSTRACT

The recent advent of positron emission tomography (PET) scanners that can image the entire human body opens up intriguing possibilities for cardiovascular research and future clinical applications. These new systems permit radiotracer kinetics to be measured in all organs simultaneously. They are particularly well suited to study cardiovascular disease and its effects on the entire body. They could also play a role in quantitatively measuring physiologic, metabolic, and immunologic responses in healthy individuals to a variety of stressors and lifestyle interventions, and may ultimately be instrumental for evaluating novel therapeutic agents and their molecular effects across different tissues. In this review, we summarize recent progress in PET technology and methodology, discuss several emerging cardiovascular applications for total-body PET, and place this in the context of multiorgan and systems medicine. Finally, we discuss opportunities that will be enabled by the technology, while also pointing to some of the challenges that still need to be addressed.

PMID:37676207 | DOI:10.1016/j.jcmg.2023.06.022

J Nucl Med. 2023 Nov;64(11):1821-1830. doi: 10.2967/jnumed.123.265723. Epub 2023 Aug 17.

ABSTRACT

Conventional whole-body static ¹⁸F-FDG PET imaging provides a semiquantitative evaluation of overall glucose metabolism without insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric ¹⁸F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19). Methods: The study included 13 healthy subjects and 12 recovering COVID-19 subjects within 8 wk of confirmed diagnosis. Each subject had a 1-h dynamic ¹⁸F-FDG scan on the uEXPLORER total-body PET/CT system. Semiquantitative SUV and the SUV ratio relative to blood (SUVR) were calculated for different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify the microparametric blood-to-tissue ¹⁸F-FDG delivery rate [Formula: see text] and the phosphorylation rate k ₃, as well as the macroparametric ¹⁸F-FDG net influx rate ([Formula: see text]). Statistical tests were performed to examine differences between healthy subjects and recovering COVID-19 subjects. The effect of COVID-19 vaccination was also investigated. Results: We detected no significant difference in lung SUV but significantly higher lung SUVR and [Formula: see text] in COVID-19 recovery, indicating improved sensitivity of kinetic quantification for detecting the difference in glucose metabolism. A significant difference was also observed in the lungs with the phosphorylation rate k ₃ but not with [Formula: see text], which suggests that glucose phosphorylation, rather than glucose delivery, drives the observed difference of glucose metabolism. Meanwhile, there was no or little difference in bone marrow ¹⁸F-FDG metabolism measured with SUV, SUVR, and [Formula: see text] but a significantly higher bone marrow [Formula: see text] in the COVID-19 group, suggesting a difference in glucose delivery. Vaccinated COVID-19 subjects had a lower lung [Formula: see text] and a higher spleen [Formula: see text] than unvaccinated COVID-19 subjects. Conclusion: Higher lung glucose metabolism and bone marrow glucose delivery were observed with total-body multiparametric ¹⁸F-FDG PET in recovering COVID-19 subjects than in healthy subjects, implying continued inflammation during recovery. Vaccination demonstrated potential protection effects. Total-body multiparametric PET of ¹⁸F-FDG can provide a more sensitive tool and more insights than conventional whole-body static ¹⁸F-FDG imaging to evaluate metabolic changes in systemic diseases such as COVID-19.

PMID:37591539 | PMC:PMC10626370 | DOI:10.2967/jnumed.123.265723

Phys Med Biol. 2023 Sep 8;68(18):10.1088/1361-6560/acf027. doi: 10.1088/1361-6560/acf027.

ABSTRACT

Time-of-flight (TOF) positron emission tomography (PET) detectors improve the signal-to-noise ratio of PET images by limiting the position of the generation of two 511 keV gamma-rays in space using the arrival time difference between the two photons. Unfortunately, bismuth germanate (BGO), widely used in conventional PET detectors, was limited as a TOF PET scintillator due to the relatively slow decay time of the scintillation photons. However, prompt Cerenkov light in BGO has been identified in addition to scintillation photons. Using Cerenkov photons for timing has significantly improved the coincidence timing resolution (CTR) of BGO. Based on this, further research on improving the CTR for a BGO-based TOF PET system is being actively conducted. Wrapping materials for BGO pixels have primarily employed white reflectors to most efficiently collect scintillation light. White reflectors have customarily been used as reflectors for BGO pixels even after Cerenkov light began to be utilized for timing calculations in pixel-level experiments. However, when the arrival-time differences of the two 511 keV annihilations photons were measured with pure Cerenkov radiators, painting the lateral sides of the radiators black can improve CTR by suppressing the reflection of Cerenkov photons. The use of BGO for TOF PET detectors requires simultaneously minimizing scintillation loss for good energy information and suppressing reflected Cerenkov photons for better timing performance. Thus, reflectors for BGO pixels should be optimized for better timing and energy performance. In this study, colored polytetrafluoroethylene (PTFE) tapes with discontinuous reflectance values at specific wavelengths were applied as a BGO reflector. We hypothesized that CTR could be enhanced by selectively suppressing reflected Cerenkov photons with an optimum colored reflector on the BGO pixel while minimizing scintillation photon loss. CTRs were investigated utilizing white and three colors (yellow, red, and green) PTFE tapes as a reflector. In addition, black-painted PTFE tape and enhanced specular reflector film were investigated as reference reflector materials. When 3 × 3 × 20 mm³BGO pixels were wrapped with the yellow PTFE reflector, the CTR was significantly improved to 365 ± 5 ps from 403 ± 14 ps measured with the conventional white PTFE reflector. Adequate energy information was still obtained with only 4.1% degradation in light collection compared to the white reflector. Colored reflectors show the possibility to further improve CTR for BGO pixels with optimum reflectance design.

PMID:37579768 | PMC:PMC10722960 | DOI:10.1088/1361-6560/acf027

J Nucl Med. 2023 Nov;64(11):1831-1838. doi: 10.2967/jnumed.123.265659. Epub 2023 Aug 31.

ABSTRACT

Tissue perfusion can be affected by physiology or disease. With the advent of total-body PET, quantitative measurement of perfusion across the entire body is possible. [¹¹C]-butanol is a perfusion tracer with a superior extraction fraction compared with [¹⁵O]-water and [¹³N]-ammonia. To develop the methodology for total-body perfusion imaging, a pilot study using [¹¹C]-butanol on the uEXPLORER total-body PET/CT scanner was conducted. Methods: Eight participants (6 healthy volunteers and 2 patients with peripheral vascular disease [PVD]) were injected with a bolus of [¹¹C]-butanol and underwent 30-min dynamic acquisitions. Three healthy volunteers underwent repeat studies at rest (baseline) to assess test-retest reproducibility; 1 volunteer underwent paired rest and cold pressor test (CPT) studies. Changes in perfusion were measured in the paired rest-CPT study. For PVD patients, local changes in perfusion were investigated and correlated with patient medical history. Regional and parametric kinetic analysis methods were developed using a 1-tissue compartment model and leading-edge delay correction. Results: Estimated baseline perfusion values ranged from 0.02 to 1.95 mL·min^-1·cm^-3 across organs. Test-retest analysis showed that repeat baseline perfusion measurements were highly correlated (slope, 0.99; Pearson r = 0.96, P < 0.001). For the CPT subject, the largest regional increases were in skeletal muscle (psoas, 142%) and the myocardium (64%). One of the PVD patients showed increased collateral vessel growth in the calf because of a peripheral stenosis. Comorbidities including myocardial infarction, hypothyroidism, and renal failure were correlated with variations in organ-specific perfusion. Conclusion: This pilot study demonstrates the ability to obtain reproducible measurements of total-body perfusion using [¹¹C]-butanol. The methods are sensitive to local perturbations in flow because of physiologic stressors and disease.

PMID:37652544 | PMC:PMC10626376 | DOI:10.2967/jnumed.123.265659

Phys Med Biol. 2023 Aug 9;68(16):165016. doi: 10.1088/1361-6560/ace8ee.

ABSTRACT

Objective.Recent SiPM developments and improved front-end electronics have opened new doors in TOF-PET with a focus on prompt photon detection. For instance, the relatively high Cherenkov yield of bismuth-germanate (BGO) upon 511 keV gamma interaction has triggered a lot of interest, especially for its use in total body positron emission tomography (PET) scanners due to the crystal's relatively low material and production costs. However, the electronic readout and timing optimization of the SiPMs still poses many questions. Lab experiments have shown the prospect of Cherenkov detection, with coincidence time resolutions (CTRs) of 200 ps FWHM achieved with small pixels, but lack system integration due to an unacceptable high power uptake of the used amplifiers.Approach.Following recent studies the most practical circuits with lower power uptake (<30 mW) have been implemented and the CTR performance with BGO of newly developed SiPMs from Fondazione Bruno Kessler tested. These novel SiPMs are optimized for highest single photon time resolution (SPTR).Main results.We achieved a best CTR FWHM of 123 ps for 2 × 2 × 3 mm³and 243 ps for 3 × 3 × 20 mm³BGO crystals. We further show that with these devices a CTR of 106 ps is possible using commercially available 3 × 3 × 20 mm³LYSO:Ce,Mg crystals. To give an insight in the timing properties of these SiPMs, we measured the SPTR with black coated PbF₂of 2 × 2 × 3 mm³size. We confirmed an SPTR of 68 ps FWHM published in literature for standard devices and show that the optimized SiPMs can improve this value to 42 ps. Pushing the SiPM bias and using 1 × 1 mm²area devices we measured an SPTR of 28 ps FWHM.Significance.We have shown that advancements in readout electronics and SiPMs can lead to improved CTR with Cherenkov emitting crystals. Enabling time-of-flight with BGO will trigger a high interest for its use in low-cost and total-body PET scanners. Furthermore, owing to the prompt nature of Cherenkov emission, future CTR improvements are conceivable, for which a low-power electronic implementation is indispensable. In an extended discussion we will give a roadmap to best timing with prompt photons.

PMID:37467766 | PMC:PMC10410404 | DOI:10.1088/1361-6560/ace8ee

J Nucl Med. 2023 Jul;64(7):1145-1153. doi: 10.2967/jnumed.122.265362. Epub 2023 Jun 8.

ABSTRACT

We introduce the Fast Algorithm for Motion Correction (FALCON) software, which allows correction of both rigid and nonlinear motion artifacts in dynamic whole-body (WB) images, irrespective of the PET/CT system or the tracer. Methods: Motion was corrected using affine alignment followed by a diffeomorphic approach to account for nonrigid deformations. In both steps, images were registered using multiscale image alignment. Moreover, the frames suited to successful motion correction were automatically estimated by calculating the initial normalized cross-correlation metric between the reference frame and the other moving frames. To evaluate motion correction performance, WB dynamic image sequences from 3 different PET/CT systems (Biograph mCT, Biograph Vision 600, and uEXPLORER) using 6 different tracers (¹⁸F-FDG, ¹⁸F-fluciclovine, ⁶⁸Ga-PSMA, ⁶⁸Ga-DOTATATE, ¹¹C-Pittsburgh compound B, and ⁸²Rb) were considered. Motion correction accuracy was assessed using 4 different measures: change in volume mismatch between individual WB image volumes to assess gross body motion, change in displacement of a large organ (liver dome) within the torso due to respiration, change in intensity in small tumor nodules due to motion blur, and constancy of activity concentration levels. Results: Motion correction decreased gross body motion artifacts and reduced volume mismatch across dynamic frames by about 50%. Moreover, large-organ motion correction was assessed on the basis of correction of liver dome motion, which was removed entirely in about 70% of all cases. Motion correction also improved tumor intensity, resulting in an average increase in tumor SUVs by 15%. Large deformations seen in gated cardiac ⁸²Rb images were managed without leading to anomalous distortions or substantial intensity changes in the resulting images. Finally, the constancy of activity concentration levels was reasonably preserved (<2% change) in large organs before and after motion correction. Conclusion: FALCON allows fast and accurate correction of rigid and nonrigid WB motion artifacts while being insensitive to scanner hardware or tracer distribution, making it applicable to a wide range of PET imaging scenarios.

PMID:37290795 | DOI:10.2967/jnumed.122.265362

medRxiv [Preprint]. 2023 Mar 30:2023.03.26.23287673. doi: 10.1101/2023.03.26.23287673.

ABSTRACT

Conventional whole-body ¹⁸ F-FDG PET imaging provides a semi-quantitative evaluation of overall glucose metabolism without gaining insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric ¹⁸ F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19).

METHODS: The study included thirteen healthy subjects and twelve recovering COVID-19 subjects within eight weeks of confirmed diagnosis. Each subject had a dynamic ¹⁸ F-FDG scan on the uEXPLORER total-body PET/CT system for one hour. Semiquantitative standardized uptake value (SUV) and SUV ratio relative to blood (SUVR) were calculated for regions of interest (ROIs) in different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify microparametric rate constants K ₁ and k ₃ that characterize ¹⁸ F-FDG blood-to-tissue delivery and intracellular phosphorylation, respectively, and a macroparameter K _i that represents ¹⁸ F-FDG net influx rate. Statistical tests were performed to examine differences between the healthy controls and recovering COVID-19 subjects. Impact of COVID-19 vaccination was investigated. We further generated parametric images to confirm the ROI-based analysis.

RESULTS: We detected no significant difference in lung SUV but significantly higher lung SUVR and K _i in the recovering COVID-19 subjects, indicating an improved sensitivity of kinetic quantification for detecting the difference in glucose metabolism. A significant difference was also observed in the lungs with the phosphorylation rate k ₃ , but not with the delivery rate K ₁ , which suggests it is glucose phosphorylation, not glucose delivery, that drives the observed difference of glucose metabolism in the lungs. Meanwhile, there was no or little difference in bone marrow metabolism measured with SUV, SUVR and K _i , but a significant increase in bone-marrow ¹⁸ F-FDG delivery rate K ₁ in the COVID-19 group ( p < 0.05), revealing a difference of glucose delivery in this immune-related organ. The observed differences were lower or similar in vaccinated COVID-19 subjects as compared to unvaccinated ones. The organ ROI-based findings were further supported by parametric images.

CONCLUSIONS: Higher lung glucose metabolism and bone-marrow glucose delivery were observed with total-body multiparametric ¹⁸ F-FDG PET in recovering COVID-19 subjects as compared to healthy subjects, which suggests continued inflammation due to COVID-19 during the early stages of recovery. Total-body multiparametric PET of ¹⁸ F-FDG delivery and metabolism can provide a more sensitive tool and more insights than conventional static whole-body ¹⁸ F-FDG imaging to evaluate metabolic changes in systemic diseases such as COVID-19.

PMID:37034643 | PMC:PMC10081414 | DOI:10.1101/2023.03.26.23287673

J Nucl Med. 2023 Jul;64(7):1154-1161. doi: 10.2967/jnumed.122.264810. Epub 2023 Apr 28.

ABSTRACT

Tracer kinetic modeling in dynamic PET has the potential to improve the diagnosis, prognosis, and research of lung diseases. The advent of total-body PET systems with much greater detection sensitivity enables high-temporal-resolution (HTR) dynamic PET imaging of the lungs. However, existing models may become insufficient for modeling the HTR data. In this paper, we investigate the necessity of additional corrections to the input function for HTR lung kinetic modeling. Methods: Dynamic scans with HTR frames of as short as 1 s were performed on 13 healthy subjects with a bolus injection of about [Formula: see text] of ¹⁸F-FDG using the uEXPLORER total-body PET/CT system. Three kinetic models with and without time-delay and dispersion corrections were compared for the quality of lung time-activity curve fitting using the Akaike information criterion. The impact on quantification of ¹⁸F-FDG delivery rate [Formula: see text], net influx rate [Formula: see text] and fractional blood volume [Formula: see text] was assessed. Parameter identifiability analysis was also performed to evaluate the reliability of kinetic quantification with respect to noise. Correlation of kinetic parameters with age was investigated. Results: HTR dynamic imaging clearly revealed the rapid change in tracer concentration in the lungs and blood supply (i.e., the right ventricle). The uncorrected input function led to poor time-activity curve fitting and biased quantification in HTR kinetic modeling. The fitting was improved by time-delay and dispersion corrections. The proposed model resulted in an approximately 85% decrease in [Formula: see text], an approximately 75% increase in [Formula: see text], and a more reasonable [Formula: see text] (∼0.14) than the uncorrected model (∼0.04). The identifiability analysis showed that the proposed models had good quantification stability for [Formula: see text], [Formula: see text], and [Formula: see text] The [Formula: see text] estimated by the proposed model with simultaneous time-delay and dispersion corrections correlated inversely with age, as would be expected. Conclusion: Corrections to the input function are important for accurate lung kinetic analysis of HTR dynamic PET data. The modeling of both delay and dispersion can improve model fitting and significantly impact quantification of [Formula: see text], [Formula: see text], and [Formula: see text].

PMID:37116916 | PMC:PMC10315691 | DOI:10.2967/jnumed.122.264810

medRxiv [Preprint]. 2023 Mar 20:2023.03.14.23287121. doi: 10.1101/2023.03.14.23287121.

ABSTRACT

With the majority of CD8⁺ T cells residing and functioning in tissue, not blood, developing noninvasive methods for in vivo quantification of their biodistribution and kinetics in humans offers the means for studying their key role in adaptive immune response and memory. This study is the first report on using positron emission tomography (PET) dynamic imaging and compartmental kinetic modeling for in vivo measurement of whole-body biodistribution of CD8⁺ T cells in human subjects. For this, a ⁸⁹Zr-labeled minibody with high affinity for human CD8 (⁸⁹Zr-Df-Crefmirlimab) was used with total-body PET in healthy subjects (N=3) and in COVID-19 convalescent patients (N=5). The high detection sensitivity, total-body coverage, and the use of dynamic scans enabled the study of kinetics simultaneously in spleen, bone marrow, liver, lungs, thymus, lymph nodes, and tonsils, at reduced radiation doses compared to prior studies. Analysis and modeling of the kinetics was consistent with T cell trafficking effects expected from immunobiology of lymphoid organs, suggesting early uptake in spleen and bone marrow followed by redistribution and delayed increasing uptake in lymph nodes, tonsils, and thymus. Tissue-to-blood ratios from the first 7 h of CD8-targeted imaging showed significantly higher values in the bone marrow of COVID-19 patients compared to controls, with an increasing trend between 2 and 6 months post-infection, consistent with net influx rates obtained by kinetic modeling and flow cytometry analysis of peripheral blood samples. These results provide the platform for using dynamic PET scans and kinetic modelling to study total-body immunological response and memory.

PMID:36993568 | PMC:PMC10055575 | DOI:10.1101/2023.03.14.23287121

Nucl Med Mol Imaging. 2023 Feb;57(1):16-25. doi: 10.1007/s13139-022-00780-4. Epub 2022 Oct 11.

ABSTRACT

PURPOSE: We evaluated the kinetics of the hypoxia PET radiotracers, [18F]fluoromisonidazole ([18F]FMISO) and [18F]fluoroazomycin-arabinoside ([18F]FAZA), for tumor hypoxia detection and to assess the correlation of hypoxic kinetic parameters with static imaging measures in canine spontaneous tumors.

METHODS: Sixteen dogs with spontaneous tumors underwent a 150-min dynamic PET scan using either [18F]FMISO or [18F]FAZA. The maximum tumor-to-muscle ratio (TMR_max) > 1.4 on the last image frame was used as the standard threshold to determine tumor hypoxia. The tumor time-activity curves were analyzed using irreversible and reversible two-tissue compartment models and graphical methods. TMR_max was compared with radiotracer trapping rate (k ₃), influx rate (K _i), and distribution volume (V _T).

RESULTS: Tumor hypoxia was detected in 7/8 tumors in the [18F]FMISO group and 4/8 tumors in the [18F]FAZA group. All hypoxic tumors were detected at > 120 min with [18F]FMISO and at > 60 min with [18F]FAZA. [18F]FAZA showed better fit with the reversible model. TMR_max was strongly correlated with the irreversible parameters (k ₃ and K _i) for [18F]FMISO at > 90 min and with the reversible parameter (V _T) for [18F]FAZA at > 120 min.

CONCLUSIONS: Our results showed that [18F]FAZA provided a promising alternative radiotracer to [18F]FMISO with detecting the presence of tumor hypoxia at an earlier time (60 min), consistent with its favorable faster kinetics. The strong correlation between TMR_max over the 90-150 min and 120-150 min timeframes with [18F]FMISO and [18F]FAZA, respectively, with kinetic parameters associated with tumor hypoxia for each radiotracer, suggests that a static scan measurement (TMR_max) is a good alternative to quantify tumor hypoxia.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13139-022-00780-4.

PMID:36643946 | PMC:PMC9832187 | DOI:10.1007/s13139-022-00780-4

BMC Med Imaging. 2023 Jan 10;23(1):9. doi: 10.1186/s12880-022-00957-5.

ABSTRACT

BACKGROUND: Total-body positron emission tomography/computed tomography (PET/CT) scanners are characterized by higher signal collection efficiency and greater spatial resolution compared to conventional scanners, allowing for delayed imaging and improved image quality. These advantages may also lead to better detection of physiological processes that diagnostic imaging professionals should be aware of. The gallbladder (GB) is not usually visualized as an ¹⁸F-2-fluorodeoxyglucose (¹⁸F-FDG)-avid structure in routine clinical PET/CT studies; however, with the total-body PET/CT, we have been increasingly visualizing GB activity without it being involved in an inflammatory or neoplastic process. The aim of this study was to report visualization rates and characteristics of GB ¹⁸F-FDG uptake observed in both healthy and oncological subjects scanned on a total-body PET/CT system.

MATERIALS AND METHODS: Scans from 73 participants (48 healthy and 25 with newly diagnosed lymphoma) who underwent ¹⁸F-FDG total-body PET/CT were retrospectively reviewed. Subjects were scanned at multiple timepoints up to 3 h post-injection. Gallbladder ¹⁸F-FDG activity was graded using liver uptake as a reference, and the pattern was qualified as present in the wall, lumen, or both. Participants' characteristics, such as age, sex, body-mass index, blood glucose, and other clinical parameters, were collected to assess for any significant correlation with GB ¹⁸F-FDG uptake.

RESULTS: All 73 subjects showed GB uptake at one or more imaging timepoints. An increase in uptake intensity overtime was observed up until the 180-min scan, and the visualization rate of GB ¹⁸F-FDG uptake was 100% in the 120- and 180-min post-injection scans. GB wall uptake was detected in a significant number of patients (44/73, 60%), especially at early timepoint scans, whereas luminal activity was detected in 71/73 (97%) subjects, especially at later timepoint scans. No significant correlation was found between GB uptake intensity/pattern and subjects' characteristics.

CONCLUSION: The consistent observation of GB ¹⁸F-FDG uptake recorded in this study in healthy participants and subjects with a new oncological diagnosis indicates that this is a normal physiologic finding rather than representing an exception.

PMID:36627570 | PMC:PMC9832624 | DOI:10.1186/s12880-022-00957-5

J Nucl Med. 2023 Mar;64(3):416-422. doi: 10.2967/jnumed.122.264550. Epub 2022 Sep 29.

ABSTRACT

Ultrasensitive, high-resolution, extended-field-of-view total-body (TB) PET using the first-of-its-kind 194-cm axial-field-of-view uEXPLORER may facilitate the interrogation of biologic hallmarks of hitherto difficult-to-evaluate low-signal vessel wall pathology in cardiovascular disease. Methods: Healthy volunteers were imaged serially for up to 12 h after a standard dose of ¹⁸F-FDG (n = 15) or for up to 3 h after injection of a very low dose (about 5% of a standard dose; n = 15). A cohort undergoing standard ¹⁸F-FDG PET (n = 15) on a conventional scanner with a 22-cm axial field of view served as a comparison group. Arterial wall signal, crosstalk with hematopoietic and lymphoid organs, and image quality were analyzed using standardized techniques. Results: TB PET depicted the large vessel walls with excellent quality. The arterial wall could be imaged with high contrast up to 12 h after tracer injection. Ultralow-dose TB ¹⁸F-FDG images yielded a vessel wall signal and target-to-background ratio comparable to those of conventional-dose, short-axial-field-of-view PET. Crosstalk between vessel wall and lymphoid organs was identified with better accuracy in both TB PET cohorts than in conventional PET. Conclusion: TB PET enables detailed assessment of in vivo vessel wall biology and its crosstalk with other organs over an extended time window after tracer injection or at an ultralow tracer dose. These initial observations support the feasibility of serial imaging in low-risk populations and will stimulate future mechanistic studies or therapy monitoring in atherosclerosis and other vessel wall pathologies.

PMID:36175139 | PMC:PMC10071799 | DOI:10.2967/jnumed.122.264550

Front Nucl Med. 2022;2:963067. doi: 10.3389/fnume.2022.963067. Epub 2022 Aug 10.

ABSTRACT

The current generation of total-body positron emission tomography (PET) scanners offer significant sensitivity increase with an extended axial imaging extent. With the large volume of lutetium-based scintillation crystals that are used as detector elements in these scanners, there is an increased flux of background radiation originating from ¹⁷⁶Lu decay in the crystals and higher sensitivity for detecting it. Combined with the ability of scanning the entire body in a single bed position, this allows more effective utilization of the lutetium background as a transmission source for estimating 511 keV attenuation coefficients. In this study, utilization of the lutetium background radiation for attenuation correction in total-body PET was studied using Monte Carlo simulations of a 3D whole-body XCAT phantom in the uEXPLORER PET scanner, with particular focus on ultralow-dose PET scans that are now made possible with these scanners. Effects of an increased acceptance angle, reduced scan durations, and Compton scattering on PET quantification were studied. Furthermore, quantification accuracy of lutetium-based attenuation correction was compared for a 20-min scan of the whole body on the uEXPLORER, a one-meter-long, and a conventional 24-cm-long scanner. Quantification and lesion contrast were minimally affected in both long axial field-of-view scanners and in a whole-body 20-min scan, the mean bias in all analyzed organs of interest were within a ±10% range compared to ground-truth activity maps. Quantification was affected in certain organs, when scan duration was reduced to 5 min or a reduced acceptance angle of 17° was used. Analysis of the Compton scattered events suggests that implementing a scatter correction method for the transmission data will be required, and increasing the energy threshold from 250 keV to 290 keV can reduce the computational costs and data rates, with negligible effects on PET quantification. Finally, the current results can serve as groundwork for transferring lutetium-based attenuation correction into research and clinical practice.

PMID:36172601 | PMC:PMC9513593 | DOI:10.3389/fnume.2022.963067

J Nucl Med. 2022 Dec;63(12):1941-1948. doi: 10.2967/jnumed.122.264063. Epub 2022 Jun 30.

ABSTRACT

We introduce multiple-organ objective segmentation (MOOSE) software that generates subject-specific, multiorgan segmentation using data-centric artificial intelligence principles to facilitate high-throughput systemic investigations of the human body via whole-body PET imaging. Methods: Image data from 2 PET/CT systems were used in training MOOSE. For noncerebral structures, 50 whole-body CT images were used, 30 of which were acquired from healthy controls (14 men and 16 women), and 20 datasets were acquired from oncology patients (14 men and 6 women). Noncerebral tissues consisted of 13 abdominal organs, 20 bone segments, subcutaneous fat, visceral fat, psoas muscle, and skeletal muscle. An expert panel manually segmented all noncerebral structures except for subcutaneous fat, visceral fat, and skeletal muscle, which were semiautomatically segmented using thresholding. A majority-voting algorithm was used to generate a reference-standard segmentation. From the 50 CT datasets, 40 were used for training and 10 for testing. For cerebral structures, 34 ¹⁸F-FDG PET/MRI brain image volumes were used from 10 healthy controls (5 men and 5 women imaged twice) and 14 nonlesional epilepsy patients (7 men and 7 women). Only ¹⁸F-FDG PET images were considered for training: 24 and 10 of 34 volumes were used for training and testing, respectively. The Dice score coefficient (DSC) was used as the primary metric, and the average symmetric surface distance as a secondary metric, to evaluate the automated segmentation performance. Results: An excellent overlap between the reference labels and MOOSE-derived organ segmentations was observed: 92% of noncerebral tissues showed DSCs of more than 0.90, whereas a few organs exhibited lower DSCs (e.g., adrenal glands [0.72], pancreas [0.85], and bladder [0.86]). The median DSCs of brain subregions derived from PET images were lower. Only 29% of the brain segments had a median DSC of more than 0.90, whereas segmentation of 60% of regions yielded a median DSC of 0.80-0.89. The results of the average symmetric surface distance analysis demonstrated that the average distance between the reference standard and the automatically segmented tissue surfaces (organs, bones, and brain regions) lies within the size of image voxels (2 mm). Conclusion: The proposed segmentation pipeline allows automatic segmentation of 120 unique tissues from whole-body ¹⁸F-FDG PET/CT images with high accuracy.

PMID:35772962 | PMC:PMC9730926 | DOI:10.2967/jnumed.122.264063

Nat Photonics. 2021 Dec;15(12):914-918. doi: 10.1038/s41566-021-00871-2. Epub 2021 Oct 14.

ABSTRACT

X-ray and gamma-ray photons are widely used for imaging but require a mathematical reconstruction step, known as tomography, to produce cross-sectional images from the measured data. Theoretically, the back-to-back annihilation photons produced by positron-electron annihilation can be directly localized in three-dimensional space using time-of-flight information without tomographic reconstruction. However, this has not yet been demonstrated due to the insufficient timing performance of available radiation detectors. Here, we develop techniques based on detecting prompt Cerenkov photons, which when combined with a convolutional neural network for timing estimation resulted in an average timing precision of 32 picoseconds, corresponding to a spatial precision of 4.8 mm. We show this is sufficient to produce cross-sectional images of a positron-emitting radionuclide directly from the detected coincident annihilation photons, without using any tomographic reconstruction algorithm. The reconstruction-free imaging demonstrated here directly localizes positron emission, and frees the design of an imaging system from the geometric and sampling constraints that normally present for tomographic reconstruction.

PMID:35663419 | PMC:PMC9165659 | DOI:10.1038/s41566-021-00871-2

Phys Med Biol. 2022 Jun 10;67(12):10.1088/1361-6560/ac72f1. doi: 10.1088/1361-6560/ac72f1.

ABSTRACT

Objective.This work assessed the relationship between image signal-to-noise ratio (SNR) and total-body noise-equivalent count rate (NECR)-for both non-time-of-flight (TOF) NECR and TOF-NECR-in a long uniform water cylinder and 14 healthy human subjects using the uEXPLORER total-body PET/CT scanner.Approach.A TOF-NEC expression was modified for list-mode PET data, and both the non-TOF NECR and TOF-NECR were compared using datasets from a long uniform water cylinder and 14 human subjects scanned up to 12 h after radiotracer injection.Main results.The TOF-NECR for the uniform water cylinder was found to be linearly proportional to the TOF-reconstructed image SNR²in the range of radioactivity concentrations studied, but not for non-TOF NECR as indicated by the reducedR²value. The results suggest that the use of TOF-NECR to estimate the count rate performance of TOF-enabled PET systems may be more appropriate for predicting the SNR of TOF-reconstructed images.Significance.Image quality in PET is commonly characterized by image SNR and, correspondingly, the NECR. While the use of NECR for predicting image quality in conventional PET systems is well-studied, the relationship between SNR and NECR has not been examined in detail in long axial field-of-view total-body PET systems, especially for human subjects. Furthermore, the current NEMA NU 2-2018 standard does not account for count rate performance gains due to TOF in the NECR evaluation. The relationship between image SNR and total-body NECR in long axial FOV PET was assessed for the first time using the uEXPLORER total-body PET/CT scanner.

PMID:35609588 | PMC:PMC9275089 | DOI:10.1088/1361-6560/ac72f1

J Nucl Med. 2022 Oct;63(10):1579-1585. doi: 10.2967/jnumed.121.263774. Epub 2022 May 19.

ABSTRACT

Autoimmune inflammatory arthritides (AIA), such as psoriatic arthritis and rheumatoid arthritis, are chronic systemic conditions that affect multiple joints of the body. Recently, total-body (TB) PET/CT scanners exhibiting superior technical characteristics (total-body coverage, geometric sensitivity) that could benefit AIA evaluation, compared with conventional PET/CT systems, have become available. The objectives of this work were to assess the performance of an ultra-low-dose, ¹⁸F-FDG TB PET/CT acquisition protocol for evaluating systemic joint involvement in AIA and to report the association of TB PET/CT measures with joint-by-joint rheumatologic examination and standardized rheumatologic outcome measures. Methods: Thirty participants (24 with AIA and 6 with osteoarthritis) were prospectively enrolled in this single-center, observational study. All participants underwent a TB PET/CT scan for 20 min starting at 40 min after intravenous injection of 78.1 ± 4.7 MBq of ¹⁸F-FDG. Qualitative and quantitative evaluation of ¹⁸F-FDG uptake and joint involvement were performed from the resulting images and compared with the rheumatologic assessments. Results: TB PET/CT enabled the visualization of ¹⁸F-FDG uptake at joints of the entire body, including those of the hands and feet, in a single bed position, and in the same phase of radiotracer uptake. A range of pathologies consistent with AIA (and non-AIA in the osteoarthritis group) were visualized, and the feasibility of extracting PET measures from joints examined by rheumatologic assessments was demonstrated. Of 1,997 evaluable joints, there was concordance between TB PET qualitative assessments and joint-by-joint rheumatologic evaluation in the AIA and non-AIA cohorts for 69.9% and 91.1% joints, respectively, and an additional 20.1% and 8.8% joints, respectively, deemed negative on rheumatologic examination showed PET positivity. On the other hand, 10.0% and 0% joints in the AIA and non-AIA cohorts, respectively, were positive on rheumatologic evaluation but negative on TB PET. Quantitative measures from TB PET in the AIA cohort demonstrated a moderate-to-strong correlation (Spearman ρ = 0.53-0.70, P < 0.05) with the rheumatologic outcome measures. Conclusion: Systemic joint evaluation in AIA (and non-AIA) is feasible with a TB PET/CT system and an ultra-low-dose protocol. Our results provide the foundation for future larger studies to evaluate the possible improvements in AIA joint assessment via the TB PET/CT technology.

PMID:35589405 | PMC:PMC9536697 | DOI:10.2967/jnumed.121.263774

J Nucl Med Technol. 2022 Apr 19;50(4):327-34. doi: 10.2967/jnmt.122.263905. Online ahead of print.

ABSTRACT

Total-body PET/CT allows simultaneous acquisition of all the body parts in a single bed position during the radiotracer uptake phase. Dynamic imaging protocols employing total-body PET could demonstrate findings that may not have been previously visualized or described using conventional PET/CT scanners. We examined the characteristics of blanching defects, areas of markedly reduced (partial defect) or absent (complete defect) radiotracer uptake seen at the skin/subcutaneous tissues opposite the bony prominences at pressure points. Methods: In this observational study, 77 participants underwent dynamic total-body PET/CT imaging using ¹⁸F-FDG (Group 1, N = 47, 60-min dynamic, arms-down, divided into 3 subgroups according to the injected dose) or ¹⁸F-fluciclovine (Group 2, N = 30, 25-min dynamic, arms above the head). 40 out of 47 participants in Group 1 were re-imaged at 90 min after being allowed off the scanning table. Blanching defects, partial or complete, were characterized opposite the bony prominences at 7 pressure points (the skull, scapula, and calcaneus bilaterally, as well as the sacrum). Association of the blanching defects with different clinical and technical characteristics were analyzed using uni- and multi-variate analyses. Results: A total of 124 blanching defects were seen in 68 out of 77 (88%) participants at one or more pressure points. Blanching defects were higher, on average, in Group 2 participants (3.5±1.7) compared to Group 1 (2.1±1.4; P <0.001), but it did not vary within Group 1 for different ¹⁸F-FDG dose subgroups. All defects resumed normal pattern on delayed static (90-min) images except for 14 partial defects. No complete blanching defects were seen on the 90-min images. By multivariate analysis, arm positioning above the head was associated with skull defects; scapular and sacral defects were significantly more encountered in men and with lower BMI, while calcaneal defects could not be associated to any factor. Conclusion: Blanching defects opposite the bony pressure points are common on dynamic total-body PET/CT images using different radiopharmaceuticals and injection doses. Their appearance should not be immediately interpreted as an abnormality. The current findings warrant further exploration in a prospective setting and may be utilized to study various mechano-pathologic conditions, such as pressure ulcers.

PMID:35440473 | PMC:PMC9745988 | DOI:10.2967/jnmt.122.263905

Semin Nucl Med. 2022 May;52(3):330-339. doi: 10.1053/j.semnuclmed.2022.01.002. Epub 2022 Mar 7.

ABSTRACT

Total-body PET has come a long way from its first conception to today, with both total-body and long axial field of view (> 1m) scanners now being commercially available world-wide. The conspicuous signal collection efficiency gain, coupled with high spatial resolution, allows for higher sensitivity and improved lesion detection, enhancing several clinical applications not readily available on current conventional PET/CT scanners. This technology can provide (a) reduction in acquisition times with preservation of diagnostic quality images, benefitting specific clinical situations (i.e. pediatric patients) and the use of several existing radiotracers that present transient uptake over time and where small differences in acquisition time can greatly impact interpretation of images; (b) reduction in administered activity with minimal impact on image noise, thus reducing effective dose to the patient, improving staff safety, and helping with logistical concerns for short-lived radionuclides or long-lived radionuclides with poor dosimetry profiles that have had limited use on conventional PET scanners until now; (c) delayed scanning, that has shown to increase the detection of even small and previously occult malignant lesions by improved clearance in regions of significant background activity and by reduced visibility of coexisting inflammatory processes; (d) improvement in image quality, as a consequence of higher spatial resolution and sensitivity of total-body scanners, implying better appreciation of small structures and clinical implications with downstream prognostic consequences for patients; (e) simultaneous total-body dynamic imaging, that allows the measurement of full spatiotemporal distribution of radiotracers, kinetic modeling, and creation of multiparametric images, providing physiologic and biologically relevant data of the entire body at the same time. On the other hand, the higher physical and clinical sensitivity of total-body scanners bring along some limitations and challenges. The strong impact on clinical sensitivity potentially increases the number of false positive findings if the radiologist does not recalibrate interpretation considering the new technique. Delayed scanning causes logistical issues and introduces new interpretation questions for radiologists. Data storage capacity, longer processing and reconstruction time issues are other limitations, but they may be overcome in the near future by advancements in reconstruction algorithms and computing hardware.

PMID:35272853 | PMC:PMC9439875 | DOI:10.1053/j.semnuclmed.2022.01.002

J Nucl Med. 2022 Aug;63(8):1266-1273. doi: 10.2967/jnumed.121.262968. Epub 2021 Dec 21.

ABSTRACT

Quantitative kinetic modeling requires an input function. A noninvasive image-derived input function (IDIF) can be obtained from dynamic PET images. However, a robust IDIF location (e.g., aorta) may be far from a tissue of interest, particularly in total-body PET, introducing a time delay between the IDIF and the tissue. The standard practice of joint estimation (JE) of delay, along with model fitting, is computationally expensive. To improve the efficiency of delay correction for total-body PET parametric imaging, this study investigated the use of pulse timing methods to estimate and correct for delay. Methods: Simulation studies were performed with a range of delay values, frame lengths, and noise levels to test the tolerance of 2 pulse timing methods-leading edge (LE) and constant fraction discrimination and their thresholds. The methods were then applied to data from 21 subjects (14 healthy volunteers, 7 cancer patients) who underwent a 60-min dynamic total-body ¹⁸F-FDG PET acquisition. Region-of-interest kinetic analysis was performed and parametric images were generated to compare LE and JE methods of delay correction, as well as no delay correction. Results: Simulations demonstrated that a 10% LE threshold resulted in biases and SDs at tolerable levels for all noise levels tested, with 2-s frames. Pooled region-of-interest-based results (n = 154) showed strong agreement between LE (10% threshold) and JE methods in estimating delay (Pearson r = 0.96, P < 0.001) and the kinetic parameters v_b (r = 0.96, P < 0.001), K_i (r = 1.00, P < 0.001), and K₁ (r = 0.97, P < 0.001). When tissues with minimal delay were excluded from pooled analyses, there were reductions in v_b (69.4%) and K₁ (4.8%) when delay correction was not performed. Similar results were obtained for parametric images; additionally, lesion K_i contrast was improved overall with LE and JE delay correction compared with no delay correction and Patlak analysis. Conclusion: This study demonstrated the importance of delay correction in total-body PET. LE delay correction can be an efficient surrogate for JE, requiring a fraction of the computational time and allowing for rapid delay correction across more than 10⁶ voxels in total-body PET datasets.

PMID:34933888 | PMC:PMC9364346 | DOI:10.2967/jnumed.121.262968

Phys Med Biol. 2021 Nov 25;66(23). doi: 10.1088/1361-6560/ac35d3.

NO ABSTRACT

PMID:34821222 | DOI:10.1088/1361-6560/ac35d3

J Nucl Med. 2022 Aug;63(8):1274-1281. doi: 10.2967/jnumed.121.262668. Epub 2021 Nov 18.

ABSTRACT

Quantitative dynamic PET with compartmental modeling has the potential to enable multiparametric imaging and more accurate quantification than static PET imaging. Conventional methods for parametric imaging commonly use a single kinetic model for all image voxels and neglect the heterogeneity of physiologic models, which can work well for single-organ parametric imaging but may significantly compromise total-body parametric imaging on a scanner with a long axial field of view. In this paper, we evaluate the necessity of voxelwise compartmental modeling strategies, including time delay correction (TDC) and model selection, for total-body multiparametric imaging. Methods: Ten subjects (5 patients with metastatic cancer and 5 healthy volunteers) were scanned on a total-body PET/CT system after injection of 370 MBq of ¹⁸F-FDG. Dynamic data were acquired for 60 min. Total-body parametric imaging was performed using 2 approaches. One was the conventional method that uses a single irreversible 2-tissue-compartment model with and without TDC. The second approach selects the best kinetic model from 3 candidate models for individual voxels. The differences between the 2 approaches were evaluated for parametric imaging of microkinetic parameters and the ¹⁸F-FDG net influx rate, K_iResults: TDC had a nonnegligible effect on kinetic quantification of various organs and lesions. The effect was larger in lesions with a higher blood volume. Parametric imaging of K_i with the standard 2-tissue-compartment model introduced vascular-region artifacts, which were overcome by the voxelwise model selection strategy. Conclusion: The time delay and appropriate kinetic model vary in different organs and lesions. Modeling of the time delay of the blood input function and model selection improved total-body multiparametric imaging.

PMID:34795014 | PMC:PMC9364337 | DOI:10.2967/jnumed.121.262668

Phys Med Biol. 2021 Oct 19;66(21):10.1088/1361-6560/ac2c9c. doi: 10.1088/1361-6560/ac2c9c.

ABSTRACT

OBJECTIVE: Dual-ended readout depth-encoding detectors based on bismuth germanate (BGO) scintillation crystal arrays are good candidates for high-sensitivity small animal positron emission tomography used for very-low-dose imaging. In this paper, the performance of three dual-ended readout detectors based on 15 × 15 BGO arrays with three different reflector arrangements and 8 × 8 silicon photomultiplier arrays were evaluated and compared.

APPROACH: The three BGO arrays, denoted wo-ILG (without internal light guide), wp-ILG (with partial internal light guide), and wf-ILG (with full internal light guide), share a pitch size of 1.6 mm and thickness of 20 mm. Toray E60 with a thickness of 50μm was used as inter-crystal reflector. All reflector lengths in the wo-ILG and wf-ILG BGO arrays were 20 and 18 mm, respectively; the reflectors in the wp-ILG BGO array were 18 mm at the central region of the array and 20 mm at the edge. By using 18 mm reflectors, part of the crystals in the wp-ILG and wf-ILG BGO arrays worked as internal light guides.

MAIN RESULTS: The results showed that the detector based on the wo-ILG BGO array provided the best flood histogram. The energy, timing and DOI resolutions of the three detectors were similar. The energy resolutions full width at half maximum (FWHM value) based on the wo-ILG, wp-ILG and wf-ILG BGO arrays were 27.2 ± 3.9%, 28.7 ± 4.6%, and 29.5 ± 4.7%, respectively. The timing resolutions (FWHM value) were 4.7 ± 0.5 ns, 4.9 ± 0.5 ns, and 5.0 ± 0.6 ns, respectively. The DOI resolution (FWHM value) were 3.0 ± 0.2 mm, 2.9 ± 0.2 mm, and 3.0 ± 0.2 mm, respectively. Over all, the wo-ILG detector provided the best performance.

PMID:34607324 | PMC:PMC8571945 | DOI:10.1088/1361-6560/ac2c9c

Phys Med Biol. 2021 Oct 11;66(20):10.1088/1361-6560/ac287c. doi: 10.1088/1361-6560/ac287c.

ABSTRACT

Absolute quantification of regional tissue concentration of radioactivity in positron emission tomography (PET) is a critical parameter-of-interest across various clinical and research applications and is affected by a complex interplay of factors including scanner calibration, data corrections, and image reconstruction. The emergence of long axial field-of-view (FOV) PET systems widens the dynamic range accessible to PET and creates new opportunities in reducing scan time and radiation dose, delayed or low radioactivity imaging, as well as kinetic modeling of the entire human. However, these imaging regimes impose challenging conditions for accurate quantification due to constraints from image reconstruction, low count conditions, as well as large and rapidly changing radioactivity distribution across a large axial FOV. We comprehensively evaluated the quantitative accuracy of the uEXPLORER total-body scanner in conditions that encompass existing and potential imaging applications (such as dynamic imaging and ultralow-dose imaging) using a set of total-body specific phantom and human measurements. Through these evaluations we demonstrated a relative count rate accuracy of ±3%-4% using the NEMA NU 2-2018 protocol, an axial uniformity spread of ±3% across the central 90% axial FOV, and a 3% activity bias spread from 17 to 474 MBq¹⁸F-FDG in a 210 cm long cylindrical phantom. Region-of-interest quantification spread of 1% was found by simultaneously scanning three NEMA NU 2 image quality phantoms, as well as relatively stable volume-of-interest quantification across 0.2%-100% of total counts through re-sampled datasets. In addition, an activity bias spread of -2% to +1% post-bolus injections in human subjects was found. Larger bias changes during the bolus injection phase in humans indicated the difficulty in providing accurate PET data corrections for complex activity distributions across a large dynamic range. Our results overall indicated that the quantitative performance achieved with the uEXPLORER scanner was uniform across the axial FOV and provided the accuracy necessary to support a wide range of imaging applications.

PMID:34544074 | PMC:PMC8585520 | DOI:10.1088/1361-6560/ac287c

IEEE Trans Radiat Plasma Med Sci. 2021 Sep;5(5):630-637. doi: 10.1109/trpms.2020.3024032. Epub 2020 Sep 17.

ABSTRACT

Thallium bromide (TlBr) and thallium chloride (TlCl) are semiconductor materials with high transparency to visible light, high index of refraction, and high detection efficiency for gamma rays and annihilation photons. This manuscript reports on measurements of the light intensity and timing response of Čerenkov light emitted in one 3 mm × 3 mm × 5 mm slab of each of these materials operated in coincidence with a lutetium fine silicate (LFS) crystal with dimensions of 3 mm × 3 mm × 20 mm. A ²²Na radioactive source was used. The measured average number of detected photons per event was 1.5 photons for TlBr and 2.8 photons for TlCl when these materials were coupled to a silicon photomultiplier. Simulation predicts these results with an overestimation of 12%. The best coincidence time resolution (CTR) for events in TlBr and TlCl were 329 ± 9 ps and 316 ± 9 ps, respectively, when events with 4 photons and >7 photons were selected. Simulation showed the CTR degraded from 120 ps to 405 ps in TlCl, and from 160 ps to 700 ps in TlBr when the first or second Čerenkov photon were selected. Results of this work show TlCl has a stronger Čerenkov light emission compared to TlBr and a greater potential to obtain the best timing measurements. Results also stress the importance of improving detection efficiency and transport of light to capture the first Čerenkov photon in timing measurements.

PMID:34485785 | PMC:PMC8412037 | DOI:10.1109/trpms.2020.3024032

PET Clin. 2021 Oct;16(4):613-625. doi: 10.1016/j.cpet.2021.06.009. Epub 2021 Aug 3.

ABSTRACT

The uEXPLORER total-body PET/CT system provides a very high level of detection sensitivity and simultaneous coverage of the entire body for dynamic imaging for quantification of tracer kinetics. This article describes the fundamentals and potential benefits of total-body kinetic modeling and parametric imaging focusing on the noninvasive derivation of blood input function, multiparametric imaging, and high-temporal resolution kinetic modeling. Along with its attractive properties, total-body kinetic modeling also brings significant challenges, such as the large scale of total-body dynamic PET data, the need for organ and tissue appropriate input functions and kinetic models, and total-body motion correction. These challenges, and the opportunities using deep learning, are discussed.

PMID:34353745 | PMC:PMC8453049 | DOI:10.1016/j.cpet.2021.06.009

Biomed Phys Eng Express. 2019 Jan;5(1):015018. doi: 10.1088/2057-1976/aaef03. Epub 2018 Nov 30.

ABSTRACT

This paper describes a simulation study of a positron emission tomography (PET) detector module that can reconstruct the kinematics of Compton scattering within the scintillator. We used a layer structure, with which we could recover the positions and energies for the multiple interactions of a gamma ray in the different layers. Using the Compton scattering formalism, the sequence of interactions can be estimated. The true first interaction position extracted in the Compton scattering will help minimize the degradation of the reconstructed image resolution caused by intercrystal scatter events. Because of the layer structure, this module also has readily available user-defined resolution for the depth of interaction. The semi-monolithic crystals enable high light collection efficiency and an energy resolution of ~10% has been achieved in the simulation. We used machine learning to decode the gamma ray interaction locations, achieving an average spatial resolution of 0.40 mm. Our proposed detector design provides a pathway to increase the sensitivity of a system without affecting other key performance features.

PMID:34290885 | PMC:PMC8291373 | DOI:10.1088/2057-1976/aaef03

Opt Express. 2021 Jun 7;29(12):19024-19033. doi: 10.1364/OE.421857.

ABSTRACT

Enhancing photon detection efficiency and time resolution in photodetectors in the entire visible range is critical to improve the image quality of time-of-flight (TOF)-based imaging systems and fluorescence lifetime imaging (FLIM). In this work, we evaluate the gain, detection efficiency, and timing performance of avalanche photodiodes (APD) with photon trapping nanostructures for photons with 450 nm and 850 nm wavelengths. At 850 nm wavelength, our photon trapping avalanche photodiodes showed 30 times higher gain, an increase from 16% to >60% enhanced absorption efficiency, and a 50% reduction in the full width at half maximum (FWHM) pulse response time close to the breakdown voltage. At 450 nm wavelength, the external quantum efficiency increased from 54% to 82%, while the gain was enhanced more than 20-fold. Therefore, silicon APDs with photon trapping structures exhibited a dramatic increase in absorption compared to control devices. Results suggest very thin devices with fast timing properties and high absorption between the near-ultraviolet and the near infrared region can be manufactured for high-speed applications in biomedical imaging. This study paves the way towards obtaining single photon detectors with photon trapping structures with gains above 10⁶ for the entire visible range.

PMID:34154145 | PMC:PMC8237935 | DOI:10.1364/OE.421857

Eur J Nucl Med Mol Imaging. 2021 Aug;48(9):2711-2726. doi: 10.1007/s00259-021-05390-4. Epub 2021 Jun 3.

NO ABSTRACT

PMID:34081153 | PMC:PMC8263417 | DOI:10.1007/s00259-021-05390-4

Phys Med Biol. 2021 Mar 9;66(6):065016. doi: 10.1088/1361-6560/abe558.

ABSTRACT

With the goal of developing a total-body small-animal PET system with a high spatial resolution of ∼0.5 mm and a high sensitivity >10% for mouse/rat studies, we simulated four scanners using the graphical processing unit-based Monte Carlo simulation package (gPET) and compared their performance in terms of spatial resolution and sensitivity. We also investigated the effect of depth-of-interaction (DOI) resolution on the spatial resolution. All the scanners are built upon 128 DOI encoding dual-ended readout detectors with lutetium yttrium oxyorthosilicate (LYSO) arrays arranged in 8 detector rings. The solid angle coverages of the four scanners are all ∼0.85 steradians. Each LYSO element has a cross-section of 0.44 × 0.44 mm² and the pitch size of the LYSO arrays are all 0.5 mm. The four scanners can be divided into two groups: (1) H²RS110-C10 and H²RS110-C20 with 40 × 40 LYSO arrays, a ring diameter of 110 mm and axial length of 167 mm, and (2) H²RS160-C10 and H²RS160-C20 with 60 × 60 LYSO arrays, a diameter of 160 mm and axial length of 254 mm. C10 and C20 denote the crystal thickness of 10 and 20 mm, respectively. The simulation results show that all scanners have a spatial resolution better than 0.5 mm at the center of the field-of-view (FOV). The radial resolution strongly depends on the DOI resolution and radial offset, but not the axial resolution and tangential resolution. Comparing the C10 and C20 designs, the former provides better resolution, especially at positions away from the center of the FOV, whereas the latter has 2× higher sensitivity (∼10% versus ∼20%). This simulation study provides evidence that the 110 mm systems are a good choice for total-body mouse studies at a lower cost, whereas the 160 mm systems are suited for both total-body mouse and rat studies.

PMID:33571980 | PMC:PMC8353984 | DOI:10.1088/1361-6560/abe558

Phys Med Biol. 2021 Mar 12;66(6):06RM01. doi: 10.1088/1361-6560/abd4f7.

ABSTRACT

Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances and a growing appreciation of the need for reliable, sensitive biomarkers of human function in health and disease. Over the last 30 years, a large amount of the physics and engineering effort in PET has been motivated by the dominant clinical application during that period, oncology. This has led to important developments such as PET/CT, whole-body PET, 3D PET, accelerated statistical image reconstruction, and time-of-flight PET. Despite impressive improvements in image quality as a result of these advances, the emphasis on static, semi-quantitative 'hot spot' imaging for oncologic applications has meant that the capability of PET to quantify biologically relevant parameters based on tracer kinetics has not been fully exploited. More recent advances, such as PET/MR and total-body PET, have opened up the ability to address a vast range of new research questions, from which a future expansion of applications and radiotracers appears highly likely. Many of these new applications and tracers will, at least initially, require quantitative analyses that more fully exploit the exquisite sensitivity of PET and the tracer principle on which it is based. It is also expected that they will require more sophisticated quantitative analysis methods than those that are currently available. At the same time, artificial intelligence is revolutionizing data analysis and impacting the relationship between the statistical quality of the acquired data and the information we can extract from the data. In this roadmap, leaders of the key sub-disciplines of the field identify the challenges and opportunities to be addressed over the next ten years that will enable PET to realise its full quantitative potential, initially in research laboratories and, ultimately, in clinical practice.

PMID:33339012 | PMC:PMC9358699 | DOI:10.1088/1361-6560/abd4f7

Phys Med Biol. 2021 Feb 2;66(4):044001. doi: 10.1088/1361-6560/abd419.

ABSTRACT

Assessing the position of the Bragg peak (BP) in hadron radiotherapy utilizing prompt-gamma imaging (PGI) presents many challenges in terms of detector physics. Gamma detectors with the capability of extracting the best energy, timing, and spatial information from each gamma interaction, as well as with high detection efficiency and count rate performance, are needed for this application. In this work we present the characterization of a pixel Čerenkov charge induction (CCI) thallium bromide (TlBr) detector in terms of energy and and electron drift time for its potential use in PGI. The CCI TlBr detector had dimensions of 4 × 4 × 5 mm³ and one of its electrodes was segmented in pixels with 1.7 mm pitch. A silicon photomultiplier (SiPM) was optically coupled to one of the faces of the TlBr slab to read out the Čerenkov light promptly emitted after the interaction of a gamma ray. The detector was operated stand-alone and the 1.275 prompt gammas from a ²²Na radioactive source were used for the study. The electron drift time was obtained by combining the Čerenkov and charge induction signals and then used as a measure of the depth of interaction. The electron mobility in TlBr was estimated as ∼27 cm² V^-1 s^-1. Energy resolutions between 3.4% and 4.0% at 1.275 MeV were obtained after depth-correction. These values improved to 3.0%-3.3% when events with drift times of 3-6 μs were selected. These results show the potential of pixel CCI TlBr detectors to resolve gamma interactions in the detector with mm-like accuracy in 3D and with excellent energy resolution. Previous studies with CCI TlBr devices have shown a timing resolution of <400 ps full width at half maximum when detecting 511 keV gamma rays, therefore, the timing accuracy is expected to improve with the increased energy of the gamma rays in PGI. While other important detector characteristics such as count rate capability remain to be studied, results from this work combined with other preliminary data show pixel CCI detectors can simultaneously provide excellent energy, timing, and spatial resolution performance and are a very promising option for PGI in hadron therapy.

PMID:33326951 | PMC:PMC9020464 | DOI:10.1088/1361-6560/abd419

Biomed Phys Eng Express. 2019 Apr;5(3):035033. doi: 10.1088/2057-1976/ab0f93. Epub 2019 Apr 17.

ABSTRACT

PURPOSE: We are investigating the use of promptly emitted Cerenkov photons to improve scintillation detector timing resolution for time-of-flight (TOF) positron emission tomography (PET). Bismuth germanate (BGO) scintillator was used in most commercial PET scanners until the emergence of lutetium oxyorthosilicate, which allowed for TOF PET by triggering on the fast and bright scintillation signal. Yet BGO is also a candidate to generate fast timing triggers based on Cerenkov light produced in the first few picoseconds following a gamma interaction. Triggering on the Cerenkov light produces excellent timing resolution in BGO but is complicated by the very low number of photons produced. A better understanding of the transport and collection of Cerenkov photons is needed to optimize their use for effective triggering of the detectors.

METHODS: We simultaneously generated and tracked Cerenkov and scintillation photons with a new model of light transport that we have released in GATE V8.0. This crystal reflectance model was used to study photon detection and timing properties, building realistic waveforms as measured with silicon photomultipliers.

RESULTS: We compared the behavior and effect of detecting Cerenkov and scintillation photons at several levels, including detection time stamps, travel time, and coincidence resolving time in 3 × 3 × 20 mm³ BGO crystals. Simulations showed excellent agreement with experimental results and indicated that Cerenkov photons constitute the majority of the signal rising edge. They are therefore critical to provide early triggering and improved the coincidence timing resolution by 50%.

POTENTIAL APPLICATIONS: To our knowledge, this is the first complete simulation of the generation, transport, and detection of the combination of Cerenkov and scintillation photons for TOF detectors. This simulation framework will allow for quantitative study of the factors influencing timing resolution, including the photodetector characteristics, and ultimately aid the development of BGO and other Cerenkov-based detectors for TOF PET.

PMID:33304614 | PMC:PMC7725232 | DOI:10.1088/2057-1976/ab0f93

Clin Lung Cancer. 2021 Jan;22(1):67-70. doi: 10.1016/j.cllc.2020.10.006. Epub 2020 Oct 16.

ABSTRACT

INTRODUCTION: There are currently no approved targeted therapies for lung squamous-cell carcinoma (LSCC) and KRAS-mutant lung adenocarcinoma (LUAD). About 30% of LSCC and 25% of KRAS-mutant LUAD exhibit hyperactive NRF2 pathway activation through mutations in NFE2L2 (the gene encoding NRF2) or its negative regulator, KEAP1. Preclinical data demonstrate that these tumors are uniquely sensitive to dual inhibition of glycolysis and glutaminolysis via mammalian target of rapamycin (mTOR) and glutaminase inhibitors. This phase 1 study was designed to assess safety and preliminary activity of the mTOR inhibitor MLN0128 (sapanisertib) in combination with the glutaminase inhibitor CB-839 HCl.

METHODS: Phase 1 dose finding will use the queue-based variation of the 3 + 3 dose escalation scheme with the primary endpoint of identifying the recommended expansion dose. To confirm the acceptable tolerability of the recommended expansion dose, patients will subsequently enroll onto 1 of 4 expansion cohorts (n = 14 per cohort): (1) LSCC harboring NFE2L2 or (2) KEAP1 mutations, or (3) LUAD harboring KRAS/(KEAP1 or NFE2L2) coalterations, or (4) LSCC wild type for NFE2L2 and KEAP1. The primary endpoint of the dose expansion is to determine the preliminary efficacy of MLN0128/CB-839 combination therapy.

CONCLUSION: This phase 1 study will determine the recommended expansion dose and preliminary efficacy of MLN0128 and CB-839 in advanced non-small-cell lung cancer with a focus on subsets of LSCC and KRAS-mutant LUAD harboring NFE2L2 or KEAP1 mutations.

PMID:33229301 | PMC:PMC7834952 | DOI:10.1016/j.cllc.2020.10.006

PET Clin. 2021 Jan;16(1):25-39. doi: 10.1016/j.cpet.2020.09.003. Epub 2020 Nov 5.

ABSTRACT

This article describes aspects of PET scanner design for long axial field-of-view systems and how these choices have an impact on scanner performance.

PMID:33160929 | PMC:PMC7680401 | DOI:10.1016/j.cpet.2020.09.003

Phys Med Biol. 2020 Nov 27;65(23):10.1088/1361-6560/abc365. doi: 10.1088/1361-6560/abc365.

ABSTRACT

The performance of dual-ended readout depth-encoding positron emission tomography (PET) detectors based on bismuth germanate (BGO) coupled to silicon photomultipliers (SiPM) arrays was measured for the first time and compared to lutetium-yttrium oxyorthosilicate (LYSO)-based detectors using the same readout. The BGO and LYSO crystal arrays all had a crystal pitch of 2.2 mm and were coupled to 8 × 8 SiPM arrays with a matching pitch of 2.2 mm, using a one-to-one coupling configuration. Three types of crystals with Toray reflector were used: polished LYSO, polished BGO, and unpolished BGO, and for two different crystal thicknesses of 20 mm and 30 mm. All the crystal elements in the BGO arrays were clearly resolved in the flood histogram. Better flood histograms were obtained using the LYSO arrays for a selected crystal thickness, and better flood histograms were obtained using the 20 mm thick crystal arrays for a selected crystal type. The average crystal level energy resolution and timing resolution for 20 mm polished LYSO, polished BGO and unpolished BGO crystals at their optimal SiPM bias voltage were 18.6 ± 1.3% and 1.19 ± 0.20 ns, 17.8 ± 0.8% and 4.43 ± 0.47 ns, and 18.0 ± 1.0% and 4.68 ± 1.0 ns, respectively. Depth-of-interaction (DOI) resolution of the 20 mm polished LYSO array was 2.31 ± 0.17 mm and for the 20 mm unpolished BGO array was 3.53 ± 0.25 mm. However, polished BGO arrays with Toray reflector did not provide DOI information. Our key conclusion is that dual-ended readout depth-encoding 20 mm thick unpolished BGO detectors are good candidates for low-activity PET systems with small field-of-view and low timing performance requirements, such as preclinical or compact organ-dedicated PET systems, with the advantage over LYSO of having no background radiation and significantly lower cost.

PMID:33086214 | PMC:PMC8665694 | DOI:10.1088/1361-6560/abc365

J Nucl Med. 2021 Jun 1;62(6):861-870. doi: 10.2967/jnumed.120.250597. Epub 2020 Oct 2.

ABSTRACT

The world's first total-body PET scanner with an axial field of view (AFOV) of 194 cm is now in clinical and research use at our institution. The uEXPLORER PET/CT system is the first commercially available total-body PET scanner. Here we present a detailed physical characterization of this scanner based on National Electrical Manufacturers Association (NEMA) NU 2-2018 along with a new set of measurements devised to appropriately characterize the total-body AFOV. Methods: Sensitivity, count-rate performance, time-of-flight resolution, spatial resolution, and image quality were evaluated following the NEMA NU 2-2018 protocol. Additional measurements of sensitivity and count-rate capabilities more representative of total-body imaging were performed using extended-geometry phantoms based on the world-average human height (∼165 cm). Lastly, image quality throughout the long AFOV was assessed with the NEMA image quality (IQ) phantom imaged at 5 axial positions and over a range of expected total-body PET imaging conditions (low dose, delayed imaging, short scan duration). Results: Our performance evaluation demonstrated that the scanner provides a very high sensitivity of 174 kcps/MBq, a count-rate performance with a peak noise-equivalent count rate of approximately 2 Mcps for total-body imaging, and good spatial resolution capabilities for human imaging (≤3.0 mm in full width at half maximum near the center of the AFOV). Excellent IQ, excellent contrast recovery, and low noise properties were illustrated across the AFOV in both NEMA IQ phantom evaluations and human imaging examples. Conclusion: In addition to standard NEMA NU 2-2018 characterization, a new set of measurements based on extending NEMA NU 2-2018 phantoms and experiments was devised to characterize the physical performance of the first total-body PET system. The rationale for these extended measurements was evident from differences in sensitivity, count-rate-activity relationships, and noise-equivalent count-rate limits imposed by differences in dead time and randoms fraction between the NEMA NU 2 70-cm phantoms and the more representative total-body imaging phantoms. Overall, the uEXPLORER PET system provides ultra-high sensitivity that supports excellent spatial resolution and IQ throughout the field of view in both phantom and human imaging.

PMID:33008932 | PMC:PMC8729871 | DOI:10.2967/jnumed.120.250597

J Nucl Med. 2021 May 10;62(5):738-744. doi: 10.2967/jnumed.119.238113. Epub 2020 Sep 18.

ABSTRACT

Parametric imaging has been shown to provide better quantitation physiologically than SUV imaging in PET. With the increased sensitivity from a recently developed total-body PET scanner, whole-body scans with higher temporal resolution become possible for dynamic analysis and parametric imaging. In this paper, we focus on deriving the parameter k₁ using compartmental modeling and on developing a method to acquire whole-body ¹⁸F-FDG PET parametric images using only the first 90 s of the postinjection scan data with the total-body PET system. Methods: Dynamic projections were acquired with a time interval of 1 s for the first 30 s and a time interval of 2 s for the following minute. Image-derived input functions were acquired from the reconstructed dynamic sequences in the ascending aorta. A 1-tissue-compartment model with 4 parameters (k₁, k₂, blood fraction, and delay time) was used. A maximum-likelihood-based estimation method was developed with the 1-tissue-compartment model solution. The accuracy of the acquired parameters was compared with the ones estimated using a 2-tissue-compartment irreversible model with 1-h-long data. Results: All 4 parametric images were successfully calculated using data from 2 volunteers. By comparing the time-activity curves acquired from the volumes of interest, we showed that the parameters estimated using our method were able to predict the time-activity curves of the early dynamics of ¹⁸F-FDG in different organs. The delay-time effects for different organs were also clearly visible in the reconstructed delay-time image with delay variations of as large as 40 s. The estimated parameters using both 90-s data and 1-h data agreed well for k₁ and blood fraction, whereas a large difference in k₂ was found between the 90-s and 1-h data, suggesting k₂ cannot be reliably estimated from the 90-s scan. Conclusion: We have shown that with total-body PET and the increased sensitivity, it is possible to estimate parametric images based on the very early dynamics after ¹⁸F-FDG injection. The estimated k₁ might potentially be used clinically as an indicator for identifying abnormalities.

PMID:32948679 | PMC:PMC8844261 | DOI:10.2967/jnumed.119.238113

Phys Med Biol. 2020 Aug 27;65(17):175016. doi: 10.1088/1361-6560/aba088.

ABSTRACT

Positron emission tomography (PET) using scanners incorporating lutetium-based (Lu-based) scintillators are widely used in nuclear medicine. However their application in imaging very low (<100 kBq) activity distributions is quite limited due to the intrinsic ¹⁷⁶Lu radiation emitted from the scintillators. To visualize very low activities, ¹⁷⁶Lu background needs to be reduced or removed. This study proposes a classification method to select background coincidences from true coincidences arising from the source by supervised learning using the optimal classifier as determined by investigating 5 different classifiers: logistic regression, support vector machine, random forest, extreme gradient boosting (XGBoost) and deep neural network. Five energy and time-of-flight (TOF) related features from each coincidence event are extracted to form the training and test set in the classification. The proposed method was verified on a pair of TOF-PET detector modules. Since the measured source coincidences cannot be differentiated from the background events experimentally, simulated source coincidences are used to train the classification model. The simulated feature spectra are therefore compared with those obtained from measurement to verify the feasibility of classifying measured coincidences using a model learned by simulation. XGBoost classifier performed most effectively in classifying the coincidences and provided impressively high classification accuracy (>99%). It was subsequently tested by imaging point-like source, planar Derenzo and bar phantoms with the pair of TOF-PET detectors. An 89.4% image contrast enhancement for the Derenzo phantom at an activity concentration of 100 Bq mm^-2, and a 52.4% peak-to-valley ratio improvement across the area of bar phantom at a concentration of 25 Bq mm^-2, were observed on the reconstructed images with XGBoost classification applied. The proposed method could extend the usage of Lu-based PET scanners to very low activity detection and imaging and has the potential to be used in a variety of molecular imaging tasks to detect low-level signals.

PMID:32590373 | PMC:PMC10289816 | DOI:10.1088/1361-6560/aba088

Phys Med Biol. 2020 Aug 19;65(16):165011. doi: 10.1088/1361-6560/ab9fc9.

ABSTRACT

A dual-ended readout PET detector based on two Hamamatsu 16 × 16 arrays of 1 × 1 mm² SiPMs coupled to both ends of a 25 × 25 array of 0.69 × 0.69 × 20 mm³ polished LYSOs was evaluated in terms of flood histogram, energy resolution, timing resolution, and DOI resolution. The SiPM arrays have a pitch size of 1.2 mm. Each SiPM pixel has an active area of 1 × 1 mm², and was fabricated using 15 μm microcells. The LYSO array has a pitch size of 0.75 mm, and the crystals are separated using Toray reflector with a thickness of 50 μm. The flood histogram and energy resolution were measured at different overvoltages (ranging from 1.5 to 7.0 V, in 0.5 V steps) and at four different temperatures (-7, 0, 10 and 20 °C). The timing resolution and DOI resolution were obtained at the optimal overvoltage for the flood histogram and at each different temperature. Overall, the results show better performance was obtained at lower temperatures, and that the optimal overvoltage decreased at higher temperatures. The optimal overvoltage was 5.0 V (corresponding to a bias voltage of 68.5 V) in order to achieve the highest quality flood histogram at 0 °C. Under these conditions, the flood histogram quality, energy resolution, timing resolution, and DOI resolution were 3.26 ± 0.65, 18.4 ± 4.5%, 1.70 ± 0.12 ns and 2.22 ± 0.19 mm, respectively. The flood histograms and energy resolution were also obtained at different activities. The results show that better flood histogram and energy resolution were obtained at lower activity, however all the crystals can be resolved at an event rate of over 210 k cps, indicating the DOI detector module can be used both for high resolution human brain PET and small animal PET applications.

PMID:32580180 | PMC:PMC8665693 | DOI:10.1088/1361-6560/ab9fc9

EJNMMI Res. 2020 Apr 16;10(1):37. doi: 10.1186/s13550-020-0609-3.

ABSTRACT

PURPOSE: Knowing the precise flow of cerebrospinal fluid (CSF) is important in the management of multiple neurological diseases. Technology for non-invasively quantifying CSF flow would allow for precise localization of injury and assist in evaluating the viability of certain devices placed in the central nervous system (CNS).

METHODS: We describe a near-infrared fluorescent dye for accurately monitoring CSF flow by positron emission tomography (PET) and fluorescence. IR-783, a commercially available near-infrared dye, was chemically modified and radiolabeled with fluorine-18 to give [¹⁸F]-IR783-AMBF₃. [¹⁸F]-IR783-AMBF₃ was intrathecally injected into the rat models with normal and aberrant CSF flow and evaluated by the fluorescence and PET/MRI or PET/CT imaging modes.

RESULTS: IR783-AMBF₃ was clearly distributed in CSF-containing volumes by PET and fluorescence. We compared IR783-AMBF₃ (fluorescent at 778/793 nm, ex/em) to a shorter-wavelength, fluorescein equivalent (fluorescent at 495/511 nm, ex/em). IR783-AMBF₃ was superior for its ability to image through blood (hemorrhage) and for imaging CSF-flow, through-skin, in subdural-run lumboperitoneal shunts. IR783-AMBF₃ was safe under the tested dosage both in vitro and in vivo.

CONCLUSION: The superior imaging properties of IR783-AMBF₃ could lead to enhanced accuracy in the treatment of patients and would assist surgeons in non-invasively diagnosing diseases of the CNS.

PMID:32301036 | PMC:PMC7163004 | DOI:10.1186/s13550-020-0609-3

Phys Med Biol. 2020 Mar 20;65(6):065006. doi: 10.1088/1361-6560/ab7502.

ABSTRACT

The in vivo sensitivity limits and quantification performance of Cerenkov luminescence imaging have been studied using a tissue-like mouse phantom and ⁹⁰Y. For a small, 9 mm deep target in the phantom, with no background activity present, the Cerenkov luminescence ⁹⁰Y detection limit determined from contrast-to-noise ratios is 10 nCi for a 2 min exposure with a sensitive CCD camera and no filters. For quantitative performance, the values extracted from regions of interest on the images are linear within 5% of a straight line fit versus target activity for target activity of 70 nCi and above. The small branching ratio to decay with positron emission for ⁹⁰Y also permits low-statistics PET imaging of the radionuclide. For PET imaging of the same phantom, with a small animal LSO detector-based scanner, the ⁹⁰Y detection limit is approximately 3 orders of magnitude higher at 10 µCi.

PMID:32045899 | PMC:PMC7485541 | DOI:10.1088/1361-6560/ab7502

Proc Natl Acad Sci U S A. 2020 Feb 4;117(5):2265-2267. doi: 10.1073/pnas.1917379117. Epub 2020 Jan 21.

ABSTRACT

A 194-cm-long total-body positron emission tomography/computed tomography (PET/CT) scanner (uEXPLORER), has been constructed to offer a transformative platform for human radiotracer imaging in clinical research and healthcare. Its total-body coverage and exceptional sensitivity provide opportunities for innovative studies of physiology, biochemistry, and pharmacology. The objective of this study is to develop a method to perform ultrahigh (100 ms) temporal resolution dynamic PET imaging by combining advanced dynamic image reconstruction paradigms with the uEXPLORER scanner. We aim to capture the fast dynamics of initial radiotracer distribution, as well as cardiac motion, in the human body. The results show that we can visualize radiotracer transport in the body on timescales of 100 ms and obtain motion-frozen images with superior image quality compared to conventional methods. The proposed method has applications in studying fast tracer dynamics, such as blood flow and the dynamic response to neural modulation, as well as performing real-time motion tracking (e.g., cardiac and respiratory motion, and gross body motion) without any external monitoring device (e.g., electrocardiogram, breathing belt, or optical trackers).

PMID:31964808 | PMC:PMC7007535 | DOI:10.1073/pnas.1917379117

Sci Rep. 2019 Dec 9;9(1):18626. doi: 10.1038/s41598-019-54781-z.

ABSTRACT

Soil salinity is a global environmental challenge for crop production. Understanding the uptake and transport properties of salt in plants is crucial to evaluate their potential for growth in high salinity soils and as a basis for engineering varieties with increased salt tolerance. Positron emission tomography (PET), traditionally used in medical and animal imaging applications for assessing and quantifying the dynamic bio-distribution of molecular species, has the potential to provide useful measurements of salt transport dynamics in an intact plant. Here we report on the feasibility of studying the dynamic transport of ²²Na in millet using PET. Twenty-four green foxtail (Setaria viridis L. Beauv.) plants, 12 of each of two different accessions, were incubated in a growth solution containing ²²Na⁺ ions and imaged at 5 time points over a 2-week period using a high-resolution small animal PET scanner. The reconstructed PET images showed clear evidence of sodium transport throughout the whole plant over time. Quantitative region-of-interest analysis of the PET data confirmed a strong correlation between total ²²Na activity in the plants and time. Our results showed consistent salt transport dynamics within plants of the same variety and important differences between the accessions. These differences were corroborated by independent measurement of Na⁺ content and expression of the NHX transcript, a gene implicated in sodium transport. Our results demonstrate that PET can be used to quantitatively evaluate the transport of sodium in plants over time and, potentially, to discern differing salt-tolerance properties between plant varieties. In this paper, we also address the practical radiation safety aspects of working with ²²Na in the context of plant imaging and describe a robust pipeline for handling and incubating plants. We conclude that PET is a promising and practical candidate technology to complement more traditional salt analysis methods and provide insights into systems-level salt transport mechanisms in intact plants.

PMID:31819118 | PMC:PMC6901586 | DOI:10.1038/s41598-019-54781-z

Phys Med Biol. 2019 Nov 26;64(23):235004. doi: 10.1088/1361-6560/ab4e3c.

ABSTRACT

Brain PET scanners that simultaneously provide high-resolution across the field-of-view and high-sensitivity can be constructed using detectors based on SiPM arrays coupled to both ends of scintillator arrays with finely segmented and long detector elements. To reduce the dead space between detector modules and hence improve the sensitivity of PET scanners, crystal arrays with curved surfaces are proposed. In this paper, the performance of a proof-of-concept detector module with nine detector submodules based on SiPMs coupled to both ends of a curved LYSO array with a pitch size of 1.0 × 1.0 mm² at the front-end and a length of 30 mm was evaluated. A simple signal multiplexing method using the shared-photodetector readout method was evaluated to identify the crystals. The results showed that all the LYSO elements in the detector module of interest could be clearly resolved. The energy resolution, depth-of-interaction resolution, and timing resolution were 14.6% ± 3.6%, 2.77 ± 0.39 mm, and 1.15 ± 0.07 ns, respectively, obtained at a bias voltage of 28.0 V and a temperature of 16.8 °C ± 0.2 °C.

PMID:31618708 | PMC:PMC7485540 | DOI:10.1088/1361-6560/ab4e3c

J Nucl Med. 2020 Mar;61(3):453-460. doi: 10.2967/jnumed.119.230961. Epub 2019 Sep 27.

ABSTRACT

The use of ⁸⁹Zr-antibody PET imaging to measure antibody biodistribution and tissue pharmacokinetics is well established, but current PET systems lack the sensitivity needed to study ⁸⁹Zr-labeled antibodies beyond 2-3 isotope half-lives (7-10 d), after which a poor signal-to-noise ratio is problematic. However, studies across many weeks are desirable to better match antibody circulation half-life in human and nonhuman primates. These studies investigated the technical feasibility of using the primate mini-EXPLORER PET scanner, making use of its high sensitivity and 45-cm axial field of view, for total-body imaging of ⁸⁹Zr-labeled antibodies in rhesus monkeys up to 30 d after injection. Methods: A humanized monoclonal IgG antibody against the herpes simplex viral protein glycoprotein D (gD) was radiolabeled with ⁸⁹Zr via 1 of 4 chelator-linker combinations (benzyl isothiocyanate-DFO [DFO-Bz-NCS], where DFO is desferrioxamine B; DFO-squaramide; DFO*-Bz-NCS, where DFO* is desferrioxamine*; and DFO*-squaramide). The pharmacokinetics associated with these 4 chelator-linker combinations were compared in 12 healthy young male rhesus monkeys (∼1-2 y old, ∼3 ± 1 kg). Each animal was initially injected intravenously with unlabeled antibody in a peripheral vessel in the right arm (10 mg/kg, providing therapeutic-level antibody concentrations), immediately followed by approximately 40 MBq of one of the ⁸⁹Zr-labeled antibodies injected intravenously in a peripheral vessel in the left arm. All animals were imaged 6 times over a period of 30 d, with an initial 60-min dynamic scan on day 0 (day of injection) followed by static scans of 30-45 min on approximately days 3, 7, 14, 21, and 30, with all acquired using a single bed position and images reconstructed using time-of-flight list-mode ordered-subsets expectation maximization. Activity concentrations in various organs were extracted from the PET images using manually defined regions of interest. Results: Excellent image quality was obtained, capturing the initial distribution phase in the whole-body scan; later time points showed residual ⁸⁹Zr mainly in the liver. Even at 30 d after injection, representing approximately 9 half-lives of ⁸⁹Zr and with a total residual activity of only 20-40 kBq in the animal, the image quality was sufficient to readily identify activity in the liver, kidneys, and upper and lower limb joints. Significant differences were noted in late time point liver uptake, bone uptake, and whole-body clearance between chelator-linker types, whereas little variation (±10%) was observed within each type. Conclusion: These studies demonstrate the ability to image ⁸⁹Zr-radiolabeled antibodies up to 30 d after injection while maintaining satisfactory image quality, as provided by the primate mini-EXPLORER with high sensitivity and long axial field of view. Quantification demonstrated potentially important differences in the behavior of the 4 chelators. This finding supports further investigation.

PMID:31562219 | PMC:PMC7067524 | DOI:10.2967/jnumed.119.230961

Phys Med Biol. 2019 Aug 28;64(17):175001. doi: 10.1088/1361-6560/ab35c4.

ABSTRACT

Thallium bromide (TlBr) is a semiconductor material and, simultaneously, a good Cerenkov radiator. The performance of a TlBr detector that integrates two different readouts, the charge induction readout and the detection of Cerenkov light, was evaluated. A TlBr detector with dimensions of 4 × 4 × 5 mm³, with a monolithic cathode and an anode segmented into strips, was manufactured. One of the bare and polished 4 × 4 mm² faces of the detector was coupled to a silicon photomultiplier (SiPM) to read out the Cerenkov light. Simultaneous timing and energy resolutions of <400 ps full width at half maximum (FWHM) and ~8.5% at 511 keV were measured using the Cerenkov detection and charge induction readouts, respectively. A coincidence time resolution of 330 ps was obtained when selecting Cerenkov events with amplitudes above 70 mV. The combination of both readouts showed the potential to resolve the depth-of-interaction (DOI) positioning, based on the improvement of energy resolution when selecting events with similar electron drift times. This manuscript sets the stage for a new family of semiconductor detectors that combine charge induction readout with the Cerenkov light detection. Such detectors can provide, simultaneously, outstanding timing, energy, and spatial resolution, and will be an excellent fit for applications that require the detection of high-energy gamma photons with high timing accuracy, such as time-of-flight positron emission tomography (TOF-PET) and prompt gamma imaging (PGI) to assess the particle range in hadron therapy.

PMID:31344688 | PMC:PMC8187111 | DOI:10.1088/1361-6560/ab35c4

Plant Direct. 2019 Apr 23;3(4):e00131. doi: 10.1002/pld3.131. eCollection 2019 Apr.

ABSTRACT

Heavy metals such as zinc are essential for plant growth, but toxic at high concentrations. Despite our knowledge of the molecular mechanisms of heavy metal uptake by plants, experimentally addressing the real-time whole-plant dynamics of heavy metal uptake and partitioning has remained a challenge. To overcome this, we applied a high sensitivity gamma-ray imaging system to image uptake and transport of radioactive ⁶⁵Zn in whole-plant assays of Arabidopsis thaliana and the Zn hyperaccumulator Arabidopsis halleri. We show that our system can be used to quantitatively image and measure uptake and root-to-shoot translocation dynamics of zinc in real time. In the metal hyperaccumulator Arabidopsis halleri, ⁶⁵Zn uptake and transport from its growth media to the shoot occurs rapidly and on time scales similar to those reported in rice. In transgenic A. halleri plants in which expression of the zinc transporter gene HMA4 is suppressed by RNAi, ⁶⁵Zn uptake is completely abolished.

PMID:31309170 | PMC:PMC6589544 | DOI:10.1002/pld3.131

J Nucl Med. 2020 Feb;61(2):285-291. doi: 10.2967/jnumed.119.230565. Epub 2019 Jul 13.

ABSTRACT

The world's first 194-cm-long total-body PET/CT scanner (uEXPLORER) has been built by the EXPLORER Consortium to offer a transformative platform for human molecular imaging in clinical research and health care. Its total-body coverage and ultra-high sensitivity provide opportunities for more accurate tracer kinetic analysis in studies of physiology, biochemistry, and pharmacology. The objective of this study was to demonstrate the capability of total-body parametric imaging and to quantify the improvement in image quality and kinetic parameter estimation by direct and kernel reconstruction of the uEXPLORER data. Methods: We developed quantitative parametric image reconstruction methods for kinetic analysis and used them to analyze the first human dynamic total-body PET study. A healthy female subject was recruited, and a 1-h dynamic scan was acquired during and after an intravenous injection of 256 MBq of ¹⁸F-FDG. Dynamic data were reconstructed using a 3-dimensional time-of-flight list-mode ordered-subsets expectation maximization (OSEM) algorithm and a kernel-based algorithm with all quantitative corrections implemented in the forward model. The Patlak graphical model was used to analyze the ¹⁸F-FDG kinetics in the whole body. The input function was extracted from a region over the descending aorta. For comparison, indirect Patlak analysis from reconstructed frames and direct reconstruction of parametric images from the list-mode data were obtained for the last 30 min of data. Results: Images reconstructed by OSEM showed good quality with low noise, even for the 1-s frames. The image quality was further improved using the kernel method. Total-body Patlak parametric images were obtained using either indirect estimation or direct reconstruction. The direct reconstruction method improved the parametric image quality, having a better contrast-versus-noise tradeoff than the indirect method, with a 2- to 3-fold variance reduction. The kernel-based indirect Patlak method offered image quality similar to the direct Patlak method, with less computation time and faster convergence. Conclusion: This study demonstrated the capability of total-body parametric imaging using the uEXPLORER. Furthermore, the results showed the benefits of kernel-regularized reconstruction and direct parametric reconstruction. Both can achieve superior image quality for tracer kinetic studies compared with the conventional indirect OSEM for total-body imaging.

PMID:31302637 | PMC:PMC8801950 | DOI:10.2967/jnumed.119.230565

Phys Med Biol. 2019 Aug 7;64(15):15NT03. doi: 10.1088/1361-6560/ab1c37.

ABSTRACT

Silicon photomultipliers (SiPMs) are widely used in positron emission tomography (PET), however, SiPMs from different vendors vary in their performance characteristics. In addition, the specifications provided by the manufacturers are measured under different operating conditions and using different test setups, making it difficult to choose the optimal device for a specific application using the published specifications. In this work, we evaluated four state-of-the-art 8 × 8 arrays of ~3 × 3 mm² SiPMs from SensL, KETEK, and Hamamatsu for high-resolution dual-ended readout detectors using the same experimental setup and procedures. The results showed that all four SiPM arrays are excellent candidates for high-resolution PET applications, although some interesting differences in performance were noted.

PMID:31018180 | PMC:PMC7477918 | DOI:10.1088/1361-6560/ab1c37

Phys Med Biol. 2019 May 8;64(10):10LT01. doi: 10.1088/1361-6560/ab1ba0.

ABSTRACT

In most high-resolution PET detector designs, there is an inherent trade-off between spatial resolution and detector efficiency. We have developed and tested a new geometry for the detector module which avoids this trade-off. The module uses a layered structure, in which four crystal slabs are stacked in the depth direction and optically separated by enhanced specular reflector (ESR) film. The scintillation light within each layer is measured by 16 SiPMs located on the four sides of the crystal. Analog signals from all SiPMs (4 × 16) on the four sides of the crystal are digitized individually using a 64-channel TOFPET-2 module. The four-sided readout method reduces the problem of light trapping resulting from total internal reflection when reading out the end(s) of traditional scintillation crystal arrays, thus increasing the light collection efficiency. In this work, we demonstrate the readout of a complete layered detector with 4 layers. The high light collection efficiency results in a FWHM energy resolution of 10.3%, and a FWHM timing resolution of 348 ps. The distribution of scintillation light detected by the SiPMs was used to decode the interaction position of each gamma ray using a trained neural network. A FWHM spatial resolution of 1.1 ± 0.1 mm was achieved. This design allows the detection efficiency of the module to be increased by adding additional crystal slabs along the depth direction. Since the position, energy, and timing are measured for each layer independently, increasing the system sensitivity by adding more layers will not affect the spatial/energy/timing resolution. Furthermore, the layered structure allows partial recovery of position information for events that undergo Compton scatter within the detector.

PMID:31013481 | PMC:PMC7485538 | DOI:10.1088/1361-6560/ab1ba0

Phys Med Biol. 2019 May 10;64(10):105007. doi: 10.1088/1361-6560/ab18da.

ABSTRACT

The scintillator bismuth germanate (BGO) has attractive properties for positron emission tomography (PET) systems such as high stopping power, high photo-fraction, and relatively low cost. However, its moderate scintillation light yield and slow rise and decay time compared to lutetium (yttrium) oxyorthosilicate (L(Y)SO) results in a degradation of coincidence timing resolution when scintillation photons are used for timing. Recently, it has been reported that the coincidence timing resolution of BGO can be improved by detecting Cerenkov photons, while scintillation photons still provide energy information. However, the measured coincidence timing spectrum showed much longer tails compared to the single Gaussian distribution. Because of this, TOF PET detectors based on BGO will perform worse than the full width at half maximum (FWHM) of the distribution, which is the most common metric for timing resolution, would suggest. From simulation studies, during the first few picoseconds, BGO generates ~16 Cerenkov photons per photoelectric interaction, following a 511 keV gamma ray interaction, while the probability of producing a scintillation photon during the first few picoseconds is very small. Therefore, when we configure a BGO crystal with dual-ended readout, the first arriving photons among the two opposing SiPMs are most likely Cerenkov photons, and by selecting the appropriate SiPM, an improvement in coincidence timing resolution can be achieved. In this study, both ends of a 3 × 3 × 20 mm³ BGO crystal were coupled to NUV-HD SiPMs. Trigger time differences from the dual-ended readout of BGO were widely distributed due to detecting a mixture of prompt Cerenkov and scintillation photons on both SiPMs. When using trigger times from only a single SiPM, the estimated coincidence timing resolution between two identical BGO detectors was 463 ps FWHM and 1463 ps FWTM. In contrast, when using trigger times from both SiPMs, the estimated coincidence timing resolution was 399 ps FWHM and 936 ps FWTM with no loss of events. Based on a recent report, high-bandwidth amplifiers were implemented and shown to further improve the estimated coincidence timing resolution to 331 ps FWHM and 923 ps FWTM. In summary, the coincidence timing resolution of BGO, most notably the FWTM, was significantly improved using time information from the dual-ended readout.

PMID:30978713 | PMC:PMC7323734 | DOI:10.1088/1361-6560/ab18da

J Nucl Med. 2019 Mar;60(3):295-298.

NO ABSTRACT

PMID:30824670

Phys Med Biol. 2019 Apr 8;64(8):080301. doi: 10.1088/1361-6560/ab0671.

NO ABSTRACT

PMID:30754025 | DOI:10.1088/1361-6560/ab0671

J Nucl Med. 2019 Mar;60(3):299-303. doi: 10.2967/jnumed.119.226498. Epub 2019 Feb 7.

ABSTRACT

Within the EXPLORER Consortium, the construction of the world's first total-body PET/CT scanner has recently been completed. The 194-cm axial field of view of the EXPLORER PET/CT scanner is sufficient to cover, for the first time, the entire human adult body in a single acquisition in more than 99% of the population and allows total-body pharmacokinetic studies with frame durations as short as 1 s. The large increase in sensitivity arising from total-body coverage as well as increased solid angle for detection at any point within the body allows whole-body ¹⁸F-FDG PET studies to be acquired with unprecedented count density, improving the signal-to-noise ratio of the resulting images. Alternatively, the sensitivity gain can be used to acquire diagnostic PET images with very small amounts of activity in the field of view (25 MBq, 0.7 mCi or less), with very short acquisition times (∼1 min or less) or at later time points after the tracer's administration. We report here on the first human imaging studies on the EXPLORER scanner using a range of different protocols that provide initial evidence in support of these claims. These case studies provide the foundation for future carefully controlled trials to quantitatively evaluate the improvements possible through total-body PET imaging.

PMID:30733314 | PMC:PMC6424228 | DOI:10.2967/jnumed.119.226498

Phys Med Biol. 2019 Mar 21;64(7):075004. doi: 10.1088/1361-6560/aafc6c.

ABSTRACT

As part of the EXPLORER total-body positron emission tomography (PET) project, we have designed and built a high-resolution, high-sensitivity PET/CT scanner, which is expected to have excellent performance for companion animal whole body and human brain imaging. The PET component has a ring diameter of 52 cm and an axial field of view of 48.3 cm. The detector modules are composed of arrays of lutetium (yttrium) oxyorthosilicate (LYSO) crystals of dimensions 2.76 × 2.76 × 18.1 mm³ coupled to silicon photomultipliers (SiPMs) for read-out. The CT component is a 24 detector row CT scanner with a 50 kW x-ray tube. PET system time-of-flight resolution was measured to be 409 ± 39 ps and average system energy resolution was 11.7% ± 1.5% at 511 keV. The NEMA NU2-2012 system sensitivity was found to be 52-54 kcps MBq^-1. Spatial resolution was 2.6 mm at 10 mm from the center of the FOV and 2.0 mm rods were clearly resolved on a mini-Derenzo phantom. Peak noise-equivalent count (NEC) rate, using the NEMA NU 2-2012 phantom, was measured to be 314 kcps at 9.2 kBq cc^-1. The CT scanner passed the technical components of the American College of Radiology (ACR) accreditation tests. We have also performed scans of a Hoffman brain phantom and we show images from the first canine patient imaged on this device.

PMID:30620929 | PMC:PMC6666419 | DOI:10.1088/1361-6560/aafc6c