Total-body Positron Emission Tomography Research Articles

Bidirectional dynamic frame prediction network for total-body [68Ga]Ga-PSMA-11 and [68Ga]Ga-FAPI-04 PET images

PurposeTotal-body dynamic positron emission tomography (PET) imaging with total-body coverage and ultrahigh sensitivity has played an important role in accurate tracer kinetic analyses in physiology, biochemistry, and pharmacology. However, dynamic PET scans typically entail prolonged durations (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\ge\\:$$\\end{document}60 minutes), potentially causing patient discomfort and resulting in artifacts in the final images. Therefore, we propose a dynamic frame prediction method for total-body PET imaging via deep learning technology to reduce the required scanning time.MethodsOn the basis of total-body dynamic PET data acquired from 13 subjects who received [68Ga]Ga-FAPI-04 (68Ga-FAPI) and 24 subjects who received [68Ga]Ga-PSMA-11 (68Ga-PSMA), we propose a bidirectional dynamic frame prediction network that uses the initial and final 10 min of PET imaging data (frames 1–6 and frames 25–30, respectively) as inputs. The peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) were employed as evaluation metrics for an image quality assessment. Moreover, we calculated parametric images (68Ga-FAPI: \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{K}_{1}$$\\end{document}, 68Ga-PSMA: \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{K}_{i}$$\\end{document}) based on the supplemented sequence data to observe the quantitative accuracy of our approach. Regions of interest (ROIs) and statistical analyses were utilized to evaluate the performance of the model.ResultsBoth the visual and quantitative results illustrate the effectiveness of our approach. The generated dynamic PET images yielded PSNRs of 36.056 ± 0.709 dB for the 68Ga-PSMA group and 33.779 ± 0.760 dB for the 68Ga-FAPI group. Additionally, the SSIM reached 0.935 ± 0.006 for the 68Ga-FAPI group and 0.922 ± 0.009 for the 68Ga-PSMA group. By conducting a quantitative analysis on the parametric images, we obtained PSNRs of 36.155 ± 4.813 dB (68Ga-PSMA, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{K}_{1}$$\\end{document}) and 43.150 ± 4.102 dB (68Ga-FAPI, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{K}_{i}$$\\end{document}). The obtained SSIM values were 0.932 ± 0.041 (68Ga-PSMA) and 0.980 ± 0.011 (68Ga-FAPI). The ROI analysis conducted on our generated dynamic PET sequences also revealed that our method can accurately predict temporal voxel intensity changes, maintaining overall visual consistency with the ground truth.ConclusionIn this work, we propose a bidirectional dynamic frame prediction network for total-body 68Ga-PSMA and 68Ga-FAPI PET imaging with a reduced scan duration. Visual and quantitative analyses demonstrated that our approach performed well when it was used to predict one-hour dynamic PET images. https://github.com/OPMZZZ/BDF-NET.

Hierarchical Organ-Aware Total-Body Standard-Dose PET Reconstruction From Low-Dose PET and CT Images.

Positron emission tomography (PET) is an important functional imaging technology in early disease diagnosis. Generally, the gamma ray emitted by standard-dose tracer inevitably increases the exposure risk to patients. To reduce dosage, a lower dose tracer is often used and injected into patients. However, this often leads to low-quality PET images. In this article, we propose a learning-based method to reconstruct total-body standard-dose PET (SPET) images from low-dose PET (LPET) images and corresponding total-body computed tomography (CT) images. Different from previous works focusing only on a certain part of human body, our framework can hierarchically reconstruct total-body SPET images, considering varying shapes and intensity distributions of different body parts. Specifically, we first use one global total-body network to coarsely reconstruct total-body SPET images. Then, four local networks are designed to finely reconstruct head-neck, thorax, abdomen-pelvic, and leg parts of human body. Moreover, to enhance each local network learning for the respective local body part, we design an organ-aware network with a residual organ-aware dynamic convolution (RO-DC) module by dynamically adapting organ masks as additional inputs. Extensive experiments on 65 samples collected from uEXPLORER PET/CT system demonstrate that our hierarchical framework can consistently improve the performance of all body parts, especially for total-body PET images with PSNR of 30.6 dB, outperforming the state-of-the-art methods in SPET image reconstruction.

Effect of abdominal adipose tissue glucose uptake on brain aging.

Abdominal adipose tissue (AT) mass has adverse effects on the brain. This study aimed to investigate the effect of glucose uptake by abdominal AT on brain aging. Three-hundred twenty-five participants underwent total-body positron emission tomography scan. Brain age was estimated in an independent test set (n=98) using a support vector regression model that was built using a training set (n=227). Effects of abdominal subcutaneous and visceral AT (SAT/VAT) glucose uptake on brain age delta were evaluated using linear regression. Higher VAT glucose uptake was linked to negative brain age delta across all subgroups. Higher SAT glucose uptake was associated with negative brain age delta in lean individuals. In contrast, increased SAT glucose uptake demonstrated positive trends with brain age delta in female and overweight/obese participants. Increased glucose uptake of the abdominal VAT has positive influences on the brain, while SAT may not have such influences, except for lean individuals. Higher glucose uptake of the visceral adipose tissue was linked to decelerated brain aging. Higher glucose uptake of the subcutaneous adipose tissue (SAT) was associated with negative brain age delta in lean individuals. Faster brain aging was associated with increased glucose uptake of the SAT in female and overweight and obese individuals.

Effects of deep brain stimulation on dopamine D2 receptor binding in patients with treatment-refractory depression

BackgroundDepression is a chronic psychiatric disorder related to diminished dopaminergic neurotransmission. Deep brain stimulation (DBS) has shown effectiveness in treating patients with treatment-refractory depression (TRD). This study aimed to evaluate the effect of DBS on dopamine D2 receptor binding in patients with TRD. MethodsSix patients with TRD were treated with bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS were recruited. Ultra-high sensitivity [11C]raclopride dynamic total-body positron emission tomography (PET) imaging was used to assess the brain D2 receptor binding. Each patient underwent a [11C]raclopride PET scan for 60-min under DBS OFF and DBS ON, respectively. A simplified reference tissue model was used to generate parametric images of binding potential (BPND) with the cerebellum as reference tissue. ResultsDepression and anxiety symptoms improved after 3–6 months of DBS treatment. Compared with two-day-nonstimulated conditions, one-day BNST-NAc DBS decreased [11C]raclopride BPND in the amygdala (15.9 %, p < 0.01), caudate nucleus (15.4 %, p < 0.0001) and substantia nigra (10.8 %, p < 0.01). LimitationsThis study was limited to the small sample size and lack of a healthy control group. ConclusionsChronic BNST-NAc DBS improved depression and anxiety symptoms, and short-term stimulation decreased D2 receptor binding in the amygdala, caudate nucleus, and substantia nigra. The findings suggest that DBS relieves depression and anxiety symptoms possibly by regulating the dopaminergic system.

Development of a Monte Carlo-based scatter correction method for total-body PET using the uEXPLORER PET/CT scanner

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.

The earliest optimal timing for total-body 68Ga-fibroblast activation protein inhibitor-04 PET scans: an evidence-based single-centre study.

To investigate the earliest optimal timing for positron emission tomography (PET) scans after 68Ga-fibroblast activation protein inhibitor-04 ([68Ga]Ga-FAPI-04) injection. This prospective study enrolled patients who underwent 60-min dynamic 68Ga-FAPI-04 total-body PET/CT scans; the images were reconstructed at 10-min intervals (G0-10, G10-20, G20-30, G30-40, G40-50, and G50-60), and the [68Ga]Ga-FAPI-04 uptake patterns were evaluated. The standardised uptake value (SUV), liver signal-to-noise ratio (SNR), and lesion-to-background ratios (LBRs) for different time windows were calculated to evaluate image quality and lesion detectability. The period from 30 to 40min was then split into overlapping 5-min intervals starting 1min apart for further evaluation. G50-60 was considered the reference. A total of 30 patients with suspected malignant tumours were analysed. In the images reconstructed over 10-min intervals, longer acquisition times were associated with lower background uptake and better image quality. Some lesions could not be detected until G30-40. The lesion detection rate, uptake, and LBRs did not differ significantly among G30-40, G40-50, and G50-60 (all p > 0.05). The SUVmean and LBRs of primary tumours in the reconstructed images did not differ significantly among the 5-min intervals between 30 and 40min; for metastatic and benign lesions, G34-39 and G35-40 showed significantly better SUVmean and LBR values than the other images. The G34-39 and G50-60 scans showed no significant differences in uptake, LBRs, or detection rates (all p > 0.05). The earliest optimal time to start acquisition was 34min after injection of half-dose [68Ga]Ga-FAPI-04. This study evaluated 68Ga-fibroblast activation protein inhibitor-04 ([68Ga]Ga-FAPI-04) uptake patterns by comparing the image quality and lesion detection rate with 60-min dynamic [68Ga]Ga-FAPI-04 total-body PET/CT scans and identified the earliest optimal scan time after [68Ga]Ga-FAPI-04 injection. • A prospective single-centre study showed that the earliest optimal time point to start acquisition was 34min after injection of half-dose [68Ga-fibroblast activation protein inhibitor-04 (68Ga]Ga-FAPI-04). • There were statistically significant differences in standardised uptake value, lesion-to-background ratios, and lesion detectability between scans before and after 34min from the injection of [68Ga]Ga-FAPI-04, but these values did not change further from 34 to 60min after injection. • With a reasonable acquisition time, the image quality could still meet diagnostic requirements.

Dynamic total-body PET/CT imaging with reduced acquisition time shows acceptable performance in quantification of [18F]FDG tumor kinetic metrics.

To investigate the feasibility of reducing the acquisition time for continuous dynamic positron emission tomography (PET) while retaining acceptable performance in quantifying kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) in tumors. In total, 78 oncological patients underwent total-body dynamic PET imaging for ≥ 60min, with 8, 20, and 50 patients receiving full activity (3.7 MBq/kg), half activity (1.85 MBq/kg), and ultra-low activity (0.37 MBq/kg) of [18F]FDG, respectively. The dynamic data were divided into 21-, 30-, 45- and ≥ 60-min groups. The kinetic analysis involved model fitting to derive constant rates (VB, K1 to k3, and Ki) for both tumors and normal tissues, using both reversible and irreversible two-tissue-compartment models. One-way ANOVA with repeated measures or the Freidman test compared the kinetic metrics among groups, while the Deming regression assessed the correlation of kinetic metrics among groups. All kinetic metrics in the 30-min and 45-min groups were statistically comparable to those in the ≥ 60-min group. The relative differences between the 30-min and ≥ 60-min groups ranged from 12.3% ± 15.1% for K1 to 29.8% ± 30.0% for VB, and those between the 45-min and ≥ 60-min groups ranged from 7.5% ± 8.7% for Ki to 24.0% ± 24.3% for VB. However, this comparability was not observed between the 21-min and ≥ 60-min groups. The significance trend of these comparisons remained consistent across different models (reversible or irreversible), administrated activity levels, and partial volume corrections for lesions. Significant correlations in tumor kinetic metrics were identified between the 30-/45-min and ≥ 60-min groups, with Deming regression slopes > 0.813. In addition, the comparability of kinetic metrics between the 30-min and ≥ 60-min groups were established for normal tissues. The acquisition time for dynamic PET imaging can be reduced to 30min without compromising the ability to reveal tumor kinetic metrics of [18F]FDG, using the total-body PET/CT system.

One-tenth-activity total-body positron emission tomography versus full-activity imaging in patients with a complex of hepatic malignant tumors: a retrospective study.

The value of ultra-low-activity 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) imaging in patients with hepatic malignancies remains unclear. A cross-sectional study was conducted from April 2019 to May 2021 in Zhongshan Hospital, Fudan University. A total of 49 patients with hepatic malignancies, including hepatocellular carcinoma (HCC) (n=13) or intrahepatic cholangiocarcinoma (ICC) (n=36), underwent 60-min dynamic PET imaging, with 15 undergoing full-activity 18F-FDG and 34 undergoing ultra-low-activity 18F-FDG. The kinetic metrics (K1-k3, and Ki) of tumors were calculated and compared between the activity groups. Another 54 patients (27 each group) with hepatic malignancies, including HCC (n=9), ICC (n=34), and metastases (n=11), underwent static imaging. Image qualities were compared between the groups in terms of 5-point Likert scores (with a score ≥3 fulfilling the clinical requirement), the mean standardized uptake value (SUVmean), the standard deviation of standardized uptake value (SUVSD), and the signal-to-noise ratio (SNR) of the liver; the SUVmean of blood pool and muscle; and the tumor-to-liver ratio (TLR), tumor-to-blood ratio (TBR), and tumor-to-muscle ratio (TMR) of lesions. Intergroup comparisons were performed using Chi-squared test for categorical variables and the Student's t-test or the Mann-Whitney test for continuous variables depending on the normality of variables. There was a nonsignificant difference in the kinetic metrics (K1-k3 and Ki) of tumors between the activity groups. In static imaging, 1-min full-activity (F1) and 8-min ultra-low-activity (L8) images obtained image-quality scores >3 and were thus selected for intergroup comparisons. Nonsignificant differences in SUVmean of liver, blood pool, and muscle were identified between F1 and L8 images (P=0.641, P=0.542, and P=0.073, respectively) although the liver SNR was slightly higher in F1 (13.10 vs. 11.31; P=0.003). Lesion detectability was 98.5% and 100% for F1 and L8 images, respectively, but there were no significant differences in TLR, TBR, or TMR between the groups. The results of this single-center study indicate that the performance of ultra-low-activity PET imaging is comparable to that of full-activity imaging in patients with hepatic malignancies.

First-in-human immunoPET imaging of COVID-19 convalescent patients using dynamic total-body PET and a CD8-targeted minibody.

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.

Metabolic interactions between organs in overweight and obesity using total-body positron emission tomography.

Overweight and obesity is a complex condition resulting from unbalanced energy homeostasis among various organs. However, systemic abnormalities in overweight and obese people are seldom explored in vivo by metabolic imaging techniques. The aim of this study was to determine metabolic abnormities throughout the body in overweight and obese adults using total-body positron emission tomography (PET) glucose uptake imaging. Thirty normal weight subjects [body mass index (BMI) < 25 kg/m2, 55.47 ± 13.94 years, 16 men and 14 women], and 26 overweight and obese subjects [BMI ≥ 25 kg/m2, 52.38 ± 9.52 years, 21 men and 5 women] received whole-body 18F-fluorodeoxyglucose PET imaging using the uEXPLORER. Whole-body standardized uptake value normalized by lean body mass (SUL) images were calculated. Metabolic networks were constructed based on the whole-body SUL images using covariance network approach. Both group-level and individual-level network differences between normal weight and overweight/obese subjects were evaluated. Correlation analysis was conducted between network properties and BMI for the overweight/obese subjects. Compared with normal weight subjects, overweight/obese subjects exhibited altered network connectivity strength in four network nodes, namely the pancreas (p = 0.033), spleen (p = 0.021), visceral adipose tissue (VAT) (p = 1.12 × 10-5) and bone (p = 0.021). Network deviations of overweight/obese subjects from the normal weight were positively correlated with BMI (r = 0.718, p = 3.64 × 10-5). In addition, overweight/obese subjects experienced altered connections between organs, and some of the altered connections, including pancreas-right lung and VAT-bilateral lung connections were significantly correlated with BMI. Overweight/obese individuals exhibit metabolic alterations in organ level, and altered metabolic interactions at the systemic level. The proposed approach using total-body PET imaging can reveal individual metabolic variability and metabolic deviations between organs, which would open up a new path for understanding metabolic alterations in overweight and obesity.

Short-axis PET image quality improvement based on a uEXPLORER total-body PET system through deep learning.

The axial field of view (AFOV) of a positron emission tomography (PET) scanner greatly affects the quality of PET images. Although a total-body PET scanner (uEXPLORER) with a large AFOV is more sensitive, it is more expensive and difficult to widely use. Therefore, we attempt to utilize high-quality images generated by uEXPLORER to optimize the quality of images from short-axis PET scanners through deep learning technology while controlling costs. The experiments were conducted using PET images of three anatomical locations (brain, lung, and abdomen) from 335 patients. To simulate PET images from different axes, two protocols were used to obtain PET image pairs (each patient was scanned once). For low-quality PET (LQ-PET) images with a 320-mm AFOV, we applied a 300-mm FOV for brain reconstruction and a 500-mm FOV for lung and abdomen reconstruction. For high-quality PET (HQ-PET) images, we applied a 1940-mm AFOV during the reconstruction process. A 3D Unet was utilized to learn the mapping relationship between LQ-PET and HQ-PET images. In addition, the peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) were employed to evaluate the model performance. Furthermore, two nuclear medicine doctors evaluated the image quality based on clinical readings. The generated PET images of the brain, lung, and abdomen were quantitatively and qualitatively compatible with the HQ-PET images. In particular, our method achieved PSNR values of 35.41 ± 5.45dB (p < 0.05), 33.77 ± 6.18dB (p < 0.05), and 38.58 ± 7.28dB (p < 0.05) for the three beds. The overall mean SSIM was greater than 0.94 for all patients who underwent testing. Moreover, the total subjective quality levels of the generated PET images for three beds were 3.74 ± 0.74, 3.69 ± 0.81, and 3.42 ± 0.99 (the highest possible score was 5, and the minimum score was 1) from two experienced nuclear medicine experts. Additionally, we evaluated the distribution of quantitative standard uptake values (SUV) in the region of interest (ROI). Both the SUV distribution and the peaks of the profile show that our results are consistent with the HQ-PET images, proving the superiority of our approach. The findings demonstrate the potential of the proposed technique for improving the image quality of a PET scanner with a 320mm or even shorter AFOV. Furthermore, this study explored the potential of utilizing uEXPLORER to achieve improved short-axis PET image quality at a limited economic cost, and computer-aided diagnosis systems that are related can help patients and radiologists.

AI for PET image reconstruction.

Image reconstruction for positron emission tomography (PET) has been developed over many decades, with advances coming from improved modelling of the data statistics and improved modelling of the imaging physics. However, high noise and limited spatial resolution have remained issues in PET imaging, and state-of-the-art PET reconstruction has started to exploit other medical imaging modalities (such as MRI) to assist in noise reduction and enhancement of PET's spatial resolution. Nonetheless, there is an ongoing drive towards not only improving image quality, but also reducing the injected radiation dose and reducing scanning times. While the arrival of new PET scanners (such as total body PET) is helping, there is always a need to improve reconstructed image quality due to the time and count limited imaging conditions. Artificial intelligence (AI) methods are now at the frontier of research for PET image reconstruction. While AI can learn the imaging physics as well as the noise in the data (when given sufficient examples), one of the most common uses of AI arises from exploiting databases of high-quality reference examples, to provide advanced noise compensation and resolution recovery. There are three main AI reconstruction approaches: (i) direct data-driven AI methods which rely on supervised learning from reference data, (ii) iterative (unrolled) methods which combine our physics and statistical models with AI learning from data, and (iii) methods which exploit AI with our known models, but crucially can offer benefits even in the absence of any example training data whatsoever. This article reviews these methods, considering opportunities and challenges of AI for PET reconstruction.

Accurate modeling and performance evaluation of a total-body pet scanner using Monte Carlo simulations.

The limited axial field-of-view (FOV) of conventional clinical positron emission tomography (PET) scanners (∼15 to 26cm) allows detecting only 1% of all coincidence photons, hence limiting significantly their sensitivity. To overcome this limitation, the EXPLORER consortium developed the world's first total-body PET/CT scanner that significantly increased the sensitivity, thus enabling to decrease the scan duration or injected dose. The purpose of this study is to perform and validate Monte Carlo simulations of the uEXPLORER PET scanner, which can be used to devise novel conceptual designs and geometrical configurations through obtaining features that are difficult to obtain experimentally. The total-body uEXPLORER PET scanner was modeled using GATE Monte Carlo (MC) platform. The model was validated through comparison with experimental measurements of various performance parameters, including spatial resolution, sensitivity, count rate performance, and image quality, according to NEMA-NU2 2018 standards. Furthermore, the effects of the time coincidence window and maximum ring difference on the count rate and noise equivalent count rate (NECR) were evaluated. Overall, the validation study showed that there was a good agreement between the simulation and experimental results. The differences between the simulated and experimental total sensitivityfor the NEMA and extended phantoms at the center of the FOV were2.3% and 0.0%, respectively. The difference in peakNECR was 9.9% for the NEMA phantom and 1.0% for the extended phantom. The average bias between the simulated and experimental results of the full-width-at-half maximum (FWHM) for six different positions and three directions was 0.12mm. The simulations showed that using a variable coincidence time window based on the maximum ring difference can reduce the effect of random coincidences and improve the NECR compared to a constant time coincidence window. The NECR corresponding to 252-ring difference was 2.11 Mcps, which is larger than the NECR corresponding to 336-ring difference (2.04 Mcps). The developed MC model of the uEXPLORER PET scanner was validated against experimental measurements and can be used for further assessment and design optimization of the scanner.

Different hydration protocols for the quantification of healthy tissue uptake of half-dose 18F-FDG total-body positron emission tomography-computed tomography: a prospective study.

This study aimed to investigate the effects of the volume and time of hydration on the quantification of healthy tissue uptake for 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) total-body positron emission tomography (PET)-computed tomography (CT) with half-dose activity. This study prospectively enrolled 180 patients who underwent a total-body PET-CT scan 10 min after injection of a half-dose (1.85 MBq/kg) of 18F-FDG. These patients were placed in hydration groups (30 patients in each group) according to different hydration volumes and times: oral hydration with 500 mL of water 20 min before (G1), 5 min after (G2), and 30 min after (G3) the 18F-FDG injection; and oral hydration with 200 mL of water 20 min before (G4), 5 min after (G5), and 30 min after (G6) the 18F-FDG injection. Another 30 patients underwent dynamic imaging without hydration and were used a nonhydration group. The analysis of quantification of healthy tissue uptake included the maximum standardized uptake value (SUVmax) and the mean SUV (SUVmean) of the blood pool and muscle, as well as the SUVmax, SUVmean, and signal-to-noise ratio (SNR) of the liver. The SUVmax of the blood pool (2.33±0.36), liver (3.03±0.42), and muscle (0.81±0.15) was significantly higher in the nonhydration group than in any of the 6 hydrated groups (P<0.05 for all hydration groups vs. nonhydration group). Muscle SUVmax and SUVmean were significantly (P<0.05) lower in G1 and G2 than in G3 and were lower in G4 and G5 than in G6. The SUVmax and SUVmean of the blood pool were significantly (P<0.05) lower in G1 than in G3 and G4 and lower in G3 than in G6. When total-body PET-CT with a half dose of 18F-FDG activity is performed, hydration can significantly affect the quantification of healthy tissue uptake. Oral administration of 500 mL of water 20 min before injection could reduce background radioactivity.

On timing-optimized SiPMs for Cherenkov detection to boost low cost time-of-flight PET

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 mm3 and 243 ps for 3 × 3 × 20 mm3 BGO crystals. We further show that with these devices a CTR of 106 ps is possible using commercially available 3 × 3 × 20 mm3 LYSO:Ce,Mg crystals. To give an insight in the timing properties of these SiPMs, we measured the SPTR with black coated PbF2 of 2 × 2 × 3 mm3 size. 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 mm2 area 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.

Glucose uptake and distribution across the human skeleton using state-of-the-art total-body PET/CT

A growing number of studies have demonstrated that the skeleton is an endocrine organ that is involved in glucose metabolism and plays a significant role in human glucose homeostasis. However, there is still a limited understanding of the in vivo glucose uptake and distribution across the human skeleton. To address this issue, we aimed to elucidate the detailed profile of glucose uptake across the skeleton using a total-body positron emission tomography (PET) scanner. A total of 41 healthy participants were recruited. Two of them received a 1-hour dynamic total-body 18F-fluorodeoxyglucose (18F-FDG) PET scan, and all of them received a 10-minute static total-body 18F-FDG PET scan. The net influx rate (Ki) and standardized uptake value normalized by lean body mass (SUL) were calculated as indicators of glucose uptake from the dynamic and static PET data, respectively. The results showed that the vertebrae, hip bone and skull had relatively high Ki and SUL values compared with metabolic organs such as the liver. Both the Ki and SUL were higher in the epiphyseal, metaphyseal and cortical regions of long bones. Moreover, trends associated with age and overweight with glucose uptake (SULmax and SULmean) in bones were uncovered. Overall, these results indicate that the skeleton is a site with significant glucose uptake, and skeletal glucose uptake can be affected by age and dysregulated metabolism.

Evaluation of cost-effective system designs for long axial field-of-view PET scanners

Objective. Current commercial positron emission tomography (PET) scanners have excellent performance and diagnostic image quality primarily due to improvements in scanner sensitivity and time-of-flight (TOF) resolution. Recent years have seen the development of total-body PET scanners with longer axial field-of-view (AFOV) that increase sensitivity for single organ imaging, and also image more of the patient in a single bed position thereby enabling multi-organ dynamic imaging. While studies have shown significant capabilities of these systems, cost will be a major factor in their widespread adoption in the clinic. Here we evaluate alternative designs that achieve many advantages of long AFOV PET while utilizing cost-effective detector hardware. Approach. We utilize Monte Carlo simulations and clinically relevant lesion detectability metric to study the impact of scintillator type lutetium oxyorthosilicate or bismuth germanate (LSO or BGO), scintillator thickness (10–20 mm), and TOF resolution on resultant image quality in a 72 cm long scanner. Detector TOF resolution was varied based on current scanner performance, as well as expected future performance from detector designs that currently hold most promise for scaling into a scanner. Main results. Results indicate that BGO is competitive with LSO (both 20 mm thick) if we assume that it uses TOF (e.g. Cerenkov timing with 450 ps fwhm and Lorentzian distribution) and the LSO scanner has TOF resolution similar to the latest PMT-based scanners (∼500–650 ps). Alternatively, a system using 10 mm thick LSO with 150 ps TOF resolution can also provide similar performance. Both these alternative systems can provide cost savings (25%–33%) relative to a scanner using 20 mm LSO with ∼50% of effective sensitivity, but still 500%–700% higher than a conventional AFOV scanner. Significance. Our results have relevance to the development of long AFOV PET, where reduced cost of these alternative designs can provide wider accessibility for use in situations requiring imaging of multiple organs simultaneously.

Colloquium : Positronium physics and biomedical applications

Positronium is the simplest bound state, built of an electron and a positron. Studies of positronium in vacuum and its decays in medium tell us about Quantum Electrodynamics, QED, and about the structure of matter and biological processes of living organisms at the nanoscale, respectively. Spectroscopic measurements constrain our understanding of QED bound state theory. Searches for rare decays and measurements of the effect of gravitation on positronium are used to look for new physics phenomena. In biological materials positronium decays are sensitive to the inter- and intra-molecular structure and to the metabolism of living organisms ranging from single cells to human beings. This leads to new ideas of positronium imaging in medicine using the fact that during positron emission tomography (PET) as much as 40% of positron annihilation occurs through the production of positronium atoms inside the patient's body. A new generation of the high sensitivity and multi-photon total-body PET systems opens perspectives for clinical applications of positronium as a biomarker of tissue pathology and the degree of tissue oxidation.

Long Axial Field-of-View PET/CT Could Answer Unmet Needs in Gynecological Cancers.

Gynecological malignancies currently affect about 3.5 million women all over the world. Imaging of uterine, cervical, vaginal, ovarian, and vulvar cancer still presents several unmet needs when using conventional modalities such as ultrasound, computed tomography (CT), magnetic resonance, and standard positron emission tomography (PET)/CT. Some of the current diagnostic limitations are represented by differential diagnosis between inflammatory and cancerous findings, detection of peritoneal carcinomatosis and metastases <1 cm, detection of cancer-associated vascular complications, effective assessment of post-therapy changes, as well as bone metabolism and osteoporosis assessment. As a result of recent advances in PET/CT instrumentation, new systems now offer a long-axial field-of-view (LAFOV) to image between 106 cm and 194 cm (i.e., total-body PET) of the patient's body simultaneously and feature higher physical sensitivity and spatial resolution compared to standard PET/CT systems. LAFOV PET could overcome the forementioned limitations of conventional imaging and provide valuable global disease assessment, allowing for improved patient-tailored care. This article provides a comprehensive overview of these and other potential applications of LAFOV PET/CT imaging for patients with gynecological malignancies.

Comparative studies of plastic scintillator strips with high technical attenuation length for the total-body J-PET scanner

Plastic scintillator strips are considered as one of the promising solutions for the cost-effective construction of total-body positron emission tomography, (PET) system. The purpose of the performed measurements is to compare the transparency of long plastic scintillators with dimensions 6 mm × 24 mm × 1000 mm and with all surfaces polished. Six different types of commercial, general purpose, blue-emitting plastic scintillators with low attenuation of visible light were tested, namely: polyvinyl toluene-based BC-408, EJ-200, RP-408, and polystyrene-based Epic, SP32 and UPS-923A. For determination of the best type of plastic scintillator for total-body Jagiellonian positron emission tomograph (TB-J-PET) construction, emission and transmission spectra, and technical attenuation length (TAL) of blue light-emitting by the scintillators were measured and compared. The TAL values were determined with the use of UV lamp as excitation source, and photodiode as light detector. Emission spectra of investigated scintillators have maxima in the range from 420 nm to 429 nm. The BC-408 and EJ-200 have the highest transmittance values of about 90% at the maximum emission wavelength measured through a 6 mm thick scintillator strip and the highest technical attenuation length reaching about 2000 mm, allowing assembly of long detection modules for time-of-flight (TOF) J-PET scanners. Influence of the 6 mm × 6 mm, 12 mm × 6 mm, 24 mm × 6 mm cross-sections of the 1000 mm long EJ-200 plastic scintillator on the TAL and signal intensity was measured. The highest TAL value was determined for samples with 24 mm × 6 mm cross-section.