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Aim: To assess in a phantom and in a clinical study the influence of different reconstruction parameters on quantitative SPECT/CT values in the assessment of cardiac transthyretin amyloidosis (ATTR-CA)., Method: A hybrid SPECT/CT camera with a proprietary software for SPECT/CT-based quantification of myocardial uptake of 99m Tc-DPD was used. Images were reconstructed with 6 different protocols, differing in iterations, subset and Gaussian filter. Quantitative values were tested in phantom and clinical studies across different reconstruction protocols. Values were automatically calculated both as kBq/ml and as maximum, mean and peak standardized uptake value (SUV)., Results: The standard parameters provided by the manufacturer (reconstruction 1) yielded higher accuracy in quantifying, with measuring 97.1% of the expected activity in the phantom. Reconstructions with higher Gaussian filter caused a systematic underestimation of quantified values of 27.2% (p < 0.01). Results were replicated in the clinical study consisting of 155 patients with suspected ATTR-CA, wherein changing the number of iterations and subsets was not associated with a statistically significant difference in quantitative values compared to reconstruction 1, while a higher Gaussian filter caused inaccurate quantification with up to 24% of difference measured., Conclusion: Different reconstruction parameters can impact quantitative values on 99m Tc-DPD SPECT/CT. Therefore, parameters should be maintained consistently across different acquisitions and different centres., Competing Interests: Declarations Competing interests The authors declare no competing interests. Disclosures Robin Schepers has received speaker honoraria from Siemens. Christoph Gräni receives funding from the Swiss National Science foundation, InnoSuisse, CAIM foundation, GAMBIT foundation and Novartis biomedical research foundation, outside of the submitted work. Axel Rominger has received research support and speaker honoraria from Siemens. Federico Caobelli is currently supported by a research grant by Siemens Healthineers and receives speakers Honoraria by Bracco AG and Pfizer AG for matters not related to the present manuscript. All other authors have no competing interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Total body (TB) Positron Emission Tomography (PET) / Computed Tomography (CT) scanners have revolutionized nuclear medicine by enabling whole-body imaging in a single bed position. 1 This review assesses the physical and clinical value of TB-PET/CT, with a focus on the advancements in both static and dynamic imaging, as well as the evolving quantification techniques. The significantly enhanced sensitivity of TB scanners can reduce radiation exposure and scan time, offering improved patient comfort and making it particularly useful for pediatric imaging and various other scenarios. Shorter scan times also decrease motion artifacts, leading to higher-quality images and better diagnostic accuracy. Dynamic PET imaging with TB scanners extends these advantages by capturing temporal changes in tracer uptake over time, providing real-time insights into both structural and functional assessment, and promoting the ability to monitor disease progression and treatment response. We also present CT-free attenuation correction methods that utilize the increased sensitivity of TB-PET as a potential improvement for dynamic TB-PET protocols. In static imaging, emerging quantification techniques such as dual-tracer PET using TB scanners allow imaging of two biological pathways, simultaneously, for a more comprehensive assessment of disease. In addition, positronium imaging, a novel technique utilizing positronium lifetime measurements, is introduced as a promising aspect for providing structural information alongside functional quantification. Finally, the potential of expanding clinical applications with the increased sensitivity of TB-PET/CT scanners is discussed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Narendra Rathod reports financial support was provided by University of Bern. Narendra Rathod reports a relationship with University of Bern that includes: employment. I am Narendra Rathod working as a Post-doc in University of Bern is my relation with the University and hence with the funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: High blood glucose (hBG) in patients undergoing [ 18 F]FDG PET/CT scans often results in rescheduling the examination, which may lead to clinical delay for the patient and decrease productivity for the department. The aim of this study was to evaluate whether long-axial field-of-view (LAFOV) PET/CT can minimize the effect of altered bio-distribution in hBG patients and is able to provide diagnostic image quality in hBG situations., Materials and Methods: Oncologic patients with elevated blood glucose (≥ 8.0 mmol/l) and normal blood glucose (< 8.0 mmol/l, nBG) levels were matched for tumor entity, gender, age, and BMI. hBG patients were further subdivided into two groups (BG 8-11 mmol/l and BG > 11 mmol/l). Tracer uptake in the liver, muscle, and tumor was evaluated. Furthermore, image quality was compared between long acquisitions (ultra-high sensitivity mode, 360 s) on a LAFOV PET/CT and routine acquisitions equivalent to a short-axial field-of-view scanner (simulated (sSAFOV), obtained with high sensitivity mode, 120 s). Tumor-to-background ratio (TBR) and contrast-to-noise ratio (CNR) were used as the main image quality criteria., Results: Thirty-one hBG patients met the inclusion criteria and were matched with 31 nBG patients. Overall, liver uptake was significantly higher in hBG patients (SUV mean , 3.07 ± 0.41 vs. 2.37 ± 0.33; p = 0.03), and brain uptake was significantly lower (SUV max , 7.58 ± 0.74 vs. 13.38 ± 3.94; p < 0.001), whereas muscle (shoulder/gluteal) uptake showed no statistically significant difference. Tumor uptake was lower in hBG patients, resulting in a significantly lower TBR in the hBG cohort (3.48 ± 0.74 vs. 5.29 ± 1.48, p < 0.001). CNR was higher in nBG compared to hBG patients (12.17 ± 4.86 vs. 23.31 ± 12.22, p < 0.001). However, subgroup analysis of nBG 8-11 mmol/l on sSAFOV PET/CT compared to hBG (> 11 mmol/l) patients examined with LAFOV PET/CT showed no statistical significant difference in CNR (19.84 ± 8.40 vs. 17.79 ± 9.3, p = 0.08)., Conclusion: While elevated blood glucose (> 11 mmol) negatively affected TBR and CNR in our cohort, the images from a LAFOV PET-scanner had comparable CNR to PET-images acquired from nBG patients using sSAFOV PET/CT. Therefore, we argue that oncologic patients with increased blood sugar levels might be imaged safely with LAFOV PET/CT when rescheduling is not feasible., (© 2024. The Author(s).)

Purpose: The physical properties of yttrium-90 ( 90 Y) allow for imaging with positron emission tomography/computed tomography (PET/CT). The increased sensitivity of long axial field-of-view (LAFOV) PET/CT scanners possibly allows to overcome the small branching ratio for positron production from 90 Y decays and to improve for the post-treatment dosimetry of 90 Y of selective internal radiation therapy., Methods: For the challenging case of an image quality body phantom, we compare a full Monte Carlo (MC) dose calculation with the results from the two commercial software packages Simplicit90Y and Hermes. The voxel dosimetry module of Hermes relies on the 90 Y images taken with a LAFOV PET/CT, while the MC and Simplicit90Y dose calculations are image independent., Results: The resulting doses from the MC calculation and Simplicit90Y agree well within the error margins. The image-based dose calculation with Hermes, however, consistently underestimates the dose. This is due to the mismatch of the activity distribution in the PET images and the size of the volume of interest. We found that only for the smallest phantom sphere there is a statistically significant dependence of the Hermes dose on the image reconstruction parameters and scan time., Conclusion: Our study shows that Simplicit90Y's local deposition model can provide a reliable dose estimate. On the other hand, the image based dose calculation suffers from the suboptimal reconstruction of the 90 Y distribution in small structures., Competing Interests: Declaration of competing interest HS is a full-time employee of Siemens Healthcare AG, Switzerland. AR has received research support and speaker honoraria from Siemens. All other authors have no conflicts of interest to report., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

We report the dosimetric evaluation of prostate-specific membrane antigen-based radioligand therapy (RLT) for metastatic prostate cancer in a patient with autosomal-dominant polycystic kidney disease. Methods: The patient received hemodialysis during each of 6 RLT cycles while staying as an inpatient. We used voxel dosimetry and blood sampling for the dose calculation. Results: The patient responded well to the RLT, as indicated by the prostate-specific antigen level decreasing from 298 to 7.1 ng/mL. The doses per cycle ranged from 0.19 to 0.4 Gy/GBq for the parotid gland, 0.14 to 0.28 Gy/GBq for the submandibular gland, 0.03 to 0.11 Gy/GBq per kidney, and 0.10 to 0.15 Gy/GBq for the red bone marrow. Conclusion: This case suggests that [ 177 Lu]Lu-PSMA-based RLT can be applied successfully and safely to a patient with chronic kidney disease undergoing hemodialysis., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: Long axial field-of-view (LAFOV) PET/CT showed improved performance resulting from higher sensitivity. The aim was to quantify the impact of using the full acceptance angle (UHS) in image reconstructions with the Biograph Vision Quadra LAFOV PET/CT (Siemens Healthineers) compared to the limited acceptance angle (high sensitivity mode, HS)., Methods: 38 oncological patients examined on a LAFOV Biograph Vision Quadra PET/CT were analysed. 15 patients underwent [ 18 F]FDG-PET/CT, 15 patients underwent [ 18 F]PSMA-1007 PET/CT, and 8 patients underwent [ 68 Ga]Ga-DOTA-TOC PET/CT. Signal-to-noise ratio (SNR) and standardised uptake values (SUV mean/max/peak ) were used to compare UHS and HS with different acquisition times., Results: The SNR was significantly higher for UHS compared to HS over all acquisition times (SNR UHS/HS [ 18 F]FDG: 1.35 ± 0.02, p < 0.001; [ 18 F]PSMA-1007: 1.25 ± 0.02, p < 0.001; [ 68 Ga]Ga-DOTA-TOC: 1.29 ± 0.02, p < 0.001)., Conclusion: UHS showed significantly higher SNR opening the possibility of halving short acquisition times. This is of advantage in further reduction of whole-body PET/CT acquisition., (© 2023. The Author(s).)

Purpose: Performing 2-[ 18 F]FDG PET/CT in addition to a PSMA-ligand PET/CT can assist in the detection of lesions with low PSMA expression and may help in prognostication and identification of patients who likely benefit from PSMA-radioligand therapy (PSMA-RLT). However, the cost and time needed for a separate PET/CT examination might hinder its routine implementation. In this communication, we present our initial experiences with additional low-dose 2-[ 18 F]FDG PET/CT as part of a dual-tracer and same-day imaging protocol which exploits the higher sensitivity exhibited by long-axial field-of-view (LAFOV) and total-body PET/CT systems and demonstrates its feasibility., Methods: Fourteen patients referred for evaluation for PSMA-RLT received [ 68  Ga]Ga-PSMA-11 PET/CT at 1 h p.i. with a standard activity of 150 MBq and an additional low-dose 2-[ 18 F]FDG PET/CT with 40 MBq 1 h thereafter using a long-axial field-of-view PET/CT system in a single sitting and as per institutional protocol. Scans were scrutinized by two experienced nuclear medicine physicians for mismatch findings., Results: The combined protocol identified additional lesions with low or absent PSMA-expression but high FDG-avidity in 1/14 (7%) patients. The protocol was easily implemented and well tolerated by all patients., Conclusion: Additional low-dose 2-[ 18 F]FDG-PET/CT is feasible as part of a same-day imaging protocol and can help reveal lesions of low PSMA avidity as part of therapy assessment for [ 177 Lu]-PSMA radioligand therapy and demonstrates higher sensitivity compared to [ 68  Ga]Ga-PSMA-11 PET/CT alone in some patients., (© 2022. The Author(s).)

Despite the potential of deep learning (DL)-based methods in substituting CT-based PET attenuation and scatter correction for CT-free PET imaging, a critical bottleneck is their limited capability in handling large heterogeneity of tracers and scanners of PET imaging. This study employs a simple way to integrate domain knowledge in DL for CT-free PET imaging. In contrast to conventional direct DL methods, we simplify the complex problem by a domain decomposition so that the learning of anatomy-dependent attenuation correction can be achieved robustly in a low-frequency domain while the original anatomy-independent high-frequency texture can be preserved during the processing. Even with the training from one tracer on one scanner, the effectiveness and robustness of our proposed approach are confirmed in tests of various external imaging tracers on different scanners. The robust, generalizable, and transparent DL development may enhance the potential of clinical translation., (© 2022. The Author(s).)

Purpose: Prostate-specific membrane antigen (PSMA)-targeted PET is increasingly used for staging prostate cancer (PCa) with high accuracy to detect significant PCa (sigPCa). [ 68  Ga]PSMA-11 PET/MRI-guided biopsy showed promising results but also persisting limitation of sampling error, due to impaired image fusion. We aimed to assess the possibility of intraoperative quantification of [ 18 F]PSMA-1007 PET/CT uptake in core biopsies as an instant confirmation for accurate lesion sampling., Methods: In this IRB-approved, prospective, proof-of-concept study, we included five consecutive patients with suspected PCa. All underwent [ 18 F]PSMA-1007 PET/CT scans followed by immediate PET/CT-guided and saturation template biopsy (3.1 ± 0.3 h after PET). The activity in biopsy cores was measured as counts per minute (cpm) in a gamma spectrometer. Pearson's test was used to correlate counts with histopathology (WHO/ISUP), tumor length, and membranous PSMA expression on immunohistochemistry (IHC)., Results: In 43 of 113 needles, PCa was present. The mean cpm was overall significantly higher in needles with PCa (263 ± 396 cpm) compared to needles without PCa (73 ± 44 cpm, p < 0.001). In one patient with moderate PSMA uptake (SUV max 8.7), 13 out of 24 needles had increased counts (100-200 cpm) but only signs of inflammation and PSMA expression in benign glands on IHC. Excluding this case, ROC analysis resulted in an AUC of 0.81, with an optimal cut-off to confirm PCa at 75 cpm (sens/spec of 65.1%/87%). In all 4 patients with PCa, the first or second PSMA PET-guided needle was positive for sigPCa with high counts (156-2079 cpm)., Conclusions: [ 18 F]PSMA-1007 uptake in PCa can be used to confirm accurate lesion sampling of the dominant tumor intraoperatively. This technique could improve confidence in imaging-based biopsy guidance and reduce the need for saturation biopsy., Trial Registration Number: NCT03187990, 15/06/2017., (© 2021. The Author(s).)

Purpose: Ex vivo liver machine perfusion is a promising option to rescue marginal liver grafts mitigating the donated organ shortage. Recently, a novel liver perfusion machine that can keep injured liver grafts alive for 1 week ex vivo was developed and reported in Nature Biotechnology. However, liver viability assessment ex vivo is an unsolved issue and the value of 18F-fluorodeoxyglucose (FDG)-PET/CT for such purpose was explored., Materials and Methods: Discarded two human and six porcine liver grafts underwent FDG-PET/CT for viability assessment after 1 week of ex vivo perfusion. PET parameters [standardized uptake value (SUV)max, SUVmean, SUVpeak and total lesion glycolysis] were compared between hepatic lobes and between porcine and human livers. The prevalence of FDG-negative organ parts was recorded. The estimated effective radiation dose for PET/CT was calculated., Results: All organs were viable with essentially homogeneous FDG uptake. Of note, viability was preserved in contact areas disclosing the absence of pressure necrosis. Four porcine and two human organs had small superficial FDG-negative areas confirmed as biopsy sites. Total lesion glycolysis was significantly higher in the right hepatic lobe (P = 0.012), while there was no significant difference of SUVmax, SUVmean and SUVpeak between hepatic lobes. There was no significant difference in FDG uptake parameters between porcine and human organs. The estimated effective radiation dose was 1.99 ± 1.67 mSv per organ., Conclusion: This study demonstrates the feasibility of FDG-PET/CT for viability assessment of ex vivo perfused liver grafts after 1 week., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We assessed and compared image quality obtained with clinical 18 F-FDG whole-body oncologic PET protocols used in three different, state-of-the-art digital PET/CT and two conventional PMT-based PET/CT devices. Our goal was to evaluate an  improved trade-off between administered activity (patient dose exposure/signal-to-noise ratio) and acquisition time (patient comfort) while preserving diagnostic information achievable with the recently introduced digital detector technology compared to previous analogue PET technology., Methods: We performed list-mode (LM) PET acquisitions using a NEMA/IEC NU2 phantom, with activity concentrations of 5 kBq/mL and 25 kBq/mL for the background (9.5 L) and sphere inserts, respectively. For each device, reconstructions were obtained varying the image statistics (10, 30, 60, 90, 120, 180, and 300 s from LM data) and the number of iterations (range 1 to 10) in addition to the employed local clinical protocol setup. We measured for each reconstructed dataset: the quantitative cross-calibration, the image noise on the uniform background assessed by the coefficient of variation (COV), and the recovery coefficients (RCs) evaluated in the hot spheres. Additionally, we compared the characteristic time-activity-product (TAP) that is the product of scan time per bed position × mass-activity administered (in min·MBq/kg) across datasets., Results: Good system cross-calibration was obtained for all tested datasets with < 6% deviation from the expected value was observed. For all clinical protocol settings, image noise was compatible with clinical interpretation (COV < 15%). Digital PET showed an improved background signal-to-noise ratio as compared to conventional PMT-based PET. RCs were comparable between digital and PMT-based PET datasets. Compared to PMT-based PET, digital systems provided comparable image quality with lower TAP (from ~ 40% less and up to 70% less)., Conclusions: This study compared the achievable clinical image quality in three state-of-the-art digital PET/CT devices (from different vendors) as well as in two conventional PMT-based PET. Reported results show that a comparable image quality is achievable with a TAP reduction of ~ 40% in digital PET. This could lead to a significant reduction of the administered mass-activity and/or scan time with direct benefits in terms of dose exposure and patient comfort.

Purpose: To evaluate the possible activity reduction in FDG-imaging in a Time-of-Flight (TOF) PET/MR, based on cross-evaluation of patient-based NECR (noise equivalent count rate) measurements in PET/CT, cross referencing with phantom-based NECR curves as well as initial evaluation of TOF-PET/MR with reduced activity., Materials and Methods: A total of 75 consecutive patients were evaluated in this study. PET/CT imaging was performed on a PET/CT (time-of-flight (TOF) Discovery D 690 PET/CT). Initial PET/MR imaging was performed on a newly available simultaneous TOF-PET/MR (Signa PET/MR). An optimal NECR for diagnostic purposes was defined in clinical patients (NECRP) in PET/CT. Subsequent optimal activity concentration at the acquisition time ([A]0) and target NECR (NECRT) were obtained. These data were used to predict the theoretical FDG activity requirement of the new TOF-PET/MR system. Twenty-five initial patients were acquired with (retrospectively reconstructed) different imaging times equivalent for different activities on the simultaneous PET/MR for the evaluation of clinically realistic FDG-activities., Results: The obtained values for NECRP, [A]0 and NECRT were 114.6 (± 14.2) kcps (Kilocounts per second), 4.0 (± 0.7) kBq/mL and 45 kcps, respectively. Evaluating the NECRT together with the phantom curve of the TOF-PET/MR device, the theoretical optimal activity concentration was found to be approximately 1.3 kBq/mL, which represents 35% of the activity concentration required by the TOF-PET/CT. Initial evaluation on patients in the simultaneous TOF-PET/MR shows clinically realistic activities of 1.8 kBq/mL, which represent 44% of the required activity., Conclusion: The new TOF-PET/MR device requires significantly less activity to generate PET-images with good-to-excellent image quality, due to improvements in detector geometry and detector technologies. The theoretically achievable dose reduction accounts for up to 65% but cannot be fully translated into clinical routine based on the coils within the FOV and MR-sequences applied at the same time. The clinically realistic reduction in activity is slightly more than 50%. Further studies in a larger number of patients are needed to confirm our findings.

Background: Magnetic resonance (MR)-based attenuation correction is a critical component of integrated positron emission tomography (PET)/MR scanners. It is generally achieved by segmenting MR images into tissue classes with known attenuation properties (e.g., bone, fat, soft tissue, lung, air). Ultra-short echo time (UTE) have been proposed in the past to locate bone tissue. In this study, tri-modality computed tomography data was used to develop an improved algorithm for the localization of bone in the head and neck., Methods: Twenty patients were scanned using a tri-modality setup. A UTE acquisition with 22-cm transaxial and 24-cm axial field of view was acquired, with a resolution of 1.5 × 1.5 × 2.0 mm(3). The sequence consisted of two echoes (30 μs, 1.7 ms) with a flip angle of 10° and 125-kHz bandwidth. The CT images of all patients were classified by thresholding and used to compute maps of the posterior probability of each tissue class, given a pair of UTE echo values. The Jaccard distance was used to compare with CT the bone masks obtained when using this information to segment the UTE datasets., Results: The results show the desired bony structures as a cluster pattern in the space of dual-echo measurements. The clusters obtained for the tissue classes are strongly overlapped, indicating that the MR data will not, regardless of the chosen space partition, be able to completely differentiate the bony and soft structures. The classification obtained by maximizing the posterior probability compared well to previously published methods, providing a more intuitive and robust choice of the final classification threshold. The distance between MR- and CT-based bone masks was 59% on average (0% being a perfect match), compared to 76% and 69% for two previously published methods., Conclusions: The study of tri-modality datasets shows that improved bone tissue classification can be achieved by estimating maps of the posterior probability of voxels belonging to a particular tissue class, given a measured pair of UTE echoes.