Simultaneous 18-FDG PET and MR imaging in lower extremity arterial disease.

Background: Simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) is a novel hybrid imaging method integrating the advances of morphological tissue characterization of MRI with the pathophysiological insights of PET applications. Aim: This study evaluated the use of simultaneous 18-FDG PET/MR imaging for characterizing atherosclerotic lesions in lower extremity arterial disease (LEAD). Methods: Eight patients with symptomatic stenoses of the superficial femoral artery (SFA) under simultaneous acquisition of 18-FDG PET and contrast-enhanced MRI using an integrated whole-body PET/MRI scanner. Invasive plaque characterization of the SFA was performed by intravascular imaging using optical coherence tomography. Histological analysis of plaque specimens was performed after directional atherectomy. Results: MRI showed contrast enhancement at the site of arterial stenosis, as assessed on T2-w and T1-w images, compared to a control area of the contralateral SFA (0.38 ± 0.15 cm vs. 0.23 ± 0.11 cm; 1.77 ± 0.19 vs. 1.57 ± 0.15; p-value <0.05). On PET imaging, uptake of 18F-FDG (target-to-background ratio TBR > 1) at the level of symptomatic stenosis was observed in all but one patient. Contrast medium-induced MR signal enhancement was detected in all plaques, whereas FDG uptake in PET imaging was increased in lesions with active fibroatheroma and reduced in fibrocalcified lesions. Conclusion: In this multimodal imaging study, we report the feasibility and challenges of simultaneous PET/MR imaging of LEAD, which might offer new perspectives for risk estimation.

Preclinical comparison of [177Lu]Lu-rhPSMA-10.1 and [177Lu]Lu-rhPSMA-10.2 for endoradiotherapy of prostate cancer: biodistribution and dosimetry studies.

BACKGROUND: Radiohybrid PSMA-targeted ligands (rhPSMA) have been introduced as a novel platform for theranostic applications. Among a variety of rhPSMA-ligands developed for radioligand therapy, two stereoisomers [177Lu]Lu-rhPSMA-10.1 and -10.2 have been synthesized and initially characterized in preclinical experiments with the aim to provide an optimized binding profile to human serum albumin, a reduction of charge, and thus accelerated kidney excretion, and unaffected or even improved tumor uptake. As both isomers showed similar in vitro characteristics and tumor uptake at 24 h post injection in tumor bearing mice and in order to identify the isomer with the most favorable pharmacokinetics for radioligand therapy, we carried out in-depth biodistribution and dosimetry studies in tumor-bearing and healthy mice. RESULTS: rhPSMA-10.1 and -10.2 were radiolabeled with lutetium-177 according to the established procedures of other DOTA-based PSMA ligands and displayed a high and comparable stability in all buffers and human serum (> 97%, 24 h). Biodistribution studies revealed fast clearance from the blood pool (0.3-0.6%ID/g at 1 h) and other background tissues within 48 h. Distinctive differences were found in the kidneys, where [177Lu]Lu-rhPSMA-10.1 displayed lower initial uptake and faster excretion kinetics compared to [177Lu]Lu-rhPSMA-10.2 expressed by a 1.5-fold and ninefold lower uptake value at 1 h and 24 h in healthy animals, respectively. Tumor uptake was comparable and in the range of 8.6-11.6%ID/g for both isomers over 24 h and was maintained up to 168 h at a level of 2.2 ± 0.8 and 4.1 ± 1.4%ID/g for [177Lu]Lu-rhPSMA-10.1 and [177Lu]Lu-rhPSMA-10.2, respectively. CONCLUSION: Our preclinical data on biodistribution and dosimetry indicate a more favorable profile of [177Lu]Lu-rhPSMA-10.1 compared to [177Lu]Lu-rhPSMA-10.2 for PSMA-targeted radioligand therapy. [177Lu]Lu-rhPSMA-10.1 shows fast kidney clearance kinetics resulting in excellent tumor-to-organ ratios over a therapy relevant time course. Meanwhile, [177Lu]Lu-rhPSMA-10.1 is currently being investigated in clinical phase I/II studies in patients with mCRPC (NCT05413850), in patients with high-risk localized PC (NCT06066437, Nautilus Trial) and after external beam radiotherapy (NCT06105918).

Validating a minipig model of reversible cerebral demyelination using human diagnostic modalities and electron microscopy.

BACKGROUND: Inflammatory demyelinating diseases of the central nervous system, such as multiple sclerosis, are significant sources of morbidity in young adults despite therapeutic advances. Current murine models of remyelination have limited applicability due to the low white matter content of their brains, which restricts the spatial resolution of diagnostic imaging. Large animal models might be more suitable but pose significant technological, ethical and logistical challenges. METHODS: We induced targeted cerebral demyelinating lesions by serially repeated injections of lysophosphatidylcholine in the minipig brain. Lesions were amenable to follow-up using the same clinical imaging modalities (3T magnetic resonance imaging, 11C-PIB positron emission tomography) and standard histopathology protocols as for human diagnostics (myelin, glia and neuronal cell markers), as well as electron microscopy (EM), to compare against biopsy data from two patients. FINDINGS: We demonstrate controlled, clinically unapparent, reversible and multimodally trackable brain white matter demyelination in a large animal model. De-/remyelination dynamics were slower than reported for rodent models and paralleled by a degree of secondary axonal pathology. Regression modelling of ultrastructural parameters (g-ratio, axon thickness) predicted EM features of cerebral de- and remyelination in human data. INTERPRETATION: We validated our minipig model of demyelinating brain diseases by employing human diagnostic tools and comparing it with biopsy data from patients with cerebral demyelination. FUNDING: This work was supported by the DFG under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198) and TRR 274/1 2020, 408885537 (projects B03 and Z01).

A Clinical Role of PET-MRI in Prostate Cancer?

PET/MRI is a relevant application field for prostate cancer management, offering advantages in early diagnosis, staging, and therapy planning. Despite drawbacks such as higher costs, longer acquisition time, and the need for skilled personnel, the technical integration of PET and MRI provides valuable information for detecting primary tumors, identifying metastases, and characterizing the disease, leading to more accurate staging and personalized treatment strategies. However, PET/MRI adoption has been slow, but ongoing technological advancements and AI integration might overcome challenges and improve clinical utility. As precision medicine gains importance in oncology, PET/MRI's multiparametric data can tailor treatment plans to individual patients, providing a comprehensive assessment of tumor biology and aggressiveness for more effective therapeutic strategies.

EFOMP policy statement NO. 19: Dosimetry in nuclear medicine therapy - Molecular radiotherapy.

The European Council Directive 2013/59/Euratom (BSS Directive) includes optimisation of treatment with radiotherapeutic procedures based on patient dosimetry and verification of the absorbed doses delivered. The present policy statement summarises aspects of three directives relating to the therapeutic use of radiopharmaceuticals and medical devices, and outlines the steps needed for implementation of patient dosimetry for radioactive drugs. To support the transition from administrations of fixed activities to personalised treatments based on patient-specific dosimetry, EFOMP presents a number of recommendations including: increased networking between centres and disciplines to support data collection and development of codes-of-practice; resourcing to support an infrastructure that permits routine patient dosimetry; research funding to support investigation into individualised treatments; inter-disciplinary training and education programmes; and support for investigator led clinical trials. Close collaborations between the medical physicist and responsible practitioner are encouraged to develop a similar pathway as is routine for external beam radiotherapy and brachytherapy. EFOMP's policy is to promote the roles and responsibilities of medical physics throughout Europe in the development of molecular radiotherapy to ensure patient benefit. As the BSS directive is adopted throughout Europe, unprecedented opportunities arise to develop informed treatments that will mitigate the risks of under- or over-treatments.

Preclinical Imaging of Cardiovascular Disesase.

Noninvasive imaging techniques, such as SPECT, PET, CT, echocardiography, or MRI, have become essential in cardiovascular research. They allow for the evaluation of biological processes in vivo without the need for invasive procedures. Nuclear imaging methods, such as SPECT and PET, offer numerous advantages, including high sensitivity, reliable quantification, and the potential for serial imaging. Modern SPECT and PET imaging systems, equipped with CT and MRI components in order to get access to morphological information with high spatial resolution, are capable of imaging a wide range of established and innovative agents in both preclinical and clinical settings. This review highlights the utility of SPECT and PET imaging as powerful tools for translational research in cardiology. By incorporating these techniques into a well-defined workflow- similar to those used in clinical imaging- the concept of "bench to bedside" can be effectively implemented.

The Impact of PSMA PET-Based Eligibility Criteria Used in the Prospective Phase II TheraP Trial in Metastatic Castration-Resistant Prostate Cancer Patients Undergoing Prostate-Specific Membrane Antigen-Targeted Radioligand Therapy.

Prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) has shown encouraging results for treatment of metastatic castration-resistant prostate cancer (mCRPC) in the prospective, multicenter, randomized phase II TheraP study. The inclusion criteria for that study comprised a pretherapeutic 68Ga-PSMA-11 PET scan showing sufficient tumor uptake using a predefined threshold and the absence of 18F-FDG-positive, PSMA ligand-negative tumor lesions. However, the prognostic value of these PET-based inclusion criteria remains unclear. Therefore, we evaluated the outcome of mCRPC patients treated with PSMA RLT using TheraP as well as other TheraP-based PET inclusion criteria. Methods: First, patients were dichotomized into 2 groups whose PSMA PET scans did (TheraP contrast-enhanced PSMA [cePSMA] PET-positive) or did not (TheraP cePSMA PET-negative) fulfill the inclusion criteria of TheraP. Notably, unlike in TheraP, 18F-FDG PET was not performed on our patients. Prostate-specific antigen (PSA) response (PSA decline ≥ 50% from baseline), PSA progression-free survival, and overall survival (OS) were compared. Additionally, patients were further dichotomized according to predefined SUVmax thresholds different from those used in TheraP to analyze their potential impact on outcome as well. Results: In total, 107 mCRPC patients were included in this analysis (TheraP cePSMA PET-positive, n = 77; TheraP cePSMA PET-negative, n = 30). PSA response rates were higher in TheraP cePSMA PET-positive patients than in TheraP cePSMA PET-negative patients (54.5% vs. 20%, respectively; P = 0.0012). The median PSA progression-free survival (P = 0.007) and OS (P = 0.0007) of patients were significantly longer in the TheraP cePSMA PET-positive group than in the TheraP cePSMA PET-negative group. Moreover, being in the TheraP cePSMA PET-positive group was identified as a significant prognosticator of longer OS (P = 0.003). The application of different SUVmax thresholds for a single hottest lesion demonstrated no influence on outcome in patients eligible for PSMA RLT. Conclusion: Patient selection for PSMA RLT according to the inclusion criteria of TheraP led to a better treatment response and outcome in our preselected patient cohort. However, a relevant number of patients not fulfilling these criteria also showed substantial rates of response.

Pentoxifylline reduces inflammation and prevents myocardial perfusion derangements in experimental chronic Chagas' cardiomyopathy.

BACKGROUND: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters. METHODS AND RESULTS: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm2), as compared to CH + SLN (515.1 ± 133.0 cell/mm2), but larger than CO (193.0 ± 25.7 cell/mm2). The fibrosis and TNF-α expression was higher in both infected groups. CONCLUSIONS: The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC.

Is there more than meets the eye in PSMA imaging in prostate cancer with PET/MRI? Looking closer at uptake time, correlation with PSA and Gleason score.

BACKGROUND: In patients with increasing PSA and suspicion for prostate cancer, but previous negative biopsies, PET/MRI is used to test for tumours and target potential following biopsy. We aimed to determine different PSMA PET timing effects on signal kinetics and test its correlation with the patients' PSA and Gleason scores (GS). METHODS: A total of 100 patients were examined for 900 s using PET/MRI approximately 1-2 h p.i. depending on the tracer used (68Ga-PSMA-11, 18F-PSMA-1007 or 18F-rhPSMA7). The scans were reconstructed in static and dynamic mode (6 equal frames capturing "late" PSMA dynamics). TACs were computed for detected lesions as well as linear regression plots against time for static (SUV) and dynamic (SUV, SUL, and percent injected dose per gram) parameters. All computed trends were tested for correlation with PSA and GS. RESULTS: Static and dynamic scans allowed unchanged lesion detection despite the difference in statistics. For all tracers, the lesions in the pelvic lymph nodes and bones had a mostly negative activity concentration trend (78% and 68%, resp.), while a mostly positive, stronger trend was found for the lesions in the prostate and prostatic fossa following RPE (84% and 83%, resp.). In case of 68Ga-PSMA-11, a strong negative (Rmin = - 0.62, Rmax = - 0.73) correlation was found between the dynamic parameters and the PSA. 18F-PSMA-1007 dynamic data showed no correlation with PSA, while for 18F-rhPSMA7 dynamic data, it was consistently low positive (Rmin = 0.29, Rmax = 0.33). All tracers showed only moderate correlation against GS (Rmin = 0.41, Rmax = 0.48). The static parameters showed weak correlation with PSA (Rmin = 0.24, Rmax = 0.36) and no correlation with GS. CONCLUSION: "Late" dynamic PSMA data provided additional insight into the PSMA kinetics. While a stable moderate correlation was found between the PSMA kinetics in pelvic lesions and GS, a significantly variable correlation with the PSA values was shown depending on the radiotracer used, the highest being consistently for 68Ga-PSMA-11. We reason that with such late dynamics, the PSMA kinetics are relatively stable and imaging could even take place at earlier time points as is now in the clinical routine.

Visualization of fibroblast activation using 68Ga-FAPI PET/CT after pulmonary vein isolation with pulsed field compared with cryoballoon ablation.

BACKGROUND: Pulsed-field ablation (PFA) is a novel ablation modality for atrial fibrillation (AF) ablating myocardium by electroporation without tissue-heating. With its different mechanism of tissue ablation, it is assumed that lesion creation is divergent to thermal energy sources. 68Ga-fibroblast-activation protein inhibitor (FAPI) PET/CT targets FAP-alpha expressed by activated fibroblasts. We aimed to assess 68Ga-FAPI uptake in pulmonary veins as surrogate for ablation damage after PFA and cryoballoon ablation (CBA). METHODS: 26 patients (15 PFA, 11 CBA) underwent 68Ga-FAPI-PET/CT after ablation. Standardized uptake values (SUV) and fibroblast-activation volumes of localized tracer uptake were assessed. RESULTS: Patient characteristics were comparable between groups. In PFA, focal FAPI uptake was only observed in 3/15 (20%) patients, whereas in the CBA cohort, 10/11 (90.9%) patients showed atrial visual uptake. We observed lower values of SUVmax (2.85 ± 0.56 vs 4.71 ± 2.06, P = 0.025) and FAV (1.13 ± 0.84 cm3 vs 3.91 ± 2.74 cm3, P = 0.014) along with a trend towards lower SUVpeak and SUVmean in PFA vs CBA patients, respectively. CONCLUSION: Tissue response with respect to fibroblast activation seems to be less pronounced in PFA compared to established thermal ablation systems. This functional assessment might contribute to a better understanding of lesion formation in thermal and PFA ablation potentially contributing to better safety outcomes.

Development of PSMA-PET-guided CT-based radiomic signature to predict biochemical recurrence after salvage radiotherapy.

PURPOSE: To develop a CT-based radiomic signature to predict biochemical recurrence (BCR) in prostate cancer patients after sRT guided by positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET). MATERIAL AND METHODS: Consecutive patients, who underwent 68Ga-PSMA11-PET/CT-guided sRT from three high-volume centers in Germany, were included in this retrospective multicenter study. Patients had PET-positive local recurrences and were treated with intensity-modulated sRT. Radiomic features were extracted from volumes of interests on CT guided by focal PSMA-PET uptakes. After preprocessing, clinical, radiomics, and combined clinical-radiomic models were developed combining different feature reduction techniques and Cox proportional hazard models within a nested cross validation approach. RESULTS: Among 99 patients, median interval until BCR was the radiomic models outperformed clinical models and combined clinical-radiomic models for prediction of BCR with a C-index of 0.71 compared to 0.53 and 0.63 in the test sets, respectively. In contrast to the other models, the radiomic model achieved significantly improved patient stratification in Kaplan-Meier analysis. The radiomic and clinical-radiomic model achieved a significantly better time-dependent net reclassification improvement index (0.392 and 0.762, respectively) compared to the clinical model. Decision curve analysis demonstrated a clinical net benefit for both models. Mean intensity was the most predictive radiomic feature. CONCLUSION: This is the first study to develop a PSMA-PET-guided CT-based radiomic model to predict BCR after sRT. The radiomic models outperformed clinical models and might contribute to guide personalized treatment decisions.

The impact of specific pulmonary arterial hypertension therapy on cardiac fluorodeoxyglucose distribution in PET/MRI hybrid imaging-follow-up study.

BACKGROUND: PET/MRI hybrid imaging in pulmonary arterial hypertension (PAH) provides important prognostic information identifying patients who might benefit from early therapy escalation, as right ventricle (RV) metabolic alterations are linked with hemodynamics and might precede clinical deterioration. Now, we hypothesize that adequate PAH therapy escalation may result in reversal of unfavourable increased glucose uptake of RV, which is associated with improved prognosis. METHODS: Out of twenty-six initially clinically stable PAH patients who had baseline PET/MRI scans, twenty (49.9 ± 14.9 years) had second PET/MRI after 24 months. SUVRV/SUVLV ratio was used to estimate and compare cardiac glucose uptake. Occurrences of clinical endpoints (CEP), defined as death or clinical deterioration, were assessed during 48-month follow-up from baseline. RESULTS: In first 24 months of observation, sixteen patients had CEP and needed PAH therapy escalation. At follow-up visits, we observed significant improvement of RV ejection fraction (45.1 ± 9.6% to 52.4 ± 12.9%, p = 0.01), mean pulmonary artery pressure (50.5 ± 18.3 to 42.8 ± 18.6 mmHg, p = 0.03), and SUVRV/SUVLV, which tended to decrease (mean change -0.20 ± 0.74). Patients with baseline SUVRV/SUVLV value higher than 0.54 had worse prognosis in 48 months observation (log-rank test, p = 0.0007); follow up SUVRV/SUVLV > 1 predicted CEP in the following 24 months, regardless of previously escalated treatment. CONCLUSIONS: PAH therapy escalation may influence RV glucose metabolism, what seems to be related with patients' prognosis. PET/MRI assessment may predict clinical deterioration regardless of previous clinical course, however its clinical significance in PAH requires further studies. Importantly, even mild alterations of RV glucose metabolism predict clinical deterioration in long follow-up. Clinical Trial Registration ClinicalTrials.gov, NCT03688698, 05/01/2016, https://clinicaltrials.gov/ct2/show/study/NCT03688698?term=NCT03688698&draw=2&rank=1.

Performance evaluation of a novel multi-pinhole collimator on triple-NaI-detector SPECT/CT for dedicated myocardial imaging.

BACKGROUND: In this study we evaluated the imaging capabilities of a novel Multi-pinhole collimator (MPH-Cardiac) specially designed for nuclear cardiology imaging on a Triple-NaI-detector based SPECT/CT system. METHODS: 99mTc point source measurements covering the field of view (FOV) were used to determine tomographic sensitivity (TSpointsource) and spatial resolution. Organ-size tomographic sensitivity (TSorgan) was measured with a left ventricle (LV) phantom filled with typical myocardial activity of a patient scan. Reconstructed image uniformity was measured with a 140 mm diameter uniform cylinder phantom. Using the LV phantom once filled with 99mTc and after with 123I, Contrast-to-noise ratio (CNR) was measured on the reconstructed images by ROI analysis on the myocardium activity and on the LV cavity. Furthermore, a polar map analysis was performed determining Spill-Over-Ratio in water (SORwater) and image noise. The results were compared with that of a dual-head parallel-hole low energy high resolution (LEHR) collimator system. A patient with suspected coronary artery disease (CAD) was scanned on the LEHR system using local protocol of 16 min total acquisition time, followed by a 4-min MPH-Cardiac scan. RESULTS: Peak TSpointsource was found to be 1013 cps/MBq in the axial center of the FOV while it was decreasing toward the radial edges. TSorgan in the CFOV was found to be 134 cps/MBq and 700 cps/MBq for the LEHR and MPH-Cardiac, respectively. Average spatial resolution throughout the FOV was 4.38 mm FWHM for the MPH-Cardiac collimator. Reconstructed image uniformity values were found to be 0.292% versus 0.214% for the LEHR and MPH-Cardiac measurements, respectively. CNR was found to be higher in case of MPH-Cardiac than for LEHR in case of 99mTc (15.5 vs. 11.7) as well as for 123I (13.5 vs. 8.3). SORwater values were found to be 28.83% and 21.1% for the 99mTc measurements, and 31.44% and 24.33% for the 123I measurements for LEHR and MPH-Cardiac, respectively. Pixel noise of the 99mTc polar maps resulted in values of 0.38% and 0.24% and of the 123I polar maps 0.62% and 0.21% for LEHR and MPH-Cardiac, respectively. Visually interpreting the patient scan images, MPH-Cardiac resulted in better image contrast compared to the LEHR technique with four times shorter scan duration. CONCLUSIONS: The significant image quality improvement achieved with dedicated MPH-Cardiac collimator on triple head SPECT/CT system paves the way for short acquisition and low-dose cardiovascular SPECT applications.

The influence of metastatic patterns and tumor load on therapeutic efficacy of immunotherapy in patients with metastatic melanoma as determined by quantitative PET-parameters using [ 18 F]-fluorodeoxyglucose PET/computed tomography.

The introduction of immunotherapy was a revolution in the treatment of metastatic melanoma. Nevertheless, there are only few clinical parameters to predict response to immunotherapy. The purpose of this study was to identify metastatic patterns that can predict response by using noninvasive 18 F-FDG PET/CT imaging. In 93 immunotherapy-treated patients, total metabolic tumor volume (MTV) was measured before and after treatment. The differences were compared to quantify therapy response. Patients were divided into seven subgroups regarding the affected organ systems. The results as well as clinical factors were evaluated in multivariate analyses. No subgroup of metastatic patterns had a significant difference in response rates, but with a trend towards poorer response regarding osseous and hepatic metastases. Osseous metastases presented with significant lower disease-specific survival (DSS) ( P = 0.001). Sole lymph node metastases were the only subgroup with MTV reduction and with significant higher DSS (57.6 months; P = 0.033). Patients, who ever developed brain metastases, showed a high progression of MTV of 201 ml ( P = 0.583) and poor DSS of 49.7 months ( P = 0.077). Lower numbers of affected organs indicated significantly higher DSS (hazard ratio, 1.346; P = 0.006). Osseous metastases represented a negative predictive factor for response to immunotherapy and survival. Cerebral metastases, especially when nonresponsive to immunotherapy, predicted poor survival and high increase of MTV. A high number of affected organ systems was identified as a negative factor for response and survival. Patients with only lymph node metastases showed a better response and survival.

Multi-center study of inter-rater reproducibility, image quality, and diagnostic accuracy of CZT versus conventional SPECT myocardial perfusion imaging.

BACKGROUND: Cadmium-zinc-telluride (CZT)-based detectors exhibit higher diagnostic sensitivity in myocardial perfusion imaging (MPI) than conventional Anger-MPI for detection of coronary artery disease (CAD); however, reduced specificity and diagnostic accuracy of CZT-MPI were observed. This study aims to compare these different camera systems and to examine the degree of inter-rater reproducibility among readers with varying experience in MPI. METHODS: 83 patients who underwent double stress/rest examinations using both a CZT and conventional SPECT cameras within one visit were included. Anonymized and randomized MPI-images were distributed to 15 international readers using a standardized questionnaire. Subsequent coronary angiography findings of ten patients served as a reference for analysis of sensitivity and specificity. RESULTS: Image quality was significantly better in CZT-MPI with significantly lower breast attenuation (P < 0.05). CZT-MPI exhibited higher sensitivity than Anger-MPI (87.5% vs. 62.5%) and significantly reduced specificity (40% vs. 100%). Readers experienced with both camera systems had the highest inter-rater agreement indicating higher reproducibility (CZT 0.54 vs. conv. 0.49, P < 0.05). CONCLUSIONS: Higher diagnostic sensitivity of CZT-MPI offers advantages in detection of CAD yet potentially of at the cost of reduced specificity, therefore it requires special training and a differentiated evaluation approach, especially for non-experienced readers with such camera systems.

PET scatter estimation using deep learning U-Net architecture.

Objective.Positron emission tomography (PET) image reconstruction needs to be corrected for scatter in order to produce quantitatively accurate images. Scatter correction is traditionally achieved by incorporating an estimated scatter sinogram into the forward model during image reconstruction. Existing scatter estimated methods compromise between accuracy and computing time. Nowadays scatter estimation is routinely performed using single scatter simulation (SSS), which does not accurately model multiple scatter and scatter from outside the field-of-view, leading to reduced qualitative and quantitative PET reconstructed image accuracy. On the other side, Monte-Carlo (MC) methods provide a high precision, but are computationally expensive and time-consuming, even with recent progress in MC acceleration.Approach.In this work we explore the potential of deep learning (DL) for accurate scatter correction in PET imaging, accounting for all scatter coincidences. We propose a network based on a U-Net convolutional neural network architecture with 5 convolutional layers. The network takes as input the emission and computed tomography (CT)-derived attenuation factor (AF) sinograms and returns the estimated scatter sinogram. The network training was performed using MC simulated PET datasets. Multiple anthropomorphic extended cardiac-torso phantoms of two different regions (lung and pelvis) were created, considering three different body sizes and different levels of statistics. In addition, two patient datasets were used to assess the performance of the method in clinical practice.Main results.Our experiments showed that the accuracy of our method, namely DL-based scatter estimation (DLSE), was independent of the anatomical region (lungs or pelvis). They also showed that the DLSE-corrected images were similar to that reconstructed from scatter-free data and more accurate than SSS-corrected images.Significance.The proposed method is able to estimate scatter sinograms from emission and attenuation data. It has shown a better accuracy than the SSS, while being faster than MC scatter estimation methods.

EANM guidelines for PET-CT and PET-MR routine quality control.

We present guidelines by the European Association of Nuclear Medicine (EANM) for routine quality control (QC) of PET-CT and PET-MR systems. These guidelines are partially based on the current EANM guidelines for routine quality control of Nuclear Medicine instrumentation but focus more on the inherent multimodal aspect of the current, state-of-the-art PET-CT and PET-MR scanners. We briefly discuss the regulatory context put forward by the International Electrotechnical Commission (IEC) and European Commission (EC) and consider relevant guidelines and recommendations by other societies and professional organizations. As such, a comprehensive overview of recommended quality control procedures is provided to ensure the optimal operational status of a PET system, integrated with either a CT or MR system. In doing so, we also discuss the rationale of the different tests, advice on the frequency of each test and present the relevant MR and CT tests for an integrated system. In addition, we recommend a scheme of preventive actions to avoid QC tests from drifting out of the predefined range of acceptable performance values such that an optimal performance of the PET system is maintained for routine clinical use.

Value of PET ECG gating in a cross-validation study of cardiac function assessment by PET/MR imaging.

BACKGROUND: This work investigated the impact of different cardiac gating methods on the assessment of cardiac function by FDG-PET in a cross-validation PET/MR study. METHODS AND RESULTS: MR- and PET-based left ventricular end-diastolic, end-systolic volumes, and ejection fraction (EDV, ESV, and EF) were delineated in 30 patients with a PET/MR examination. Cardiac PET imaging was performed using three ECG gating methods: fixed number of gates per beat (STD), STD with a beat acceptance window (STD-BR), and fixed gate duration (FW). High MR-PET correlations were found in all the values. ESVs correlated better than EDVs and EFs: Pearson's r coefficient [0.92, 0.92, 0.92] in ESV vs [0.75, 0.81, 0.80] in EDV and [0.79, 0.91, 0.87] in EF, for each method [STD, STD-BR, FW]. Biases with respect to MRI for all the evaluated PET methods were less than 13% in EDV, 5% in ESV, and 14% in EF, but with wide limits of agreements, in the range (59-68)% in EDV, (65-70)% in ESV, and (49-71)% in EF. STD showed the strongest disagreement, while there were no marked differences between STD-BR and FW. CONCLUSION: Based on these findings, PET- and MR-based cardiac function parameters were highly correlated but in substantial disagreement with variabilities introduced by the selected PET ECG gating method. The most significant differences were associated with the ECG gating method susceptible to highly irregular beats, while similar performance was observed in the methods using uniform adjustment of gates width per beat with the beat acceptance window, and fixed gate width along all the beats. Thus, strict quality controls of R peak detection are needed to minimize its impact on the function assessment.

The maximum standardized uptake value in patients with recurrent or persistent prostate cancer after radical prostatectomy and PSMA-PET-guided salvage radiotherapy-a multicenter retrospective analysis.

PURPOSE: This study aims to evaluate the association of the maximum standardized uptake value (SUVmax) in positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET) prior to salvage radiotherapy (sRT) on biochemical recurrence free survival (BRFS) in a large multicenter cohort. METHODS: Patients who underwent 68 Ga-PSMA11-PET prior to sRT were enrolled in four high-volume centers in this retrospective multicenter study. Only patients with PET-positive local recurrence (LR) and/or nodal recurrence (NR) within the pelvis were included. Patients were treated with intensity-modulated-sRT to the prostatic fossa and elective lymphatics in case of nodal disease. Dose escalation was delivered to PET-positive LR and NR. Androgen deprivation therapy was administered at the discretion of the treating physician. LR and NR were manually delineated and SUVmax was extracted for LR and NR. Cox-regression was performed to analyze the impact of clinical parameters and the SUVmax-derived values on BRFS. RESULTS: Two hundred thirty-five patients with a median follow-up (FU) of 24 months were included in the final cohort. Two-year and 4-year BRFS for all patients were 68% and 56%. The presence of LR was associated with favorable BRFS (p = 0.016). Presence of NR was associated with unfavorable BRFS (p = 0.007). While there was a trend for SUVmax values ≥ median (p = 0.071), SUVmax values ≥ 75% quartile in LR were significantly associated with unfavorable BRFS (p = 0.022, HR: 2.1, 95%CI 1.1-4.6). SUVmax value in NR was not significantly associated with BRFS. SUVmax in LR stayed significant in multivariate analysis (p = 0.030). Sensitivity analysis with patients for who had a FU of > 12 months (n = 197) confirmed these results. CONCLUSION: The non-invasive biomarker SUVmax can prognosticate outcome in patients undergoing sRT and recurrence confined to the prostatic fossa in PSMA-PET. Its addition might contribute to improve risk stratification of patients with recurrent PCa and to guide personalized treatment decisions in terms of treatment intensification or de-intensification. This article is part of the Topical Collection on Oncology-Genitourinary.

Platelet sTWEAK and plasma IL-6 are associated with 18F-fluorodeoxyglucose uptake in right ventricles of patients with pulmonary arterial hypertension: A pilot study.

BACKGROUND: Cytokines soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and interleukin 6 (IL-6) are involved in immune response, proliferation, apoptosis, and cardiovascular pathologies. We have previously confirmed that changes of their platelet or plasma contents are associated with pulmonary arterial hypertension (PAH). The positron emission tomography/magnetic resonance imaging (PET/MRI) hybrid imaging provides detailed insight into right ventricle (RV) hemodynamic and metabolic function. OBJECTIVES: To evaluate the relationship between RV parameters obtained using PET/MRI and concentrations of plasma and platelet sTWEAK and IL-6 in stable PAH patients. MATERIAL AND METHODS: Eighteen stable PAH patients (48.44 ±16.7 years) had simultaneous PET/MRI scans with 18F-fluorodeoxyglucose (18F-FDG) performed. Its uptake was presented as a standardized uptake value (SUV) for RV and left ventricle (LV). Cytokines concentrations were measured in platelet-poor plasma and platelet lysate. Follow-up time of this study was 58 months; the combined endpoint (CEP) was defined as death or clinical deterioration. RESULTS: We observed significant correlations between platelet sTWEAK levels, plasma IL-6 and PET parameter SUVRV/LV (r = -0.57, p = 0.011; r = 0.50, p = 0.032, respectively). In logistic regression, platelet sTWEAK and IL-6 were both prognostic factors for unfavorable ratio of SUVRV/LV higher than 1 (hazard ratio (HR) = 0.44, 95% confidence interval (95% CI): [0.23; 0.84], p = 0.017; and HR = 3.62, 95% CI: [1.21; 10.17], p = 0.011, respectively). Furthermore, their concentrations were related with prognostically important higher late gadolinium enhancement mass index (LGEMI) and RV global longitudinal strain/systolic pulmonary artery pressure (RV GLS/sPAP) values. Patients who had CEP in follow-up (n = 13) had significantly lower platelet sTWEAK content and higher plasma IL-6 at baseline than stable patients. Lower platelet sTWEAK was related to a worse prognosis in log-rank test (p = 0.006). Platelet sTWEAK and plasma IL-6 together with RV GLS/sPAP, RV ejection fraction (RVEF), mean pulmonary arterial pressure (mPAP), and SUVRV/LV were significantly associated with time to CEP in univariate Cox analysis. CONCLUSIONS: The sTWEAK and IL-6 concentrations in PAH patients are linked with metabolic and functional changes of RV visualized in PET/MRI, and both sTWEAK and IL-6 predict clinical deterioration.