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Imaging water pathways in the human body provides an excellent way of measuring accurately the blood flow directed to different organs. This makes it a powerful diagnostic tool for a wide range of diseases that are related to perfusion and oxygenation. Although water PET has a long history, its true potential has not made it into regular clinical practice. The article highlights the potential of water PET in molecular imaging and suggests its prospective role in becoming an essential tool for the 21st century precision medicine in different domains ranging from preclinical to clinical research and practice. The recent technical advances in high-sensitivity PET imaging can play a key accelerating role in empowering this technique, though there are still several challenges to overcome., Competing Interests: Declaration of Competing Interest The authors 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 © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: As novel tracers are continuously under development, it is important to obtain reliable radiation dose estimates to optimize the amount of activity that can be administered while keeping radiation burden within acceptable limits. Organ segmentation is required for quantification of specific uptake in organs of interest and whole-body dosimetry but is a time-consuming task which induces high interobserver variability. Therefore, we explored using manual segmentations versus an artificial intelligence (AI)-based automated segmentation tool as a pre-processing step for calculating whole-body effective doses to determine the influence of variability in volumetric whole-organ segmentations on dosimetry., Procedures: PET/CT data of six patients undergoing imaging with 89 Zr-labelled pembrolizumab were included. Manual organ segmentations were performed, using in-house developed software, and biodistribution information was obtained. Based on the activity biodistribution information, residence times were calculated. The residence times served as input for OLINDA/EXM version 1.0 (Vanderbilt University, 2003) to calculate the whole-body effective dose (mSv/MBq). Subsequently, organ segmentations were performed using RECOMIA, a cloud-based AI platform for nuclear medicine and radiology research. The workflow for calculating residence times and whole-body effective doses, as described above, was repeated., Results: Data were acquired on days 2, 4, and 7 post-injection, resulting in 18 scans. Overall analysis time per scan was approximately 4 h for manual segmentations compared to ≤ 30 min using AI-based segmentations. Median Jaccard similarity coefficients between manual and AI-based segmentations varied from 0.05 (range 0.00-0.14) for the pancreas to 0.78 (range 0.74-0.82) for the lungs. Whole-body effective doses differed minimally for the six patients with a median difference in received mSv/MBq of 0.52% (range 0.15-1.95%)., Conclusion: This pilot study suggests that whole-body dosimetry calculations can benefit from fast, automated AI-based whole organ segmentations., (© 2022. The Author(s).)

Purpose: The aim of this study was to retrospectively compare 18F-FDOPA versus 68Ga-DOTATOC PET in lesion detection rates and laboratory tumor markers in patients with neuroendocrine neoplasms (NENs)., Patients and Methods: All patients with histologically proven NEN between May 2015 and February 2019 were included who underwent both 18F-DOPA and 68Ga-DOTATOC PET scans within 6 months from each other (mean, 75; median, 38; range, 2-168 days). All patients, except those with pancreatic NEN, received carbidopa before 18F-DOPA PET. Based on the number of lesions on both modalities, patients were divided into 3 categories: more lesions on 18F-DOPA (DOPA > DOTA), more lesions on 68Ga-DOTATOC (DOTA > DOPA), and equal number of lesions (DOPA = DOTA). Tumor markers chromogranin A, serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) within a maximum of 3 months around either scan were retrieved from the patients' charts., Results: 18F-DOPA revealed significantly more lesions compared with 68Ga-DOTATOC (611 vs 385, P < 0.05). Twenty-four patients were included in the DOPA > DOTA group with 16 small intestinal (SI) NENs, 3 large intestinal, 4 pancreatic, and 1 tumor of unknown origin (TUO). For the 9 patients in the DOTA > DOPA group, 4 were SI, 2 pancreatic, 1 lung, and 2 TUOs. Twelve patients in the DOPA = DOTA group had 6 pancreatic tumors, 3 SI, 1 ovarian, and 2 TUOs. Only serotonin and 5-HIAA showed significant higher values for DOPA > DOTA compared with DOTA > DOPA (mean 24 vs 4, P < 0.05, and 320 vs 81, P < 0.05, respectively). Cutoff values of 20 nmol/109 for serotonin, 185 μg/L for chromogranin A, and 200 nmol/L for 5-HIAA were found to include almost exclusively DOPA > DOTA patients., Conclusions: There is an advantage of carbidopa pretreated 18F-DOPA over 68Ga-DOTATOC PET, especially for large intestinal NENs with high levels of biomarkers. There seems to be a relationship between increased biomarker value and improved lesion detection rates with the 18F-DOPA PET scan, which requires further prospective analysis., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: PET-based tumor delineation is an error prone and labor intensive part of image analysis. Especially for patients with advanced disease showing bulky tumor FDG load, segmentations are challenging. Reducing the amount of user-interaction in the segmentation might help to facilitate segmentation tasks especially when labeling bulky and complex tumors. Therefore, this study reports on segmentation workflows/strategies that may reduce the inter-observer variability for large tumors with complex shapes with different levels of user-interaction., Methods: Twenty PET images of bulky tumors were delineated independently by six observers using four strategies: (I) manual, (II) interactive threshold-based, (III) interactive threshold-based segmentation with the additional presentation of the PET-gradient image and (IV) the selection of the most reasonable result out of four established semi-automatic segmentation algorithms (Select-the-best approach). The segmentations were compared using Jaccard coefficients (JC) and percentage volume differences. To obtain a reference standard, a majority vote (MV) segmentation was calculated including all segmentations of experienced observers. Performed and MV segmentations were compared regarding positive predictive value (PPV), sensitivity (SE), and percentage volume differences., Results: The results show that with decreasing user-interaction the inter-observer variability decreases. JC values and percentage volume differences of Select-the-best and a workflow including gradient information were significantly better than the measurements of the other segmentation strategies (p-value<0.01). Interactive threshold-based and manual segmentations also result in significant lower and more variable PPV/SE values when compared with the MV segmentation., Conclusions: FDG PET segmentations of bulky tumors using strategies with lower user-interaction showed less inter-observer variability. None of the methods led to good results in all cases, but use of either the gradient or the Select-the-best workflow did outperform the other strategies tested and may be a good candidate for fast and reliable labeling of bulky and heterogeneous tumors., Competing Interests: The authors declared that no competing interests exist.

Noninvasive imaging modalities offer the possibility to dynamically evaluate cardiac motion during the cardiac cycle by means of ECG-gated acquisitions. Such motion characterization along with orientation, segmentation preprocessing, and ultimately, phase analysis, can provide quantitative estimates of ventricular mechanical synchrony. Current evidence on the role of mechanical synchrony evaluation is mainly available for echocardiography and gated single-photon emission computed tomography, but less is known about the utilization of gated positron emission tomography (PET). Although data available are sparse, there is indication that mechanical synchrony evaluation can be of diagnostic and prognostic values in patients with known or suspected coronary artery disease-related myocardial ischemia, prediction of response to cardiac resynchronization therapy, and estimation of risk for adverse cardiac events in patients' heart failure. As such, the evaluation of mechanical ventricular synchrony through phase analysis of gated acquisitions represents a value addition to modern cardiac PET imaging modality, which warrants further research and development in the evaluation of patients with cardiovascular disease.

Objectives: MYC gene rearrangements in diffuse large B cell lymphomas (DLBCLs) result in high proliferation rates and are associated with a poor prognosis. Strong proliferation is associated with high metabolic demand and tumour necrosis. The aim of this study was to investigate differences in the presence of necrosis and semiquantitative 18 F-FDG PET metrics between DLBCL cases with or without a MYC rearrangement. The prognostic impact of necrosis and semiquantitative 18 F-FDG PET parameters was investigated in an explorative survival analysis., Methods: Fluorescence in situ hybridisation analysis for MYC rearrangements, visual assesment, semiquantitative analysis of 18 F-FDG PET scans and patient survival analysis were performed in 61 DLBCL patients, treated at a single referral hospital between 2008 and 2015., Results: Of 61 tumours, 21 (34%) had a MYC rearrangement (MYC + ). MYC status was neither associated with the presence of necrosis on 18 F-FDG PET scans (necrosis PET ; p = 1.0) nor associated with the investigated semiquantitative parameters maximum standard uptake value (SUV max ; p = 0.43), single highest SUV max (p = 0.49), metabolic active tumour volume (MATV; p = 0.68) or total lesion glycolysis (TLG; p = 0.62). A multivariate patient survival analysis of the entire cohort showed necrosis PET as an independent prognostic marker for disease-specific survival (DSS) (HR = 13.9; 95% CI 3.0-65; p = 0.001)., Conclusions: MYC rearrangements in DLBCL have no influence on the visual parameter necrosis PET or the semi-quantiative parameters SUV max , MATV and TLG. Irrespective of MYC rearrangements, necrosis PET is an independent, adverse prognostic factor for DSS., Key Points: • Retrospective analysis indicates that MYC rearrangement is not associated with necrosis on 18 F-FDG PET (necrosis PET ) scans or semiquantitative 18 F-FDG PET parameters. • Necrosis PET is a potential independent adverse prognostic factor for disease-specific survival in patients with DLBCL and is not influenced by the presence of MYC rearrangements.

Purpose To assess the value of baseline and restaging fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) radiomics in predicting pathologic complete response to neoadjuvant chemotherapy and radiation therapy (NCRT) in patients with locally advanced esophageal cancer. Materials and Methods In this retrospective study, 73 patients with histologic analysis-confirmed T1/N1-3/M0 or T2-4a/N0-3/M0 esophageal cancer were treated with NCRT followed by surgery (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study regimen) between October 2014 and August 2017. Clinical variables and radiomic features from baseline and restaging 18 F-FDG PET were selected by univariable logistic regression and least absolute shrinkage and selection operator. The selected variables were used to fit a multivariable logistic regression model, which was internally validated by using bootstrap resampling with 20 000 replicates. The performance of this model was compared with reference prediction models composed of maximum standardized uptake value metrics, clinical variables, and maximum standardized uptake value at baseline NCRT radiomic features. Outcome was defined as complete versus incomplete pathologic response (tumor regression grade 1 vs 2-5 according to the Mandard classification). Results Pathologic response was complete in 16 patients (21.9%) and incomplete in 57 patients (78.1%). A prediction model combining clinical T-stage and restaging NCRT (post-NCRT) joint maximum (quantifying image orderliness) yielded an optimism-corrected area under the receiver operating characteristics curve of 0.81. Post-NCRT joint maximum was replaceable with five other redundant post-NCRT radiomic features that provided equal model performance. All reference prediction models exhibited substantially lower discriminatory accuracy. Conclusion The combination of clinical T-staging and quantitative assessment of post-NCRT 18 F-FDG PET orderliness (joint maximum) provided high discriminatory accuracy in predicting pathologic complete response in patients with esophageal cancer. © RSNA, 2018 Online supplemental material is available for this article.

Histological analysis of endomyocardial tissue is still the gold standard for the diagnosis of cardiac amyloidosis, but has its limitations. Accordingly, there is a need for non-invasive modalities to diagnose cardiac amyloidosis. Echocardiography and ultrasound and magnetic resonance imaging can show characteristics which may not be very specific for cardiac amyloid. Nuclear medicine has gained a precise role in this context: several imaging modalities have become available for the diagnosis and prognostic stratification of cardiac amyloidosis during the last two decades. The different classes of radiopharmaceuticals have the potential to bind different constituents of the amyloidotic infiltrates, with some relevant differences among the various aetiologic types of amyloidosis and the different organs and tissues involved. This review focuses on the background of the commonly used modalities, their present clinical applications, and future clinical perspectives in imaging patients with (suspected) cardiac amyloidosis. The main focus is on conventional nuclear medicine (bone scintigraphy, cardiac sympathetic innervation) and positron emission tomography.

Cardiac dysfunction leads to decreased organ perfusion. We aimed to measure cardiac and renal perfusion simultaneously with the use of (13)N-NH3-microPET in different rat models. Ten male Wistar rats underwent sham surgery (n = 5) or permanent coronary artery ligation to induce myocardial infarction (MI, n = 5). Eleven weeks later (13)N-NH3-microPET scan was performed to study the cardiac and renal perfusion. Cardiac perfusion was significantly reduced in MI group, directly correlated with ejection fraction and inversely correlated with MI size (r = 0.89; p < 0.001 and r = -0.86; p < 0.001 respectively). Renal perfusion showed a notional 17 % non-significant reduction in MI group when compared to sham (3.44 ± 0.40 vs. 4.12 ± 0.48 ml/g/min). There was a trend towards greater reduction of perfusion in cortical than medullar region. Cortex perfusion was negatively correlated with histological changes. (13)N-NH3-microPET may be a potential tool for evaluation of cardiac and renal functional and perfusion changes in presence of cardiac dysfunction in rat models.

Purpose: This study evaluates the prevalence of cardiac metastases in patients with serotonin producing neuroendocrine tumours (NET), examined with 18F-FDOPA PET/CT, and the relationship of these metastases to the presence of carcinoid heart disease (CHD) based on echocardiography., Background: CHD occurs in patients with serotonin producing NET. The diagnostic method of choice remains echocardiography. The precise prevalence of cardiac metastases is unknown given the limitations of standard technologies. Nuclear medicine modalities have the potential to visualize metastases of NET., Methods: All patients who underwent 18F-FDOPA PET/CT because of serotonin producing NET between November 2009 and May 2012 were retrospectively analyzed. The presence of cardiac metastasis was defined as myocardial tracer accumulation higher than the surrounding physiological myocardial uptake. Laboratory tests and transthoracic echocardiography (TTE) results were digitally collected., Results: 116 patients (62 male) underwent 18F-FDOPA PET/CT, mean age was 61±13 years. TTE was performed in 79 patients. Cardiac metastases were present in 15 patients, of which 10 patients also underwent TTE. One patient had both cardiac metastasis (only on 18F-FDOPA PET/CT) and echocardiographic signs of CHD. There were no differences in echocardiographic parameters for CHD between patients with and without cardiac metastases. TTE in none of the 79 patients showed cardiac metastases., Conclusion: The prevalence of cardiac metastases detected with 18F-FDOPA PET/CT in this study is 13%. 18F-FDOPA PET/CT can visualize cardiac metastases in serotonin producing NET patients. There appears to be no relationship between the presence of cardiac metastases and TTE parameters of CHD.

Purpose: Amyloidosis is a group of diseases characterized by deposition of fibrils and this deposition may be localized or systemic. The presence of giant cells is typical of localized AL amyloidosis in contrast to systemic amyloidosis. Because of this presence of giant cells we hypothesize that (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) may show uptake in localized amyloidosis but not in systemic amyloidosis. The aim of the study was to evaluate the utility of (18)F-FDG PET/CT in distinguishing systemic amyloidosis from localized amyloidosis., Methods: A retrospective search in the hospital computer system showed 21 patients with histologically proven systemic or localized amyloidosis who recently had undergone (18)F-FDG PET/CT. Twenty patients also had undergone (123)I-serum amyloid P component (SAP) scintigraphy., Results: Of 11 patients with localized amyloidosis, 10 showed markedly increased FDG uptake at the amyloid site, whereas one showed slightly increased FDG uptake. (123)I-SAP scintigraphy (in ten patients) was positive in three patients at the amyloid site and negative for any other specific organ involvement in nine patients, with a weakly positive spleen in one other patient. In ten patients with systemic amyloidosis, increased FDG uptake was not found in any affected organ containing amyloid, whereas (123)I-SAP scintigraphy was positive for specific organ involvement in nine patients., Conclusion: (18)F-FDG PET/CT may be supportive of the usual diagnostic tests in differentiating between systemic amyloidosis (no increased FDG uptake at the amyloid site) and localized amyloidosis (increased FDG uptake at the amyloid site). Apart from diagnosis, this finding has potential clinical application in therapy evaluation and follow-up.