FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0.

The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.

Technetium Tc-99m pyrophosphate for cerebrospinal fluid leaks: radiopharmaceutical considerations.

OBJECTIVE To confirm the anticipated image quality and absence of adverse reactions in patients undergoing clinical practice cerebrospinal fluid (CSF) leak imaging procedures using technetium Tc-99m pyrophosphate (PYP). METHODS Following the recent discontinuation of preservative-free calcium trisodium diethylene triamine pentaacetic acid kits, PYP was selected as a suitable alternative for CSF leak imaging procedures. Procedures were established for its preparation and dispensing, paying special attention to safety considerations, and its use in clinical practice was implemented. Medical records, including images, were reviewed for the first 15 patients undergoing clinical practice CSF imaging procedures using Tc-99m PYP to confirm anticipated image quality and absence of adverse effects. RESULTS Review of CSF leak imaging procedures using Tc-99m PYP in 15 patients showed images to be of uniformly high quality. The vast majority of injected radiopharmaceutical remained in the CSF throughout the duration of the imaging procedure, allowing visualization of CSF leaks. Only a small amount of Tc-99m PYP diffused into the blood with resultant uptake on the skeleton and excretion into the urine, which did not interfere with image interpretation. No adverse reactions were noted in any of the patients. CONCLUSION With proper attention to safety considerations, Tc-99m PYP is a safe and effective alternative for performing CSF leak imaging procedures.

Change in Management After Radionuclide Gastric Emptying Studies Showing Slow Emptying.

The radionuclide gastric emptying study is the gold standard for the diagnosis of gastroparesis. Methods: We performed a retrospective analysis of 510 patients to evaluate how often a diagnosis of slow gastric emptying determined by gastric emptying scintigraphy (GES) changes clinical management at our institution. Results: We found evidence of gastroparesis in 100 patients. A change in management was recommended for 62% within 1 mo of the GES. Conclusion: Our results illustrate the importance of performing GES on patients with clinically suspected gastroparesis.

Exploratory Study on COPD Phenotypes and their Progression: Integrating SPECT and qCT Imaging Analysis.

Background: The objective of this study is to understand chronic obstructive pulmonary disease (COPD) phenotypes and their progressions by quantifying heterogeneities of lung ventilation from the single photon emission computed tomography (SPECT) images and establishing associations with the quantitative computed tomography (qCT) imaging-based clusters and variables. Methods: Eight COPD patients completed a longitudinal study of three visits with intervals of about a year. CT scans of these subjects at residual volume, functional residual capacity, and total lung capacity were taken for all visits. The functional and structural qCT-based variables were derived, and the subjects were classified into the qCT-based clusters. In addition, the SPECT variables were derived to quantify the heterogeneity of lung ventilation. The correlations between the key qCT-based variables and SPECT-based variables were examined. Results: The SPECT-based coefficient of variation (CVTotal), a measure of ventilation heterogeneity, showed strong correlations (|r| ≥ 0.7) with the qCT-based functional small airway disease percentage (fSAD%Total) and emphysematous tissue percentage (Emph%Total) in the total lung on cross-sectional data. As for the two-year changes, the SPECT-based maximum tracer concentration (TCmax), a measure of hot spots, exhibited strong negative correlations with fSAD%Total, Emph%Total, average airway diameter in the left upper lobe, and airflow distribution in the middle and lower lobes. Conclusion: Small airway disease is highly associated with the heterogeneity of ventilation in COPD lungs. TCmax is a more sensitive functional biomarker for COPD progression than CVTotal. Besides fSAD%Total and Emph%Total, segmental airways narrowing and imbalanced ventilation between upper and lower lobes may contribute to the development of hot spots over time.

The Future of Nuclear Medicine in the United States.

Nuclear medicine (NM) in the United States is experiencing a manpower shortage that is steadily getting worse. It largely derives from inadequate production of well-trained NM physicians. It is different in the rest of the world, where NM is an independent specialty and training is more rigorous. Three suggestions are offered to help reverse the situation: (1) stop radiologists with inadequate training from practicing NM; (2) strengthen NM training programs; and (3) inform medical students of career opportunities in NM. If we do nothing, the rest of the world will move forward, leaving us behind.

Practical Aspects of Nuclear Medicine Ventriculoperitoneal Shunt Evaluation.

The radionuclide ventriculoperitoneal shunt evaluation study is a simple test that involves injecting a small volume of radionuclide into the shunt reservoir and then observing its disappearance using dynamic γ-camera imaging. Although it seems simple, there are several potential pitfalls that can result in a misinterpreted or uninterpretable study. This paper is a detailed description of how to avoid the pitfalls and also how to interpret the results.

PET/CT Imaging in Treatment Planning and Surveillance of Sinonasal Neoplasms.

Sinonasal cancers are uncommon malignancies with a generally unfavorable prognosis, often presenting at an advanced stage. Their high rate of recurrence supports close imaging surveillance and the utilization of functional imaging techniques. Whole-body 18F-FDG PET/CT has very high sensitivity for the diagnosis of sinonasal malignancies and can also be used as a "metabolic biopsy" in the characterization of some of the more common subgroups of these tumors, though due to overlap in uptake, histological confirmation is still needed. For certain tumor types, radiotracers, such as 11C-choline, and radiolabeled somatostatin analogs, including 68Ga-DOTATATE/DOTATOC, have proven useful in treatment planning and surveillance. Although serial scans for posttreatment surveillance allow the detection of subclinical lesions, the optimal schedule and efficacy in terms of survival are yet to be determined. Pitfalls of 18F-FDG, such as post-surgical and post-radiotherapy crusting and inflammation, may cause false-positive hypermetabolism in the absence of relapse.

Fibroblast Activation Protein Inhibitor-Based Radionuclide Therapies: Current Status and Future Directions.

Metastatic malignancies have limited management strategies and variable treatment responses. Cancer cells develop beside and depend on the complex tumor microenvironment. Cancer-associated fibroblasts, with their complex interaction with tumor and immune cells, are involved in various steps of tumorigenesis, such as growth, invasion, metastasis, and treatment resistance. Prooncogenic cancer-associated fibroblasts emerged as attractive therapeutic targets. However, clinical trials have achieved suboptimal success. Fibroblast activation protein (FAP) inhibitor-based molecular imaging has shown encouraging results in cancer diagnosis, making them innovative targets for FAP inhibitor-based radionuclide therapies. This review summarizes the results of preclinical and clinical FAP-based radionuclide therapies. We will describe advances and FAP molecule modification in this novel therapy, as well as its dosimetry, safety profile, and efficacy. This summary may guide future research directions and optimize clinical decision-making in this emerging field.

Head and Neck Cancer Segmentation in FDG PET Images: Performance Comparison of Convolutional Neural Networks and Vision Transformers.

Convolutional neural networks (CNNs) have a proven track record in medical image segmentation. Recently, Vision Transformers were introduced and are gaining popularity for many computer vision applications, including object detection, classification, and segmentation. Machine learning algorithms such as CNNs or Transformers are subject to an inductive bias, which can have a significant impact on the performance of machine learning models. This is especially relevant for medical image segmentation applications where limited training data are available, and a model's inductive bias should help it to generalize well. In this work, we quantitatively assess the performance of two CNN-based networks (U-Net and U-Net-CBAM) and three popular Transformer-based segmentation network architectures (UNETR, TransBTS, and VT-UNet) in the context of HNC lesion segmentation in volumetric [F-18] fluorodeoxyglucose (FDG) PET scans. For performance assessment, 272 FDG PET-CT scans of a clinical trial (ACRIN 6685) were utilized, which includes a total of 650 lesions (primary: 272 and secondary: 378). The image data used are highly diverse and representative for clinical use. For performance analysis, several error metrics were utilized. The achieved Dice coefficient ranged from 0.833 to 0.809 with the best performance being achieved by CNN-based approaches. U-Net-CBAM, which utilizes spatial and channel attention, showed several advantages for smaller lesions compared to the standard U-Net. Furthermore, our results provide some insight regarding the image features relevant for this specific segmentation application. In addition, results highlight the need to utilize primary as well as secondary lesions to derive clinically relevant segmentation performance estimates avoiding biases.

Automated measurement of uptake in cerebellum, liver, and aortic arch in full-body FDG PET/CT scans.

PURPOSE: The purpose of this work was to develop and validate fully automated methods for uptake measurement of cerebellum, liver, and aortic arch in full-body PET/CT scans. Such measurements are of interest in the context of uptake normalization for quantitative assessment of metabolic activity and/or automated image quality control. METHODS: Cerebellum, liver, and aortic arch regions were segmented with different automated approaches. Cerebella were segmented in PET volumes by means of a robust active shape model (ASM) based method. For liver segmentation, a largest possible hyperellipsoid was fitted to the liver in PET scans. The aortic arch was first segmented in CT images of a PET/CT scan by a tubular structure analysis approach, and the segmented result was then mapped to the corresponding PET scan. For each of the segmented structures, the average standardized uptake value (SUV) was calculated. To generate an independent reference standard for method validation, expert image analysts were asked to segment several cross sections of each of the three structures in 134 F-18 fluorodeoxyglucose (FDG) PET/CT scans. For each case, the true average SUV was estimated by utilizing statistical models and served as the independent reference standard. RESULTS: For automated aorta and liver SUV measurements, no statistically significant scale or shift differences were observed between automated results and the independent standard. In the case of the cerebellum, the scale and shift were not significantly different, if measured in the same cross sections that were utilized for generating the reference. In contrast, automated results were scaled 5% lower on average although not shifted, if FDG uptake was calculated from the whole segmented cerebellum volume. The estimated reduction in total SUV measurement error ranged between 54.7% and 99.2%, and the reduction was found to be statistically significant for cerebellum and aortic arch. CONCLUSIONS: With the proposed methods, the authors have demonstrated that automated SUV uptake measurements in cerebellum, liver, and aortic arch agree with expert-defined independent standards. The proposed methods were found to be accurate and showed less intra- and interobserver variability, compared to manual analysis. The approach provides an alternative to manual uptake quantification, which is time-consuming. Such an approach will be important for application of quantitative PET imaging to large scale clinical trials.

Clinical molecular imaging with radiotracers: current status.

Molecular imaging is defined as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Most clinical molecular imaging is currently done using radioisotope-labeled agents to define the activity of various metabolic pathways in vivo or to determine the distribution and density of various receptors relevant to human disease. This paper briefly reviews most of the commonly used radiopharmaceuticals in nuclear medicine, as well as newer agents that are likely to become available in the near future. The metabolic pathways include those relevant to the thyroid, parathyroid, heart, brain, bones, kidneys, liver, pancreas, adrenals and tumor. The receptor systems include agents useful in evaluating movement disorders, dementia, cardiac sympathetic enervation and neoangiogenesis. Receptor systems relevant to tumors include somatostatin receptors (neuroendocrine tumors), prostate-specific membrane antigen, carbonic anhydrase IX (renal cancer), and CD-20 (lymphoma). These agents, and newer agents that are being developed, are likely to become critical in the development of personalized medicine, where it will become increasingly important to determine whether a treatment that is targeted to a specific metabolic pathway or receptor is likely to be successful.

Quantification of uptake in pelvis F-18 FLT PET-CT images using a 3D localization and segmentation CNN.

PURPOSE: The purpose of this work was to develop and validate a deep convolutional neural network (CNN) approach for the automated pelvis segmentation in computed tomography (CT) scans to enable the quantification of active pelvic bone marrow by means of Fluorothymidine F-18 (FLT) tracer uptake measurement in positron emission tomography (PET) scans. This quantification is a critical step in calculating bone marrow dose for radiopharmaceutical therapy clinical applications as well as external beam radiation doses. METHODS: An approach for the combined localization and segmentation of the pelvis in CT volumes of varying sizes, ranging from full-body to pelvis CT scans, was developed that utilizes a novel CNN architecture in combination with a random sampling strategy. The method was validated on 34 planning CT scans and 106 full-body FLT PET-CT scans using a cross-validation strategy. Specifically, two different training and CNN application options were studied, quantitatively assessed, and statistically compared. RESULTS: The proposed method was able to successfully locate and segment the pelvis in all test cases. On all data sets, an average Dice coefficient of 0.9396 ± $\pm$ 0.0182 or better was achieved. The relative tracer uptake measurement error ranged between 0.065% and 0.204%. The proposed approach is time-efficient and shows a reduction in runtime of up to 95% compared to a standard U-Net-based approach without a localization component. CONCLUSIONS: The proposed method enables the efficient calculation of FLT uptake in the pelvis. Thus, it represents a valuable tool to facilitate bone marrow preserving adaptive radiation therapy and radiopharmaceutical dose calculation. Furthermore, the method can be adapted to process other bone structures as well as organs.

Multimodality imaging in a case of multiple pulmonary hyalinizing granulomas - A decade follow-up.

A 44-year-old male was referred to our clinic (2015) to evaluate multiple lung nodules with increasing fatigue, dyspnea, and weight loss. He was being assessed to an outside hospital for the same since 2010. The X-ray and computed-tomography (CT)-chest showed numerous pulmonary nodules and bilateral hilar adenopathy. Imaging workup at our institute (2015) redemonstrated extensive calcified pulmonary nodules. 18fluoro-2-deoxy-d-glucose positron emission tomographyCT showed widespread pulmonary nodules with low-grade uptake. Video-assisted thoracic surgery lung biopsy revealed pulmonary hyalinizing granuloma (PHG). Recently because of increasing symptoms, he is being evaluated for a lung transplant. This case represents a rare diagnosis of PHG with a decade follow-up.

Role of FDG PET/CT for detection of primary tumor in patients with extracervical metastases from carcinoma of unknown primary.

AIM: To explore the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) to detect the primary tumor site in patients with extracervical metastases from carcinoma of unknown primary (CUP). We evaluated patient outcomes as overall survival (OS). MATERIALS AND METHODS: In a single-center, retrospective study (2005-2019), patients with extracervical metastases from CUP underwent FDG PET/CT to detect primary tumor sites. The final diagnosis was based on histopathology/or clinical follow-up of at least 12 months. RESULTS: A total of 83 patients [Male 41 (49%), mean age 59 ± 14 years, range: 32-83 years] fulfilled the inclusion/exclusion criteria and were enrolled for analysis. The primary tumor was detected in 36 out of 83 (43%) patients based on histopathology/or clinical follow-up. PET/CT suggested the primary tumor site in 39 (47%) patients with diagnostic accuracy of 87%, sensitivity 89%, specificity 85%, PPV 82%, NPV 91% and detection rate 39%. Patients with oligometastases (<3) (2.16 years, 1.04-2.54) and primary unidentified (1 year, 0.34-2.14) had longer median survival time compared to the patients with multiple metastases (0.67 years, 0.17-1.58, p = 0.009) and primary identified (0.67 years,0.16-1.33, p = 0.002). The SUVmax of the primary or metastatic lesions with maximum uptake was not significantly related to survival. CONCLUSIONS: PET/CT could reveal the primary tumor site in 39% of the patients. It demonstrated the metastatic disease burden and distribution in patients with 'primary obscured', which directs management. Patients with multiple metastases and primary identified had a poorer prognosis. In patients with primary unidentified after PET/CT, a further search was futile.

Multiparametric magnetic resonance imaging and positron emission tomography findings in neurodegenerative diseases: Current status and future directions.

Neurodegenerative diseases (NDDs) are characterized by progressive neuronal loss, leading to dementia and movement disorders. NDDs broadly include Alzheimer's disease, frontotemporal lobar degeneration, parkinsonian syndromes, and prion diseases. There is an ever-increasing prevalence of mild cognitive impairment and dementia, with an accompanying immense economic impact, prompting efforts aimed at early identification and effective interventions. Neuroimaging is an essential tool for the early diagnosis of NDDs in both clinical and research settings. Structural, functional, and metabolic imaging modalities, including magnetic resonance imaging (MRI) and positron emission tomography (PET), are widely available. They show encouraging results for diagnosis, monitoring, and treatment response evaluation. The current review focuses on the complementary role of various imaging modalities in relation to NDDs, the qualitative and quantitative utility of newer MRI techniques, novel radiopharmaceuticals, and integrated PET/MRI in the setting of NDDs.

Theranostics: The Role of Quantitative Nuclear Medicine Imaging.

Theranostics is a precision medicine discipline that integrates diagnostic nuclear medicine imaging with radionuclide therapy in a manner that provides both a tumor phenotype and personalized therapy to patients with cancer using radiopharmaceuticals aimed at the same target-specific biological pathway or receptor. The aim of quantitative nuclear medicine imaging is to plan the alpha or beta-emitting therapy based on an accurate 3-dimensional representation of the in-vivo distribution of radioactivity concentration within the tumor and normal organs/tissues in a noninvasive manner. In general, imaging may be either based on positron emission tomography (PET) or single photon emission computed tomography (SPECT) invariably in combination with X-ray CT (PET/CT; SPECT/CT) or, to a much lesser extent, MRI. PET and SPECT differ in terms of the radionuclides and physical processes that give rise to the emission of high energy photons, as well as the sets of technologies involved in their detection. Using a variety of standardized quantitative parameters, system calibration, patient preparation, imaging acquisition and reconstruction protocols, and image analysis protocols, an accurate quantification of the tracer distribution can be obtained, which helps prescribe the therapeutic dose for each patient.

Global trends in hybrid imaging.

At the 2009 Scientific Assembly and Annual Meeting of the Radiological Society of North America, a special session was devoted to global trends in hybrid imaging. This article expands on the key points of the session, focusing primarily on positron emission tomography/computed tomography. Global trends in hybrid imaging equipment acquisition, usage, and image interpretation practices are reviewed, and emerging requirements for training and clinical privileging are discussed. Also considered are the current benefits of hybrid imaging for patient care and workflow and the potential of hybrid imaging for advancing drug development and personalized medicine.

Association of gallbladder hyperkinesia with acalculous chronic cholecystitis: A case-control study.

BACKGROUND: This is the first case-control study investigating an association between gallbladder hyperkinesia and symptomatic acalculous chronic cholecystitis. METHODS: This retrospective study in a single academic center compared resolution of biliary pain in adults with gallbladder hyperkinesia, defined as a hepatobiliary iminodiacetic acid scan ejection fraction ≥80%, undergoing cholecystectomy (study group) with those treated medically without cholecystectomy (control group). Of 1,477 hepatobiliary iminodiacetic acid scans done between 2013 and 2018, a total of 296 adults without gallstones had an ejection fraction ≥80%, of whom 46 patients met predetermined eligibility criteria. Demographic data, hepatobiliary iminodiacetic acid scan ejection fraction, chronicity of pain, and resolution of pain were compared between groups. RESULTS: Demographics (mean ± standard deviation) in the control group (n = 25) and in the study group (n = 21) were, respectively, age 40 y ± 16 y and 39 y ± 14 y, body mass index 28.9 ± 5.2 and 29.1 ± 7.1 kg/m2, with 15 (60%) and 18 (86%) females in each. Resolution of pain after cholecystectomy occurred in 18 of 21 patients (86%); however, pain persisted in 20 of 25 patients (80%) treated medically after mean follow-up of 36 ± 28 months (range 10-120 months) (P < .01). Pain resolution with cholecystectomy was independent of demographic variables, hepatobiliary iminodiacetic acid scan ejection fraction, and chronicity of pain. The odds of pain resolution was 19.7 times greater with cholecystectomy than without (odds ratio, 19.7; 95% confidence interval, 4.34, 89.43; P < .01), and remained robust even with the odds adjusted for each covariate. Gallbladder histopathology confirmed chronic cholecystitis in all 21 cholecystectomy specimens. CONCLUSION: Symptomatic gallbladder hyperkinesia could be a new indication for cholecystectomy in adults.

A 3D deep convolutional neural network approach for the automated measurement of cerebellum tracer uptake in FDG PET-CT scans.

PURPOSE: The purpose of this work was to assess the potential of deep convolutional neural networks in automated measurement of cerebellum tracer uptake in F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. METHODS: Three different three-dimensional (3D) convolutional neural network architectures (U-Net, V-Net, and modified U-Net) were implemented and compared regarding their performance in 3D cerebellum segmentation in FDG PET scans. For network training and testing, 134 PET scans with corresponding manual volumetric segmentations were utilized. For segmentation performance assessment, a fivefold cross-validation was used, and the Dice coefficient as well as signed and unsigned distance errors were calculated. In addition, standardized uptake value (SUV) uptake measurement performance was assessed by means of a statistical comparison to an independent reference standard. Furthermore, a comparison to a previously reported active-shape-model-based approach was performed. RESULTS: Out of the three convolutional neural networks investigated, the modified U-Net showed significantly better segmentation performance. It achieved a Dice coefficient of 0.911 ± 0.026, a signed distance error of 0.220 ± 0.103 mm, and an unsigned distance error of 1.048 ± 0.340 mm. When compared to the independent reference standard, SUV uptake measurements produced with the modified U-Net showed no significant error in slope and intercept. The estimated reduction in total SUV measurement error was 95.1%. CONCLUSIONS: The presented work demonstrates the potential of deep convolutional neural networks in automated SUV measurement of reference regions. While it focuses on the cerebellum, utilized methods can be generalized to other reference regions like the liver or aortic arch. Future work will focus on combining lesion and reference region analysis into one approach.