The Role of PET Imaging in Patients with Prion Disease: A Literature Review.

Prion diseases are rare, rapidly progressive, and fatal incurable degenerative brain disorders caused by the misfolding of a normal protein called PrPC into an abnormal protein called PrPSc. Their highly variable clinical presentation mimics various degenerative and non-degenerative brain disorders, making diagnosis a significant challenge for neurologists. Currently, definitive diagnosis relies on post-mortem examination of nervous tissue to detect the pathogenic prion protein. The current diagnostic criteria are limited. While structural magnetic resonance imaging (MRI) remains the gold standard imaging modality for Creutzfeldt-Jakob disease (CJD) diagnosis, positron emission tomography (PET) using 18fluorine-fluorodeoxyglucose (18F-FDG) and other radiotracers have demonstrated promising potential in the diagnostic assessment of prion disease. In this context, a comprehensive and updated review exclusively focused on PET imaging in prion diseases is still lacking. We review the current value of PET imaging with 18F-FDG and non-FDG tracers in the diagnostic management of prion diseases. From the collected data, 18F-FDG PET mainly reveals cortical and subcortical hypometabolic areas in prion disease, although fails to identify typical pattern or laterality abnormalities to differentiate between genetic and sporadic prion diseases. Although the rarity of prion diseases limits the establishment of a definitive hypometabolism pattern, this review reveals some more prevalent 18F-FDG patterns associated with each disease subtype. Interestingly, in both sporadic and genetic prion diseases, the hippocampus does not show significant glucose metabolism alterations, appearing as a useful sign in the differential diagnosis with other neurodegenerative disease. In genetic prion disease forms, PET abnormality precedes clinical manifestation. Discordant diagnostic value for amyloid tracers among different prion disease subtypes was observed, needing further investigation. PET has emerged as a potential valuable tool in the diagnostic armamentarium for CJD. Its ability to visualize functional and metabolic brain changes provides complementary information to structural MRI, aiding in the early detection and confirmation of CJD.

Short 2-[18F]Fluoro-2-Deoxy-D-Glucose PET Dynamic Acquisition Protocol to Evaluate the Influx Rate Constant by Regional Patlak Graphical Analysis in Patients With Non-Small-Cell Lung Cancer.

Purpose: To test a short 2-[18F]Fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET dynamic acquisition protocol to calculate Ki using regional Patlak graphical analysis in patients with non-small-cell lung cancer (NSCLC). Methods: 24 patients with NSCLC who underwent standard dynamic 2-[18F]FDG acquisitions (60 min) were randomly divided into two groups. In group 1 (n = 10), a population-based image-derived input function (pIDIF) was built using a monoexponential trend (10-60 min), and a leave-one-out cross-validation (LOOCV) method was performed to validate the pIDIF model. In group 2 (n = 14), Ki was obtained by standard regional Patlak plot analysis using IDIF (0-60 min) and tissue response (10-60 min) curves from the volume of interests (VOIs) placed on descending thoracic aorta and tumor tissue, respectively. Moreover, with our method, the Patlak analysis was performed to obtain Ki,s using IDIFFitted curve obtained from PET counts (0-10 min) followed by monoexponential coefficients of pIDIF (10-60 min) and tissue response curve obtained from PET counts at 10 min and between 40 and 60 min, simulating two short dynamic acquisitions. Both IDIF and IDIFFitted curves were modeled to assume the value of 2-[18F]FDG plasma activity measured in the venous blood sampling performed at 45 min in each patient. Spearman's rank correlation, coefficient of determination, and Passing-Bablok regression were used for the comparison between Ki and Ki,s. Finally, Ki,s was obtained with our method in a separate group of patients (group 3, n = 8) that perform two short dynamic acquisitions. Results: Population-based image-derived input function (10-60 min) was modeled with a monoexponential curve with the following fitted parameters obtained in group 1: a = 9.684, b = 16.410, and c = 0.068 min-1. The LOOCV error was 0.4%. In patients of group 2, the mean values of Ki and Ki,s were 0.0442 ± 0.0302 and 0.33 ± 0.0298, respectively (R 2 = 0.9970). The Passing-Bablok regression for comparison between Ki and Ki,s showed a slope of 0.992 (95% CI: 0.94-1.06) and intercept value of -0.0003 (95% CI: -0.0033-0.0011). Conclusions: Despite several practical limitations, like the need to position the patient twice and to perform two CT scans, our method contemplates two short 2-[18F]FDG dynamic acquisitions, a population-based input function model, and a late venous blood sample to obtain robust and personalized input function and tissue response curves and to provide reliable regional Ki estimation.

Cavernous Hemangioma: A Potential Pitfall at Delayed 18F-FDG PET/CT Scan.

ABSTRACT: We report the case of a 72-year-old woman who underwent neoadjuvant chemotherapy, right quadrantectomy (invasive ductal carcinoma, G3, pT2pN1pMx), and adjuvant radiotherapy. Two years later, a follow-up CT revealed a hepatic nodule of approximately 1 cm suspected for metastasis. 18F-FDG PET/CT was performed for restaging. Standard total-body 18F-FDG PET/CT acquisition showed no abnormal 18F-FDG uptake in the hepatic nodule. A delayed 18F-FDG PET/CT acquisition of upper abdomen was performed at 180 minutes postradiopharmaceutical injection and showed increased 18F-FDG uptake in the hepatic nodule. After nodule resection, the histological examination proved a cavernous hemangioma.

The Prognostic Value of 18F-FDG PET Imaging at Staging in Patients with Malignant Pleural Mesothelioma: A Literature Review.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy, frequently diagnosed at locally-advanced/metastatic stages. Due to a very poor prognosis and limited treatment options, the need to identify new prognostic markers represents a great clinical challenge. The prognostic role of metabolic information derived from Positron Emission Tomography (PET) with 18F-Fluoro-deoxy-glucose (18F-FDG) has been investigated in different MPM settings, however with no definitive consensus. In this comprehensive review, the prognostic value of FDG-PET imaging exclusively performed at staging in MPM patients was evaluated, conducting a literature search on PubMed/MEDLINE from 2010 to 2020. From the 19 selected studies, despite heterogeneity in several aspects, staging FDG-PET imaging emerges as a valuable prognostic biomarker, with higher tumor uptake predictive of worse prognosis, and with volumetric metabolic parameters like Metabolic Tumor Volume, (MTV) and Total Lesion Glycolisis (TLG) performing better than SUVmax. However, PET uptake parameters were not always confirmed as independent prognostic factors, especially in patients previously treated with pleurodesis and with a non-epithelioid histotype. Future prospective studies in larger and clinically homogeneous populations, and using more standardized methods of PET images analysis, are needed to further validate the value of staging FDG-PET in the prognostic MPM stratification, with a potential impact on better patient-tailored treatment planning, in the perspective of personalized medicine.

Detection of recurrent pancreatic cancer: value of second-opinion interpretations of cross-sectional images by subspecialized radiologists.

PURPOSE: To investigate the value of second-opinion interpretation of cross-sectional images by subspecialized radiologists to diagnose recurrent pancreatic cancer after surgery. METHODS: The IRB approved and issued a waiver of informed consent for this retrospective study. Initial and second-opinion interpretations of 69 consecutive submitted MRI or CT follow-up after pancreatic cancer resection between January 1, 2009 and December 31, 2013 were evaluated by one oncologic imaging radiologist, who was blinded to patient's clinical details and histopathologic data. The reviewer was asked to classify each interpretation in reference of the diagnosis of PDAC recurrence. It was also recorded if the radiologic interpretation recommended additional imaging studies to confirm recurrence. The diagnosis of recurrence was determined by pathology when available, otherwise by imaging follow-up, clinical, or laboratory assessments. Cohen's kappa statistic was used to assess agreement between initial and second-opinion interpretations. The differences between the initial and second-opinion interpretations were examined using McNemar test or Bowker's test of symmetry. RESULTS: Disagreement on recurrence between the initial report and the second-opinion interpretation was observed in 32% of cases (22/69; k = 0.44). Second-opinion interpretations had a higher sensitivity and a higher specificity on recurrence compared to the initial interpretations (0.93 vs. 0.75 and 0.90 vs. 0.68, respectively), and the difference in specificity was significant (p = 0.016). Additional imaging studies were recommended more frequently in the initial interpretation (22% vs. 6%, p = 0.006). CONCLUSIONS: Our study shows the second-opinion interpretation by subspecialized radiologists improves the detection of pancreatic cancer recurrence after surgical resection.

PET/MRI for neuroendocrine tumors: a match made in heaven or just another hype?

PURPOSE: To evaluate the current literature on technical feasibility and diagnostic value of PET/MRI in management of patients with neuroendocrine tumors (NETs). METHODS: A systematic literature search of the PubMed/MEDLINE database identified studies that evaluated the role of simultaneous PET/MRI for the evaluation of neuroendocrine tumors in human subjects. Exclusion criteria included studies lacking simultaneous PET/MRI, absence of other than attenuation-correction MRI pulse sequences, and case reports. No data-pooling or statistical analysis was performed due to the small number of articles and heterogeneity of the methodologies. RESULTS: From the 21 identified articles, five were included, which demonstrated successful technical feasibility of simultaneous PET/MRI through various imaging protocols in a total of 105 patients. All articles demonstrated equal or superior detection of liver lesions by PET/MRI over PET/CT. While one study reported superior detection of bone lesions by PET/MRI, two demonstrated favorable detection by PET/CT. Two studies demonstrated superiority of PET/CT in detection of nodal metastases; three studies reported the pitfall of PET/MRI in detection of lung lesion. CONCLUSION: The current literature reports successful technical feasibility of PET/MRI for imaging of NETs. While whole-body PET/CT in conjunction with an abdominal MRI may serve as a comprehensive approach for baseline staging, follow up with PET/MRI may be preferred for those with liver-only disease. Another possible role for PET/MRI is to provide a multiparametric approach to follow up of response to treatment. With further advances in MRI imaging acquisitions and post-processing techniques, PET/MRI may become more applicable to a broader group of patients with NETs, and possibly the imaging modality of choice for this patient population.

State of the art in magnetic resonance imaging of hepatocellular carcinoma.

Background Liver cancer is the sixth most common cancer worldwide and the second leading cause of cancer mortality. Chronic liver disease caused by viral infection, alcohol abuse, or other factors can lead to cirrhosis. Cirrhosis is the most important clinical risk factor for hepatocellular carcinoma (HCC) whereby the normal hepatic architecture is replaced by fibrous septa and a spectrum of nodules ranging from benign regenerative nodules to HCC, each one of them with different imaging features. Conclusions Furthermore, advanced techniques including the quantification of hepatic and intralesional fat and iron, magnetic resonance elastography, radiomics, radiogenomics, and positron emission tomography (PET)-MRI are highly promising for the extraction of new imaging biomarkers that reflect the tumor microenvironment and, in the future, may add decision-making value in the management of patients with HCC.

Complete metabolic response to therapy of hepatic epithelioid hemangioendothelioma evaluated with 18F-fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography: A CARE case report.

RATIONALE: Hepatic epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor of endothelial origin with a highly variable clinical presentation and natural history. Given its vascular origin, new therapies with inhibitors of vascular endothelial growth factor (VEGF) have been introduced in the treatment of these patients and have shown promising results. Few reports have described the role of F-Fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography (F-FDG PET/CT) in the evaluation of this tumor after treatment with anti-angiogenic agents. Our case reports how F-FDG PET-CT scan was critical in the assessment of this tumor after treatment with an anti-angiogenic agent, Pazopanib, demonstrating complete metabolic response. PATIENT CONCERNS: A 30-year-old man with no previous significant medical history presented with pain in the right upper quadrant for over a year. DIAGNOSES: Multiple hepatic masses were found on abdominal ultrasound. Liver biopsy confirmed the diagnosis of epithelioid hemangioendothelioma. F-FDG PET/CT was performed for staging. Multiple FDG-avid hepatic, splenic, and lymph nodes lesions were detected on F-FDG PET/CT. A subsequent spleen biopsy confirmed splenic involvement. Immunohistochemistry was positive for CD31, CD34, and ERG, supporting the diagnosis of epithelioid hemangioendothelioma. INTERVENTIONS: A 1-year cyclophosphamide treatment was provided followed by Pazopanib for 17 months. OUTCOMES: Six years after the first F-FDG PET/CT, F-FDG PET/CT performed for restaging demonstrated complete metabolic response to therapy. Follow-up CT demonstrated no interval changes in size of some of the treated lesions. LESSON: F-FDG PET/CT is useful for baseline assessment and posttreatment follow-up of this rare cancer.