State-of-the-Art Hybrid Imaging of Neuroendocrine Neoplasms.

ABSTRACT: Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines.

Integrating Theranostics Into Patient Care Pathways: AJR Expert Panel Narrative Review.

Theranostics describes the coupling of a diagnostic biomarker and a therapeutic agent (i.e., a theranostic pair) that have a common target in tumor cells or their microenvironment. The term is increasingly associated with in vivo nuclear medicine oncologic applications that couple diagnostic imaging by means of gamma radiation with concomitant localized high-energy particulate radiation to a tissue expressing the common target. Several theranostic pairs have been translated into clinical practice in the United States and are poised to become a mainstay of cancer treatment. The purposes of this article are to review experience with theranostics for solid-organ malignancies and to address the practical integration into care pathways of ß-emitting therapies that include somatostatin analogue radioligands for neuroendocrine tumors, PSMA-directed therapy for prostate cancer, and 131I-MIBG therapy for tumors of neural crest origin. Toxicities related to theranostics administration and indications for cessation of therapy in patients who experience adverse events are also discussed. A multidisciplinary team-based approach for identifying patients most likely to respond to these agents, determining the optimal time for therapy delivery, and managing patient care throughout the therapeutic course is critical to the success of a radiotheranostic program.

Extracellular Vesicle Analysis Allows for Identification of Invasive IPMN.

BACKGROUND AND AIMS: Advances in cross-sectional imaging have resulted in increased detection of intraductal papillary mucinous neoplasms (IPMNs), and their management remains controversial. At present, there is no reliable noninvasive method to distinguish between indolent and high risk IPMNs. We performed extracellular vesicle (EV) analysis to identify markers of malignancy in an attempt to better stratify these lesions. METHODS: Using a novel ultrasensitive digital extracellular vesicle screening technique (DEST), we measured putative biomarkers of malignancy (MUC1, MUC2, MUC4, MUC5AC, MUC6, Das-1, STMN1, TSP1, TSP2, EGFR, EpCAM, GPC1, WNT-2, EphA2, S100A4, PSCA, MUC13, ZEB1, PLEC1, HOOK1, PTPN6, and FBN1) in EV from patient-derived cell lines and then on circulating EV obtained from peripheral blood drawn from patients with IPMNs. We enrolled a total of 133 patients in two separate cohorts: a clinical discovery cohort (n = 86) and a validation cohort (n = 47). RESULTS: From 16 validated EV proteins in plasma samples collected from the discovery cohort, only MUC5AC showed significantly higher levels in high-grade lesions. Of the 11 patients with invasive IPMN (inv/HG), 9 had high MUC5AC expression in plasma EV of the 11 patients with high-grade dysplasia alone, only 1 had high MUC5AC expression (sensitivity of 82%, specificity of 100%). These findings were corroborated in a separate validation cohort. The addition of MUC5AC as a biomarker to imaging and high-riskstigmata allowed detection of all cases requiring surgery, whereas imaging and high-risk stigmata alone would have missed 5 of 14 cases (36%). CONCLUSIONS: MUC5AC in circulating EV can predict the presence of invasive carcinoma within IPMN. This approach has the potential to improve the management and follow-up of patients with IPMN including avoiding unnecessary surgery.

Tuberous sclerosis complex-associated nonfunctional pancreatic neuroendocrine tumors: Management and surgical outcomes.

We aimed to further characterize pancreatic involvement in tuberous sclerosis complex (TSC), with a focus on management of TSC-associated nonfunctional pancreatic neuroendocrine tumors (PNETs). This was a retrospective chart review of a large cohort of TSC patients. A total of 637 patients with a confirmed diagnosis of TSC were seen at the Herscot Center for Tuberous Sclerosis Complex at Massachusetts General Hospital. Of the 637 total patients with a confirmed diagnosis of TSC, 28 patients were found to have varying pancreatic findings ranging from simple-appearing cysts to well-differentiated PNETs. Thirteen of the 28 patients had PNET confirmed on pathology; 10 of these tumors were resected at Massachusetts General Hospital. None of the patients had serious perioperative or postoperative complications; only one of the patients had a recurrence following resection. As roughly 4.4% of our TSC patient population had pancreatic involvement, surveillance abdominal imaging should include evaluation of the pancreas instead of limiting to a renal protocol. Additionally, given the low risk of complications and recurrence combined with documented risk of metastasis in TSC-associated PNET, TSC patients with pancreatic lesions suspicious for PNETs should be considered as surgical candidates.

Robustness of dual-energy CT-derived radiomic features across three different scanner types.

OBJECTIVES: To investigate the robustness of radiomic features between three dual-energy CT (DECT) systems. METHODS: An anthropomorphic body phantom was scanned on three different DECT scanners, a dual-source (dsDECT), a rapid kV-switching (rsDECT), and a dual-layer detector DECT (dlDECT). Twenty-four patients who underwent abdominal DECT examinations on each of the scanner types during clinical follow-up were retrospectively included (n = 72 examinations). Radiomic features were extracted after standardized image processing, following ROI placement in phantom tissues and healthy appearing hepatic, splenic and muscular tissue of patients using virtual monoenergetic images at 65 keV (VMI65keV) and virtual unenhanced images (VUE). In total, 774 radiomic features were extracted including 86 original features and 8 wavelet transformations hereof. Concordance correlation coefficients (CCC) and analysis of variances (ANOVA) were calculated to determine inter-scanner robustness of radiomic features with a CCC of ≥ 0.9 deeming a feature robust. RESULTS: None of the phantom-derived features attained the threshold for high feature robustness for any inter-scanner comparison. The proportion of robust features obtained from patients scanned on all three scanners was low both in VMI65keV (dsDECT vs. rsDECT:16.1% (125/774), dlDECT vs. rsDECT:2.5% (19/774), dsDECT vs. dlDECT:2.6% (20/774)) and VUE (dsDECT vs. rsDECT:11.1% (86/774), dlDECT vs. rsDECT:2.8% (22/774), dsDECT vs. dlDECT:2.7% (21/774)). The proportion of features without significant differences as per ANOVA was higher both in patients (51.4-71.1%) and in the phantom (60.6-73.4%). CONCLUSIONS: The robustness of radiomic features across different DECT scanners in patients was low and the few robust patient-derived features were not reflected in the phantom experiment. Future efforts should aim to improve the cross-platform generalizability of DECT-derived radiomics. KEY POINTS: • Inter-scanner robustness of dual-energy CT-derived radiomic features was on a low level in patients who underwent clinical examinations on three DECT platforms. • The few robust patient-derived features were not confirmed in our phantom experiment. • Limited inter-scanner robustness of dual-energy CT derived radiomic features may impact the generalizability of models built with features from one particular dual-energy CT scanner type.

Hereditary and Sporadic Pheochromocytoma: Comparison of Imaging, Clinical, and Laboratory Features.

BACKGROUND. A considerable fraction of pheochromocytomas initially suspected to be sporadic, whether or not symptomatic, are a result of germline mutations. OBJECTIVE. The purpose of this article is to compare imaging features between hereditary and sporadic pheochromocytomas. METHODS. This retrospective study included 71 patients (39 women, 32 men; median age, 48 years) who underwent adrenal pheochromocytoma resection from January 2002 to October 2021 after preoperative CT or MRI. Two radiologists independently reviewed examinations to assess features of the largest resected pheochromocytoma. Interreader agreement was assessed by prevalence-adjusted bias-adjusted kappa coefficients; a third radiologist resolved discrepancies for further analysis. Genetic testing was used to classify pheochromocytomas as hereditary or sporadic and to classify hereditary pheochromocytomas by germline mutation clusters. Symptoms associated with pheochromocytomas and preoperative biochemical laboratory values were recorded. Groups were compared using Kruskal-Wallis, Fisher exact, and chi-square tests, and false-discovery rate-adjusted p values were computed to account for multiple comparisons. RESULTS. Hereditary pheochromocytoma (n = 32), compared with sporadic pheochromocytoma (n = 39), was associated with younger median age (38 vs 52 years, p = .001) and smaller median size (24 vs 40 mm, p < .001). Interreader agreement for CT and MRI features, expressed as kappa, ranged from 0.44 to 1.00. Hereditary and sporadic pheochromocytoma showed no difference in frequency of calcifications, hemorrhage, cystic change/necrosis, or macroscopic fat on CT, or in frequency of hemorrhage, cystic change/necrosis, macroscopic fat, or microscopic fat on MRI (p > .05). When combining CT and MRI, cystic change/necrosis was observed in 35% of hereditary versus 67% of sporadic pheochromocytomas (p = .10). Hereditary pheochromocytoma, compared with sporadic, had lower frequency of symptoms (31% vs 74%; p = .004) and lower 24-hour urinary normetanephrines (1.1 vs 5.1 times upper limits of normal, p = .006). Among hereditary pheochromocytomas, cystic change/necrosis (when assessable on imaging) was present in 18% and 45% of those with cluster 1 (n = 11) and cluster 2 (n = 21) germ-line mutations, respectively. CONCLUSION. Hereditary pheochromocytomas, compared with sporadic, are detected at a younger age and smaller size, produce lower 24-hour urinary normetanephrines, are less often symptomatic, and may less frequently show cystic change/necrosis. CLINICAL IMPACT. Imaging findings may complement clinical and biochemical features in raising suspicion for a previously unsuspected germline mutation in patients with pheochromocytoma.

Rare Mesenchymal Tumors of the Pelvis: Imaging and Pathologic Correlation.

Most pelvic tumors originate from the organs. Less commonly, tumors can arise from the various anatomic pelvic compartments and are comprised of mesenchymal tissue: muscles, connective tissue, vessels, lymphatics, and fat. Among some of the rarer entities are benign tumors (eg, angiomyxoma, cellular angiofibroma, and desmoid fibromatosis), malignant tumors (eg, sarcoma), and tumors that can manifest as benign or malignant (eg, solitary fibrous tumor or nerve sheath tumor). Because these tumors are uncommon and often manifest with nonspecific clinical features, imaging (usually MRI) is an initial step in the evaluation. Radiologists interpreting these images are asked to help narrow the differential diagnosis and assess the likelihood of malignancy for treatment planning. Thus, the MRI report should include the imaging features that would indicate the underlying tissue histology for pathologic diagnosis as well as a description of the anatomic extent and pattern of growth. The authors describe multiple locally aggressive benign and malignant mesenchymal tumors and highlight characteristic clinical and imaging features that enable the radiologist to narrow the differential diagnosis. The anatomic spaces of the pelvis are reviewed with illustrations to aid the radiologist in describing these tumors, which often span multiple pelvic compartments. Tumor appearance at T2-weighted, diffusion-weighted, and postcontrast MRI is summarized and illustrated with correlation at CT or fluorodeoxyglucose PET/CT, when available. MRI features that correspond to specific types of tissue (eg, myxoid, fibrous, or vascular) are highlighted and correlated with images from pathologic evaluation. Online supplemental material is available for this article. ©RSNA, 2021.

PI-RADS: multiparametric MRI in prostate cancer.

Multiparametric MRI of the prostate gland has become the initial evaluation of biopsy naïve men with a clinical suspicion for prostate cancer. PI-RADS 2.1 is a joint initiative and framework for prostate MRI acquisition and reporting, which aims to standardize technique and interpretation across centers. Building upon experience accrued following the introduction of PI-RADS 2.0, version 2.1 provides key updates and important clarifications, although it is intended to be an active document, which continues to be updated. Continued advances in our understanding of prostate cancer and progress in imaging technology will undoubtedly shape future iterations of the reporting system.

US Elastography in Hepatic Fibrosis-Radiology In Training.

A 72-year-old woman with an elevated body mass index and moderate alcohol intake was seen in the gastroenterology clinic. The patient had a past history of abnormal liver function tests and previous biopsy-proven steatosis with early fibrosis. She was reevaluated, following an initial loss to follow-up, by using US elastography to assess for fibrosis progression. The utility of US elastography in the noninvasive diagnosis and longitudinal monitoring of hepatic fibrosis is discussed. An overview of available technologies, including transient elastography and shear-wave elastography, is provided. ©RSNA, 2021 Online supplemental material is available for this article.

Multisystem Assessment of the Imaging Manifestations of Coagulopathy in Hospitalized Patients With Coronavirus Disease (COVID-19).

BACKGROUND. Coronavirus disease (COVID-19) is known to be associated with a distinct form of coagulopathy. OBJECTIVE. The purpose of this study was to describe the imaging manifestations of COVID-19-associated coagulopathy across anatomic sites and modalities in hospitalized patients and to identify clinical variables associated with positive imaging findings. METHODS. We conducted a retrospective review of consecutive adult patients with COVID-19 admitted to our hospital over a 3-week period. Data on patient demographics, hematologic values, cross-sectional imaging examinations, and clinical outcomes (death and intubation) were collected. Imaging was reviewed for manifestations of coagulopathy. Multivariable logistic regression analyses were performed to assess associations of patient demographics, hematologic markers, and outcomes with the need for imaging and imaging manifestations of coagulopathy. RESULTS. Of 308 hospitalized patients with COVID-19, 142 (46%) underwent 332 cross-sectional imaging examinations. Of these, 37 (26%) had imaging results positive for coagulopathy. The most common imaging manifestations of coagulopathy were pulmonary embolus (n = 21) on contrast-enhanced CT or CTA, thrombus in the upper- or lower-extremity veins (n = 13) on Doppler ultrasound, end-organ infarction in the bowel (n = 4) and kidney (n = 4) on contrast-enhanced CT, and thrombus or parenchymal infarction in the brain (n = 2) on contrast-enhanced CTA or MRI with MRA. Among patients with imaging results positive for coagulopathy, eight (22%) had multisite involvement. Thrombi were multifocal in four of five patients with positive upper-extremity and three of eight patients with positive lower-extremity examination results and involved superficial veins, deep veins, or both. In multivariable analysis, intubation (p < .001) and prolonged prothrombin time (p = .04) were significantly associated with undergoing imaging. No patient variable was significantly associated with imaging results positive for coagulopathy (p > .05). CONCLUSION. Imaging commonly shows manifestations of coagulopathy in hospitalized patients with COVID-19. Over one-fifth of patients with such manifestations show multisite involvement. Clinical variables poorly predict which patients have positive imaging results, indicating a complementary role of imaging in detecting COVID-19-associated coagulopathy. CLINICAL IMPACT. In patients with COVID-19 with suspected systemic coagulopathy, pulmonary CTA, extremity Doppler ultrasound, contrast-enhanced abdominal CT, and contrast-enhanced brain MRI and MRA may all be appropriate in the absence of imaging contraindications.

PI-RADS Versions 2 and 2.1: Interobserver Agreement and Diagnostic Performance in Peripheral and Transition Zone Lesions Among Six Radiologists.

BACKGROUND. PI-RADS version 2.1 (v2.1) modifications primarily address transition zone (TZ) interpretation. The revisions also impact peripheral zone (PZ) interpretation, which has received less attention. OBJECTIVE. The purpose of this study was to compare interobserver agreement of PI-RADS version 2 (v2) and v2.1 in the prostate PZ and TZ and perform a pilot comparison of their diagnostic performance in the two zones. METHODS. Six radiologists with varying experience retrospectively assessed 80 prostate lesions (40 PZ, 40 TZ) on MRI in separate sessions for PI-RADS v2 and v2.1. Interobserver agreement was assessed using Conger kappa (κ). For 50 lesions with pathology data, average AUC for detecting clinically significant cancer was compared between versions using multireader multicase statistical methods. Error variance and covariance results informed post hoc power analysis. RESULTS. Interobserver agreement for PI-RADS category 4 or greater was higher for version 2.1 (κ = 0.64) than version 2 (κ = 0.51) in the PZ, but similar for version 2 (κ = 0.64) and version 2.1 (κ = 0.60) in the TZ. The PI-RADS v2.1 DWI descriptor "linear/wedge-shaped" had higher agreement than its predecessor version 2 descriptor "indistinct hypointense" (κ = 0.52 vs κ = 0.18) and yielded 14 more true-negative versus five more false-negative interpretations. The ADC signal descriptor "markedly hypointense," for which only version 2.1 provides a specific definition, had lower agreement in version 2.1 (κ = 0.26) than version 2 (κ = 0.52). Modified TZ T2-weighted category 2 descriptors in version 2.1 had fair agreement (κ = 0.21), and agreement for PI-RADS category 2 in the TZ was lower in version 2.1 (κ = 0.31) than version 2 (κ = 0.57). DWI upgraded a TZ lesion category from 2 to 3 in four patients, detecting two additional cancers. Average AUC was not different between versions 2 and 2.1 for the PZ (AUC, 0.81 vs 0.85; p = .24) or the TZ (AUC, 0.69 vs 0.69; p = .94), though among experienced readers AUC was higher for version 2.1 than version 2 for the PZ (0.91 vs 0.82; p = .001). Overall performance comparison had sufficient power (0.8) to detect a 0.085 difference in AUC. CONCLUSION. Interobserver agreement improved using PI-RADS v2.1 in the PZ but not the TZ. Diagnostic performance improved using version 2.1 only in the PZ for experienced readers. Specific version 2.1 modifications yielded mixed results. CLINICAL IMPACT. The impact of PI-RADS v2.1 in the PZ is notable given the emphasis on version 2.1 TZ modifications. The findings suggest areas in which additional modification could further improve interobserver agreement and performance.

Quality of same-day CT colonography following incomplete optical colonoscopy.

OBJECTIVES: Same-day CT colonography (CTC) following incomplete optical colonoscopy allows patients to avoid both a delayed diagnosis and the need for repeat bowel preparation. The aim of our study is to establish the diagnostic quality of same-day CT colonography following an incomplete optical colonoscopy. METHODS: We performed a retrospective review of patients undergoing same-day CT colonography following an incomplete colonoscopy at our center between July 2015 and December 2017 (N = 245). We divided the large bowel into thirteen subsegments in each patient. Using a semiquantitative scoring system, the quality of bowel preparation, adequacy of fecal tagging, and luminal distension were assessed in each subsegment on all views performed. A combined score for each subsection was obtained. RESULTS: Ninety-nine percent of studies did not require a repeat CTC or optical colonoscopy. Median values for bowel preparation and fecal tagging were satisfactory across the bowel segments for the cohort and luminal distension was acceptable in all but three patients. CONCLUSIONS: Same-day CTC should be considered in centers with capacity, following an incomplete optical colonoscopy. Same-day completion CTCs are of high diagnostic quality and this approach allows patients to avoid repeat bowel cleansing or a delayed diagnosis. KEY POINTS: • Same-day CT colonography is a high-quality examination that can be performed following incomplete optical colonoscopy. • Same-day CT colonography should be considered for patients with incomplete optical colonoscopy in centers with the capacity to offer this service. • Same-day CTC can avoid a delay in diagnosis and avoids repeat bowel preparation.

Update on Renal Neoplasms: Clinicopathologic-Radiologic Correlation With Case-Based Examples.

OBJECTIVE. This article provides a brief overview of the clinicopathologic and radiologic correlation of 12 renal neoplasms, encompassing the conventional subtypes of renal cell carcinoma and a few of the newly recognized subtypes from the 2016 World Health Organization classification of renal tumors. In addition, we touch upon infrequent neoplasms that may enter the differential diagnosis of a renal mass, with corresponding radiologic and gross images and histologic findings of case-based examples. CONCLUSION. Familiarity with the radiologic and pathologic characteristics of renal cell carcinoma and other renal neoplasms is important to correctly identify and treat these masses.

Multimodality Imaging Features of Immunoglobulin G4-related Vessel Involvement.

Immunoglobulin 4 (IgG4)-related disease is a chronic immune-mediated fibroinflammatory disorder. Involvement of the vascular system, including large- and medium-sized vessels, is increasingly recognized. The varied appearances of vascular involvement reflect the sequela of chronic inflammation and fibrosis and can include aortitis and periaortitis with resultant complications such as aneurysm formation and dissection. A diagnosis of IgG4-related large vessel involvement should be considered when there is known or suspected IgG4-related disease elsewhere. Other organs that are typically affected in IgG4-related disease include the lacrimal and salivary glands, thyroid, pancreas, biliary tree, lungs, kidneys, and meninges. Diagnosis typically requires careful correlation with clinical, imaging, serum, and pathologic findings. Patients may be managed with corticosteroid therapy or the anti-CD20 monoclonal antibody, rituximab, if needed. The varied clinical presentations and imaging features of large vessel involvement are discussed herein. Keywords: Vascular, Inflammation, Aorta, IgG4-related Vessel Involvement © RSNA, 2024.

Neurolymphomatosis in Recrudescent Diffuse Large B-cell Lymphoma.

Neurolymphomatosis is an uncommon manifestation of lymphoma, often presenting with painful polyneuropathy or polyradiculopathy and concomitant distal extremity weakness. Differentiation from other etiologies resulting in similar neuropathic symptoms such as compressive or inflammatory pathologies can be difficult and often results in delayed diagnosis. Here we describe a case of neurolymphomatosis affecting a 64-year-old man with a history of diffuse large B-cell lymphoma (DLBCL) in remission presenting with a right-sided foot drop following a gunshot wound. MRI at that time demonstrated thickening and enhancement of the cauda equina nerve roots. Over the course of the subsequent eight months, he developed left lower extremity sensory symptoms, left-sided foot drop and signs of upper motor neuron involvement, including left facial weakness, dysphonia, and dysphagia. 18F-FDG PET/CT revealed intensely avid left lumbosacral nerve roots, bilateral lower extremity and left upper extremity neurovascular bundles. Left sural nerve biopsies showed infiltration of DLBCL and confirmed neurolymphomatosis. We highlight the role of 18F-FDG PET/CT, with histological verification, for the diagnosis of an extended course of neurolymphomatosis occurring in the absence of typical painful neuropathy but with cranial and peripheral neuropathies.

Extracellular vesicle analysis of plasma allows differential diagnosis of atypical pancreatic serous cystadenoma.

Increased use of cross-sectional imaging has resulted in frequent detection of incidental cystic pancreatic lesions. Serous cystadenomas (SCAs) are benign cysts that do not require surgical intervention unless symptomatic. Unfortunately, up to half of SCAs do not have typical imaging findings ("atypical SCAs"), overlap with potentially malignant precursor lesions, and thus pose a diagnostic challenge. We tested whether the analysis of circulating extracellular vesicle (EV) biomarkers using a digital EV screening technology (DEST) could enhance the discrimination of cystic pancreatic lesions and avoid unnecessary surgical intervention in these atypical SCAs. Analysis of 25 different protein biomarkers in plasma EV from 68 patients identified a putative biomarker signature of Das-1, Vimentin, Chromogranin A, and CAIX with high discriminatory power (AUC of 0.99). Analysis of plasma EV for multiplexed markers may thus be helpful in clinical decision-making.