Evaluation of Malignancy Risk of Ampullary Tumors Detected by Endoscopy Using 2-[18F]FDG PET/CT.

OBJECTIVE: We aimed to investigate whether 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. MATERIALS AND METHODS: This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[18F]FDG PET/CT for endoscopy-detected ampullary tumors 5-87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. RESULTS: The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in early-phase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13-36.18; P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80-13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41-19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00-14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16-21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874-0.956] vs. 0.815 [0.732-0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816-0.967) in candidates for endoscopic papillectomy. CONCLUSION: Adding 2-[18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

Use of Technetium-99m-Pyrophosphate Single-Photon Emission Computed Tomography/Computed Tomography in Monitoring Therapeutic Changes of Eplontersen in Patients With Hereditary Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: Hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) is a progressive and fatal disease. Recent evidence indicates that bone scintigraphy may serve as a tool to monitor the effectiveness of hATTR-CM treatment. The objective of this study was to examine how eplontersen therapy influences the semiquantitative uptake of technetium-99m-pyrophosphate in individuals diagnosed with hATTR-CM. METHODS AND RESULTS: We retrospectively analyzed a prospective cohort from the NEURO-TTRansform trial, including patients with hATTR-CM receiving eplontersen (45 mg/4 weeks). A control group comprised patients with hATTR-CM who had not received eplontersen, inotersen, tafamidis, or patisiran. Technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography was conducted at baseline and during follow-up. Thirteen patients with hATTR-CM were enrolled, with 6 receiving eplontersen and 7 serving as the control group. The median follow-up time was 544 days. The eplontersen group exhibited a significant decrease in volumetric heart and lung ratio (3.774 to 2.979, P=0.028), whereas the control group showed no significant change (4.079 to 3.915, P=0.237). Patients receiving eplontersen demonstrated a significantly greater reduction in volumetric heart and lung ratio compared with the control group (-20.7% versus -3.4%, P=0.007). CONCLUSIONS: The volumetric heart and lung ratio used to quantify technetium-99m-pyrophosphate uptake showed a significant reduction subsequent to eplontersen treatment in individuals diagnosed with hATTR-CM. These findings suggest the potential efficacy of eplontersen in treating hATTR-CM and highlight the value of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography as a tool for monitoring therapeutic effectiveness.

Myocardial Flow Assessment After Heart Transplantation Using Dynamic Cadmium-Zinc-Telluride Single-Photon Emission Computed Tomography With 201Tl and 99mTc Tracers and Validated by 13N-NH3 Positron Emission Tomography.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse form of vasculopathy and is the most common cause of long-term cardiovascular mortality in heart transplant patients. This study aimed to investigate the diagnostic performance of 99mTc and 201Tl tracers in the assessment of CAV using cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) for myocardial blood flow (MBF) and myocardial flow reserve (MFR) quantification, which was further validated using 13 N-NH3 positron emission tomography (PET). METHODS: Thirty-eight patients with prior heart transplantation who underwent CZT SPECT and 13 N-NH3 PET dynamic scans were included in this study. CZT SPECT with 99mTc-sestamibi was used in the first 19 patients and 201Tl-chloride for the remaining patients. To determine the diagnostic accuracy of angiographically defined moderate-to-severe CAV, the analysis included patients who underwent angiographic examinations within 1 year of their second scan. RESULTS: There were no significant differences in the patient characteristics between the 201Tl and 99mTc tracer groups. Both 201Tl and 99mTc CZT SPECT-derived stress MBF and MFR values globally and in 3 coronary territories showed good correlations with 13 N-NH3 PET. The 201Tl and 99mTc cohorts did not differ significantly in the correlation coefficients of CZT SPECT versus PET for MBF and MFR, except for stress MBF (201Tl:0.95 versus 99mTc:0.80, P=0.03). 201Tl and 99mTc CZT SPECT were satisfactory for detecting PET MFR <2.0 (201Tl area under the curve, 0.92 [0.71-0.99], 99mTc area under the curve, 0.87 [0.64-0.97]) and angiographically defined moderate-to-severe CAV, and CZT SPECT results were comparable to that of 13 N-NH3 PET (CZT area under the curve, 0.90 [0.70-0.99], PET area under the curve, 0.86 [0.64-0.97]). CONCLUSIONS: This small study suggests that CZT SPECT using 201Tl and 99mTc tracers showed comparable MBF and MFR, and the results correlated well with those of 13 N-NH3 PET. Hence, CZT SPECT with 201Tl or 99mTc tracers can be used to detect moderate-to-severe CAV in patients with prior heart transplantation. However, validation using larger studies is warranted.

Prognostic Value of Interim 18F-DOPA and 18F-FDG PET/CT Findings in Stage 3-4 Pediatric Neuroblastoma.

PURPOSE: This retrospective study aimed to determine the prognostic value of imaging parameters derived from midtherapy 18F-fluorodihydroxyphenylalanine (18F-DOPA) and 18F-FDG PET in pediatric patients with stage 3-4 neuroblastoma. METHODS: We enrolled 32 stage 3-4 pediatric neuroblastoma patients who underwent 18F-DOPA and 18F-FDG PET/CT scans before and after 3 chemotherapy cycles. We measured metabolic and volumetric parameters and applied a metabolic burden scoring system to evaluate the primary tumor extent and soft tissue metastases and that of bone/bone marrow involvement. The associations between these parameters and clinical outcomes were investigated. RESULTS: Over a median follow-up period of 47 months (range, 3-137 months), 16 patients experienced disease progression, and 13 died. After adjustment for clinical factors, multivariate Cox proportional hazard models showed that interim tumor FDG/FDOPA SUVmax (hazard ratio [HR], 5.94; 95% confidence interval [CI], 1.10-34.98) and interim FDOPA whole-body metabolic burden scores (WBMB) (HR, 7.30; 95% CI, 1.50-35.50) were significant prognostic factors for overall survival (OS). Only interim FDOPA WBMB scores (HR, 7.05; 95% CI, 1.02-48.7) were predictive of progression-free survival. Based on median cutoff values, prognosis (OS and progression-free survival) was significantly associated with an interim FDOPA WBMB score ≥21.92 (all P < 0.05) and interim tumor FDG/FDOPA (SUVmax) score ≥0.57 with poor OS (P < 0.05). CONCLUSIONS: Our results indicate that midtreatment FDG and FDOPA PET/CT could serve as prognostic markers in stage 3-4 neuroblastoma patients.

Preoperative 2-[18F]FDG PET-CT aids in the prognostic stratification for patients with primary ampullary carcinoma.

OBJECTIVES: We sought to investigate whether preoperative dual-phase 2-[18F]FDG PET-CT identify predictors for poor survival in patients with ampullary carcinoma receiving pancreaticoduodenectomy. METHODS: The preoperative PET-CT images of patients with resected ampullary carcinoma from June 2007 to July 2017 were analyzed. Survival curves were analyzed using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard model was used to identify potential prognostic factors associated with disease-free survival (DFS) and overall survival (OS). RESULTS: Fifty-four subjects (26 men, 28 women) were enrolled with a median tumor size of 20 mm. All patients were followed for a median period of 36.9 months with 3- and 5-year DFS of 50.3% and 44.2%, and OS of 77.0% and 68.2%, respectively. Parameters associated with DFS in multivariate analysis were lymphovascular invasion (hazard ratio [HR]: 9.45, p < 0.001), involved margin in pathology (HR: 7.67, p < 0.001), and tumor retention index (RI) from the dual-phase PET (HR: 2.41, p = 0.03), whereas involved margin (HR: 13.14, p < 0.001), post-recurrence chemotherapy (HR: 0.10, p < 0.001), and metabolic tumor volume (MTV) (HR: 4.62, p = 0.009) emerged as independent prognostic factors for OS. CONCLUSIONS: Preoperative 2-[18F]FDG PET-CT offered independent prognostic biomarkers in patients with ampullary carcinoma receiving standard surgical resection. KEY POINTS: • 2-[18F]FDG PET-CT offers good survival prediction before operation in primary malignant neoplasms at ampulla of Vater. • Dual-phase PET scan with bowel distention can better delineate Ampulla of Vater and characterize tumor physiology. • Preoperative risk stratification might aid in better treatment planning.

Increased heterogeneity of brain perfusion predicts the development of cerebrovascular accidents.

ABSTRACT: The heterogeneity of brain perfusion is related to the risk factors of thromboembolic events such as antiphospholipid syndrome. However, the effectiveness of brain perfusion heterogeneity as a marker to predict thromboembolic events has not been confirmed. Our objective was to evaluate the effectiveness of brain perfusion heterogeneity as a marker to predict the development of cerebrovascular accidents. In this retrospective cohort study, patients who underwent Tc-99m ECD brain SPECT from January 1, 2006 through December 31, 2008 were included. Each study was reoriented with the Talairach space provided by the NeuroGam Software package. Heterogeneity of brain perfusion was measured as the coefficient of variation. The study outcome was the risk of cerebral vascular accidents in patients with increased heterogeneity of brain perfusion between January 1, 2006 and December 31, 2015. A multiple Cox proportional hazards model was applied to evaluate the risk of cerebrovascular accidents. A total of 70 patients were included in this study. The median age was 39 years (range, 28 - 59 years). There were 55 (78.6%) women. For increased heterogeneity of brain perfusion, the hazard ratio of cerebrovascular accidents was 2.68 (95% CI, 1.41 - 5.09; P = .003) after adjusting for age, sex, hypertension, diabetes mellitus, and dyslipidemia. Our study suggests that increased heterogeneity of brain perfusion is associated with an increased risk of cerebrovascular accidents.

Clinical Utility of FDG PET/CT in Patients with Autoimmune Pancreatitis: a Case-Control Study.

Autoimmune pancreatitis (AIP) shares overlapping clinical features with pancreatic cancer (PC). Importantly, treatment of the two conditions is different. We investigated the clinical usefulness of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with suspected AIP before treatment. From September 2008 to July 2016, 53 patients with suspected AIP at National Taiwan University Hospital had PET/CT prior to therapy to exclude malignancy and evaluate the extent of inflammation. Their scans were compared with those from 61 PC patients. PET imaging features were analyzed using logistic regression. Significant differences in pancreatic tumor uptake morphology, maximum standardized uptake value, high-order primary tumor texture feature (i.e. high-gray level zone emphasis value), and numbers and location of extrapancreatic foci were found between AIP and PC. Using the prediction model, the area under curve of receiver-operator curve was 0.95 (P < 0.0001) with sensitivity, specificity, positive predictive, and negative predictive values of 90.6%, 84.0%, 87.9%, and 87.5% respectively, in differentiating AIP from PC. FDG PET/CT offers high sensitivity, albeit slightly lower specificity in differentiating AIP from PC. Nonetheless, additional systemic inflammatory foci detected by the whole body PET/CT help confirm diagnosis of AIP in these patients before initiating steroid therapy, especially when biopsy is inconclusive.

PET/MRI for evaluating subclinical inflammation of ulcerative colitis.

PURPOSE: To explore the utility of integrated positron emission tomography (PET) / magnetic resonance imaging (MRI) for evaluating subclinical inflammation in patients with ulcerative colitis (UC). MATERIALS AND METHODS: This prospective study was approved by the Institutional Review Board and informed consent was obtained. Between November 2015 and April 2016, 19 consecutive patients with UC in clinical remission were enrolled. These patients underwent 18F-fluorodeoxyglucose PET/MRI (3T) and colonoscopy. Serum high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FC) levels were also obtained. The findings of colonoscopy were graded using the Mayo endoscopic subscore. Quantitative (minimum apparent diffusion coefficient [ADCmin ] and maximum standardized uptake value [SUVmax ]), semiquantitative, and qualitative parameters of PET/MRI were evaluated and correlated with colonoscopic findings. RESULTS: In per-segment analysis, ADCmin was significantly lower and SUVmax and ratio of SUVmax to ADCmin were significantly higher in the colonic segments with active inflammation (Mayo endoscopic subscore ≥2) (P < 0.05). Qualitative MRI score, PET activity grade, and PET/MRI score were also significantly higher in the colonic segments with active inflammation (P < 0.05). Among these parameters, the ratio of SUVmax to ADCmin exhibited the highest area under the receiver operating characteristic curve (AUC) (0.763). In per-patient analysis, the AUC of PET activity grade was 0.778, higher than those of hs-CRP (0.589) and FC (0.722). Using a combined index of FC and PET, an even higher AUC (0.867) was achieved. CONCLUSION: PET/MRI is a potentially useful tool in identifying subclinical inflammation in patients with UC. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:737-745.

Increased heterogeneity of brain perfusion is an early marker of central nervous system involvement in antiphospholipid antibody carriers.

OBJECTIVE: The non-criteria neuropsychiatric manifestations of antiphospholipid syndrome include headache, dizziness, vertigo, seizure, depression and psychosis. There were still no objective methods qualified to detect the early central nervous system involvement in non-criteria antiphospholipid syndrome. We evaluated the effectiveness of Tc-99m ECD SPECT in assessing circulatory insufficiency in the brains of patients with antiphospholipid antibodies and neuropsychiatric symptoms but without thromboembolism. MATERIALS AND METHODS: Patients with a history of positive antiphospholipid antibodies and neuropsychiatric symptoms composed the case group; patients without antiphospholipid antibody served as the control group. Subjects with a history of thromboembolism or autoantibodies to extractable nuclear antigens were excluded. All patients received Tc-99m ECD SPECT studies and were classified by the number of positive antiphospholipid antibodies they carried. The heterogeneity of brain perfusion was defined as the coefficient of variation of the SPECT signals. Analysis of variance (ANOVA) was applied to evaluate the differences between the groups. RESULTS: Total 60 adult patients were included in this study. There were 54 patients in the case group and 6 patients in the control group. The mean age was 38.3 ± 11.5 years. There were 52 women and 8 men. There was no significant difference in the mean brain perfusion between groups (P = 0.69). However, Tc-99m ECD SPECT demonstrated significant heterogeneity of brain perfusion in relation to the number of antiphospholipid antibodies (P = 0.01). CONCLUSIONS: This is the first study demonstrating that Tc-99m ECD SPECT can early detect the increased heterogeneity of brain circulation in non-criteria antiphospholipid antibody carriers.

Risk Stratification of Pediatric Patients With Neuroblastoma Using Volumetric Parameters of 18F-FDG and 18F-DOPA PET/CT.

PURPOSE: This study determined the prognostic value of volumetric parameters derived from pretreatment F-FDG and F-DOPA PET/CT of neuroblastoma and their correlation with clinical and histopathologic features. PATIENTS AND METHODS: A total of 25 children with neuroblastoma underwent pretreatment F-FDG and F-DOPA PET/CT within 4 weeks. The SUVmax of primary tumors on F-FDG and F-DOPA PET were recorded as SUVFDG and SUVDOPA, respectively. For volumetric parameters of primary tumors, 40% of SUVmax was used to generate volume of interest. If the 40% of SUVmax was below 2.5, an SUV threshold of 2.5 was used instead. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), dopaminergic tumor volume (DTV), and total lesion F-DOPA activity (TLDA) were recorded as F-FDG and F-DOPA volumetric parameters. All indices were compared between groups distinguished by survival status and clinical features, including bone marrow involvement, lymph node metastasis, amplification of the MYCN oncogene, invasive features on anatomic images, and risk categories. The Kaplan-Meier method and log-rank test were used to compare the survival curves between groups. RESULTS: The median follow-up period was 28.2 months. Nonsurvivors (20%) tended to have lower SUVDOPA, DTV, and TLDA (P ≤ 0.05), and higher SUVFDG, MTV, and TLG (all P < 0.05). Lower F-DOPA uptake is associated with bone marrow and lymph node metastases (all P < 0.05). Higher F-FDG uptake is associated with MYCN amplification (all P < 0.05) and anatomic invasive features of tumors such as vascular encasement or adjacent organ invasion (TLG, P = 0.05). Only volumetric indices (DTV, TLDA, MTV, and TLG) significantly differed among risk groups (all P < 0.05). CONCLUSIONS: Pretherapeutic F-DOPA and F-FDG PET provided complementary information, and both can be served for risk stratification. Volumetric indices of F-DOPA and F-FDG PET correlate more highly with risk grouping.

Intratumoral Heterogeneity of Pretreatment 18F-FDG PET Images Predict Disease Progression in Patients With Nasal Type Extranodal Natural Killer/T-cell Lymphoma.

PURPOSE: The aim of this study was to investigate whether the textural features of pretreatment F-FDG PET images can predict prognosis for nasal type extranodal natural killer/T-cell lymphoma (ENKTL). MATERIALS AND METHODS: A retrospective analysis of the pretreatment F-FDG PET images of the patients with newly diagnosed nasal type ENKTL from 2008 to 2013 was conducted. Progression-free survival (PFS) was the main outcome measure. The primary tumor was identified and then delineated using the 40% maximum standardized uptake value (SUVmax) thresholding method. The textural features of the pretreatment F-FDG PET images were extracted. The prognostic significance of the textural features of the PET images were examined using the receiver operating characteristic (ROC) curves and Cox regression analysis. P values <0.05 were considered statistically significant. RESULTS: In total, 17 patients were enrolled, among whom 11 showed disease progression and 6 died from the disease during the median follow-up period of 27.2 months. Dissimilarity and low-intensity short-zone emphasis (LISZE) were identified as independent predictors of PFS by using the ROC curves and multivariate Cox analysis after adjusting for the clinical variables. CONCLUSIONS: Dissimilarity and LISZE were the significant predictors of disease progression in patients with nasal type ENKTL and can improve their prognostic stratification.

Comparison of biventricular ejection fractions using cadmium-zinc-telluride SPECT and planar equilibrium radionuclide angiography.

BACKGROUND: We compared biventricular ejection fractions (EFs) from gated blood-pool single-photon emission computed tomography (SPECT) using a cadmium-zinc-telluride camera (CZT-SPECT) with planar equilibrium radionuclide angiography (ERNA) using a NaI gamma camera (NaI-planar). We also evaluated whether imaging time can be reduced without compromising image quality using the CZT camera. METHODS: Forty-eight patients underwent NaI-planar and CZT-SPECT on the same day. CZT-SPECT datasets were re-projected at an LAO orientation similar to ERNA acquisition, forming CZT-repro planar datasets. The resulting biventricular volumetric measurements and EFs were compared. RESULTS: LVEF calculated from CZT-SPECT and CZT-repro correlated better with NaI-planar (r = 0.93 and 0.99, respectively) than RVEF (r = 0.76 and 0.82, respectively). Excellent intra-class correlation and low bias in intra-observer comparisons were observed for the biventricular EFs derived from three datasets. A wider limit of agreement in CZT-SPECT-derived LVEFs, lower correlation and significant bias for NaI-planar, and CZT-repro-derived RVEFs was found in the inter-observer analyses. Nonetheless, the imaging time can be reduced to 4 minutes without increasing variability in EFs using the CZT camera (P = NS). CONCLUSIONS: LVEFs calculated from CZT-SPECT and CZT-repro correlated well with NaI-planar. CZT camera may reduce imaging time while preserving image quality in the assessment of biventricular EFs.