Adequacy of sigmoidoscopy as compared to colonoscopy for assessment of disease activity in patients of ulcerative colitis: a prospective study.

Background/Aims: Patients of ulcerative colitis (UC) on follow-up are routinely evaluated by sigmoidoscopy. There is no prospective literature to support this practice. We assessed agreement between sigmoidoscopy and colonoscopy prospectively in patients with disease extent beyond the sigmoid colon. Methods: We conducted a prospective observational study at a tertiary care institute for agreement between sigmoidoscopy and colonoscopy. We assessed endoscopic activity using the Mayo Endoscopic Score (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and histological activity using the Nancy Index (NI), Robarts Histopathology Index (RHI), and Simplified Geboes Score (SGS). Results: Sigmoidoscopy showed a strong agreement with colonoscopy for MES and UCEIS with a kappa (K) of 0.96 and 0.94 respectively. The misclassification rate for MES and UCEIS was 3% and 5% respectively. Sigmoidoscopy showed perfect agreement (K = 1.00) with colonoscopy for assessment of the presence of endoscopic activity in the colon using MES ??1 as activity criteria and strong agreement (K = 0.93) using MES > 1 as activity criteria. Sigmoidoscopy showed strong agreement with colonoscopy for assessment of the presence of endoscopic activity using UCEIS (K = 0.92). Strong agreement was observed between sigmoidoscopy and colonoscopy using NI (K = 0.86), RHI (K = 1.00), and SGS (K = 0.92) for the detection of histological activity. The misclassification rate for the detection of histological activity was 2%, 0%, and 1% for NI, RHI, and SGS respectively. Conclusions: Sigmoidoscopy showed strong agreement with colonoscopy for endoscopic and histologic disease activity. Sigmoidoscopy is adequate for assessment of disease activity in patients with UC during follow-up evaluation.

Challenges in Diagnosis of Esophageal Tuberculosis.

Esophageal tuberculosis (TB) is a rare manifestation of extrapulmonary TB, accounting for <0.2% of all TB cases. Esophageal TB most commonly presents with dysphagia, odynophagia, retrosternal pain, and systemic symptoms like decreased appetite, loss of weight, and low-grade fever as associated or other presentations. We report a similar case recently encountered as an elderly male patient presented with chronic dysphagia to solids, loss of appetite, and significant loss of weight. Radiological and endoscopy pictures looked like esophageal cancer with histopathological examination (twice) negative for the same. Diagnosis of esophageal TB was confirmed by GeneXpert Ultra of biopsy sample and histopathological examination was suggestive of granulomatous esophagitis. The patient improved on 6 months antitubercular therapy. The unique aspect of this case was how the lesion mimicked an esophageal carcinoma on imaging which posed a diagnostic challenge.

A Rare Cause of Acute on Chronic Liver Failure (ACLF): Bakuchi-Induced Liver Injury.

Psoralea corylifolia Linn (Bakuchi or Babchi), commonly known as purple fleabane, is a popular herb used in Ayurvedic traditional medicine. Its seeds, called Fructus Psoraleae, are traditionally used for treating leprosy, vitiligo, and psoriasis in the absence of empirical evidence. We report the first case of acute on chronic liver failure (ACLF) caused by Bakuchi, a well-documented hepatotoxic agent, in a middle-aged female. Her liver function deteriorated progressively which prompted us to go for a liver biopsy which was consistent with diagnosis of herb-induced liver injury after excluding all competing causes. Fortunately, the patient improved gradually after herb withdrawal and supportive care. Patients with underlying chronic liver disease (CLD) should be aware of risks in using untested herbal formulations. This case emphasizes the need for increased surveillance to formulate guidelines regarding the regulation and informed use of herbal supplements in patients with chronic liver disease.

A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2-Induced Glycolytic Reprogramming in Glioblastoma.

PURPOSE: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and patients with GBM. EXPERIMENTAL DESIGN: [18F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/µmol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next, we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers and a pilot cohort of patients with glioma. RESULTS: In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio of 3.6 ± 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared. In patients with GBM, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced MRI. The uptake of [18F]DASA-23 was markedly elevated in GBMs compared with normal brain, and it identified a metabolic nonresponder within 1 week of treatment initiation. CONCLUSIONS: We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy-induced normalization of aberrant cancer metabolism.

Low-count whole-body PET with deep learning in a multicenter and externally validated study.

More widespread use of positron emission tomography (PET) imaging is limited by its high cost and radiation dose. Reductions in PET scan time or radiotracer dosage typically degrade diagnostic image quality (DIQ). Deep-learning-based reconstruction may improve DIQ, but such methods have not been clinically evaluated in a realistic multicenter, multivendor environment. In this study, we evaluated the performance and generalizability of a deep-learning-based image-quality enhancement algorithm applied to fourfold reduced-count whole-body PET in a realistic clinical oncologic imaging environment with multiple blinded readers, institutions, and scanner types. We demonstrate that the low-count-enhanced scans were noninferior to the standard scans in DIQ (p < 0.05) and overall diagnostic confidence (p < 0.001) independent of the underlying PET scanner used. Lesion detection for the low-count-enhanced scans had a high patient-level sensitivity of 0.94 (0.83-0.99) and specificity of 0.98 (0.95-0.99). Interscan kappa agreement of 0.85 was comparable to intrareader (0.88) and pairwise inter-reader agreements (maximum of 0.72). SUV quantification was comparable in the reference regions and lesions (lowest p-value=0.59) and had high correlation (lowest CCC = 0.94). Thus, we demonstrated that deep learning can be used to restore diagnostic image quality and maintain SUV accuracy for fourfold reduced-count PET scans, with interscan variations in lesion depiction, lower than intra- and interreader variations. This method generalized to an external validation set of clinical patients from multiple institutions and scanner types. Overall, this method may enable either dose or exam-duration reduction, increasing safety and lowering the cost of PET imaging.

Human biodistribution and radiation dosimetry of [18F]DASA-23, a PET probe targeting pyruvate kinase M2.

PURPOSE: To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[18F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in healthy volunteers. METHODS: We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.0 ± 8.2 MBq of [18F]DASA-23 intravenously. Immediately following injection, a dynamic scan of the brain was acquired for 15 min. This was followed by serial whole-body PET/MRI scans acquired up to 3 h post-injection. Blood samples were collected at regular intervals, and vital signs monitored pre- and post-radiotracer administration. Regions of interest were drawn around multiple organs, time-activity curves were calculated, and organ uptake and dosimetry were estimated with OLINDA/EXM (version 1.1) software. RESULTS: All subjects tolerated the PET/MRI examination, without adverse reactions to [18F]DASA-23. [18F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [18F]DASA-23 was noted in organs such as the gallbladder, liver, small intestine, and urinary bladder, suggesting hepatobiliary and urinary clearance. The effective dose of [18F]DASA-23 was 23.5 ± 5.8 µSv/MBq. CONCLUSION: We successfully completed a pilot first-in-human study of [18F]DASA-23. Our results indicate that [18F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [18F]DASA-23 to visualize intracranial malignancies, NCT03539731. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03539731 (registered 28 May 2018).

18F-FDG PET/MRI in Chronic Sciatica: Early Results Revealing Spinal and Nonspinal Abnormalities.

Chronic sciatica is a major cause of disability worldwide, but accurate diagnosis of the causative pathology remains challenging. In this report, the feasibility of an 18F-FDG PET/MRI approach for improved diagnosis of chronic sciatica is presented. Methods:18F-FDG PET/MRI was performed on 9 chronic sciatica patients and 5 healthy volunteers (healthy controls). Region-of-interest analysis using SUVmax was performed, and 18F-FDG uptake in lesions was compared with that in the corresponding areas in healthy controls. Results: Significantly increased 18F-FDG uptake was observed in detected lesions in all patients and was correlated with pain symptoms. 18F-FDG-avid lesions not only were found in impinged spinal nerves but also were associated with nonspinal causes of pain, such as facet joint degeneration, pars defect, or presumed scar neuroma. Conclusion: The feasibility of 18F-FDG PET/MRI for diagnosing pain generators in chronic sciatica was demonstrated, revealing various possible etiologies.

Biodistribution and Radiation Dosimetry of 18F-FTC-146 in Humans.

The purpose of this study was to assess safety, biodistribution, and radiation dosimetry in humans for the highly selective σ-1 receptor PET agent 18F-6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one (18F-FTC-146). Methods: Ten healthy volunteers (5 women, 5 men; age ± SD, 34.3 ± 6.5 y) were recruited, and written informed consent was obtained from all participants. Series of whole-body PET/MRI examinations were acquired for up to 3 h after injection (357.2 ± 48.8 MBq). Blood samples were collected, and standard vital signs (heart rate, pulse oximetry, and body temperature) were monitored at regular intervals. Regions of interest were delineated, time-activity curves were calculated, and organ uptake and dosimetry were estimated. Results: All subjects tolerated the PET/MRI examination well, and no adverse reactions to 18F-FTC-146 were reported. High accumulation of 18F-FTC-146 was observed in σ-1 receptor-dense organs such as the pancreas and spleen, moderate uptake in the brain and myocardium, and low uptake in bone and muscle. High uptake was also observed in the kidneys and bladder, indicating renal tracer clearance. The effective dose of 18F-FTC-146 was 0.0259 ± 0.0034 mSv/MBq (range, 0.0215-0.0301 mSv/MBq). Conclusion: First-in-human studies with clinical-grade 18F-FTC-146 were successful. Injection of 18F-FTC-146 is safe, and absorbed doses are acceptable. The potential of 18F-FTC-146 as an imaging agent for a variety of neuroinflammatory diseases is currently under investigation.