Johnson, Geoffrey B.

Abstract Disclosure: P. Hopmann: None. S. Lund: None. T. Foster: None. B. Dy: None. T. McKenzie: None. G. Johnson: None. R.A. Wermers: None. M. Lyden: None. Background: Previous studies have demonstrated that C11 choline positron emission tomography/computed tomography (Choline-PET/CT) can localize abnormal parathyroid glands in the re-operative setting. This study assesses a large volume of patients with primary hyperparathyroidism (1HPT) who underwent Choline-PET/CT to confirm its utility in the setting of negative or equivocal conventional imaging. Methods: All patients who underwent Choline-PET/CT for evaluation of 1HPT from July 2017 to July 2024 at a single institution were reviewed. Inclusion criteria were patients who underwent parathyroidectomy and had lab testing to assess for cure (defined as >50% drop from baseline PTH and into normal range, or resolution of hypercalcemia at follow-up). Sensitivity, positive predictive value (PPV), false negative rate (FNR), and accuracy were compared to conventional imaging (neck ultrasound, parathyroid scan, and parathyroid four-dimensional CT (4D-CT)). Subgroup analysis was conducted comparing sensitivity of modalities among index operations, and separately in re-operations. Results: 176 patients were identified. 85 underwent parathyroidectomy, 1 patient was excluded due to lacking data to evaluate for cure. Of 91 patients who did not undergo parathyroidectomy, 45 were non-localizing on all imaging, and 46 had positive Choline-PET/CT findings but opted against surgery due to mild disease or prohibitive re-operative risk. Of the included 84 parathyroidectomy patients, 61 failed to localize on at least one conventional modality, and 15 failed to localize on all conventional studies. 67 patients (80%) achieved cure, of whom 53 were re-operations (range of 1-4 prior operations, average 1.5). Choline-PET/CT outperformed conventional modalities across sensitivity, PPV, FNR, and accuracy. Among index operations, Choline-PET/CT had significantly higher sensitivity than conventional modalities (100% vs 27% for ultrasound, 30% for parathyroid scan, 29% for 4D-CT; p values ≤0.01). This was also true in re-operations (95% for Choline-PET/CT vs 13% for ultrasound, 30% for parathyroid scan, 32% for 4D-CT; p values <0.01). Conclusion: C11 choline-PET/CT is a valuable imaging modality in the re-operative setting and demonstrates utility for index operations. It provides localization when other modalities fail and allows for a high surgical cure rate. Further investigation into its utility as a primary imaging modality is warranted. Presentation: Monday, July 14, 2025

Simultaneous positron emission tomography and MRI (PET/MRI) is a technology that combines the anatomic and quantitative strengths of MR imaging with physiologic information obtained from PET. PET and computed tomography (PET/CT) performed in a single scanning session is an established technology already in widespread and accepted use worldwide. Given the higher cost and complexity of operating and interpreting the studies obtained on a PET/MRI system, there has been question as to which patients would benefit most from imaging with PET/MRI versus PET/CT. In this article, we compare PET/MRI with PET/CT, detail the applications for which PET/MRI has shown promise and discuss impediments to future adoption. It is our hope that future work will prove the benefit of PET/MRI to specific groups of patients, initially those in which PET/CT and MRI are already performed, leveraging simultaneity and allowing for greater degrees of multiparametric evaluation.Level of Evidence: 5Technical Efficacy: Stage 5J. Magn. Reson. Imaging 2017;46:1247–1262.

Abstract Systemic inflammatory response syndrome (SIRS) is typically associated with trauma, surgery, or acute pancreatitis. SIRS resembles sepsis, triggered by exogenous macromolecules such as LPS acting on Toll-like receptors. What triggers SIRS in the absence of infection, however, is unknown. In this study, we report that a SIRS-like response can be induced in mice by administration of soluble heparan sulfate, a glycosaminoglycan associated with nucleated cells and extracellular matrices, and by elastase, which cleaves and releases heparan sulfate proteoglycans. The ability of heparan sulfate and elastase to induce SIRS depends on functional Toll-like receptor 4, because mutant mice lacking that receptor or its function do not respond. These results provide a molecular explanation for the initiation of SIRS.

Abstract Perturbations to the well-being of tissues in plants and invertebrates generate fragments of endogenous molecules that are recognized by innate immune receptors. Vertebrates have homologous receptors on specialized cells such as dendritic cells, but whether these receptors respond to fragments of endogenous molecules is not known. We tested the idea that Toll-like receptors on dendritic cells might recognize polysaccharide fragments of heparan sulfate proteoglycan. Dendritic cells were found to mature in response to heparan sulfate as measured by costimulatory protein expression, morphology, and T lymphocyte stimulation, but this maturation was absent when Toll-like receptor 4 was mutated or inhibited. These findings suggest that Toll-like receptors in vertebrates may monitor tissue well-being by recognizing fragments of endogenous macromolecules.