Systematic Review of Magnetic Resonance Lymphangiography From a Technical Perspective

Background Clinical examination and lymphoscintigraphy are the current standard for investigating lymphatic function. Magnetic resonance imaging (MRI) facilitates three‐dimensional (3D), nonionizing imaging of the lymphatic vasculature, including functional assessments of lymphatic flow, and may improve diagnosis and treatment planning in disease states such as lymphedema. Purpose To summarize the role of MRI as a noninvasive technique to assess lymphatic drainage and highlight areas in need of further study. Study Type Systematic review. Population In October 2019, a systematic literature search (PubMed) was performed to identify articles on magnetic resonance lymphangiography (MRL). Field Strength/Sequence No field strength or sequence restrictions. Assessment Article quality assessment was conducted using a bespoke protocol, designed with heavy reliance on the National Institutes of Health quality assessment tool for case series studies and Downs and Blacks quality checklist for health care intervention studies. Statistical Tests The results of the original research articles are summarized. Results From 612 identified articles, 43 articles were included and their protocols and results summarized. Field strength was 1.5 or 3.0 T in all studies, with 25/43 (58%) employing 3.0 T imaging. Most commonly, imaging of the peripheries, upper and lower limbs including the pelvis (32/43, 74%), and the trunk (10/43, 23%) is performed, including two studies covering both regions. Imaging protocols were heterogenous; however, T2‐weighted and contrast‐enhanced T1‐weighted images are routinely acquired and demonstrate the lymphatic vasculature. Edema, vessel, quantity and morphology, and contrast uptake characteristics are commonly reported indicators of lymphatic dysfunction. Data Conclusion MRL is uniquely placed to yield large field of view, qualitative and quantitative, 3D imaging of the lymphatic vasculature. Despite study heterogeneity, consensus is emerging regarding MRL protocol design. MRL has the potential to dramatically improve understanding of the lymphatics and detect disease, but further optimization, and research into the influence of study protocol differences, is required before this is fully realized. Level of Evidence 2 Technical Efficacy Stage

Role of the Mitochondria in Immune-Mediated Apoptotic Death of the Human Pancreatic β Cell Line βLox5

Mitochondria are indispensable in the life and death of many types of eukaryotic cells. In pancreatic beta cells, mitochondria play an essential role in the secretion of insulin, a hormone that regulates blood glucose levels. Unregulated blood glucose is a hallmark symptom of diabetes. The onset of Type 1 diabetes is preceded by autoimmune-mediated destruction of beta cells. However, the exact role of mitochondria has not been assessed in beta cell death. In this study, we examine the role of mitochondria in both Fas- and proinflammatory cytokine-mediated destruction of the human beta cell line, βLox5. IFNγ primed βLox5 cells for apoptosis by elevating cell surface Fas. Consequently, βLox5 cells were killed by caspase-dependent apoptosis by agonistic activation of Fas, but only after priming with IFNγ. This beta cell line undergoes both apoptotic and necrotic cell death after incubation with the combination of the proinflammatory cytokines IFNγ and TNFα. Additionally, both caspase-dependent and -independent mechanisms that require proper mitochondrial function are involved. Mitochondrial contributions to βLox5 cell death were analyzed using mitochondrial DNA (mtDNA) depleted βLox5 cells, or βLox5 ρ0 cells. βLox5 ρ0 cells are not sensitive to IFNγ and TNFα killing, indicating a direct role for the mitochondria in cytokine-induced cell death of the parental cell line. However, βLox5 ρ0 cells are susceptible to Fas killing, implicating caspase-dependent extrinsic apoptotic death is the mechanism by which these human beta cells die after Fas ligation. These data support the hypothesis that immune mediators kill βLox5 cells by both mitochondrial-dependent intrinsic and caspase-dependent extrinsic pathways