As microscopic tumour infiltration of glioblastomas is not visible on conventional magnetic resonance (MR) imaging, an isotropic expansion of 1–2 cm around the visible tumour is applied to define the clinical target volume for radiotherapy. An opportunity to visualize microscopic infiltration arises with advanced MR imaging. In this review, various advanced MR biomarkers are explored that could improve target volume delineation for radiotherapy of glioblastomas. Various physiological processes in glioblastomas can be visualized with different advanced MR techniques. Combining maps of oxygen metabolism (CMRO2), relative cerebral blood volume (rCBV), vessel size imaging (VSI), and apparent diffusion coefficient (ADC) or amide proton transfer (APT) can provide early information on tumour infiltration and high-risk regions of future recurrence. Oxygen consumption is increased 6 months prior to tumour progression being visible on conventional MR imaging. However, presence of the Warburg effect, marking a switch from an infiltrative to a proliferative phenotype, could result in CMRO2 to appear unaltered in high-risk regions. Including information on biomarkers representing angiogenesis (rCBV and VSI) and hypercellularity (ADC) or protein concentration (APT) can omit misinterpretation due to the Warburg effect. Future research should evaluate these biomarkers in radiotherapy planning to explore the potential of advanced MR techniques to personalize target volume delineation with the aim to improve local tumour control and/or reduce radiation-induced toxicity.
Macrophages are crucial mediators in the development of inflammatory diseases, including kidney diseases. Unresolved renal inflammation can progressively develop into chronic kidney disease (CKD), resulting in structural and functional impairment of the injured kidney due to renal fibrosis and leading to irreversible end-stage renal disease (ESRD). Increasing evidence suggests that phenotypic changes in macrophages are essential for CKD development and progression. Interestingly, advanced bioinformatics and single-cell RNA-sequencing analyses have revealed the crucial mechanism of macrophage-myofibroblast transition, which may be a novel therapeutic target for renal fibrosis. Therefore, a better understanding of the immunodynamics of macrophages in diseased kidneys may help identify effective therapeutic strategies for unmet clinical needs. This review summarizes the regulatory roles and underlying mechanisms of macrophages in renal fibrosis and their therapeutic implications in kidney diseases, including ESRD.
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