Spatially Distinct Bone Marrow Sites Are Asymmetrically Impacted by Inflammatory Cardiovascular Disease

Cardiovascular disease, a leading cause of mortality globally, is increasingly recognized to involve complex bone marrow-driven inflammatory mechanisms, yet the impact on spatially distinct bone marrow sites and comorbidities remains poorly understood. To address this, we developed MarrowMet, a methodology for whole-body, site-specific quantification of bone marrow activity. The approach involves intravenously injecting the metabolic tracer 18F-fluorodeoxyglucose (¹⁸F-FDG) in mice, followed by bone excision to quantify site-specific bone marrow activity, with values then superimposed on a whole-body mouse atlas. After establishing that ¹⁸F-FDG bone marrow uptake strongly correlated with inflammatory activity, we applied MarrowMet to map site-specific activation patterns across diverse cardiovascular pathologies, including mouse models of inflammatory atherosclerosis, acute ischemic events, acute respiratory distress syndrome, metabolic syndrome, and aging. MarrowMet guided the selection of bone marrow regions of interest for in-depth mass cytometric analyses, with the skull and sternum emerging as critical sites exhibiting distinct immune and metabolic profiles in cardiovascular disease. These results challenge the prevailing view that femoral marrow represents systemic activity. Together, this work lays a foundation for whole-body exploration of bone marrow heterogeneity, yielding critical insights into cardiovascular disease and associated inflammatory responses, and MarrowMet can be readily adopted to profile other immune mechanisms in a variety of pathologies, including cancer and autoimmune diseases.