Towards high-resolution quantitative assessment of vascular dysfunction

Neurovascular alterations are increasingly recognized as a key feature of many brain diseases. They can manifest as a reduction in resting cerebral blood flow or cerebrovascular reactivity (CVR) in the whole brain or in specific regions, depending on the underlying condition. Neurovascular impairment is observed in hypertension, Alzheimer’s disease, stroke, multiple sclerosis and cerebral small vessel disease. Magnetic resonance imaging (MRI)-derived CVR mapping is a reliable marker of vascular dysfunction and has been performed mainly at standard functional MRI (fMRI) resolutions of 2–3 mm using the blood oxygen level dependent (BOLD) contrast. However, vascular alterations may occur at a finer scale (i.e., in the capillary bed) which would be better characterized with smaller voxel sizes. Capillaries in gray matter deliver oxygen and glucose to neural tissue and are arranged in a mesh structure, with variable density across the cortical depth. Given that the human cortex is, on average, 2.5 mm thick, submillimetric voxel sizes are effective in increasing the spatial specificity of measurements of hemodynamic and metabolic changes. Novel MRI sequences offer the possibility to map physiological parameters at high resolution with relatively simple experimental setups. In particular, pairing the BOLD acquisition with a contrast sensitive to blood volume changes, while administering a mild hypercapnic challenge, allows for simultaneous mapping of CVR, cerebral metabolic rate of oxygen consumption and other relevant parameters at a high resolution and can be performed at the clinical field strength of 3 T. We propose that this approach will help provide crucial insights into vascular impairment.