Cerebral artery and brain pathology correlates of antemortem cerebral artery 4D flow MRI

Large-scale clinical research studies often incorporate neuroimaging biomarkers to understand underlying pathologic changes that occur in aging and neurodegenerative disease and are associated with cognitive decline and clinical impairment. Of particular interest are neuroimaging methods designed to understand various aspects of cerebrovascular disease that can lead to dementia and also co-occur with neurodegenerative diseases such as Alzheimer's disease. Neurovascular 4D flow magnetic resonance imaging is one such method that measures hemodynamic characteristics of medium-large cerebral vessels, but it remains unclear how measures derived from 4D flow imaging including pulsatility index, cerebral blood flow, and cross-sectional area relate to underlying pathologic changes in cerebral arteries and downstream cerebrovascular pathology. For example, pulsatility index is thought to be a marker of vessel compliance, which may be due to fibrotic and/or atherosclerotic changes. This observational study investigates imaging-pathologic correlates of cerebral artery 4D flow MRI in 20 initial brain donors (mean (SD) age at death 78.2 (10.3) years; 3.2 (1.4) years from MRI to autopsy) from the Wisconsin Alzheimer's Disease Research Center that underwent antemortem imaging and postmortem assessment of cerebral artery and brain pathology to identify possible pathologic correlates of 4D flow MRI. Our results suggest that 4D flow MRI measures recapitulate expected hemodynamic and structural relationships across cerebral arteries, but also that measures like MRI cross-sectional area may reflect arterial fibrosis whereas mean blood flow may indicate downstream cerebrovascular disease including white matter rarefaction and arteriolosclerosis. In contrast, associations were minimal with pulsatility index and cerebral artery or brain pathology across participants but were moderate across arterial segments. To our knowledge, this is the first study to investigate pathologic correlates of antemortem 4D flow MRI in cerebral arteries. These results provide preliminary insights regarding the pathologic processes contributing to cerebral artery hemodynamics measured with 4D flow MRI that will help inform interpretation of large-scale clinical aging and dementia studies utilizing this method. Future work with larger samples is needed to confirm these findings.