Functional and Physiological MRI Measures as Early Biomarkers for Huntington’s Disease

Huntington’s disease (HD) is a devastating neurodegenerative disease affecting the brain resulting in neuronal dysfunction and degeneration. The pathogenesis of HD is progressive with a long premanifest phase in which subtle changes in the brain occur up to two decades before the onset of clinical symptoms. Early biomarkers reflecting the subtle changes in the HD brain for better understanding disease progression and evaluating treatment efficacy far from onset are greatly needed for developing disease-modifying treatment that improves the patient’s quality of life. Noninvasive functional and physiological MRI measures, including functional connectivity, task-based neuronal activity, cerebral blood volume/flow, brain oxygen metabolism, and blood brain barrier integrity, distinguish premanifest or early manifest HD individuals from normal subjects, showing great promise as biomarkers for detecting early HD pathophysiology before clinical onset. This chapter will provide an overview of the functional and physiological MRI studies conducted in the premanifest and early-stage HD patients, as well as in preclinical HD models, focusing on discussing the potential of different MRI measures as early biomarkers. Further, we will elaborate the limitations and future directions in using these functional and physiological MRI measures as biomarkers in HD.