Dr Axel Montagne
Dr. Montagne’s research training has provided him with comprehensive and diverse background in a wide variety of scientific disciplines including molecular and cellular biology, magnetic resonance imaging (MRI), translational research, and the pathophysiology of neurodegenerative diseases such as Alzheimer’s disease (AD) and related dementias as well as ischemic and hemorrhagic strokes. He completed his PhD in neuroscience and neuroimaging techniques in France, and furthered his path in this field by developing and optimizing an arsenal of skills particularly in brain/spinal cord MRI methods for pre-clinical and clinical research. This includes (1) molecular MRI of cerebrovascular inflammation targeting inflamed vessels using a laboratory-developed contrast agent; (2) dynamic contrast-enhanced (DCE) and dynamic susceptibility-contrast (DSC)-MRI Gadolinium-based techniques allowing quantitative measures of neurovascular dysfunctions including blood-brain barrier (BBB)/ blood-spinal cord barrier (BSCB) integrity, cerebral blood flow (CBF) and volume (CBV); (3) diffusion tensor imaging (DTI) methods allowing brain structural and connectivity studies including white matter fibers tracing with 3D-tractography mapping; and (4) high-resolution 3D-T2*-weighted imaging allowing detection of microbleed events, hemosiderin plaques, calcification, and amyloid plaques. In collaboration with CalTech, Dr. Montagne recently developed a software suite (Rocketship) allowing the use of multiple pharmacokinetic models that can be applied to both pre-clinical and clinical datasets in order to get quantitative and precise measures of subtle BBB/BSCB permeability changes.
“My current research focuses on how neurovascular dysfunctions influence cognitive decline using both clinical and pre-clinical datasets. After several years of extensive technical development, I am now ready to study how genetic (i.e., APOE, PSEN1, PICALM, CLU), vascular (i.e., hypertension, hypercholesterolemia, diabetes), environmental (i.e., pollution) risk factors, and lifestyle (i.e., diet, exercise) can influence AD using novel MRI methods such as DCE-, DSC-, DTI-MRI, among others. Using our new high-field 7T human MRI here at USC Keck School of Medicine and our new high-field 7T MR Solutions magnet for rodents here at USC ZNI, we hope to elucidate the temporal sequence of vascular dysfunction events in the early stages of AD – for instance, does BBB breakdown or reduced CBF occur first, or happen simultaneously?
I am also interested in expanding my research on pericytes that have an important role in maintaining BBB integrity and CBF in capillaries. I’m currently examining the role of these mural cells in controlling CBF and BBB permeability in a context of AD, as well as in small vessel disease (SVD). I recently collected data in both humans and animal models demonstrating that pericyte loss causes regional BBB breakdown that leads to white matter (WM) damage (e.g., deep subcortical WM degeneration including Wallerian degeneration, demyelination, and axonal degeneration processes). I showed a maturation-dependent sensitivity of oligodendrocyte lineages to BBB breakdown combined with reduced CBF that leads to WM fiber injuries before neuronal loss. The next step would be to scan SVD patients longitudinally, and correlate WM damage with BBB breakdown (DCE-MRI and biofluid biomarkers), decreased CBF (DSC-/ASL-MRI), connectivity changes (DTI-MRI), and neuropsychological tests (cognitive function tests). I would like to pursue my research in animal models of WM disease (i.e., pericyte-deficient mice, Notch3 mutant mice (CADASIL syndrome), and endothelin-1 (ET-1)-injected subcortical stroke mouse models) to further understand the role of pericytes within the brain parenchyma, especially in WM regions.”