Cerebral Blood Flow Differences in Major Depressive Disorder using Arterial Spin Labeling: Preliminary Results from the EMBARC Study

Background: Arterial spin labeling (ASL) is a noninvasive neuroimaging technique used to measure cerebral blood flow (CBF; i.e., perfusion) and could be used as an effective tool to understand resting state abnormalities in patient populations such as major depressive disorder (MDD). So far, previous research using ASL in depression revealed CBF abnormalities in the default mode network in some cases (Orosz et al., 2012). ASL has also been observed to accurately classify unipolar from bipolar depression based on differences in CBF of the anterior cingulate cortex (ACC; Almeida et al., 2013). Given these findings, ASL could become a prospective biomarker of disease state as well as treatment choice and monitoring in the clinical setting with more research. The EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care) study is a nation-wide randomized control trial investigating such biomarkers in MDD. ASL is being investigated in order identify differences in CBF between patients with MDD and healthy controls. Methods: Participants consist of 40 healthy controls and 100 patients with MDD before starting medication. All participants were scanned in one of four sites, and underwent 3T MRI scanning, which included an ASL scan that used pseudo-continuous labeling, i.e. PCASL, and lasted approximately 6 minutes. CBF was compared between the healthy control and MDD groups using a whole-brain voxel-by-voxel analysis. Results: Preliminary results show several regions of interest to be significantly different between the two groups. These include regions such as the ACC, insula cortex, and caudate. Clusters in these regions were significant at t = 3.21; p < .001; with at least 50 continuous voxels set at the extent threshold. Patients with MDD were observed to have reduced perfusion in the ACC, insula, and caudate relative to healthy controls. Discussion: While ASL has been more widely used as a research tool, it has the prospects of being used as a tool for clinical diagnostics and informing treatment decisions. Our present work provides further evidence to the role of ASL in detecting abnormalities in resting CBF for multiple brain regions including those that are implicated in the default mode network as well as other regions thought to be important in the phenotype of MDD. These preliminary results may have implications for future studies aimed at further developing CBF as a biomarker in clinical populations. In this regard, the final sample of the EMBARC study, which will include roughly 400 patients with MDD and their outcomes data, will provide evidence for the application of CBF to predict treatment outcomes in MDD.