The magnetization-prepared rapid gradient-echo (MP-RAGE) T1-weighted high resolution structural MRI is a mainstay tool used to identify morphometric biomarkers of disease conditions, progression and treatment effects despite a critical limitation: the relaxation signal on which inferences are based is nearly indistinguishable for gray matter vs. blood flow (Lu et al., 2004; Wright et al., 2008). Thus, apparent reported morphometric findings might be at least partially related to transient changes in blood flow or other physiological signals.

Consistent with this technical limitation, using a standard analysis technique, voxel based morphometry (VBM), we recently reported that a single dose of a medication had “apparent” effects on T1-weighted MRIs (Franklin et al., 2013). Specifically, we observed medication-induced decreases in gray matter volume in the anterior cingulate and other regions that overlapped with changes in brain blood flow (perfusion). Similarly, others have shown effects of medication on T1-weighted scans that are likely transient. For example, acute levodopa administration altered gray matter indices on T1-weighted images in the midbrain (Salgado-Pineda et al., 2006). Further, in a well-controlled longitudinal VBM study of patients with attention deficit hyperactivity disorder (ADHD), Hoekzema et al.