Use of HIV-1 humanized mice allows the evaluation of brain morphology affected by disease and disease altering therapies. We posit that such studies can elucidate the pathobiology of HIV-1 associated neurological disorders. As irradiation, administered at birth, is a required step for long-term graft integrity we evaluated the effect of irradiation on mouse brain development using manganese-enhanced MRI (MEMRI) atlas-based segmentation. Brain size reductions in irradiated mice showed substantive morphological alterations. Thus, evaluation of irradiation effects on brain morphology is a requisite step in assessments of virus-induced brain pathology.