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Bigler EK, Tate DF. Brain volume, intracranial volume, and dementia. Invest Radiol 2001;36:539–546.Using a large magnetic resonance (MR) imaging data set (n = 532), we investigated the utility of total intracranial volume (TICV) as a correction factor for head size variability when assessing total brain volume (TBV) and the subcortical volumes of the temporal horn of the lateral ventricular system and the hippocampus.A uniform tissue segmentation procedure (analyze) was used to calculate volumes. Total brain volume was compared with TICV in 357 control subjects and 175 patients with various dementing and neuropsychiatric disorders (mixed dementia/neuropsychiatric group). These MR-based TBV/TICV relationships were compared with actual postmortem (n = 87) values obtained from a study of neurologically healthy subjects at the time of death. Comparisons were also made in which temporal horn and hippocampal volumes were corrected by TICV and TBV. Lastly, the ability of corrected TBV and temporal horn and hippocampal volumes to distinguish subjects in the mixed dementia/neuropsychiatric group from controls was examined by logistic regression.In the control sample, brain volume averaged 9% of TICV, regardless of age. In contrast, TBV in the mixed dementia/neuropsychiatric subjects showed, on average, a 22% reduction compared with TICV. By plotting TBV/TICV curves, highly significant but different regression lines emerged, wherein a reduction in brain volume in conditions of mixed dementia/neuropsychiatric disorder showed a distinct separation from the norm. The TBV/TICV regression line generated from MR imaging in controls did not differ from the postmortem TBV/TICV regression line. Logistic regression showed a 96% correct classification of mixed dementia/neuropsychiatric subjects from controls by using the TBV/TICV ratio. This technique has the advantage that each subject serves as his or her own control.In cases of dementia and neuropsychiatric disorder in persons 65 and older, TBV corrected by TICV readily differentiated this clinical population from controls. This technique is easy and simple to use and has various clinical applications. For temporal horn and hippocampal volume, corrections with TBV rather than TICV may provide more clinically meaningful corrections.