Normalization of cerebral volumes by use of intracranial volume: Implications for longitudinal quantitative MR imaging

BACKGROUND AND PURPOSE: MR-based volumetric measures of cerebral structures are increasingly used for diagnostic purposes and to measure progression o f atrophy. Variations in individual bead size may be corrected by normaliza tion with use of a total intracranial volume (TIV) measurement. The TIV als o may be used to correct for voxel size fluctuations in serial studies. The TIV should be measured from the same images used for structural volumetry, usually TI-weighted imaging. The objectives were to show that normalizatio n with TIV reduces interindividual variation, to develop and validate a sim ple protocol for measuring TIV from Tl-weighted MR images, and to apply TIV normalization to serial brain measures in controls and subjects with Alzhe imer disease (AD). METHODS: We measured TIN with a semiautomated segmentation technique on T1- and T2-weighted MR images in 55 controls, 10 AD patients, and two persons at risk of familial AD. Whole-brain volumes also were measured and normaliz ed with TIVs. RESULTS: The TIV normalization of cross-sectional brain volumes significant ly reduced interindividual variation; the coefficient of variation (CV) was reduced from 10.0% to 6.0% in controls (P < .001). The TIVs measured on Tl -weighted images had low variability (CV, 0.16%) and did not differ signifi cantly from those measured on T2-weighted images (P = .16). The TIV normali zation of serial brain-volume measurements reduced interimage differences c aused by voxel-scaling variations (CV reduced from 1.3% to 0.5%, P = .002) in 10 controls and five AD patients. CONCLUSION: Structural volumes should be normalized with a TIV, measured cr oss-sectionally, to reduce interindividual variation, and longitudinally wi th a concurrent measurement, to reduce subtle interimage differences. This may have important implications in progression studies.