Adjustment for Whole Brain and Cranial Size in Volumetric Brain Studies: A Review of Common Adjustment Factors and Statistical Methods

Abstract

In this article we address analytic challenges inherent in brain volumetrics (i.e., the study of volumes of brains and brain regions). It has sometimes been assumed in the literature that deviations in regional brain size in clinical samples are directly related to maldevelopment or pathogenesis. However, this assumption may be incorrect; such volume differences may, instead, be wholly or partly attributable to individual differences in overall dimension (e.g., for head, brain, or body size). What quantitative approaches can be used to take these factors into account? Here, we provide a review of volumetric and nonvolumetric adjustment factors. We consider three examples of common statistical methods by which one can adjust for the effects of body, head, or brain size on regional volumetric measures: the analysis of covariance, the proportion, and the residual approaches. While the nature of the adjustment will help dictate which method is most appropriate, the choice is context sensitive, guided by numerous considerations-chiefly the experimental hypotheses, but other factors as well (including characteristic features of the disorder and sample size). These issues come into play in logically framing the assessment of putative abnormalities in regional brain volumes.

Selectively Reduced Posterior Corpus Callosum Size in a Population-Based Sample of Young Adults Born with Low Birth Weight

“…Finally, the use of slightly different adjustment techniques represents another source of diverging results. 29 The finding of a smaller posterior third among the LBW group compared with the control group is noteworthy, because this finding was consistent across the differing techniques used to adjust for overall forebrain size. Others have reported similar findings in younger cohorts of VLBW survivors and by using smaller sample sizes.…”

“…Second, analyzing the size of the CC represents a potential difficulty, because relating callosal area given in square millimeters to brain volume given in cubic millimeters may carry the risk of overadjusting for brain size. 24,29 To address this problem, we expressed the volume as an area (volume 0.667 ), as suggested previously. 24,30 Because the 2 different volume expressions differ in their mean values, they cannot be used interchangeably when creating relCC areas.…”

Development of the Selection and Manipulation of Self-Generated Thoughts in Adolescence

“…Structural scans were segmented into CSF, gray and white matter; modulation for nonlinear warping only was performed using the Jacobian determinants. This method approximates a proportional adjustment of volumes for overall head size (O'Brien et al, 2006). Images were resampled into 1.5 ϫ 1.5 ϫ 1.5 voxels and smoothed with an isotropic 12 mm, full-width, half-maximum Gaussian kernel.…”

Detecting corpus callosum abnormalities in autism subtype using planar conformal mapping

“…To take into account the effect of the brain volume, we normalize the raw CC volume by the total brain volume (TBV) and the intracranial volume (ICV), respectively. TBV includes gray matter and white matter and excludes ventricles [14], and ICV is the sum of white matter, gray matter, and inner and outer cerebrospinal fluid spaces [15]. A choice can be made between using TBV or ICV as an adjustment factor [14], but our results show that the two choices do not make any difference.…”