Standardized Calculation of Brain Parenchymal Fraction: An Approach to Objective Assessment of Cerebral Atrophy

Various approaches to measure brain atrophy in MR imaging have been applied until now, including measures of ventricular width and volume estimates of the whole brain or of limited regions of interest. Recently, Ge et al (1) proposed a semiautomated segmentation algorithm calculating fractional gray matter (GM) and white matter (WM) volumes from volumetric MR imaging data sets that were normalized to total intracranial volume.

Ge et al demonstrated a marked age dependency of GM and WM fractional volumes. If one combines the values of fractional GM and WM volumes into the ratio of brain parenchymal volume to total intracranial volume, the resulting measure is the brain parenchymal fraction (BPF). This measure, first introduced by Rudick et al (2), has been validated as a useful quantitative MR imaging marker for investigating destructive processes ongoing in relapsing-remitting multiple sclerosis and has been applied for intraindividual longitudinal monitoring (eg, in controlled therapy trials [3]).

Such standardized measures, however, have yet to enter into general clinical practice. Although many of previous approaches for quantifying brain atrophy suffered from major drawbacks—availability of (costly) software, reproducibility of measures, and comparability with previously published results—standardized protocols offer a possible solution for quantitative assessment of atrophy instead of visual inspection alone. BPF may also be calculated in a highly automated and observer-independent way by using the algorithms implemented in Statistical Parametric Mapping software (4; SPM2b, Wellcome Department of Cognitive Neurology, London, [http://www.fil.ion.ucl.ac.uk/spm/spm2b.html]). Because SPM, in all its versions from 1994 until 2002, is freely available to the scientific public and has meanwhile gained a general acceptance for application to clinical studies, there now exists a fast, widely available, and validated method to generate an accurate measure of global brain atrophy in terms of BPF values that may be included in every single report of an individual MR imaging scan in routine diagnostics for neurodegenerative disease.

Discriminating between shrinkage of the brain considered to be appropriate for the patients’ age and atrophy because of neurodegenerative disease may thus turn from an inherently subjective diagnosis to a rational diagnosis based on an objectively quantified measure. Prerequisite, however, for correct interpretation of BPF values from a single patient is the presence of BPF values from an age- and sex-matched normal database, as age and sex effects have been demonstrated previously (1, 5). Because of its standardized calculation, BPF values from normal controls can easily be shared with the neuroimaging community.