The effects of intracranial volume adjustment approaches on multiple regional MRI volumes in healthy aging and Alzheimer's disease

Abstract

In neurodegeneration research, normalization of regional volumes by intracranial volume (ICV) is important to estimate the extent of disease-driven atrophy. There is little agreement as to whether raw volumes, volume-to-ICV fractions or regional volumes from which the ICV factor has been regressed out should be used for volumetric brain imaging studies. Using multiple regional cortical and subcortical volumetric measures generated by Freesurfer (51 in total), the main aim of this study was to elucidate the implications of these adjustment approaches. Magnetic resonance imaging (MRI) data were analyzed from two large cohorts, the population-based PIVUS cohort (N = 406, all subjects age 75) and the Alzheimer disease Neuroimaging Initiative (ADNI) cohort (N = 724). Further, we studied whether the chosen ICV normalization approach influenced the relationship between hippocampus and cognition in the three diagnostic groups of the ADNI cohort (Alzheimer's disease, mild cognitive impairment, and healthy individuals). The ability of raw vs. adjusted hippocampal volumes to predict diagnostic status was also assessed. In both cohorts raw volumes correlate positively with ICV, but do not scale directly proportionally with it. The correlation direction is reversed for all volume-to-ICV fractions, except the lateral and third ventricles. Most gray matter fractions are larger in females, while lateral ventricle fractions are greater in males. Residual correction effectively eliminated the correlation between the regional volumes and ICV and removed gender differences. The association between hippocampal volumes and cognition was not altered by ICV normalization. Comparing prediction of diagnostic status using the different approaches, small but significant differences were found. The choice of normalization approach should be carefully considered when designing a volumetric brain imaging study.

Measuring Global Brain Atrophy with the Brain Volume/Cerebrospinal Fluid Index: Normative Values, Cut-Offs and Clinical Associations

“…In the present study, greater global brain atrophy was significantly associated with older age, larger ICV, lower education and presence of the ApoE ε4 allele [45,52,53,54,55,56], while gender and the cohort used did not have any significant effect, as previously reported [54,55,57,58]. To the best of our knowledge, this is the only study investigating the influence of all these confounding factors on global brain atrophy in the same sample.…”

Biomarkers and Functional Decline in Prodromal Alzheimer’s Disease

“…FreeSurfer software (http://surfer.nmr.mgh.harvard.edu) was utilised to extract MRI (1.5 T) measured hippocampal volume where an atlas-based approach was implemented and has been validated for use in subjects with a great deal of morphologic variability. Uncorrected hippocampal volume for head size was used as a previous study showed that the association between hippocampal volumes and cognition was not altered by intracranial volume normalization [29]. Peptide CSF measures were generated from aliquot samples collected at the same time [30] …”

A 3 tesla magnetic resonance imaging volumetric analysis of the hippocampal formation: dependence on handedness and age

“…The HF changes in volume were also seen in patients with cognitive impairment, including those with Alzheimer's disease [1,46]. Reduction in the HF volume was observed in heavy cannabis use, in epilepsy, mild cognitive decline, dementia, major depression, the aged, traumatic brain injury, posttraumatic stress disorder, chronic alcoholism, borderline and antisocial personality disorders, obsessive-compulsive disorder, herpes simplex encephalitis, Parkinson's and Huntington's disease, Down's and Turner's syndrome, cardiac arrest, and Cushing's disease [1,10,14,38,42].…”

“…Firstly, the MR equipment and the used imaging parameters differ among the institutions, for example the strength of the magnetic field, the pulse sequence and the slice thickness [5,16,24,27,34]. Secondly, the application of various methods for the HF delineation, either the manual tracing or the automatic segmentation, may influence the final result as well [30,36,46,47]. Thirdly, the brain size of the participants exerts substantial statistical influences on the HF volume values [4].…”