Wortinger, L. A. | Search bioRxiv

bioRxiv2022

A comparison of intracranial volume estimation methods and their cross-sectional and longitudinal associations with age

Intracranial volume (ICV) is frequently used in volumetric brain magnetic resonance imaging (MRI) studies, both as an adjustment factor for head size and as a variable of interest. Associations with age have been reported in both longitudinal and cross-sectional studies, but results have varied, potentially due to differences in ICV estimation methods. Here, we compared five commonly used ICV estimation methods and their cross-sectional and longitudinal associations with age. T1-weighted cross-sectional MRI data was included for 651 healthy individuals recruited through the NORMENT Centre (mean age = 46.1 years, range = 12.0-85.8 years) and 2,410 healthy individuals recruited through the UK Biobank study (UKB, mean age = 63.2 years, range = 47.0-80.3 years), where follow-up data was also available with a mean follow-up interval of 2.3 years. ICV was estimated with FreeSurfer (eTIV and sbTIV), SPM12, CAT12, and FSL. We assessed Pearson correlations, performed Bland-Altman analysis, and tested the explained variance of sex, height, body weight, and age on pairwise differences between ICV estimation methods. We fitted regression models to test linear and non-linear cross-sectional associations between age and ICV. For the UKB dataset, we further assessed longitudinal ICV change using linear mixed-effects (LME) models. We found overall high correlations across ICV estimation method, with the lowest correlations between FSL and eTIV (r=0.87) and between FSL and CAT12 (r=0.89). Widespread proportional bias was found in the Bland-Altman analyses, i.e., agreement between methods varying as a function of head size. Body weight, age, and sex explained the most variance in the differences between ICV estimation methods, indicating possible confounding by these variables for some estimation methods. In the NORMENT dataset, cross-sectional associations with age were found only for FSL and SPM12, indicating a positive association. For the UKB dataset, we observed negative cross-sectional associations with age for all ICV estimation methods. Longitudinal associations with age were found for all ICV estimation methods, with estimated annual percentage change ranging from -0.291 % to -0.416 % across the sampled age range. This convergence of longitudinal results across ICV estimation methods, in the largest dataset to date, offers strong evidence for age-related ICV reductions in mid- to late adulthood. HighlightsO_LICorrelations between the five assessed estimation methods were very high (r>0.90) with the exception of FSL and eTIV (r=0.87), and FSL and CAT12 (r=0.89). C_LIO_LIExplained variance of estimated ICV differences by body weight, age, and sex indicate possible confounding for some ICV estimation methods. C_LIO_LIPositive cross-sectional associations with age, from adolescence to old age, were observed for the SPM12 and FSL estimation methods in one dataset. C_LIO_LIIn the other dataset, negative cross-sectional associations with age, from mid- to late adulthood, were found for all estimation methods. C_LIO_LILongitudinal ICV changes were observed for all estimation methods, indicating an annual percentage ICV reduction of -0.29 % to -0.42 % in mid- to late adulthood. C_LI

neuroscience↗

bioRxiv2019

Trajectories of brain volume change over 13 years in chronic schizophrenia.

ImportanceSchizophrenia is a leading cause of disability worldwide, with an illness course that putatively deteriorates over time. Whether the notion of a progressive brain disease holds in its chronic stage is debated. ObjectiveTo investigate brain volume change and the impact of iatrogenic factors in chronic schizophrenia patients (duration of illness at baseline 16.17 {+/-} 8.14 years) and controls over 13 years. DesignParticipants were recruited as part of the Human Brain Informatics study. Data acquisition took place between 1999 and 2018, including baseline, 5- and 13-years follow-up. SettingNaturalistic longitudinal case-control study. ParticipantsThe sample consisted of 143 participants, of whom 64 were patients with chronic schizophrenia (20% female, mean age at baseline 40.5 {+/-} 7.7 years) and 79 healthy controls (37% female, mean age at baseline 42.8 {+/-} 8.4 years). T1-weighted structural imaging and information about medication use were obtained at each time point. ExposureAntipsychotic medication and other prescribed drugs. Main Outcome(s) and Measure(s)Individual total and tissue-specific brain volumes, as well as two-time point percentage brain and ventricle volume change. ResultsPatients had lower total brain volume at baseline. Yet, trajectories in total brain volume and gray matter volume loss as well as ventricular enlargement did not differ relative to controls. White matter volume was similar between groups at baseline and 5-year but diverged between 5-year and 13-year follow-up, with accelerated loss in patients. While antipsychotic exposure did not show an association with brain volume loss over time, higher medication load was associated with lower brain volume across time points. Patients on second-generation antipsychotics alone showed lowest total brain volume, only after accounting for add-on drug use. Conclusion and RelevanceWe found limited evidence for progressive brain volume loss in chronic schizophrenia, beyond normal aging. Stable differences in patient brain volumes relative to controls may primarily occur during the first years of illness. All prescribed drugs need to be considered when examining the impact of antipsychotic medication on brain structure. Key PointsO_ST_ABSQuestionC_ST_ABSIs chronic schizophrenia associated with progressive brain volume loss beyond normal aging? FindingsWhile brain volume was lower at baseline, patient trajectories of brain volume change over a 13-year follow-up period differed little from healthy individuals. Small effects indicated greater white matter volume loss in patients during the late phase of follow-up. Stable differences in patient brain volumes seem explicable by antipsychotic medication class and respective add-on drugs. MeaningWe found limited evidence of progressive brain volume loss, beyond normal aging, in chronic schizophrenia over 13 years.

neuroscience↗