Whether head size and/or biological sex influence proxies of white matter (WM) microstructure such as fractional anisotropy (FA) and mean diffusivity (MD) remains controversial. Diffusion tensor ...imaging (DTI) indices are also associated with age, but there are large discrepancies in the spatial distribution and timeline of age‐related differences reported. The aim of this study was to evaluate the associations between intracranial volume (ICV), sex, and age and DTI indices from WM in a population‐based study of healthy individuals (n = 812) aged 50–66 in the Nord‐Trøndelag health survey. Semiautomated tractography and tract‐based spatial statistics (TBSS) analyses were performed on the entire sample and in an ICV‐matched sample of men and women. The tractography results showed a similar positive association between ICV and FA in all major WM tracts in men and women. Associations between ICV and MD, radial diffusivity and axial diffusivity were also found, but to a lesser extent than FA. The TBSS results showed that both men and women had areas of higher and lower FA when controlling for age, but after controlling for age and ICV only women had areas with higher FA. The ICV matched analysis also demonstrated that only women had areas of higher FA. Age was negatively associated with FA across the entire WM skeleton in the TBSS analysis, independent of both sex and ICV. Combined, these findings demonstrated that both ICV and sex contributed to variation in DTI indices and emphasized the importance of considering ICV as a covariate in DTI analysis.
The results showed a similar positive association between intracranial volume (ICV) and fractional anisotropy (FA) in all major white matter tracts in men and women. Both men and women had areas of higher and lower FA when controlling for age, but after controlling for age and ICV, and when performing the analysis in the ICV‐matched sample, only women had areas with higher FA. Combined, these findings demonstrated that both ICV and sex contributed to variation in diffusion tensor imaging (DTI) indices and emphasized the importance of considering ICV as a covariate in DTI analysis.
Abstract
Cortical surface area is an increasingly used brain morphology metric that is ontogenetically and phylogenetically distinct from cortical thickness and offers a separate index of ...neurodevelopment and disease. However, the various existing methods for assessment of cortical surface area from magnetic resonance images have never been systematically compared. We show that the surface area method implemented in FreeSurfer corresponds closely to the exact, but computationally more demanding, mass-conservative (pycnophylactic) method, provided that images are smoothed. Thus, the data produced by this method can be interpreted as estimates of cortical surface area, as opposed to areal expansion. In addition, focusing on the joint analysis of thickness and area, we compare an improved, analytic method for measuring cortical volume to a permutation-based nonparametric combination (NPC) method. We use the methods to analyze area, thickness and volume in young adults born preterm with very low birth weight, and show that NPC analysis is a more sensitive option for studying joint effects on area and thickness, giving equal weight to variation in both of these 2 morphological features.
There is a growing realization that early life influences have lasting impact on brain function and structure. Recent research has demonstrated that genetic relationships in adults can be used to ...parcellate the cortex into regions of maximal shared genetic influence, and a major hypothesis is that genetically programmed neurodevelopmental events cause a lasting impact on the organization of the cerebral cortex observable decades later. Here we tested how developmental and lifespan changes in cortical thickness fit the underlying genetic organizational principles of cortical thickness in a longitudinal sample of 974 participants between 4.1 and 88.5 y of age with a total of 1,633 scans, including 773 scans from children below 12 y. Genetic clustering of cortical thickness was based on an independent dataset of 406 adult twins. Developmental and adult age-related changes in cortical thickness followed closely the genetic organization of the cerebral cortex, with change rates varying as a function of genetic similarity between regions. Cortical regions with overlapping genetic architecture showed correlated developmental and adult age change trajectories and vice versa for regions with low genetic overlap. Thus, effects of genes on regional variations in cortical thickness in middle age can be traced to regional differences in neurodevelopmental change rates and extrapolated to further adult aging-related cortical thinning. This finding suggests that genetic factors contribute to cortical changes through life and calls for a lifespan perspective in research aimed at identifying the genetic and environmental determinants of cortical development and aging.
Glioblastomas are primary malignant brain tumors with a dismal prognosis. Knowledge of growth rates and underlying growth dynamics is useful for understanding basic tumor biology, developing ...realistic tumor models, and planning treatment logistics.
By using repeated pretreatment contrast-enhanced T1-weighted MRI scans from 106 patients (aged 26-83 years), we studied the growth dynamics of untreated glioblastomas in vivo. Growth rates were calculated as specific growth rates and equivalent volume doubling times. The fit of different possible growth models was assessed using maximum likelihood estimations.
There were large variations in growth rates between patients. The median specific growth rate of the tumors was 1.4% per day, and the equivalent volume doubling time was 49.6 days. Exploring 3 different tumor growth models showed similar statistical fit for a Gompertzian growth model and a linear radial growth model and worse fit for an exponential growth model. However, large tumors had significantly lower growth rates than smaller tumors, supporting the assumption that glioblastomas reach a plateau phase and thus exhibit Gompertzian growth.
Based on the fast growth rate of glioblastoma shown in this study, it is evident that poor treatment logistics will influence tumor size before surgery and can cause significant regrowth before adjuvant treatment. Since there is a known association between tumor volume, extent of surgical resection, and response to adjuvant therapy, it is likely that waiting times play a role in patient outcomes.
The main arteries that supply blood to the brain originate from the Circle of Willis (CoW). The CoW exhibits considerable anatomical variations which may have clinical importance, but the variability ...is insufficiently characterised in the general population. We assessed the anatomical variability of CoW variants in a community-dwelling sample (N = 1,864, 874 men, mean age = 65.4, range 40-87 years), and independent and conditional frequencies of the CoW's artery segments. CoW segments were classified as present or missing/hypoplastic (w/1mm diameter threshold) on 3T time-of-flight magnetic resonance angiography images. We also examined whether age and sex were associated with CoW variants. We identified 47 unique CoW variants, of which five variants constituted 68.5% of the sample. The complete variant was found in 11.9% of the subjects, and the most common variant (27.8%) was missing both posterior communicating arteries. Conditional frequencies showed patterns of interdependence across most missing segments in the CoW. CoW variants were associated with mean-split age (P = .0147), and there was a trend showing more missing segments with increasing age. We found no association with sex (P = .0526). Our population study demonstrated age as associated with CoW variants, suggesting reduced collateral capacity with older age.
Even though age-related white matter hyperintensities (WMH) begin to emerge in middle age, their effect on brain micro- and macrostructure in this age group is not fully elucidated. We have examined ...how presence of WMH and load of WMH affect regional brain volumes and microstructure in a validated, representative general population sample of 873 individuals between 50 and 66 years. Presence of WMH was determined as Fazakas grade ≥1. WMH load was WMH volume from manual tracing of WMHs divided on intracranial volume. The impact of age appropriate WMH (Fazakas grade 1) on the brain was also investigated. Major novel findings were that even the age appropriate WMH group had widespread macro- and microstructural changes in gray and white matter, showing that the mere presence of WMH, not just WMH load is an important clinical indicator of brain health. With increasing WMH load, structural changes spread centrifugally. Further, we found three major patterns of FA and MD changes related to increasing WMH load, demonstrating a heterogeneous effect on white matter microstructure, where distinct patterns were found in the proximity of the lesions, in deep white matter and in white matter near the cortex. This study also raises several questions about the onset of WMH related pathology, in particular, whether some of the aberrant brain structural and microstructural findings are present before the emergence of WMH. We also found, similar to other studies, that WMH risk factors had low explanatory power for WMH, making it unclear which factors lead to WMH.
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To date, there is no consensus whether sexual dimorphism in the size of neuroanatomical structures exists, or if such differences are caused by choice of intracranial volume (ICV) correction method. ...When investigating volume differences in neuroanatomical structures, corrections for variation in ICV are used. Commonly applied methods are the ICV-proportions, ICV-residuals and ICV as a covariate of no interest, ANCOVA. However, these different methods give contradictory results with regard to presence of sex differences. Our aims were to investigate presence of sexual dimorphism in 18 neuroanatomical volumes unrelated to ICV-differences by using a large ICV-matched subsample of 304 men and women from the HUNT-MRI general population study, and further to demonstrate in the entire sample of 966 healthy subjects, which of the ICV-correction methods gave results similar to the ICV-matched subsample. In addition, sex-specific subsamples were created to investigate whether differences were an effect of head size or sex. Most sex differences were related to volume scaling with ICV, independent of sex. Sex differences were detected in a few structures; amygdala, cerebellar cortex, and 3rd ventricle were larger in men, but the effect sizes were small. The residuals and ANCOVA methods were most effective at removing the effects of ICV. The proportions method suffered from systematic errors due to lack of proportionality between ICV and neuroanatomical volumes, leading to systematic mis-assignment of structures as either larger or smaller than their actual size. Adding additional sexual dimorphic covariates to the ANCOVA gave opposite results of those obtained in the ICV-matched subsample or with the residuals method. The findings in the current study explain some of the considerable variation in the literature on sexual dimorphisms in neuroanatomical volumes. In conclusion, sex plays a minor role for neuroanatomical volume differences; most differences are related to ICV.
The aim of this study was to explore the prognostic value of visible traumatic axonal injury (TAI) loads in different MRI sequences from the early phase after adjusting for established prognostic ...factors. Likewise, we sought to explore the prognostic role of early apparent diffusion coefficient (ADC) values in normal-appearing corpus callosum. In this prospective study, 128 patients (mean age, 33.9 years; range, 11-69) with moderate (n = 64) and severe traumatic brain injury (TBI) were examined with MRI at a median of 8 days (range, 0-28) postinjury. TAI lesions in fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and T2*-weighted gradient echo (T2*GRE) sequences were counted and FLAIR lesion volumes estimated. In patients and 47 healthy controls, mean ADC values were computed in 10 regions of interests in the normal-appearing corpus callosum. Outcome measure was the Glasgow Outcome Scale-Extended (GOS-E) at 12 months. In patients with severe TBI, number of DWI lesions and volume of FLAIR lesions in the corpus callosum, brain stem, and thalamus predicted outcome in analyses with adjustment for age, Glasgow Coma Scale score, and pupillary dilation (odds ratio, 1.3-6.9; p = <0.001-0.017). The addition of Rotterdam CT score and DWI lesions in the corpus callosum yielded the highest R2 (0.24), compared to all other MRI variables, including brain stem lesions. For patients with moderate TBI only the number of cortical contusions (p = 0.089) and Rotterdam CT score (p = 0.065) tended to predict outcome. Numbers of T2*GRE lesions did not affect outcome. Mean ADC values in the normal-appearing corpus callosum did not differ from controls. In conclusion, the loads of visible TAI lesions in the corpus callosum, brain stem, and thalamus in DWI and FLAIR were independent prognostic factors in patients with severe TBI. DWI lesions in the corpus callosum were the most important predictive MRI variable. Interestingly, number of cortical contusions in MRI and CT findings seemed more important for patients with moderate TBI.
Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has ...remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4–88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother–Child Cohort study were identified as such early factors of possible lifelong influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain–cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course.
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