Age-related Changes In Fractional Anisotropy Research Articles

Within-person changes in the aging white matter microstructure and their modifiers: A meta-analysis and systematic review of longitudinal diffusion tensor imaging studies

Abstract This meta-analysis and systematic review synthesized data from 30 longitudinal diffusion tensor imaging (DTI) studies on the magnitude, direction, spatial patterns, and modifiers of naturally occurring within-person changes in healthy adult white matter (WM) microstructure. Results revealed: (1) significant within-person declines in fractional anisotropy (FA) in the whole WM (d = -0.12), genu (d = -0.16), and splenium (d = -0.13); (2) greater declines in FA associated with older age, longer follow-up times, and female sex; (3) a possible yet inconclusive vulnerability of late-myelinating WM (the “development-to-degeneration” gradient); and (4) factors decelerating (e.g., physical activity and social activities) and accelerating (e.g., vascular risk factors, biomarkers for Alzheimer’s disease, and alcohol consumption) age-related FA changes. Our findings encourage the consideration of WM as a new target for treatments and interventions against cognitive decline and lay the foundation for studying the plastic and regenerative potential of adult WM in clinical trials. Individual differences in WM changes could aid in the preclinical diagnosis of dementia, opening a window for earlier, more effective treatments.

Total-Body Irradiation Alters White Matter Volume and Microstructural Integrity in Rhesus Macaques

Long-term survivors of brain irradiation can suffer from irreversible injury and cognitive impairment. T1-weighted and diffusion tensor magnetic resonance imaging are used to evaluate brain volumes and white matter (WM) microstructure in neurodevelopmental and neurodegenerative conditions. The goal of this study was to evaluate the long-term effects of single-dose total-body irradiation (TBI) or TBI with 5% partial-body sparing on brain volumetrics and WM integrity in macaques. We utilized MRI scans from a cohort of male rhesus macaques (age range: 3.6-22.8 years), to compare global and regional brain volumes and WM diffusion in survivors of TBI (T1w: n=137, DTI: n=121, dose range: 3.5-10 Gy) against unirradiated controls (T1w: n=48, DTI: n=38). In all ROIs, radiation affected the age-related changes in fractional anisotropy (FA); in general, FA increased across age in both groups, but to a lesser extent in the irradiated group (interaction p-values <0.01). Depending on the ROI, mean diffusivity (MD) decreased or remained the same across age in unirradiated animals, while it increased or did not change in irradiated animals. The increases in MD were driven by changes in radial diffusivity (RD) which followed similar trends across age. Axial diffusivity (AD) did not differ by irradiation status. Age-related changes in relative volumes in controls reflected normal trends in humans with increasing WM and decreasing gray matter (GM) until middle age. Cerebrospinal fluid (CSF) volume did not differ across age in controls. WM volume was lower and CSF volume was higher in young, irradiated macaques. WM volume was similar between groups and CSF volume reduced in older irradiated macaques. GM volume was unaffected by radiation. TBI results in delayed WM expansion and long-term disruption of WM integrity. Diffusion changes suggest that myelin injury in WM is a hallmark of late-delayed radiation induced brain injury.

Spatiotemporal changes in diffusivity and anisotropy in fetal brain tractography.

Population averaged diffusion atlases can be utilized to characterize complex microstructural changes with less bias than data from individual subjects. In this study, a fetal diffusion tensor imaging (DTI) atlas was used to investigate tract‐based changes in anisotropy and diffusivity in vivo from 23 to 38 weeks of gestational age (GA). Healthy pregnant volunteers with typically developing fetuses were imaged at 3 T. Acquisition included structural images processed with a super‐resolution algorithm and DTI images processed with a motion‐tracked slice‐to‐volume registration algorithm. The DTI from individual subjects were used to generate 16 templates, each specific to a week of GA; this was accomplished by means of a tensor‐to‐tensor diffeomorphic deformable registration method integrated with kernel regression in age. Deterministic tractography was performed to outline the forceps major, forceps minor, bilateral corticospinal tracts (CST), bilateral inferior fronto‐occipital fasciculus (IFOF), bilateral inferior longitudinal fasciculus (ILF), and bilateral uncinate fasciculus (UF). The mean fractional anisotropy (FA) and mean diffusivity (MD) was recorded for all tracts. For a subset of tracts (forceps major, CST, and IFOF) we manually divided the tractograms into anatomy conforming segments to evaluate within‐tract changes. We found tract‐specific, nonlinear, age related changes in FA and MD. Early in gestation, these trends appear to be dominated by cytoarchitectonic changes in the transient white matter fetal zones while later in gestation, trends conforming to the progression of myelination were observed. We also observed significant (local) heterogeneity in within‐tract developmental trajectories for the CST, IFOF, and forceps major.

Postnatal Guinea Pig Brain Development, as Revealed by Magnetic Resonance and Diffusion Kurtosis Imaging.

This study used in vivo magnetic resonance imaging (MRI) to identify age dependent brain structural characteristics in Dunkin Hartley guinea pigs. Anatomical T2-weighted images, diffusion kurtosis (DKI) imaging, and T2 relaxometry measures were acquired from a cohort of male guinea pigs from postnatal day (PND) 18–25 (juvenile) to PND 46–51 (adolescent) and PND 118–123 (young adult). Whole-brain diffusion measures revealed the distinct effects of maturation on the microstructural complexity of the male guinea pig brain. Specifically, fractional anisotropy (FA), as well as mean, axial, and radial kurtosis in the corpus callosum, amygdala, dorsal-ventral striatum, and thalamus significantly increased from PND 18–25 to PND 118–123. Age-related alterations in DKI measures within these brain regions paralleled the overall alterations observed in the whole brain. Age-related changes in FA and kurtosis in the gray matter-dominant parietal cerebral cortex and dorsal hippocampus were less pronounced than in the other brain regions. The regional data analysis revealed that between-age changes of diffusion kurtosis metrics were more pronounced than those observed in diffusion tensor metrics. The age-related anatomical differences reported here may be important determinants of the age-dependent neurobehavior of guinea pigs in different tasks.

White matter abnormalities across the lifespan of schizophrenia: a harmonized multi-site diffusion MRI study.

Several prominent theories of schizophrenia suggest that structural white matter pathologies may follow a developmental, maturational, and/or degenerative process. However, a lack of lifespan studies has precluded verification of these theories. Here, we analyze the largest sample of carefully harmonized diffusion MRI data to comprehensively characterize age-related white matter trajectories, as measured by fractional anisotropy (FA), across the course of schizophrenia. Our analysis comprises diffusion scans of 600 schizophrenia patients and 492 healthy controls at different illness stages and ages (14-65 years), which were gathered from 13 sites. We determined the pattern of age-related FA changes by cross-sectionally assessing the timing of the structural neuropathology associated with schizophrenia. Quadratic curves were used to model between-group FA differences across whole-brain white matter and fiber tracts at each age; fiber tracts were then clustered according to both the effect-sizes and pattern of lifespan white matter FA differences. In whole-brain white matter, FA was significantly lower across the lifespan (up to 7%; p < 0.0033) and reached peak maturation younger in patients (27 years) compared to controls (33 years). Additionally, three distinct patterns of neuropathology emerged when investigating white matter fiber tracts in patients: (1) developmental abnormalities in limbic fibers, (2) accelerated aging and abnormal maturation in long-range association fibers, (3) severe developmental abnormalities and accelerated aging in callosal fibers. Our findings strongly suggest that white matter in schizophrenia is affected across entire stages of the disease. Perhaps most strikingly, we show that white matter changes in schizophrenia involve dynamic interactions between neuropathological processes in a tract-specific manner.

A multisample study of longitudinal changes in brain network architecture in 4-13-year-old children.

Recent advances in human neuroimaging research have revealed that white-matter connectivity can be described in terms of an integrated network, which is the basis of the human connectome. However, the developmental changes of this connectome in childhood are not well understood. This study made use of two independent longitudinal diffusion-weighted imaging data sets to characterize developmental changes in the connectome by estimating age-related changes in fractional anisotropy (FA) for reconstructed fibers (edges) between 68 cortical regions. The first sample included 237 diffusion-weighted scans of 146 typically developing children (4-13 years old, 74 females) derived from the Pediatric Longitudinal Imaging, Neurocognition, and Genetics (PLING) study. The second sample included 141 scans of 97 individuals (8-13 years old, 62 females) derived from the BrainTime project. In both data sets, we compared edges that had the most substantial age-related change in FA to edges that showed little change in FA. This allowed us to investigate if developmental changes in white matter reorganize network topology. We observed substantial increases in edges connecting peripheral and a set of highly connected hub regions, referred to as the rich club. Together with the observed topological differences between regions connecting to edges showing the smallest and largest changes in FA, this indicates that changes in white matter affect network organization, such that highly connected regions become even more strongly imbedded in the network. These findings suggest that an important process in brain development involves organizing patterns of inter-regional interactions. Hum Brain Mapp 39:157-170, 2018. © 2017 Wiley Periodicals, Inc.

Age-related changes in fractional anisotropy in corpus callosum with MR diffusion tensor imaging

Objective To analyze age-related changes in fractional anisotropy(FA) in sub-regions of corpus callosum on diffusion tensor imaging(DTI).Methods DTI was obtained from 171 healthy individuals(80 men,91 women; age 12 to 73 years; median age 44 years).All the subjects were stratified into the following seven age groups(10-19,20-29,30-39,40-49,50-59,60-69,70-79 years).Corpus callosum was divided into 5 subregions(Ⅰ-Ⅴ region).DTI FA values of sub-regions of corpus callosum were measured.Mean FA values changes in corpus callosum sub-regions with advancing age were evaluated with hierarchical polynomial regression analyses.Results The mean FA value in the Ⅴ region was the highest within the same age group.The corresponding values from group 1 to 7 were 0.77±0.06,0.80±0.03,0.79±0.03,0.79±0.03,0.78±0.03,0.77±0.03,0.77±0.03,respectively.The mean FA value in the Ⅲ region was the lowest within the same age group.The corresponding values from group 1 to 7 were 0.51 ±0.08,0.59± 0.06,0.59±0.06,0.56±0.07,0.55±0.07,0.52±0.07,0.43±0.07,respectively.The change of FA values in subregions of the corpus callosum on DTI followed an inverted U-shaped curve with advancing age(ROI1-ROI5,R2=0.162,0.214,0.164,0.098,0.070,respectively,all P＜0.05).FA peak appeared at 20 to 30 years old in all regions.Conclusions The study demonstrated age-related changes in FA value in sub-regions of the corpus callosum on DTI as following a curve,reflecting the age-related changes of physiological processes,which could serve as a basis for corpus callosum research. Key words: Corpus callosum; Magnetic resonance imaging; Age factors

Cerebellar Pathway Changes Following Cerebral Hemispherectomy

Following unilateral cerebral injury, several patterns of cerebellar metabolism have been noted on positron emission tomography (PET); these changes have been attributed both to the distant diaschisis as well as to reorganizational changes within the cerebellum. We used diffusion tensor magnetic resonance imaging (MRI) to study 14 children who had undergone cerebral hemispherectomy because of intractable epilepsy and compared them with those from 17 controls. In 10 children who had preoperative and postoperative scans, a paired comparison was performed. Our findings showed significantly higher fractional anisotropy values in corticopontocerebellar pathways postoperatively compared to preoperatively. When compared to controls, we found a higher rate of age-related fractional anisotropy changes of corticopontocerebellar pathways in the postoperative scans. Our results indicate reorganizational changes in the contralateral (intact) corticopontocerebellar pathway and the cerebellar white matter. These changes likely contribute to the far better motor outcomes seen in children compared to adults sustaining such cortical injuries.

Diffusion tensor imaging in the developing human cerebellum with histologic correlation

Diffusion tensor imaging was performed on 24 freshly aborted human fetuses with gestational age ranging from 20 to 37 weeks to observe age-related fractional anisotropy changes in cerebellar cortex and cerebellar white matter. Quantitative immunohistochemical analysis was performed for glial fibrillary acidic protein in each fetus molecular layer of cerebellar cortex and myelin basic protein expression was quantified in myelinated areas of the middle cerebellar peduncles. The cerebellar cortical fractional anisotropy reached its peak value at 28 weeks, and then decreased gradually until 37 weeks. The time course of glial fibrillary acidic protein expression paralleled that of fractional anisotropy in the cerebellar cortex from 20 weeks of gestation upto the gestational age at which the fractional anisotropy reached its peak value (28 weeks). In the middle cerebellar peduncles, the fractional anisotropy increased continuously upto 37 weeks of gestational age and showed a significant positive correlation with myelin basic protein immunostained fibers. The fractional anisotropy quantification can be used to assess the migrational and maturation changes during the development of the human fetal cerebellum supported by the immunohistochemical analysis.

Comparative Evaluation of the Cerebral and Cerebellar White Matter Development in Pediatric Age Group using Quantitative Diffusion Tensor Imaging

Age-dependent changes in the normal cerebral white matter have been reported; however, there is no study on normal cerebellar white matter maturation in developing brain using diffusion tensor imaging (DTI). We performed DTI in 21 children who had normal neurological assessment along with no evidence of any abnormality on imaging. The aim of this study was to compare the age-related changes in fractional anisotropy (FA) and mean diffusivity (MD) quantified from cerebral white matter (splenium and genu of the corpus callosum and posterior limb of the internal capsule) and cerebellar white matter (middle cerebellar peduncles, superior cerebellar peduncles, and inferior cerebellar peduncles) regions in healthy children ranging in age from birth to 132 months. Log-linear regression model showed best fit to describe the age-related changes in FA and MD both for cerebral and cerebellar white matter. In cerebral white matter, an initial sharp increase in FA was observed up to the age of 24 months followed by a gradual increase up to 132 months. In cerebellar white matter, sharp increase in FA was observed up to 36 months, which then followed a gradual increase. However, MD showed a sharp decrease in cerebral white matter up to 24 months followed by a more gradual decrease thereafter, while in cerebellar white matter after an initial decrease (6 months), it followed a stable pattern. This study provides normative database of brain white matter development from neonates to childhood. This quantitative information may be useful for assessing brain maturation in patients with developmental delay of the cerebral and cerebellar white matter.

Changes in white matter microstructure during adolescence

Postmortem histological studies have demonstrated that myelination in human brain white matter (WM) continues throughout adolescence and well into adulthood. We used in vivo diffusion-weighted magnetic resonance imaging to test for age-related WM changes in 42 adolescents and 20 young adults. Tract-Based Spatial Statistics (TBSS) analysis of the adolescent data identified widespread age-related increases in fractional anisotropy (FA) that were most significant in clusters including the body of the corpus callosum and right superior corona radiata. These changes were driven by changes in perpendicular, rather than parallel, diffusivity. These WM clusters were used as seeds for probabilistic tractography, allowing us to identify the regions as belonging to callosal, corticospinal, and prefrontal tracts. We also performed voxel-based morphometry-style analysis of conventional T1-weighted images to test for age-related changes in grey matter (GM). We identified a cluster including right middle frontal and precentral gyri that showed an age-related decrease in GM density through adolescence and connected with the tracts showing age-related WM FA increases. The GM density decrease was highly significantly correlated with the WM FA increase in the connected cluster. Age-related changes in FA were much less prominent in the young adult group, but we did find a significant age-related increase in FA in the right superior longitudinal fascicle, suggesting that structural development of this pathway continues into adulthood. Our results suggest that significant microstructural changes in WM continue throughout adolescence and are associated with corresponding age-related changes in cortical GM regions.

Quantitative Diffusion Tensor Tractography of Association and Projection Fibers in Normally Developing Children and Adolescents

Whole-brain diffusion tensor tractography (DTT) at high signal-to-noise ratio and angular and spatial resolutions were utilized to study the effects of age, sex differences, and lateral asymmetries of 6 white matter pathways (arcuate fasciculus [AF], inferior longitudinal fasciculus, inferior fronto-occipital fasciculus [IFOF], uncinate fasciculus [UF], corticospinal tract [CST], and somatosensory pathway [SS]) in 31 right-handed children (6-17 years). Fractional anisotropy (FA), a measure of the orientational variance in water molecular diffusivity, and the magnitude of water diffusivity (parallel, perpendicular, and mean diffusivity) along the pathways were quantified. Three major patterns of maturation were observed: 1) significant increase in FA with age, accompanied by significant decreases in all 3 diffusivities (e.g., left IFOF); 2) significant decreases in all three diffusivities with age without significant changes in FA (e.g., left CST); and 3) no significant age-related changes in FA or diffusivity (e.g., SS). Sex differences were minimal. Many pathways showed lateral asymmetries. In the right hemisphere, the frontotemporal (FT) segment of AF was not visualized in a substantial (29%) number of participants. FA was higher in the left hemisphere in the FT segment of AF, UF, and CST, whereas it was lower in the frontoparietal segment of AF. This study provides normative data essential for the interpretation of pediatric brain DTT measurements in both health and disease.

Age-related degeneration of corpus callosum measured with diffusion tensor imaging

The corpus callosum is the major commissure connecting the cerebral hemispheres, and there is evidence of its change with aging. The sub-regions of the corpus callosum (genu, rostral body, anterior midbody, posterior midbody, isthmus, splenium) respectively comprise fibers connecting heteromodal- and unimodal-associated cortical regions, and it is known that abnormalities of the corpus callosum are correlated with abnormalities in cognition and behavior. Yet, little is known about changes in the tissue characteristics of its sub-regions. We assessed age-related changes in fractional anisotropy and mean diffusivity in the sub-regions of the corpus callosum using diffusion tensor imaging. We studied 42 healthy right-handed individuals aged 21–73 years. There were no significant interactions of sex × region. Age has significant negative correlation with fractional anisotropy in the genu ( P < 0.001), rostral body ( P < 0.001), and isthmus ( P = 0.005). Fractional anisotropy of the anterior midbody was correlated negatively with age at a trend level ( P = 0.022). Age was significantly positively correlated with mean diffusivity in the genu ( P = 0.001), rostral body ( P = 0.002), anterior midbody ( P = 0.001), and isthmus ( P = 0.001). Age-related changes were detected in the sub-regions where their projection areas are thought to be vulnerable to normal aging. This suggested that fractional anisotropy and mean diffusivity values of the corpus callosum sub-regions could serve as markers of disturbance across the respective projection areas.