The Human Brain

Mitigating the loss of brain tissue due to age is a major problem for an ageing population. Improving cardiorespiratory fitness has been suggested as a possible strategy, but the influence on brain morphology has not been fully characterized. To investigate the dependent shifts in brain tissue distribution as a function of cardiorespiratory fitness, we used a 3D transport-based morphometry approach. In this study of 172 inactive older adults aged 58–81 (66.5 ± 5.7) years, cardiorespiratory fitness was determined by VO2 peak (ml/kg/min) during graded exercise and brain morphology was assessed through structural magnetic resonance imaging. After correcting for covariates including age (in the fitness model), gender and level of education, we compared dependent tissue shifts with age to those due to VO2 peak. We found a significant association between cardiorespiratory fitness and brain tissue distribution (white matter, r = 0.30, P = 0.003; grey matter, r = 0.40, P < 0.001) facilitated by direct visualization of the brain tissue shifts due to cardiorespiratory fitness through inverse transformation—a key capability of 3D transport-based morphometry. A strong statistical correlation was found between brain tissue changes related to ageing and those associated with lower cardiorespiratory fitness (white matter, r = 0.62, P < 0.001; grey matter, r = 0.74, P < 0.001). In both cases, frontotemporal regions shifted the most while basal ganglia shifted the least. Our results highlight the importance of cardiorespiratory fitness in maintaining brain health later in life. Furthermore, this work demonstrates 3D transport-based morphometry as a novel neuroinformatic technology that may aid assessment of therapeutic approaches for brain ageing and neurodegenerative diseases.

Cognitive deficits are among the most commonly reported post-concussive symptoms, yet the underlying microstructural injury is poorly understood. Our aim was to discover white matter injury underlying reaction time in mild traumatic brain injury DTI by applying transport-based morphometry. In this retrospective study, we performed DTI on 64 postconcussive patients (10–28 years of age; 69% male, 31% female) between January 2006 and March 2013. We measured the reaction time percentile by using Immediate Post-Concussion Assessment and Cognitive Testing. Using the 3D transport-based morphometry technique we developed, we mined fractional anisotropy maps to extract the common microstructural injury associated with reaction time percentile in an automated manner. Permutation testing established statistical significance of the extracted injuries. We visualized the physical substrate responsible for reaction time through inverse transport-based morphometry transformation. The direction in the transport space most correlated with reaction time was significant after correcting for covariates of age, sex, and time from injury (Pearson r = 0.44, P < .01). Inverting the computed direction using transport-based morphometry illustrates physical shifts in fractional anisotropy in the corpus callosum (increase) and within the optic radiations, corticospinal tracts, and anterior thalamic radiations (decrease) with declining reaction time. The observed shifts are consistent with biologic pathways underlying the visual-spatial interpretation and response-selection aspects of reaction time. Transport-based morphometry discovers complex white matter injury underlying postconcussive reaction time in an automated manner. The potential influences of edema and axonal loss are visualized in the visual-spatial interpretation and response-selection pathways. Transport-based morphometry can bridge the gap between brain microstructure and function in diseases in which the structural basis is unknown.

Craniosynostosis is a condition in which one or more of the calvarial sutures fuses prematurely. In addition to the cosmetic ramifications attributable to premature suture fusion, aberrations in neurophysiological parameters are seen, which may result in more significant damage. This work examines the microstructural integrity of white matter, using diffusion tensor imaging (DTI) in a homogeneous strain of rabbits with simple, familial coronal suture synostosis before and after surgical correction. After diagnosis, rabbits were assigned to different groups, wild-type (WT), rabbits with early-onset complete fusion of the coronal suture (BC), and rabbits that had undergone surgical correction with suturectomy (BC-SU) at 10 days of age. Fixed rabbit heads were imaged at 12, 25, or 42 days of life using a 4.7-T, 40-cm bore Avance scanner with a 7.2-cm radiofrequency coil. For DTI, a 3D spin echo sequence was used with a diffusion gradient (b = 2000 sec/mm2) applied in 6 directions. As age increased from 12 to 42 days, the DTI differences between WT and BC groups became more pronounced (p < 0.05, 1-way ANOVA), especially in the corpus callosum, cingulum, and fimbriae. Suturectomy resulted in rabbits with no significant differences compared with WT animals, as assessed by DTI of white matter tracts. Also, it was possible to predict to which group an animal belonged (WT, BC, and BC-SU) with high accuracy based on imaging data alone using a linear support vector machine classifier. The ability to predict to which group the animal belonged improved as the age of the animal increased (71% accurate at 12 days and 100% accurate at 42 days). Craniosynostosis results in characteristic changes of major white matter tracts, with differences becoming more apparent as the age of the rabbits increases. Early suturectomy (at 10 days of life) appears to mitigate these differences.