Water diffusion in a tissue model is studied both analytically and numerically. Tissue is regarded as a periodic array of boxes surrounded by partially permeable membranes (cells), embedded in an extracellular medium. intracellular and extracellular diffusion coefficients may differ. Expressions for the apparent diffusion coefficients (ADC) in isotropic and nonisotropic tissues are derived and compared with Monte Carlo simulations. Calculated ADCs disagree with values obtained from the widely used "fast exchange" formula. Effects of differences between intracellular and extracellular T2 relaxation times on measured values of ADC and T2 are discussed. The general analysis is specifically applied to the changes occurring in ADC following ischemic insults to brain tissue. It is found that although membranes affect ADC significantly, the observed changes in diffusion cannot be due to reduced membrane permeabilities. They may result from the combined effect of changes in cellular volume fraction, extracellular and intracellular diffusion.

The factors affecting the rate of loss of transverse magnetization in gradient echo and spin-echo pulse sequences have been quantified using computer modeling for media containing arrays of susceptibility variations. The results are particularly relevant for describing the signal losses that occur in tissues containing capillaries of altered intrinsic susceptibility from the administration of exogenous contrast agents or arising from changes in blood oxygenation. The precise magnitudes and relationship of gradient echo and spin-echo decay rates depend on geometrical factors such as the sizes and spacings of the inhomogeneities, the rate of water diffusion, field strength, and echo times. The conventional separation of contributions to transverse decay rates arising from so-called static field effects and diffusion is shown to be inappropriate for many situations of practical interest because diffusion introduces a motional averaging of the static field even in gradient echo sequences. The result of diffusion in some regimes is to reduce the decay rate from field inhomogeneities in gradient echo sequences, so that T2* is longer in media such as tissue where water diffuses reasonably rapidly, than would be the case for stationary nuclei. The effects of different types of contrast agent and the implications for functional imaging based on the effects of deoxyhemoglobin in brain tissue are considered.

The goal of the current investigation was to detect clinically important axonal damage in cerebral white matter after mild traumatic brain injury (TBI) using diffusion tensor imaging (DTI). To this end, we evaluated a prospective, pilot study of six subjects with isolated mild TBI and six matched orthopedic controls. All subjects underwent DTI scanning, post-concussive symptom (PCS) assessment, and neurobehavioral testing within 72 h of injury. Fractional anisotropy (FA) and trace values in white matter voxels of whole brain and five preselected regions of interest (ROI) were compared in mild TBI and control subjects using a quantile approach. In addition, whole brain images were analyzed using voxel-based morphometry. All subjects underwent quality of life and repeat PCS assessment at 1 month. Whole brain images revealed significantly lower 1(st) percentile trace values (mean 0.465 vs. 0.488, p = 0.049) among mild TBI subjects. These trace values correlated with PCS scores at both 72 h (r = -0.57, p = 0.05) and 1 month (r = -0.61, p = 0.04). Analysis of ROIs showed mild TBI subjects to have significantly lower mean trace in the left anterior internal capsule (0.536 vs. 0.574, p = 0.007) and higher maximum ROI-specific median FA values (mean 0.801 vs. 0.756, p = 0.035) in the posterior corpus callosum. These FA values correlated with 72-h PCS score (r = -0.63, p = 0.03), and two neurobehavioral tests (visual motor speed [r = 0.63, p = 0.03] and impulse control [r = 0.59, p = 0.04]). Collectively, DTI detected significantly lower trace and elevated FA values in mild TBI subjects compared to controls. These abnormalities correlated to poor clinical outcome. We believe these findings represent axonal swelling, an early step in the process of axonal injury.

IntroductionRepetitive head impacts (RHI) sustained in contact sports are thought to be necessary for the long-term development of chronic traumatic encephalopathy (CTE). Our objectives were to: 1) characterize the magnitude and persistence of RHI-induced white matter (WM) changes; 2) determine their relationship to kinematic measures of RHI; and 3) explore their clinical relevance.MethodsProspective, observational study of 10 Division III college football players and 5 non-athlete controls during the 2011-12 season. All subjects underwent diffusion tensor imaging (DTI), physiologic, cognitive, and balance testing at pre-season (Time 1), post-season (Time 2), and after 6-months of no-contact rest (Time 3). Head impact measures were recorded using helmet-mounted accelerometers. The percentage of whole-brain WM voxels with significant changes in fractional anisotropy (FA) and mean diffusivity (MD) from Time 1 to 2, and Time 1 to 3 was determined for each subject and correlated to head impacts and clinical measures.ResultsTotal head impacts for the season ranged from 431–1,850. No athlete suffered a clinically evident concussion. Compared to controls, athletes experienced greater changes in FA and MD from Time 1 to 2 as well as Time 1 to 3; most differences at Time 2 persisted to Time 3. Among athletes, the percentage of voxels with decreased FA from Time 1 to 2 was positively correlated with several helmet impact measures. The persistence of WM changes from Time 1 to 3 was also associated with changes in serum ApoA1 and S100B autoantibodies. WM changes were not consistently associated with cognition or balance.ConclusionsA single football season of RHIs without clinically-evident concussion resulted in WM changes that correlated with multiple helmet impact measures and persisted following 6 months of no-contact rest. This lack of WM recovery could potentially contribute to cumulative WM changes with subsequent RHI exposures.

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