Maj Hedehus

Microstructure of Temporo-Parietal White Matter as a Basis for Reading Ability: Evidence from Diffusion Tensor Magnetic Resonance Imaging

Diffusion tensor magnetic resonance imaging (MRI) was used to study the microstructural integrity of white matter in adults with poor or normal reading ability. Subjects with reading difficulty exhibited decreased diffusion anisotropy bilaterally in temporoparietal white matter. Axons in these regions were predominantly anterior-posterior in direction. No differences in T1-weighted MRI signal were found between poor readers and control subjects, demonstrating specificity of the group difference to the microstructural characteristics measured by diffusion tensor imaging (DTI). White matter diffusion anisotropy in the temporo-parietal region of the left hemisphere was significantly correlated with reading scores within the reading-impaired adults and within the control group. The anisotropy reflects microstructure of white matter tracts, which may contribute to reading ability by determining the strength of communication between cortical areas involved in visual, auditory, and language processing.

Age-related decline in brain white matter anisotropy measured with spatially corrected echo-planar diffusion tensor imaging.

Echo planar (EP) diffusion tensor imaging (DTI) permits in vivo identification of the orientation and coherence of brain white matter tracts but suffers from field inhomogeneity‐induced geometric distortion. To reduce spatial distortion, polynomial warping corrections were applied and the effects tested on measures of fractional anisotropy (FA) in the genu and splenium of corpus callosum. Implementation entailed spatially warping EP images obtained without diffusion weighting (b = 0) to long‐echo T2‐weighted fast spin echo images, collected for anatomical delineation, tissue segmentation, and coregistration with the diffusion images. Using the optimal warping procedure (third‐order polynomial), the effects of age on FA and a quantitative measure of intervoxel coherence (C) in the genu, splenium, centrum semiovale, and frontal and parietal pericallosal white matter were examined in 31 healthy men (23–76 years). FA declined significantly with age in all regions except the splenium, whereas intervoxel coherence positively correlated with age in the genu. Magn Reson Med 44:259–268, 2000.

Myelination and organization of the frontal white matter in children: a diffusion tensor MRI study.

Myelination is critical for the functional development of the brain, but the time course of myelination during childhood is not well known. Diffusion tensor MR imaging (DTI) provides a new method for estimating myelination in vivo. Myelin restricts diffusion of water transverse to the axons, causing diffusion to be anisotropic. By quantifying the anisotropy, the progressive myelination of axons can be studied. Central white matter of the frontal lobe was studied in seven children (mean age 10 years) and five adults (mean age 27 years). Anisotropy in the frontal white matter was significantly lower in children than in adults, suggesting less myelination in children. Measurement of the coherence of white matter revealed that the right frontal lobe had a more regular organization of axons than the left frontal lobe, in both children and adults. The results demonstrate that maturation of the frontal white matter continues into the second decade of life. The time course of prefrontal maturation makes it possible that myelination is a basis for the gradual development of prefrontal functions, such as increased working memory capacity.

Equivalent disruption of regional white matter microstructure in ageing healthy men and women.

Diffusion tensor imaging was used to measure regional differences in brain white matter microstructure (intravoxel coherence) and macrostructure (intervoxel coherence) and age-related differences between men and women. Neuropsychiatrically healthy men and women, spanning the adult age range, showed the same pattern of variation in regional white matter coherence. The greatest coherence measured was in corpus callosum, where commissural fibers have one primary orientation, lower in the centrum semiovale, where fibers cross from multiple axes, and lowest in pericallosal areas, where fibers weave and interstitial fluid commonly pools. Age-related declines in intravoxel coherence was equally strong and strikingly similar in men and women, with evidence for greater age-dependent deterioration in frontal than parietal regions. Degree of regional white matter coherence correlated with gait, balance, and interhemispheric transfer test scores.

In vivo mapping of the fast and slow diffusion tensors in human brain

Recent studies have shown that the diffusional signal decay in human brain is non‐monoexponential and may be described in terms of compartmentalized water fractions. Diffusion tensor imaging (DTI), which provides information about tissue structure and orientation, typically uses b values up to 1000 s mm−2 so that the signal is dominated by the fast diffusing fraction. In this study b factors up to 3500 s mm−2 are utilized, allowing the diffusion tensor properties of the more slowly diffusing fraction to be mapped for the first time. The mean diffusivity (MD) of the slow diffusion tensor was found to exhibit strong white/gray matter (WM/GM) contrast. Maps depicting the principal direction of the slow tensor indicated alignment with the fast tensor and the known orientation of the WM pathways. Magn Reson Med 47:623–628, 2002.

Diffusion time dependence of the apparent diffusion tensor in healthy human brain and white matter disease.

The diffusion time dependence of the brain water diffusion tensor provides information regarding diffusion restriction and hindrance but has received little attention, primarily due to limitations in gradient amplitude available on clinical MRI systems, required to achieve short diffusion times. Using new, more powerful gradient hardware, the diffusion time dependence of tensor‐derived metrics were studied in human brain in the range 8–80 ms, which encompasses the shortest diffusion times studied to date. There was no evidence for a change in mean diffusivity, fractional anisotropy, or in the eigenvalues with diffusion time in healthy human brain. The findings are consistent with a model of unrestricted, but hindered water diffusion with semipermeable membranes, likely originating from the extracellular space in which the average extracellular separation is less than 7 microns. Similar findings in two multiple sclerosis plaques indicated that the size of the water diffusion space in the lesion did not exceed this dimension. Magn Reson Med 45:1126–1129, 2001.

Diffusion- and perfusion-weighted magnetic resonance imaging of focal cerebral ischemia and cortical spreading depression under conditions of mild hypothermia.

In a model of experimental stroke, we characterize the effects of mild hypothermia, an effective neuroprotectant, on fluid shifts, cerebral perfusion and spreading depression (SD) using diffusion- (DWI) and perfusion-weighted MRI (PWI). Twenty-two rats underwent 2 h of middle cerebral artery (MCA) occlusion and were either kept normothermic or rendered mildly hypothermic shortly after MCA occlusion for 2 h. DWI images were obtained 0.5, 2 and 24 h after MCA occlusion, and maps of the apparent diffusion coefficient (ADC) were generated. SD-like transient ADC decreases were also detected using DWI in animals subjected to topical KCl application (n=4) and ischemia (n=6). Mild hypothermia significantly inhibited DWI lesion growth early after the onset of ischemia as well as 24 h later, and improved recovery of striatal ADC by 24 h. Mild hypothermia prolonged SD-like ADC transients and further decreased the ADC following KCl application and immediately after MCA occlusion. Cerebral perfusion, however, was not affected by temperature changes. We conclude that mild hypothermia is neuroprotective and suppresses infarct growth early after the onset of ischemia, with better ADC recovery. The ADC decrease during SD was greater during mild hypothermia, and suggests that the source of the ADC is more complex than previously believed.

Brain gray and white matter transverse relaxation time in schizophrenia

Recent in vivo diffusion brain imaging studies of schizophrenic patients have revealed microstructural abnormalities, with low diffusion anisotropy present throughout much of cortical white matter. Brain anisotropy is produced when proton movement reflects physically restricted water movement, for example, by myelin sheaths. Conditions that increase self-diffusion, such as edema, may also alter the longitudinal and transverse relaxation time of protons, and it is possible that such changes could explain the observed anisotropy diminution seen in schizophrenia. To test this possibility, we calculated pixel-by-pixel transverse relaxation time (T2) and proton density (PD) maps for gray matter and white matter across eight 5-mm-thick axial slices of fast spin echo MRI in 10 control men (age 30-57 years) and 10 men with schizophrenia (age 32-64 years). Schizophrenics had significantly longer mean white matter T2 (84.0 vs. 81.9 ms, P<0.03) and gray matter T2 (95.1 vs. 92.2, P = 0.003); their mean white and gray matter PD values were not significantly different from those of controls. Correlations were not significant between anisotropy and T2 in either grey or white matter but were significant between anisotropy and PD in white matter. T2 relaxation times are longer in schizophrenics than in controls in both gray and white matter whereas anisotropy reduction is restricted to white matter. Taken together, these results suggest that the process producing prolonged T2 does not fully account for the abnormally low anisotropy observed selectively in white matter in this group of schizophrenic patients.

N-Acetylaspartate Distribution in Rat Brain Striatum During Acute Brain Ischemia

Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (1H-MRS) and is used in clinical settings as a marker of neuronal density. It is, however, uncertain whether the change in brain NAA content in acute stroke is reliably measured by 1H-MRS and how NAA is distributed within the ischemic area. Rats were exposed to middle cerebral artery occlusion. Preischemic values of [NAA] in striatum were 11 mmol/L by 1H-MRS and 8 mmol/kg by HPLC. The methods showed a comparable reduction during the 8 hours of ischemia. The interstitial level of [NAA] ([NAA]e) was determined by microdialysis using [3H]NAA to assess in vivo recovery. After induction of ischemia, [NAA]e increased linearly from 70 µmol/L to a peak level of 2 mmol/L after 2 to 3 hours before declining to 0.7 mmol/L at 7 hours. For comparison, [NAA]e was measured in striatum during global ischemia, revealing that [NAA]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA.

Diffusion-weighted magnetic resonance imaging: theory and potential applications to child neurology.

Magnetic resonance imaging (MRI) is an excellent tool for the investigation of neurological disorders in children. Diffusion-weighted MRI (DWI) is sensitive to the diffusion (or molecular displacement) of water in tissue. The purpose of this article is to describe briefly the basic theory behind DWI and to discuss its potential applications to neurological disorders in children. We demonstrate that DWI is a sensitive technique for the detection of acute brain injury, and that it is well suited for monitoring brain development, particularly myelination and white matter changes.