Cortical Diffusivity Research Articles

Diffusion-weighted imaging of the kidneys in haemolytic uraemic syndrome.

To evaluate the kidneys of patients with haemolytic uraemic syndrome (HUS) using diffusion-weighted imaging (DWI) and Doppler ultrasound (US) compared with healthy controls. Fifteen patients (mean age 33.3 years; three male; 12 female) with diarrhoea-positive HUS and 15 healthy volunteers were prospectively evaluated with DWI and Doppler US. A total apparent diffusion coefficient (ADCTOT), and ADCs predominantly reflecting microperfusion (ADCLOW) and diffusion (ADCHIGH) were calculated. Doppler US evaluated renal vascularity and flow. When compared with controls, kidneys affected by HUS showed reduced cortical ADC values (ADCTOT 1.79±0.22 vs. 2.04±0.1x10-3 mm2/s, P 0.001), resulting in either low corticomedullary differences (11/15 patients) or an inverted corticomedullary pattern (4/15 patients). Reduction of cortical ADC values was associated with a decrease of cortical vascularity on Doppler US (ADCTOT, P<0.001; ADCLOW, P 0.047). Kidneys with complete absence of the cortical vasculature on Doppler US (four patients) also demonstrated limited diffusion (ADCHIGH, P 0.002). Low glomerular filtration rate, requirement for haemodialysis during hospitalization, and longer duration of haemodialysis were associated with decreased cortical diffusivity (ADCTOT: P 0.04, 0.007, and <0.001, respectively). DWI shows qualitative and quantitative abnormalities in kidneys affected by HUS, thereby extending the non-invasive assessment of renal parenchymal damage. • In HUS, DWI is feasible for functional characterization of kidney involvement. • Kidneys affected by HUS showed reduced cortical diffusivity. • Decreased cortical diffusivity was associated with lower kidney function. • Requirement and duration of haemodialysis was linked to degree of cortical alterations.

0944 SUPERFICIAL WHITE MATTER AND CORTICAL THICKNESS ASSOCIATED WITH PARASOMNIAS IN CHILDREN

The human brain changes during development. Cortical gray matter (GM) and superficial white matter (SWM) may be related to certain neurological diseases. Parasomnias such as sleepwalking and bedwetting are common in children and decrease in frequency by age. Although functional and anatomical changes of youth in neuronal circuits have been suggested in parasomnia, this has never been systematically studied. We evaluated multimodal data from 866 children who were part of the Philadelphia Neurdevelopmental Cohort (PNC). The PNC database included semistructured clinical interviews, which included questions to children and their parents regarding problems with sleepwalking and bedwetting after 5 years old (lifetime past or current). We investigated demographic data including age, sex, ethnicity, and medical conditions reported. There were 17 children who reported having current sleepwalking, 774 children without any history of sleepwalking, 42 children having current bedwetting and 702 children without history of bedwetting. Structural MRI data and Diffusion Tensor Imaging data were analyzed to sample values of cortical thickness and mean diffusivity (MD) of SWM at each vertex scattered on the surface of white matter of the brain. In Thickness-MD coordinate system at each vertex, we calculate the distance between the coordinate point, obtained from actual value of thickness and MD, and the regression line made by MRI data of normal children in PNC data. We sampled the distance called ThickMD at vertex point again. The values of Thickness, MD and ThickMD of each vertex were analyzed with the General Linear Model to test for the effects of diseases corrected by age and sex. There were only limited numbers of vertexes having significant effects of sleepwalking and bedwetting on Thickness and MD. However, there were many vertexes, which spread diffusely over brain, having significant effects of sleepwalking and bedwetting on ThickMD. Significant effect of diseases on ThickMD rather than thickness and MD would suggest that disconnectivity between cortical GM and SWM beneath the GM are associated with the underlying pathophysiology of parasomnias in children. Larger studies are needed to investigate potential neurobiological mechanisms underling parasomnias. no

Genetic and environmental influences on cortical mean diffusivity

Magnetic resonance imaging (MRI) has become an important tool in the early detection of age-related and neuropathological brain changes. Recent studies suggest that changes in mean diffusivity (MD) of cortical gray matter derived from diffusion MRI scans may be useful in detecting early effects of Alzheimer's disease (AD), and that these changes may be detected earlier than alterations associated with standard structural MRI measures such as cortical thickness. Thus, due to its potential clinical relevance, we examined the genetic and environmental influences on cortical MD in middle-aged men to provide support for the biological relevance of this measure and to guide future gene association studies. It is not clear whether individual differences in cortical MD reflect neuroanatomical variability similarly detected by other MRI measures, or whether unique features are captured. For instance, variability in cortical MD may reflect morphological variability more commonly measured by cortical thickness. Differences among individuals in cortical MD may also arise from breakdowns in myelinated fibers running through the cortical mantle. Thus, we investigated whether genetic influences on variation in cortical MD are the same or different from those influencing cortical thickness and MD of white matter (WM) subjacent to the cortical ribbon. Univariate twin analyses indicated that cortical MD is heritable in the majority of brain regions; the average of regional heritability estimates ranged from 0.38 in the cingulate cortex to 0.66 in the occipital cortex, consistent with the heritability of other MRI measures of the brain. Trivariate analyses found that, while there was some shared genetic variance between cortical MD and each of the other two measures, this overlap was not complete (i.e., the correlation was statistically different from 1). A significant amount of distinct genetic variance influences inter-individual variability in cortical MD; therefore, this measure could be useful for further investigation in studies of neurodegenerative diseases and gene association studies.

Microstructural and microglial changes after repetitive mild traumatic brain injury in mice.

Traumatic brain injury (TBI) is a major public health issue, with recently increased awareness of the potential long-term sequelae of repetitive injury. Although TBI is common, objective diagnostic tools with sound neurobiological predictors of outcome are lacking. Indeed, such tools could help to identify those at risk for more severe outcomes after repetitive injury and improve understanding of biological underpinnings to provide important mechanistic insights. We tested the hypothesis that acute and subacute pathological injury, including the microgliosis that results from repeated mild closed head injury (rmCHI), is reflected in susceptibility-weighted magnetic resonance imaging and diffusion-tensor imaging microstructural abnormalities. Using a combination of high-resolution magnetic resonance imaging, stereology, and quantitative PCR, we studied the pathophysiology of male mice that sustained seven consecutive mild traumatic brain injuries over 9 days in acute (24 hr) and subacute (1 week) time periods. rmCHI induced focal cortical microhemorrhages and impaired axial diffusivity at 1 week postinjury. These microstructural abnormalities were associated with a significant increase in microglia. Notably, microgliosis was accompanied by a change in inflammatory microenvironment defined by robust spatiotemporal alterations in tumor necrosis factor-α receptor mRNA. Together these data contribute novel insight into the fundamental biological processes associated with repeated mild brain injury concomitant with subacute imaging abnormalities in a clinically relevant animal model of repeated mild TBI. These findings suggest new diagnostic techniques that can be used as biomarkers to guide the use of future protective or reparative interventions. © 2016 Wiley Periodicals, Inc.

Sleep reverts changes in human gray and white matter caused by wake-dependent training

Learning leads to rapid microstructural changes in gray (GM) and white (WM) matter. Do these changes continue to accumulate if task training continues, and can they be reverted by sleep? We addressed these questions by combining structural and diffusion weighted MRI and high-density EEG in 16 subjects studied during the physiological sleep/wake cycle, after 12h and 24h of intense practice in two different tasks, and after post-training sleep. Compared to baseline wake, 12h of training led to a decline in cortical mean diffusivity. The decrease became even more significant after 24h of task practice combined with sleep deprivation. Prolonged practice also resulted in decreased ventricular volume and increased GM and WM subcortical volumes. All changes reverted after recovery sleep. Moreover, these structural alterations predicted cognitive performance at the individual level, suggesting that sleep's ability to counteract performance deficits is linked to its effects on the brain microstructure. The cellular mechanisms that account for the structural effects of sleep are unknown, but they may be linked to its role in promoting the production of cerebrospinal fluid and the decrease in synapse size and strength, as well as to its recently discovered ability to enhance the extracellular space and the clearance of brain metabolites.

Measurement of cortical mean diffusivity detects early microstructural breakdown of the cerebral cortex in presymptomatic familial Alzheimer’s disease

Measurement of cortical mean diffusivity detects early microstructural breakdown of the cerebral cortex in presymptomatic familial Alzheimer’s disease

Measurement of cortical mean diffusivity detects early microstructural breakdown of the cerebral cortex in presymptomatic familial Alzheimer’s disease

Measurement of cortical mean diffusivity detects early microstructural breakdown of the cerebral cortex in presymptomatic familial Alzheimer’s disease

Diffusion imaging changes in grey matter in Alzheimer's disease: a potential marker of early neurodegeneration.

Alzheimer’s disease (AD) is recognized to have a long presymptomatic period, during which there is progressive accumulation of molecular pathology, followed by inexorable neuronal damage. The ability to identify presymptomatic individuals with evidence of neurodegenerative change, to stage their disease, and to track progressive changes will be important for early diagnosis and for prevention trials. Despite recent advances, particularly in magnetic resonance imaging, our ability to identify early neurodegenerative changes reliably is limited. The development of diffusion-weighted magnetic resonance imaging, which is sensitive to microstructural changes not visible with conventional volumetric techniques, has led to a number of diffusion imaging studies in AD; these have largely focused on white matter changes. However, in AD cerebral grey matter is affected very early, with pathological studies suggesting that grey matter changes predate those in white matter. In this article we review the growing number of studies that assess grey matter diffusivity changes in AD. Although use of the technique is still at a relatively early stage, results so far have been promising. Initial studies identified changes in diffusion measures in the hippocampi of patients with mild cognitive impairment, which predated macroscopic volume loss, with positive predictive value for progression to AD dementia. More recent studies have identified abnormalities in multiple neocortical areas (particularly the posterior cingulate) at various stages of disease progression. Studies of patients who carry genetic mutations predisposing to autosomal dominant familial AD have shown cortical and subcortical grey matter diffusivity changes several years before the expected onset of the first clinical symptoms. The technique is not without potential methodological difficulties, especially relating to partial volume effects, although recent advances appear to be reducing such issues. Going forward, further utilization of grey matter diffusion measurements in AD may improve our understanding with regards to the timing and nature of the earliest presymptomatic neurodegenerative changes. This imaging technique may also be useful in comparing and contrasting subtle variations in different disease subgroups, and as a sensitive outcome measure for presymptomatic clinical trials in AD and other neurodegenerative diseases.

Characterizing topological patterns in amnestic mild cognitive impairment by quantitative water diffusivity.

Mean diffusivity (MD) derived from diffusion tensor imaging has shown its ability to assess the microscopic structural integrity damage of gray matter in amnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer's disease (AD). However, little is known about the small world topology networks constructed by cortical MD in cognitive disease. In this work, we measured the cortical MD in the entire brain in patients with aMCI (n = 30) and AD (n = 30) compared with cognitive-normal (CNs) controls (n = 30), and then constructed the cortical diffusivity network by using graph-theoretical analysis. Compared with CNs, patients with aMCI and AD showed abnormal small-world property of cortical diffusivity networks (higher degree of clustering and longer path length), reflecting a less optimal topological organization. Moreover, the mean degree of connections of network in aMCI patients was characterized by lower than CNs but higher than AD. In addition, 11 hub regions were identified by negative correlations between MD and the score of Montreal Cognitive Assessment after multiple regression analysis, including bilateral hippocampi and related limbic system. Among those hub regions, the connectivity of the right olfactory cortex and middle orbital gyrus to the rest of brain regions were disrupted earlier than the other 9 regions in aMCI when compared to CN. In conclusion, the change of cortical diffusivity in topological network organization, mean degree of connections, and disrupted hub regions in aMCI may serve to identify patients in the prodromal stage of AD and reflect microstructural deterioration of neurodegeneration.

Application of quantitative DTI metrics in sporadic CJD

Diffusion Weighted Imaging is extremely important for the diagnosis of probable sporadic Jakob–Creutzfeldt disease, the most common human prion disease. Although visual assessment of DWI MRI is critical diagnostically, a more objective, quantifiable approach might more precisely identify the precise pattern of brain involvement. Furthermore, a quantitative, systematic tracking of MRI changes occurring over time might provide insights regarding the underlying histopathological mechanisms of human prion disease and provide information useful for clinical trials. The purposes of this study were: 1) to describe quantitatively the average cross-sectional pattern of reduced mean diffusivity, fractional anisotropy, atrophy and T1 relaxation in the gray matter (GM) in sporadic Jakob–Creutzfeldt disease, 2) to study changes in mean diffusivity and atrophy over time and 3) to explore their relationship with clinical scales. Twenty-six sporadic Jakob–Creutzfeldt disease and nine control subjects had MRIs on the same scanner; seven sCJD subjects had a second scan after approximately two months. Cortical and subcortical gray matter regions were parcellated with Freesurfer. Average cortical thickness (or subcortical volume), T1-relaxiation and mean diffusivity from co-registered diffusion maps were calculated in each region for each subject. Quantitatively on cross-sectional analysis, certain brain regions were preferentially affected by reduced mean diffusivity (parietal, temporal lobes, posterior cingulate, thalamus and deep nuclei), but with relative sparing of the frontal and occipital lobes. Serial imaging, surprisingly showed that mean diffusivity did not have a linear or unidirectional reduction over time, but tended to decrease initially and then reverse and increase towards normalization. Furthermore, there was a strong correlation between worsening of patient clinical function (based on modified Barthel score) and increasing mean diffusivity.

Brain development after neonatal intermittent hyperoxia-hypoxia in the rat studied by longitudinal MRI and immunohistochemistry.

BackgroundNeonatal intermittent hyperoxia-hypoxia (IHH) is involved in the pathogenesis of retinopathy of prematurity. Whether similar oxygen fluctuations will create pathological changes in the grey and white matter of the brain is unknown. MethodsFrom birth until postnatal day 14 (P14), two litters (total n = 22) were reared in IHH: hyperoxia (50% O2) interrupted by three consecutive two-minute episodes of hypoxia (12% O2) every sixth hour. Controls (n = 8) were reared in room-air (20.9% O2). Longitudinal MRI (Diffusion Tensor Imaging and T2-mapping) was performed on P14 and P28 and retinal and brain tissue were examined for histopathological changes. Long-term neurodevelopment was assessed on P20 and P27. ResultsMean, radial and axial diffusivity were higher in white matter of IHH versus controls at P14 (p < 0.04), while fractional anisotropy (FA) was lower in the hippocampal fimbria and tended to be lower in corpus callosum (p = 0.08) and external capsule (p = 0.05). White matter diffusivity in IHH was similar to controls at P28. Higher cortical vessel density (p = 0.005) was observed at P14. Cortical and thalamic T2-relaxation time and mean diffusivity were higher in the IHH group at P14 (p ≤ 0.03), and albumin leakage was present at P28. Rats in the IHH group ran for a longer time on a Rotarod than the control group (p ≤ 0.005). Pups with lower bodyweight had more severe MRI alterations and albumin leakage.ConclusionIHH led to subtle reversible changes in brain white matter diffusivity, grey matter water content and vascular density. However, alterations in blood-brain barrier permeability may point to long-term effects. The changes seen after IHH exposure were more severe in animals with lower bodyweight and future studies should aim at exploring possible interactions between IHH and growth restriction.

Improvement of Partial Volume Segmentation for Brain Tissue on Diffusion Tensor Images Using Multiple-Tensor Estimation

To improve evaluations of cortical and subcortical diffusivity in neurological diseases, it is necessary to improve the accuracy of brain diffusion tensor imaging (DTI) data segmentation. The conventional partial volume segmentation method fails to classify voxels with multiple white matter (WM) fiber orientations such as fiber-crossing regions. Our purpose was to improve the performance of segmentation by taking into account the partial volume effects due to both multiple tissue types and multiple WM fiber orientations. We quantitatively evaluated the overall performance of the proposed method using digital DTI phantom data. Moreover, we applied our method to human DTI data, and compared our results with those of a conventional method. In the phantom experiments, the conventional method and proposed method yielded almost the same root mean square error (RMSE) for gray matter (GM) and cerebrospinal fluid (CSF), while the RMSE in the proposed method was smaller than that in the conventional method for WM. The volume overlap measures between our segmentation results and the ground truth of the digital phantom were more than 0.8 in all three tissue types, and were greater than those in the conventional method. In visual comparisons for human data, the WM/GM/CSF regions obtained using our method were in better agreement with the corresponding regions depicted in the structural image than those obtained using the conventional method. The results of the digital phantom experiment and human data demonstrated that our method improved accuracy in the segmentation of brain tissue data on DTI compared to the conventional method.

Regional changes of cortical mean diffusivities with aging after correction of partial volume effects.

Accurately measuring the cortical mean diffusivity (MD) derived from diffusion tensor imaging (DTI) at the comprehensive lobe, gyral and voxel level of young, elderly healthy brains and those with Alzheimer's disease (AD) may provide insights on heterogeneous cortical microstructural changes caused by aging and AD. Due to partial volume effects (PVE), the measurement of cortical MD is overestimated with contamination of cerebrospinal fluid (CSF). The bias is especially severe for aging and AD brains because of significant cortical thinning of these brains. In this study, we aimed to quantitatively characterize the unbiased regional cortical MD changes due to aging and AD and delineate the effects of cortical thinning of elderly healthy and AD groups on MD measurements. DTI and T1-weighted images of 14 young, 15 elderly healthy subjects and 17 AD patients were acquired. With the parcellated cortical gyri and lobes from T1 weighted image transformed to DTI, regional cortical MD of all subjects before and after PVE correction were measured. CSF contamination model was used to correct bias of MD caused by PVE. Compared to cortical MD of young group, significant increases of corrected MD for elderly healthy and AD groups were found only in frontal and limbic regions, respectively, while there were significant increases of uncorrected MD all over the cortex. Uncorrected MD are significantly higher in limbic and temporal gyri in AD group, compared to those in elderly healthy group but higher MD only remained in limbic gyri after PVE correction. Cortical thickness was also measured for all groups. The correlation slopes between cortical MD and thickness for elderly healthy and AD groups were significantly decreased after PVE correction compared to before correction while no significant change of correlation slope was detected for young group. It suggests that the cortical thinning in elderly healthy and AD groups is a significant contributor to the bias of uncorrected cortical MD measurement. The established comprehensive unbiased cortical MD profiles of young, elderly healthy subjects and AD patients at the lobe, gyral and voxel level may serve as clinical references for cortical microstructure.

Neuroanatomical correlates of tinnitus revealed by cortical thickness analysis and diffusion tensor imaging

Tinnitus is a poorly understood auditory perception of sound in the absence of external stimuli. Convergent evidence proposes that tinnitus perception involves brain structural alterations as part of its pathophysiology. The aim of this study is to investigate the structural brain changes that might be associated with tinnitus-related stress and negative emotions. Using high-resolution magnetic resonance imaging and diffusion tensor imaging, we investigated grey matter and white matter (WM) alterations by estimating cortical thickness measures, fractional anisotropy and mean diffusivity in 14 tinnitus subjects and 14 age- and sex-matched non-tinnitus subjects. Significant cortical thickness reductions were found in the prefrontal cortex (PFC), temporal lobe and limbic system in tinnitus subjects compared to non-tinnitus subjects. Tinnitus sufferers were found to have disrupted WM integrity in tracts involving connectivity of the PFC, temporal lobe, thalamus and limbic system. Our results suggest that such neural changes may represent neural origins for tinnitus or consequences of tinnitus and its associations.

The brain dynamics of intellectual development: Waxing and waning white and gray matter

Distributed brain areas support intellectual abilities in adults. How structural maturation of these areas in childhood enables development of intelligence is not established. Neuroimaging can be used to monitor brain development, but studies to date have typically considered single imaging modalities. To explore the impact of structural brain maturation on the development of intelligence, we used a combination of cortical thickness, white matter (WM) volume and WM microstructure in 168 healthy participants aged 8–30 years. Principal component analyses (PCAs) were conducted separately for cortical thickness, WM volume, fractional anisotropy (FA) and mean diffusivity (MD) in 64 different brain regions. For all four parameters, the PCAs revealed a general factor explaining between 40% and 53% of the variance across regions. When tested separately, negative age-independent relationships were found between intellectual abilities and cortical thickness and MD, respectively, while WM volume and FA were positively associated with intellectual abilities. The relationships between intellectual abilities and brain structure varied with age, with stronger relationships seen in children and adolescents than in young adults. Multiple regression analysis with the different imaging measures as simultaneous predictors, showed that cortical thickness, WM volume and MD all yielded unique information in explaining intellectual abilities in development. The present study demonstrates that different imaging modalities and measures give complementary information about the neural substrates of intellectual abilities in development, emphasizing the importance of multimodal imaging in investigations of neurocognitive development.

Diffusion tensor imaging and cognitive function in older adults with no dementia

To determine the patterns of diffusivity associated with cognitive domain functions in older adults without dementia. We studied older adults without dementia (n = 220) who underwent neuropsychometric testing and a diffusion tensor imaging (DTI) examination at 3 T in a cross-sectional study. Memory, language, attention/executive function, and visual-spatial processing domains were assessed within 4 months of the MRI examination. A fluid-attenuated inversion recovery-based DTI sequence that enabled uncontaminated cortical diffusion measurements was performed. Associations between cortical mean diffusivity (MD) and cognitive function were tested using voxel-based regression analysis. Association between tract diffusivity and cognitive function was tested with regions of interest drawn on color-coded fractional anisotropy (FA) maps. Memory function was associated with the medial temporal lobe cortical MD on voxel-based analysis (p < 0.001, corrected for multiple comparisons), and inferior longitudinal fasciculus and posterior and anterior cingulum FA on tract-based analysis (p < 0.001). Language function was associated with the left temporal lobe cortical MD (p < 0.001, corrected for multiple comparisons), inferior longitudinal fasciculus, fornix, and posterior cingulum FA (p < 0.05). Attention and executive function was associated with the posterior and anterior cingulum FA, and visual-spatial function was associated with posterior cingulum FA (p < 0.01). Specific cognitive domain functions are associated with distinct patterns of cortical and white matter diffusivity in elderly with no dementia. Posterior cingulum tract FA was associated with all 4 cognitive domain functions, in agreement with the hypothesis that the posterior cingulate cortex is the main connectivity hub for cognitive brain networks. Microstructural changes identified on DTI may be associated with neurodegenerative pathologies underlying cognitive changes in older adults without dementia.

Pre-dementia Memory Impairment is Associated with White Matter Tract Affection

Mild cognitive impairment (MCI), especially amnestic, often represents pre-dementia Alzheimer's disease, characterized by medial temporal lobe atrophy, while white matter (WM) alterations are insufficiently described. We analyze both cortical morphometric and WM diffusivity differences in amnestic versus non-amnestic subtypes and ask if memory and WM tract affection are related independently of cortical atrophy. Forty-nine patients from a university-hospital based memory clinic with a score of 3 on the Global Deterioration Scale aged 43-77 years (45% female) were included. Two neuropsychologists have classified cases as amnestic (aMCI), non-amnestic (naMCI), or less advanced (laMCI), not satisfying criteria for aMCI/naMCI. Diffusion tensor imaging (DTI) WM tract and morphometric data of the temporal-parietal memory network were compared among patient subtypes and related to story, word list, and visual memory. WM radial and mean diffusivity (DR and MD), underlying the entorhinal cortex, were higher in aMCI compared with laMCI. WM DR and MD, underlying the entorhinal, parahippocampal, and middle temporal cortex, explained unique variance in word list and story memory, and this was not due to secondary effects of cortical thinning. DTI may thus potentially aid diagnosis in early disease stages. ).

Partial volume estimation and segmentation of brain tissue based on diffusion tensor MRI

Brain tissue segmentation based on diffusion tensor magnetic resonance imaging (DT-MRI) data has been attempted by previous researchers. Due to inherent low spatial resolution of DT-MRI data, conventional methods suffered from partial volume averaging among the different types of tissues, which may result in inaccurate segmentation results. The purpose was to develop a new brain tissue segmentation method for DT-MRI data in which effect of the partial volume averaging is taken into account. The method estimates the partial volume fractions of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) within each voxel using a maximum a posteriori probability principle, based on five DT parameters (three eigenvalues, apparent diffusion coefficient, and fractional anisotropy). The authors evaluated the performance of the proposed method quantitatively by using digital phantom data. Moreover, the authors applied the method to real DT-MRI data of the human brain, and compared the results with those of a conventional segmentation method. In the digital phantom experiments, the root mean square error in term of partial volume fraction with the method for WM, GM, and CSF were 0.137, 0.049, and 0.085, respectively. The volume overlap measures between the segmentation results and the ground truth of the digital phantom were more than 0.9 in all three tissue types, while those between the results by the conventional method and the ground truth ranged between 0.550 and 0.854. In visual comparisons for real DT-MRI, WM/GM/CSF regions estimated by the method were more similar to the corresponding regions depicted in the structural image than those estimated by the conventional method. The results of the digital phantom experiment and real DT-MRI data demonstrated that the method improved accuracy in estimation and segmentation of brain tissue on DT-MRI data over the conventional method. This method may be useful in evaluating the cortical and subcortical diffusivity in neurological diseases.

Novel method to estimate and display cerebral cortical degeneration using diffusion‐weighted magnetic resonance imaging

Previous studies have shown that diffusion-weighted imaging (DWI) is useful for detecting microstructural degradation of neuronal tissue in neurodegenerative diseases. Mapping of cortical degeneration by DWI is potentially useful, but is extremely difficult, mainly because of the partial volume effect resulting from the surrounding cerebrospinal fluid (CSF). In this study a novel method to map and display the cortical damage in neurodegenerative diseases using DWI is proposed. Instead of measuring the cortical diffusivity, the diffusivity of white matter directly beneath the cortex, where neuronal fibers enter or exit the overlying cortex, was measured and mapped onto the cortical surface. The map was viewed in a form of three-dimensional (3D) rendering. Patients with Alzheimer's disease (AD) showed cortical damage in the temporal and parietal cortices, and a patient with frontotemporal dementia showed damage in the frontal lobe, consistent with the typical topographical distribution of histopathological cortical damage in each of these diseases. The results suggest that subcortical diffusivity closely reflects cortical damage, and that the current mapping technique is a promising tool for evaluating neurodegenerative diseases.

Time course of the cerebral circulatory response to metabolic depression.

Baboons anesthetized with halothane and N2O/O2 were given an intravenous steroid anesthetic (Althesin; Glaxo Laboratories Ltd., U.K.). The drug bolus was labeled with 99mTc, and the time from central venous injection to peak radioactivity in the brain was designated drug brain arrival (DBA-peak). The electroencephalogram slowed 1.2 +/- 0.9 s after DBA-peak (P greater than 0.2), and approximately 2 s after DBA-peak, internal carotid blood flow (ICarBF) decreased and calculated internal carotid vascular resistance (ICarVR) rose. During this 2-s delay in the cerebrovascular response to the arrival of a cerebral metabolic depressant in the brain, the decrease in mean cortical Pco2 was calculated to be less than 0.26 mmHg from cortical CO2 solubility, and less than 0.32 mmHg from cortical CO2 diffusivity, which indicated that mean cortical Pco2 changes do not control cerebral blood flow (CBF). The unaltered time course of the changes in EEG, ICarBF, and ICarVR after acute cervical sympathectomy and alpha-adrenergic receptor blockade excluded the involvement of the sympathetic nervous system in the vasoconstrictor response. Intracarotid Althesin showed that the cerebral vasoconstriction was not a direct effect of the drug. The postulated link between the effects of Althesin on CBF and cerebral metabolism remains to be elucidated but is probably indirect, involving the brainstem.