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Cortical Damage in Alzheimer’s Disease

Rationale and Objectives

A method of estimating and mapping the cortical damage resulting from neurodegenerative diseases based on diffusion-weighted imaging was recently proposed. We improved on this method to visualize the cortical damage in Alzheimer’s disease (AD) in the lateral and medial aspects of the cerebral hemispheres and to provide anatomic references.

Materials and Methods

Damage in the cerebral cortex was estimated based on diffusivity in the subcortical white matter according to a previously published method. A map of subcortical mean diffusivity (MD) was superimposed on the corresponding anatomic image so that the spatial extent of the abnormality could be anatomically localized. The right and left hemispheres were separated to evaluate the medial and lateral aspects of each hemisphere. This method was applied to 10 healthy subjects and 11 AD patients. MDs within 20 cortical regions were visually evaluated and statistically compared between AD and healthy subjects at a significance level of P < .01.

Results

In addition to the involvement of the lateral aspects of the bilateral parietal and temporal lobes and clear sparing of the bilateral pericentral regions that were previously reported, significant MD elevation was observed in the medial aspects of the right frontal, bilateral parietal, and right temporal lobes. The extent of MD abnormalities was easily identified by the background anatomic image.

Conclusions

Results suggested that AD damage in the lateral and medial cerebral cortex can be visualized with an anatomic reference using our method.

Diffusion-weighted (DW) imaging has been used to detect the microstructural alteration of brain tissue in neurodegenerative diseases such as Alzheimer’s disease (AD). An abnormally increased apparent diffusion coefficient (ADC) of water molecules in the hippocampus ( ) and an increased ADC and decreased diffusion anisotropy in the white matter regions ( ) have been reported. Although there have been only a few studies of histologic correlation, these abnormalities in DW images in neurodegenerative diseases have been considered to reflect degenerative changes in local brain tissue including neuronal loss, axonal degeneration, demyelination, and gliosis ( ), which result in reduced restriction on the motion of water molecules. In neurodegenerative diseases such as AD, neurons in the gray matter are considered to be the primary site of damage. Evaluation of the cerebral cortex using DW imaging may be of value to investigate the topographic distribution of degenerative damage within the cerebrum. However, direct measurement of the cortical ADC is extremely difficult because of the partial volume averaging of the signal from the adjacent cerebrospinal fluid (CSF), which may result in a substantial overestimation of the ADC. Recently, a DW imaging-based method for estimating the distribution of neurodegenerative damage in the cerebral cortex was proposed ( ). In this method, diffusivity in the subcortical white matter is measured and mapped onto the overlying cortical surface. Preliminary results have shown that the topographic pattern of the subcortical abnormality revealed by this method was in close agreement with that of pathologic cortical abnormality typically observed in patients with AD ( ). Such a method would potentially be useful for assessing the extent of cortical damage, and perhaps could facilitate the differential diagnosis of neurodegenerative diseases.

In this article, we improved on the original method to examine the medial surface of the cerebral hemisphere and to provide an anatomic reference for the estimated cortical damage.

Materials and methods

Subjects

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MRI Data Acquisition

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Image Analysis

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Figure 1, Diagram of the present mapping method. For both the high-resolution T1-weighted anatomic image and the subcortical mean diffusivity (MD) map, the right and left hemispheres were separately extracted such that the lateral and medial aspects of each hemisphere could be visualized. The brain stem and cerebellum were manually removed.

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Evaluation and Statistical Analysis

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Figure 2, Three-dimensional maps of the subcortical mean diffusivity (MD) for 6 healthy, aged subjects (a) and 11 patients with Alzheimer’s disease (AD) (b) . For each AD patient, the score on the Mini-Mental State Examination is indicated in parentheses. For each subject, the lateral and medial aspects of the left cerebral hemisphere are shown. Each MD map is superimposed on a corresponding high-resolution brain surface image. The MD values are indicated ×10 −3 mm 2second.

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Results

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Figure 3, Summary of the visual ratings of subcortical mean diffusivity in the lateral and medial aspects of the right and left cerebral hemispheres. In each graph, the upper bar represents the results obtained from Alzheimer’s disease patients, whereas the lower bar represents those of healthy subjects. * P < .01 uncorrected for multiple comparisons. ** P < .05 after Bonferroni correction.

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Discussion

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References

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