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Structural neuroimaging in Altheimer's disease: do white matter hyperintensities matter?

Brickman AM, Muraskin J, Zimmerman ME - Dialogues Clin Neurosci (2009)

Bottom Line: The targeted brain dysfunction that accompanies aging can have a devastating effect on cognitive and intellectual abilities.Studies suggest that WMH distributed in anterior brain regions are related to decline in executive abilities that is typical of normal aging, whereas WMH distributed in more posterior brain regions are common in AD.Although epidemiological, observational, and pathological studies suggest that WMH may be ischemic in origin and caused by consistent or variable hypoperfusion, there is emerging evidence that they may also reflect vascular deposition of beta-amyloid, particularly when they are distributed in posterior areas and are present in patients with AD.

View Article: PubMed Central - PubMed

Affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. amb2139@columbia.edu

ABSTRACT
The targeted brain dysfunction that accompanies aging can have a devastating effect on cognitive and intellectual abilities. A significant proportion of older adults experience precipitous cognitive decline that negatively impacts functional activities. Such individuals meet clinical diagnostic criteria for dementia, which is commonly attributed to Alzheimer's disease (AD). Structural neuroimaging, including magnetic resonance imaging (MRI), has contributed significantly to our understanding of the morphological and pathology-related changes that may underlie normal and disease-associated cognitive change in aging. White matter hyperintensities (WMH), which are distributed patches of increased hyperintense signal on T2-weighted MRI, are among the most common structural neuroimaging findings in older adults. In recent years, WMH have emerged as robust radiological correlates of cognitive decline. Studies suggest that WMH distributed in anterior brain regions are related to decline in executive abilities that is typical of normal aging, whereas WMH distributed in more posterior brain regions are common in AD. Although epidemiological, observational, and pathological studies suggest that WMH may be ischemic in origin and caused by consistent or variable hypoperfusion, there is emerging evidence that they may also reflect vascular deposition of beta-amyloid, particularly when they are distributed in posterior areas and are present in patients with AD. Findings from the literature highlight the potential contribution of small-vessel cerebrovascular disease to the pathogenesis of AD, and suggest a mechanistic interaction, but future longitudinal studies using multiple imaging modalities are required to fully understand the complex role of WMH in AD.

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Related in: MedlinePlus

Segmented ventricular volume (in red) superimposed on axial and sagittal orthogonal images from high resolution T1weighted anatomical scan. By segmenting the ventricular system, we are able to calculate the distance from the ventricular walls of each white matter hyperintensity voxel.
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DialoguesClinNeurosci-11-181-g004.tif: Segmented ventricular volume (in red) superimposed on axial and sagittal orthogonal images from high resolution T1weighted anatomical scan. By segmenting the ventricular system, we are able to calculate the distance from the ventricular walls of each white matter hyperintensity voxel.

Mentions: Optimal characterization of the severity of WMH among older adults has been a matter of some debate. Some authors have argued that periventricular WMH are clinically less important than deep WMH. Others have stressed the importance of regional, or lobar, distribution of WMH. These characteristics are reflected in many visual rating scales, such as the Scheltens Scale, 17 which are commonly used to evaluate the severity and distribution of WMH. Our laboratory has developed a quantitative approach for regional WMH severity analysis. Briefly, by considering the distribution of voxel intensities on individual fluid attenuated inverse recovery (FLAIR) images, we fit Gaussian curves to each cerebral hemisphere and derive the mean and standard deviation for each hemisphere. White matter hyperintensity seeds are defined as greater than or equal to 2.5 standard deviations above the mean. The left and right seeds are combined, and each seed is then passed into a mean intensity-based region-growing algorithm. The algorithm uses the seed voxel intensity as its starting mean and, applying a 10-point connectivity scheme (x-y plane, and 1 up in z and 1 down in z-plane) it searches for and labels voxels that fall within 5% of the seed mean. Neighboring voxels that fall within 5% are added to the image and a new mean is created. This process continues iteratively until all seeds have been included in the final WMH image. The summation of the number of voxels labeled as WMH multiplied by voxel dimensions yields the total WMH volume. By spatially normalizing an anatomical atlas18 to each image, we are able to derive WMH volumes in each of the major anatomical lobes, basal ganglia, and cerebellum. (Figure 3) illustrates three orthogonal views of a FLAIR image with WMH labeled and regionally parcellated. Furthermore, through segmentation of the lateral ventricles (Figure 4) we are able to calculate the distance in three dimensions of each voxel from the ventricular wall. Thus, our quantitative processing approach can be used to derive total WMH volume, regional WMH volume, and periventricular vs deep regional WMH volumes.


Structural neuroimaging in Altheimer's disease: do white matter hyperintensities matter?

Brickman AM, Muraskin J, Zimmerman ME - Dialogues Clin Neurosci (2009)

Segmented ventricular volume (in red) superimposed on axial and sagittal orthogonal images from high resolution T1weighted anatomical scan. By segmenting the ventricular system, we are able to calculate the distance from the ventricular walls of each white matter hyperintensity voxel.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2864151&req=5

DialoguesClinNeurosci-11-181-g004.tif: Segmented ventricular volume (in red) superimposed on axial and sagittal orthogonal images from high resolution T1weighted anatomical scan. By segmenting the ventricular system, we are able to calculate the distance from the ventricular walls of each white matter hyperintensity voxel.
Mentions: Optimal characterization of the severity of WMH among older adults has been a matter of some debate. Some authors have argued that periventricular WMH are clinically less important than deep WMH. Others have stressed the importance of regional, or lobar, distribution of WMH. These characteristics are reflected in many visual rating scales, such as the Scheltens Scale, 17 which are commonly used to evaluate the severity and distribution of WMH. Our laboratory has developed a quantitative approach for regional WMH severity analysis. Briefly, by considering the distribution of voxel intensities on individual fluid attenuated inverse recovery (FLAIR) images, we fit Gaussian curves to each cerebral hemisphere and derive the mean and standard deviation for each hemisphere. White matter hyperintensity seeds are defined as greater than or equal to 2.5 standard deviations above the mean. The left and right seeds are combined, and each seed is then passed into a mean intensity-based region-growing algorithm. The algorithm uses the seed voxel intensity as its starting mean and, applying a 10-point connectivity scheme (x-y plane, and 1 up in z and 1 down in z-plane) it searches for and labels voxels that fall within 5% of the seed mean. Neighboring voxels that fall within 5% are added to the image and a new mean is created. This process continues iteratively until all seeds have been included in the final WMH image. The summation of the number of voxels labeled as WMH multiplied by voxel dimensions yields the total WMH volume. By spatially normalizing an anatomical atlas18 to each image, we are able to derive WMH volumes in each of the major anatomical lobes, basal ganglia, and cerebellum. (Figure 3) illustrates three orthogonal views of a FLAIR image with WMH labeled and regionally parcellated. Furthermore, through segmentation of the lateral ventricles (Figure 4) we are able to calculate the distance in three dimensions of each voxel from the ventricular wall. Thus, our quantitative processing approach can be used to derive total WMH volume, regional WMH volume, and periventricular vs deep regional WMH volumes.

Bottom Line: The targeted brain dysfunction that accompanies aging can have a devastating effect on cognitive and intellectual abilities.Studies suggest that WMH distributed in anterior brain regions are related to decline in executive abilities that is typical of normal aging, whereas WMH distributed in more posterior brain regions are common in AD.Although epidemiological, observational, and pathological studies suggest that WMH may be ischemic in origin and caused by consistent or variable hypoperfusion, there is emerging evidence that they may also reflect vascular deposition of beta-amyloid, particularly when they are distributed in posterior areas and are present in patients with AD.

View Article: PubMed Central - PubMed

Affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. amb2139@columbia.edu

ABSTRACT
The targeted brain dysfunction that accompanies aging can have a devastating effect on cognitive and intellectual abilities. A significant proportion of older adults experience precipitous cognitive decline that negatively impacts functional activities. Such individuals meet clinical diagnostic criteria for dementia, which is commonly attributed to Alzheimer's disease (AD). Structural neuroimaging, including magnetic resonance imaging (MRI), has contributed significantly to our understanding of the morphological and pathology-related changes that may underlie normal and disease-associated cognitive change in aging. White matter hyperintensities (WMH), which are distributed patches of increased hyperintense signal on T2-weighted MRI, are among the most common structural neuroimaging findings in older adults. In recent years, WMH have emerged as robust radiological correlates of cognitive decline. Studies suggest that WMH distributed in anterior brain regions are related to decline in executive abilities that is typical of normal aging, whereas WMH distributed in more posterior brain regions are common in AD. Although epidemiological, observational, and pathological studies suggest that WMH may be ischemic in origin and caused by consistent or variable hypoperfusion, there is emerging evidence that they may also reflect vascular deposition of beta-amyloid, particularly when they are distributed in posterior areas and are present in patients with AD. Findings from the literature highlight the potential contribution of small-vessel cerebrovascular disease to the pathogenesis of AD, and suggest a mechanistic interaction, but future longitudinal studies using multiple imaging modalities are required to fully understand the complex role of WMH in AD.

Show MeSH
Related in: MedlinePlus