- Email: [email protected]
P1-226: Deformation morphometry reveals longitudinal atrophy related to cognitive decline and APOE-e4 status
Poster Presentations P1 Background: Accurate quantification of whole-brain-tissue (WBT), hippocampal (HIP), and lateral-ventricle (LV) volumes in patients with AD is an important goal. Accuracy can be affected, however, by local-volume changes related to MRI-scanner-gradient nonlinearities and inconsistent positioning of subjects within the scanner (particularly along the Z-axis). Furthermore, standard canthomeatal (CM) alignment results in the cerebrum being centered several cms away from isocenter. Objective: To quantify the effect of Z-shifts into, and out of, the scanner on WBT, HIP, and LV volumes. Methods: High resolution, volumetric T1-weighted MRI data were acquired in 9 normal adults on a Siemens Sonata Vision 1.5T scanner: first, with CM-alignment, and then with the scanner bed moved 50-mm out of the magnet. A gradient-distortion correction field (GDCF) was generated using spherical harmonic expansion to map coordinates from an “ideal” coordinate system (a Lego-DUPLO® phantom) to the imaging coordinate system of the scanner. FreeSurfer v4.0.1 was used to automatically classify voxels in each MRI dataset as WBT, HIP, and LV. The effect of Z-shift on tissue volume was simulated in 4-mm steps from -50-mm to ⫹50-mm by applying the GDCF to each of the FreeSurfer tissuemasks, z-shifting these masks, applying the inverse-GDCF, shifting the resulting masks back, and calculating the resulting volumes by integrating the intensities. Results: Simulated 50-mm Z-shifts into, and out of, the magnet had asymmetric effects on both mean WBT-volumes [out: 18.8-cc decrease (-1.5%), p⫽0.02; in: 98.8-cc decrease (-7.4%), p⬍0.0001) and mean LVvolumes [out: 0.1-cc decrease (-0.8%), p⫽0.16; in: 1.3-cc decrease (-8.2%), p⬍0.0001); they had symmetric effects on mean HIP-volumes [out: 0.5-cc decrease (-5.2%), p⬍0.0001; in: 0.4-cc decrease (-4.0%), p⬍0.0001). Volumes obtained from the actual 50-mm-out Z-shifts were highly correlated with those from the simulated 50-mm-out Z-shifts (WBT: r⫽0.996, p⬍0.0001; HIP: r⫽0.905, p⫽0.0008; LV: r⫽0.999, p⬍0.0001).
investigate how APOE status is related to longitudinal atrophy. Methods: 3D T1-weighted MRI were obtained from 27 subjects with some cognitive impairment (72⫾8 yrs of age, 12 women, MMSE 28.3⫾1.5) and 11 controls (68⫾6 yrs, 6 women, MMSE 29.5⫾0.7); MRI and cognitive testing was repeated every 6 months. We applied deformation based morphometry [1] and investigated the relationship between longitudinal brain atrophy and future cognitive decline. Maps of longitudinal tissue change over 1 year in common space were dependent variables in regression analyses. We compared subjects whose group diagnosis changed (n⫽9) to stable subjects, covarying for baseline MMSE. We also compared subjects positive for the APOE e4 allele (3/4 or 4/4) to those without (3/3), again covarying for baseline MMSE. Results: The figure (right brain is image left) shows T-statistic maps overlaid on the group average spatially normalized MRI. Accelerated tissue loss over 1 year was observed in subjects whose diagnosis changed (from control to cognitively impaired, or from cognitively impaired to demented) compared to subjects whose diagnoses were stable, most significantly in the right hippocampus, right entorhinal cortex, and anterior corpus callosum (top panel of figure). In addition, orbitofrontal cortex, insular cortex, and parietal cortex showed less significant accelerations of tissue loss. The time from baseline study to diagnosis change varied, averaging about 2 years. Accelerated tissue loss over 1 year was also observed in APOE e4⫹ compared to APOE e4- subjects, as shown in the bottom panel of the figure, particularly in the posterior cingulate, and frontal and parietal white matter. Conclusions: Deformation morphometry reveals focal brain atrophy on MRI that is associated with cognitive decline and APOE e4 status. Longitudinal change on MRI may be predictive of future cognitive status, and may allow earlier and more precise separation of normal aging from early Alzheimer’s disease. [1] C. Studholme et al, IEEE TransMedImaging 2006;25(5):626-39.
P1-227
Conclusions: Z-shifts can have significant effects on observed tissue-volumes. Depending on a structure’s location relative to the magnet’s isocenter, these effects can either be symmetric (HIP) or asymmetric (WBT and LV). Accordingly, inadvertent Z-shifts should be avoided or corrected. Aligning the centers of the cerebrum and the magnet may help decrease the effects of gradient nonlinearities on observed tissue-specific brain-volumes. P1-226
DEFORMATION MORPHOMETRY REVEALS LONGITUDINAL ATROPHY RELATED TO COGNITIVE DECLINE AND APOE-e4 STATUS
Valerie A. Cardenas, Linda L. Chao, Colin Studholme, Norbert Schuff, Michael W. Weiner, San Francisco VA/University of California, San Francisco, CA, USA. Contact e-mail: [email protected] Background: Previous studies have shown that brain atrophy predicts conversion to dementia, but investigated limited brain regions or were limited to a single timepoint. The objectives of this study were to determine the spatial pattern of longitudinal brain atrophy associated with cognitive decline, and to
T277
LONGITUDINAL CHANGES IN COGNITION AND CEREBROVASCULAR DISEASE IN THE ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE
Owen T. Carmichael, David Drucker, Christopher Schwarz, UC Davis, Davis, CA, USA. Contact e-mail: [email protected] Background: The goal of ADNI is to develop methods that will lead to uniformity of longitudinal, multisite MRI and PET data as well as biomarker profiles for patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Although the focus is on degenerative pathology, cerebrovascular disease (CVD), which has the potential to increase over time and influence cognitive trajectories, is also common to these subjects. We hypothesize that MRI measures of CVD, consisting of baseline and change in white matter hyperintensity (WMH) volume and MRI infarction, will be associated with change in cognition. Methods: MRI of 758 subjects at baseline, including 634 subjects with follow-up, were analyzed (Table 1). All images were skullstripped, coregistered, and nonlinearly warped to a standardized template image. WMH were automatically detected based on T1, PD, and T2 image intensity profiles constrained by anatomical prior knowledge. Individual change in WMH volume and cognitive performance was quantified by computing the linear slope over time. Linear regression, adjusting for baseline age, sex, education, ethnicity and Hachinksi ischemic score was used to examine
investigate how APOE status is related to longitudinal atrophy. Methods: 3D T1-weighted MRI were obtained from 27 subjects with some cognitive impairment (72⫾8 yrs of age, 12 women, MMSE 28.3⫾1.5) and 11 controls (68⫾6 yrs, 6 women, MMSE 29.5⫾0.7); MRI and cognitive testing was repeated every 6 months. We applied deformation based morphometry [1] and investigated the relationship between longitudinal brain atrophy and future cognitive decline. Maps of longitudinal tissue change over 1 year in common space were dependent variables in regression analyses. We compared subjects whose group diagnosis changed (n⫽9) to stable subjects, covarying for baseline MMSE. We also compared subjects positive for the APOE e4 allele (3/4 or 4/4) to those without (3/3), again covarying for baseline MMSE. Results: The figure (right brain is image left) shows T-statistic maps overlaid on the group average spatially normalized MRI. Accelerated tissue loss over 1 year was observed in subjects whose diagnosis changed (from control to cognitively impaired, or from cognitively impaired to demented) compared to subjects whose diagnoses were stable, most significantly in the right hippocampus, right entorhinal cortex, and anterior corpus callosum (top panel of figure). In addition, orbitofrontal cortex, insular cortex, and parietal cortex showed less significant accelerations of tissue loss. The time from baseline study to diagnosis change varied, averaging about 2 years. Accelerated tissue loss over 1 year was also observed in APOE e4⫹ compared to APOE e4- subjects, as shown in the bottom panel of the figure, particularly in the posterior cingulate, and frontal and parietal white matter. Conclusions: Deformation morphometry reveals focal brain atrophy on MRI that is associated with cognitive decline and APOE e4 status. Longitudinal change on MRI may be predictive of future cognitive status, and may allow earlier and more precise separation of normal aging from early Alzheimer’s disease. [1] C. Studholme et al, IEEE TransMedImaging 2006;25(5):626-39.
P1-227
Conclusions: Z-shifts can have significant effects on observed tissue-volumes. Depending on a structure’s location relative to the magnet’s isocenter, these effects can either be symmetric (HIP) or asymmetric (WBT and LV). Accordingly, inadvertent Z-shifts should be avoided or corrected. Aligning the centers of the cerebrum and the magnet may help decrease the effects of gradient nonlinearities on observed tissue-specific brain-volumes. P1-226
DEFORMATION MORPHOMETRY REVEALS LONGITUDINAL ATROPHY RELATED TO COGNITIVE DECLINE AND APOE-e4 STATUS
Valerie A. Cardenas, Linda L. Chao, Colin Studholme, Norbert Schuff, Michael W. Weiner, San Francisco VA/University of California, San Francisco, CA, USA. Contact e-mail: [email protected] Background: Previous studies have shown that brain atrophy predicts conversion to dementia, but investigated limited brain regions or were limited to a single timepoint. The objectives of this study were to determine the spatial pattern of longitudinal brain atrophy associated with cognitive decline, and to
T277
LONGITUDINAL CHANGES IN COGNITION AND CEREBROVASCULAR DISEASE IN THE ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE
Owen T. Carmichael, David Drucker, Christopher Schwarz, UC Davis, Davis, CA, USA. Contact e-mail: [email protected] Background: The goal of ADNI is to develop methods that will lead to uniformity of longitudinal, multisite MRI and PET data as well as biomarker profiles for patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Although the focus is on degenerative pathology, cerebrovascular disease (CVD), which has the potential to increase over time and influence cognitive trajectories, is also common to these subjects. We hypothesize that MRI measures of CVD, consisting of baseline and change in white matter hyperintensity (WMH) volume and MRI infarction, will be associated with change in cognition. Methods: MRI of 758 subjects at baseline, including 634 subjects with follow-up, were analyzed (Table 1). All images were skullstripped, coregistered, and nonlinearly warped to a standardized template image. WMH were automatically detected based on T1, PD, and T2 image intensity profiles constrained by anatomical prior knowledge. Individual change in WMH volume and cognitive performance was quantified by computing the linear slope over time. Linear regression, adjusting for baseline age, sex, education, ethnicity and Hachinksi ischemic score was used to examine