- Email: [email protected]
MRI-derived cortical thickness measurements from APP transgenic mice
e36
Developing Topics
52-62%. The parietal lobe atrophy on MRI was 67.8% to 84.4%, but the atrophy of the MTL was 26.7%-35.6%. The VBM OF 24 pure AD patients showed that parietal lobe atrophy was the most severe part of the cortical atrophy. The FDG-PET follow up of a few cases showed us that the hypometabolism in the parietal lobe occurred earlier than in the post cingulate. The hypometabolism of the MTL was extended more later. Conclusions: The hypometabolism and cortex atrophy of the parietal lobe could be valuable for AD diagnosis.
surement of cortical thickness using anatomical MRI data acquired from mutant human amyloid precursor protein (APP) transgenic mice ranging from 3 to 19 months-of-age. Methods: Anatomical MRI data was acquired from 3-4 month-old (young group), 10-12 month-old (middle-aged group), 18-19 month-old (old group) APP TG (J20 line) and wild-type (WT) mice (n ¼ 20 mice per group). Images were acquired from anesthetized mice using a 3D balanced steady-state free-precession (b-SSFP) pulse sequence and a 7T Bruker Pharmascan system. A field-of-view of 1.8 3 1.8 3 0.9 cm allowed for whole brain coverage and an isotropic spatial resolution of 14031403140 micrometers provided good delineation of the mouse neuroanatomy. The cortical surface from each mouse brain was labeled using an automated, atlas-based approach and the cortical thickness was measured at each vertex across the entire cortical mantle. ROI-based analysis was performed on the cortical thickness maps. Results: The cerebral cortex of APP TG mice was thicker than that of the WT mice in the young group. The entorhinal, frontal, and temporal-parietal cortices demonstrated an age-dependent thinning in the APP mice, while no change or increasing thickness was observed in WT mice. Conclusions: We have demonstrated regional differences in MRI-derived cortical thickness measures between APP TG and WT mice at different ages. Given that the young APP TG mice, which do not exhibit beta-amyloid plaques, demonstrated increased cortical thickness relative to age-matched WT mice implicates pathological processes other than beta-amyloid deposition as contributors to quantitative MRI measures. A greater understanding of these underlying factors should translate to improved interpretation of cortical thickness measures in human AD MRI studies.
P4-357
FUNCTIONAL CONNECTIVITY IN THE EPISODIC MEMORY NETWORK
Christiane Oedekoven2, Andreas Jansen2, Johannes Bedenbender2, Dirk Leube1, 1Clinic for Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany; 2Philipps-University Marburg, Marburg, Germany.
P4-356
MRI-DERIVED CORTICAL THICKNESS MEASUREMENTS FROM APP TRANSGENIC MICE
Francois Hebert1, Ming-Kai Ho1, Jason Lerch2, Edith Hamel1, Barry Bedell1, 1Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; 2Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. Background: Quantitative analysis of anatomical MRI data has proven to be an exceptionally valuable tool in Alzheimer’s disease (AD) studies. Studies employing sophisticated methods for extraction of the cortical surface from MR images of the human brain have demonstrated that cortical thickness measurements allow for monitoring of disease progression. While a number of groups have reported volumetric changes in the brains of mouse models of AD, cortical thickness measurement from in vivo MRI data have not been assessed. In this study, we have utilized a fully-automated approach for the mea-
Background: Event-related fMRI-studies investigating episodic memory report activation in medial-temporal, prefrontal and parietal regions indicating strong functional connectivity within a distributed memory network. This ongoing study aims to investigate functional connectivity of this memory network in patients with MCI and healthy elderly subjects. Methods: Participants in this study were 32 elderly subjects, (age range 50-89), 8 MCI and 24 healthy subjects. Using a face-name memory task, previously seen and new faces are presented and participants decide if they have seen the face before. The measure of Retrieval Success, contrasting activation during correctly identified old stimuli (Hits) with correctly identified new stimuli (Correct rejections) is used in SPM8 analysis. Functional Connectivity is computed using a Seed-Voxel-Analysis (SVA) based on whole-brain exploration. Seed Voxel is in left inferior parietal lobe (IPL) (-54 -56 42). Functional connectivity for left hippocampus is based on ROI time series using the AAL left hippocampus template. Results: During Retrieval 1 MCI patients recognized less stimuli (64.5%) compared to the healthy elderly sample (73.8%, p <0.05).Within the group of healthy participants, left IPL showed functional connectivity with bilateral medial temporal gyri and left hippocampus, whereas in the group of MCI patients left IPL was correlated with activation in left fusiform gyrus. Using the hippocampal ROI as seed, strongest functional connectivity was found in bilateral precunei, right superior parietal cortex and left inferior parietal lobe in healthy elderly participants. Based on the hippocampal seed, there was no functional connectivity found in MCI patients. Conclusions: Functional connectivity was shown to be impaired in MCI patients in comparison to elderly subjects, underlined by a significant difference in episodic memory performance. In our study we demonstrated differences in functional connectivity in healthy elderly and MCI patients. Specific to the findings is not only the group of subjects examined, but also the fact that we conducted a whole-brain analysis instead of using ROI masks and this analysis was based on the contrast of Retrieval Success instead of contrasting against baseline. Our results argue for impairment in the network underlying episodic memory. A next step will be the comparison of functional as well as structural connectivity (DTI).
Developing Topics
52-62%. The parietal lobe atrophy on MRI was 67.8% to 84.4%, but the atrophy of the MTL was 26.7%-35.6%. The VBM OF 24 pure AD patients showed that parietal lobe atrophy was the most severe part of the cortical atrophy. The FDG-PET follow up of a few cases showed us that the hypometabolism in the parietal lobe occurred earlier than in the post cingulate. The hypometabolism of the MTL was extended more later. Conclusions: The hypometabolism and cortex atrophy of the parietal lobe could be valuable for AD diagnosis.
surement of cortical thickness using anatomical MRI data acquired from mutant human amyloid precursor protein (APP) transgenic mice ranging from 3 to 19 months-of-age. Methods: Anatomical MRI data was acquired from 3-4 month-old (young group), 10-12 month-old (middle-aged group), 18-19 month-old (old group) APP TG (J20 line) and wild-type (WT) mice (n ¼ 20 mice per group). Images were acquired from anesthetized mice using a 3D balanced steady-state free-precession (b-SSFP) pulse sequence and a 7T Bruker Pharmascan system. A field-of-view of 1.8 3 1.8 3 0.9 cm allowed for whole brain coverage and an isotropic spatial resolution of 14031403140 micrometers provided good delineation of the mouse neuroanatomy. The cortical surface from each mouse brain was labeled using an automated, atlas-based approach and the cortical thickness was measured at each vertex across the entire cortical mantle. ROI-based analysis was performed on the cortical thickness maps. Results: The cerebral cortex of APP TG mice was thicker than that of the WT mice in the young group. The entorhinal, frontal, and temporal-parietal cortices demonstrated an age-dependent thinning in the APP mice, while no change or increasing thickness was observed in WT mice. Conclusions: We have demonstrated regional differences in MRI-derived cortical thickness measures between APP TG and WT mice at different ages. Given that the young APP TG mice, which do not exhibit beta-amyloid plaques, demonstrated increased cortical thickness relative to age-matched WT mice implicates pathological processes other than beta-amyloid deposition as contributors to quantitative MRI measures. A greater understanding of these underlying factors should translate to improved interpretation of cortical thickness measures in human AD MRI studies.
P4-357
FUNCTIONAL CONNECTIVITY IN THE EPISODIC MEMORY NETWORK
Christiane Oedekoven2, Andreas Jansen2, Johannes Bedenbender2, Dirk Leube1, 1Clinic for Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany; 2Philipps-University Marburg, Marburg, Germany.
P4-356
MRI-DERIVED CORTICAL THICKNESS MEASUREMENTS FROM APP TRANSGENIC MICE
Francois Hebert1, Ming-Kai Ho1, Jason Lerch2, Edith Hamel1, Barry Bedell1, 1Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; 2Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. Background: Quantitative analysis of anatomical MRI data has proven to be an exceptionally valuable tool in Alzheimer’s disease (AD) studies. Studies employing sophisticated methods for extraction of the cortical surface from MR images of the human brain have demonstrated that cortical thickness measurements allow for monitoring of disease progression. While a number of groups have reported volumetric changes in the brains of mouse models of AD, cortical thickness measurement from in vivo MRI data have not been assessed. In this study, we have utilized a fully-automated approach for the mea-
Background: Event-related fMRI-studies investigating episodic memory report activation in medial-temporal, prefrontal and parietal regions indicating strong functional connectivity within a distributed memory network. This ongoing study aims to investigate functional connectivity of this memory network in patients with MCI and healthy elderly subjects. Methods: Participants in this study were 32 elderly subjects, (age range 50-89), 8 MCI and 24 healthy subjects. Using a face-name memory task, previously seen and new faces are presented and participants decide if they have seen the face before. The measure of Retrieval Success, contrasting activation during correctly identified old stimuli (Hits) with correctly identified new stimuli (Correct rejections) is used in SPM8 analysis. Functional Connectivity is computed using a Seed-Voxel-Analysis (SVA) based on whole-brain exploration. Seed Voxel is in left inferior parietal lobe (IPL) (-54 -56 42). Functional connectivity for left hippocampus is based on ROI time series using the AAL left hippocampus template. Results: During Retrieval 1 MCI patients recognized less stimuli (64.5%) compared to the healthy elderly sample (73.8%, p <0.05).Within the group of healthy participants, left IPL showed functional connectivity with bilateral medial temporal gyri and left hippocampus, whereas in the group of MCI patients left IPL was correlated with activation in left fusiform gyrus. Using the hippocampal ROI as seed, strongest functional connectivity was found in bilateral precunei, right superior parietal cortex and left inferior parietal lobe in healthy elderly participants. Based on the hippocampal seed, there was no functional connectivity found in MCI patients. Conclusions: Functional connectivity was shown to be impaired in MCI patients in comparison to elderly subjects, underlined by a significant difference in episodic memory performance. In our study we demonstrated differences in functional connectivity in healthy elderly and MCI patients. Specific to the findings is not only the group of subjects examined, but also the fact that we conducted a whole-brain analysis instead of using ROI masks and this analysis was based on the contrast of Retrieval Success instead of contrasting against baseline. Our results argue for impairment in the network underlying episodic memory. A next step will be the comparison of functional as well as structural connectivity (DTI).