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Atrophy-specific MRI brain template for Alzheimer's disease and mild cognitive impairment
S58
Alzheimer’s Imaging Consortium: IC-P-Poster Imaging
attention and executive functioning. References: [1] Bartzokis G. (2004). Neurobiol Aging. 25, 5-18. [2] Benes FM. (2004). Neurobiol Aging. 25, 41-43. [3] Desai MK, Sudol KL, Janelsins MC, et al. (2009). Glia. 57, 54-65. [4] Malone MJ, Szoke MC. (1985). Arch. Neurol. 42, 1063-1066. [5] Deoni SCL et al. (2008). Magn. Reson. Med. 60, 1372-1387. [6] Catani M. (2008) Cortex; 44: 1105-1132. [7] Deoni SCL et al. (2010). Magn. Reson. Med. (ahead of print). IC-P-121
INVESTIGATING WHITE MATTER MYELIN CONTENT ACROSS THE SPECTRUM OF ALZHEIMER’S DISEASE
Sean Deoni1, Steve Correia2, Tanja Su1, Jessica Man1, Katie Lehman3, Paul Malloy3, Stephen Salloway3, 1Brown University, Providence, Rhode Island, United States; 2Brown University, Veterans Affairs Hospital, Providence, Rhode Island, United States; 3Brown University, Butler Hospital, Providence, Rhode Island, United States. Background: Alzheimer’s disease (AD) is a degenerative neurological disease characterized by the progressive loss of memory, attention, and other cognitive functions. While most early AD investigations target beta-amyloid deposits and neurofibrillary tangle formation, a growing number of diffusion tensor imaging studies (DT-MRI) suggest early white matter (WM) alteration. While reduced myelin content has been suggested in AD, direct assessment of myelin damage and its possible relationship to disease severity has not been performed. Here we use the mcDESPOT1 multicomponent relaxometry technique to investigate changes in myelin content across the AD spectrum. Myelin content (MWF) was directly measured in patients with varying severity, as well as healthy controls, and correlated with degree of disability (Mini Mental State Exam, MMSE), and a composite index of executive functioning (EXEC). Methods: Participants: 25 elderly individuals; including 3 healthy controls (CDR ¼ 0 and MMSE > 27, mean age ¼ 75.5); 9 MCI patients (CDR ¼ 0.5-1.0 and MMSE > 24, mean age ¼ 75.4), 4 mild AD (CDR ¼ 0.5-1.0 and MMSE ¼ 19-26, mean age ¼ 78), and 9 moderate-severe AD (CDR > 1.0 or MMSE < 18, mean age ¼ 82.0). MRI: Whole-brain mcDESPOT data1 were acquired on a Siemens Tim Trio scanner (32-channel head array), with incorporated B0 and B1 field correction2. Following MWF map calculation1, each participants data was co-registered to a study template in MNI space. Cognitive performance was assessed using a composite z-score (based on standard normative corrections) index for executive function comprised of Letter-Number Sequencing and Stroop Color-Word trial. ANALYSIS: Non-parametric correlation analysis between MWF and MMSE and EXEC scores were performed voxel-wise using the Randomise tool (www.fmrib.ox.ac.uk/fsl) with subject age and education level included as co-variates. Figures 1a and b details regions with significant (p < 0.05 FDR) positive correlation between MWF and MMSE score; and EXEC score, respectively. These results are the first direct investigation of myelin content alteration in AD. Based on the relationship with symptom severity, they suggest a role for WM and myelin disruption in AD. Conclusions: [1] Deoni SCL et al. (2008). Magn. Reson. Med. 60, 1372-1387. [2] Deoni SCL et al. (2010). Magn. Reson. Med. (ahead of print).
IC-P-122
ATROPHY-SPECIFIC MRI BRAIN TEMPLATE FOR ALZHEIMER’S DISEASE AND MILD COGNITIVE IMPAIRMENT
Vladimir Fonov, Pierrick Coupe, Simon Eskildsen, D. Collins, Montreal Neurological Institute, Montreal, Quebec, Canada. Background: Rapid brain loss is characteristic for the patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) [1]. Increase of the lateral ventricular volume is strongly correlated with the progression of the disease. High variability in the degree of atrophy for subjects with AD and MCI makes use of a single disease-specific template challenging. We propose a novel approach to generate a continuous four-dimensional template, where the 4th dimension is a surrogate measure of overall brain atrophy. Methods: We used MRI scans obtained from the ADNI database (www.loni.ucla.edu/ADNI). Automated methods to estimate intracranial capacity (ICC) and lateral ventricles volume (LVV) [2] was applied to all available datasets at base line. The ratio between LVV and ICC (RLVV) was used as a surrogate measure of overall brain atrophy with mean(standard deviation) value of 2.46(0.87)%. Subsets from all subjects (CN, MCI and AD) were selected with uniform distribution of RLVV from 1.0 to 6.0% , resulting in a total of 160 subjects. Our algorithm [3] was modified to perform simultaneous 1) creation of the template and 2) linear regression of image intensity and shape versus RLVV. Results: The ratio between LVV and ICC yielded values of mean(sd) 2.13(0.72)% for NC, 2.45(0.84)% for MCI and 2.84(0.91)% for AD. The continuous, four dimensional anatomical template was created. For a given RLVV, an appropriate three dimensional anatomical template may be constructed, reflecting the average shape of the brain and the contrast between different tissue types for the given level of atrophy. Figure 1 shows images through 6 example values of increasing RLVV. Conclusions: The proposed method and resulting template will be useful tools for the development of robust automatic image processing methods targeted to the study of the populations with high degree of variability of atrophy. Furthermore, method presented is not limited to be used only with MCI and AD subjects, but can also be easily adopted for other neuro-degenerative studies. [1] Carlson, NE, et al. Neurology, 2008. 70(11). [2] Fonov, VS, et al. Alzheimer’s and Dementia, 2010. 6(4, Supplement 1). [3] Fonov, V, et al. NeuroImage, 2011. 54(1).
IC-P-123
MR ELASTOGRAPHY OF ALZHEIMER’S DISEASE
John Huston, Matthew Murphy, Clifford Jack, Richard Ehman, Armando Manduca, Joel Felmlee, Kevin Glaser, Mayo Clinic, Rochester, Minnesota, United States.
Figure 1. (a) Areas of significant (p<0.95 FDR) correlation between myelin water fraction and MMSE score (corrected for age).(b) Areas of significant (p<0.95 FDR) correlation between myelin water fraction and an Executive Functioning composite score (corrected for age).
Background: To determine if 3D MR elastography (MRE) can noninvasively measure a change in the elastic properties of the brain due to Alzheimer’s disease (AD). Methods: To examine the effect of AD on brain stiffness, 28 subjects were recruited including 7 with AD, 14 age and gender-matched Pittsburgh Compound B (PIB)-negative cognitively normal controls (CN-) and 7 age and gender-matched PIB-positive cognitively normal controls (CN +). Shear waves were introduced into the brain with a soft pillow-like vibration source utilizing a pneumatic actuator. MRE data were collected with a single shot spin echo EPI pulse sequence on a 3T MR
Alzheimer’s Imaging Consortium: IC-P-Poster Imaging
attention and executive functioning. References: [1] Bartzokis G. (2004). Neurobiol Aging. 25, 5-18. [2] Benes FM. (2004). Neurobiol Aging. 25, 41-43. [3] Desai MK, Sudol KL, Janelsins MC, et al. (2009). Glia. 57, 54-65. [4] Malone MJ, Szoke MC. (1985). Arch. Neurol. 42, 1063-1066. [5] Deoni SCL et al. (2008). Magn. Reson. Med. 60, 1372-1387. [6] Catani M. (2008) Cortex; 44: 1105-1132. [7] Deoni SCL et al. (2010). Magn. Reson. Med. (ahead of print). IC-P-121
INVESTIGATING WHITE MATTER MYELIN CONTENT ACROSS THE SPECTRUM OF ALZHEIMER’S DISEASE
Sean Deoni1, Steve Correia2, Tanja Su1, Jessica Man1, Katie Lehman3, Paul Malloy3, Stephen Salloway3, 1Brown University, Providence, Rhode Island, United States; 2Brown University, Veterans Affairs Hospital, Providence, Rhode Island, United States; 3Brown University, Butler Hospital, Providence, Rhode Island, United States. Background: Alzheimer’s disease (AD) is a degenerative neurological disease characterized by the progressive loss of memory, attention, and other cognitive functions. While most early AD investigations target beta-amyloid deposits and neurofibrillary tangle formation, a growing number of diffusion tensor imaging studies (DT-MRI) suggest early white matter (WM) alteration. While reduced myelin content has been suggested in AD, direct assessment of myelin damage and its possible relationship to disease severity has not been performed. Here we use the mcDESPOT1 multicomponent relaxometry technique to investigate changes in myelin content across the AD spectrum. Myelin content (MWF) was directly measured in patients with varying severity, as well as healthy controls, and correlated with degree of disability (Mini Mental State Exam, MMSE), and a composite index of executive functioning (EXEC). Methods: Participants: 25 elderly individuals; including 3 healthy controls (CDR ¼ 0 and MMSE > 27, mean age ¼ 75.5); 9 MCI patients (CDR ¼ 0.5-1.0 and MMSE > 24, mean age ¼ 75.4), 4 mild AD (CDR ¼ 0.5-1.0 and MMSE ¼ 19-26, mean age ¼ 78), and 9 moderate-severe AD (CDR > 1.0 or MMSE < 18, mean age ¼ 82.0). MRI: Whole-brain mcDESPOT data1 were acquired on a Siemens Tim Trio scanner (32-channel head array), with incorporated B0 and B1 field correction2. Following MWF map calculation1, each participants data was co-registered to a study template in MNI space. Cognitive performance was assessed using a composite z-score (based on standard normative corrections) index for executive function comprised of Letter-Number Sequencing and Stroop Color-Word trial. ANALYSIS: Non-parametric correlation analysis between MWF and MMSE and EXEC scores were performed voxel-wise using the Randomise tool (www.fmrib.ox.ac.uk/fsl) with subject age and education level included as co-variates. Figures 1a and b details regions with significant (p < 0.05 FDR) positive correlation between MWF and MMSE score; and EXEC score, respectively. These results are the first direct investigation of myelin content alteration in AD. Based on the relationship with symptom severity, they suggest a role for WM and myelin disruption in AD. Conclusions: [1] Deoni SCL et al. (2008). Magn. Reson. Med. 60, 1372-1387. [2] Deoni SCL et al. (2010). Magn. Reson. Med. (ahead of print).
IC-P-122
ATROPHY-SPECIFIC MRI BRAIN TEMPLATE FOR ALZHEIMER’S DISEASE AND MILD COGNITIVE IMPAIRMENT
Vladimir Fonov, Pierrick Coupe, Simon Eskildsen, D. Collins, Montreal Neurological Institute, Montreal, Quebec, Canada. Background: Rapid brain loss is characteristic for the patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) [1]. Increase of the lateral ventricular volume is strongly correlated with the progression of the disease. High variability in the degree of atrophy for subjects with AD and MCI makes use of a single disease-specific template challenging. We propose a novel approach to generate a continuous four-dimensional template, where the 4th dimension is a surrogate measure of overall brain atrophy. Methods: We used MRI scans obtained from the ADNI database (www.loni.ucla.edu/ADNI). Automated methods to estimate intracranial capacity (ICC) and lateral ventricles volume (LVV) [2] was applied to all available datasets at base line. The ratio between LVV and ICC (RLVV) was used as a surrogate measure of overall brain atrophy with mean(standard deviation) value of 2.46(0.87)%. Subsets from all subjects (CN, MCI and AD) were selected with uniform distribution of RLVV from 1.0 to 6.0% , resulting in a total of 160 subjects. Our algorithm [3] was modified to perform simultaneous 1) creation of the template and 2) linear regression of image intensity and shape versus RLVV. Results: The ratio between LVV and ICC yielded values of mean(sd) 2.13(0.72)% for NC, 2.45(0.84)% for MCI and 2.84(0.91)% for AD. The continuous, four dimensional anatomical template was created. For a given RLVV, an appropriate three dimensional anatomical template may be constructed, reflecting the average shape of the brain and the contrast between different tissue types for the given level of atrophy. Figure 1 shows images through 6 example values of increasing RLVV. Conclusions: The proposed method and resulting template will be useful tools for the development of robust automatic image processing methods targeted to the study of the populations with high degree of variability of atrophy. Furthermore, method presented is not limited to be used only with MCI and AD subjects, but can also be easily adopted for other neuro-degenerative studies. [1] Carlson, NE, et al. Neurology, 2008. 70(11). [2] Fonov, VS, et al. Alzheimer’s and Dementia, 2010. 6(4, Supplement 1). [3] Fonov, V, et al. NeuroImage, 2011. 54(1).
IC-P-123
MR ELASTOGRAPHY OF ALZHEIMER’S DISEASE
John Huston, Matthew Murphy, Clifford Jack, Richard Ehman, Armando Manduca, Joel Felmlee, Kevin Glaser, Mayo Clinic, Rochester, Minnesota, United States.
Figure 1. (a) Areas of significant (p<0.95 FDR) correlation between myelin water fraction and MMSE score (corrected for age).(b) Areas of significant (p<0.95 FDR) correlation between myelin water fraction and an Executive Functioning composite score (corrected for age).
Background: To determine if 3D MR elastography (MRE) can noninvasively measure a change in the elastic properties of the brain due to Alzheimer’s disease (AD). Methods: To examine the effect of AD on brain stiffness, 28 subjects were recruited including 7 with AD, 14 age and gender-matched Pittsburgh Compound B (PIB)-negative cognitively normal controls (CN-) and 7 age and gender-matched PIB-positive cognitively normal controls (CN +). Shear waves were introduced into the brain with a soft pillow-like vibration source utilizing a pneumatic actuator. MRE data were collected with a single shot spin echo EPI pulse sequence on a 3T MR