- Email: [email protected]
Quantifying T1-rho in Alzheimer’s disease
S42
Abstracts: Imaging / 1 (Suppl 1) (2005)
PET imaging for 90 minutes after iv injection of 370 MBq 11C-PIB. Regional clearance t1/2 and distribution volume ratios (DVR) were calculated through graphical analysis using the cerebellum as reference region. PIB parameters were compared with FDG uptake. Images showed marked binding in all AD subjects, especially in frontal, parietal and lateral temporal cortices as well as in the caudate nuclei with relative sparing of occipital and sensorimotor cortex, and very low uptake in cerebellar cortex. Images in LBD subjects were similar to AD subjects, though slightly higher uptake was observed in occipital and sensorimotor cortex. Cortical PIB clearance was significantly slower in LBD (t1/2 109 ⫹/- 28 min) and AD patients (t1/2 92 ⫹/- 13 min) when compared with control subjects (t1/2 61 ⫹/- 9 min). Clearance from cerebellar cortex was the same in all groups. Significantly higher DVR in neocortical areas were observed in AD (1.99 ⫹/- 0.36, p⬍0.01) and LBD patients (1.81 ⫹/- 0.25, p⬍0.01) when compared with control subjects (1.25 ⫹/- 0.23). There was an inverse correlation between PIB binding and glucose metabolism (r ⫽-0.67, p⬍0.0001). Regional uptake asymmetry indices were greater in LBD both in PIB and FDG studies. Conclusion: 11C-PIB PET suggests that cortical A is present in LBD subjects with progressive dementia in a similar degree to AD subjects. Longitudinal studies are warranted to more clearly define the role of A deposition in the development of dementia in both AD and LBD.
P-106
the ratio of the standard deviations from the two ROI’s and compared for each subject at both field strengths. A radiologist ranked comparative visual artefact in each randomised pair of 1.5T vs. 3T images on a 5-point scale. Conclusions: Flow artefacts arising from the carotid siphons, affecting the hippocampal region, are more than twice as large on average at 3T than at 1.5T (P⬍0.01) and have different intensity patterns (Table 1 & Fig2). A radiologist visually rated images acquired from 8 volunteers as having more pronounced flow artefacts at 3T(P⬍0.05). Sagittal slab acquisition reduces these artefacts substantially. Increased artefact at 3T can potentially offset the signal to noise ratio advantage of higher field strength. Sequences for longitudinal neuroimaging need to be carefully optimised to minimise artefacts, and provide data that can be compared with that from 1.5T studies. Table 1 Comparison of artefact level at different field strengths Ratio of Birdcage results SDs of ROIs at: Vol1 Vol2 Vol3 1.5T 3T
Array coil results Vol4
Vol5
Average Vol6
1.495 1.636 1.252 1.859 1.347 1.518 3.124 3.910 3.216 3.797 2.792 3.368
Vol7
Vol8
Vol9
Vol10 Average
2.180 2.209 1.835 2.124 1.919 5.002 3.755 4.487 6.263 4.826
2.053 4.886
Collated Average 1.785 4.117
SERIAL MR NEUROIMAGING: COMPARISON AT 3T AND 1.5T
B. Sneller1, M. A. Dresner2, R. A. Heckemann2, J. V. Hajnal2, DL G. Hill1; 1Medical Image Computing Centre (MedIC), UCL, London, United Kingdom; 2Imaging Sciences Department, Imperial College, London, United Kingdom Background: Alzheimer’s can be detected early in its progression by identifying subtle temporal changes in brain structure with serial magnetic resonance (MR) neuroimaging. These studies have traditionally been done at 1.5T. It is now feasible to transfer these protocols to increasingly available 3T scanners that provide higher signal to noise ratios, therefore potentially greater sensitivity to small changes, but which also have different artefact properties. Objective: To assess the consequences of this field strength difference on serial MR studies, we compare serial MR images from 10 volunteers and their resulting subtraction images acquired with similar protocols at both 1.5T and 3T. Methods: Baseline and repeat scans acquired from 10 volunteers on both 1.5T and 3T Philips Intera scanner; 5 with 8-element array coil, 5 with birdcage coil. 3D gradient echo sequence: matched between scanners, MPRAGE, transverse slab, flip angle: 8°, matrix: 208x256, 1.2mm cubic voxels, readout AP, inversion time (TI) optimised giving similar contrast (TI ⫽ 900 ms (1.5T)/1250 ms (3T)). Difference images (registered and subtracted baseline/repeat scans from same field strength) were re-formatted in the coronal plane. Regions of interest (ROI) were placed, in the difference image slice with the most severe flow artefact (visually assessed), over an area of: most severe artefact, and no apparent artefact. Artefact was quantified as
P-107
QUANTIFYING T1-RHO IN ALZHEIMER’S DISEASE Ari Borthakur, Gul Moonis, Andrew J. Wheaton, Elias R. Melhem, Christopher Clark, Ravinder Reddy; University of Pennsylvania, Philadelphia, PA, USA Background: Conventional MRI techniques have proven inadequate in observing the underlying pathology of Alzheimer’s Disease (AD) in humans in vivo. In previous studies, differences in T2 relaxation times could not discern between patient and control populations. The spin-lattice relaxation time constant in the rotating frame, or T1, is an alternate contrast mechanism. Whereas quantifying T2* with MRI can be prone to errors from susceptibility-induced signal losses and the T2-weighted MR signal is degraded by diffusion, T1weighted MR images are not affected by any such losses and T1 typically has a greater dynamic range than T2* or T2 in biological tissues. T1-weighted MRI has been shown to generate tissue contrast based on variations in protein content. Objective: To determine whether there are any changes in T1 relaxation times in patients with AD compared to age-matched controls. Methods: MRI was performed on 7 patients (mean age:77⫾7) with AD (diagnosed by a neurologist) and 5 controls (mean age:73⫾7) on a Siemens Sonata 1.5 Tesla clinical scanner. T1-weighted image of a slice perpendicular to the AC/PC plane was obtained and included the head of the hippocampus. A T1 pre-encoded Turbo Spin-Echo pulse sequence was employed with
Abstracts: Imaging / 1 (Suppl 1) (2005) TE/TR⫽12/2000ms, TSL(duration of spin-lock pulse)⫽ 20, 40, 60 and 80ms, slice thickness⫽2mm, 860m pixel-size, for a total imaging time of 6 minutes for four images. Each pixel’s signal intensity was fitted as a function of TSL by a linear least-squares algorithm to generate T1 maps. A region of interest was manually selected in the parenchyma in the right medial temporal lobe and average T1 values recorded. A student’s t-test was performed to determine any significance in the difference in T1 values between groups. Conclusions: Average T1 for the AD group was 95.3⫾1.4ms (mean ⫾ std. error) and for controls was 87.5⫾1.7ms and the difference was statistically significant (p⬍0.005). Typical T1 MR images (grayscale images) and corresponding T1 maps (color images) are shownin the figure. This is the first demonstration of imaging AD pathology in humans using T1 imaging. Our results indicate that clinically-confirmed AD results in the prolongation of T1 relaxation time in brain tissue.
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consent on a 1.5T Siemens Magnetom Vision scanner (3D sequence, TR⫽11.6ms, TE⫽4.9ms, FA ⫽ sagittal, 256 (SI) x 204 (AP) mm pixels, 1mm slices). Pre-processing - All scans were corrected for intensity inhomogeneity, linearly registered in stereotaxic space and intensity normalized. Rectangular volumes of interest (VOI) were defined on the left and right MTL (80x52x60 voxels). Each VOI was further linearly and nonlinearly registered to a reference target image. Two features were defined for classification: the linear registered, normalized intensity and the trace of the Jacobian of the nonlinear deformation fields, providing a measure of local volume change. Analysis Normative spaces were created from 152 normal young subjects using principal components analysis of the intensity and trace VOIs. Pre-processed scans from the cohort subjects were projected in the normative spaces. Logistic regression (2 ⬍ 4.04 , P ⬍ 0.045) was used to identify significant eigenvectors that were then retained for forward stepwise linear discriminant analyses. With 12 eigenvectors (P-to-enter ⬍ 0.2) the classifier sensitivity to AD was 93% and to MCI 100%, while it achieved 100% specificity. Conclusion: Our results indicate that MR data projected in multidimensional feature domains can adequately discriminate NA, AD and MCI populations. This single-scan, practical and objective method holds promise for AD or MCI detection from normal aging. P-109
GRAY MATTER REDUCTION IN COGNITIVELY INTACT ADULTS WITH THE APOE E4 ALLELE
Heather A. Wishart, Andrew J. Saykin, Thomas W. McAllister, Laura A. Rabin, Brenna C. McDonald, Laura A. Flashman, Robert M. Roth, Alexander C. Mamourian, Gregory J. Tsongalis, C. Harker Rhodes; Dartmouth Medical School, Lebanon, NH, USA
P-108
SUCCESSFUL AD AND MCI DIFFERENTIATION FROM NORMAL AGING VIA AUTOMATED ANALYSIS OF MR IMAGE FEATURES
Simon Duchesne1, Jens C. Pruessner2, Stefan Teipel3, Harald Hampel3, D. Louis Collins1; 1Montreal Neurological Institute, Montreal, PQ, Canada; 2Douglas Hospital Research Center, Montreal, PQ, Canada; 3 Ludwig-Maximilian University, Munich, Germany Background: Neuropathological studies in Alzheimer’s dementia (AD) have shown that brain degeneration in the medial temporal lobes (MTL) occurs early in the course of the disease. Our hypothesis is that microscopic changes will impact the T1-weighted (T1w) MR signal intensity, while macroscopic alterations in structure shape can be detected via image registration. Objective: We aimed at differentiating AD and mild cognitive impairment (MCI) from normal aging (NA) with ⬎ 95% sensitivity and specificity using a recently developed automated classification technique. Methods: Subjects- 15 clinical AD [age 70(8), MMSE 22.45(5.5)], 7 MCI [age 74(8), MMSE 25.1(1.7)] and 22 NA [age 62(9), MMSE 26.6(5.5)]. T1w MRI were acquired after informed
Background: Reduced volume of medial temporal lobe structures has been demonstrated in some, but not all, studies of cognitively intact APOE E4 carriers. Objective(s): The present study was designed to determine whether cognitively intact E3/E4 adults show reduced gray matter (GM) density on voxel-based morphometry (VBM) compared to those homozygous for the E3 allele. VBM is an automated, reliable and unbiased technique with certain advantages for detecting subtle brain changes relative to the region-of-interest approaches used in prior studies. Methods: Participants were cognitively intact, healthy adults who completed genotyping, neuropsychological testing and magnetic resonance imaging, including a T1-weighted 1.5mm coronal volume acquired at 1.5T. Fifty-nine participants had the E3/3 genotype and 26 had the E3/E4 genotype. Participants ranged in age from 19 to 80. Groups did not differ in age, sex, education, handedness or memory performance. For VBM, SPGR volumes were spatially normalized, segmented, smoothed, and gray matter images analyzed using the GLM approach implemented in the Statistical Parametric Mapping package. Conclusions: The E3/3 participants showed higher gray matter density than the E3/4 participants in medial and inferior temporal regions bilaterally (Fig. 1) among other areas. There were no regions in which E3/4 participants showed higher GM density than E3/3 participants. The overall pattern of findings remained the same after covarying for age and sex. These results indicate that regionally reduced GM density is evident in cognitively intact adults who possess a genetic risk factor for AD. The findings also suggest that a combination of genotyping and neuroimaging may assist in monitoring at-risk individuals prior to the onset of clinical symptoms.
Abstracts: Imaging / 1 (Suppl 1) (2005)
PET imaging for 90 minutes after iv injection of 370 MBq 11C-PIB. Regional clearance t1/2 and distribution volume ratios (DVR) were calculated through graphical analysis using the cerebellum as reference region. PIB parameters were compared with FDG uptake. Images showed marked binding in all AD subjects, especially in frontal, parietal and lateral temporal cortices as well as in the caudate nuclei with relative sparing of occipital and sensorimotor cortex, and very low uptake in cerebellar cortex. Images in LBD subjects were similar to AD subjects, though slightly higher uptake was observed in occipital and sensorimotor cortex. Cortical PIB clearance was significantly slower in LBD (t1/2 109 ⫹/- 28 min) and AD patients (t1/2 92 ⫹/- 13 min) when compared with control subjects (t1/2 61 ⫹/- 9 min). Clearance from cerebellar cortex was the same in all groups. Significantly higher DVR in neocortical areas were observed in AD (1.99 ⫹/- 0.36, p⬍0.01) and LBD patients (1.81 ⫹/- 0.25, p⬍0.01) when compared with control subjects (1.25 ⫹/- 0.23). There was an inverse correlation between PIB binding and glucose metabolism (r ⫽-0.67, p⬍0.0001). Regional uptake asymmetry indices were greater in LBD both in PIB and FDG studies. Conclusion: 11C-PIB PET suggests that cortical A is present in LBD subjects with progressive dementia in a similar degree to AD subjects. Longitudinal studies are warranted to more clearly define the role of A deposition in the development of dementia in both AD and LBD.
P-106
the ratio of the standard deviations from the two ROI’s and compared for each subject at both field strengths. A radiologist ranked comparative visual artefact in each randomised pair of 1.5T vs. 3T images on a 5-point scale. Conclusions: Flow artefacts arising from the carotid siphons, affecting the hippocampal region, are more than twice as large on average at 3T than at 1.5T (P⬍0.01) and have different intensity patterns (Table 1 & Fig2). A radiologist visually rated images acquired from 8 volunteers as having more pronounced flow artefacts at 3T(P⬍0.05). Sagittal slab acquisition reduces these artefacts substantially. Increased artefact at 3T can potentially offset the signal to noise ratio advantage of higher field strength. Sequences for longitudinal neuroimaging need to be carefully optimised to minimise artefacts, and provide data that can be compared with that from 1.5T studies. Table 1 Comparison of artefact level at different field strengths Ratio of Birdcage results SDs of ROIs at: Vol1 Vol2 Vol3 1.5T 3T
Array coil results Vol4
Vol5
Average Vol6
1.495 1.636 1.252 1.859 1.347 1.518 3.124 3.910 3.216 3.797 2.792 3.368
Vol7
Vol8
Vol9
Vol10 Average
2.180 2.209 1.835 2.124 1.919 5.002 3.755 4.487 6.263 4.826
2.053 4.886
Collated Average 1.785 4.117
SERIAL MR NEUROIMAGING: COMPARISON AT 3T AND 1.5T
B. Sneller1, M. A. Dresner2, R. A. Heckemann2, J. V. Hajnal2, DL G. Hill1; 1Medical Image Computing Centre (MedIC), UCL, London, United Kingdom; 2Imaging Sciences Department, Imperial College, London, United Kingdom Background: Alzheimer’s can be detected early in its progression by identifying subtle temporal changes in brain structure with serial magnetic resonance (MR) neuroimaging. These studies have traditionally been done at 1.5T. It is now feasible to transfer these protocols to increasingly available 3T scanners that provide higher signal to noise ratios, therefore potentially greater sensitivity to small changes, but which also have different artefact properties. Objective: To assess the consequences of this field strength difference on serial MR studies, we compare serial MR images from 10 volunteers and their resulting subtraction images acquired with similar protocols at both 1.5T and 3T. Methods: Baseline and repeat scans acquired from 10 volunteers on both 1.5T and 3T Philips Intera scanner; 5 with 8-element array coil, 5 with birdcage coil. 3D gradient echo sequence: matched between scanners, MPRAGE, transverse slab, flip angle: 8°, matrix: 208x256, 1.2mm cubic voxels, readout AP, inversion time (TI) optimised giving similar contrast (TI ⫽ 900 ms (1.5T)/1250 ms (3T)). Difference images (registered and subtracted baseline/repeat scans from same field strength) were re-formatted in the coronal plane. Regions of interest (ROI) were placed, in the difference image slice with the most severe flow artefact (visually assessed), over an area of: most severe artefact, and no apparent artefact. Artefact was quantified as
P-107
QUANTIFYING T1-RHO IN ALZHEIMER’S DISEASE Ari Borthakur, Gul Moonis, Andrew J. Wheaton, Elias R. Melhem, Christopher Clark, Ravinder Reddy; University of Pennsylvania, Philadelphia, PA, USA Background: Conventional MRI techniques have proven inadequate in observing the underlying pathology of Alzheimer’s Disease (AD) in humans in vivo. In previous studies, differences in T2 relaxation times could not discern between patient and control populations. The spin-lattice relaxation time constant in the rotating frame, or T1, is an alternate contrast mechanism. Whereas quantifying T2* with MRI can be prone to errors from susceptibility-induced signal losses and the T2-weighted MR signal is degraded by diffusion, T1weighted MR images are not affected by any such losses and T1 typically has a greater dynamic range than T2* or T2 in biological tissues. T1-weighted MRI has been shown to generate tissue contrast based on variations in protein content. Objective: To determine whether there are any changes in T1 relaxation times in patients with AD compared to age-matched controls. Methods: MRI was performed on 7 patients (mean age:77⫾7) with AD (diagnosed by a neurologist) and 5 controls (mean age:73⫾7) on a Siemens Sonata 1.5 Tesla clinical scanner. T1-weighted image of a slice perpendicular to the AC/PC plane was obtained and included the head of the hippocampus. A T1 pre-encoded Turbo Spin-Echo pulse sequence was employed with
Abstracts: Imaging / 1 (Suppl 1) (2005) TE/TR⫽12/2000ms, TSL(duration of spin-lock pulse)⫽ 20, 40, 60 and 80ms, slice thickness⫽2mm, 860m pixel-size, for a total imaging time of 6 minutes for four images. Each pixel’s signal intensity was fitted as a function of TSL by a linear least-squares algorithm to generate T1 maps. A region of interest was manually selected in the parenchyma in the right medial temporal lobe and average T1 values recorded. A student’s t-test was performed to determine any significance in the difference in T1 values between groups. Conclusions: Average T1 for the AD group was 95.3⫾1.4ms (mean ⫾ std. error) and for controls was 87.5⫾1.7ms and the difference was statistically significant (p⬍0.005). Typical T1 MR images (grayscale images) and corresponding T1 maps (color images) are shownin the figure. This is the first demonstration of imaging AD pathology in humans using T1 imaging. Our results indicate that clinically-confirmed AD results in the prolongation of T1 relaxation time in brain tissue.
S43
consent on a 1.5T Siemens Magnetom Vision scanner (3D sequence, TR⫽11.6ms, TE⫽4.9ms, FA ⫽ sagittal, 256 (SI) x 204 (AP) mm pixels, 1mm slices). Pre-processing - All scans were corrected for intensity inhomogeneity, linearly registered in stereotaxic space and intensity normalized. Rectangular volumes of interest (VOI) were defined on the left and right MTL (80x52x60 voxels). Each VOI was further linearly and nonlinearly registered to a reference target image. Two features were defined for classification: the linear registered, normalized intensity and the trace of the Jacobian of the nonlinear deformation fields, providing a measure of local volume change. Analysis Normative spaces were created from 152 normal young subjects using principal components analysis of the intensity and trace VOIs. Pre-processed scans from the cohort subjects were projected in the normative spaces. Logistic regression (2 ⬍ 4.04 , P ⬍ 0.045) was used to identify significant eigenvectors that were then retained for forward stepwise linear discriminant analyses. With 12 eigenvectors (P-to-enter ⬍ 0.2) the classifier sensitivity to AD was 93% and to MCI 100%, while it achieved 100% specificity. Conclusion: Our results indicate that MR data projected in multidimensional feature domains can adequately discriminate NA, AD and MCI populations. This single-scan, practical and objective method holds promise for AD or MCI detection from normal aging. P-109
GRAY MATTER REDUCTION IN COGNITIVELY INTACT ADULTS WITH THE APOE E4 ALLELE
Heather A. Wishart, Andrew J. Saykin, Thomas W. McAllister, Laura A. Rabin, Brenna C. McDonald, Laura A. Flashman, Robert M. Roth, Alexander C. Mamourian, Gregory J. Tsongalis, C. Harker Rhodes; Dartmouth Medical School, Lebanon, NH, USA
P-108
SUCCESSFUL AD AND MCI DIFFERENTIATION FROM NORMAL AGING VIA AUTOMATED ANALYSIS OF MR IMAGE FEATURES
Simon Duchesne1, Jens C. Pruessner2, Stefan Teipel3, Harald Hampel3, D. Louis Collins1; 1Montreal Neurological Institute, Montreal, PQ, Canada; 2Douglas Hospital Research Center, Montreal, PQ, Canada; 3 Ludwig-Maximilian University, Munich, Germany Background: Neuropathological studies in Alzheimer’s dementia (AD) have shown that brain degeneration in the medial temporal lobes (MTL) occurs early in the course of the disease. Our hypothesis is that microscopic changes will impact the T1-weighted (T1w) MR signal intensity, while macroscopic alterations in structure shape can be detected via image registration. Objective: We aimed at differentiating AD and mild cognitive impairment (MCI) from normal aging (NA) with ⬎ 95% sensitivity and specificity using a recently developed automated classification technique. Methods: Subjects- 15 clinical AD [age 70(8), MMSE 22.45(5.5)], 7 MCI [age 74(8), MMSE 25.1(1.7)] and 22 NA [age 62(9), MMSE 26.6(5.5)]. T1w MRI were acquired after informed
Background: Reduced volume of medial temporal lobe structures has been demonstrated in some, but not all, studies of cognitively intact APOE E4 carriers. Objective(s): The present study was designed to determine whether cognitively intact E3/E4 adults show reduced gray matter (GM) density on voxel-based morphometry (VBM) compared to those homozygous for the E3 allele. VBM is an automated, reliable and unbiased technique with certain advantages for detecting subtle brain changes relative to the region-of-interest approaches used in prior studies. Methods: Participants were cognitively intact, healthy adults who completed genotyping, neuropsychological testing and magnetic resonance imaging, including a T1-weighted 1.5mm coronal volume acquired at 1.5T. Fifty-nine participants had the E3/3 genotype and 26 had the E3/E4 genotype. Participants ranged in age from 19 to 80. Groups did not differ in age, sex, education, handedness or memory performance. For VBM, SPGR volumes were spatially normalized, segmented, smoothed, and gray matter images analyzed using the GLM approach implemented in the Statistical Parametric Mapping package. Conclusions: The E3/3 participants showed higher gray matter density than the E3/4 participants in medial and inferior temporal regions bilaterally (Fig. 1) among other areas. There were no regions in which E3/4 participants showed higher GM density than E3/3 participants. The overall pattern of findings remained the same after covarying for age and sex. These results indicate that regionally reduced GM density is evident in cognitively intact adults who possess a genetic risk factor for AD. The findings also suggest that a combination of genotyping and neuroimaging may assist in monitoring at-risk individuals prior to the onset of clinical symptoms.