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Alzheimers Imaging Consortium: IC-P-Poster Imaging

DPC tomography. Hyper-intense dots were detected throughout the 5xFAD brain in contrast to wild type, suggesting that APs could be detected by DPC tomography. In order to conrm those observations, brains were sectioned after the DPC scans and subjected to Thioavine-S staining, followed by two-photon imaging. Both signals were highly correlated, demonstrating that the set-up was indeed detecting APs. Finally, local DPC tomography of the 5xFAD brain was performed at the level of the hippocampus. The high resolution obtained allowed us to visualize the structure of APs. Conclusions: We demonstrated that DPC tomography could be used to detect APs across the entire brain of a transgenic mouse model of AD at a high resolution, without using any contrast agents. This new tool yields AP structural details, including size and morphology. Future researches, directed towards reducing the X-ray dose, will reveal if DPC tomography could be applicable to in vivo imaging.

IC-P-117

A COMPARATIVE STUDY OF VOXEL AND SURFACE-BASED CORTICAL THICKNESS METHODS IN FRONTOTEMPORAL DEMENTIA

Figure 1. A comparison of 3 methods, showing FDR corrected p-values (red - yellow is p < 0.05), comparing control subjects with SD patients (top) and PNFA patients (bottom). tage of voxel based methods is their fast computation time, which may lead to clinically useful diagnostic tools. IC-P-118 CEREBRAL MICROBLEED DETECTION ON 7T MRI: RELIABILITY AND EFFECTS OF IMAGE PROCESSING

Matthew Clarkson, Jorge Cardoso, Marc Modat, Gerard Ridgway, Kelvin Leung, Jonathan Rohrer, Sebastien Ourselin, Nick Fox, University College London, London, United Kingdom. Background: Cortical thickness estimation performed in-vivo via magnetic resonance imaging is an important technique for the diagnosis and understanding of neurodegenerative diseases such as Alzheimers disease (AD). The aim of this study was to compare the surface based FreeSurfer method, with two voxel based Methods: a Laplacian based method that solves the Laplace equation in the grey matter voxels and calculates thickness by solving partial differential equations and also a Registration method that nonlinearly deforms a white matter mask to match the combined grey and white matter mask, and measures the distance the grey matter boundary moves during registration. Methods: 28 controls, 30 patients with clinically diagnosed progressive non-uent aphasia (PNFA) and 43 patients with semantic dementia (SD) received a volumetric MRI on 4 different 1.5T GE Signa scanners. The FreeSurfer, Laplacian and Registration methods were run on all subjects. A vertex by vertex generalised linear model was run to assess differences in thickness between the control subjects and either the SD or PNFA patients. Two-tailed un-paired t-tests were computed at each vertex, with signicance assessed at the p < 0.05 level, corrected for multiple comparisons using the False Discovery Rate. A support vector machine (SVM) was used to classify the control group from the patient groups using the thickness data. Results: Figure 1. shows a visual comparison of statistically signicantly thinner (red - yellow) areas of cortical thickness for SD patients (top) and PNFA patients (bottom) when compared to control subjects. All methods detect left more than right atrophy, with SD more widespread than PNFA. The voxel based methods appear to be more sensitive than FreeSurfer. The SVM scores in Table 1. did not show statistically signicant evidence of a difference between methods, though there is evidence that the Laplacian method may provide more accurate classication. Conclusions: Though widely thought to be less accurate, this preliminary test has shown that voxel based methods can perform as well as established surface based methods such as FreeSurfer for group-wise comparisons. A potential advan-

Jeroen de Bresser, Manon Brundel, Mandy Conijn, Jeroen van Dillen, Mirjam Geerlings, Max Viergever, Peter Luijten, Geert-Jan Biessels, University Medical Center Utrecht, Utrecht, Netherlands. Background: 7T MRI allows detection of smaller cerebral microbleeds than MRI at lower eld strength. However, susceptibility effects of other structures do also complicate microbleed detection at higher eld strength. Image processing by means of minimum intensity projection (minIP) is required for visual rating because of the large number of slices in high resolution scans. The present study determined optimal minIP conditions to detect susceptibility artefacts of microbleeds on 7T MRI, based on sensitivity of detection and rating time. Furthermore, intra - and inter-rater reliability of this visual microbleed detection on 7T MRI were assessed. Methods: 3D T2*-weighted images were acquired on a 7T MR system and scored by using the Microbleed Anatomical Rating Scale. First, eight different conditions of minIP processing, involving variations of slice thickness and gap, were applied to scans from three subjects with multiple microbleeds. Two of these conditions (slice thickness/gap in mm: 2/0, 4/-2) were applied to 7T scans of ten subjects to assess intra - and inter-rater reliability, with four raters, one of whom scored all scans twice. We veried that inter-rater reliability of these raters for visual scoring of regular, 1.5T, 3D T2*weighted scans of the same subjects was within the range reported in previous studies. Results: Of the eight conditions, 2/0 and 4/-2 minIP showed a good and comparable tradeoff between sensitivity for detection and rating time. Susceptibility artefacts of microbleeds from 0.7 mm in diameter or more could be detected on 7T scans (See gure for example). More microbleeds were detected on 7T (median (range): 2 (0-11) than 1.5T scans (0 (0-3). Intra-rater reliability for detection of number of microbleeds on 7T

Table 1 SVM classication comparing control subjects with SD and PNFA patients where +/- CI are respectively the upper and lower limits of a 95% condence interval. Method FreeSurfer Laplacian Registration FreeSurfer Laplacian Registration Group SD SD SD PNFA PNFA PNFA Accuracy (%) 95.8 97.2 95.8 79.3 84.5 75.9 -CI (%) 88.1 90.2 88.1 66.6 72.6 62.8 +CI (%) 99.1 99.2 99.1 88.8 92.7 86.1

Alzheimers Imaging Consortium: IC-P-Poster Imaging was good (Intraclass Correlation Coefcient: 0.73), but inter-rater reliability was only moderate (0.46). Conclusions: With optimal minIP processing at 7T MRI, susceptibility artefacts of microbleeds from 0.7 mm in diameter or more were detected. However, the limited size of some of the lesions and susceptibility effects of adjacent other structures also complicated detection, reducing inter-rater reliability of visual scoring. Automated lesion detection techniques may be required to optimally benet from the increased spatial resolution offered by 7T MRI. IC-P-119 IMPAIRED CONNECTIVITY BETWEEN FUNCTIONAL BRAIN MODULES REFLECTS COGNITIVE DYSFUNCTION IN ALZHEIMERS DISEASE

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scale brain connectivity, and illustrates the relevance of viewing Alzheimers disease as a network disorder. IC-P-120 INVESTIGATING LIMBIC SYSTEM MYELIN ALTERATION IN ALZHEIMERS DISEASE

Sean Deoni1, Steve Correia2, Tanja Su2, Jessica Man2, Katie Lehman1, Paul Malloy2, Stephen Salloway3, 1Brown University, Providence, Rhode Island, United States; 2Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States; 3Butler Hospital, Providence, Rhode Island, United States. Background: Alongside beta-amyloid deposits and neurobrillary tangle formation, white matter (WM) damage is commonly reported in Alzheimers disease (AD). A WM hypothesis posits the earliest stages of AD is associated with marked myelin alteration and reduction1-4. While diffusion tensor (DT-) MRI is providing additional support for this hypothesis, many studies lack anatomical precision and/or microstructural specicity. That is, the bulk of DT-MRI studies investigate differences throughout the brain, without focusing on specic brain networks. Further, DT-MRI assess many microstructural features (i.e. bre size, density and coherence) and is not specic to myelin. In this work, we investigated myelin content (using the mcDESPOT5 multicomponent relaxometry technique) along the limbic system WM pathways (cingulum, fornix, anterior commissure, and uncinate) supporting the behaviour and memory functions impaired in AD. Methods: Participants: 18 age-matched elderly individuals, including 9 MCI patients [CDR 0.5-1.0 and MMSE > 24 (mean 27.7), mean age 77.4] and 9 ModSev AD [CDR > 1.0 or MMSE < 18 (mean 14.2), mean age 80.3]. MRI: Whole-brain mcDESPOT data5 were acquired on a Siemens Tim Trio scanner (32-channel head array), with incorporated B0 and B1 eld correction6. ANALYSIS: Following MWF map calculation5, each participants data was co-registered to MNI space. Using a popullation-based WM atlas7 (Figure 1) MWF histograms were obtained for the anterior commissure (AC red), fornix (blue), and right and left cingulum (green) and uncinate (purple) tracts in each individual. These distributions were then normalized with respect to area, averaged across the MCI and ModSev groups, and compared. Results: Figure 1 shows averaged tract MWF histograms obtained for the MCI (dotted) and ModSev (solid) groups. Within the right and left cingulum and left uncinate pathways, signicantly (p < 0.05) reduced myelin content was found in the ModSev group. Conclusions: This work provides preliminary evidence for reduced limbic system myelin content in ModSev AD patients. Results from this small cohort point to a signicantly altered cingulum bundle and uncinate in AD, pathways previously implicated due to their involvement in memory,

Willem de Haan, Wiesje van der Flier, Ted Koene, Lieke Smits, Philip Scheltens, Cornelis Stam, VU University Medical Center, Amsterdam, Netherlands. Background: The mechanisms of cognitive dysfunction in Alzheimers disease are still not completely understood, although disturbed communication between different brain regions is almost certainly involved. Here we use graph theoretical analysis of magnetoencephalography recordings to study the role of functional sub-networks (modules) in explaining cognitive failure in Alzheimers disease. Methods: Whole-head resting-state magnetoencephalography was performed in 18 Alzheimer patients (mean age 67 6 9, male/female ratio 12:6, mini-mental state examination 23 6 5) and 18 healthy controls (mean age 66 6 9, male/female ratio 7:11, mini-mental state examination 29 6 1). We constructed brain networks based on functional connectivity measurements, and performed graph analysis with a focus on modularity. Additionally, these measures were correlated to cognitive testscores. Results: Alzheimer patient networks showed a weaker modular organization in the higher frequency bands. The parietal cortical region contained most highly connected nodes, but it also showed the strongest Alzheimer-related loss of connectivity and modular strength. However, the loss of connections between functional modules in the delta and theta bands was more strongly linked to cognitive impairment than the observed withinmodule disturbance of the parietal hub region. More detailed analysis of modular features is in progress. Conclusions: Modular organization of large-scale spontaneous brain activity is disturbed in Alzheimers disease. Our results support the disconnection syndrome hypothesis of Alzheimers disease, demonstrating vulnerability of a highly connected hub region and a - clinically more relevant loss of communication between functional brain regions. This underlines the close relationship between cognition and large-

Figure 1. Comparison of tract-specic myelin water fraction distributions along each tract of the limbic system between MCI (dotted) and moderate/severe AD (Solid) patients. Whilist there is a gradual shift towards lower MWF in the severe patients, it is partcularly pronounced bilaterally in the cingulum and left uncinate (p < 0.002)