P2-021: A method to quantitate amyloid plaque load in a transgenic mouse model of Alzheimer's disease

Poster Presentations P2 Cognitive Abilities Screening Instrument (CASI) were deteriorated except for long-term memory and visual construction in the MCI participants compared with healthy adults, suggesting that MCI is similar to very mild Alzheimer’s disease (AD). Objective: We herein report the neuropsychological features of MCI with reference to regional cerebral blood flow (rCBF) especially in the hippocampus and frontal lobe. Methods: Patients: 24 MCI subjects were studied. They met the following criteria: subjective memory complaints and/or family observation for their memory impairment; the score on WMS-R Logical Memory I to be less 13; the MMSE scores were greater than 24; normal daily living; and the CDR score was 0.5 with memory domain being 0.5 and other domains being 0 or 0.5. Written informed consent was obtained from all the participants. Cognitive assessments: The CASI and the Trail-Making Tests A (TMT-A) and B (TMT-B) were used. The CASI was used for assessing 9 domains, i.e., remote memory, recent memory, attention, concentration/ mental manipulation, orientation, visual construction, abstraction & judgment, listgenerating fluency, and language. SPECT: The rCBF was measured qualitatively using the [123I]-N-isopropyl-p- iodoamphetamine and single photon emission tomography (SPECT), and region of interest (ROI) analysis was performed using 3DSRT software. We evaluated the relationship between the scores of CASI domains and rCBF of the frontal and hippocampal ROIs using the cerebellum as a reference. Results: We found that decreased rCBF in the hippocampus was correlated with CASI domains recent memory (Spearman, p⬍0.01). Decreased rCBF in the frontal lobes were associated with frontal executive dysfunction as measured by the TMT-A and TMT-B (Spearman, p⬍0.01). The MCI subjects with more decreased executive function were rated as 0.5 in the non-memory CDR domains. Conclusions: Clinical subtypes of MCI based on CDR domains were associated with neurological and neuropsychological backgrounds. Further decline to dementia with reference to such backgrounds would be investigated. P2-021

A METHOD TO QUANTITATE AMYLOID PLAQUE LOAD IN A TRANSGENIC MOUSE MODEL OF ALZHEIMER’S DISEASE

George Iordanescu1,2, Palamadai N. Venkatasubramanian1,2, Jason C. Pych1,3, Marina V. Yasvoina1,4, Alice M. Wyrwicz1,5, 1ENH Research Institute, Evanston, IL, USA; 2Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 3 Neurobiology and Physiology, Northwestern University Weinberg College of Arts and Sciences, Evanston, IL, USA; 4NUIN, Northwestern University, Evanston, IL, USA; 5Radiology, Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Contact e-mail: [email protected] Background: Although successful visualization of amyloid deposits in the APP transgenic mouse brain with MR imaging has been reported recently, there is no suitable method to measure plaque load (PL). We present a novel method based on simulated flooding (watersheds) to segment amyloid plaques in mouse brain images. In this method, the image is segmented into catchment basins (CB) associated with local minima and CBs that correspond to plaques are selected using the data Laplacian as a feature describing local variation. Besides PL (volume fraction) estimation, our method can be also used to analyze other plaque characteristics such as size, shape and distribution. Methods: The automatic plaque segmentation algorithm has two steps: First, simulated flooding is used to extract regions with low intensities completely surrounded by higher intensity neighbors. The resulting map defines the CBs of the MR local minima. Second, the image Laplacian L(I) ⫽ div (grad (I)) is used to model the plaque cores, defined as regions with small derivatives, surrounded by rapidly increasing neighbors. Plaques are segmented by taking the CBs that have maximum Laplacians larger than the background noise. The algorithm was used to compute PL in the subiculum of 2 and 10 months old 5XFAD APP/PS1 transgenic mice. RARE 3D-images of fixed brains acquired on a 14.1T microimager using TR/TEeff 2500ms/40ms and pixel size 35␮m x35␮m x35␮m were analyzed. The algorithm was applied to histology data from

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the same brains and PL results were compared for validation. Results: The computed PL values increased with age for the 5XFAD mice from 1.25% at 2 months to 25.0% at 10 months. A non-transgenic control mouse had a PL of nearly 0% as expected. Our results are consistent with the known evolution of plaque deposition in this strain. Amyloid plaques begin to appear in the subiculum of 2 month old 5XFAD mice and by 10 months of age numerous plaques are found in subiculum, hippocampus and deep layers of the cortex. Conclusions: Our automatic computational method for the quantitation of plaques can be applied to evaluate disease progression and efficacy of therapy in transgenic mouse models of AD. P2-022

DIRECT COMPARISON OF IN VIVO ACCUMULATION OF 11C-PIB AND 11C-BF227 IN ALZHEIMER’S DISEASE

Kenji Ishii1, Masaya Hashimoto1, Yuichi Kimura1,2, Muneyuki Sakata1, Keiichi Oda1, Keiichi Kawasaki1, Kiichi Ishiwata1, Nobuyuki Okamura3, Kazuhiko Yanai3, 1Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan; 2National Institute of Radiological Sciences, Chiba, Japan; 3 Tohoku Univ School of Med, Sendai, Japan. Contact e-mail: [email protected] Background: The amyloid imaging has recently emerged as a promising tool to evaluate the progression of disease objectively by assessing in vivo accumulation of amyloid-␤ (A␤) in Alzheimer’s disease (AD) brain. The purpose of this study is a direct comparison of the characteristics of two benzothiazole derivative amyloid probes for PET, 11C-PIB and 11C-BF227, in the same patients of AD. Methods: We studied 5 patients of probable AD, 2 patient of frontotemporal dementia (FTD), one patient of cerebral amyloid angiopathy (CAA) and 2 healthy controls (HC). All the subjects participated in two dynamic PET scans for 60 min using 11C-PIB and 11 C-BF227, with serial arterial blood sampling and metabolite analysis. The accumulation of each probe was evaluated by distribution volume ratio (DVR) estimated by Logan’s graphical method with arterial input, and by standardized uptake value ratio (SUVR) in the summing image of 40 to 60 min after injection, in either of them the cerebellar cortex was used as a reference region. Results: Significant increase in the probe accumulation was observed in both tracers in AD and CAA brains, but not in FTD brains. The 11C-PIB accumulation in the gray matter of AD and AA increased 90-160% from the healthy control brains. However, 11C-BF227 accumulation remained 17-26% above the control level. In addition, the accumulation patterns in terms of the regional profile and the laterality were not identical in two tracers; the highest accumulation of 11C-PIB was observed in the precuneus, but in the temporal and parietal cortices was the highest with 11C-BF227, and the laterality was found to be reversed in some cases (Figure). Conclusions: The accumulation of 11C-BF227 seems to be specific for A␤ as well as PIB. However, the sensitivity of 11C-PIB to detect A␤ accumulation may be superior to that of 11C-BF227. The difference in the regional distribution of two probes presumably reflects their different preference to various conformations of A␤ in the senile plaque generation process. The comparison of two tracers may give us additional pathophysiological information in the amyloid cascade in AD.