regions were segmented by FreeSurfer and compared with manually- delineated regions. Results: Absolute volumes from FreeSurfer d

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regions were segmented by FreeSurfer and compared with manually-

delineated regions. Results: Absolute volumes from FreeSurfer differed

from manual volumes to different extents depending on region and subject

group but were largely due to differences in protocols - with more temporal

stem white matter included in FreeSurfer regions. Volume differences

(FreeSurfer-manual) were different between controls and SD (p0.05), but

not between control-AD or between AD-SD groups. Importantly however,

expressed as fraction of control volume the FreeSurfer results showed a

very similar pattern of loss to that found with manual measures (Table). In

the SD group the most severely atrophied regions were the left entorhinal

cortex, left amygdala and left parahippocampal gyrus. Furthermore, great-

est atrophy in the AD group was shown bilaterally in the entorhinal cortex

and hippocampus. There was no evidence for left-right asymmetry in the

control or AD groups. In the SD group the left temporal volumes were

significantly smaller than the equivalent right-sided structures (p0.0001)

(Figure). Conclusions: Despite absolute volumes differing for FreeSurfer

and manual segmentations, between-group comparisons revealed remark-

ably similar patterns of loss with the two methods: in AD symmetrical

losses were most marked in the entorhinal cortex and hippocampus whereas

SD showed profound asymmetrical, predominantly left-sided, atrophy af-

fecting in particular the anterior and medial temporal lobe structures.

IC-P3-196 CLINICAL EVALUATION OF 18F-LABELED AV-

138 FOR PET AMYLOID IMAGING IN

ALZHEIMER’S DISEASE

Val Lowe, Mayo Clinic, Rochester, MN, USA. Contact e-mail:

vlowe@mayo.edu

Background: 11C PIB PET has been shown to correlate with the presence

of brain amyloid in patients with neurodegenerative disease. The short

half-life of 11C makes the clinical use of 11C PIB problematic. Imaging

using 18F-PET amyloid ligands would be preferable. Therefore, the brain

amyloid imaging agent 18F AV-138 was evaluated clinically. Methods:

Five normal control (MMSE median 29.5, range 29-30) subjects (NC) and

mild to moderate 4 Alzheimer’s Disease (MMSE median 22, range 14-24)

patients (AD) were imaged with 18F AV-138 PET. Subjects received 5 mCi

(mean 4.6, range 3.0-5.5) of 18F AV-138 and thereafter dynamic brain PET

imaging for 3 hrs was performed. Regional brain accumulation was eval-

uated with Logan plot analysis over 90 minutes to obtain a distribution

volume ratio (DVR) and a 40-60 minute frame set was used to obtain a

delay phase uptake ratio (DUR); the cerebellum was used as a reference

region for both. PET image volumes were co-registered the individuals

MRI scans. MRI scans were spatially normalized to the MNI template by

which regions were defined. Global DVR and DUR ratios were calculated

using a summation of pre-frontal, orbito-frontal, parietal, temporal, anterior

cingulate, and posterior cingulate regional activity. Results from NC and

AD subjects were compared. Results: Median global DVR (DUR) values

were 1.14 (1.18) and 1.55 (1.51) for NC and AD subjects, respectively,

which showed good separation of the groups (p0.030 for DVR and

p0.056 for DUR). Bland-Altman plot comparing the DVR and DUR

methods suggested good correlation. The DUR for 11C PIB and 18F AV-

138 in an AD patient was 2.23 and 1.53 respectively, and was 1.10 and 1.11

in a NC subject. Conclusions: 18F AV-138 is able to distinguish NC from

AD subjects based on amyloid-related uptake as seen on PET.

IC-P3-197 APOLIPOPROTEIN GENOTYPE PREDICTS RATE

OF BRAIN ATROPHY IN HEALTHY ELDERLY

ADULTS: A TENSOR-BASED MORPHOMETRY

STUDY

Po-Haong Lu, Paul Thompson, Alex Leow, Grace Lee, Agatha Lee,

Daniel Geschwind, Stephanie Stewart, George Bartzokis, UCLA, Los

Angeles, CA, USA. Contact e-mail: plu@mednet.ucla.edu

Background: Apolipoprotein (APOE) ε4 genotype, coded on chromosome

19, is a strong risk factor for developing Alzheimer’s disease (AD).

Conversely, the presence of the ε2 allele has been shown to mitigate

against cognitive decline. Tensor-based morphometry (TBM), a novel

computational approach for visualizing longitudinal progression of brain

atrophy, was used to determine whether cognitively intact elderly partici-

pants with the ε4 allele demonstrate greater volume reduction than those

with the ε2 allele. Methods: Healthy elderly volunteers, aged 55 or older,

were recruited from the community and hospital staff. They were evaluated

with a baseline and follow-up MRI scan (mean scan interval

4.72 years,

0.55) and completed APOE genotyping. Nineteen participants were

included in the study of which 11 had the ε4 allele (2 were homozygous for

the ε4 allele) and 8 had the ε2/ε3 genotype. The two groups did not differ

significantly on any demographic characteristics. TBM was used to create

3D maps of local brain tissue atrophy rates for individual participants by

globally aligning and non-linearly deforming all images to a common brain

template. Each scan pair was then deformed to each other using high

density elastic image registration. These spatially detailed 3D maps were

compared between the two groups. Results: A whole brain analysis was

performed and annual atrophy rates were significantly greater for ε4 car-

riers compared to the ε2 carriers. Specifically, the ε4 group demonstrated

greater volume loss in white and gray matter regions of the lateral frontal

lobe, insula, and temporal lobes, including the hippocampus. Conclusions:

TBM appears to be useful in tracking longitudinal progression of brain

atrophy in cognitively asymptomatic adults and possession of the ε4 allele

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Alzheimer’s Imaging Consortium IC-P3: Poster Presentations

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is associated with greater brain volume reduction well before the onset of

cognitive deficits.

IC-P3-198 MEMORY FORMATION IN MIDDLE-AGED

ADULTS: DYNAMICS OF THE BOLD SIGNAL

ACROSS REPETITIONS

Donald G. McLaren1,2, Michele L. Ries1,2, Barbara B. Bendlin1,2,

Erik K. Kastman1,2, Kristopher J. Kosmatka1,2, Guofan Xu1,2,

Britta M. Jabbar1,2, Lisa M. Newman1,2, Michele E. Fitzgerald1,2,

Sterling C. Johnson1,2, 1William S. Middleton Memorial Veteran’s

Hospital, Madison, WI, USA; 2University of Wisconsin - Madison,

Madison, WI, USA. Contact e-mail: dm10@medicine.wisc.edu

Background: Memory formation and retrieval is a dynamic process

that employs a network of brain regions. Here we aim to investigate the

neural correlates of memory formation in healthy middle-aged individ-

uals using an event-related fMRI paradigm. Methods: Participants were

asked to remember forty simple line drawings of objects that were

presented and repeated three times in a pseudo-random order while

collecting fMRI data. Two conceptual approaches were used to analyze

the fMRI images. First, we used a traditional approach with parametric

modulation based on repetition to investigate which regions showed

attenuation in the BOLD response over repetitions. In the second

approach, we examined how the hippocampus interacts with other brain

regions across repetitions. Using an in-house variant of psychophysio-

logical interactions (PPI) to investigate context-dependent connectivity,

we were able to identify regions where connectivity with the left and

right hippocampus did not change over repetition (repetition-invariant

connectivity [RI]) and regions that changed with repetition (repetition-

dependent connectivity [RD]). Results: The first approach revealed

numerous regions exhibiting an adaptation response including the fusi-

form gyrus, parahippocampal gyrus, hippocampus, amygdala, ventral

occipital lobes, and lateral frontal lobes. The second approach provides

a dynamic picture of memory representation in the network over time.

Early memory representation, at least for visual stimuli, appears depen-

dent upon synchronous activation of the hippocampus, occipital lobes,

and frontal regions; whereas representation during later encoding re-

quires less connectivity between hippocampus and visual processing

areas [RD], but continues to evoke similar connectivity with frontal

regions [RI]. Conclusions: Importantly, these findings demonstrate a

need to consider the effects of repetition on the BOLD signal in any

memory paradigm. In addition to informing our understanding of nor-

mal memory function in terms of functional brain networks, we believe

these methods will be critical to investigating memory change in aging

and disease. Specifically, our in-house variant of PPI allows investiga-

tors to identify which connections, involved in a cognitive process,

might be altered between groups. In the future, we aim at investigating

the impact of risk-factors for Alzheimer’s disease on the alteration of

these memory systems.

IC-P3-199 SODIUM MRI DETECTION OF MILD

ALZHEIMER’S DISEASE

Eric A. Mellon, David T. Pilkinton, Christopher M. Clark,

Mark A. Elliott, Walter R. Witschey, Ravinder Reddy, Arijitt Borthakur,

University of Pennsylvania, Philadelphia, PA, USA. Contact e-mail:

eric@mail.mmrrcc.upenn.edu

Background: There is significant interest in the development of novel

non-invasive techniques for the diagnosis of Alzheimer’s disease (AD)

and tracking its progression. Because magnetic resonance imaging

(MRI) is non-invasive and routinely performed in the setting of neuro-

logical disease, implementation of new MRI-based techniques for the

diagnosis and prognosis of AD are especially advantageous. Since

sodium (23Na) MRI has been shown be sensitive to cell death and

viability, we tested whether changes would be seen in Alzheimer

disease, a disease where neural cell death has been well established.

Methods: Approval for this study was granted by our institution’s

Institutional Review Board and informed consent was obtained from

each participant after explanation of the procedures. A total of 10

patients-5 mild AD (mean MMSE 24) and 5 age-matched controls

(MMSE 30 in all)-were scanned with a brief proton anatomical brain

scan followed by a 20 minute sodium MRI protocol on a 3T clinical

scanner. Example images from two volunteers are shown. Results:

After normalizing the signal from the medial temporal lobes to the

ventricular signal, it was possible to detect an increased signal in the

brains of AD patients (AD 63.63% /- 3.21 vs. Control 57.17 /-

3.77). This signal enhancement inversely correlated with manually

segmented hippocampal volume (AD 3.24cm3

/- 0.42 vs. Control 3.98

/- 0.51), r2

.35 in these patients. In this very preliminary study,

sodium enhancement was found to correlate to mild AD (p.007) more

than hippocampal volume (p.047, p.033 when normalized to total

intracranial volume), the currently most developed MRI research tech-

nique. Conclusions: Here it is shown that there are alterations in

sodium in the brains of AD patients compared to non-demented elderly

controls that can be detected by sodium MRI. This suggests that 23Na

imaging may be a clinically useful tool for detecting the neuropatho-

logical changes associated with AD.

IC-P3-200 PATTERNS OF HIPPOCAMPAL ATROPHY IN

ALZHEIMER’S DISEASE, MILD COGNITIVE

IMPAIRMENT AND APOE4

Susanne Mueller1, Norbert Schuff1, Sky Raptentsetsang1,

Krstine Yaffe2, Catherine Madison3, Bruce Miller4, Michael Weiner1,

1Center for Imaging of Neurodegenerative Diseases, San Francisco, CA,

USA; 2Memory Clinic VAMC San Francisco, San Francisco, CA, USA;

3Memory Clinic, California Pacific Medical Center, San Francisco, CA,

USA; 4Memory and Aging Clinic, UCSF, San Francisco, CA, USA.

Contact e-mail: susanne.mueller@ucsf.edu

Background: Histopathological and animal studies suggest that hip-

pocampal subfields are differently affected by aging, AD and other

diseases. High-resolution images at 4T depict details of the internal

structure of the hippocampus allowing for in vivo volumetry of differ-

ent hippocampal subfields. The aims of this study were: 1. To determine

patterns of subfield atrophy in AD and MCI. 2. To determine if subfield

measurements provide advantages over total hippocampal volume for

differentiation between groups. 3. To study the influence of ApoE4 on

subfields in elderly controls and AD. Methods: Seventy-five subjects

(47 cognitively healthy elderly controls (mean age: 68.48.0), 14 MCI

(mean age 75.36.5 and 14 AD (mean age70.48.2) were studied with

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Alzheimer’s Imaging Consortium IC-P3: Poster Presentations