Automated VOI Analysis in FDDNP PET Using Structural Warping: Validation through Classification of Alzheimer's Disease Patients

We evaluate an automated approach to the cortical surface mapping (CSM) method of VOI analysis in PET. Although CSM has been previously shown to be successful, the process can be long and tedious. Here, we present an approach that removes these difficulties through the use of 3D image warping to a common space. We test this automated method using studies of FDDNP PET in Alzheimer's disease and mild cognitive impairment. For each subject, VOIs were created, through CSM, to extract regional PET data. After warping to the common space, a single set of CSM-generated VOIs was used to extract PET data from all subjects. The data extracted using a single set of VOIs outperformed the manual approach in classifying AD patients from MCIs and controls. This suggests that this automated method can remove variance in measurements of PET data and can facilitate accurate, high-throughput image analysis

Plasma NfL is associated with the APOE ε4 allele, brain imaging measurements of neurodegeneration, and lower recall memory scores in cognitively unimpaired late-middle-aged and older adults

BACKGROUND: Plasma neurofilament light (NfL) is an indicator of neurodegeneration and/or neuroaxonal injury in persons with Alzheimer's disease (AD) and a wide range of other neurological disorders. Here, we characterized and compared plasma NfL concentrations in cognitively unimpaired (CU) late-middle-aged and older adults with two, one, or no copies of the APOE ε4 allele, the major genetic risk factor for AD. We then assessed plasma NfL associations with brain imaging measurements of AD-related neurodegeneration (hippocampal atrophy and a hypometabolic convergence index [HCI]), brain imaging measurements of amyloid-β plaque burden, tau tangle burden and white matter hyperintensity volume (WMHV), and delayed and total recall memory scores. METHODS: Plasma NfL concentrations were measured in 543 CU 69 ± 9 year-old participants in the Arizona APOE Cohort Study, including 66 APOE ε4 homozygotes (HM), 165 heterozygotes (HT), and 312 non-carriers (NC). Robust regression models were used to characterize plasma NfL associations with APOE ε4 allelic dose before and after adjustment for age, sex, and education. They were also used to characterize plasma NfL associations with MRI-based hippocampal volume and WMHV measurements, an FDG PET-based HCI, mean cortical PiB PET measurements of amyloid-β plaque burden and meta-region-of-interest (meta-ROI) flortaucipir PET measurements of tau tangle burden, and Auditory Verbal Learning Test (AVLT) Delayed and Total Recall Memory scores. RESULTS: After the adjustments noted above, plasma NfL levels were significantly greater in APOE ε4 homozygotes and heterozygotes than non-carriers and significantly associated with smaller hippocampal volumes (r =  - 0.43), greater tangle burden in the entorhinal cortex and inferior temporal lobes (r = 0.49, r = 0.52, respectively), and lower delayed (r =  - 0.27), and total (r =  - 0.27) recall memory scores (p < 0.001). NfL levels were not significantly associated with PET measurements of amyloid-β plaque or total tangle burden. CONCLUSIONS: Plasma NfL concentrations are associated with the APOE ε4 allele, brain imaging biomarkers of neurodegeneration, and less good recall memory in CU late-middle-aged and older adults, supporting its value as an indicator of neurodegeneration in the preclinical study of AD

Brain Warping Via Landmark Points and Curves with a Level Set Representation

Abstract. This paper presents and validates a non-linear image registration method driven by points and curved landmarks using implicit representation. This approach produces smooth one-to-one mappings between topologically equivalent images by constraining the transformations to adhere to continuum mechanical laws. In this paper, the elastic operator is used for fast computation when only small deformation is needed. For large deformation, the same strategy is coupled with the method of infinite dimensional group actions to generate highly non-linear diffeomorphic maps. We applied this method to register brain magnetic resonance images in a flattened parameter space, and visualize sulcal variability by pulling back the mapping to 3D. Results show accurate registration of MRI images using delineated sulcal landmarks, while relaxing the registration field along the sulcal lines. I

IC‐P‐155: Association between the Alzheimer’s disease‐related hypometabolic convergence index and clinical ratings in cognitively normal older adults with and without significant fibrillar amyloid burden: Findings from the Alzheimer’s Disease Neuroimaging Initiative

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152779/1/alzjjalz201305152.pd

O4–08–01: Association between the Alzheimer’s disease–related hypometabolic convergence index and clinical ratings in cognitively normal older adults with and without significant fibrillar amyloid burden: Findings from the Alzheimer’s Disease Neuroimaging Initiative

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153281/1/alzjjalz201304377.pd

P3–111: The pattern of cerebral hypometabolism and its association with clinical ratings in cognitively normal older adults with and without significant fibrillar amyloid burden: Findings from the Alzheimer’s Disease Neuroimaging Initiative

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152964/1/alzjjalz2013051182.pd

Molecular imaging of the association between serotonin degeneration and beta-amyloid deposition in mild cognitive impairment

Background: Degeneration of the serotonin system has been observed in Alzheimer’s disease (AD) and in mild cognitive impairment (MCI). In transgenic amyloid mouse models, serotonin degeneration is detected prior to widespread cortical beta-amyloid (Aβ) deposition, also suggesting that serotonin degeneration may be observed in preclinical AD. Methods: The differences in the distribution of serotonin degeneration (reflected by the loss of the serotonin transporter, 5-HTT) relative to Aβ deposition was measured with positron emission tomography in a group of individuals with MCI and a group of healthy older adults. A multi-modal partial least squares (mmPLS) algorithm was applied to identify the spatial covariance pattern between 5-HTT availability and Aβ deposition. Results: Forty-five individuals with MCI and 35 healthy older adults were studied, 22 and 27 of whom were included in the analyses who were “amyloid positive” and “amyloid negative”, respectively. A pattern of lower cortical, subcortical and limbic 5-HTT availability and higher cortical Aβ deposition distinguished the MCI from the healthy older control participants. Greater expression of this pattern was correlated with greater deficits in memory and executive function in the MCI group, not in the control group. Conclusion: A spatial covariance pattern of lower 5-HTT availability and Aβ deposition was observed to a greater extent in an MCI group relative to a control group and was associated with cognitive impairment in the MCI group. The results support the application of mmPLS to understand the neurochemical changes associated with Aβ deposition in the course of preclinical AD

P2‐217: Capitalizing on complementary FDG PET and florbetapir PET data sets to distinguish between early and late mild cognitive impairment using multi‐modal partial least squares

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152928/1/alzjjalz201205924.pd