Lin, L., Chen, K., Valla, J., Jiping, H. e., Reiman, E. M., Galons, J., Hauss-Wegrzyniak, B., & Alexander, G. E. (2005). MRI template and atlas toolbox for the C57BL/6J mouse brain. 2nd International IEEE EMBS Conference on Neural Engineering, 2005, 6-8.
Abstract:
In order to compare brain-imaging measurements from different subjects, brain-mapping algorithms are commonly used to register individual brain onto a standardized brain atlas. In this study, SPM99 was used to linearly and nonlinearly coregister a spatially standardized T2-weighted template of C57BL/6J to the atlas by Paxinos and Franklin (2001), local accuracy of between atlas and template was evaluated, and a toolbox was developed. This study provides a foundation for the region of interest analysis for mouse brain images. © 2005 IEEE.
Alexander, G. E., Greenwood, P. M., Parasuraman, R., Mentis, M. J., Furey, M. L., Desmond, R. E., Szczepanik, J., Levine, B., Pietrini, P., Schapiro, M. B., & Rapoport, S. I. (1998). Functional brain response in right prefrontal cortex with increasing distraction during visual selective attention. NeuroImage, 7(4 PART II), S77.
Reiman, E. M., Chen, K., Langbaum, J. B., Lee, W., Reschke, C., Bandy, D., Alexander, G. E., & Caselli, R. J. (2010). Higher serum total cholesterol levels in late middle age are associated with glucose hypometabolism in brain regions affected by Alzheimer's disease and normal aging. NeuroImage, 49(1), 169-176.
PMID: 19631758;PMCID: PMC2888804;Abstract:
Epidemiological studies suggest that higher midlife serum total cholesterol levels are associated with an increased risk of Alzheimer's disease (AD). Using fluorodeoxyglucose positron emission tomography (PET) in the study of cognitively normal late middle-aged people, we demonstrated an association between apolipoprotein E (APOE) e{open}4 gene dose, the major genetic risk factor for late-onset AD, and lower measurements of the cerebral metabolic rate for glucose (CMRgl) in AD-affected brain regions, we proposed using PET as a pre-symptomatic endophenotype to evaluate other putative AD risk modifiers, and we then used it to support an aggregate cholesterol-related genetic risk score in the risk of AD. In the present study, we used PET to investigate the association between serum total cholesterol levels and cerebral metabolic rate for glucose metabolism (CMRgl) in 117 cognitively normal late middle-aged APOE e{open}4 homozygotes, heterozygotes and non-carriers. Higher serum total cholesterol levels were associated with lower CMRgl bilaterally in precuneus, parietotemporal and prefrontal regions previously found to be preferentially affected by AD, and in additional frontal regions previously found to be preferentially affected by normal aging. The associations were greater in APOE e{open}4 carriers than non-carriers in some of the AD-affected brain regions. We postulate that higher midlife serum total cholesterol levels accelerate brain processes associated with normal aging and conspire with other risk factors in the predisposition to AD. We propose using PET in proof-of-concept randomized controlled trials to rapidly evaluate the effects of midlife cholesterol-lowering treatments on the brain changes associated with normal aging and AD. © 2009 Elsevier Inc. All rights reserved.
Huang, W., Alexander, G. E., Chang, L., Shetty, H. U., Krasuski, J. S., Rapoport, S. I., & Schapiro, M. B. (2001). Brain metabolite concentration and dementia severity in Alzheimer's disease: A 1H MRS study. Neurology, 57(4), 626-632.
PMID: 11524470;Abstract:
Objective: 1H-MRS studies have shown abnormalities in brain levels of myo-inositol (mI) and N-acetyl aspartate (NAA) in AD, but the relation of these abnormalities with dementia severity was not examined. The authors sought to determine whether altered brain levels of mI and other metabolites occur in mild AD and whether they change as dementia severity worsens. Methods: The authors used 1H-MRS with external standards to measure absolute brain concentrations of mI, NAA, total creatine (Cr), and choline (Cho)-containing compounds in 21 subjects with AD and 17 age- and sex-matched controls in occipital and left and right parietal regions. Results: Concentrations of NAA were significantly decreased, whereas mI and Cr concentrations were significantly increased in all three brain regions in subjects with AD compared with controls. Higher concentrations of mI and Cr occurred even in mild AD. A discriminant analysis of the 1H-MRS data combined with CSF volume measurements distinguished subjects with AD, ranging from mild to severe dementia, from controls with 100% correct classification. NAA concentration, though not other metabolites, was positively correlated with Mini-Mental State Examination score. Conclusion: The measurements with 1H-MRS of absolute metabolite concentrations in the neocortex showed abnormal concentrations of brain metabolites in AD; these metabolite concentrations do not necessarily correlate with disease severity. Although changes in myo-inositol and creatine occur in the early stages of AD, abnormalities of N-acetyl aspartate do not occur in mild AD but progressively change with dementia severity. Further, subjects with mild AD can be differentiated from controls with 1H-MRS.
Smith, J. F., Chen, K., Johnson, S., Morrone-Strupinsky, J., Reiman, E. M., Nelson, A., Moeller, J. R., & Alexandera, G. E. (2006). Network analysis of single-subject fMRI during a finger opposition task. NeuroImage, 32(1), 325-332.
PMID: 16733091;Abstract:
The analysis of functional magnetic resonance imaging (fMRI) data has typically relied on univariate methods to identify areas of brain activity related to cognitive and behavioral task performance. We investigated the ability of multivariate network analysis using a modified form of principal component analysis, the Scaled Subprofile Model (SSM), applied to single-subject fMRI data to identify patterns of interactions among brain regions over time during an anatomically well-characterized simple motor task. We hypothesized that each subject would exhibit correlated patterns of brain activation in several regions known to participate in the regulation of movement including the contralateral motor cortex and the ipsilateral cerebellum. EPI BOLD images were acquired in six healthy participants as they performed a visually and auditorally paced finger opposition task. SSM analysis was applied to the fMR time series on a single-subject basis. Linear combinations of the major principal components that predicted the expected hemodynamic response to the order of experimental conditions were identified for each participant. These combinations of SSM patterns were highly associated with the expected hemodynamic response, an indicator of local neuronal activity, in each participant (0.84 ≤ R2 ≤ 0.97, all P's 0.0001). As predicted, the combined pattern in each subject was characterized most prominently by relatively increased activations in contralateral sensorimotor cortex and ipsilateral cerebellum. Additionally, all subjects showed areas of relatively decreased activation in the ipsilateral sensorimotor cortex and contralateral cerebellum. The application of network analysis methods, such as SSM, to singlesubject fMRI data can identify patterns of task-specific, functionally interacting brain areas in individual subjects. This approach may helpidentify individual differences in the task-related functional connectivity, track changes in task-related patterns of activity within or between fMRI sessions, and provide a method to identify individual differences in response to treatment.
