Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI.
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ABSTRACT:
SUBMITTER: Amirbekian V
PROVIDER: S-EPMC1766334 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Diagnosing frontotemporal dementia may be challenging. New methods for analysis of regional brain atrophy patterns on magnetic resonance imaging (MRI) could add to the diagnostic assessment. Therefore, we aimed to develop automated imaging biomarkers for differentiating frontotemporal dementia subtypes from other diagnostic groups, and from one another. METHODS:In this retrospective multicenter cohort study, we included 1213 patients (age 67 ± 9, 48% females) from two memory clinic cohorts: 116 frontotemporal dementia, 341 Alzheimer's disease, 66 Dementia with Lewy bodies, 40 vascular dementia, 104 other dementias, 229 mild cognitive impairment, and 317 subjective cognitive decline. Three MRI atrophy biomarkers were derived from the normalized volumes of automatically segmented cortical regions: 1) the anterior vs. posterior index, 2) the asymmetry index, and 3) the temporal pole left index. We used the following performance metrics: area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. To account for the low prevalence of frontotemporal dementia we pursued a high specificity of 95%. Cross-validation was used in assessing the performance. The generalizability was assessed in an independent cohort (n = 200). RESULTS:The anterior vs. posterior index performed with an AUC of 83% for differentiation of frontotemporal dementia from all other diagnostic groups (Sensitivity = 59%, Specificity = 95%, positive likelihood ratio = 11.8, negative likelihood ratio = 0.4). The asymmetry index showed highest performance for separation of primary progressive aphasia and behavioral variant frontotemporal dementia (AUC = 85%, Sensitivity = 79%, Specificity = 92%, positive likelihood ratio = 9.9, negative likelihood ratio = 0.2), whereas the temporal pole left index was specific for detection of semantic variant primary progressive aphasia (AUC = 85%, Sensitivity = 82%, Specificity = 80%, positive likelihood ratio = 4.1, negative likelihood ratio = 0.2). The validation cohort provided corresponding results for the anterior vs. posterior index and temporal pole left index. CONCLUSION:This study presents three quantitative MRI biomarkers, which could provide additional information to the diagnostic assessment and assist clinicians in diagnosing frontotemporal dementia.
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Project description:The macrophage-rich core of advanced human atheroma has been demonstrated to be hypoxic, which may have implications in plaque stability. The goal of this study was to determine the feasibility of the hypoxia PET imaging agent 64Cu-ATSM to detect hypoxia in a rabbit model of atherosclerosis imaged on a simultaneous PET/MR scanner, using MR for both attenuation correction and depiction of lesion location.New Zealand White rabbits fed a Western diet for 4-6 wk underwent endothelial denudation of the right femoral artery by air desiccation to induce an atherosclerotic-like lesion and underwent a sham operation on the left femoral artery. Four and 8 wk after injury, a 0- to 60-min dynamic whole-body PET/MR examination was performed after injection of approximately 111 MBq of 64Cu-ATSM. After 24 h, a 0- to 75-min dynamic PET/MR examination after injection of approximately 111 MBq of 18F-FDG was performed. The rabbits were euthanized, and the injured femoral artery (IF) and sham-operated femoral artery (SF) were collected for immunohistochemistry assessment of hypoxic macrophages (hypoxia marker pimonidazole, macrophage marker RAM-11, and hypoxia-inducible factor-1 ? subunit [HIF-1?]). Regions of interest of IF, SF, and background muscle (BM) were drawn on fused PET/MR images, and IF-to-BM and SF-to-BM SUV ratios were compared using the Student t test.Elevated uptake of 64Cu-ATSM was found in the rabbits' IF compared with the SF. 64Cu-ATSM imaging demonstrated IF-to-SF SUVmean ratios (±SD) of 1.75 ± 0.21 and 2.30 ± 0.26 at 4 and 8 wk after injury, respectively. 18F-FDG imaging demonstrated IF-to-SF SUVmean ratios of 1.84 ± 0.12 at 8 wk after injury. IF-to-BM SUVmean ratios were significantly higher (P < 0.001) than SF-to-BM SUVmean ratios both 4 and 8 wk after injury for 64Cu-ATSM and 8 wk after injury for 18F-FDG (P < 0.05). Pimonidazole immunohistochemistry at 8 wk colocalized to RAM-11 and HIF-1?.The results show that hypoxia is present in this rabbit model of atherosclerosis and suggest that 64Cu-ATSM PET/MR is a potentially promising method for the detection of hypoxic and potentially vulnerable atherosclerotic plaque in human subjects.
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