Multivariate and Univariate Analysis of Continuous Arterial Spin Labeling Perfusion MRI in Alzheimer's Disease

Abstract

Continuous arterial spin labeling (CASL) magnetic resonance imaging (MRI) was combined with multivariate analysis for detection of an Alzheimer's disease (AD)-related cerebral blood flow (CBF) covariance pattern. Whole-brain resting CBF maps were obtained using spin echo, echo planar imaging (SE-EPI) CASL in patients with mild AD (n = 12, age = 70.7 ± 8.7 years, 7 males, modified Mini-Mental State Examination (mMMS) = 38.7/57 ± 11.1) and age-matched healthy controls (HC) (n = 20; age = 72.1 ± 6.5 years, 8 males). A covariance pattern for which the mean expression was significantly higher (P < 0.0005) in AD than in HC was identified containing posterior cingulate, superior temporal, parahippocampal, and fusiform gyri, as well as thalamus, insula, and hippocampus. The results from this analysis were supplemented with those from the more standard, region of interest (ROI) and voxelwise, univariate techniques. All ROIs (17/hemisphere) showed significant decrease in CBF in AD (P < 0.001 for all ROIs, a corrected = 0.05). The area under the ROC curve for discriminating AD versus HC was 0.97 and 0.94 for covariance pattern and gray matter ROI, respectively. Fewer areas of depressed CBF in AD were detected using voxelwise analysis (corrected, P < 0.05). These areas were superior temporal, cingulate, middle temporal, fusiform gyri, as well as inferior parietal lobule and precuneus. When tested on extensive split-half analysis to map out the replicability of both multivariate and univariate approaches, the expression of the pattern from multivariate analysis was superior to that of the univariate.

Pathophysiology of Hypoperfusion of the Precuneus in Early Alzheimer's Disease

“…The present findings indicate that these changes are not simply late‐stage manifestations of AD but are demonstrable even in early AD (ie, in Braak stage III–IV disease) in the precuneus, a region that is amongst the first affected by hypoperfusion 2, 6, 7, 13, 28, 30, 53. Indeed, the MAG:PLP1 ratio, an indicator of the adequacy of ante‐mortem tissue oxygenation, was lower in early than late AD (Braak stage V–VI) when the reduction was less pronounced, possibly reflecting falling oxygen demand, for example, as a result of reduced synaptic activity.…”

“…Blood flow and glucose utilization decline in the precuneus at a very early stage of Alzheimer's disease (AD) 2, 6, 7, 13, 28, 30, 53. Reduction in cerebral blood flow precedes the development of dementia in AD 52 and occurs well before any behavioral or pathological abnormalities in animal models of the disease 24, 39.…”

Arterial spin labelling at 3-T MR imaging for detection of individuals with Alzheimer’s disease

“…The pattern of hypoperfusion revealed in our study is consistent with the patterns found in the previous ASL and PET studies, although hypoperfusion in the lateral parietal lobe did not show up. A very recent report by Asllani et al [22] showed that ASL at 1.5-T MR imaging combined with multivariate analysis can differentiate 12 AD patients from 20 healthy control subjects at a high AUC value in ROC analysis. Our result was consistent with theirs, although we used only univariate analysis.…”

Clinical Application of 3D Arterial Spin-Labeled Brain Perfusion Imaging for Alzheimer Disease: Comparison with Brain Perfusion SPECT

“…13 Although many recent ASL perfusion studies were performed on 3T MR imaging, it has been shown in other studies that ASL with 1.5T MR imaging could detect regional hypoperfusion, mainly in the temporoparietal association cortex and the posterior cingulate gyrus. 8,10,25 Another study suggested that CBF mapping by ASL may perform better than MR morphologic analysis by using voxel-based morphometry in discriminating patients with AD from healthy control subjects and that the combination of the 2 methods was more effective than either method alone. 26 This result may support our proposal for the combination of structural MR imaging and ASL MR perfusion imaging.…”