Spatial coefficient of variation of arterial spin labeling MRI as a cerebrovascular correlate of carotid occlusive disease

Clinical interpretation of arterial spin labeling (ASL) perfusion MRI in cerebrovascular disease remains challenging mainly because of the method’s sensitivity to concomitant contributions from both intravascular and tissue compartments. While acquisition of multi-delay images can differentiate between the two contributions, the prolonged acquisition is prone to artifacts and not practical for clinical applications. Here, the utility of the spatial coefficient of variation (sCoV) of a single-delay ASL image as a marker of the intravascular contribution was evaluated by testing the hypothesis that sCoV can detect the effects of differences in label arrival times between ipsi- and contra-lateral hemispheres even in the absence of a hemispheric difference in CBF. Hemispheric lateralization values for sCoV and CBF were computed from ASL images acquired on 28 patients (age 73.9 ± 10.2 years, 8 women) with asymptomatic unilateral carotid occlusion. The results showed that sCoV lateralization predicted the occluded side with 96.4% sensitivity, missing only 1 patient. In contrast, the sensitivity of the CBF lateralization was 71.4%, with 8 patients showing no difference in CBF between hemispheres. The findings demonstrate the potential clinical utility of sCoV as a cerebrovascular correlate of large vessel disease. Using sCoV in tandem with CBF, vascular information can be obtained in image processing without the need for additional scan-time

Late-life brain perfusion after prenatal famine exposure

Early nutritional deprivation may cause irreversible damage to the brain and seems to affect cognitive function in older age. We investigated whether prenatal undernutrition was associated with brain perfusion differences in older age. We acquired Arterial spin labeling scans in 118 Dutch famine birth cohort members. Using linear regression analyses, cerebral blood flow was compared between exposed and unexposed groups in gray matter (GM) and white matter (WM), perfusion territories, the neurodegeneration-related regions anterior and posterior cingulate cortex and precuneus. Furthermore, we compared the GM/WM ratio and the spatial coefficient of variation as a proxy of overall cerebrovascular health. The WM arterial spin labeling signal and the GM/WM ratio were significantly lower and higher, respectively, among exposed participants (−2.5 mL/100 g/min [95% CI: −4.3 to −0.8; p = 0.01] and 0.48 [0.19 to 0.76; p = 0.002], respectively). Exposed men had lower cerebral blood flow in anterior and posterior cingulate cortices (−8.0 mL/100 g/min [−15.1 to −0.9; p = 0.03]; −11.4 mL/100 g/min [−19.6 to −3.2; p = 0.02]) and higher spatial coefficient of variation (0.05 [0.00 to 0.09; p = 0.05]). The latter seemed largely mediated by higher 2h-glucose levels at age 50. Our findings suggest that prenatal undernutrition affects brain perfusion parameters providing further evidence for life-long effects of undernutrition during early brain development

The association between frailty and MRI features of cerebral small vessel disease

Abstract: Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype

CEREBRAL PERFUSION AS AN IMAGING BIOMARKER OF PRESYMPTOMATIC GENETIC FRONTOTEMPORAL DEMENTIA:PRELIMINARY RESULTS FROM THE GENETIC FRONTOTEMPORAL DEMENTIA INITIATIVE (GENFI)

Background Frontotemporal dementia (FTD) is a common cause of early onset dementia. While three genetic mutations are responsible for the majority of genetic FTD, imaging biomarkers that predict symptom onset are needed1. Recent work shows volumetric changes several years before the predicted age at disease onset2. Herein, we extend on this work by investigating whether perfusion patterns derived from non-invasive arterial spin labeling (ASL) MRI can be used as an early functional neuroimaging biomarker of presymptomatic genetic FTD. Methods Data were drawn from the GENetic Frontotemporal dementia Initiative (GENFI)2. From the first GENFI data freeze (n=220), 168 subjects had 3T ASL from which this analysis considers only the presymptomatic carriers and controls (n=144, Table 1). Cerebral blood flow (CBF)-maps were scaled to a mean grey matter (GM) CBF of 50 mL/100g/min per ASL sequence (four different ASL sequences were used) and registered to SPM12 3D T1 GM segmentations that were registered to MNI using DARTEL. In pre-selected ROIs associated with FTD, we investigated the effects of mutation status and years to expected age of disease onset on CBF, accounting for gender and family membership as fixed and random covariates. ROI CBF-values were corrected for partial volume fractions. Results Years to expected age of disease onset (p0.1), there was an interaction effect between mutation carrier status and years to expected age of disease onset on CBF (Table 2). This interaction effect was significant for all ROIs except for the parietal and occipital cortices, anterior cingulate and putamen with the strongest effects being seen in the insula and the caudate nucleus (Figure 1). Conclusions CBF decreased as individuals approached the expected age of disease onset and this CBF decrease was accelerated in the presymptomatic mutation carriers compared to controls, in key regions implicated in FTD. These preliminary findings demonstrate the potential utility of non-invasive perfusion MRI as an early biomarker for genetic FTD. References 1. Montine et al., Neurology 2014 2. Rohrer et al., Lancet Neurol 201

Effects of systematic partial volume errors on the estimation of gray matter cerebral blood flow with arterial spin labeling MRI

Objective: Partial volume (PV) correction is an important step in arterial spin labeling (ASL) MRI that is used to separate perfusion from structural effects when computing the mean gray matter (GM) perfusion. There are three main methods for performing this correction: (1) GM-threshold, which includes only voxels with GM volume above a preset threshold; (2) GM-weighted, which uses voxel-wise GM contribution combined with thresholding; and (3) PVC, which applies a spatial linear regression algorithm to estimate the flow contribution of each tissue at a given voxel. In all cases, GM volume is obtained using PV maps extracted from the segmentation of the T1-weighted (T1w) image. As such, PV maps contain errors due to the difference in readout type and spatial resolution between ASL and T1w images. Here, we estimated these errors and evaluated their effect on the performance of each PV correction method in computing GM cerebral blood flow (CBF). Materials and methods: Twenty-two volunteers underwent scanning using 2D echo planar imaging (EPI) and 3D spiral ASL. For each PV correction method, GM CBF was computed using PV maps simulated to contain estimated errors due to spatial resolution mismatch and geometric distortions which are caused by the mismatch in readout between ASL and T1w images. Results were analyzed to assess the effect of each error on the estimation of GM CBF from ASL data. Results: Geometric distortion had the largest effect on the 2D EPI data, whereas the 3D spiral was most affected by the resolution mismatch. The PVC method outperformed the GM-threshold even in the presence of combined errors from resolution mismatch and geometric distortions. The quantitative advantage of PVC was 16% without and 10% with the combined errors for both 2D and 3D ASL. Consistent with theoretical expectations, for error-free PV maps, the PVC method extracted the true GM CBF. In contrast, GM-weighted overestimated GM CBF by 5%, while GM-threshold underestimated it by 16%. The presence of PV map errors decreased the calculated GM CBF for all methods. Conclusion: The quality of PV maps presents no argument for the preferential use of the GM-threshold method over PVC in the clinical application of ASL

The effects of intracranial stenosis on cerebral perfusion and cognitive performance

Background: Intracranial stenosis (ICS) may contribute to cognitive dysfunction by decreased cerebral blood flow (CBF) which can be measured quantitatively by arterial spin labelling (ASL). Interpretation of CBF measurements with ASL, however, becomes difficult in patients with vascular disease due to prolonged arterial transit time (ATT). Recently, spatial coefficient of variation (sCoV) of ASL signal has been proposed that approximates ATT and utilized as a proxy marker for assessment of hemodynamic status of cerebral circulation. Objective: We investigate the association of ICS with CBF and sCoV parameters and its eventual effects on cognition in a memory clinic population. Methods: We included 381 patients (mean age = 72.3 ± 7.9 years, women = 53.7%) who underwent 3T MRI and detailed neuropsychological assessment. ICS was defined as ≥ 50% stenosis in any intracranial vessel on 3D Time-of-Flight MR Angiography. Gray matter sCoV and CBF were obtained from 2D EPI pseudo-continuous ASL images. Results: ICS was present in 58 (15.2%) patients. Patients with ICS had higher gray matter sCoV and lower CBF. The association with sCoV remained statistically significant after correction for cardiovascular risk factors. Moreover, ICS was associated with worse performance on visuoconstruction, which attenuated with higher sCoV. Mediation analysis showed that there was an indirect effect of ICS on visuoconstruction via sCoV. Conclusion: These findings suggest that compromised CBF as detected by higher sCoV is related to cognitive impairment among individuals diagnosed with ICS. We also showed that sCoV partially mediates the link between ICS and cognition. Therefore, sCoV may provide valuable hemodynamic information in patients with vascular disease

Comparison of velocity- and acceleration-selective arterial spin labeling with [15O]H2O positron emission tomography

In the last decade spatially nonselective arterial spin labeling (SNS-ASL) methods such as velocity-selective ASL (VS-ASL) and acceleration-selective ASL have been introduced, which label spins based on their flow velocity or acceleration rather than spatial localization. Since labeling also occurs within the imaging plane, these methods suffer less from transit delay effects than traditional ASL methods. However, there is a need for validation of these techniques. In this study, a comparison was made between these SNS-ASL techniques with [(15)O]H2O positron emission tomography (PET), which is regarded as gold standard to measure quantitatively cerebral blood flow (CBF) in humans. In addition, the question of whether these techniques suffered from sensitivity to arterial cerebral blood volume (aCBV), as opposed to producing pure CBF contrast, was investigated. The results show high voxelwise intracranial correlation (0.72 to 0.89) between the spatial distribution of the perfusion signal from the SNS-ASL methods and the PET CBF maps. A similar gray matter (GM) CBF was measured by dual VS-ASL compared with PET (46.7 ± 4.1 versus 47.1 ± 6.5 mL/100 g/min, respectively). Finally, only minor contribution of aCBV patterns in GM to all SNS-ASL methods was found compared with pseudo-continuous ASL. In conclusion, VS-ASL provides a similar quantitative CBF, and all SNS-ASL methods provide qualitatively similar CBF maps as [(15)O]H2O PE