Henk Mutsaerts1, Lena Vaclavu2, Jan-Willem van Dalen2, Andrew Robertson1, Paul Groot2, Mario Masellis1, Edo Richard2, Aart J Nederveen2, and Bradley MacIntosh1
1Sunnybrook Research Institute, Toronto, ON, Canada, 2Academic Medical Center, Amsterdam, Netherlands
Synopsis
In
this work, we propose a novel method to infer an ATT estimate from the spatial
signal distribution of single-time point ASL CBF maps, using a spatial
Coefficient of Variation (CoV). In a large population of elderly with
hypertension, we compare crushed (C CBF) and non-crushed CBF maps (NC CBF),
from which we derive C CoV and NC CoV, and the FEAST-based ATT estimate. These
explorative results show that both ATT and BMI are associated with NC CoV but
not with NC CBF, suggesting that ATT ‒ as estimated by the
spatial CoV ‒ might serve as a global biomarker of cerebrovascular disease.Purpose
Arterial transit time (ATT) reflects
the time taken for the arterial spin labeling (ASL) tracer to travel from the
labeling plane to an imaging voxel. This parameter reflects the hemodynamic status
of the cerebral vasculature and has added value to conventional cerebral blood
flow (CBF) measurements in ASL
1-3. One approach to measure ATT with ASL
4, 5 is Flow Encoding Arterial Spin Tagging (FEAST)
6, 7. Here, we investigate associations between various ASL and FEAST-based
metrics in a large sample of elderly with hypertension. It has previously been shown
that spatial coupling of high macro-vascular signal and low tissue signal in a
single-PLD CBF image is an indication of prolonged ATT, which is problematic
for CBF quantification but nonetheless carries clinical information reflecting
cerebrovascular attributes
2. We hypothesize that macro-vascular contamination of CBF will
contribute to an increased spatial Coefficient of Variation (CoV) of a single
mean CBF map ‒ not to be confused with temporal signal fluctuations. E.g., if
the ASL tracer has not arrived in the tissue, the CBF signal intensity
difference between vascular and tissue regions will be high, whereas if the ASL
tracer has arrived in the tissue then the CBF signal intensity will be spatially
homogeneous (Figure 1). The aims of the current study were to 1) relate the
spatial CoV with other ASL-derived metrics and 2) explore potential
associations with vascular risk factors.
Methods
194 community-dwelling elderly (46% male, aged 77.4 yrs (SD 2.5)) were selected
from the Prevention of Dementia by Intensive VAscular care (PreDIVA) study
8. Two consecutive GE-EPI background suppressed pseudo-continuous ASL
scans, with and without vascular crushing (Venc, 5 cm/s; b, 0.6 s/mm2) were
acquired ‒ labeling duration = 1650 ms, PLD = 1525-2080 ms and NSA = 20 for
each scan. ATT maps were calculated using the FEAST equation, with the ratio
between crushed (C CBF) and non-crushed CBF (NC CBF) as input
6, 7. C CBF and NC CBF were quantified with a single compartment model
9. 3D-T1 scans were segmented and non-linearly registered to MNI space
using SPM12 and DARTEL; the same transformations were applied to the CBF maps
6. The spatial CoV was calculated as SD CBF/mean CBF spatially across all
GM voxels for an individual subjects CBF map. Linear regression analyses were
performed to explore associations between the various ASL metrics and vascular
risk factors age, gender and body mass index (BMI).
Results
Visually, the CoV was related to the heterogeneity in the CBF and ATT
maps. Note the relative homogeneity of the mean NC CBF maps for the 10 subjects
with the lowest GM CoV (Figure 1a) compared to the heterogeneous and angiographic-like
appearance of the mean NC CBF maps for the 10 subjects with the highest GM CoV
(Figure 1b). Although this difference is still visible, it is less pronounced
for C CBF. The size of the cortices and space between the cortices on Figure 1 suggest
that subjects with high CoV have less GM mass than subjects with low CoV (Figure
1b vs. 1a, 3rd row). Figure 2 displays scatter plots and correlation values
between the ASL-based measures, which all corresponded to p<0.0001, except for the correlation between ATT and NC CBF (p=0.3). ATT was associated with gender (men
having longer ATT, t=-6.2, p<0.001),
NC CoV (t=2.4, p=0.019) and C CBF
(t=-3.0, p=0.004) but not with age
nor with NC CBF (p>0.9). Furthermore,
BMI was associated with ATT (t=-2.2, p=0.026)
and NC CoV (t=3.1, p=0.002) but
surprisingly it was not associated with C CBF nor NC CBF in this sample (p>0.7).
Discussion
Our results show that ATT increases linearly in
relation to the non-crushed CBF CoV estimate, representing a “free-lunch”
method to assess ATT effects on CBF images. Furthermore, our results suggest
that the signal variability between macro- and micro-vascular components in the
NC CBF scans are related to ATT, which are minimized by crushing. These results
show the potential of the spatial CoV in studies where ATT is not acquired. An
advantage of the spatial CoV in elderly could be its relative insensitivity to the
signal-to-noise ratio of tissue perfusion, if macro-vascular signal is still suspected
despite optimized ASL acquisition parameters. This could explain the stronger
association with BMI that we observed for spatial CoV compared to ATT, as well
as the normal histogram shape of CoV compared to the skewed appearance of the
ATT histogram. Therefore, our data suggest that ATT ‒ as estimated by the
spatial CoV ‒ might serve as a global ASL-based biomarker of cerebrovascular
disease, with relevance to vascular dementia.
Acknowledgements
This study was carried out within the context of the preDIVA study which was supported by the Dutch Ministry of Health, Welfare and Sports, the Dutch Innovation fund of collaborative health insurances and the Netherlands Organization for Health Research and Development. The MRI substudy was supported by the 'Internationale Stichting Alzheimer Onderzoek’ and the MRI data analyses by the Canadian Partnership for Stroke Recovery. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The authors are grateful to I Stijnman and C Miedema for logistics and planning and to AM van den Berg and RD Snoeks for data acquisition.References
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