Shokufeh Sadaghiani1, William Tackett1, M. Dylan Tisdall2, John A. Detre1, and Sudipto Dolui2
1Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States, 2Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States
Synopsis
Cerebral blood flow (CBF) in periventricular white matter
(PVWM) may provide a mechanistically specific biomarker of cerebral small
vessel disease. We compared the reliability of PVWM CBF obtained from arterial
spin labeling MRI acquired twice separated by a week, using different protocols
involving standard, long labeling duration, single and multiple inflow
saturation (MIS), and level of background suppression (BS), in young healthy
participants. The MIS protocol with 99% BS significantly improved the temporal
signal to noise ratio of the acquisition, with a subtle improvement of
intersession-reliability. Reliability of PVWM CBF was of the same order as
other conventional regions of interest.
Introduction
Cerebral small vessel disease (CSVD) is a leading cause of
cognitive impairment and likely the most prevalent neurological disorder.1 White matter hyperintensities
(WMH) currently provide the most commonly used biomarker of CSVD, but are not
mechanistically specific for SVD.2 The earliest and most common location for
WMHs in CSVD is the periventricular white matter (PVWM) region.3 We recently proposed that cerebral blood flow
(CBF) measured from the periventricular region using arterial spin labeled
(ASL) perfusion MRI may provide a mechanistically specific and predictive
biomarker of CSVD3 and showed its reliability
using concurrently acquired ASL and 15O-positron emission tomography
data acquired on a PET-MRI scanner.4 Here we compared the reliability of ASL-derived
PVWM CBF using different ASL protocols involving different labeling durations,
inflow saturation, and background suppression protocols.5Methods
Healthy
subjects with no history of cerebrovascular disease were recruited at the
University of Pennsylvania (N=23, mean age=34.5±13.8 y, 10 female) and
underwent two scanning sessions separated by one week, both at the same time of
the day. ASL MRI data were acquired on a Siemens 3T scanner, using four
different protocols, all acquired with background-suppressed pseudocontinuous
ASL using a 4-shot and z-accelerated 3D stack-of-spirals readout. The protocols
are listed in Table 1 and differed in labeling duration (LD; 1.8s versus 3s),
slightly different postlabeling delay (PLD; 1.8s versus 2s), inflow saturation
(single versus multiple) and background suppression (90% versus 99%). The
labeling plane was manually placed at an optimal location determined by a
time-of-flight angiography scan. Eight label/control pairs were obtained for
each protocol. The MRI protocol also included a Hadamard encoded multi-PLD
sequence to measure arterial transit time (ATT). The ASL data were processed
using in-house developed pipelines following the recommendation by
the ASL white paper.6 CBF quantification of the
single-PLD data used a single compartment model while multi-PLD data was used
to calculate ATT7 by decoding a
Hadamard-encoded matrix of 7 PLDs. Mean CBF was measured in whole brain (WB),
gray matter (GM), white matter (WM), and a previously defined PVWM region of
interest (ROI).3 Relative CBF in the PVWM ROI
was also obtained by normalization with WB CBF.
The reliability of the PVWM measurements
obtained a week apart using the different protocols were assessed using within
subject coefficient of variation (wsCV) and were compared using a bootstrapping
method. We also computed and compared the temporal signal to noise ratio (tSNR)
in the PVWM region for each protocol. The tSNR was obtained by measuring the
mean CBF in each ROI in each CBF volume of the time series and computing the
ratio of the mean and the standard deviation of the values. Results
Table 2 shows the ASL-derived CBF and tSNR values in the
different ROIs. Consistent CBF values were observed across the protocols. TSNR
was significantly different between the protocols with MIS using 99% BS having
highest tSNR and LD=3 with SIS-90% BS protocol having the lowest tSNR.
The wsCV values for the different ASL protocols in the
different ROIs are listed in Table 3. The MIS protocol with 99% BS had lowest
wsCV on average though there was no significant difference between wsCV values
of the different protocols. When compared across ROIs, the wsCV values of the
PVWM region was significantly higher than the other ROIs for all the ASL
protocols, though they are all of the same order. Repeatability for relative
PVWM CBF was significantly better (p<0.005) than absolute measures.
Finally, ATT of the GM, WM and PVWM regions as
assessed by the Hadamard encoded sequence was found to be 1385±179, 1522±199
and 1664±201 ms, respectively.Discussion
ATT
in PVWM was in agreement with recent reports8 confirming that periventricular ATT is not
dramatically longer than in WM more generally, and supporting the notion that
PVWM CBF can be quantified using ASL MRI using standard PLD. WsCV values were comparable across all
regions, albeit slightly higher for the smaller PVWM ROI. However, wsCV for
relative CBF in the PVWM ROI was considerably improved, suggesting that global
effects such as differences in labeling efficiency underlie much of the
variance in repeated measures. Significantly higher tSNR was observed for the
longer LD/PLD data with MIS and 99% BS, but its improved tSNR did not
significantly reduce wsCV suggesting that SNR was not limiting for any of the
acquisitions and that similar repeatability can be obtained with fewer averages
using this sequence.Conclusion
CBF can be reliably measured in the periventricular region
using background suppressed 3D ASL using both standard and long labeling
duration and standard PLD values in young healthy subjects. In older subjects or patients with SVD,
longer LD and longer PLD values may be more advantageous than the results of
this study suggest.Acknowledgements
Research
reported in this abstract was supported by the National Institutes of Health
under award numbers R01 NS111115 and R03 AG063213.References
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