Christian Beaulieu1, Leka Sivakumar2, Ken Butcher2, Sarah Treit1, Derek Emery3, and Robert Stobbe1
1Biomedical Engineering, University of Alberta, Edmonton, AB, Canada, 2Neurology, University of Alberta, Edmonton, AB, Canada, 3Radiology, University of Alberta, Edmonton, AB, Canada
Synopsis
Different spatial scales of
micro-structural alteration with disease can be interrogated by varying the
time water has to interact with its surroundings (e.g. membranes, etc).
Oscillating gradient spin echo (OGSE) diffusion MRI enables much shorter
diffusion times (e.g. 6 ms) than typical pulsed gradient spin-echo (PGSE) (e.g.
40 ms). The large diffusion reduction typically observed with PGSE in ischemic
lesions in human stroke was markedly less with OGSE, and the OGSE-PGSE
difference was greatest for radial diffusivity in ischemic white matter. This
result is consistent with the swelling and beading of the axons underlying
diffusion contrast in cerebral ischemia.
Introduction
Diffusion-weighted
imaging of acute stroke is used diagnostically daily, but despite being
discovered 27 years ago there are still uncertainties in the origin of the
reduced mean diffusivity (MD). Different spatial scales of micro-structural
alteration with disease can be interrogated by varying the time water has to
interact with its surroundings (e.g. membranes, etc). Oscillating gradient spin
echo (OGSE) diffusion MRI enables much shorter diffusion times (e.g. 4 ms) than
the typical pulsed gradient spin-echo (PGSE) (e.g. 40 ms). Ischemic brain still
shows reduced diffusion with OGSE, but by not nearly as much as with PGSE in
post-mortem rat1 and mouse hypoxia-ischemia2. The
implementation of OGSE for human MRI is challenging. The only human stroke OGSE
study used a frequency of 50 Hz (i.e. ~ 4 ms diffusion time) and very low b=300
s/mm2 on a 4.7T MRI to show only 8% MD reduction in the white matter
of human stroke, as opposed to the typical 37% MD reduction with PGSE3.
The purpose here was to evaluate OGSE of acute human stroke on a typical 3T MRI.Methods
Both
OGSE and PGSE were acquired with single shot spin-echo EPI on a 3T Siemens
Prisma (Advanced Diffusion WIP) with: 20 3 mm axial slices, 1.7x1.7 mm2
resolution, GRAPPA R=2, TR 5600 ms, TE 78 ms, b=500 s/mm2 (higher
than in reference [3]), 6 directions, 3 averages, and scan time 2:26 min. The
OGSE used trapezoid cosines with 40 Hz (i.e. ~ 6 ms diffusion time, longer than
in reference [3]) while PGSE had a diffusion time of 40 ms. The stroke patient
characteristics were: Patient 1 - 57 year female, right lacunar stroke in white
matter, 0.4 cc lesion volume, scan 55 hours post-onset, NIHSSS 0; Patient 2 - 58
year male, right MCA stroke mostly in gray matter, 9.9 cc lesion volume, scan
19 hours post-onset, NIHSSS 4. DTI was fit with ExploreDTI and custom software
was used for ROI measurements to compare OGSE and PGSE-derived DTI metrics in
well-defined white matter regions either within the lesion or the corresponding
contralateral hemisphere.Results
There
was diminished stroke lesion contrast on the OGSE MD maps relative to the PGSE
MD maps (Figure 1). A very
interesting observation in the larger stroke of Patient 2 was that MD within
the lesion was lower in white matter than gray matter as measured by PGSE, but
this gray/white MD difference was attenuated on OGSE. Thus the effect of
microstructure alteration on diffusion becomes more similar for gray and white
matter when querying small spatial scales of diffusion. Quantitative MD analyses
for both patients are shown in Figure 2.
Relative to the contralateral side, MD was reduced in the lesion to a greater
extent with PGSE than with OGSE {Patient 1 (P1): -22% drop PGSE vs -11% drop
OGSE; Patient 2 (P2): -59% drop PGSE vs -46% drop OGSE}. OGSE yields 8%(P1) and
10%(P2) greater MD than PGSE in contra-lateral white matter (in agreement with
reference [4]), but this increase is much greater in the lesion white matter at
19%(P1) and 31%(P2). OGSE also yields greater radial diffusivity than PGSE in
contra-lateral white matter {12%(P1) and 17%(P2)}, and this increase is greater
than that of axial diffusivity {3%(P1) and 4%(P2)}. Again, OGSE-PGSE differences
are greater in the stroke lesion {radial 23%(P1) and 41%(P2) increase versus
axial 14%(P1) and 24%(P2) increase}.Discussion and Conclusions
The
restrictive effects on water diffusion in an ischemic stroke lesion are less
apparent at the short diffusion times enabled by OGSE. This is consistent with
previous animal models1,2 and the only other human study3.
Relative to reference [3], the current study used a more standard field
strength of 3T (versus 4.7T), and a higher b value of 500 s/mm2 (versus
300 s/mm2) to better measure the DTI metrics, but a lower frequency
of 40 Hz (versus 50 Hz), and a longer diffusion time of 6 ms (versus 4 ms). The
longer diffusion times in this study are consistent with smaller OGSE/PGSE
differences than in reference [3]. Greater radial than axial diffusion increase
in going from 40 ms (PGSE) to 6 ms (OGSE) diffusion time in ischemic white
matter suggests an enlargement of micro-structural space in that dimension. The
results of the previous OGSE/PGSE stroke study at 4.7T suggested diffusion
contrast in stroke was well explained by axonal swelling and beading3.
The result of the current study at 3T with greater b-value also supports this
diffusion contrast theory in acute stroke.
Acknowledgements
Canada Research Chairs, Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research.References
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