Björn Lampinen1, Jimmy Lätt2, Johan Wasselius3, Danielle van Westen4, and Markus Nilsson4
1Medical Radiation Physics, Lund University, Lund, Sweden, 2Center for Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden, 3Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden, 4Clinical Sciences Lund, Diagnostic Radiology, Lund University, Lund, Sweden
Synopsis
Many patients with ischemic stroke that would
benefit from ‘late’ recanalization go untreated, as current imaging-based predictions
of outcome are insufficiently individualized. This study investigated whether diffusion
MRI (dMRI), a standard tool in stroke diagnostics, provides additional information
through effects of diffusion time dependence. Results showed elevated rates of water
exchange within lesions of subacute stroke patients. The absence of such
exchange appeared predictive of tissue viability in the
chronic stage, even in regions normally considered irreversibly injured. Information
on diffusion time dependence may thus improve penumbra definitions and help identifying
subjects with favorable outcome of late recanalization.
Introduction
Advances in recanalization therapy have enabled
effective treatment of ischemic stroke for patients presenting before 4–5 hours1 and may benefit some patients up until 16–24
hours.2,3 Most patients that
would respond to such ‘late’ recanalization go untreated, however, because predicting
whether treatment will be beneficial or detrimental is challenging in
individual cases. The outcome of late recanalization depends on the extent of remaining
salvageable tissue (penumbra) versus the extent of already infarcted tissue risking
hemorrhage (core).4 Standard
estimates of these quantities using CT-perfusion and diffusion MRI (dMRI) have
low accuracy,5 but the
diagnostic potential of dMRI may be enhanced by going beyond conventional
mapping of the apparent diffusion coefficient (ADC). In
particular, ischemic stroke is associated with diffusion time dependence,6,7 which is rare in both healthy and
diseased brain, that may reflect neurite beading or increased permeability.
This study explored whether such time dependence may inform on tissue viability
by examining subacute stroke patients longitudinally using dMRI with multiple
diffusion times. Results revealed a heterogenous pattern of elevated water exchange rates within lesions that was related
to the viability of tissue in the chronic stage.Methods
Five non-recanalized patients with ischemic stroke were scanned
on an Achieva 3T system (Philips, Best, the Netherlands) at approximately two, nine and ninety days
after symptom onset. dMRI data were acquired with a diffusion-weighted spin-echo sequence using two
different diffusion
times, TD = 30 ms and TD = 60 ms, for δ/TE/TR = 21/105/2000 ms/ms/ms, 2×2×4
mm3 resolution, and b = 0.2, 0.5, …, 6.0 ms/μm2 repeated across six
directions. A DTI
analysis was performed to estimate the fractional anisotropy (FA). Orientationally averaged data were
analysed as in Ning et al. (2018)8 by fitting
S = S0 exp(–b · MD + b2 · MK · MD2 · (1 – Γ · AXR) / 6)
to estimate the mean
diffusivity (MD), the mean kurtosis (MK) and the apparent exchange rate (AXR), where
the ‘exchange-weighting time’ Γ is a function of TD and δ. All data were co-registered to the first exam
using Elastix.9 The lesions were defined as coherent regions of MD-hypointensity
at day two, and the voxels within lesions were labelled as
either ‘viable d90’ or
‘liquid d90’ based on whether their MD was below or above 1.2 μm2/ms at day ninety, respectively.Results
A diffusion time dependence
dominated by elevated AXR values were detected at day two within lesions but
not within normal-appearing tissue (Fig 2). This pattern was visible although weaker at day
nine and gone by day ninety (Fig. 3). At day ninety, the MD within lesions was high in some
regions, indicating liquification, while being normal-appearing in other
regions (Fig. 3). The patterns of elevated AXR at day two and day nine tended to
overlap with the patterns of high MD at day ninety (Fig. 4). Also, the AXR
values were higher within the parts of lesions classified as ‘liquid’ at day ninety compared with parts
that would be classified as ‘viable’, both at day two (9.6 ± 3.4 s–1 vs.
3.4 ± 2.7 s–1) and at day nine (7.1 ± 3.9 s–1 vs.
3.8 ± 1.2 s–1; Table 1). The MD and MK showed little relation to
tissue outcome but the FA tended to be lower within parts that would be classified as ‘liquid’ (Table 1).Discussion
Ischemic stroke lesions exhibited elevated rates
of water exchange in the subacute stage with a pattern that appeared predictive
of tissue viability in the chronic stage, although the limited number of
subjects prevented rigorous statistical analysis. An increased water exchange in
ischemia could potentially be due to increased water permeability from swelling-activated
volume regulatory anion channels (VRAC)10,11
or increased surface-to-volume ratio from dendritic beading.12 As this exchange appears related to tissue
that is under irreversible ischemia (thus the true core) rather than tissue that may recover
(Fig. 4; Table 1), its mapping using the AXR could potentially
improve penumbra definitions and help identifying subjects who would have a favorable
outcome of late recanalization.13,14Conclusion
Absence of diffusional exchange within ischemic
stroke lesions appeared predictive of tissue viability, even in regions normally
considered irreversibly injured. Future studies should explore whether this
information may be used for predicting the outcome of late recanalization.Acknowledgements
We thank Philips for providing
access to the pulse programming environment. The study was supported by grants
from the Swedish Research Council (2016-03443).References
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