Synopsis
Ischemic
stroke treatment with a thrombolytic agent given in the hyperacute phase can greatly
impact the outcome for stroke patients, however stroke status monitoring with CT
and MRI is generally only possible once patients are admitted to a hospital.
Here, we demonstrate T1 contrast at ultra-low magnetic field strength in a rat
model of stroke, with subtle changes noticeable as early as t=20min, and more
clearly at t=3h and t=24h following stroke onset. We believe that the use of portable,
ultra-low field MRI scanners as an early-detection methodology could have great
impact on the treatment and monitoring of ischemic stroke.Purpose
Ischemic stroke caused by intracranial occlusion is a major cause of mortality worldwide
1. Over the last two decades, significant progress in the use of thrombolytic agents for the treatment of acute stroke has significantly improved the outcome for stroke patients
2,3. However, it is known that intravenous recombinant tissue plasminogen activator (tPA), when needed, is efficacious only if administered less than 3 hours after symptom onset,
i.e. in the early stage of hyperacute ischemic stroke
3,4. Diffusion weighted MR imaging has shown to give good sensitivity to probe hyperacute cerebral ischemia
5, provided that patients have access to an MRI scanner at this very early stage. In previous work
6 we have demonstrated fast 3D MRI
in vivo in the human brain at ultra-low magnetic field and we believe that practical implementation of ultra-low field MRI scanners could provide clinically relevant images in robust portable devices. We have also previously shown that MR Fingerprinting techniques can be applied at ultra-low magnetic field
7. Here, we show distinct
T1 contrast at ultra-low magnetic field during the hyperacute and acute phase of brain ischemia in rat brains
in vivo.
Methods
MR fingerprinting was performed
in vivo in two male Wistar rats in the previously described ultra-low field scanner
6. A custom-made Tx/Rx rat head NMR probe
8 was used that provides both high homogeneity and sensitivity. For each rat, permanent ischemia was induced by surgically occluding the middle cerebral artery (MCA). Balanced steady state free precession (b-SSFP) was used for imaging, with Cartesian acquisition and random sampling of 40% of
k-space with a variable density Gaussian pattern
9. The sequence was set with matrix size=128×35×11, corresponding voxel size = (1.7×2.2×4.2) mm
3, and number of average NA=3. The minimum TR was 47.8 ms with 9091 Hz bandwidth. The total acquisition time was 18.2 min. A flip angle/TR trajectory of length N=20 was generated using an optimization method previously described
7 (Fig. 1). The optimization scheme used here has FA ranging from 1 to 180°, and TR from 47.8ms to 191 ms. After each experiment, the animals were sacrificed and their brain extracted for staining with 2,3,5-Triphenyltetrazolium chloride (TTC).
Results
The MRF acquisitions were reconstructed by best match to a pre-computed dictionary, and the resultant images reveal five different types of quantitative maps: Proton density,
T1 (ms),
T2 (ms), off-resonance (Hz) and
B1 homogeneity (% of total field) (Fig. 2).
T1 images at three different time points following occlusion (t1=20min, t2=3h, and t3=24h) are shown for the two occluded rats (Fig. 3a). In rat 1 and 2,
T1 increase of about 25% can be seen at t=20 min, up to 75% at t=3h, and more than 100% at t=24h (red arrows). TTC staining of the extracted and then sliced animal brains reveals large infarcts in the same regions where
T1 changes were observed (Fig. 3b) in both animals. The infarcted hemisphere also shows significant herniation resulting from what we assume is cytotoxic edema.
Conclusion
We have
demonstrated that quantitative
T1 maps in ischemic animals at ultra-low
magnetic field reveal changes in the hyperacute phase of ischemic stroke,
noticeable at t=20 min after occlusion, and clearly observable at t=3 h.
We believe that these observed changes in
T1 result from cytotoxic edema in the
damaged region. Optimized MR fingerprinting techniques enable the generation of
relevant contrast unique to the ultra-low field regime. Further work will aim
at investigating
T1 contrast more frequently in the hyperacute phase of ischemic
stroke, in particular at t<3h, as well as providing quantitative maps at
high magnetic field strength for comparison purpose. This preliminary work
shows that monitoring of ischemic stroke at ultra-low magnetic field is
possible at a very early stage. We believe that this application for ultra-low field
MRI could lead to disruptive technology where safe and portable mobile ultra-low
field scanners sited in an ambulance are able to diagnose early ischemia and
have potential to change the outcome for the patient as a pre-hospital imaging
tool.
Acknowledgements
This
research was supported by the National Institute of Health (NINDS/BINP 5R21NS087344).References
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