A marker for hyperacute ischemic stroke at ultra-low magnetic field
Mathieu Sarracanie1,2,3, Fanny Herisson4, Najat Salameh1,2,3, Cenk Ayata4, and Matthew Rosen1,2,3

1MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, 2Harvard Medical School, Boston, MA, United States, 3Department of Physics, Harvard University, Cambridge, MA, United States, 4Department of Radiology, MGH/Neurovascular Research Lab, Boston, MA, United States


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.


Ischemic stroke caused by intracranial occlusion is a major cause of mortality worldwide1. 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 patients2,3. 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 stroke3,4. Diffusion weighted MR imaging has shown to give good sensitivity to probe hyperacute cerebral ischemia5, provided that patients have access to an MRI scanner at this very early stage. In previous work6 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 field7. 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.


MR fingerprinting was performed in vivo in two male Wistar rats in the previously described ultra-low field scanner6. A custom-made Tx/Rx rat head NMR probe8 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 pattern9. The sequence was set with matrix size=128×35×11, corresponding voxel size = (1.7×2.2×4.2) mm3, 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 described7 (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).


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.


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.


This research was supported by the National Institute of Health (NINDS/BINP 5R21NS087344).


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4.The NINDS t-PA Stroke Study Group. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. Stroke 1997; 28:2109-2118.

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6. Sarracanie M, LaPierre C, Salameh N, et al. Low-cost high-performance MRI. Sci Rep 2015;5:15177

7. Sarracanie M, Armstrong B, and Rosen M. High Speed MR Fingerprinting at 6.5 mT. Proceedings of the ISMRM 2014 #6370;

8. Waddington DEJ, Sarracanie M, Salameh N, et al. High performance probe for in vivo Overhauser MRI. Proceedings of the ISMRM 2015 #6710;

9. Sarracanie M, Armstrong B, Stockmann J, et al. High Speed 3D Overhauser-Enhanced MRI Using Combined b-SSFP and Compressed Sensing. Magn Res Med 2014; 71:735–745


Figure 1: Optimized MRF sequence with the flip angle (blue) and TR (red) series used here, N=20.

Figure 2: MRF reconstructed images in rat #2 at t1=20min following stroke onset, after a best match was found from data matching to a pre-computed dictionary. The “*” indicates a spherical fiducial filled with saline and placed onto the skull of the animal at bregma.

Figure 3: a. T1 maps in the whole head (only the 3 central slices are shown) of two ischemic rats at t=20min, t=3h and t=24h following stroke onset, and b. TTC staining of the rats brain showing healthy (red) versus infarcted (white) brain tissue.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)