Diffusion Weighted Imaging Evaluation for Understanding Stroke Evolution Study-2 (DEFUSE-2)

Currently, the only approved therapy for acute stroke patients is a medication called tissue
plasminogen activator (tPA). This medication is given as an intravenous infusion and can
dissolve blood clots, thereby restoring blood flow to the brain. Early restoration of blood
flow can prevent the permanent damage to the brain which typically occurs after a stroke. As
a result, patients who achieve early restoration of blood flow have less disability than
stroke patients in whom blood flow is not restored. Unfortunately, only a very small
fraction of stroke patients is treated with tPA and benefits from tPA. Nationwide only 3
percent of stroke patients receive this therapy. The short treatment time-window is one of
the main reasons that patients are not eligible for this treatment. Previously, tPA was only
recommended in the 0 - 3 hour time window after stroke onset, but recent studies have shown
efficacy our to 4 ½ hours. AHA guidelines now recommend treatment with iv tPA up to 4 ½ hrs.
However, the number of stroke patients who will benefit from treatment remains small despite
expansion of the time-window from 3 to 4 ½ hrs. This is the result of two main limitations
of tPA. First, the majority of stroke patients present beyond the 4 ½ hour time-window and
will therefore remain ineligible for treatment. Second, stroke patients who receive tPA do
not always benefit because the treatment does not restore blood flow in all patients. Our
research has shown that depending on the location of the blood clot, blood flow is restored
in only 20 to 50% of stroke patients treated with tPA.

Patients with persistent blood vessel occlusions and no improvement in their clinical
condition after receiving tPA or those arriving at the hospital outside the 4 1/2 hour time
window routinely undergo mechanical clot removal to open an occluded blood vessel in the
brain.

Mechanical clot removal increases the percentage of stroke patients who achieve
recanalization, and as a result may increase the proportion of patients who have good
clinical outcomes. However it is unclear for which stroke patients mechanical thrombectomy
is most suitable. Although effective at removing blood-clots, it appears that mechanical
clot retrieval is not beneficial for all patients. Whereas some patients benefit, others
experience no effect, and yet others are likely harmed by mechanical clot retrieval. In
order to avoid harm and maximize benefit it is important to know, prior to initiation of the
mechanical clot retrieval procedure, if the procedure is likely to result in a clinical
improvement. The investigators hypothesize that the response to mechanical clot retrieval
can be predicted based on characteristics of an MRI scan obtained just prior to the
retrieval procedure. The investigators hope to learn if new MRI techniques can help identify
which patients are most likely to benefit from mechanical clot removal after receiving tPA.

Inclusion Criteria:

1. Age 18 years and older

2. Clinical diagnosis of ischemic stroke and a score of 5 or more points in the NIHSS.

3. Planned to undergo intra-arterial (IA) therapy for acute hemispheric stroke (Either
as primary therapy or as adjuvant therapy following intravenous tPA treatment)

4. Planned to have a standard MRI including perfusion imaging and MR angiography of the
circle of Willis (MRA) prior to IA therapy

5. Intra-arterial thrombectomy can be started within 90 minutes of completion of MRI
scan and within 12 hours of symptom onset. (Start of IA therapy is defined as the
time of insertion of the femoral artery sheath; Time of brain scan is defined as the
time that the scan is completed)

6. Able to obtain informed consent (informed consent should be obtained prior to the
baseline MRI scan).

Exclusion Criteria:

1. Any pre-existing neurological illness resulting in a modified Rankin Scale Score of 3
or higher prior to the qualifying stroke

2. Pregnancy