MRI Profile Helps Target Candidates for Endovascular Treatment

SAN DIEGO – Stroke patients who are likely to benefit from endovascular reperfusion can be identified on the basis of their MRI profile, results from a multicenter study demonstrated.

"These results are largely independent of stroke onset time," Dr. Michael P. Marks said at the annual meeting of the Society of Neurointerventional Surgery. "Our belief is that if the right patients are identified, it can be shown that endovascular therapy will be of benefit in the treatment of their acute strokes."

Endovascular treatment is increasingly used in the management of acute stroke, said Dr. Marks, an interventional neuroradiologist at Stanford (Calif.) University. "A randomized trial has shown benefit for intra-arterial thrombolytic agents in this setting," he said (JAMA 1999;282:2003-11). "Single-armed prospective studies have shown that thrombectomy devices improve outcome in patients when reperfusion is successfully attained. Nevertheless, tremendous controversy exists because there is an absence of any study with randomized data and concurrent controls. In addition, many questions remain as to which candidates are best suited for revascularization and whether imaging can help identify those patients," Dr. Marks said.

Against this backdrop, he and his associates at nine clinical sites carried out the DEFUSE-2 (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study-2) to identify patients who might fit into a randomized controlled trial. DEFUSE-2 is a prospective study of acute stroke patients who underwent endovascular therapy following MRI. The primary hypothesis was that a target mismatch profile (TMM) could be identified where patients had a relatively small area of injured tissue as seen on diffusion-weighted imaging (DWI) relative to a larger volume of ischemic tissue that was still salvageable as identified by perfusion-weighted imaging (PWI); and that patients with a TMM would respond more favorably to endovascular reperfusion therapy than patients without a TMM.

To be eligible for the trial, patients had to have endovascular therapy started within 12 hours of an anterior circulation stroke. They underwent a baseline MRI within 90 minutes of endovascular therapy, a second MRI following reperfusion in the catheter lab, and a third MRI at 5 days to assess infarct volume. This was followed by clinical assessments at day 30 and day 90 using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS).

A TMM was defined as PWI volume over the DWI volume of 1.8 or greater, when the PWI volume had a Tmax of more than 6 seconds. PWI reperfusion was defined as a reduction in PWI lesion volume of greater than 50% between baseline and follow-up.

The investigators defined reperfusion as a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3. In this study, TICI 1 was defined as perfusion past the initial obstruction but little or slow distal perfusion with limited branch filling. TICI 2a was defined as partial perfusion of less than half of the vascular distribution of the occluded artery, TICI 2b was defined as partial perfusion of half or more of the vascular distribution of the occluded artery, and TICI 3 was defined as full perfusion filling of all distal branches.

Dr. Marks reported on outcomes from 78 patients who had a target mismatch and 21 who did not have a target mismatch. The researchers found that reperfusion was associated with a significantly increased odds of a favorable clinical response (odds ratio, 2.8), which was defined as an improvement in NIHSS score between baseline and day 30 of 8 points or more, or an NIHSS score of 0-1 at day 30. This outcome was driven by the target mismatch group, which had significantly greater odds of a favorable response to reperfusion than the no target mismatch group (OR, 5.0 vs. 0.2; P = .004).

A significantly higher percentage of patients in the target mismatch group achieved a 90-day mRS of 0-2 when there was reperfusion, compared with their counterparts in the no target mismatch group (57% vs. 25%), as well as when there was no reperfusion (31% vs. 22%).

The median time to the onset of vascular therapy was 6 hours. "When we divided patients into those started less than 6 hours versus those started greater than 6 hours, the results were very comparable," he said.

Dr. Marks also reported that by day 90, 29% of patients a TICI score of 0-1 achieved an mRS score of 0-2, compared with 25% of patients with a TICI score of 2a, 61% of patients with a score of 2b, and 50% of those with a score of 3. "This was driven by having a target mismatch," he said.

Dr. Marks and his associates are proposing a randomized controlled trial in which the primary hypothesis is that treatment with an approved thrombectomy device within 18-24 hours is more likely to result in a good clinical outcome at 90 days when patients are selected on the basis of a favorable MRI profile.

"The time is right to do this study, because current stentrievers have a high rate of recanalization," Dr. Marks said. "Physiologic imaging can identify patients who will benefit from recanalization in an extended time period."

DEFUSE-2 was funded by the National Institute of Neurological Disorders and Stroke. Dr. Marks said that he had no relevant financial conflicts to disclose.

SAN DIEGO – Stroke patients who are likely to benefit from endovascular reperfusion can be identified on the basis of their MRI profile, results from a multicenter study demonstrated.

"These results are largely independent of stroke onset time," Dr. Michael P. Marks said at the annual meeting of the Society of Neurointerventional Surgery. "Our belief is that if the right patients are identified, it can be shown that endovascular therapy will be of benefit in the treatment of their acute strokes."

Endovascular treatment is increasingly used in the management of acute stroke, said Dr. Marks, an interventional neuroradiologist at Stanford (Calif.) University. "A randomized trial has shown benefit for intra-arterial thrombolytic agents in this setting," he said (JAMA 1999;282:2003-11). "Single-armed prospective studies have shown that thrombectomy devices improve outcome in patients when reperfusion is successfully attained. Nevertheless, tremendous controversy exists because there is an absence of any study with randomized data and concurrent controls. In addition, many questions remain as to which candidates are best suited for revascularization and whether imaging can help identify those patients," Dr. Marks said.

Against this backdrop, he and his associates at nine clinical sites carried out the DEFUSE-2 (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study-2) to identify patients who might fit into a randomized controlled trial. DEFUSE-2 is a prospective study of acute stroke patients who underwent endovascular therapy following MRI. The primary hypothesis was that a target mismatch profile (TMM) could be identified where patients had a relatively small area of injured tissue as seen on diffusion-weighted imaging (DWI) relative to a larger volume of ischemic tissue that was still salvageable as identified by perfusion-weighted imaging (PWI); and that patients with a TMM would respond more favorably to endovascular reperfusion therapy than patients without a TMM.

To be eligible for the trial, patients had to have endovascular therapy started within 12 hours of an anterior circulation stroke. They underwent a baseline MRI within 90 minutes of endovascular therapy, a second MRI following reperfusion in the catheter lab, and a third MRI at 5 days to assess infarct volume. This was followed by clinical assessments at day 30 and day 90 using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS).

A TMM was defined as PWI volume over the DWI volume of 1.8 or greater, when the PWI volume had a Tmax of more than 6 seconds. PWI reperfusion was defined as a reduction in PWI lesion volume of greater than 50% between baseline and follow-up.

The investigators defined reperfusion as a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3. In this study, TICI 1 was defined as perfusion past the initial obstruction but little or slow distal perfusion with limited branch filling. TICI 2a was defined as partial perfusion of less than half of the vascular distribution of the occluded artery, TICI 2b was defined as partial perfusion of half or more of the vascular distribution of the occluded artery, and TICI 3 was defined as full perfusion filling of all distal branches.

Dr. Marks reported on outcomes from 78 patients who had a target mismatch and 21 who did not have a target mismatch. The researchers found that reperfusion was associated with a significantly increased odds of a favorable clinical response (odds ratio, 2.8), which was defined as an improvement in NIHSS score between baseline and day 30 of 8 points or more, or an NIHSS score of 0-1 at day 30. This outcome was driven by the target mismatch group, which had significantly greater odds of a favorable response to reperfusion than the no target mismatch group (OR, 5.0 vs. 0.2; P = .004).

A significantly higher percentage of patients in the target mismatch group achieved a 90-day mRS of 0-2 when there was reperfusion, compared with their counterparts in the no target mismatch group (57% vs. 25%), as well as when there was no reperfusion (31% vs. 22%).

The median time to the onset of vascular therapy was 6 hours. "When we divided patients into those started less than 6 hours versus those started greater than 6 hours, the results were very comparable," he said.

Dr. Marks also reported that by day 90, 29% of patients a TICI score of 0-1 achieved an mRS score of 0-2, compared with 25% of patients with a TICI score of 2a, 61% of patients with a score of 2b, and 50% of those with a score of 3. "This was driven by having a target mismatch," he said.

Dr. Marks and his associates are proposing a randomized controlled trial in which the primary hypothesis is that treatment with an approved thrombectomy device within 18-24 hours is more likely to result in a good clinical outcome at 90 days when patients are selected on the basis of a favorable MRI profile.

"The time is right to do this study, because current stentrievers have a high rate of recanalization," Dr. Marks said. "Physiologic imaging can identify patients who will benefit from recanalization in an extended time period."

DEFUSE-2 was funded by the National Institute of Neurological Disorders and Stroke. Dr. Marks said that he had no relevant financial conflicts to disclose.

SAN DIEGO – Stroke patients who are likely to benefit from endovascular reperfusion can be identified on the basis of their MRI profile, results from a multicenter study demonstrated.

"These results are largely independent of stroke onset time," Dr. Michael P. Marks said at the annual meeting of the Society of Neurointerventional Surgery. "Our belief is that if the right patients are identified, it can be shown that endovascular therapy will be of benefit in the treatment of their acute strokes."

Endovascular treatment is increasingly used in the management of acute stroke, said Dr. Marks, an interventional neuroradiologist at Stanford (Calif.) University. "A randomized trial has shown benefit for intra-arterial thrombolytic agents in this setting," he said (JAMA 1999;282:2003-11). "Single-armed prospective studies have shown that thrombectomy devices improve outcome in patients when reperfusion is successfully attained. Nevertheless, tremendous controversy exists because there is an absence of any study with randomized data and concurrent controls. In addition, many questions remain as to which candidates are best suited for revascularization and whether imaging can help identify those patients," Dr. Marks said.

Against this backdrop, he and his associates at nine clinical sites carried out the DEFUSE-2 (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study-2) to identify patients who might fit into a randomized controlled trial. DEFUSE-2 is a prospective study of acute stroke patients who underwent endovascular therapy following MRI. The primary hypothesis was that a target mismatch profile (TMM) could be identified where patients had a relatively small area of injured tissue as seen on diffusion-weighted imaging (DWI) relative to a larger volume of ischemic tissue that was still salvageable as identified by perfusion-weighted imaging (PWI); and that patients with a TMM would respond more favorably to endovascular reperfusion therapy than patients without a TMM.

To be eligible for the trial, patients had to have endovascular therapy started within 12 hours of an anterior circulation stroke. They underwent a baseline MRI within 90 minutes of endovascular therapy, a second MRI following reperfusion in the catheter lab, and a third MRI at 5 days to assess infarct volume. This was followed by clinical assessments at day 30 and day 90 using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS).

A TMM was defined as PWI volume over the DWI volume of 1.8 or greater, when the PWI volume had a Tmax of more than 6 seconds. PWI reperfusion was defined as a reduction in PWI lesion volume of greater than 50% between baseline and follow-up.

The investigators defined reperfusion as a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3. In this study, TICI 1 was defined as perfusion past the initial obstruction but little or slow distal perfusion with limited branch filling. TICI 2a was defined as partial perfusion of less than half of the vascular distribution of the occluded artery, TICI 2b was defined as partial perfusion of half or more of the vascular distribution of the occluded artery, and TICI 3 was defined as full perfusion filling of all distal branches.

Dr. Marks reported on outcomes from 78 patients who had a target mismatch and 21 who did not have a target mismatch. The researchers found that reperfusion was associated with a significantly increased odds of a favorable clinical response (odds ratio, 2.8), which was defined as an improvement in NIHSS score between baseline and day 30 of 8 points or more, or an NIHSS score of 0-1 at day 30. This outcome was driven by the target mismatch group, which had significantly greater odds of a favorable response to reperfusion than the no target mismatch group (OR, 5.0 vs. 0.2; P = .004).

A significantly higher percentage of patients in the target mismatch group achieved a 90-day mRS of 0-2 when there was reperfusion, compared with their counterparts in the no target mismatch group (57% vs. 25%), as well as when there was no reperfusion (31% vs. 22%).

The median time to the onset of vascular therapy was 6 hours. "When we divided patients into those started less than 6 hours versus those started greater than 6 hours, the results were very comparable," he said.

Dr. Marks also reported that by day 90, 29% of patients a TICI score of 0-1 achieved an mRS score of 0-2, compared with 25% of patients with a TICI score of 2a, 61% of patients with a score of 2b, and 50% of those with a score of 3. "This was driven by having a target mismatch," he said.

Dr. Marks and his associates are proposing a randomized controlled trial in which the primary hypothesis is that treatment with an approved thrombectomy device within 18-24 hours is more likely to result in a good clinical outcome at 90 days when patients are selected on the basis of a favorable MRI profile.

"The time is right to do this study, because current stentrievers have a high rate of recanalization," Dr. Marks said. "Physiologic imaging can identify patients who will benefit from recanalization in an extended time period."

DEFUSE-2 was funded by the National Institute of Neurological Disorders and Stroke. Dr. Marks said that he had no relevant financial conflicts to disclose.