Lawrence L. Latour

Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison

BACKGROUND Although the use of magnetic resonance imaging (MRI) for the diagnosis of acute stroke is increasing, this method has not proved more effective than computed tomography (CT) in the emergency setting. We aimed to prospectively compare CT and MRI for emergency diagnosis of acute stroke. METHODS We did a single-centre, prospective, blind comparison of non-contrast CT and MRI (with diffusion-weighted and susceptibility weighted images) in a consecutive series of patients referred for emergency assessment of suspected acute stroke. Scans were independently interpreted by four experts, who were unaware of clinical information, MRI-CT pairings, and follow-up imaging. RESULTS 356 patients, 217 of whom had a final clinical diagnosis of acute stroke, were assessed. MRI detected acute stroke (ischaemic or haemorrhagic), acute ischaemic stroke, and chronic haemorrhage more frequently than did CT (p<0.0001, for all comparisons). MRI was similar to CT for the detection of acute intracranial haemorrhage. MRI detected acute ischaemic stroke in 164 of 356 patients (46%; 95% CI 41-51%), compared with CT in 35 of 356 patients (10%; 7-14%). In the subset of patients scanned within 3 h of symptom onset, MRI detected acute ischaemic stroke in 41 of 90 patients (46%; 35-56%); CT in 6 of 90 (7%; 3-14%). Relative to the final clinical diagnosis, MRI had a sensitivity of 83% (181 of 217; 78-88%) and CT of 26% (56 of 217; 20-32%) for the diagnosis of any acute stroke. INTERPRETATION MRI is better than CT for detection of acute ischaemia, and can detect acute and chronic haemorrhage; therefore it should be the preferred test for accurate diagnosis of patients with suspected acute stroke. Because our patient sample encompassed the range of disease that is likely to be encountered in emergency cases of suspected stroke, our results are directly applicable to clinical practice.

Comparison of MRI and CT for Detection of Acute Intracerebral Hemorrhage

CONTEXT Noncontrast computed tomography (CT) is the standard brain imaging study for the initial evaluation of patients with acute stroke symptoms. Multimodal magnetic resonance imaging (MRI) has been proposed as an alternative to CT in the emergency stroke setting. However, the accuracy of MRI relative to CT for the detection of hyperacute intracerebral hemorrhage has not been demonstrated. OBJECTIVE To compare the accuracy of MRI and CT for detection of acute intracerebral hemorrhage in patients presenting with acute focal stroke symptoms. DESIGN, SETTING, AND PATIENTS A prospective, multicenter study was performed at 2 stroke centers (UCLA Medical Center and Suburban Hospital, Bethesda, Md), between October 2000 and February 2003. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain MRI followed by noncontrast CT. MAIN OUTCOME MEASURES Acute intracerebral hemorrhage and any intracerebral hemorrhage diagnosed on gradient recalled echo (GRE) MRI and CT scans by a consensus of 4 blinded readers. RESULTS The study was stopped early, after 200 patients were enrolled, when it became apparent at the time of an unplanned interim analysis that MRI was detecting cases of hemorrhagic transformation not detected by CT. For the diagnosis of any hemorrhage, MRI was positive in 71 patients with CT positive in 29 (P<.001). For the diagnosis of acute hemorrhage, MRI and CT were equivalent (96% concordance). Acute hemorrhage was diagnosed in 25 patients on both MRI and CT. In 4 other patients, acute hemorrhage was present on MRI but not on the corresponding CT--each of these 4 cases was interpreted as hemorrhagic transformation of an ischemic infarct. In 3 patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In 1 patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. In 49 patients, chronic hemorrhage, most often microbleeds, was visualized on MRI but not on CT. CONCLUSION MRI may be as accurate as CT for the detection of acute hemorrhage in patients presenting with acute focal stroke symptoms and is more accurate than CT for the detection of chronic intracerebral hemorrhage.

Early blood–brain barrier disruption in human focal brain ischemia

Loss of integrity of the blood–brain barrier (BBB) resulting from ischemia/reperfusion is believed to be a precursor to hemorrhagic transformation (HT) and poor outcome. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in human focal brain ischemia and tested for associations with reperfusion, HT, and poor outcome (modified Rankin score >2). BBB disruption was found in 47 of 144 (33%) patients, having a median time from stroke onset to observation of 10.1 hours. Reperfusion was found to be the most powerful independent predictor of early BBB disruption (p = 0.018; odds ratio, 4.09; 95% confidence interval, 1.28–13.1). HT was observed in 22 patients; 16 (72.7%) of those also had early BBB disruption (p < 0.001; odds ratio, 8.11; 95% confidence interval, 2.85–23.1). In addition to baseline severity (National Institutes of Health Stroke Scale score >6), early BBB disruption was found to be an independent predictor of HT. Because the timing of the disruption was early enough to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by this imaging biomarker may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome. Ann Neurol 2004

Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood-brain barrier disruption

Loss of integrity of the blood–brain barrier (BBB) resulting from ischemia and reperfusion is a hypothesized precursor to hemorrhagic transformation (HT) and worse clinical outcome than would be expected from the beneficial effects of reperfusion. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in acute focal brain ischemia and tested associations with reperfusion, HT, and poor outcome (modified Rankin score >2). The BBB disruption was evident as delayed gadolinium enhancement of cerebrospinal fluid space on fluid-attenuated inversion recovery (FLAIR) images and, for convenience, has been termed hyperintense acute reperfusion marker (HARM). HARM was found in 47 of 144 (33%) ischemic stroke patients. Reperfusion was found to be the strongest independent predictor of early BBB disruption (P=0.018) in multivariate analysis. HARM was associated with HT and worse clinical outcome (after adjustment for initial severity). It was also associated with more severe strokes at onset and greater age. Because the timing of the disruption was early enough (median estimate 3.8 hours from onset) to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by HARM may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome.

Transcranial amelioration of inflammation and cell death after brain injury

Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function. At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury.

Early magnetic resonance imaging findings in patients receiving tissue plasminogen activator predict outcome: Insights into the pathophysiology of acute stroke in the thrombolysis era†

We measured ischemic brain changes with diffusion and perfusion MRI in 42 ischemic stroke patients before and 2 hours (range approximately 1.5 to 4.5 hours) after standard intravenous tissue plasminogen activator (tPA) therapy. The median time from stroke onset to tPA was 131 minutes. Clinical and MRI variables (change in perfusion and/or diffusion weighted lesion volume) were compared between those with excellent outcome defined as 3‐month modified Rankin score (mRS) of 0 to 1 and those with incomplete recovery (mRS >1). In multivariate logististic regression analysis, the most powerful independent predictor for excellent outcome was improved brain perfusion: hypoperfusion volume on mean transit time (MTT) map decrease >30% from baseline to 2‐hour post tPA scan (p=0.009; odds ratio [95% confidence interval], 20.7 [2.1‐203.9]). Except for age < 70 years, no other baseline clinical or imaging variable was an independent predictor of outcome. We propose MTT lesion volume decrease more than 30% 2 hours after tPA as an early marker of long‐term clinical benefit of thrombolytic therapy.

Blood–Brain Barrier Disruption in Humans Is Independently Associated With Increased Matrix Metalloproteinase-9

Background and Purpose— Matrix metalloproteinases (MMP) may play a role in blood–brain barrier (BBB) disruption after ischemic stroke. We hypothesized that plasma concentrations of MMP-9 are associated with a marker of BBB disruption in patients evaluated for acute stroke. Methods— Patients underwent MRI on presentation and ≈24 hours later. The MRI marker, termed hyperintense acute reperfusion injury marker (HARM), is gadolinium enhancement of cerebrospinal fluid on fluid-attenuated inversion recovery MRI. Plasma MMP-9 and tissue inhibitor of matrix metalloproteinase-1 were measured by enzyme-linked immunosorbent assay. Logistic regression models tested for predictors of HARM on 24-hour follow-up scans separately for MMP-9 and the ratio of MMP-9 to TIMP-1. Results— For the 41 patients enrolled, diagnoses were: acute ischemic cerebrovascular syndrome, 33 (80.6%); intracerebral hemorrhage, 6 (14.6%); stroke mimic, 1 (2.4%); and no stroke, 1 (2.4%). HARM was present in 17 (41.5%) patients. In model 1, HARM was associated with baseline plasma MMP-9 concentration (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.001–1.019; P=0.033). In model 2, HARM was associated with the ratio of MMP-9 to tissue inhibitor of matrix metalloproteinase-1 (OR, 4.94; 95% CI, 1.27–19.14; P=0.021). Conclusions— Baseline MMP-9 was a significant predictor of HARM at 24-hour follow-up, supporting the hypothesis that MMP-9 is associated with BBB disruption. If the association between MMP-9 and BBB disruption is confirmed in future studies, HARM may be a useful imaging marker to evaluate MMP-9 inhibition in ischemic stroke and other populations with BBB disruption.

Distal hyperintense vessels on FLAIR: An MRI marker for collateral circulation in acute stroke?

Background: Hyperintense vessels (HV) on fluid-attenuated inversion recovery imaging are frequently observed in acute ischemic stroke patients. However, the exact mechanism and clinical implications of this sign have not yet been clearly defined. The features of HV and its relevance to other imaging factors are presented here. Methods: Prominence and location of HV were documented in 52 consecutive patients with middle cerebral artery (MCA) territory infarction, before treatment with IV recombinant tissue plasminogen activator. Pretreatment ischemic lesion volume, perfusion lesion volume, and vessel occlusion were determined in addition to recanalization status and ischemic lesion volume on follow-up imaging. NIH Stroke Scale (NIHSS) was used as a measure of clinical severity. Results: HV distal to arterial occlusion was observed in 73% of patients; more frequent in proximal than distal MCA occlusion patients. Among the 38 patients with proximal MCA occlusion, initial perfusion lesion volume was comparable among patients with different grade distal HV. However, patients with more prominent distal HV had smaller initial, 24-hour, and subacute ischemic lesion volumes and lower initial NIHSS scores. Conclusions: The presence of distal hyperintense vessels before thrombolytic treatment is associated with large diffusion–perfusion mismatch and smaller subacute ischemic lesion volumes in patients with proximal middle cerebral artery occlusion. DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; GRE = gradient recalled echo; HV = hyperintense vessels; MCA = middle cerebral artery; MRA = magnetic resonance angiography; MTT = mean transit time; NIHSS = NIH Stroke Scale; PWI = perfusion-weighted imaging; rt-PA = recombinant tissue plasminogen activator; TE = echo time; TI = inversion time; TIMI = thrombolysis in myocardial infarction; TR = repetition time.

Early ischemic lesion recurrence within a week after acute ischemic stroke

Previous observations suggested that multiple ischemic lesions on diffusion‐weighted imaging (DWI) are common in acute stroke patients. We hypothesized that a source of these multiple lesions was the recurrence of ischemic lesions within a week after a clinically symptomatic stroke. We analyzed 99 acute ischemic stroke patients scanned within 6 hours of onset and at subsequent times within the first week. Ischemic lesion recurrence was defined as any new lesion separate from the index lesion. Recurrent lesions occurring outside initial perfusion deficit were termed ‘distant lesion recurrence’. We estimated the hazard ratio (HR) of recurrence associated with clinical and imaging characteristics using log‐rank test. Any lesion recurrence was found in 34%, with distant lesion recurrence in 15%, while clinical recurrence was evident in 2%. Initial multiple DWI lesions were associated with any lesion recurrence (HR, 2.83; 95% confidence interval [CI], 1.65–10.29; p = 0.002) and with distant lesion recurrence (HR, 5.99; 95% CI, 4.05–64.07; p < 0.0001). Large‐artery atherosclerosis was the most frequent stroke subtype associated with any lesion recurrence (p = 0.026). These results may indicate a prolonged state of increased ischemic risk over the first week and suggest DWI as a possible surrogate measure for recurrent stroke. Ann Neurol 2003

Common data elements in radiologic imaging of traumatic brain injury.

Traumatic brain injury (TBI) has a poorly understood pathology. Patients suffer from a variety of physical and cognitive effects that worsen as the type of trauma worsens. Some noninvasive insights into the pathophysiology of TBI are possible using magnetic resonance imaging (MRI), computed tomography (CT), and many other forms of imaging as well. A recent workshop was convened to evaluate the common data elements (CDEs) that cut across the imaging field and given the charge to review the contributions of the various imaging modalities to TBI and to prepare an overview of the various clinical manifestations of TBI and their interpretation. Technical details regarding state‐of‐the‐art protocols for both MRI and CT are also presented with the hope of guiding current and future research efforts as to what is possible in the field. Stress was also placed on the potential to create a database of CDEs as a means to best record information from a given patient from the reading of the images. J. Magn. Reson. Imaging 2010;32:516–543.