Katie D. Vo

Magnetic resonance cerebral metabolic rate of oxygen utilization in hyperacute stroke patients

The purpose of this study was to explore the feasibility of obtaining magnetic resonance–measured cerebral metabolic rate of oxygen utilization (MR‐CMRO2) in acute ischemic stroke patients. Seven stroke patients were serially imaged: 4.5 ± 0.9 hours (tp1), 3 to 5 days (tp2), and 1 to 3 months (tp3) after symptom onset. Diffusion‐weighted, perfusion‐weighted, and multiecho gradient‐echo/spin‐echo images were acquired; cerebral blood flow and oxygen extraction fraction maps were obtained from which CMRO2 was calculated as the product of cerebral blood flow and oxygen extraction fraction. The final infarct lesions obtained from tp3 T2‐weighted images and the “penumbra” obtained from the tp1 perfusion‐weighted image–defined lesion were coregistered onto tp1 CMRO2 maps. CMRO2 values in the region of brain that eventually infarcted were reduced to 0.40 ± 0.24 of the respective region on the contralateral hemisphere. The “salvaged penumbra” defined by the area of mismatch between the final infarct and the tp1 perfusion‐weighted lesion demonstrated an average CMRO2 value of 0.55 ± 0.11 of the contralateral hemisphere. Although our results are preliminary and require further evaluation, the ability to obtain in vivo measurements of MR‐CMRO2 noninvasively potentially can provide information for determining brain tissue viability in acute ischemic stroke patients.

Vascular Permeability Precedes Spontaneous Intracerebral Hemorrhage in Stroke-Prone Spontaneously Hypertensive Rats

Background and Purpose— Stroke-prone spontaneous hypertensive rats (SHRsp) fed a high-salt diet develop malignant hypertension, blood–brain barrier breakdown, and spontaneous intracerebral hemorrhage (ICH). The precise spatial and temporal relationship between these events has not been well-delineated. Methods— Ten SHRsp male rats, fed a high-salt diet, were imaged weekly using MRI, starting at 12 weeks of age. T1-weighted (with and without Gd), T2-weighted, and T2* sequences were acquired. Permeability maps were calculated. Results— Seven SHRsp rats had spontaneous ICH develop before death. Five of the 7 rats had focally increased vascular permeability at the site of the ICH; 3 of these rats had vascular permeability 1 to 2 weeks before spontaneous ICH. Conclusions— Salt-loaded SHRsp rats have increased vascular permeability up to 2 weeks before ICH, predicting hemorrhage both in space and time. These results suggest that hypertensive ICH is preceded by focal vasculopathy detectable by Gd leak.

Accuracy of computed tomography detection of superior canal dehiscence.

Hypothesis High-resolution temporal bone computed tomography (CT) may erroneously demonstrate a superior semicircular canal dehiscence (SSCD) where none exists and inaccurately display the size of a dehiscence. Background CT is an integral component of the diagnosis of SSCD. The prevalence of dehiscence as measured on computed tomographic scan is approximately eightfold higher than that on histologic studies, suggesting that CT may have a relatively low specificity for identifying canal dehiscence. This, in turn, can lead to an inappropriate diagnosis and treatment plan. Methods We quantified the accuracy of CT in identifying a dehiscence of the superior semicircular canal in a cadaver model using microCT as a gold standard. The superior canals of 11 cadaver heads were blue lined. Twelve of the 22 ears were further drilled to create fenestrations of varying sizes. Heads were imaged using medical CT, followed by microCT scans of the temporal bones at 18-µm resolution. Diagnosis of dehiscence and measurements of dehiscence size were performed on clinical CT and compared with that of microCT. Results Clinical CT identified 7 of 8 intact canals as dehiscent and tended to overestimate the size of smaller fenestrations, particularly those surrounded by thin bone. Conclusion These findings confirm that medical CT cannot be used as the exclusive gold standard for SSCD and that, particularly for small dehiscences on CT, clinical symptoms must be clearly indicative of a dehiscence before surgical treatment is undertaken. Preoperative counseling for small dehiscences may need to include the possibility that no dehiscence may be found despite radiologic evidence for it.

Defining the Ischemic Penumbra Using Magnetic Resonance Oxygen Metabolic Index

Background and Purpose— Penumbral biomarkers promise to individualize treatment windows in acute ischemic stroke. We used a novel magnetic resonance imaging approach that measures oxygen metabolic index (OMI), a parameter closely related to positron emission tomography–derived cerebral metabolic rate of oxygen utilization (CMRO2), to derive a pair of ischemic thresholds: (1) an irreversible-injury threshold that differentiates ischemic core from penumbra and (2) a reversible-injury threshold that differentiates penumbra from tissue not-at-risk for infarction. Methods— Forty patients with acute ischemic stroke underwent magnetic resonance imaging at 3 time points after stroke onset: <4.5 hours (for OMI threshold derivation), 6 hours (to determine reperfusion status), and 1 month (for infarct probability determination). A dynamic susceptibility contrast method measured cerebral blood flow, and an asymmetrical spin echo sequence measured oxygen extraction fraction, to derive OMI (OMI=cerebral blood flow×oxygen extraction fraction). Putative ischemic threshold pairs were iteratively tested using a computation-intensive method to derive infarct probabilities in 3 tissue groups defined by the thresholds (core, penumbra, and not-at-risk tissue). An optimal threshold pair was chosen based on its ability to predict infarction in the core, reperfusion-dependent survival in the penumbra, and survival in not-at-risk tissue. The predictive abilities of the thresholds were then tested within the same cohort using a 10-fold cross-validation method. Results— The optimal OMI ischemic thresholds were found to be 0.28 and 0.42 of normal values in the contralateral hemisphere. Using the 10-fold cross-validation method, median infarct probabilities were 90.6% for core, 89.7% for nonreperfused penumbra, 9.95% for reperfused penumbra, and 6.28% for not-at-risk tissue. Conclusions— OMI thresholds, derived using voxel-based, reperfusion-dependent infarct probabilities, delineated the ischemic penumbra with high predictive ability. These thresholds will require confirmation in an independent patient sample.

Preexisting Statin Use Is Associated With Greater Reperfusion in Hyperacute Ischemic Stroke

Background and Purpose— Statin pretreatment has been associated with improved outcomes in patients with ischemic stroke. Although several mechanisms have been examined in animal models, few have been examined in patients. We hypothesized that patients using statins before stroke onset may have greater reperfusion than patients not using statins. Methods— Acute ischemic stroke patients underwent 2 MR scans: within 4.5 (tp1) and at 6 hours (tp2) after stroke onset. Regions of reperfusion were defined by prolonged mean transit time (MTT) at tp1, which normalized at tp2. Four MTT thresholds were assessed to ensure that results were not spuriously based on an arbitrary threshold. Baseline characteristics, relative reperfusion, and change in NIHSS between tp1 and 1-month follow-up (&Dgr;NIHSS) were compared between patients who were using statins at stroke onset and those who were not. Results— Thirty-one stroke patients were prospectively enrolled; 12 were using statins and 19 were not. Baseline characteristics did not differ between the 2 groups except the statin group had greater coronary artery disease (P=0.03). Patients using statins showed significantly greater reperfusion compared to untreated patients across all MTT thresholds. For MTT of 4 seconds, median relative reperfusion was 50% (interquartile range, 30%–56%) in the preexisting statin group versus 13% (interquartile range, 5%–36%) in the untreated group (P=0.014). The statin group had greater &Dgr;NIHSS (8.8±4.0 points) compared to the untreated group (4.4±5.7 points; P=0.028). Conclusions— Statin use before ischemic stroke onset was associated with greater early reperfusion and NIHSS improvement. Further studies in larger populations are required to confirm our preliminary findings.

Streamlined Hyperacute Magnetic Resonance Imaging Protocol Identifies Tissue-Type Plasminogen Activator–Eligible Stroke Patients When Clinical Impression Is Stroke Mimic

Background and Purpose— Stroke mimics (SM) challenge the initial assessment of patients presenting with possible acute ischemic stroke (AIS). When SM is considered likely, intravenous tissue-type plasminogen activator (tPA) may be withheld, risking an opportunity to treat AIS. Although computed tomography is routinely used for tPA decision making, magnetic resonance imaging (MRI) may diagnose AIS when SM is favored but not certain. We hypothesized that a hyperacute MRI (hMRI) protocol would identify tPA-eligible AIS patients among those initially favored to have SM. Methods— A streamlined hMRI protocol was designed based on barriers to rapid patient transport, MRI acquisition, and post-MRI tPA delivery. Neurologists were trained to order hMRI when SM was favored and tPA was being withheld. The use of hMRI for tPA decision making, door-to-needle times, and outcomes were compared before hMRI implementation (pre-hMRI: August 1, 2011 to July 31, 2013) and after (post-hMRI, August 1, 2013, to January 15, 2015). Results— Post hMRI, 57 patients with suspected SM underwent hMRI (median MRI-order-to-start time, 29 minutes), of whom, 11 (19%) were diagnosed with AIS and 7 (12%) received tPA. Pre-hMRI, no tPA-treated patients were screened with hMRI. Post hMRI, 7 of 106 (6.6%) tPA-treated patients underwent hMRI to aid in decision making because of suspected SM (0% versus 6.6%; P=0.001). To ensure standard care was maintained after implementing the hMRI protocol, pre- versus post-hMRI tPA-treated cohorts were compared and did not differ: door-to-needle time (39 versus 37 minutes; P=0.63), symptomatic hemorrhage rate (4.5% versus 1.9%; P=0.32), and favorable discharge location (85% versus 89%; P=0.37). Conclusions— A streamlined hMRI protocol permitted tPA administration to a small, but significant, subset of AIS patients initially considered to have SM.

Imaging Oxygen Metabolism in Acute Stroke Using MRI

The ability to image the ischemic penumbra during hyperacute stroke promises to identify patients who may benefit from treatment intervention beyond population-defined therapeutic time windows. MR blood oxygenation level-dependent (BOLD) contrast imaging has been explored in ischemic stroke. This review provides an overview of several BOLD-based methods, including susceptibility-weighted imaging, R2, R2*, R2′, R2* under oxygen challenge, MR_OEF and MROMI approaches to assess cerebral oxygen metabolism in ischemic stroke. We will review the underlying pathophysiological basis of the imaging approaches, followed by a brief introduction of BOLD contrast. Finally, we will discuss the applications of the BOLD approaches in patients with ischemic stroke. BOLD-based methods hold promise for imaging tissue oxygenation during acute ischemia. Further technical refinement and validation studies in stroke patients against positron emission tomography measurements are needed.

Neurologic and neuroimaging manifestations of Cantú syndrome A case series

Objective: To describe the neurologic and neuroimaging manifestations associated with Cantú syndrome. Methods: We evaluated 10 patients with genetically confirmed Cantú syndrome. All adult patients, and pediatric patients who were able to cooperate and complete the studies, underwent neuroimaging, including vascular imaging. A salient neurologic history and examination was obtained for all patients. Results: We observed diffusely dilated and tortuous cerebral blood vessels in all patients who underwent vascular imaging. White matter changes were observed in all patients who completed an MRI brain study. Two patients had a persistent trigeminal artery. One patient had an occluded right middle cerebral artery. One patient had transient white matter changes suggestive of posterior reversible encephalopathic syndrome. Four patients had migraines with one patient having complicated migraines. Seizures were seen in early life but infrequent. The majority of patients had mild developmental delays and one patient had a diagnosis of autism. Conclusions: Cantú syndrome is associated with various neurologic manifestations, particularly cerebrovascular findings including dilated and tortuous cerebral vessels, white matter changes, and persistent fetal circulation. Involvement of the KATP SUR2/Kir6.1 subtype potentially plays an important role in the neurologic manifestations of Cantú syndrome.

Oxygen Metabolism in Ischemic Stroke Using Magnetic Resonance Imaging

Detecting “at-risk” but potentially salvageable brain tissue, known as the ischemic penumbra, is of importance for identifying patients who may benefit from thrombolytic or other treatments beyond the currently FDA-approved short therapeutic window for tissue plasminogen activator. Since the magnetic resonance blood oxygenation level-dependent (BOLD) contrast may provide information concerning tissue oxygen metabolism, its utilization in ischemic stroke has been explored. The focus of this review is to provide an introduction of several BOLD-based methods, including susceptibility-weighted imaging, R2 BOLD, R2*, R2′, MR_OEF, and MR_OMI approaches to assess cerebral oxygenation changes induced by ischemia. Specifically, we will review the underlying pathophysiological basis of the imaging approaches, followed by a brief introduction of BOLD contrast, and finally the applications of BOLD approaches in ischemic stroke. The advantages and disadvantages of each method are addressed. In summary, the BOLD-based methods are promising for imaging oxygenation in ischemic tissue. Future steps would include technical refinement and vigorous validation against another independent method, such as positron emission tomography.

Evidence-based neuroimaging in acute ischemic stroke.

The imaging work-up of patients with acute neurologic deficits should begin with noncontrast CT to exclude intracerebral hemorrhage. Based on positive results from the NINDS t-PA trial, the overriding objectives of imaging in the selection of patients for t-PA treatment are the detection of hemorrhage and rapid evaluation (speed of imaging). Despite its limited sensitivity for the identification of an ischemic stroke lesion, CT has multiple advantages over MR imaging in the initial diagnostic work-up. Advanced MR techniques promise to provide anatomic, physiologic, and vascular information in a single examination, and the ability to increase treatment specificity and improve outcome. Clinical outcome data are lacking; therefore, the routine use of screening MR imaging before t-PA therapy is not supported. Rigorous validation and correlation to clinical outcomes will be required.