Xinjian Du

Use of Quantitative Magnetic Resonance Angiography to Stratify Stroke Risk in Symptomatic Vertebrobasilar Disease

Background and Purpose— Symptomatic vertebrobasilar disease (VBD) carries a high risk of recurrent stroke. We sought to determine whether a management algorithm consisting of quantitative hemodynamic assessment could stratify stroke risk and guide the need for intervention. Methods— All patients with symptomatic VBD at our institution are evaluated by a standard protocol including quantitative magnetic resonance angiography (QMRA). Patients are stratified on the basis of the presence or absence of distal flow compromise. Those with low distal flow are offered intervention (surgical or endovascular); all patients receive standard medical therapy. We reviewed the clinical outcome of patients managed with this protocol from 1998 to 2003. Results— Follow-up was available for 47 of 50 patients over a mean interval of 28 months. Stroke and combined stroke/transient ischemic attack free survival at 2 years was calculated using the Kaplan–Meier curve. Patients with normal distal flow (n=31) had an event-free survival of 100% and 96%, respectively. Comparatively, patients with low distal flow (n=16) experienced a 71% and 53% event-free survival, demonstrating a significantly higher risk of recurrent ischemia (P=0.003). Patients with low flow who subsequently underwent treatment (n=12) had an 82% event-free survival. Cox proportional hazards analysis demonstrated that flow status affected event-free survival regardless of covariates. Conclusions— Patients with symptomatic VBD demonstrating low distal flow on QMRA appear to have a high risk of stroke; conversely, those with normal flow seem to have a benign course and may be optimally managed with medical therapy alone.

The cut flow index: An intraoperative predictor of the success of extracranial-intracranial bypass for occlusive cerebrovascular disease

OBJECTIVE: There has been a resurgence of interest in selective extracranial-intracranial bypass for revascularization of cerebrovascular occlusive disease. We evaluated the usefulness of intraoperative blood flow measurements in predicting graft success after extracranial-intracranial bypass. METHODS: A retrospective review of 51 cases of extracranial-intracranial bypass for purposes of flow augmentation in the setting of cerebrovascular occlusive disease was performed. In all cases, free flow from the cut end of the donor vessel, termed cut flow, was measured. The cut flow index (CFI) (bypass flow [ml/min] / cut flow [ml/min]) was derived and correlated with bypass patency, postoperative bypass flow, cerebrovascular reserve testing, and clinical outcome. RESULTS: The CFI was a significant predictor of bypass patency (P = 0.002). Using a CFI of 0.5 as a threshold, the bypass patency rate was 92% in cases with a CFI greater than 0.5 compared with 50% in cases with a CFI less than 0.5. Intraoperative bypass flow correlated well with postoperative measurements obtained from quantitative phase-contrast magnetic resonance imaging. An analysis of cases with a poor CFI indicated that a logical interpretation of bypass function can be performed during surgery. CONCLUSION: A poor CFI can alert surgeons to potential difficulties with the donor vessel, anastomosis, or recipient vessel during surgery. Furthermore, a CFI closely approximating 1.0 provides physiological confirmation of impaired cerebrovascular reserve in the recipient bed.

Brain tissue PO2, PCO2, and pH during cerebral vasospasm

BACKGROUND The purpose of the present study was to assess brain tissue monitoring for detection of ischemia due to vasospasm in aneurysmal subarachnoid hemorrhage (SAH) patients. METHODS After obtaining informed consent, a burr hole was made in 10 patients and a Neurotrend 7 probe was inserted ipsilateral to the region of SAH. In eight patients the probe was inserted during surgery for clipping the aneurysm and in two patients the probe was inserted in the neurosurgery ICU. Brain tissue gases and pH were collected over 6-hour periods for 7 to 10 days until the termination of monitoring. The onset of vasospasm was confirmed by angiography and xenon computed tomography (Xe/CT) cerebral blood flow studies. RESULTS Seven patients did not develop vasospasm during monitoring and were considered as controls. In this group, brain tissue oxygen pressure (PO(2)) remained above 20 mmHg, carbon dioxide pressure (PCO(2)) stabilized at 40 mmHg and pH remained between 7.1 and 7.2. In three patients who developed vasospasm during monitoring, PO(2) was not different from the control group. However, PCO(2) increased to 60 mmHg and pH decreased to 6.7 (p < 0.001). CONCLUSION In this study, patients with SAH who developed vasospasm had significantly lower brain tissue pH and higher PCO(2) compared to controls. However, there was no significant change in PO(2) levels associated with vasospasm. Brain tissue monitoring can provide an indication of ischemia during vasospasm.

In Vivo Evaluation of Quantitative MR Angiography in a Canine Carotid Artery Stenosis Model

BACKGROUND AND PURPOSE: Large-vessel cerebral blood flow quantification has emerged as a potential predictor of stroke risk. QMRA uses phase-contrast techniques to noninvasively measure vessel flows. To evaluate the in vivo accuracy of QMRA for measuring the effects of progressive arterial stenosis, we compared this technique with invasive flow measurements from a sonographic transit-time flow probe in a canine model. MATERIALS AND METHODS: A sonographic flow probe was implanted around the CCA of hound dogs (n = 4) under general anesthesia. Pulsatile blood flow and arterial pressure were continuously recorded during CCA flow measurements with QMRA. A vascular tourniquet was applied around the CCA to produce progressive stenosis and varying flow rates. Statistical comparisons were made by using the Pearson product moment correlation coefficient. RESULTS: A total of 60 paired CCA flow measurements were compared. Mean blood flows ranged between 21 and 691 mL/min during QMRA acquisition as measured by the flow probe. The correlation coefficients between flow probe and QMRA measurements for mean, maximum, and minimum volume flow rates were 0.99 (P < .0001), 0.98 (P < .0001), and 0.96 (P < .0001), respectively. The overall proportional difference between the 2 techniques was 7.8 ± 1%. Measurements at higher flow rates and in the absence of arterial stenosis had the lowest PD. CONCLUSIONS: Noninvasive CCA flow measurements by using QMRA are accurate compared with invasive flow-probe measurements in a canine arterial flow model with stenosis and may be useful for the evaluation of the hemodynamic effects of stenosis caused by cerebrovascular atherosclerosis.

Effect of Hemodynamics on Stroke Risk in Symptomatic Atherosclerotic Vertebrobasilar Occlusive Disease

IMPORTANCE Atherosclerotic vertebrobasilar (VB) occlusive disease is a significant etiology of posterior circulation stroke, with regional hypoperfusion as an important potential contributor to stroke risk. OBJECTIVE To test the hypothesis that, among patients with symptomatic VB stenosis or occlusion, those with distal blood flow compromise as measured by large-vessel quantitative magnetic resonance angiography (QMRA) are at higher risk of subsequent posterior circulation stroke. DESIGN, SETTING, AND PARTICIPANTS A prospective, blinded, longitudinal cohort study was conducted at 5 academic hospital-based centers in the United States and Canada; 82 patients from inpatient and outpatient settings were enrolled. Participants with recent VB transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries underwent large-vessel flow measurement in the VB territory using QMRA. Physicians performing follow-up assessments were blinded to QMRA flow status. Follow-up included monthly telephone calls for 12 months and biannual clinical visits (for a minimum of 12 months, and up to 24 months or the final visit). Enrollment took place from July 1, 2008, to July 31, 2013, with study completion on June 30, 2014; data analysis was performed from October 1, 2014, to April 10, 2015. EXPOSURE Standard medical management of stroke risk factors. MAIN OUTCOMES AND MEASURES The primary outcome was VB-territory stroke. RESULTS Of the 82 enrolled patients, 72 remained eligible after central review of their angiograms. Sixty-nine of 72 patients completed the minimum 12-month follow-up; median follow-up was 23 (interquartile range, 14-25) months. Distal flow status was low in 18 of the 72 participants (25%) included in the analysis and was significantly associated with risk for a subsequent VB stroke (P = .04), with 12- and 24-month event-free survival rates of 78% and 70%, respectively, in the low-flow group vs 96% and 87%, respectively, in the normal-flow group. The hazard ratio, adjusted for age and stroke risk factors, in the low distal flow status group was 11.55 (95% CI, 1.88-71.00; P = .008). Medical risk factor management at 6-month intervals was similar between patients with low and normal distal flow. Distal flow status remained significantly associated with risk even when controlling for the degree of stenosis and location. CONCLUSIONS AND RELEVANCE Distal flow status determined using a noninvasive and practical imaging tool is robustly associated with risk for subsequent stroke in patients with symptomatic atherosclerotic VB occlusive disease. Identification of high-risk patients has important implications for future investigation of more aggressive interventional or medical therapies.

Effect of Age and Vascular Anatomy on Blood Flow in Major Cerebral Vessels

Measurement of volume flow rates in major cerebral vessels can be used to evaluate the hemodynamic effects of cerebrovascular disease. However, both age and vascular anatomy can affect flow rates independent of disease. We prospectively evaluated 325 healthy adult volunteers using phase contrast quantitative magnetic resonance angiography to characterize these effects on cerebral vessel flow rates and establish clinically useful normative reference values. Flows were measured in the major intracranial and extracranial vessels. The cohort ranged from 18 to 84 years old, with 157 (48%) females. All individual vessel flows and total cerebral blood flow (TCBF) declined with age, at 2.6 mL/minute per year for TCBF. Basilar artery (BA) flow was significantly decreased in individuals with one or both fetal posterior cerebral arteries (PCAs). Internal carotid artery flows were significantly higher with a fetal PCA and decreased with a hypoplastic anterior cerebral artery. Indexing vessel flows to TCBF neutralized the age effect, but anatomic variations continued to impact indexed flow in the BA and internal carotid artery. Variability in normative flow ranges were reduced in distal vessels and by examining regional flows. Cerebral vessel flows are affected by age and cerebrovascular anatomy, which has important implications for interpretation of flows in the disease state.

Leptomeningeal Collateral Volume Flow Assessed by Quantitative Magnetic Resonance Angiography in Large-Vessel Cerebrovascular Disease

Leptomeningeal collateral volume flow has not been previously quantified. Quantitative magnetic resonance angiography (QMRA) can determine flow in the large vessels of the intracranial circulation.

Hemodynamic Features of Symptomatic Vertebrobasilar Disease

Background and Purpose— Atherosclerotic vertebrobasilar disease is an important cause of posterior circulation stroke. To examine the role of hemodynamic compromise, a prospective multicenter study, Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS), was conducted. Here, we report clinical features and vessel flow measurements from the study cohort. Methods— Patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries (BA) were enrolled. Large-vessel flow in the vertebrobasilar territory was assessed using quantitative MRA. Results— The cohort (n=72; 44% women) had a mean age of 65.6 years; 72% presented with ischemic stroke. Hypertension (93%) and hyperlipidemia (81%) were the most prevalent vascular risk factors. BA flows correlated negatively with percentage stenosis in the affected vessel and positively to the minimal diameter at the stenosis site (P<0.01). A relative threshold effect was evident, with flows dropping most significantly with ≥80% stenosis/occlusion (P<0.05). Tandem disease involving the BA and either/both vertebral arteries had the greatest negative impact on immediate downstream flow in the BA (43 mL/min versus 71 mL/min; P=0.01). Distal flow status assessment, based on an algorithm incorporating collateral flow by examining distal vessels (BA and posterior cerebral arteries), correlated neither with multifocality of disease nor with severity of the maximal stenosis. Conclusions— Flow in stenotic posterior circulation vessels correlates with residual diameter and drops significantly with tandem disease. However, distal flow status, incorporating collateral capacity, is not well predicted by the severity or location of the disease.

Wall shear stress in major cerebral arteries as a function of age and gender--a study of 301 healthy volunteers.

The hemodynamic force of wall shear stress (WSS) has demonstrated a critical role in atherogenesis.

Effects of Extracranial Carotid Stenosis on Intracranial Blood Flow

Background and Purpose— The hemodynamic effects of extracranial carotid stenosis on intracranial blood flow are not well characterized. We sought to determine the impact of degree of stenosis, stenosis length, and residual lumen on intracranial blood flow in patients with extracranial carotid stenosis. Methods— Carotid stenosis patients who had undergone both vessel flow rate measurements using quantitative magnetic resonance angiography and digital subtraction angiography were examined. The impact of the anatomic measurements of the stenosis relative to ipsilateral internal carotid artery (ICA) flow and ipsilateral-to-contralateral middle cerebral artery (MCA) flow ratio were assessed. Results— Forty-four patients (mean age, 67 years; 64% symptomatic) were included. Higher percentage stenosis and smaller residual lumen were associated with a significant decrease in ICA flow (P<0.01 and 0.04, respectively). On multivariate analysis, percentage stenosis remained as the primary predictor of ICA flow (P<0.001). MCA flow ratio was not significantly associated with percentage stenosis, stenosis length, or residual lumen. However, mean MCA flow ratio was significantly lower in symptomatic compared with asymptomatic patients (0.92 versus 1.22; P=0.001). In contrast, mean ICA flow ratio was similar among these 2 groups (0.55 versus 0.55; P=0.99). Conclusions— Percentage stenosis and residual lumen are significantly associated with ICA but not MCA flow, suggesting that local hemodynamic effects of carotid stenosis do not translate directly to distal vasculature, because intracranial flows can be maintained through collaterals. The lower MCA flow ratio in symptomatic patients highlights the potential importance of distal hemodynamics in symptomatic presentation.