Jay S. Han

Mapping Cerebrovascular Reactivity Using Blood Oxygen Level-Dependent MRI in Patients With Arterial Steno-occlusive Disease: Comparison With Arterial Spin Labeling MRI

Background and Purpose— Blood oxygen level-dependent MRI (BOLD MRI) of hypercapnia-induced changes in cerebral blood flow is an emerging technique for mapping cerebrovascular reactivity (CVR). BOLD MRI signal reflects cerebral blood flow, but also depends on cerebral blood volume, cerebral metabolic rate, arterial oxygenation, and hematocrit. The purpose of this study was to determine whether, in patients with stenoocclusive disease, the BOLD MRI signal response to hypercapnia is directly related to changes in cerebral blood flow. Methods— Thirty-eight patients with steno-occlusive disease underwent mapping of CVR by both BOLD MRI and arterial spin labeling MRI. The latter technique was used as a reference standard for measurement of cerebral blood flow changes. Results— Hemispheric CVR measured by BOLD MRI was significantly correlated with that measured by arterial spin labeling MRI for both gray matter (R=0.83, P<0.0001) and white matter (R=0.80, P<0.0001). Diagnostic accuracy (area under receiver operating characteristic curve) for BOLD MRI discrimination between normal and abnormal hemispheric CVR was 0.90 (95% CI=0.81 to 0.98; P<0.001) for gray matter and 0.82 (95% CI=0.70 to 0.94; P<0.001) for white matter. Regions of paradoxical CVR on BOLD MRI had a moderate predictive value (14 of 19 hemispheres) for spatially corresponding paradoxical CVR on arterial spin labeling MRI. Complete absence of paradoxical CVR on BOLD MRI had a high predictive value (31 of 31 hemispheres) for corresponding nonparadoxical CVR on arterial spin labeling MRI. Conclusions— Arterial spin labeling MRI confirms that, even in patients with stenoocclusive disease, the BOLD MRI signal response to hypercapnia predominantly reflects changes in cerebral blood flow.

CO2 Blood Oxygen Level–dependent MR Mapping of Cerebrovascular Reserve in a Clinical Population: Safety, Tolerability, and Technical Feasibility

PURPOSE To evaluate the safety, tolerability, and technical feasibility of mapping cerebrovascular reactivity (CVR) in a clinical population by using a precise prospectively targeted CO(2) stimulus and blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging. MATERIALS AND METHODS A chart review was performed of all CVR studies from institutional review board-approved projects at a tertiary care hospital between January 1, 2006, and December 1, 2010. Informed consent was obtained. Records were searched for the incidence of adverse events and failed examinations. CVR maps were evaluated for diagnostic quality by two blinded observers and were categorized as good, diagnostic but suboptimal, or nondiagnostic. Outcomes were presented as raw data and descriptive statistics (means ± standard deviations). Intraclass correlation coefficient was used to determine interobserver variability. RESULTS Four hundred thirty-four consecutive CVR examinations from 294 patients (51.8% female patients) were studied. Patient age ranged from 9 to 88 years (mean age, 45.9 years ± 20.6). Transient symptoms, such as shortness of breath, headache, and dizziness, were reported in 48 subjects (11.1% of studies) during hypercapnic phases only. There were no neurologic ischemic events, myocardial infarctions, or other major complications. The success rate in generating CVR maps was 83.9% (364 of 434). Of the 70 (16.1%) failed examinations, 25 (35.7%) were due to discomfort; eight (11.4%), to head motion; two (2.9%), to inability to cooperate; seven (10.0%), to technical difficulties with equipment; and 28 (40.0%), to unknown or unspecified conditions. Among the 364 remaining successful examinations, good quality CVR maps were obtained in 340 (93.4%); diagnostic but suboptimal, in 12 (3.3%); and nondiagnostic, in 12 (3.3%). CONCLUSION CVR mapping by using a prospectively targeted CO(2) stimulus and BOLD MR imaging is safe, well tolerated, and technically feasible in a clinical patient population.

Selective Reduction of Blood Flow to White Matter During Hypercapnia Corresponds With Leukoaraiosis

Background and Purpose— Age-related white matter disease (leukoaraiosis) clusters in bands in the centrum semiovale, about the occipital and frontal horns of the lateral ventricles, in the corpus callosum, and internal capsule. Cerebrovascular anatomy suggests that some of these locations represent border zones between arterial supply territories. We hypothesized that there are zones of reduced cerebrovascular reserve (susceptible to selective reductions in blood flow, ie, steal phenomenon) in the white matter of young, healthy subjects, the physiological correlate of these anatomically defined border zones. Furthermore, we hypothesized that these zones spatially correspond with the regions where the elderly develop leukoaraiosis. Methods— Twenty-eight healthy volunteers underwent functional MR mapping of the cerebrovascular response to hypercapnia. We studied 18 subjects by blood oxygen level-dependent MRI and 10 subjects by arterial spin labeling MRI. We controlled both end-tidal pco2 and po2. All functional data was registered in Montreal Neurological Institute space and generated composite blood oxygen level-dependent MR and arterial spin labeling MR maps of cerebrovascular reserve. We compared these maps with frequency maps of leukoaraiosis published previously. Results— Composite maps demonstrated significant (90% CI excluding the value zero) steal phenomenon in the white matter. This steal was induced by relatively small changes in end-tidal pco2. It occurred precisely in those locations where elderly patients develop leukoaraiosis. Conclusions— This steal phenomenon likely represents the physiological correlate of the previously anatomically defined internal border zones. Spatial concordance with white matter changes in the elderly raises the possibility that this steal phenomenon may have a pathogenetic role.

Impact of Extracranial–Intracranial Bypass on Cerebrovascular Reactivity and Clinical Outcome in Patients With Symptomatic Moyamoya Vasculopathy

Background and Purpose— The purpose of this study was to evaluate in symptomatic moyamoya patients the effect of surgical revascularization on impaired cerebrovascular reactivity (CVR) and its relationship to clinical outcome. Methods— Brain revascularization was performed using a direct superficial temporal artery to middle cerebral artery bypass or indirect encephalo-dural–arterial synangiosis. CVR was measured pre- and 3 months postoperatively using blood oxygen level-dependent MRI during iso-oxic hypercapnic changes in end-tidal carbon dioxide. Outcomes were assessed by MRI, clinical examination, and modified Rankin Scale scores. Results— Fifty-five hemispheres were revascularized in 39 patients (superficial temporal artery to middle cerebral artery in 47, encephalo-dural–arterial synangiosis in 8). Surgery reversed CVR impairment in 52 hemispheres (94.5%) and in 36 of 39 patients (92.3%; Fisher exact test, P<0.001), and this was predictive of a patent extracranial–intracranial bypass. New, clinically silent perioperative hemorrhages, cortical foci of ischemia, or new white matter T2 hyperintensities were detected after 11 surgeries (20%), but no new lesions arose after 3 postoperative months. One patient had a clinical perioperative stroke (1.8%). In clinical follow-up, 37 of 39 patients (95%) had stable or improved modified Rankin Scale scores and 2 patients (5.1%) worsened. No patients with patent bypasses or CVR improvements exhibited new clinical symptoms, but failure of CVR improvement corresponded to a poorer long-term outcome (Fisher exact test, P<0.001). Conclusions— Cerebral revascularization surgery is a safe and effective treatment for reversing preoperative CVR defects and may prevent recurrence of preoperative symptoms. Moreover, CVR measurements may be useful in long-term follow-up and for predicting bypass patency.

Quantitative Measurement of Cerebrovascular Reactivity by Blood Oxygen Level-Dependent MR Imaging in Patients with Intracranial Stenosis: Preoperative Cerebrovascular Reactivity Predicts the Effect of Extracranial-Intracranial Bypass Surgery

BACKGROUND AND PURPOSE: CVR is a measure of cerebral hemodynamic impairment. A recently validated technique quantifies CVR by using a precise CO2 vasodilatory stimulus and BOLD MR imaging. Our aim was to determine whether preoperative CO2 BOLD CVR predicts the hemodynamic effect of ECIC bypass surgery in patients with intracranial steno-occlusive disease. MATERIALS AND METHODS: Twenty-five patients undergoing ECIC bypass surgery for treatment of intracranial stenosis or occlusion were recruited. CVR was measured preoperatively and postoperatively and expressed as %ΔBOLD MR signal intensity per mm Hg ΔPetCO2. Using normative data from healthy subjects, we stratified patients on the basis of preoperative CVR into 3 groups: normal CVR, reduced CVR, and negative (paradoxical) CVR. Wilcoxon 2-sample tests (2-sided, α = 0.05) were used to determine whether the 3 groups differed with respect to change in CVR following bypass surgery. RESULTS: The group with normal preoperative CVR demonstrated no significant change in CVR following bypass surgery (mean, 0.22% ± 0.05% to 0.22% ± 0.01%; P = .881). The group with reduced preoperative CVR demonstrated a significant improvement following bypass surgery (mean, 0.08% ± 0.05% to 0.21 ± 0.08%; P < .001), and the group with paradoxical preoperative CVR demonstrated the greatest improvement (mean change, −0.04% ± 0.03% to 0.27% ± 0.03%; P = .028). CONCLUSIONS: Preoperative measurement of CVR by using CO2 BOLD MR imaging predicts the hemodynamic effect of ECIC bypass in patients with intracranial steno-occlusive disease. The technique is potentially useful for selecting patients for surgical revascularization.

Impaired Cerebrovascular Reactivity With Steal Phenomenon Is Associated With Increased Diffusion in White Matter of Patients With Moyamoya Disease

Background and Purpose— Reduced cerebrovascular reactivity (CVR) with steal phenomenon is an independent predictor for stroke and may indicate tissue exposed to episodic low-grade ischemia. The apparent diffusion coefficient (ADC) calculated using diffusion-weighted MRI is effective in characterizing focal brain ischemia and subtle structural changes in normal-appearing white matter (WM). We hypothesized that regions of steal phenomenon are associated with increased ADC in normal-appearing WM of patients with Moyamoya disease. Methods— Twenty-two patients with unilateral CVR impairment secondary to Moyamoya disease and 12 healthy control subjects underwent diffusion-weighted MRI and functional MRI mapping of the cerebrovascular response to hypercapnia. Parametric maps of ADC and CVR were calculated, coregistered, and segmented using automated image processing methods. ADC of normal-appearing WM was compared between hemispheres, and between WM with negative CVR (ie, steal phenomenon) and WM with positive CVR. Results— In patients, ADC of normal-appearing WM was elevated in the hemisphere ipsilateral to the CVR impairment compared with the contralateral hemisphere (P<0.005) and in WM with negative CVR compared with WM with positive CVR (P<0.001). WM in regions of steal phenomenon within the affected hemisphere had higher ADC than homologous contralateral WM (P<0.005). In control subjects, negative CVR in WM was not associated with elevated ADC. Conclusions— Regions of steal phenomenon are spatially correlated with elevated ADC in normal-appearing WM of patients with Moyamoya disease. This structural abnormality may reflect low-grade ischemic injury after exhaustion of the cerebrovascular reserve capacity.

Impaired peri-nidal cerebrovascular reserve in seizure patients with brain arteriovenous malformations

Epileptic seizures are a common presentation in patients with newly diagnosed brain arteriovenous malformations, but the pathophysiological mechanisms causing the seizures remain poorly understood. We used magnetic resonance imaging-based quantitative cerebrovascular reactivity mapping and conventional angiography to determine whether seizure-prone patients with brain arteriovenous malformations exhibit impaired cerebrovascular reserve or morphological angiographic features predictive of seizures. Twenty consecutive patients with untreated brain arteriovenous malformations were recruited (10 with and 10 without epileptic seizures) along with 12 age-matched healthy controls. Blood oxygen level-dependent MRI was performed while applying iso-oxic step changes in end-tidal partial pressure of CO(2) to obtain quantitative cerebrovascular reactivity measurements. The brain arteriovenous malformation morphology was evaluated by angiography, to determine to what extent limitations of arterial blood supply or the presence of restricted venous outflow and tissue congestion correlated with seizure susceptibility. Only patients with seizures exhibited impaired peri-nidal cerebrovascular reactivity by magnetic resonance imaging (0.11 ± 0.10 versus 0.25 ± 0.07, respectively; P < 0.001) and venous drainage patterns suggestive of tissue congestion on angiography. However, cerebrovascular reactivity changes were not of a magnitude suggestive of arterial steal, and were probably compatible with venous congestion in aetiology. Our findings demonstrate a strong association between impaired peri-nidal cerebrovascular reserve and epileptic seizure presentation in patients with brain arteriovenous malformation. The impaired cerebrovascular reserve may be associated with venous congestion. Quantitative measurements of cerebrovascular reactivity using blood oxygen level-dependent MRI appear to correlate with seizure susceptibility in patients with brain arteriovenous malformation.

Quantification of cerebrovascular reactivity by blood oxygen level-dependent MR imaging and correlation with conventional angiography in patients with Moyamoya disease.

BACKGROUND AND PURPOSE: BOLD MR imaging combined with a technique for precision control of end-tidal pCO2 was used to produce quantitative maps of CVR in patients with Moyamoya disease. The technique was validated against measures of disease severity by using conventional angiography; it then was used to study the relationship between CVR, vascular steal, and disease severity. MATERIALS AND METHODS: A retrospective analysis comparing conventional angiography with BOLD MR imaging was performed on 11 patients with Moyamoya disease. Iso-oxic cycling of end-tidal pCO2 between 2 target values was performed during BOLD MR imaging. CVR was calculated as the BOLD signal difference per ΔpCO2. CVR was correlated with the presence of Moyamoya or pial collaterals and the degree of Moyamaya disease as graded by using a modified Suzuki score. RESULTS: A good correlation between mean CVR and Suzuki score was found for the MCA and ACA territories (Pearson correlation coefficient, −0.7560 and −0.6140, respectively; P < .0001). A similar correlation was found between mean CVR and the presence of pial and Moyamoya collateral vessels for combined MCA and ACA territories (Pearson correlation coefficient, −0.7466; P < .0001). On a voxel-for-voxel basis, there was a greater extent of steal within vascular territories with increasing disease severity (higher modified Suzuki score). Mean CVR was found to scale nonlinearly with the extent of vascular steal. CONCLUSIONS: Quantitative measures of CVR show direct correlation with impaired vascular supply as measured by the modified Suzuki score and enable direct investigation of the physiology of autoregulatory reserve, including steal phenomenon, within a given vascular territory.

BOLD signal responses to controlled hypercapnia in human spinal cord.

Functional MRI of the spinal cord is challenging due to the small cross section of the cord and high level of physiological noise. Though blood oxygenation level-dependent (BOLD) contrast has been used to study specific responses of the spinal cord to various stimuli, it has not been demonstrated using a controlled stimulus. In this paper, we use hypercapnic manipulation to study the sensitivity and specificity of functional MRI in the human cervical spinal cord. Simultaneous MR imaging in the brain and spinal cord was performed for direct comparison with the brain, in which responses to hypercapnia have been more extensively characterized. Original contributions include: (i) prospectively controlled hypercapnic changes in end-tidal PCO(2), (ii) simultaneous recording of BOLD responses in the brain and spinal cord, and (iii) generation of statistical maps of BOLD responses throughout the brain and spinal cord, taking into account physiological noise sources. Results showed significant responses in all subjects both in the brain and the spinal cord. In anatomically-defined regions of interest, mean percent changes were 0.6% in the spinal cord and 1% in the brain. Analysis of residual variance demonstrated significantly larger contribution of physiological noise in the spinal cord (P<0.005). To obtain more reliable results from fMRI in the spinal cord, it will be necessary to improve sensitivity through the use of highly parallelized coil arrays and better modeling of physiological noise. Finely, we believe that the use of controlled global stimuli, such as hypercapnia, will help assess the effectiveness of new acquisition techniques.

BOLD-MRI cerebrovascular reactivity findings in cocaine-induced cerebral vasculitis

Background An 18-year-old woman presented to a regional stroke center with dysphasia and right hemiparesis 2 days after consuming alcohol and inhaling cannabis and—for the first time—cocaine.Investigations Physical examination, blood tests for inflammatory markers, vasculitis and toxicology screen, echocardiography, electrocardiography, CT scanning, brain MRI, magnetic resonance angiography, magnetic resonance vessel wall imaging, catheter angiography, and correlation of blood oxygen level-dependent (BOLD)-MRI signal intensity with changes in end-tidal partial pressure of carbon dioxide.Diagnosis Cocaine-induced cerebral vasculitis.Management No specific therapy was initiated. The patients vital signs and neurological status were monitored during her admission. Follow-up medical imaging was performed after the patients discharge from hospital.