Normal Cerebrovascular Reactivity Research Articles

Abstract WP127: Diagnostic Value of the Ivy Sign Compared to MR With Cerebrovascular Reactivity in Decompensated Moyamoya Arteriopathy

Introduction: MR cerebrovascular reactivity (CVR) mapping during rapid manipulation of end-tidal pCO2 is used to assess hemodynamic compromise in patients with Moyamoya arteriopathy (MMA). Leptomeningeal ivy sign on MRI FLAIR sequence may indicate regions of decreased perfusion, which would be an inexpensive and easy way to screen for hemodynamic compromise. The purpose of this study was to examine the diagnostic value of the ivy sign compared to MR CVR. Methods: For this retrospective cross-sectional study, we included consecutive patients with uncompensated MMA who were eligible for extracranial-intracranial bypass surgery and completed a preoperative MRI FLAIR with CVR study. Patients with incomplete or artefact degraded imaging were excluded. Two neuroradiologists who were blinded for the CVR result independently assessed the degree of ivy sign on axial 2D FLAIR imaging as grade 0, 1 or 2 in 8 predefined brain regions. Two different readers, blinded for ivy sign, independently assessed the presence or absence of steal in the same regions on MR CVR. Consensus was reached for discordant findings. We assessed interrater agreement using weighted kappa followed by diagnostic accuracy measures for the ivy sign using MR CVR as a reference. Results: We enrolled 73 patients (41/73 (56.1%) female; mean age 43). 47/73 (64%) patients had bilateral MMA with on average 3 brain regions with abnormal CVR. Interrater agreement was good for ivy sign (weighted kappa 0.63 (95%CI 0.54-0.71)) and excellent for CVR (kappa 0.95 (95% CI 0.87-1.00)). For a total of 156/584 (26.7%) brain regions, there was agreement between a positive ivy sign and the presence of steal on CVR and 240/584 (41%) brain regions had no ivy sign and normal CVR. The sensitivity of the ivy sign was 64.5%, specificity 70.2%, positive predictive value 60.5% and negative predictive value 73.6% with an AUC of 0.68 (95% CI 0.64-0.72) Conclusions: In this preselected cohort with high pretest probability for hemodynamic compromise, the diagnostic accuracy of the ivy sign compared to MR CVR was limited and needs to be used with caution to determine haemodynamic status in MMA.

Brain Stress Test for Assessing Risk for Hemodynamic Stroke.

In patients with intracranial steno-occlusive disease (SOD), the risk of hemodynamic stroke depends on the poststenotic vasodilatory reserve. Cerebrovascular reactivity (CVR) is a test for vasodilatory reserve. We tested for vasodilatory reserve by using PETCO2 as the stressor, and Blood Oxygen Level Dependent (BOLD) MRI as a surrogate of blood flow. We correlate the CVR to the incidence of stroke after a 1-year follow-up in patients with symptomatic intracranial SOD. In this retrospective study, 100 consecutive patients with symptomatic intracranial SOD that had undergone CVR testing were identified. CVR was measured as % BOLD MR signal intensity/mmHg PETCO2. All patients with normal CVR were treated with optimal medical therapy; those with abnormal CVR were offered revascularization where feasible. We determined the incidence of stroke at 1 year. 83 patients were included in the study. CVR was normal in 14 patients and impaired in 69 patients ipsilateral to the lesion. Of these, 53 underwent surgical revascularization. CVR and symptoms improved in 86% of the latter. The overall incidence of stroke was 4.8 % (4/83). All strokes occurred in patients with impaired CVR (4/69; 2/53 in the surgical group, all in the nonrevascularized hemisphere), and none in patients with normal CVR (0/14). Our study confirms that CO2-BOLD MRI CVR can be used as a brain stress test for the assessment of cerebrovascular reserve. Impaired CVR is associated with a higher incidence of stroke and normal CVR despite significant stenosis is associated with a low risk for stroke.

Abstract TP168: Quantitative Cerebrovascular Reactivity Atlas In Children

Introduction: Cerebrovascular reactivity (CVR) can be measured by inducing carbon dioxide (CO 2 ) changes in the circulation and measuring subsequent changes in blood flow with functional MRI blood oxygen level dependent sequences (BOLD). In clinical practice, abnormalities in CVR imaging can serve as a biomarker of ischemic risk. To characterize pathological aberrations in CVR, it is essential to have quantitative reference data as to what constitutes normal CVR across brain regions at various stages of development. Methods: Prospective enrollment of healthy children ages 6 to 18. Target N of 40. Two datasets are being generated within the atlas using two different methods of administering the vasoactive stimulus (CO 2 ): a breath-hold CVR dataset (endogenous stimulus) and a RespirAct TM CVR dataset (exogenous). A test of normality is performed on CVR values for each voxel across subjects, with mean and standard deviation calculations. This will allow for generation of a Z-score for each CVR value per voxel in any clinical CVR study. Voxel-wide validation of breath-hold CVR values against the gold standard RespirAct TM CVR values will be performed using within subject t-test and between group comparisons. Subgroup analysis based on gender and age will also be performed. Results: Preliminary CVR data for 8 healthy right-handed children is presented (4 female, median age 13, range 9 -14 years). All participants tolerated CVR studies well and no side effects were reported. Group datasets acquired to date passed tests of normality with no significant differences in CVR values between the two methods found. Conclusions: This study will generate the first atlas of quantitative CVR-fMRI data in healthy children. Normative physiological data on CVR changes throughout childhood, and associations between CVR, blood pressure, age, and gender will be obtained. CVR imaging is performed clinically in patients with a risk of recurrent arterial ischemic stroke such as those with intracranial arteriopathies, sickle cell disease and other genetic and metabolic disorders. Our atlas can provide clinicians with objective measures regarding extent and distribution of CVR abnormalities, allow for stroke risk stratification, and aid in determining the optimal time for intervention.

Cerebrovascular reactivity changes in acute concussion: a controlled cohort study.

Evidence suggests that cerebrovascular reactivity (CVR) increases within the first week after the incidence of concussion, indicating a disruption of normal autoregulation. We sought to extend these findings by investigating the effects of acute concussion on the speed of CVR response and by visualizing global and regional impairments in individual patients with acute concussion. Twelve patients aged 18-40 years who experienced concussion less than a week before this prospective study were included. Twelve age and sex-matched healthy subjects constituted the control group. In all subjects, CVR was assessed using blood oxygenation level-dependent (BOLD) echo-planar imaging with a 3.0T MRI scanner, in combination with changes in end-tidal partial pressure of CO2 (PETCO2). In each subject, we calculated the CVR amplitude and CVR response time in the gray and white matter using a step and ramp PETCO2 challenge. In addition, a separate group of 39 healthy controls who underwent the same evaluation was used to create atlases with voxel-wise mean and standard deviation of CVR amplitude and CVR response time. This allowed us to convert each metric of the 12 patients with concussion and the 12 healthy controls into z-score maps. These maps were then used to generate and compare z-scores for each of the two groups. Group differences were calculated using an unpaired t-test. All studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study subjects. No differences in CO2 stimulus and O2 targeting were observed between the two participant groups during BOLD MRI. With regard to the gray matter, the CVR magnitude step (P=0.117) and ramp + 10 (P=0.085) were not significantly different between patients with concussion and healthy controls. However, the tau value was significantly lower in patients with concussion than in the healthy controls (P=0.04). With regard to the white matter, the CVR magnitude step (P=0.003) and ramp + 10 (P=0.031) were significantly higher and the tau value (P=0.024) was significantly shorter in patients with concussion than in healthy controls. After z-score transformation, the z tau value was significantly lower in patients with concussion than in healthy controls (Grey matter P=0.021, White matter P=0.003). Comparison of the three parameters, z ramp + 10, z step, and z tau, between the two groups showed that z step (Grey matter P=0.035, White matter P=0.005) was the most sensitive parameter and that z ramp + 10 (Grey matter P=0.073, White matter P=0.126) was the least sensitive parameter. Concussion is associated with patient-specific abnormalities in BOLD cerebrovascular responsiveness that occur in the setting of normal global CVR. This study demonstrates that the measurement of CVR using BOLD MRI and precise CO2 control is a safe, reliable, reproducible, and clinically useful method for evaluating the state of patients with concussion. It has the potential to be an important tool for assessing the severity and duration of symptoms after concussion.

The Reproducibility of Cerebrovascular Reactivity Across MRI Scanners.

Cerebrovascular reactivity (CVR) is defined as the ratio of the cerebral blood flow (CBF) response to an increase in a vasoactive stimulus. We used changes in blood oxygenation level-dependent (BOLD) MRI as surrogates for changes of CBF, and standardized quantitative changes in arterial partial pressure of carbon dioxide as the stimulus. Despite uniform stimulus and test conditions, differences in voxel-wise BOLD changes between testing sites may remain, attributable to physiologic and machine variability. We generated a reference atlas of normal CVR metrics (voxel-wise mean and SD) for each of two sites. We hypothesized that there would be no significant differences in CVR between the two atlases enabling each atlas to be used at any site. A total of 69 healthy subjects were tested to create site-specific atlases, with 20 of those individuals tested at both sites. 38 subjects were scanned at Site 1 (17F, 37.5 ± 16.8 y) and 51 subjects were tested at Site 2 (22F, 40.9 ± 17.4 y). MRI platforms were: Site 1, 3T Magnetom Skyra Siemens scanner with 20-channel head and neck coil; and Site 2, 3T HDx Signa GE scanner with 8-channel head coil. To construct the atlases, test results of individual subjects were co-registered into a standard space and voxel-wise mean and SD CVR metrics were calculated. Map comparisons of z scores found no significant differences between white matter or gray matter in the 20 subjects scanned at both sites when analyzed with either atlas. We conclude that individual CVR testing, and atlas generation are compatible across sites provided that standardized respiratory stimuli and BOLD MRI scan parameters are used. This enables the use of a single atlas to score the normality of CVR metrics across multiple sites.

Cerebrovascular Reactivity Assays Collateral Function in Carotid Stenosis.

In patients with carotid artery stenosis (CAS), the risk of stroke, its severity, and response to revascularization are strongly related to the availability of collateral blood flow. Unfortunately, there is poor agreement between observers in assessing collateral flow using flow-based imaging. We used changes in blood-oxygen-level-dependent (BOLD) MRI as a surrogate of changes in regional cerebral blood flow in response to a hypercapnic stimulus [i.e., cerebrovascular reactivity (CVR)] as indicating flow reserve ipsilateral to CAS. We hypothesized that some patients with hemodynamically significant CAS develop functional collateral flow as indicated by normalization of ipsilateral CVR. We identified 55 patients in our CVR database with various degrees of CAS assessed by angiography and classed them as <50% stenosis, 50–69% stenosis, 70–90% stenosis, >90% stenosis, and full occlusion. CVR was measured as the change in BOLD signal in response to changes in end-tidal partial pressure of CO2 (Δ BOLD/Δ PETCO2) and normalized voxel-wise relative to the mean and standard deviation of the CVR in the corresponding voxels of an atlas of 46 healthy controls (CVR z scores). CVR and z scores were then averaged over gray matter (GM) and white matter (WM) on each side of the middle cerebral artery (MCA) territory. As hypothesized, CVR varied for each severity of CAS. Ipsilateral MCA territory CVR was less than normal in each class, including that with <50% stenosis (Student t-test, two-tailed; p = 0.0014 for GM and p = 0.030 for WM), with a trend of decreasing average CVR with increasing stenosis. Remarkably, the considerable individual variability in MCA CVR included some patients with normal CVR in each class – including that with complete occlusion. We conclude that, in general, CAS depresses downstream vascular reserve, but the extent of collateralization is highly variable and not predictable from the degree of stenosis, including both <50% stenosis and complete occlusion. CVR may be the more reliable marker for recruitable collateral blood flow than degree of CAS.

Assessment of Cerebrovascular Reserve in the Heart Failure Patients Supported with the HeartMate3

We previously showed that cerebrovascular reactivity (CVR) is reduced in heart failure (HF) patients and does not improve after left ventricular assist device (LVAD) HeartMate II (HMII) implantation, possibly because of low pulsatile physiology. Therefore, it is possible that the artificial pulse of the latest generation LVAD, the HeartMate3 (HM3), restores normal CVR. HM3 patients will have an increased CVR to a CO2-retention challenge compared with HF and HMII. A total of 79 subjects (17 healthy, 30 HF, 15 HMII and 17 HM3) underwent angle-corrected transcranial Doppler sonography. Middle cerebral artery (MCA) velocity profiles were recorded before and at the end of a 30s breath hold. Mean flow velocity (MFV), peak flow velocity (Vmax), minimal flow velocity (Vmin), Pulsatility Index (PI) and Resistance Index (RI) were quantified. Statistical differences were determined using 2-way ANOVA (Breathhold x group). At baseline, HF patients with and without LVAD implantation had a decreased Vmax, MFV, PI and RI compared to healthy (all P < 0.05). With CO2-retention the absolute and relative increase in MFV was highest in the HM3 group significantly compared with HMII (7.8±2.4 vs 1.6±2.1 cm/s; +16% vs +3%, p<0.01). HM3 and HF subjects exhibited similar absolute and relative changes in MFV and both were lower than health controls. Similar results were seen for Vmax and Vmin, however, there was no change PI or RI in any groups (Fig. 1). The change with MFV with breath-holding was not different when considering HF subjects on inotropes, or when comparing beats with and without artificial pulse in HM3 patients. HM3 patients have a significantly improved CVR to a CO2-retention challenge compared with HMII patients. However, the acute CVR is not altered by the artificial pulse. Since CVR of HM3 patients remains reduced compared with healthy controls, further research is needed to understand the pathophysiology of cerebrovascular complications in LVAD.

Impaired Cerebral Hemodynamics and Frailty in Patients with Cardiovascular Disease.

Recent studies suggest that impaired cerebrovascular reactivity (CVR), a marker of cerebral microvascular damage, is associated with a higher risk of stroke, cognitive decline, and mortality. We tested whether abnormal cerebrovascular status is associated with late-life frailty among men with pre-existing cardiovascular disease. A subset of 327 men (mean age at baseline 56.7 ± 6.5 years) who previously participated in the Bezafibrate Infarction Prevention (BIP) trial (1990-1997) and then in the BIP Neurocognitive Study underwent a neurovascular evaluation 14.6 ± 1.9 years after baseline (T1) and were evaluated for frailty 19.9 ± 1.0 years after baseline (T2). CVR was measured at T1 using the breath-holding index and carotid large-vessel disease using ultrasound. Frailty status was measured at T2 according to the physical phenotype developed by Fried. Patients were categorized into CVR tertiles with cutoff points at ≤0.57, 0.58-0.94, and ≥0.95 and also as normal or impaired (<0.69) CVR. We assessed the change in the odds of being in the advanced rank of frailty status (normal, prefrail, and frail) using ordered logistic regression. After adjustment, the estimated OR (95% confidence intervals) for increasing frailty in the lower tertile was 1.94 (1.09-3.46) and in the middle tertile 1.24 (0.70-2.19), compared with the higher CVR tertile. The estimated OR for increasing frailty for patients with impaired vs. normal CVR was 1.76 (1.11-2.80). These findings provide support that cerebral microvascular dysfunction among patients with pre-existing cardiovascular disease is related to prefrailty and frailty and suggest an added value of assessing the cerebral vascular functional status for identifying patients at-risk of developing frailty.

Invalidation of fMRI experiments secondary to neurovascular uncoupling in patients with cerebrovascular disease.

Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a technique used to infer neuronal activity from the observed changes in blood flow. Cerebrovascular reactivity (CVR) is the ability of arterioles to increase blood flow in response to vasodilatory stimulus. We hypothesize that in areas of disease where there is exhausted vascular reserve and impaired CVR there will be diminished blood flow response following neuronal activation, and that these areas would appear as false-negative tests on BOLD fMRI. Patients with steno-occlusive disease and unilateral hemodynamic impairment received a standardized hypercapnic stimuli while being imaged with BOLD fMRI to generate CVR maps. These were compared to traditional BOLD fMRI maps of neuronal activation in the motor cortex in response to a motor task. Neuronal activation from the motor task was found to be linearly correlated with CVR (n = 11 patients, R = 0.82). Regions with positive (normal) CVR showed positive activation on BOLD fMRI, while regions with negative CVR had attenuated neuronal activation on BOLD fMRI. In areas with cerebrovascular disease where CVR is impaired, there is uncoupling of neuronal activation and blood flow that confounds traditional BOLD fMRI. CVR mapping is a noninvasive MRI-based imaging technique that can provide information about the vascular reactivity of the brain that is important to consider when interpreting traditional BOLD fMRI studies. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1448-1455.

Determining Significant Within‐Subject Changes of BOLD MRI Cerebrovascular Reactivity to CO2

Cerebrovascular reactivity (CVR) is the ratio of the cerebral blood flow (CBF) response to an increase in a vasoactive stimulus. Current measurement of CVR uses the BOLD MRI signal as an indicator of CBF in response to standardized changes in CO2. Despite uniform test conditions, there are still test‐to‐test differences in CVR due to variations in physiology and technology over time. Thus performing longitudinal studies requires the quantification of abnormal differences in CVR over time. We therefore generated a database of normal CVR test‐retest variability as a normal reference to statistically score differences in CVR. Two standardized CVR tests were conducted in fifteen healthy males (36.7 ± 16.1 y) within a three week period. All scans were co‐registered into standard space and a normal difference CVR map was calculated from the two time points for all voxels for each of the 15 subjects consisting of the mean and standard deviation of the differences to generate an interval test difference (ID) atlas. We illustrate our concept by generating ID z‐maps for patients with steno‐occlusive disease who had CVR tests done before and after surgical intervention. Differences in CVR values for the patients were compared to the ID atlas and scored as z‐values, the fractional standard deviation from the corresponding voxel of the atlas. The ID z‐maps confirmed improvement brought about by surgical intervention, and gave an indication of the extent and distribution of changes in CVR. The application of ID z‐maps will enable study of the natural history of cerebrovascular disease and response to treatment.

Abstract T P105: Decrease in Noninvasive Fractional Flow on MRA Is a Useful Marker of Misery Perfusion on SPECT

Background: Cerebrovascular reactivity to acetazolamide on 123I-IMP SPECT is used to detect misery perfusion due to intracranial atherosclerosis. Noninvasive fractional flow reserve (FFR) on time-of-flight magnetic resonance angiography (TOF-MRA) can provide a feasible alternative to identify high-risk intracranial atherosclerosis. We here demonstrate the association between FFR on TOF-MRA and cerebral blood flow pattern on 123I-IMP SPECT. Methods: Patients with a unilateral middle cerebral artery (MCA) stenosis who underwent both TOF-MRA and 123I-IMP SPECT with acetazolamide administration were retrospectively recruited from our radiology database. Signal intensity (SI) was measured in the background, proximal and distal to the stenotic lesion in the MCA on TOF-MRA. Adjusted FFR was calculated: FFR = [distal SI - background SI] / [proximal SI - background SI]. Mean cerebral blood flow (CBF) at rest, CBF after acetazolamide administration, and cerebrovascular reactivity (CVR) were measured in the target MCA territory. CBF patterns of MCA were divided into three: Stage II, CBF at rest of &lt; 80% in that of normal subject and CVR below 10%; Stage 0, CVR over 30% regardless of CBF at rest, and Stage I, any other CBF patterns. We sought the optimum cut-off point for FFR to identify MCA territories with Stage II CBF on 123I-IMP SPECT. Results: A total of 41 sets of diagnostic imaging in 23 patients (mean age 57 y; 14 men, 9 women) was assessed. Four (9.8%) MCA territories demonstrated Stage II, 21 (51.2%) stage I, and 16 (39.0%) stage 0. Mean FFR of MCA with Stage II pattern was 0.59 (IQR 0.38 - 0.69), Stage I was 0.78 (IQR 0.70- 0.92), and Stage 0 was 0.90 (IQR 0.81 - 0.93). The optimal cut-off point for FFR to predict Stage II was ≤ 0.7 (sensitivity 100%; specificity 86%). Conclusion: In patients with unilateral MCA lesions, an FFR decrease was correlated with misery perfusion on 123I-IMP SPECT with acetazolamide, which may be a more feasible predictor of high-risk intracranial stenosis.

Pathophysiology of acute cerebrovascular syndrome in patients with carotid artery stenosis: a magnetic resonance imaging/single-photon emission computed tomography study.

The mechanisms underlying acute cerebrovascular syndrome in patients with carotid artery stenosis remain unclear. To assess the relationships among infarct localization, hemodynamics, and plaque components. This prospective study included 38 patients with acute cerebrovascular syndrome resulting from ipsilateral carotid artery stenosis. Cerebral infarct localization was categorized into 3 patterns (cortical, border zone, and mixed pattern). Carotid plaque components were evaluated with T1-weighted magnetic resonance imaging and time-of-flight imaging. Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were also quantified. Infarcts were identified in 38 patients with the use of diffusion-weighted magnetic resonance imaging. On the basis of the assessment of hemodynamics, the cortical pattern was seen in 18 of 21 patients with type 1 ischemia (normal CBF, normal CVR), whereas the mixed pattern was seen in 2 patients with type 2 ischemia (normal CBF, impaired CVR) and 12 of 15 patients with type 3 ischemia (impaired CBF, impaired CVR). The plaque components were categorized into fibrous (4 patients), lipid-rich (14 patients), and intraplaque hemorrhage (IPH; 20 patients). Of the patients with fibrous plaque, 2 had border-zone and 2 had mixed-pattern infarcts. Of the patients with lipid-rich plaque, 7 had cortical and 6 had mixed-pattern infarcts. Of patients with intraplaque hemorrhage, 11 had cortical and 9 had mixed-pattern infarcts. Cortical infarction occurs as a result of vulnerable plaque. Reduced cerebral perfusion induces border-zone infarction. Both factors are implicated in mixed-pattern infarction. Developments in noninvasive diagnostic modalities allow us to explore the mechanisms behind acute cerebrovascular syndrome in carotid artery stenosis and to determine the ideal therapies.

Impaired cerebrovascular reactivity after acute traumatic brain injury can be detected by wavelet phase coherence analysis of the intracranial and arterial blood pressure signals

The objective of the study was to evaluate the wavelet spectral energy of oscillations in the intracranial pressure (ICP) signal in patients with acute traumatic brain injury (TBI). The wavelet phase coherence and phase shift in the 0.006–2 Hz interval between the ICP and the arterial blood pressure (ABP) signals were also investigated. Patients were separated into normal or impaired cerebrovascular reactivity, based on the pressure reactivity index (PRx). Spectral energy, phase coherence and phase shift in the low frequency and cardiorespiratory intervals were compared for the two groups. Data were prospectively collected and analyzed retrospectively in 22 patients, within the first week after acute TBI. The ICP and ABP signals were continuously recorded for cong 40 min and the wavelet transform was used to calculate the spectral energy and phase of the signals. The average ICP wavelet energy spectrum showed distinct peaks around 1.0 (cardiac), 0.25 (respiratory) and 0.03 Hz. Patients with normal cerebrovascular reactivity (negative PRx) had 38.6 % (±SD 16.7 %) of the mean wavelet energy below the lower limit of the respiratory frequency band (0.14 Hz) compared to only 18.1 % (±SD 17.8 %) in patients with altered cerebrovascular reactivity (positive PRx) (difference: p = 0.0057). Wavelet phase coherence between the ABP and ICP signals was statistically significant (p < 0.05) in the 0.006–2 Hz interval. The phase shift between the ABP and ICP signals was around zero in the 0.14–1.0 Hz interval. Seven patients with PRx between −0.4943 and −0.1653 had a phase shift in the interval 0.07–0.14 Hz, whereas 15 patients with PRx between −0.1019 and 0.3881 had a phase shift in the interval 0.006–0.07 Hz. We conclude that the wavelet transform of the ICP signal shows spectral peaks at the cardiac, respiratory and 0.03 Hz frequencies. Normal cerebrovascular reactivity seems to be manifested as increased spectral energy in the frequency interval <0.14 Hz. A phase shift between the ICP and ABP signals in the interval 0.07–0.14 Hz indicates normal cerebrovascular reactivity, while a phase shift in the interval 0.006–0.07 Hz indicates altered cerebrovascular reactivity.

Abstract TP83: Impaired Cerebrovascular Reactivity to Acetazolamide in Parent Arterial Territory of Major Artery Aneurysms in Adult Patients with Moyamoya Disease

Background— Recent studies have suggested that haemodynamic stress probably induces the formation of major artery aneurysms around the circle of Willis in adult patients with moyamoya disease (MMD). Theoretically, cerebrovascular reactivity (CVR) to acetazolamide (ACZ) is gradually reduced in the conditions that cerebral perfusion pressure is decreased. If arterial narrowing progress, CVR to ACZ would be reduced (Kuroda’s Type 2 or 3 ischemia) in the parent arterial territory of these aneurysms owing to elevated cerebrovascular resistance. This study was aimed to test the hypothesis whether the CVR to ACZ is reduced in the parent arterial territory of the major artery aneurysms. Methods— This retrospective study included 172 adult patients with MMD diagnosed at our institutes between 1980 and 2011. Eight major artery aneurysms was found in 7 (4.1%) of these patients, including 5 women and 3 men at the mean age of 47.4 years. Aneurysm location and perfusion territory of the parent artery were determined on digital subtraction angiography. Regional cerebral blood flow (CBF) was quantitatively measured, using 123 I-IMP SPECT. Subsequently, ACZ was intravenously injected to determine the reactivity of CBF. CVR to ACZ in the parent arterial territory was calculated (n=8). CVR in the contralateral arterial territory of the parent artery was utilized as a control (n=6). Results— Four (50%) of 8 major artery aneurysms were located in the vertebrobasilar system. All aneurysms were saccular and small, ranging from 2.0 and 5.0 mm. CVR to ACZ were reduced in 5 (62.5%) of 8 parent arterial territory (Type 2 or 3). All the contralateral arterial territory of the parent artery had normal CBF and CVR to ACZ (Type 1). Compared with contralateral side (32.0 ± 10.7%), CVR to ACZ was not significantly reduced in the parent artery side (16.5 ± 19.0%, P=0.11; paired-t). Fisher’s exact test, however, demonstrated a significant association between the existence of major artery aneurysms and reduced CVR to ACZ in the parent arterial territory (P=0.03). Conclusions— These findings suggest that reduced CVR in the parent arterial territory of the major artery aneurysms indicates underlying hemodynamic vascular stress inducing aneurysm formation in adult patients with MMD.

Coil Embolization of a Ruptured Basilar Tip Aneurysm Associated with Bilateral Cervical Internal Carotid Artery Occlusion: A Case Report and Literature Review

We report here on a rare case of a ruptured basilar tip aneurysm that was successfully treated with coil embolization in the bilateral cervical internal carotid artery (ICA) occlusions with abnormal vascular networks from the posterior circulation. A 43-year old man with a familial history of moyamoya disease presented with subarachnoid hemorrhage. Digital subtraction angiography demonstrated complete occlusion of the bilateral ICAs at the proximal portion and a ruptured aneurysm at the basilar artery bifurcation. Each meningeal artery supplied the anterior cranial base, but most of both hemispheres were supplied with blood from the basilar artery and the posterior cerebral arteries through a large number of collateral vessels to the ICA bifurcation as well as the anterior cerebral and middle cerebral arteries. The perfusion computed tomography (CT) scans with acetazolamide (ACZ) injection revealed no reduction of cerebral blood flow and normal cerebrovascular reactivity to ACZ. An abdominal CT aortogram showed no other extracranial vessel abnormalities. A ruptured basilar tip aneurysm was successfully treated with coil embolization without complications. Endovascular embolization may be a good treatment option with excellent safety for a ruptured basilar tip aneurysm that accompanies proximal ICA occlusion with vulnerable collateral flow.

Cerebrovascular Reactivity Impairment after Sport-Induced Concussion

This study evaluated cerebrovascular reactivity (CVR) after a sport-induced concussion, also called mild traumatic brain injury (mTBI), by monitoring middle cerebral artery blood velocity (vMCA) with transcranial Doppler ultrasonography and simultaneous end-tidal carbon dioxide (PETCO(2)) measurements. Thirty-one athletes (16-25 yr old) participated in this study. The participants were divided into two groups-healthy (n = 21) and mTBI (n = 10). Participants in the mTBI group suffered an mTBI within the last 7 d (x- = 4.5 ± 1.1 d). Outcome measures included vMCA and PETCO(2) in response to breath holding (5 × 20 s, 40-s rest) and hyperventilation (5 × 20 s, 40-s rest). Resting vMCA values between groups were not significantly different. Percentage change of vMCA was significantly different after the recovery period of the second hyperventilation (P = 0.034). mTBI subjects failed to return to resting levels after each breath hold. PETCO(2) changes mirrored the vMCA changes. These data suggest that normal CVR responses may be disrupted in the days immediately after occurrence of mTBI. Transcranial Doppler ultrasonography combined with expired gas measurements provides a useful method for assessing CVR impairment after mTBI. Further research, including serial monitoring after mTBI and analysis of CVR response to exercise, is warranted before any firm conclusions can be drawn.

Autonomic dysfunction in mild cognitive impairment: a transcranial Doppler study

The contribution of early microvascular and autonomic derangements to the pathogenesis of mild cognitive impairment (MCI) is unclear. Aim of this study is to evaluate cerebrovascular reactivity (CVR) and cardiac autonomic function in patients with MCI by means of transcranial Doppler (TCD). Fifteen patients with MCI and 28 controls underwent carotid ultrasound and TCD evaluation, including assessment of mean flow velocity (MFV) in the middle cerebral artery at baseline, after CO(2) inhalation and after hyperpnoea. End-tidal CO(2) , mean arterial blood pressure (MAP), heart rate (HR), and respiratory rate were monitored throughout the procedure, and CVR was calculated. MAP, end-tidal CO(2) , and MFV variations during hypercapnia and hyperventilation showed no between-group differences. CVR was similar in controls and MCI (2.30 vs 2,39, respectively, P = 0.767). HR significantly increased in hypercapnia (+9.4%, P < 0.0001) and hyperventilation (+18.7%, P < 0.0001) in controls, while in MCI it significantly increased in hyperventilation (+10.4%, P = 0.002), but not in hypercapnia (+1.1%, P = 0.635). This study demonstrates that patients with MCI have a normal CVR, but they exhibit signs of autonomic dysfunction after CO(2) challenge. Should this finding be confirmed in larger studies, HR response to CO(2) challenge could become a marker of MCI.

Normal Cerebrovascular Reactivity in Stroke-Like Migraine Attacks After Radiation Therapy Syndrome

Stroke-like Migraine Attacks after Radiation Therapy (SMART) syndrome is a rare complication of cranial irradiation. Radiation is well-known to impair vascular vessel architecture and function. We investigated the hypothesis of radiation-induced cerebral vascular reserve dysfunction as the underlying mechanism of SMART. Interictal cerebrovascular reactivity was investigated using Tc-99m hexamethylpropyleneamine oxime-SPECT and acetazolamide challenge in 3 patients. We found interictal hypoperfusion and normal cerebrovascular reactivity in all patients. Neither ictal restriction of the apparent diffusion coefficient nor MR angiography abnormalities were observed. These findings do not support a vascular mechanism in SMART syndrome. Postradiation neuronal dysfunction may be the underlying mechanism. Further investigations on larger series are needed to confirm this hypothesis.

Cerebrovascular Carbon Dioxide Reactivity and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

To determine the predictors of impaired cerebrovascular reactivity (CVR) and the value of CVR in predicting delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Prospective observational study. We evaluated CVR during the following intervals: period 1, SAH days 0 to 3; period 2, SAH days 4 to 7; and period 3, SAH days 8 to 10. Normal CVR was defined as an increase in mean blood flow velocity of at least 2% per 1-mm Hg increase in PCO(2). Neurointensive care unit of the Columbia Presbyterian Medical Center. Thirty-four consecutive patients with acute SAH who underwent measurement of changes in the middle cerebral artery mean blood flow velocity after carbon dioxide challenge. Occurrence of DCI. Delayed cerebral ischemia occurred in 10 patients (29%). Impaired CVR was more frequent in patients with a poor clinical grade on admission and at the time of examination. During period 1, there was only a trend toward lower CVR in patients who later developed DCI (1.1% vs 1.9% per 1-mm Hg increase in PCO(2); P = .07). However, those who developed DCI had progressively lower CVR during periods 2 (0.7%/mm Hg vs 2.1%/mm Hg; P < .001) and 3 (0.6%/mm Hg vs 2.4%/mm Hg; P < .001). Independent predictors of DCI included a decrease in CVR between periods 1 and 2 (P = .03) and a poor Hunt-Hess score (P = .04). Impaired CVR at any point had a sensitivity for subsequent DCI of 91% and a specificity of 49%. Impaired CVR in response to carbon dioxide challenge is frequent after SAH, particularly in patients with a poor clinical grade. Progressive loss of normal CVR identifies patients at high risk for DCI, and persistently normal reactivity implies a low risk.

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

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. Thirty-eight patients with stenoocclusive 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. 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. 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.