Hemodynamic Failure Staging With Blood Oxygenation Level-Dependent Cerebrovascular Reactivity and Acetazolamide-Challenged (15^{15}O-)H2_{2}O-Positron Emission Tomography Across Individual Cerebrovascular Territories

BACKGROUND Staging of hemodynamic failure (HF) in symptomatic patients with cerebrovascular steno-occlusive disease is required to assess the risk of ischemic stroke. Since the gold standard positron emission tomography-based perfusion reserve is unsuitable as a routine clinical imaging tool, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) with CO$_{2}$ is a promising surrogate imaging approach. We investigated the accuracy of standardized BOLD-CVR to classify the extent of HF. METHODS AND RESULTS Patients with symptomatic unilateral cerebrovascular steno-occlusive disease, who underwent both an acetazolamide challenge ($^{15}$O-)H$_{2}$O-positron emission tomography and BOLD-CVR examination, were included. HF staging of vascular territories was assessed using qualitative inspection of the positron emission tomography perfusion reserve images. The optimum BOLD-CVR cutoff points between HF stages 0-1-2 were determined by comparing the quantitative BOLD-CVR data to the qualitative ($^{15}$O-)H$_{2}$O-positron emission tomography classification using the 3-dimensional accuracy index to the randomly assigned training and test data sets with the following determination of a single cutoff for clinical application. In the 2-case scenario, classifying data points as HF 0 or 1-2 and HF 0-1 or 2, BOLD-CVR showed an accuracy of >0.7 for all vascular territories for HF 1 and HF 2 cutoff points. In particular, the middle cerebral artery territory had an accuracy of 0.79 for HF 1 and 0.83 for HF 2, whereas the anterior cerebral artery had an accuracy of 0.78 for HF 1 and 0.82 for HF 2. CONCLUSIONS Standardized and clinically accessible BOLD-CVR examinations harbor sufficient data to provide specific cerebrovascular reactivity cutoff points for HF staging across individual vascular territories in symptomatic patients with unilateral cerebrovascular steno-occlusive disease

Vascular Steal Explains Early Paradoxical Blood Oxygen Level-Dependent Cerebrovascular Response in Brain Regions with Delayed Arterial Transit Times

Introduction: Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) during manipulation of inhaled carbon dioxide (CO2) can be used to measure cerebrovascular reactivity (CVR) and map regions of exhausted cerebrovascular reserve. These regions exhibit a reduced or negative BOLD response to inhaled CO2. In this study, we sought to clarify the mechanism behind the negative BOLD response by investigating its time delay (TD). Dynamic susceptibility contrast (DSC) MRI with the injection of a contrast agent was used as the gold standard in order to provide measurement of the blood arrival time to which CVR TD could be compared. We hypothesize that if negative BOLD responses are the result of a steal phenomenon, they should be synchronized with positive BOLD responses from healthy brain tissue, even though the blood arrival time would be delayed. Methods: On a 3-tesla MRI system, BOLD CVR and DSC images were collected in a group of 19 patients with steno-occlusive cerebrovascular disease. For each patient, we generated a CVR magnitude map by regressing the BOLD signal with the end-tidal partial pressure of CO2 (PETCO2), and a CVR TD map by extracting the time of maximum cross-correlation between the BOLD signal and PETCO2. In addition, a blood arrival time map was generated by fitting the DSC signal with a gamma variate function. ROI masks corresponding to varying degrees of reactivity were constructed. Within these masks, the mean CVR magnitude, CVR TD and DSC blood arrival time were extracted and averaged over the 19 patients. CVR magnitude and CVR TD were then plotted against DSC blood arrival time. Results: The results show that CVR magnitude is highly correlated to DSC blood arrival time. As expected, the most compromised tissues with the longest blood arrival time have the lowest (most negative) CVR magnitude. However, CVR TD shows a noncontinuous relationship with DSC blood arrival time. CVR TD is well correlated to DSC blood arrival time (p Conclusion: These results support the hypothesis that negative reactivity is the result of a steal phenomenon, lowering the BOLD signal as soon as healthier parts of the brain start to react and augment their blood flow. BOLD CVR MRI is capable of identifying this steal distribution, which has particular diagnostic significance as it represents an actual reduction in flow to already compromised tissue

Intra-vascular blood velocity and volumetric flow rate calculated from dynamic 4D CT angiography using a time of flight technique

We examine a time of flight (TOF) approach for the analysis of contrast enhanced 4D volumetric CT angiography scans to derive and display blood velocity in arteries. Software was written to divide blood vessels into a series of cross sections and to track contrast bolus TOF along the central vessel axis, which was defined by a user, from 4D CT source data. Time density curves at each vessel cross section were fit with quadratic, Gaussian, and gamma variate functions to determine bolus time to peak (TTP). A straight line was used to plot TTP versus vessel path length for all three functions and the slope used to calculate intraluminal velocity. Software was validated in a simulated square channel and non-pulsatile flow phantom prior to the calculation of blood velocity in the major cerebral arteries of 8 normal patients. The TOF algorithm correctly calculates intra-luminal fluid velocity in eight flow conditions of the CT flow phantom where quadratic functions were used. Across all conditions, in phantoms and in vivo, the success of calculations depended strongly on having a sufficiently long path length to make measurements and avoiding venous contamination. Total blood flow into the brain was approximately 17 % of a normal 5 L cardiac output. The technique was explored in vivo in a patient with subclavian steal syndrome, in the pulmonary arteries and in the iliac artery from clinical 4D CT source data. Intravascular blood velocity and flow may be calculated from 4D CT angiography using a TOF approach

Surgical Revascularization Reverses Cerebral Cortical Thinning in Patients With Severe Cerebrovascular Steno-Occlusive Disease

Background and Purpose-Chronic deficiencies in regional blood flow lead to cerebral cortical thinning without evidence of gross tissue loss at the same time as potentially negatively impacting on neurological and cognitive performance. This is most pronounced in patients with severe occlusive cerebrovascular disease in whom affected brain areas exhibit "steal physiology," a paradoxical reduction of cerebral blood flow in response to a global vasodilatory stimulus intended to increase blood flow. We tested whether surgical brain revascularization that eliminates steal physiology can reverse cortical thinning. Methods-We identified 29 patients from our database who had undergone brain revascularization with pre- and postoperative studies of cerebrovascular reactivity using blood oxygen(ation) level-dependent MRI and whose preoperative study exhibited steal physiology without MRI-evident structural abnormalities. Cortical thickness in regions corresponding to steal physiology, and where applicable corresponding areas in the normal hemisphere, were measured using Freesurfer software. Results-At an average of 11 months after surgery, cortical thickness increased in every successfully revascularized hemisphere (n = 30). Mean cortical thickness in the revascularized regions increased by 5.1% (from 2.40 +/- 0.03 to 2.53 +/- 0.03; P <0.0001). Conclusions-Successful regional revascularization and reversal of steal physiology is followed by restoration of cortical thickness. (Stroke. 2011;42:1631-1637.

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

Hemodynamic Failure Staging With Blood Oxygenation Level–Dependent Cerebrovascular Reactivity and Acetazolamide‐Challenged (15O‐)H2O‐Positron Emission Tomography Across Individual Cerebrovascular Territories

Background Staging of hemodynamic failure (HF) in symptomatic patients with cerebrovascular steno‐occlusive disease is required to assess the risk of ischemic stroke. Since the gold standard positron emission tomography‐based perfusion reserve is unsuitable as a routine clinical imaging tool, blood oxygenation level–dependent cerebrovascular reactivity (BOLD‐CVR) with CO2 is a promising surrogate imaging approach. We investigated the accuracy of standardized BOLD‐CVR to classify the extent of HF. Methods and Results Patients with symptomatic unilateral cerebrovascular steno‐occlusive disease, who underwent both an acetazolamide challenge (15O‐)H2O‐positron emission tomography and BOLD‐CVR examination, were included. HF staging of vascular territories was assessed using qualitative inspection of the positron emission tomography perfusion reserve images. The optimum BOLD‐CVR cutoff points between HF stages 0–1–2 were determined by comparing the quantitative BOLD‐CVR data to the qualitative (15O‐)H2O‐positron emission tomography classification using the 3‐dimensional accuracy index to the randomly assigned training and test data sets with the following determination of a single cutoff for clinical application. In the 2‐case scenario, classifying data points as HF 0 or 1–2 and HF 0–1 or 2, BOLD‐CVR showed an accuracy of >0.7 for all vascular territories for HF 1 and HF 2 cutoff points. In particular, the middle cerebral artery territory had an accuracy of 0.79 for HF 1 and 0.83 for HF 2, whereas the anterior cerebral artery had an accuracy of 0.78 for HF 1 and 0.82 for HF 2. Conclusions Standardized and clinically accessible BOLD‐CVR examinations harbor sufficient data to provide specific cerebrovascular reactivity cutoff points for HF staging across individual vascular territories in symptomatic patients with unilateral cerebrovascular steno‐occlusive disease

Impaired dynamic cerebrovascular response to hypercapnia predicts development of white matter hyperintensities

Purpose: To evaluate the relationship between both dynamic and steady-state measures of cerebrovascular reactivity (CVR) and the progression of age-related white matter disease. Methods: Blood oxygen level-dependent (BOLD) MRI CVR scans were acquired from forty-five subjects (age range: 50–90 years, 25 males) with moderate to severe white matter disease, at baseline and one-year follow-up. To calculate the dynamic (τ) and steady-state (ssCVR) components of the BOLD signal response, the PETCO2 signal waveform was convolved with an exponential decay function. The τ corresponding to the best fit between the convolved PETCO2 and BOLD signal defined the speed of response, and the slope of the regression between the convolved PETCO2 and BOLD signal defined ssCVR. ssCVR and τ were compared between normal-appearing white matter (NAWM) that remains stable over time and NAWM that progresses to white matter hyperintensities (WMHs). Results: In comparison to contralateral NAWM, NAWM that progressed to WMH had significantly lower ssCVR values by mean (SD) 46.5 (7.6)%, and higher τ values by 31.9 (9.6)% (both P < 0.01). Conclusions: Vascular impairment in regions of NAWM that progresses to WMH consists not only of decreased magnitude of ssCVR, but also a pathological decrease in the speed of vascular response. These findings support the association between cerebrovascular dysregulation and the development of WMH

Intra-vascular blood velocity and volumetric flow rate calculated from dynamic 4D CT angiography using a time of flight technique

We examine a time of flight (TOF) approach for the analysis of contrast enhanced 4D volumetric CT angiography scans to derive and display blood velocity in arteries. Software was written to divide blood vessels into a series of cross sections and to track contrast bolus TOF along the central vessel axis, which was defined by a user, from 4D CT source data. Time density curves at each vessel cross section were fit with quadratic, Gaussian, and gamma variate functions to determine bolus time to peak (TTP). A straight line was used to plot TTP versus vessel path length for all three functions and the slope used to calculate intraluminal velocity. Software was validated in a simulated square channel and non-pulsatile flow phantom prior to the calculation of blood velocity in the major cerebral arteries of 8 normal patients. The TOF algorithm correctly calculates intra-luminal fluid velocity in eight flow conditions of the CT flow phantom where quadratic functions were used. Across all conditions, in phantoms and in vivo, the success of calculations depended strongly on having a sufficiently long path length to make measurements and avoiding venous contamination. Total blood flow into the brain was approximately 17 % of a normal 5 L cardiac output. The technique was explored in vivo in a patient with subclavian steal syndrome, in the pulmonary arteries and in the iliac artery from clinical 4D CT source data. Intravascular blood velocity and flow may be calculated from 4D CT angiography using a TOF approach