Assessing Perfusion in Steno-Occlusive Cerebrovascular Disease Using Transient Hypoxia-Induced Deoxyhemoglobin as a Dynamic Susceptibility Contrast Agent

BACKGROUND AND PURPOSE Resting brain tissue perfusion in cerebral steno-occlusive vascular disease can be assessed by MR imaging using gadolinium-based susceptibility contrast agents. Recently, transient hypoxia-induced deoxyhemoglobin has been investigated as a noninvasive MR imaging contrast agent. Here we present a comparison of resting perfusion metrics using transient hypoxia-induced deoxyhemoglobin and gadolinium-based contrast agents in patients with known cerebrovascular steno-occlusive disease. MATERIALS AND METHODS Twelve patients with steno-occlusive disease underwent DSC MR imaging using a standard bolus of gadolinium-based contrast agent compared with transient hypoxia-induced deoxyhemoglobin generated in the lungs using an automated gas blender. A conventional multi-slice 2D gradient echo sequence was used to acquire the perfusion data and analyzed using a standard tracer kinetic model. MTT, relative CBF, and relative CBV maps were generated and compared between contrast agents. RESULTS The spatial distributions of the perfusion metrics generated with both contrast agents were consistent. Perfusion metrics in GM and WM were not statistically different except for WM MTT. CONCLUSIONS Cerebral perfusion metrics generated with noninvasive transient hypoxia-induced changes in deoxyhemoglobin are very similar to those generated using a gadolinium-based contrast agent in patients with cerebrovascular steno-occlusive disease

Transfer function analysis assesses resting cerebral perfusion metrics using hypoxia-induced deoxyhemoglobin as a contrast agent

Introduction: Use of contrast in determining hemodynamic measures requires the deconvolution of an arterial input function (AIF) selected over a voxel in the middle cerebral artery to calculate voxel wise perfusion metrics. Transfer function analysis (TFA) offers an alternative analytic approach that does not require identifying an AIF. We hypothesised that TFA metrics Gain, Lag, and their ratio, Gain/Lag, correspond to conventional AIF resting perfusion metrics relative cerebral blood volume (rCBV), mean transit time (MTT) and relative cerebral blood flow (rCBF), respectively.Methods: 24 healthy participants (17 M) and 1 patient with steno-occlusive disease were recruited. We used non-invasive transient hypoxia-induced deoxyhemoglobin as an MRI contrast. TFA and conventional AIF analyses were used to calculate averages of whole brain and smaller regions of interest.Results: Maps of these average metrics had colour scales adjusted to enhance contrast and identify areas of high congruence. Regional gray matter/white matter (GM/WM) ratios for MTT and Lag, rCBF and Gain/Lag, and rCBV and Gain were compared. The GM/WM ratios were greater for TFA metrics compared to those from AIF analysis indicating an improved regional discrimination.Discussion: Resting perfusion measures generated by The BOLD analysis resulting from a transient hypoxia induced variations in deoxyhemoglobin analyzed by TFA are congruent with those analyzed by conventional AIF analysis

Measuring Cerebrovascular Reactivity: Sixteen Avoidable Pitfalls

An increase in arterial PCO$_{2}$ is the most common stressor used to increase cerebral blood flow for assessing cerebral vascular reactivity (CVR). That CO$_{2}$ is readily obtained, inexpensive, easy to administer, and safe to inhale belies the difficulties in extracting scientifically and clinically relevant information from the resulting flow responses. Over the past two decades, we have studied more than 2,000 individuals, most with cervical and cerebral vascular pathology using CO$_{2}$ as the vasoactive agent and blood oxygen-level-dependent magnetic resonance imaging signal as the flow surrogate. The ability to deliver different forms of precise hypercapnic stimuli enabled systematic exploration of the blood flow-related signal changes. We learned the effect on CVR of particular aspects of the stimulus such as the arterial partial pressure of oxygen, the baseline PCO$_{2}$, and the magnitude, rate, and pattern of its change. Similarly, we learned to interpret aspects of the flow response such as its magnitude, and the speed and direction of change. Finally, we were able to test whether the response falls into a normal range. Here, we present a review of our accumulated insight as 16 "lessons learned." We hope many of these insights are sufficiently general to apply to a range of types of CO$_{2}$-based vasoactive stimuli and perfusion metrics used for CVR

L-arginine effects on cerebrovascular reactivity, perfusion and neurovascular coupling in MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) syndrome.

ObjectiveWe previously showed that MELAS patients have decreased cerebrovascular reactivity (CVR) (p≤ 0.002) and increased cerebral blood flow (CBF) (pG tRNALeu(UUR)) with variable % mutant blood mtDNA to assess effects of L-Arginine (L-Arg) (single dose and 6-wk steady-state trial) on regional CBF, arterial CVR and neurovascular coupling.MethodsPatients were studied with 3T MRI using arterial spin labeling (ASL) to measure CBF and changes in % Blood Oxygen Level Dependent (BOLD) signal to changes in arterial partial pressure of CO2 to measure CVR. Task fMRI consisted of an alternating black and white checkerboard to evaluate visual cortex response in MELAS and controls.ResultsFollowing L-Arg, there was restoration of serum Arg (76-230 μM) in MELAS sibs and a trend towards increasing CVR in frontal and corresponding decrease in occipital cortex; CVR was unchanged globally. There was a 29-37% reduction in baseline CBF in one patient following 6 wks of L-Arg. Pre-treatment fMRI activation in response to visual cortex stimulus was markedly decreased in the same patient compared to controls in primary visual striate cortex V1 and extrastriate regions V2 to V5 with a marked increase toward control values following a single dose and 6 wks of L-Arg.ConclusionProposed "healing" effect may be due to more efficient utilization of energy substrates with increased cellular energy balances and ensuing reduction in signalling pathways that augment flow in the untreated state.Classification of evidenceThis prospective pilot study provides Class III evidence that oral L-Arginine (100 mg/kg single dose or 100 mg/kg three times daily po X 6 weeks) normalizes resting blood flow from elevated pre-treatment levels in patients with MELAS syndrome, selectively increases their CVR from reduced pre-treatment levels in regions most impaired at the expense of less abnormal regions, and normalizes reduced BOLD fMRI activation in response to visual cortex stimulus.Clinical trials.gov (nih)NCT01603446

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 postopera-tively and expressed as%BOLDMR signal intensity per mmHg PetCO2. 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, 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 preoper-ative 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)

Mapping white matter diffusion and cerebrovascular reactivity in carotid occlusive disease

Objective: To characterize the relationship between cerebrovascular reactivity (CVR) and white matter (WM) diffusion in patients with internal carotid artery (ICA) occlusive disease. Methods: In this exploratory observational study, 41 patients with severe stenosis or occlusion of the extracranial ICA and 12 healthy control subjects underwent CVR mapping using the fMRI response to hypercapnia. Conventional anatomic and diffusion-weighted MRI sequences were used to calculate maps of the apparent diffusion coefficient (ADC) and to exclude areas of previous ischemic injury. In all subjects, ADC was compared between WM with positive and negative CVR. In 27 patients with unilateral ICA involvement, ADC and CVR were compared between ipsilateral and contralateral WM while covarying for relevant clinical risk factors. Results: In patients with bilateral disease and in the ipsilateral hemisphere of patients with unilateral disease, negative CVR was associated with increased WM ADC (p <0.01 and p <0.005, respectively). In patients with unilateral disease, the ipsilateral CVR deficit was correlated with the degree of hemispheric WM ADC elevation (p <0.005). ADC elevation remained significant after correction for potential confounding risk factors. Conclusions: CVR impairment is associated with ADC elevation in normal-appearing WM of patients with severe stenosis or occlusion of the extracranial ICA. This finding is consistent with the presence of early, low-grade ischemic injury. Neurology (R) 2011;77:431-43