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.

Approaches to brain stress testing: BOLD magnetic resonance imaging with computer-controlled delivery of carbon dioxide.

BACKGROUND: An impaired vascular response in the brain regionally may indicate reduced vascular reserve and vulnerability to ischemic injury. Changing the carbon dioxide (CO(2)) tension in arterial blood is commonly used as a cerebral vasoactive stimulus to assess the cerebral vascular response, changing cerebral blood flow (CBF) by up to 5-11 percent/mmHg in normal adults. Here we describe two approaches to generating the CO(2) challenge using a computer-controlled gas blender to administer: i) a square wave change in CO(2) and, ii) a ramp stimulus, consisting of a continuously graded change in CO(2) over a range. Responses were assessed regionally by blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI). METHODOLOGY/PRINCIPAL FINDINGS: We studied 8 patients with known cerebrovascular disease (carotid stenosis or occlusion) and 2 healthy subjects. The square wave stimulus was used to study the dynamics of the vascular response, while the ramp stimulus assessed the steady-state response to CO(2). Cerebrovascular reactivity (CVR) maps were registered by color coding and overlaid on the anatomical scans generated with 3 Tesla MRI to assess the corresponding BOLD signal change/mmHg change in CO(2), voxel-by-voxel. Using a fractal temporal approach, detrended fluctuation analysis (DFA) maps of the processed raw BOLD signal per voxel over the same CO(2) range were generated. Regions of BOLD signal decrease with increased CO(2) (coded blue) were seen in all of these high-risk patients, indicating regions of impaired CVR. All patients also demonstrated regions of altered signal structure on DFA maps (Hurst exponents less than 0.5; coded blue) indicative of anti-persistent noise. While 'blue' CVR maps remained essentially stable over the time of analysis, 'blue' DFA maps improved. CONCLUSIONS/SIGNIFICANCE: This combined dual stimulus and dual analysis approach may be complementary in identifying vulnerable brain regions and thus constitute a regional as well as global brain stress test.

Human skin hypoxia modulates cerebrovascular and autonomic functions.

Because the skin is an oxygen sensor in amphibians and mice, we thought to confirm this function also in humans. The human upright posture, however, introduces additional functional demands for the maintenance of oxygen homeostasis in which cerebral blood flow and autonomic nervous system (ANS) function may also be involved. We examined nine males and three females. While subjects were breathing ambient air, at sea level, we changed gases in a plastic body-bag during two conditions of the experiment such as to induce skin hypoxia (with pure nitrogen) or skin normoxia (with air). The subjects performed a test of hypoxic ventilatory drive during each condition of the experiment. We found no differences in the hypoxic ventilatory drive tests. However, ANS function and cerebral blood flow velocities were modulated by skin hypoxia and the effect was significantly greater on the left than right middle cerebral arteries. We conclude that skin hypoxia modulates ANS function and cerebral blood flow velocities and this might impact life styles and tolerance to ambient hypoxia at altitude. Thus the skin in normal humans, in addition to its numerous other functions, is also an oxygen sensor.

Measurement of the optical properties of a two-layer model of the human head using broadband near-infrared spectroscopy.

We present the development of a continuous-wave method of quantifying the optical properties of a two-layered model of the human head using a broadband spectral approach. Absolute absorption and scattering properties of the upper and lower layers of phantoms with known optical properties were reconstructed from steady-state multi-distance measurements by performing differential fit analysis of the near-infrared reflectance spectrum between 700 and 1000 nm. From spectra acquired at 10, 20, and 30 mm, the concentration of a chromophore in the bottom layer was determined within an error of 10% in the presence of a 15 mm thick top layer. These results demonstrate that our method was able to determine the optical properties of the lower layer, which represents brain, with acceptable error at specific source-detector distances.