Current methods of forcing end-tidal P CO 2 (P ETCO 2 ) and P O 2 (P ETO 2 ) rely on breath-by-breath adjustment of inspired gas concentrations using feedback loop algorithms. Such servo-control mechanisms are complex because they have to anticipate and compensate for the respiratory response to a given inspiratory gas concentration on a breath-by-breath basis. In this paper, we introduce a low gas flow method to prospectively target and control P ETCO 2 and P ETO 2 independent of each other and of minute ventilation in spontaneously breathing humans. We used the method to change P ETCO 2 from control (40 mmHg for P ETCO 2 and 100 mmHg for P ETO 2 ) to two target P ETCO 2 values (45 and 50 mmHg) at iso-oxia (100 mmHg), P ETO 2 to two target values (200 and 300 mmHg) at normocapnia (40 mmHg), and P ETCO 2 with P ETO 2 simultaneously to the same targets (45 with 200 mmHg and 50 with 300 mmHg). After each targeted value, P ETCO 2 and P ETO 2 were returned to control values. Each state was maintained for 30 s. The average difference between target and measured values for P ETCO 2 was ± 1 mmHg, and for P ETO 2 was ± 4 mmHg. P ETCO 2 varied by ± 1 mmHg and P ETO 2 by ± 5.6 mmHg (S.D.) over the 30 s stages. This degree of control was obtained despite considerable variability in minute ventilation between subjects (± 7.6 l min −1 ). We conclude that targeted end-tidal gas concentrations can be attained in spontaneously breathing subjects using this prospective, feed-forward, low gas flow system.

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

Accurate measurements of arterial P CO 2 (P a,CO 2 ) currently require blood sampling because the end-tidal P CO 2 (P ET,CO 2 ) of the expired gas often does not accurately reflect the mean alveolar P CO 2 and P a,CO 2 . Differences between P ET,CO 2 and P a,CO 2 result from regional inhomogeneities in perfusion and gas exchange. We hypothesized that breathing via a sequential gas delivery circuit would reduce these inhomogeneities sufficiently to allow accurate prediction of P a,CO 2 from P ET,CO 2 . We tested this hypothesis in five healthy middle-aged men by comparing their P ET,CO 2 values with P a,CO 2 values at various combinations of P ET,CO 2 (between 35 and 50 mmHg), P O 2 (between 70 and 300 mmHg), and breathing frequencies (f ; between 6 and 24 breaths min −1 ). Once each individual was in a steady state, P a,CO 2 was collected in duplicate by consecutive blood samples to assess its repeatability. The difference between P ET,CO 2 and average P a,CO 2 was 0.5 ± 1.7 mmHg (P = 0.53; 95% CI −2.8, 3.8 mmHg) whereas the mean difference between the two measurements of P a,CO 2 was −0.1 ± 1.6 mmHg (95% CI −3.7, 2.6 mmHg). Repeated measures ANOVAs revealed no significant differences between P ET,CO 2 and P a,CO 2 over the ranges of P O 2 , f and target P ET,CO 2 . We conclude that when breathing via a sequential gas delivery circuit, P ET,CO 2 provides as accurate a measurement of P a,CO 2 as the actual analysis of arterial blood. Accurate measurement of arterial P CO 2 (P a,CO 2 ) is important for the clinical assessment of patients and, in physiological studies, for the assessment of control of breathing and cerebral blood flow. Currently, the reference standard for measuring P a,CO 2 is analysis of arterial blood via direct arterial puncture. This invasive approach has a number of disadvantages for both the subject (discomfort and potential arterial wall damage) and investigator (restricted mobility of the catheter insertion site, cost, time delay for blood analysis, and limited temporal resolution of changes in P a,CO 2 ). As a result, investigators have long sought a suitable non-invasive method to measure P a,CO 2 .Non-invasive methods of predicting P a,CO 2 from alveolar P CO 2 (P A,CO 2 ) consider the lung to be a tonometer in which CO 2 equilibrates between alveolar gas and capillary blood. In reality, however, the lung is not a single homogeneous time-invariant gas exchange compartment. Rather, P CO 2 varies in different regions of the lung as a result of differences in ventilation-to-perfusion matching (V A /Q ) throughout the lung and, in each lung region, throughout the respiratory cycle (Dubois et al. 1952;Lenfant, 1967). The contribution to the P a,CO 2 of blood passing each alveolus reflects the average P CO 2 in that alveolus during the respiratory cycle (Jones et al. 1979;Robbins et al. 1990). P a,CO 2 , then, reflects the timeand flow-weighted averages of all alveolar ventilatory fluctuations in allV A /Q regions throughout the lung, i.e. the mean P A,CO 2 (Lenfant, 1967). As a result, the r...

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 pCO 2 and pO 2 . 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 pCO 2 . It occurred precisely in those locations where elderly patients develop leukoaraiosis. Key Words: cerebrovascular accident Ⅲ cerebrovascular disorders Ⅲ magnetic resonance imaging S ince the advent of CT, physicians and researchers have noted the prevalence of abnormality in the white matter of elderly human brain. Characterized by patchy or diffuse low density on CT images, and corresponding hyperintensity on T2-weighted MRIs, this abnormality histopathologically represents rarefaction of myelin, loss of axons and oligodendrocytes, dilatation of perivascular spaces, and mild gliosis. 1 It is simply called white matter disease, or leukoaraiosis, 2 literally meaning diminution of white matter density. Leukoaraiosis clusters in several locations: cigar-shaped bands in the deep white matter of the centrum semiovale, 3,4 in the white matter about the occipital and frontal horns of the lateral ventricles, [3][4][5] in the genu and splenium of the corpus callosum, 3,5 and in the posterior limb of the internal capsule. 4 Prevalence increases with age with some degree of leukoaraiosis in more than half of those older than 60 years of age. 6 It was initially considered a benign age-related change, but more recent studies suggest it may be associated with cognitive dysfunction 7 and the development of dementia. 8 Despite growing appreciation of its clinical significance, the pathogenesis of leukoaraiosis is poorly understood. 9 Evidence suggests an ischemic process, 10 but what causes the ischemia? Conclusions-ThisOne theory is based on a concept of "internal border zon...

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.

Our findings indicate that a spatial correspondence exists between impairment of autoregulatory capacity with steal physiology and cortical thinning.

The BOLD reactivity to PETO(2) was much smaller than that to PETCO(2). However, BOLD reactivity can be significantly distorted by CO(2)-induced changes in PETO(2). We conclude that PETO(2) should be carefully controlled during studies that use BOLD reactivity as an indicator of CVR.

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 (PϽ0.005) and in WM with negative CVR compared with WM with positive CVR (PϽ0.001). WM in regions of steal phenomenon within the affected hemisphere had higher ADC than homologous contralateral WM (PϽ0.005). In control subjects, negative CVR in WM was not associated with elevated ADC. Conclusions-Regions