Should all inflow stenoses be treated in failing autogenous hemodialysis fistulae?

PURPOSE: To determine whether angioplasty of inflow stenosis in malfunctioning but patent autogenous hemodialysis fistulae has an impact on postintervention primary patency in patients without a clinical indicator of inflow-related access malfunction. MATERIALS AND METHODS: Medical records for 76 procedures in 62 patients with inflow stenoses undergoing fistulography in nonthrombosed mature autogenous fistulae without an inflow-related indication of access malfunction over a 5-year period were reviewed retrospectively. Control and treatment arms were defined as patients with untreated (26 procedures in 23 patients) and treated (50 procedures in 39 patients) inflow stenoses, respectively. All patients in both arms of the study had concurrent intrafistula and/or venous outflow stenosis, which were treated successfully with angioplasty. The clinical endpoint was defined as return for a failing or thrombosed access (ie, primary patency). A two-tailed unpaired Student t test was performed to compare primary patency and percent inflow stenosis in treatment (angioplasty) and control (untreated inflow stenoses) groups, with significance defined at P < .05. Kaplan-Meier analysis was performed. RESULTS: There was no significant difference in percent inflow stenosis between control and treatment arms (P = .95). There was no significant difference in access patency between the two groups (139 and 124 d for control and treated groups, respectively; P = .95). No procedural complications occurred in either arm of the study. CONCLUSIONS: Angioplasty of inflow stenosis in failing autogenous fistulae without an appropriate clinical indicator of an inflow pathologic process does not improve postintervention primary patency.

Coupling of cerebral blood flow and oxygen metabolism is conserved for chromatic and luminance stimuli in human visual cortex.

The ratio of the changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) during brain activation is a critical determinant of the magnitude of the blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI). Cytochrome oxidase (CO), a key component of oxidative metabolism in the mitochondria, is non-uniformly distributed in visual area V1 in distinct blob and interblob regions, suggesting significant spatial variation in the capacity for oxygen metabolism. The goal of this study was to test whether CBF/CMRO(2) coupling differed when these subpopulations of neurons were preferentially stimulated, using chromatic and luminance stimuli to preferentially stimulate either the blob or interblob regions. A dual-echo spiral arterial spin labeling (ASL) technique was used to measure CBF and BOLD responses simultaneously in 7 healthy human subjects. When the stimulus contrast levels were adjusted to evoke similar CBF responses (mean 65.4% ± 19.0% and 64.6% ± 19.9%, respectively for chromatic and luminance contrast), the BOLD responses were remarkably similar (1.57% ± 0.39% and 1.59% ± 0.35%) for both types of stimuli. We conclude that CBF-CMRO(2) coupling is conserved for the chromatic and luminance stimuli used, suggesting a consistent coupling for blob and inter-blob neuronal populations despite the difference in CO concentration.

Catheter-based intraaccess blood flow measurement as a problem-solving tool in hemodialysis access intervention.

PURPOSE: To investigate retrospectively the use of catheter-based intraaccess blood flow measurements as an adjunct to physical examination and fistulography in hemodialysis access interventions. MATERIALS AND METHODS: Among 1,540 dialysis interventions performed at a single institution in a 2.5-year period, 104 qualifying catheter-based flow measurements were made in 70 mature native fistula interventions in 55 patients and 34 graft interventions in 31 patients. The flow rate threshold prompting intervention was generally 600 mL/min, but some variation existed depending on the clinical setting. RESULTS: The most common indication for measurement of blood flow was to determine the hemodynamic significance of a fistula inflow stenosis (n = 25), of which only four had subsequent intervention. Other common indications included decision-making resulting in further angioplasty or stent implantation of noninflow lesions (fistulas, n = 10; grafts, n = 23) versus termination of the procedure (n = 23), problem-solving in cases in which there was no visible lesion to explain the clinical indicator of access failure (n = 17), evaluation for high-flow-related cardiac risk in aneurysmal fistulas (n = 13), suboptimal evaluation of the inflow (n = 8), and suboptimal physical examination (n = 6). Overall, flow measurements supported a decision to perform angioplasty (n = 11) or stent placement (n = 3) in 17% of fistula interventions and 35% of graft interventions. CONCLUSIONS: The major benefit of flow measurement was to support a decision to withhold further angioplasty or stent placement.

Depression of cortical activity in humans by mild hypercapnia.

The effects of neural activity on cerebral hemodynamics underlie human brain imaging with functional magnetic resonance imaging and positron emission tomography. However, the threshold and characteristics of the converse effects, wherein the cerebral hemodynamic and metabolic milieu influence neural activity, remain unclear. We tested whether mild hypercapnia (5% CO2 ) decreases the magnetoencephalogram response to auditory pattern recognition and visual semantic tasks. Hypercapnia induced statistically significant decreases in event-related fields without affecting behavioral performance. Decreases were observed in early sensory components in both auditory and visual modalities as well as later cognitive components related to memory and language. Effects were distributed across cortical regions. Decreases were comparable in evoked versus spontaneous spectral power. Hypercapnia is commonly used with hemodynamic models to calibrate the blood oxygenation level-dependent response. Modifying model assumptions to incorporate the current findings produce a modest but measurable decrease in the estimated cerebral metabolic rate for oxygen change with activation. Because under normal conditions, low cerebral pH would arise when bloodflow is unable to keep pace with neuronal activity, the cortical depression observed here may reflect a homeostatic mechanism by which neuronal activity is adjusted to a level that can be sustained by available bloodflow. Animal studies suggest that these effects may be mediated by pH-modulating presynaptic adenosine receptors. Although the data is not clear, comparable changes in cortical pH to those induced here may occur during sleep apnea, sleep, and exercise. If so, these results suggest that such activities may in turn have generalized depressive effects on cortical activity.

Effects of aging on cerebral blood flow, oxygen metabolism, and blood oxygenation level dependent responses to visual stimulation.

Calibrated functional magnetic resonance imaging (fMRI) provides a noninvasive technique to assess functional metabolic changes associated with normal aging. We simultaneously measured both the magnitude of the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) responses in the visual cortex for separate conditions of mild hypercapnia (5% CO(2)) and a simple checkerboard stimulus in healthy younger (n = 10, mean: 28-years-old) and older (n = 10, mean: 53-years-old) adults. From these data we derived baseline CBF, the BOLD scaling parameter M, the fractional change in the cerebral metabolic rate of oxygen consumption (CMRO(2)) with activation, and the coupling ratio n of the fractional changes in CBF and CMRO(2). For the functional activation paradigm, the magnitude of the BOLD response was significantly lower for the older group (0.57 +/- 0.07%) compared to the younger group (0.95 +/- 0.14%), despite the finding that the fractional CBF and CMRO(2) changes were similar for both groups. The weaker BOLD response for the older group was due to a reduction in the parameter M, which was significantly lower for older (4.6 +/- 0.4%) than younger subjects (6.5 +/- 0.8%), most likely reflecting a reduction in baseline CBF for older (41.7 +/- 4.8 mL/100 mL/min) compared to younger (59.6 +/- 9.1 mL/100 mL/min) subjects. In addition to these primary responses, for both groups the BOLD response exhibited a post-stimulus undershoot with no significant difference in this magnitude. However, the post-undershoot period of the CBF response was significantly greater for older compared to younger subjects. We conclude that when comparing two populations, the BOLD response can provide misleading reflections of underlying physiological changes. A calibrated approach provides a more quantitative reflection of underlying metabolic changes than the BOLD response alone.

CT-based calcium scoring to screen for coronary artery disease: why aren't we there yet?

OBJECTIVE: The purpose of this article is to examine the value of coronary artery calcium scoring as a screening tool for identifying individuals at risk of experiencing a catastrophic coronary event. CONCLUSION: Because of the noninvasive nature of CT and the large societal burden of coronary atherosclerosis, there is great interest in developing CT-based techniques for detection of coronary artery calcium, a known marker of underlying atherosclerosis. However, important questions remain including the role of calcium in the process of acute plaque rupture, the utility of this technique in the asymptomatic population, and the statistical distribution of calcium scores and hard cardiac events in the general population.

Regional differences in the coupling of cerebral blood flow and oxygen metabolism changes in response to activation: implications for BOLD-fMRI.

Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, but quantitative interpretation of the BOLD response is problematic. The BOLD response is primarily driven by cerebral blood flow (CBF) changes, but is moderated by M, a scaling parameter reflecting baseline deoxyhemoglobin, and n, the ratio of fractional changes in CBF to cerebral metabolic rate of oxygen consumption (CMRO(2)). We compared M and n between cortical (visual cortex, VC) and subcortical (lentiform nuclei, LN) regions using a quantitative approach based on calibrating the BOLD response with a hypercapnia experiment. Although M was similar in both regions (~5.8%), differences in n (2.21+/-0.03 in VC and 1.58+/-0.03 in LN; Cohen d=1.71) produced substantially weaker (~3.7x) subcortical than cortical BOLD responses relative to CMRO(2) changes. Because of this strong sensitivity to n, BOLD response amplitudes cannot be interpreted as a quantitative reflection of underlying metabolic changes, particularly when comparing cortical and subcortical regions.

Reproducibility of BOLD, perfusion, and CMRO2 measurements with calibrated-BOLD fMRI.

The coupling of changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) during brain activation can be characterized by an empirical index, n, defined as the ratio between fractional CBF change and fractional CMRO(2) change. The combination of blood oxygenation level dependent (BOLD) imaging with CBF measurements from arterial spin labeling (ASL) provides a potentially powerful experimental approach for measuring n, but the reproducibility of the technique previously has not been assessed. In this study, inter-subject variance and intra-subject reproducibility of the method were determined. Block design %BOLD and %CBF responses to visual stimulation and mild hypercapnia (5% CO(2)) were measured, and these data were used to compute the BOLD scaling factor M, %CMRO(2) change with activation, and the coupling index n. Reproducibility was determined for three approaches to defining regions-of-interest (ROIs): 1) Visual area V1 determined from prior retinotopic maps, 2) BOLD-activated voxels from a separate functional localizer, and 3) CBF-activated voxels from a separate functional localizer. For estimates of %BOLD, %CMRO(2) and n, intra-subject reproducibility was found to be best for regions selected according to CBF activation. Among all fMRI measurements, estimates of n were the most robust and were substantially more stable within individual subjects (coefficient of variation, CV=7.4%) than across the subject pool (CV=36.9%). The stability of n across days, despite wider variability of CBF and CMRO(2) responses, suggests that the reproducibility of blood flow changes is limited by variation in the oxidative metabolic demand. We conclude that the calibrated BOLD approach provides a highly reproducible measurement of n that can serve as a useful quantitative probe of the coupling of blood flow and energy metabolism in the brain.

CBF/CMRO2 coupling measured with calibrated BOLD fMRI: sources of bias.

The coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during brain activation can be characterized by an empirical index n, the ratio of fractional CBF changes to fractional CMRO2 changes. Measurements of n have yielded varying results, and it is not known if the observed variability is due to measurement techniques or underlying physiology. The calibrated BOLD approach using hypercapnia offers a promising tool for assessing changes in CBF/CMRO2 coupling in health and disease, but potential systematic errors have not yet been characterized. The goal of this study was to experimentally evaluate the magnitude of bias in the estimate of n that arises from the way in which a region of interest (ROI) is chosen for averaging data and to relate this potential bias to a more general theoretical consideration of the sources of systematic errors in the calibrated BOLD experiment. Results were compared for different approaches for defining an ROI within the visual cortex based on: (1) retinotopically defined V1; (2) a functional CBF localizer; and (3) a functional BOLD localizer. Data in V1 yielded a significantly lower estimate of n (2.45) compared to either CBF (n=3.45) or BOLD (n=3.18) localizers. Different statistical thresholds produced biases in estimates of n with values ranging from 3.01 (low threshold) to 4.37 (high threshold). Possible sources of the observed biases are discussed. These results underscore the importance of a critical evaluation of the methodology, and the adoption of consistent standards for applying the calibrated BOLD approach to the evaluation of CBF/CMRO2 coupling.