Local cerebral blood flow measured by CT after stable xenon inhalation

A theoretical assessment is made of the validity of assumptions underlying the theory for estimating local cerebral blood flow with diffusible tracer in the tissue under normal and ischemic conditions. First, Kety's derivation of equations that have commonly been used for calculating local cerebral blood flow values is examined in order to define the problems and assumptions. Second, the brain:blood partition coefficient of diffusible tracer, λ and the diffusion-limited factor, m, under normal and ischemic conditions are reviewed. An examination of the literature suggested that contrary to common belief, λ appears to change very little in ischemia if the tissue constituents remain unchanged, whereas m does change with ischemia if the diffusible tracer used is greatly diffusion-limited in the exchange between brain and blood. Even when a gas with an m value close to unity is used as the diffusible tracer, the prolonged mean transit time of blood through the ischemic tissue would make it difficult to maintain the exponential assumptions. As part of the ischemic tissue became infarcted, which is the case with most stroke patients, so the assumptions of homogeneous perfusion would become invalid. This inevitably renders it difficult to estimate local cerebral blood flow with diffusible tracer in ischemic tissue containing an infarcted mass.

Section: A Under Normal Conditionssupporting

confidence: 83%

Local Cerebral Blood Flow Values as Estimated with Diffusible Tracers: Validity of Assumptions in Normal and Ischemic Tissue

Tomita

Gotoh

1981

“…Xenon pigs in the 'severe neuropathology' group had received a similar insult compared with other treatment groups. Results of past studies of the effects of xenon on cerebral blood flow have been inconsistent, with some studies showing an increase, 26,27 and others showing no change 28 or regional differences. 29 These differences in outcome are likely to be because of differences in Figure 5.…”

Section: Discussionmentioning

confidence: 96%

Effects of Xenon and Hypothermia on Cerebrovascular Pressure Reactivity in Newborn Global Hypoxic—ischemic Pig Model

Chakkarapani

Dingley

Aquilina

et al. 2013

Autoregulation of cerebral perfusion is impaired in hypoxic-ischemic encephalopathy. We investigated whether cerebrovascular pressure reactivity (PRx), an element of cerebral autoregulation that is calculated as a moving correlation coefficient between averages of intracranial and mean arterial blood pressure (MABP) with values between À 1 and þ 1, is impaired during and after a hypoxic-ischemic insult (HI) in newborn pigs. Associations between end-tidal CO 2 , seizures, neuropathology, and PRx were investigated. The effect of hypothermia (HT) and Xenon (Xe) on PRx was studied. Pigs were randomized to Sham, and after HI to normothermia (NT), HT, Xe or xenon hypothermia (XeHT). We defined PRx 40.2 as peak and negative PRx as preserved. Neuropathology scores after 72 hours of survival was grouped as 'severe' or 'mild.' Secondary PRx peak during recovery, predictive of severe neuropathology and associated with insult severity (P ¼ 0.05), was delayed in HT (11.5 hours) than in NT (6.5 hours) groups. Seizures were associated with impaired PRx in NT pigs (P ¼ 0.0002), but not in the HT/XeHT pigs. PRx was preserved during normocapnia and impaired during hypocapnia. Xenon abolished the secondary PRx peak, increased (mean (95% confidence interval (CI)) MABP (6.5 (3.8, 9.4) mm Hg) and cerebral perfusion pressure (5.9 (2.9, 8.9) mm Hg) and preserved the PRx (regression coefficient, À 0.098 (95% CI ( À 0.18, À 0.01)), independent of the insult severity.

mentioning

confidence: 99%

“…Such simulations were run as a feasibility study for a new technique to measure regional cerebral blood flow (rCBF) in hu mans using computed tomographic (CT) brain scans and xenon inhalation (Rottenberg et al, 1981a,b). Xenon inhalation does not produce anesthesia when the inspired concentration is less than 50% (Cullen and Gross, 1951); at higher inspired concentrations, slowing of the EEG becomes apparent when the inhalation exceeds 3 min (Meyer et al, 1980). The results of the simulations provided information on the design of the experiments in terms of number and timing of scans and size of region of interest for which measurements would be obtained, as well as on the limits of accuracy of the technique.…”

mentioning

confidence: 99%

Repeated Least Squares Analysis of Simulated Xenon Computed Tomographic Measurements of Regional Cerebral Blood Flow

Thaler

Baglivo²,

et al. 1982

Summary: Computer simulations were done as a feasibility study of xenon computed tomographic measurements of regional cerebral blood flow. Accu racy of initial least squares estimates of gray matter and white matter rate constants from a two-compartment model depended very little on the number and timing of scans, but did depend significantly on the enhancement-to-noise ratio as well as on the true values of the rate constants and gray/white ratio. Nonlinear least squares gives an optimal fit of the predicted wash-in-wash-out curve to the data rather than optimal estimates of the rate constants. A polynomial correction factor was obtained by regressing initial estimates on the true values used to generate the simulations. The correction factor substan tially reduced error in the estimates and, in particular, eliminated large outliers. Key Words: Computed tomographic brain scan-Correction factor-Least squares analysis-Regional cerebral blood flow-Xenon inhalation.Computer simulations afford the opportunity to evaluate the effect of various input parameters in an experiment when the quantities of primary interest are nonlinear functions of the input parameters and directly observable output variables, and are esti mated using least squares. Such simulations were run as a feasibility study for a new technique to measure regional cerebral blood flow (rCBF) in hu mans using computed tomographic (CT) brain scans and xenon inhalation (Rottenberg et al., 1981a,b). Xenon inhalation does not produce anesthesia when the inspired concentration is less than 50% (Cullen and Gross, 1951); at higher inspired concentrations, slowing of the EEG becomes apparent when the inhalation exceeds 3 min (Meyer et al., 1980). The 408results of the simulations provided information on the design of the experiments in terms of number and timing of scans and size of region of interest for which measurements would be obtained, as well as on the limits of accuracy of the technique. The primary motivation for the estimation tech nique proposed here is that least squares finds the curve that best fits the data, but not necessarily the best estimates of the parameters themselves. Dis crepancies between initial least squares estimates for the primary parameters of interest on the one hand-namely, gray matter and white matter rate constants and the relative proportion of gray matter in the region of interest-and the "true" values used to generate the data on the other hand could be regressed back on the estimated values to obtain polynomial correction factors yielding substantially reduced bias and mean squared error. Since the mathematical formulas in this paper are quite de tailed, we have included, as an aid to the reader, an appendix of notations used.