A new approach to non-invasive oxygenated mixed venous PCO(sub)2

A clinically practical technique was developed to calculate mixed venous CO2 partial pressure for the calculation of cardiac output by the Fick technique. The Fick principle states that the cardiac output is equal to the CO2 production divided by the arterio-venous CO2 content difference of the pulmonary vessels. A review of the principles involved in the various techniques used to estimate venous CO2 partial pressure is presented

Supplementary oxygen for nonhypoxemic patients: O2 much of a good thing?

Supplementary oxygen is routinely administered to patients, even those with adequate oxygen saturations, in the belief that it increases oxygen delivery. But oxygen delivery depends not just on arterial oxygen content but also on perfusion. It is not widely recognized that hyperoxia causes vasoconstriction, either directly or through hyperoxia-induced hypocapnia. If perfusion decreases more than arterial oxygen content increases during hyperoxia, then regional oxygen delivery decreases. This mechanism, and not (just) that attributed to reactive oxygen species, is likely to contribute to the worse outcomes in patients given high-concentration oxygen in the treatment of myocardial infarction, in postcardiac arrest, in stroke, in neonatal resuscitation and in the critically ill. The mechanism may also contribute to the increased risk of mortality in acute exacerbations of chronic obstructive pulmonary disease, in which worsening respiratory failure plays a predominant role. To avoid these effects, hyperoxia and hypocapnia should be avoided, with oxygen administered only to patients with evidence of hypoxemia and at a dose that relieves hypoxemia without causing hyperoxia

Object oriented simulation tools for discrete-continuous, stochastic-deterministic simulation models

In this thesis an introduction to simulation and object oriented programming discusses the need for the creation of several classes which directly support object oriented simulation. The author places no restrictions on the type of simulations that can be conducted and simulation practitioners will find that the classes provided lay the groundwork for a robust object oriented simulation language. In order to appreciate the development of the simulation classes, three examples from the literature demonstrate their use in continuous deterministic and discrete stochastic simulations. In addition to the creation of several basic simulation constructs, two advanced simulation tools were developed. Inter-object communication and intelligent simulation capabilities will increase the power and flexibility available to simulation modeler's. Programmers, scientists, and engineers will appreciate the object oriented simulation engine and generic simulation objects that were created

Intrinsic noise and discrete-time processes

A general formalism is developed to construct a Markov chain model that converges to a one-dimensional map in the infinite population limit. Stochastic fluctuations are therefore internal to the system and not externally specified. For finite populations an approximate Gaussian scheme is devised to describe the stochastic fluctuations in the non-chaotic regime. More generally, the stochastic dynamics can be captured using a stochastic difference equation, derived through an approximation to the Markov chain. The scheme is demonstrated using the logistic map as a case study.Comment: Modified version accepted for publication in Phys. Rev. E Rapid Communications. New figures adde

MRI-based cerebrovascular reactivity using transfer function analysis reveals temporal group differences between patients with sickle cell disease and healthy controls

AbstractObjectivesCerebrovascular reactivity (CVR) measures the ability of cerebral blood vessels to change their diameter and, hence, their capacity to regulate regional blood flow in the brain. High resolution quantitative maps of CVR can be produced using blood-oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in combination with a carbon dioxide stimulus, and these maps have become a useful tool in the clinical evaluation of cerebrovascular disorders. However, conventional CVR analysis does not fully characterize the BOLD response to a stimulus as certain regions of the brain are slower to react to the stimulus than others, especially in disease. Transfer function analysis (TFA) is an alternative technique that can account for dynamic temporal relations between signals and has recently been adapted for CVR computation. We investigated the application of TFA in data on children with sickle cell disease (SCD) and healthy controls, and compared them to results derived from conventional CVR analysis.Materials and methodsData from 62 pediatric patients with SCD and 34 age-matched healthy controls were processed using conventional CVR analysis and TFA. BOLD data were acquired on a 3Tesla MRI scanner while a carbon dioxide stimulus was quantified by sampling the end-tidal partial pressures of each exhaled breath. In addition, T1 weighted structural imaging was performed to identify grey and white matter regions for analysis. The TFA method generated maps representing both the relative magnitude change of the BOLD signal in response to the stimulus (Gain), as well as the BOLD signal speed of response (Phase) for each subject. These were compared to CVR maps calculated from conventional analysis. The effect of applying TFA on data from SCD patients versus controls was also examined.ResultsThe Gain measures derived from TFA were significantly higher than CVR values based on conventional analysis in both SCD patients and healthy controls, but the difference was greater in the SCD data. Moreover, while these differences were uniform across the grey and white matter regions of controls, they were greater in white matter than grey matter in the SCD group. Phase was also shown to be significantly correlated with the amount that TFA increases CVR estimates in both the grey and white matter.ConclusionsWe demonstrated that conventional CVR analysis underestimates vessel reactivity and this effect is more prominent in patients with SCD. By using TFA, the resulting Gain and Phase measures more accurately characterize the BOLD response as it accounts for the temporal dynamics responsible for the CVR underestimation. We suggest that the additional information offered through TFA can provide insight into the mechanisms underlying CVR compromise in cerebrovascular diseases

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

Feasibility and precision of cerebral blood flow and cerebrovascular reactivity MRI measurements using a computer-controlled gas delivery system in an anesthetised juvenile animal model

Purpose: To demonstrate the feasibility and repeatability of cerebrovascular reactivity (CVR) imaging using a controlled CO2 challenge in mechanically ventilated juvenile pigs. Materials and Methods: Precise end-tidal partial pressure CO2 (PETCO2) control was achieved via a computer-controlled model-driven prospective end-tidal targeting (MPET) system integrated with mechanical ventilation using a custom-built secondary breathing circuit. Test-retest blood-oxygen level dependent (BOLD) CVR images were collected in nine juvenile pigs by quantifying the BOLD response to iso-oxic square-wave PETCO2 changes. For comparison, test-retest baseline arterial spin labeling (ASL) cerebral blood flow (CBF) images were collected. Repeatability was quantified using the intra-class correlation coefficient (ICC) and coefficient of variation (CV). Results: The repeatability of the PETCO2 (CV \u3c 2%) step changes resulted in BOLD CVR ICC \u3e 0.94 and CV \u3c 6% for cortical brain regions, which was similar to ASL CBF repeatability (ICC \u3e 0.96 and CV \u3c 4%). Conclusion: This study demonstrates the feasibility and precision of CVR imaging with an MPET CO2 challenge in mechanically ventilated subjects using an animal model. Translation of this method into clinical imaging protocols may enable CVR imaging in young children with cerebrovascular disease who require general anesthesia. © 2010 Wiley-Liss, Inc

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