Introduction
Xenon-enhanced computed tomography (Xe-CT) is a powerful physiologic imaging tool that provides a clinician with quantitative cerebral blood flow (CBF) data, allows the physiologic response to various interventions to be measured, and provides prognostic data to guide patient management. Though the data provided are in a tomographic format, it provides quantitative information for critical decision making when needed. In this way Xe-CT CBF is similar to the CBF monitors discussed in subsequent chapters rather than imaging technologies. This chapter discusses the theory and physics behind the data provided, the practical aspects of Xe-CT, and the clinical decision-making process in several neurologic conditions encountered in the neurocritical care unit (NCCU) based on quantitative CBF data.
Technology
Theory and Physiology
CBF can be measured by a number of diffusible tracers. Xenon 133 was an ideal early tracer because xenon is highly lipid soluble and its 133 isotope can be readily tracked with external scintillation counters. Using this technology, early studies showed that hemispheric and then superficial regional flow could be measured in mL/100 g/min. However, because radioisotope precautions were needed and resolution in the depth of the brain was limited, routine intensive care unit (ICU) application was not possible. In the late 1970s, once it was reported that stable xenon was radiodense, similar to iodine, CT imaging techniques and the ability to tomographically image CBF were reported. Tens of thousands of Xe-CT CBF studies have been done since then without significant complications. When first available clinically, use of xenon in the United States received “grandfather” approval as a contrast agent from the U.S. Food and Drug Administration (FDA). When Praxair, the company that supplied medical-grade xenon, withdrew from the rare-gas market, xenon lost clinical approval, and currently its use in the United States occurs under investigational new drug (IND) and research protocols. A reapplication for clinical approval has been submitted to the FDA.
Studies with xenon 133 use the “wash-out” curve of this tracer, whereas studies with stable xenon focus on the “wash-in” curve. Use of a wash-in curve reduces any theoretical alteration of flow measurement due to an activation of CBF after xenon inhalation and has been validated in other quantitative CBF studies. In 2000 the dose of xenon was reduced to 28% because newer CT scanners had a lower noise level. This helped reduce the few sensorial effects associated with 33% xenon and reduced cost. With 28% xenon, studies can be routinely performed in cooperative outpatients and in ventilated ICU patients.
To calculate CBF using Xe-CT requires a modification of the Kety-Schmidt equation. Two variables are needed to solve the equation: (1) the arterial concentration curve of the agent and (2) the extent and time course of tissue arrival that depends on the blood flow and the blood-brain partition coefficient, or lambda. The arterial concentration is measured indirectly from the end-tidal xenon concentration; this is a very good approximation of a highly diffusible gas such as xenon. The brain partition coefficient and flow is calculated for each CT pixel by solving the Kety-Schmidt for both variables using an iterative mathematical approach:
Cxe br ( t ) = λ k o ∫ t Cxe Art ( u ) e − k ( t − u ) du
where Cxe br (t) is the time dependent brain xenon concentration, λ is the blood-brain partition coefficient, k is the brain uptake flow rate constant, Cxe Art (u) is the time-dependent arterial xenon concentration. This calculation is performed typically at 4 CT levels; however, 8 to 10 levels can be used with newer multidetector scanners.
The calculated CBF values then are represented graphically in a standardized color-coded fashion for each pixel ( Figs. 27.1 to 27.3 ). A bell-shaped filter is applied to aid visual display. To obtain useful regional values, the cortical mantle can automatically be divided into 20 2-cm-deep regions of interest (ROI), and the average for each region displayed. Alternatively, any ROI of regular or irregular shape and size can be selected by the user on either the CT or the CBF image (see Fig. 27.1 ). Additional analysis can be performed to assess the validity and further manipulate the data ( Figs. 27.2 to 27.7 ). For mixed cortical sources, CBF in the range of 54 plus or minus 10 mL/100 g/min is normal. Values less than 15 to 20 mL/100 g/min represent ischemia and are associated with neurologic deficit and infarction. Normal gray matter blood flow is 84 mL/100 g/min and white matter is 20 mL/100 g/min. The mixed cortical flow and gray matter flow decrease with age, but white matter flow remains constant ( Fig. 27.8 ).
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