Development and Validation of an Integrated Computational Model of Cerebral Blood Flow and Oxygenation Iain K. Moppett, DM, FRCA Jonathan G. Hardman, DM, FRCA BACKGROUND: Various groups have constructed simulations and models of cerebral blood flow and oxygenation, each with its strengths and weaknesses. We describe the development and validation of a novel computational model, the Nottingham cerebral simulator (NCS), designed for experimental and teaching use. METHODS: Physiological hypotheses were converted into differential equations; these are solved numerically with respect to time. A battery of tests was derived from published literature against which to test the simulation: static and dynamic autoregulation responses; carbon dioxide reactivity; brain tissue oxygenation. The NCS was programmed to simulate the methodologies of published experiments and the results of the simulation and the published data were compared. RESULTS: The NCS results are qualitatively and quantitatively similar to published data. The values for regulatory indices were (published values in parentheses): index of autoregulation 0.9 (0.9); transient hyperemic response ratio 1.3 (1.3), carbon dioxide reactivity 2.4%– 4.7% mm Hg -1 (2– 4.5); brain tissue oxygen tension 22 mm Hg (20 –100). CONCLUSIONS: The NCS is a credible model of cerebral blood flow and oxygenation, which warrants further use as an experimental and teaching tool. (Anesth Analg 2007;105:1094 –103) Abnormalities of cerebral blood flow (CBF) and oxygenation are common in patients requiring sur- gery or intensive care, commonly due to traumatic brain injury, cerebrovascular disease secondary to hypertension, atheroma, or diabetes, and intracranial hemorrhage. Although clinicians have had a basic understanding of the various physiological principles underlying CBF and metabolism for many years, the complexity of pathology, temporal changes, and non- linear interactions has made simple mental constructs inadequate to explain clinical findings. To improve this situation, various groups have con- structed simulations or models of CBF and metabolism, each with its strengths and weaknesses (1– 6). Many of these models are research tools written using math- ematical modeling software without easily accessible user interfaces. This article describes the development of a computational model of CBF and oxygenation, the Nottingham cerebral simulator (NCS), which is scien- tifically robust and designed to be usable both as an experimental and teaching tool. An accompanying article describes its use for investigating this aspect of cerebral oxygenation adequacy (7). METHODS Model Development The NCS uses a lumped-parameter, iterative ap- proach to generate a time-dependent simulation of blood flow and metabolism. A full description of the modeling equations is given in the online supplemen- tary material (please see supplementary material available at www.anesthesia-analgesia.org). Pertinent aspects of the compartments used, simulation of fluid flow, passive and regulatory behavior of the various compartments, nutrient and gas exchange, and pa- rameter assignment are described below. Compartments The system to be modeled (brain, blood vessels, cerebrospinal fluid (CSF), cranium) is split conceptu- ally into various connected compartments, each of which has its own patterns of behavior. These com- partments represent the average behavior of their physiological correlates (e.g., proximal arterioles), but are not intended to replicate any single identifiable vessel or cell. There is a compromise between increas- ing anatomical and physical correlation (requiring more compartments), and verifiable modeling of be- havior and realistic computational load (requiring less compartments). The Monroe–Kellie hypothesis (8) is a This article has supplementary material on the Web site: www.anesthesia-analgesia.org. From the Division of Anaesthesia and Intensive Care, Queen’s Medical Centre Campus, Nottingham University Hospitals, Not- tingham, UK. Accepted for publication July 5, 2007. Reprints will not be available from the author. Address correspondence to Iain K. Moppett, Division of Anaesthe- sia and Intensive Care, Queen’s Medical Centre Campus, Nottingham University Hospitals, NG7 2UH, Nottingham, UK. Address e-mail to iain.moppett@nottingham.ac.uk. Copyright © 2007 International Anesthesia Research Society DOI: 10.1213/01.ane.0000284620.37846.e5 Vol. 105, No. 4, October 2007 1094