Dissertation/Thesis Abstract

Intra-arterial selective brain cooling for stroke: Mathematical modeling, and MRI spectroscopic thermometry
by Neimark, Matthew A., Ph.D., Columbia University, 2008, 252; 3299360
Abstract (Summary)

Although stroke is the third leading cause of death in the United States, there are not many effective therapies for it. Further, those therapies which exist must be implemented in a very narrow time window after the onset of symptoms. Recently, hypothermia has emerged as a promising new treatment option for stroke due to its success in experiments with animal models of focal ischemia, and human clinical trials of similar ischemic conditions (cardiac arrest and perinatal asphyxia). Therapeutic hypothermia is usually induced systemically through surface cooling methods or venous catheters which circulate cool fluid. There are two problems associated with systemic methods: they are relatively slow, normally achieving therapeutic target temperatures in 3-6 hours, and systemic hypothermia is associated with side-effects such as arrhythmia, coagulopathies, and infection. A local method selective brain hypothermia has been proposed, infra-carotid cold saline infusion (ICSI) which is potentially much faster and more selective than the systemic methods.

This study involves the development of a brain cooling model to test the feasibility of ICSI. The model was based on a hemispheric representation of brain tissue and surrounding skull and scalp, and was propagated using the Pennes bio-heat equation. The model was tested with different constant flow rates of cold saline (10-50 ml/min), and 1 hour simulations were run to observe spatial and temporal patterns of cooling. According to the model, cooling to therapeutic temperatures (32-33°C) could be achieved with flow rates of 30-40 ml/min within 10 minutes. Hematocrit levels were not reduced below 25% (when initial hematocrit was 42%). The model was enhanced by adding different anatomical and physiological components including venous return, circle of Willis, and a two-compartment systemic hemodilution model. A control procedure was implemented to initiate hypothermia and maintain constant temperature (32°C) within a voxel in the brain model. Through this control procedure, it was determined that although a cooling cap could not effectively induce brain hypothermia when used alone, it greatly enhanced cooling when used in conjunction with ICSI.

Magnetic resonance spectroscopic thermometry was developed and evaluated in phantoms and in humans both with a single voxel method, and a fast echo planar method. In both humans and phantoms, spectra were characterized in terms of signal to noise ratio and damping rates and these parameters were correlated with temperature precision via simulations. In phantoms, thermometry was calibrated and performed with measurement precision of 0.15°C.

Indexing (document details)
Advisor: Laine, Andrew F., Brown, Truman R.
School: Columbia University
School Location: United States -- New York
Source: DAI-B 69/01, Dissertation Abstracts International
Subjects: Biomedical engineering, Physiology
Keywords: Brain cooling, Hypothermia, Spectroscopic thermometry, Stroke
Publication Number: 3299360
ISBN: 978-0-549-43059-9
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