Development of Cerebral Blood Flow and Cerebral Blood Volume Quantification Procedures using MRI without Contrast Agents

Modern medical imaging methods have transformed the diagnosis and treatment of a number of diseases. To date, most imaging has been used to show only the location of disease in organs such as the brain, helping doctors make diagnoses that include cancer or stroke. Recently a number of techniques have been developed that are able to provide additional information on the brain, such as the amount of blood supplying the tissue, or the density of blood vessels in different parts of the brain. As well as being useful in hospitals, these techniques are also being used by drug companies to provide better information on whether their new drugs are working well. However, many of these newer imaging techniques involve invasive procedures, such as injections, or involve exposing the patient to ionizing radiation. We wish to develop new totally non-invasive techniques using magnetic resonance imaging (MRI) that will be able to make accurate and absolute measurements of blood flow and vessel density in the brain. After verifying the accuracy of these measurements against more established invasive techniques, we will then use them to determine how useful they are in detecting changes caused by introducing a drug into the body. We will also use the new techniques to assess their ability to detect abnormal patterns in patients whose arteries that feed their brain have become partially blocked. If successful, these techniques could then find wider application in the more rapid development of new drugs to treat disease, and in the diagnosis and treatment of a number of brain diseases.

Imaging methods that are able to report on tissue function, in addition to structure/pathology, are becoming increasingly important in clinical research and in the pharmaceutical development process. Magnetic resonance imaging is a particularly prominent example of a non-invasive, or minimally invasive, tool for studying neurophysiology, due to its great versatility. However, there is still a need to develop MRI methods for measuring neurophysiological parameters that are truly quantitative and non-invasive. This proposal sets out to develop new quantitative MRI methods for measuring cerebral blood flow (CBF) and cerebral blood volume (CBV). Both these parameters are important in a number of neuropsychiatric disorders, and are also of great utility when assessing the effects of pharmacological intervention. We will use the requirement for signal averaging in the current class of non-invasive CBF and CBV methods to provide an opportunity to optimize the scan parameters in a subject-by-subject manner. This is accomplished by analyzing the data in real time as it is acquired by the MRI scanner. In a collaboration with industry we will validate the robustness of our approach against the gold standard method of positron emission tomography and will also test for reproducibility of the measurements. The methods will then be applied to measure CBF and CBV changes associated with a pharmacological intervention, and will also be tested in a clinical population suffering from cerebrovascular disease. Once validated and demonstrated, these techniques will provide vital new tools to study resting neurophysiology and its modulation following pharmacological intervention of disease.