Absolute Quantification of Corrected 3D Perfusion for MR Imaging of Stroke

Ischemic stroke is the third leading cause of death in the industrialized world. In order to manage a stroke, three important factors are usually considered: treatment options, time since onset, and infarct volume. Generally, the different treatment options are medical therapy and surgical intervention. Clinical studies have reported high unsuccessful rates of treating stroke in patients using either medical therapy or surgical intervention. It is thought that this high rate is due to the variability within patients; despite the high risk, patient specific treatment may yield better outcome for those that can actually benefit. Cerebrovascular reserve may be a potent marker of determining patients for treatment, as past studies have shown that patients with very low cerebrovascular reserve have positive postoperative outcome, for example. Another factor in managing a stroke is infarct volume; by knowing the size of the infarct, it provides information to assess the risk and the success of the treatment. In order to provide information of infarct volume and perfusion such as cerebrovascular reserve, the applicant’s Specific Aim 1 is to develop a whole head 3D EPI pulse sequence capable of calculating absolute quantitative cerebral blood volume, cerebral blood flow and cerebrovascular reserve with perfusion correction to display more accurate infarct regions. As Specific Aim 2, the next step will be structured on validating the pulse sequence development done in Specific Aim 1. The pulse sequence development will consist of researching 3D dynamic susceptibility contrast bolus tracking along with T1 quantification of volumes by using a Look-Locker sequence. These sequences will employ radial acquisition methods and EPI. For 3D T1 quantification, a novel method will be developed that will measure the T1 regrowth efficiently and minimize scan times. This T1 measurement will be confirmed in phantoms. After the 3D quantitative perfusion sequence has been developed, the applicant will validate the sequence by using an animal model. The animal model will consist of mongrel dogs that will be scanned with the developmental pulse sequence and a commonly used 2D perfusion sequence at baseline and during a controlled ischemia. Microspheres will be injected during the experiment to obtain reference values to compare with MRI derived perfusion. By the end of this research, the following objectives will be achieved: 1) 3D quantitative MR perfusion pulse sequence with 1.7 mm isotropic resolution, frame rates of 800 ms, and scan time of less than 2 minutes will be developed; 2) this pulse sequence will be validated with microspheres in an animal model where success will be determined by high correlation (r > .8); and 3) the effect of perfusion correction will be analyzed by comparison with a non-corrected perfusion, in which finding a significant difference (p < .05) using a t-test will be deemed successful.