Improved Techniques for Acquisition and Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Detecting Vascular Permeability in the Central Nervous System

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique for quantitative assessment of the integrity of blood-brain barrier and blood-spinal cord barrier (BSCB) in the presence of central nervous system pathologies. However, the results of DCE-MRI show substantial variability. The high variability can be caused by a number of factors including inaccurate T1 estimation, insufficient temporal resolution and poor contrast-to-noise ratio. My thesis work is to develop improved methods to reduce the variability of DCE-MRI results. To obtain fast and accurate T1 map, the Look-Locker acquisition technique was implemented with a novel and truly centric k-space segmentation scheme. In addition, an original multi-step curve fitting procedure was developed to increase the accuracy of T1 estimation. A view sharing acquisition method was implemented to increase temporal resolution, and a novel normalization method was introduced to reduce image artifacts. Finally, a new clustering algorithm was developed to reduce apparent noise in the DCE-MRI data. The performance of these proposed methods was verified by simulations and phantom studies. As part of this work, the proposed techniques were applied to an in vivo DCE-MRI study of experimental spinal cord injury (SCI). These methods have shown robust results and allow quantitative assessment of regions with very low vascular permeability. In conclusion, applications of the improved DCE-MRI acquisition and analysis methods developed in this thesis work can improve the accuracy of the DCE-MRI results.

Are anatomic brain locations important in determining the clinical outcomes in acute ischemic stroke? --- An exploratory analysis of the NINDS Stroke Trial data

Background and purpose. Brain lesions in acute ischemic stroke measured by imaging tools provide important clinical information for diagnosis and final infarct volume has been considered as a potential surrogate marker for clinical outcomes. Strong correlations have been found between lesion volume and clinical outcomes in the NINDS t-PA Stroke Trial but little has been published about lesion location and clinical outcomes. Studies of the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Trial data found the direction of the t-PA treatment effect on a decrease in CT lesion volume was consistent with the observed clinical effects at 3 months, but measure of t-PA treatment benefits using CT lesion volumes showed a diminished statistical significance, as compared to using clinical scales. ^ Methods. We used the global test to evaluate the hypothesis that lesion locations were strongly associated with clinical outcomes within each treatment group at 3 months after stroke. The anatomic locations of CT scans were used for analysis. We also assessed the effect of t-PA on lesion location using a global statistical test. ^ Results. In the t-PA group, patients with frontal lesions had larger infarct volumes and worse NIHSS score at 3 months after stroke. The clinical status of patients with frontal lesions in t-PA group was less likely to be affected by lesion volume, as compared to those who had no frontal lesions in at 3 months. For patients within the placebo group, both brain stem and internal capsule locations were significantly associated with a lower odd of having favorable outcomes at 3 months. Using a global test we could not detect a significant effect of t-PA treatment on lesion location although differences between two treatment groups in the proportion of lesion findings in each location were found. ^ Conclusions. Frontal, brain stem, and internal capsule locations were significantly related to clinical status at 3 months after stroke onset. We detect no significant t-PA effect on all 9 locations although proportion of lesion findings in differed among locations between the two treatment groups.^