WU, Lin2024-01-052024-01-052023https://hdl.handle.net/11299/259677University of Minnesota Ph.D. dissertation.-- 2023. Major: Biomedical Engineering. Advisors: Shalom Michaeli, Silvia Mangia. 1 computer file (PDF); xi, 134 pages.Introduction: Deep Brain Stimulation (DBS) treatment for Alzheimer’s disease (AD) is becoming increasingly evident. In this study, we exploited a novel orientation-selective (OS) strategy recently introduced by our group for DBS, entitled orientation-selective DBS (OS-DBS). This strategy entails that, by using multiple contacts with independent current sources within a multi-electrode array, the electric field can be oriented along any desired orientation in space. Therefore, axons parallel to the electric field spatial gradients are preferentially activated. Moreover, we applied the OS methodology to epidural spinal cord stimulation. In order to detect pathological processes of AD non-invasively with magnetic resonance imaging (MRI) technology, an alternating Look-Locker (aLL) method was developed to study novel MRI biomarkers such as T1? based on rotating frame MRI methods tailored to reveal neurodegeneration. Objectives and Methods: 1) For OS-ESCS, we introduced a similar OS approach for ESCS, and demonstrated orientation dependent brain activations as detected by brain fMRI. 2) To study OS-DBS of the subthalamic nucleus (STN), AD related targets including the entorhinal cortex (EC) and medial septal nucleus (MSN), to demonstrate the basic principle of OS and prove its feasibility and advantage in optimizing the stimulation of the target. Here, OS-DBS with a three-channel electrode was utilized to stimulate the rat STN, EC, and MSN to modulate the activation of brain networks connected to the stimulation sites. The induced brain activity was monitored with fMRI by Multi-Band Sweep Imaging with Fourier Transformation (MB-SWIFT) readout at 9.4 T. 3) The aLL method was proposed to perform simultaneous quantitative T1 and T1?, or T1 and B1 3D MRI mapping. Look-Locker scheme that alternates magnetization from the laboratory frame’s +Z and -Z axes is combined with a 3D MB-SWIFT readout. The analytical solution describing the spin evolution during aLL and the correction required for segmented acquisition were derived. The simultaneous B1 and T1 mapping were demonstrated on a phantom. T1? values in the rat brain in vivo and the Gd-DTPA phantom were compared to those obtained with a previously introduced steady–state (SS) method. Results: 1) For ESCS, orientation dependent activations were detected in brain areas that transmit the motor and sensory information. 2) OS-DBS of the STN reached maximal activation of related brain areas in correspondence with an in-plane 180° stimulation angle, which was consistent with the main mediolateral direction of the STN fibers confirmed with high resolution diffusion imaging and histology. Varying the in-plane OS-DBS stimulation angle in the EC resulted in the modulation of multiple downstream brain areas involved in memory and cognition. In contrast, no angle dependence of brain activation was observed when stimulating the MSN, consistent with predictions based on the electrode configuration and on the main axonal directions of the targets derived from diffusion MRI tractography and histology. 3) The aLL method allows for simultaneous T1 and B1 mapping, while the aLL method with the application of MP modules can provide simultaneous T1 and T1? maps. T1? values were similar with both aLL and SS techniques. However, aLL resulted in more robust quantitative mapping as compared with the SS method and provided the advantage of generating T1 maps in a single acquisition. Conclusions: 1) OS-ESCS allows the targeting of spinal fibers of different orientations, ultimately making stimulation less dependent on the precision of the electrode implantation. 2) OS-DBS stimulation angle modulates the activation of brain areas relevant to AD and Parkinson’s disease (PD), thus holding great promise for DBS treatment of the diseases. 3) The proposed aLL method offers a new flexible tool for quantitative T1, T1?, and B1 mappings.enalternating Look-LockerAlzheimer’s diseaseDeep brain stimulationMRIorientation-selectiveThesis or Dissertation