Monday, December 30, 2024
12/30/2024
Project Summary/Abstract Kidney stones are prevalent and one of the costliest urologic diseases. The available treatment options such as ureteroscopy or shockwave wave lithotripsy break the stone into small fragments that can lead to future growth and recurrence of symptoms. This proposal investigates the underlying mechanisms to use acoustic radiation force produced by an ultrasound multi-element array that can trap a stone, steer it out of the kidney collecting space, and deposit it in the renal pelvis or UPJ to facilitate its natural clearance. The project seeks to answer the fundamental scientific hurdles to target and maneuver the stone toward passage. Aim 1 develops the analytical framework to optimize pulsing mechanisms to trap and manipulate natural stones. A proposed semi-analytical approach approximates the scattering with spherical functions to calculate the forces on natural stones. Predictions will be combined with the investigation of pulsing parameters to optimize trap robustness and achieve stable trapping of natural stones. Pulsing parameters such as pulse length, repetition rate, frequency, and phase excitation that control beam shape and uniformity will be adjusted to eliminate instabilities from rotation and asymmetric forces to achieve stable trapping of natural stones. The aim success is measured by performing manipulation maneuver natural stones along predetermined paths. In Aim 2, the stone acts as a target that can reflect and scatter ultrasound waves which are received back by the multi-element array. Correction algorithms use the received signal to calculate the element excitations necessary to correct for beam aberrations from the tissue heterogeneity. Hydrophone measurements will compare the beams before and after corrections with the unaberrated beam. Finally, manipulation of stones in kidney phantoms and ex vivo are performed to mimic in vivo conditions. In Aim 3, the safety and efficacy of acoustic forceps manipulation will be evaluated. First, different acoustic intensity exposures will be investigated in ex vivo porcine kidneys for thermal and mechanical injury. Afterward, natural stones of various sizes will be implemented in the kidney collecting space of live pigs. The stone will be targeted, trapped, and steered from the kidney collecting space toward the kidney exit using the acoustic forceps. The treated group will be evaluated against an untreated control group to evaluate efficacy. Tissue injury mechanisms will be assessed through histological analysis. In addition to my research, I will also pursue other activities guided by my mentors toward my career goal of becoming an independent investigator. These activities include interacting with researchers, industry partners, and clinicians through seminars and conferences; and participating in workshops on the responsible conduct of research, and grant proposals and management so that I will be able to pursue independent R-level funding toward the end of the K25 award. The Applied Physics Laboratory offers the facilities and inter-departmental collaboration necessary for successful career development in translational research.
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