SBIR-STTR Award

Significance: Ureteroscopic laser lithotripsy is currently the most common surgical treatment for urinarystones-a painful disease affecting 1 in 11 people and imposing a significant burden on the U.S.healthcare system, with the cost of care exceeding $10 billion annually. Although laser lithotripsy breaksall types of stones, an emergent concern is that a large fraction of patients (around one in two) is leftwith residual stone fragments when evaluated with computed tomography that are too small to laserefficiently but too large to pass spontaneously with urine flow. While the residual fragments are small incomparison with the pre-treatment stone, the residual fragments nonetheless lead to high rates of post-operative emergency department visits, additional interventions, and recurrence of stones.Preliminary studies suggest that specially engineered microbubbles augment laser lithotripsy, producingsmaller residual fragments, which should lead to improved clinical outcomes. We hypothesize thatengineered microbubbles augment laser lithotripsy by focusing energy into stones and stone fragmentsvia two main mechanisms: optical and mechanical. This is consistent with the mechanisms by whichconventional laser lithotripsy ablates urinary stones, via direct laser light interactions with the stonesurface as well as mechanical effects due to the rapid vaporization and subsequent violent collapse ofthe aqueous environment concomitant with each laser pulse.The objective of this Phase I SBIR is to determine the feasibility of using specially engineeredmicrobubbles to significantly reduce residual stone fragments and improve laser lithotripsy. In Aim 1,we will identify mechanisms and sites of action of engineered microbubbles in laser lithotripsy. In Aim 2,we will develop strategies to improve the effectiveness of laser lithotripsy with engineered microbubbles.The innovation of the proposed approach is the use of engineered microbubbles that accumulate onurinary stones to augment stone fragmentation and reduce residual stone fragments in laser lithotripsy.This approach has the potential to significantly improve the treatment for urinary stones by reducing therisk of injury, procedural complications, and additional procedures, as well as result in a significantreduction in procedural time and cost. In addition, the knowledge gained from this feasibility study willaid our understanding of the mechanisms by which conventional laser lithotripsy operates, and producefurther insights into the treatment of biomineralization-related diseases.

Public Health Relevance Statement:
Public Health Relevance Urinary stones afflict millions of Americans every year and are associated not only with severe pain, but also with high treatment costs and potentially life-threatening complications. Currently, the most common treatment for urinary stones involves a minimally invasive ureteroscopic laser procedure that intends to break urinary stones into sufficiently small fragments to allow them to pass naturally out of the urinary system. This project aims at improving the laser procedure by using engineered microbubbles that will further reduce the residual stone fragment size-an innovative way to pulverize stones into easily passed fragments.

Project Terms:
Affect ; Disease ; Disorder ; Dust ; Engineering ; Environment ; Feasibility Studies ; Goals ; Healthcare Systems ; Health Care Systems ; Irrigation ; Lavage ; Nonvaginal irrigation ; Nonvaginal lavage ; irrigation therapy ; lavage therapy ; other than vaginal Douching ; other than vaginal Irrigation ; Lasers ; Laser Electromagnetic ; Laser Radiation ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Light ; Photoradiation ; Lipids ; Longevity ; Length of Life ; life span ; lifespan ; Optics ; optical ; Pain ; Painful ; Patients ; Postoperative Period ; Post-Operative ; Postoperative ; pressure ; Recurrence ; Recurrent ; Research ; Risk ; Shock ; Circulatory Collapse ; circulatory shock ; Time ; X-Ray Computed Tomography ; CAT scan ; CT X Ray ; CT Xray ; CT imaging ; CT scan ; Computed Tomography ; Tomodensitometry ; X-Ray CAT Scan ; X-Ray Computerized Tomography ; Xray CAT scan ; Xray Computed Tomography ; Xray computerized tomography ; catscan ; computed axial tomography ; computer tomography ; computerized axial tomography ; computerized tomography ; Treatment Protocols ; Treatment Regimen ; Treatment Schedule ; Urinary Calculi ; Urinary Stones ; Urinary Tract Stones ; Urolith ; Urine ; Urine Urinary System ; Violence ; violent ; violent behavior ; Water ; Hydrogen Oxide ; Work ; Treatment Cost ; Injury ; injuries ; base ; detector ; sensor ; Ureteroscopes ; improved ; Procedures ; Left ; Distal ; Site ; Surface ; Clinical ; Penetration ; Residual state ; Residual ; Specific qualifier value ; Specified ; Phase ; Laser Lithotripsy ; Chemicals ; Fiber ; Pulse Rates ; insight ; Video Microscopy ; Videomicrography ; Videomicroscopy ; Knowledge ; Life ; mechanical ; Mechanics ; Pulse ; Physiologic pulse ; Frequencies ; Pattern ; Techniques ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; vaporization ; American ; vapor ; aqueous ; Speed ; Devices ; Intervention Strategies ; interventional strategy ; Intervention ; patient safety ; Microbubbles ; Effectiveness ; Renal/Urologic Organ System ; Urologic/Renal Body System ; Urinary system ; Data ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; energy density ; cost ; Outcome ; innovation ; innovate ; innovative ; biomineralization ; therapy development ; develop therapy ; intervention development ; treatment development ; public health relevance ; minimally invasive ; common treatment ; product development ; Emergency department visit ; ED visit ; ER visit ; Emergency care visit ; Emergency hospital visit ; Emergency room visit ; care costs ;