The major goal of this effort is to utilize existing ultrasound platforms and the concept of image-guided therapy to control traumatic bleeding, ablate benign and malignant tumors, and to diagnose and reposition kidney stones. We address (1) Lack of advanced therapeutic capability, (2) lack of capability to treat renal stones, and (3) lack of non-invasive diagnostic imaging capabilities. The original specific aims (SAs) are 1) Support ongoing leveraged efforts in Acoustic Hemostasis and High-intensity Focused Ultrasound (HIFU) Tumor Ablation by addressing fundamental scientific issues as well as to ensure National Space Biomedical Research Institute (NSBRI) relevance. 2) Develop methods and technologies that would enable detection of renal stones with ultrasound. 3) Develop technology and perform in vitro studies of stone comminution. 4) Utilizing technology and protocols developed in SAs 2 and 3, perform in vivo studies in a porcine model. The main findings and associated research productivity for year 4 are:
Proposed plan for the next year. We have developed extensive plans to continue forward and have submitted many proposals to continue funding. The efforts are on three fronts. One is to conduct a human feasibility study. The second is to start the company. The third is to secure NSBRI funding to develop the same capabilities for the FUS and to refine and test the system for NASA's unique applications. We were subcontract on one proposal to develop the FUS but did not receive that award. The NSBRI proposal aims are to refine and validate probes to detect, reposition, and fragment kidney stones.
Tasks are 1. Implement capability to image and reposition stones on the selected FUS manufacturer's state-of-the-art kidney imaging probe. 2. Integrate a clinical mechanically scanned 4D imaging probe with the FUS and refine and validate stone imaging and repositioning. 3. Develop and integrate a prototype 2D array probe to reposition and fragment stones. 4. Refine and validate capability to displace a large blocking stone, to detect a ureter stone, to displace a ureter stone, to expel a stone attached to tissue, and to measure the size of kidney stones.More »
We have been encouraged by our interactions with the urology, ultrasound, and business communities that our technology to detect and reposition stones could significantly alter the way kidney stones are treated in clinical medicine. We have won awards in the six poster or business plan competitions we have entered. Most stones are small enough to pass naturally and thus patients are encouraged, through hydration, to try to pass the stone without intervention. This natural process might take 6-8 weeks and result in considerable discomfort to the patient over this interval. With our innovative technology, a stone could potentially be cleared in the first office visit. Many stones do not clear with hydration, and thus more aggressive approaches are required. More invasive procedures are often necessary if the stone is in the lower pole because even if fragmented, the pieces are unlikely to pass from this location. Our technological approach would keep the least invasive option open for these patients. In most existing procedures, there is a significant chance stone pieces will remain behind as seeds for future stones and further surgery. Our technology could help these pieces pass. In addition, stones are often recurrent; recurring-stone patients are often monitored, so that new stones can be detected early—this monitoring could be done with our precise stone imaging approach. Our technology could also move these stones to the kidney exit before they are symptomatic. This technology reduces risk of surgery, complications of surgery for the patient, and the cost of surgery to the insurance companies; furthermore, the technology does not preclude any surgical options. Lastly, the algorithms to detect kidney stones alone stand to spare many patients the ionizing radiation of a CT scan, or to provide options to pregnant women or children with stones who are unlikely to receive CT. NSBRI quickly recognized the value of this technology and helped us initiate our commercialization effort that now has the full support of the UW, the Washington Research Foundation, and a commercial hardware provider, as well as the interest of several venture capitalists and ultrasound companies.
The applications of our technology to the control of bleeding and for tumor ablation are at least as profound. Specifically, this year we have worked with the latest clinical HIFU machine—one developed by Philips Medical. This machine is intended for many clinical applications. We have used some of our effort to characterize the output of the machine and assess its potential bio-effects. Our work provides the clinicians, who intend to use this machine, the ability to select a treatment dose. At UW alone, it helps train the clinicians and establish the specificity of what size targets are treated. With our contribution, the clinicians are then likely to pursue their own clinical studies, and regulatory approval for various tumor treatments. Before our involvement, the machine sat dormant for a year. We are also exploring the effects of HIFU on the immune system and have proposed clinical trials to combine HIFU with chemical therapeutic agents. We believe that our efforts to carefully describe outputs and bio-effects will help the U.S. catch up with the rest of the world where over 400,000 patients have been treated by HIFU. In addition, our intimate knowledge of these details enables us to consider ways in which a similar, much reduced-in-size system could be developed for NASA to reduce some critical risks to astronauts during long duration space travel.More »
|Organizations Performing Work||Role||Type||Location|
|National Space Biomedical Research Institute (NSBRI)||Lead Organization||Industry||Houston, TX|
|University of Washington||Supporting Organization||Academic||Seattle, WA|
Task 1A. Perform studies of bleeding detection in a flow-phantom model: Successfully detected and treated sites in a phantom developed with Defense Advanced Research Projects Agency (DARPA) and FDA in a blind test with an automated system.
Task 1B. Perform studies to determine pressure and temperature in ex vivo tissue exposed to HIFU: Published several papers, which led to invitation to join IEC (International Electrotechnical Commission) working group on HIFU standards and the AIUM (American Institute of Ultrasound in Medicine) sub-committee on Transiently Increased Outputs, and to measure acoustic output of Philips clinical HIFU machine. Also, discovered and submitted patent application for a method to emulsify tissue with ultrasound.
Task 2A. Develop new stone detection techniques based on radiation force and reverberation responsible for twinkling artifact: As part of our graduate student's dissertation, discovered that bubbles are responsible for the twinkling artifact. We have developed, implemented, tested, and patented new software to better detect stones.
Task 2B. Test stone sizing technology in tissue: Published paper, filed U.S. and international utility patent applications, and are negotiating licensing. We have initiated human clinical studies to test ultrasound stone sizing versus CT.
Task 3A. We utilized the YUANDE HIFU tumor ablation device as a test platform: Performed a number of studies.
Task 3B. Engineer and optimize an image-guided, two-frequency HIFU system for renal stone comminution: We will work with Exploration Medical Capabilities (ExMC) Human Research Program Element to implement on the FUS system capability to detect, reposition, and comminute stones. All are implemented in a prototype for which we are pursuing an investigational device exemption (IDE) with the FDA. We have developed a concept of expelling small stones from a kidney before they require comminution or surgery. A system to detect and reposition stones based on an OEM diagnostic ultrasound platform has been built and demonstrated to be safe and effective in studies in a porcine model. Commercialization efforts are well underway. Our technology was called a "game changer" in the plenary session of the American Urological Association (AUA) Annual meeting in May 2012.
Task 4A. Perform in vivo tests of the imaging protocols developed in Task 2: our paper is in press comparing twinkling to standard B-mode for stone detection in patients. New algorithm for stone detection implemented on clinical machine and tests of the algorithm initiated on human subjects. Data from 15 subjects has been collected.
Task 4B. Performed studies to determine the potential for HIFU-induced stone comminution as well as any associated tissue injury. We used our stone repositioning system to fragment stones in an excised porcine kidney in which they were grown. In vivo tests scheduled for Oct 22, 2012. In vivo studies of our stone clearance system have been shown to be safe and effective. Several studies of safety in pigs have been complete and are in press. These data have been presented to the FDA as part of our application for investigational device exemption for a human feasibility study.More »
This is a historic project that was completed before the creation of TechPort on October 1, 2012. Available data has been included. This record may contain less data than currently active projects.