As exploration missions evolve, NASA’s protocol for medical emergencies switches from a stabilize and transport home approach to a stand and fight approach. As a result, space travelers must be able to diagnose and treat a myriad of medical conditions. Dr. Lawrence A. Crum is developing a lightweight, portable device that would use diagnostic ultrasound to determine a site of internal bleeding and High Intensity Focused Ultrasound to stop the bleeding. The device could also be used for a number of other medical conditions, such as the identification and treatment of benign and malignant tumors and kidney stones.
Overview
Smart Therapeutic Ultrasound Device for Mission-Critical Medical Care
Principal Investigator:
Lawrence A. Crum, Ph.D.
Organization:
University of Washington
Technical Summary
Original Aims
The principal, long-term objective of this project is to develop a smart medical device that would be lightweight, portable, FDA approved, under commercial development and capable of addressing various risks. In particular, we seek to address the risk of blunt internal trauma and internal bleeding resulting, for example, from a collision in microgravity between an astronaut and a heavy object. The device would be capable of detecting internal bleeding and inducing transcutaneous hemostasis. As recent experiences in Antarctica demonstrate, the risk of malignant tumors that require some form of surgery may well appear without warning, especially in the high-radiation load of outside low Earth orbit, even when extensive pre-screening is undertaken. The device would be capable of performing bloodless ablation of detectable tumors without fear of metastasis. Another risk, the formation of renal calculi has been suggested as a likely result in extended spaceflight; indeed, a precedent exists of early mission termination due to a ureteral stone. The device we propose would be capable of detecting and sufficiently comminuting a renal calculus for it to pass without obstruction through the urinary system.
Our Specific Aims have been achieved. Smart medical systems and techniques have been developed for bleeding, cancer and kidney stones. Each is at the gateway of Technical Readiness Level/Countermeasure Readiness Level 6. Army surgeons have tested the system on bleeding in animals and complementary Phase II funding from the Defense Advanced Research Project Agency (DARPA) has been received to build and test, in partnership with a company, a specific portable hemostasis device for human use. An Investigational Device Exemption (IDE) has been obtained for an ultrasound-guided High-Intensity Focused Ultrasound (HIFU) system for cancer treatment, and we are in the process of setting up clinical trials. A patient study has been proposed to the National Institutes of Health and our Human Subjects Division to test our imaging feedback and guidance systems for acoustic therapy for kidney stones. One of our feedback techniques could be used on International Space Station today to detect kidney stones.
The principal, long-term objective of this project is to develop a smart medical device that would be lightweight, portable, FDA approved, under commercial development and capable of addressing various risks. In particular, we seek to address the risk of blunt internal trauma and internal bleeding resulting, for example, from a collision in microgravity between an astronaut and a heavy object. The device would be capable of detecting internal bleeding and inducing transcutaneous hemostasis. As recent experiences in Antarctica demonstrate, the risk of malignant tumors that require some form of surgery may well appear without warning, especially in the high-radiation load of outside low Earth orbit, even when extensive pre-screening is undertaken. The device would be capable of performing bloodless ablation of detectable tumors without fear of metastasis. Another risk, the formation of renal calculi has been suggested as a likely result in extended spaceflight; indeed, a precedent exists of early mission termination due to a ureteral stone. The device we propose would be capable of detecting and sufficiently comminuting a renal calculus for it to pass without obstruction through the urinary system.
Specific Aims
- To expand the capability of our existing smart medical device for transcutaneous acoustic hemostasis to include a fully integrated ultrasound detection, targeting and therapy system.
- To develop the capability of the integrated image-guided therapy system in Specific Aim 1 to target and ablate specific tissue volumes such as benign and malignant tumors.
- To develop the capability of the integrated image-guided therapy system in Specific Aim 1 to target and comminute renal calculi.
Our Specific Aims have been achieved. Smart medical systems and techniques have been developed for bleeding, cancer and kidney stones. Each is at the gateway of Technical Readiness Level/Countermeasure Readiness Level 6. Army surgeons have tested the system on bleeding in animals and complementary Phase II funding from the Defense Advanced Research Project Agency (DARPA) has been received to build and test, in partnership with a company, a specific portable hemostasis device for human use. An Investigational Device Exemption (IDE) has been obtained for an ultrasound-guided High-Intensity Focused Ultrasound (HIFU) system for cancer treatment, and we are in the process of setting up clinical trials. A patient study has been proposed to the National Institutes of Health and our Human Subjects Division to test our imaging feedback and guidance systems for acoustic therapy for kidney stones. One of our feedback techniques could be used on International Space Station today to detect kidney stones.
In addition to moving devices to patient testing, we have these findings that above all contribute to obtaining approval for clinical use and increase the efficiency and therefore portability of the systems:
- We offered a new explanation, nonlinear acoustic propagation, as to how HIFU can be used in vivo and in developing commercial systems to enhance heating.
- We discovered advantages of ultrasound guidance over Magnetic Resonance Imaging (MRI) guidance that will benefit HIFU in space where MRI is not an option.
- A novel hydrophone, a tool necessary for characterizing the output of a HIFU device, was created and characterized and has some advantages over the existing high amplitude hydrophone.
- The gold standard hydrophone was re-calibrated to improve its accuracy at high frequencies, which are important in HIFU heating.
- A method to derate water measurements to tissue was devised and tested.
- Tools, e.g., monitoring voltage to the source as a detector or localized boiling, to use the derating method in real-time were developed.
- We found that tissue ablation can span a spectrum from nearly purely thermal to nearly purely mechanical based on the HIFU pulsing scheme to control boiling created by nonlinearly enhanced heating.
- An automated system, which detects bleeds, distinguishing them from patient vessels, targets the bleed site, and treats and stops treatment when the bleed is no longer detected, was built and submitted as an invention disclosure and is the subject of a peer-reviewed manuscript.
- An acoustic system was developed, patented and reported to size kidney stone fragments during ureteroscopy to prevent the clinician or astronaut (as may be needed) from attempting to extract too large a fragment.
- Following on our work to obtain an IDE last year from the FDA, a contract was secured to for a new HIFU system to begin treating patients for pancreatic cancer.
- Based on successful preliminary work benefiting from knowledge gained through NSBRI-funded research, a Phase II Department of Defense grant was secured to build an acoustic hemostasis device.
Impact
We have begun work on a second generation of these systems as part of a renewal project and other leveraged proposals. The new systems are automated, integrated with other smart medical systems technology, more efficient and smaller with novel imaging feedback, and are not only used for treatment but for prevention.
Earth Applications
We will develop a smart medical device that would have specific applications to the risks associated with space travel. Due to the major constraints and uniqueness of that environment, this device, as presently conceived, would most probably not, in itself, be of value to Earth-based clinical medicine. However, the various technologies that are to be incorporated into this device have many important clinical applications. In particular, we seek to build a lightweight, image-guided, therapy device that would have the capability to ablate tumors, stop bleeding and to detect, as well as to comminute, small kidney stonesall in a single device. These medical conditions are also commonplace on Earth.
Uncontrolled, occult bleeding due to trauma is a major Earth-based risk. In a multi-center review of 72,151 trauma admissions at a civilian health center, 62 percent of those requiring emergent operative treatment were in shock on arrival in the operating room, and the actual cause of death was credited to bleeding in 82 percent of the cases. Indeed, exsanguination is often reported as the major cause of mortality (~50 percent) in combat casualties. Accordingly, we have been undertaking a major effort, funded by a variety of federal agencies, principally the Department of Defense (DoD) and in partnership with Philips Medical and Siemens Ultrasound, to develop a portable device that could be used in forward echelons of the battlefield to address the risk of death by exsanguination. We have leveraged this extensive DoD-funded effort in our research for NSBRI. Several companies, in addition to Philips Medical and Siemens Ultrasound, have product development programs underway on this concept. Therus Corporation and AcousTx Corporation, based in Seattle, have licensed technology from the University of Washington (UW).
This image-guided therapy approach utilizes the capability of High-Intensity Focused Ultrasound (HIFU) to rapidly elevate the temperature to coagulative necrosis levels (> 55 Celsius). The capability to induce coagulative necrosis, particularly under image guidance, provides a unique opportunity to treat benign and malignant tumors. Two Seattle-based start-up companies, Mirabilis Medica and UltraSound Technologies, Inc., have licensed UW technology to develop products that would use image-guided HIFU to ablate tumors. Our NSBRI team has also assisted Yuande, a Chinese company, in its application to the FDA for an Investigational Device Exemption to treat patients with advanced stage pancreatic cancer.
Our laboratory has had considerable experience in the treatment of kidney stone disease. We are now participating in the 15th year of a National Institutes of Health Program Project Grant to study the physical basis of stone comminution and tissue damage in shock-wave lithotripsy. Between 5 percent and 15 percent of the general population will develop a urinary calculus during their lifetime, which will account for about seven to ten of every 1000 hospital admissions in the United States. One of our major contributions to lithotripsy research has been the determination that acoustic cavitation plays a major role in stone comminution. Our NSBRI project builds upon this extensive experience to develop a system for detecting and comminuting a kidney stone in the unique and remote environment of space. Because fluoroscopy will probably not be available in extended space travel missions, our ultrasound-based detection and comminution approach has been developed. In performing this research, we developed unique techniques and methodologies for monitoring the progress of lithotripsy treatment that appear to have immediate Earth-based applications.
This project's funding ended in 2008