Internal bleeding is one of the most difficult medical conditions to treat, especially in environments such as space where full medical facilities are not available. This project involves the design of a lightweight, portable device that would use diagnostic ultrasound to determine a site of bleeding and High Intensity Focused Ultrasound to induce hemostasis. The device could also be used for a number of other medical conditions, such as the identification and treatment of benign and malignant tumors.
Overview
Guided High Intensity Focused Ultrasound (HIFU) for Mission-Critical Care
Principal Investigator:
Lawrence A. Crum, Ph.D.
Organization:
University of Washington
Technical Summary
The principal objective of this NSBRI Smart Medical Systems Team project is to develop an image-guided ultrasound therapy system for mission critical care. In long-term space flight missions, a number of medical situations could develop that if not adequately addressed would result in mission failure. For example, although gravity is significantly reduced in space, inertia is not, and the collision of an astronaut with a heavy object could result in blunt internal trauma and is often associated internal bleeding. In addition, as recent experiences in Antarctica demonstrate, medical conditions that require some form of surgery may well appear without warning, even when extensive pre-screening is undertaken. We are developing a smart medical device that will provide a versatile capability to treat a variety of these mission-critical medical conditions. We have demonstrated that a device that produces High Intensity Focused Ultrasound (HIFU) can be combined with a device that provides ultrasound imaging to produce a duplex system that can both image a particular condition of interest and provide therapy to relieve the condition. Image-Guided Therapy provides enormous potential for the treatment of a variety of medical conditions. In addition, we have demonstrated that the components of such a smart medical system can reasonably be expected to be lightweight and portable.
Specific Aims:
Specific Aim 1: To develop a combined ultrasound guidance and therapy system. This first-generation system should have the following components: (A) Laptop computer control, (B) Software control, (C) Compatibility with commercial ultrasound imaging systems, (D) Single element resonant transducer, and (E) Dynamic depth focusing.
Specific Aim 2: To perform studies on the combined system that would lead to optimal performance parameters. Among the studies to be performed are the following: (A) Biological effects, tissue necrosis, acoustic hemostasis, (B) Image quality for diagnosis, (C) Targeting and monitoring capabilities, (D) Acoustic focusing and power requirements, and (E) Thermal focusing limitations.
Specific Aim 3: Utilizing the results of Aims 1 & 2, to develop an integrated ultrasound guidance and therapy system. This second-generation system would have the following characteristics: (A) Integrated imaging and HIFU therapy transducers, (B) Cavitation feedback, (C) Attenuation/thermal feedback to localize treatment site, (D) Perfusion and back-scatter imaging for treatment localization, and (E) Software control and friendly user interface.
Key Findings of the Project:
Our three Specific Aims have been met. Aim 1 was completed and reported in Year One. The ability to use ultrasound to guide HIFU is the foundation of the integrated system developed in Aim 3.
Aim 2 is the science to make the system clinically useful. Our group continues to lead the world in the field of acoustic hemostasis. The NSBRI project has leveraged other funding to use HIFU to stop bleeding. And we have found we can break kidney stones with HIFU. In particular the NSBRI research has led to the two most powerful ways to enhance or optimize tissue heating short, strong pulses to exploit nonlinear wave propagation (initiated in Year 2) and dual-frequency mixing to exploit cavitation bubbles (discovered in Year 3).
Aim 3 has lead to the most portable and versatile guided HIFU system we know of. We have developed (A) Integrated imaging and HIFU therapy transducers, (B) Cavitation feedback, (C) Attenuation/thermal feedback to localize treatment site, (D) Perfusion and back-scatter imaging for treatment localization, and (E) Software control and friendly user interface.
Key Findings of Year 3: We had three key findings in Year 3.
First, we found we could integrate the three key findings of Year 2 into a useful part of our system and expand of those findings. The findings were not solely academic discoveries but became enabling technologies. The protocol of using short high-amplitude pulses has been integrated in the system. We showed that doubling the acoustic amplitude of the source cuts the treatment time by more than one half. In Year 3, we utilized this technology and defined the mechanisms underlying the effect. Two, our lesion identification algorithm has been improved to even measure temperature of HIFU heated tissue before a lesion even forms. This enables safe and accurate targeting. Tests are underway of the system connected to the HDI-1000 imager with this imaging capability. Three, the patenting and licensing process continues for our circuit to permit real-time synchronization of HIFU therapy with an arbitrary ultrasound imager. Commercial partners may soon be using the technology to develop even smaller and more powerful systems than we have developed.
Second, we developed a complete integrated guided system within a suitcase. The system could be synchronized with an arbitrary ultrasound imager, such as the Philips HDI-5000 on the ISS. Or we added in Year 3 to use a simplified Doppler imaging system to locate the HIFU focus on a major bleed by visual or audio guidance. This is an uncomplicated user-friendly device to rapidly and accurately treat a mission critical bleed.
Third, we discovered that by using two frequencies instead of one HIFU frequency, we could accelerate hemostasis times 25 percent. We completed a careful study numerically and experimentally in vivo and in vitro that showed how two frequencies can increase cavitation, enhance heat deposition and accelerate hemostasis.
Impact
The components now weigh less than 7 kg, down from more than 30 kg in Year 1, and 40 kg at the start of the project. They are packaged in a single chassis (a suitcase) and operate with the Philips HDI-5000 ultrasound imager on the ISS or whatever imager is chosen for long-duration missions (i.e., a Terason or a Sonosite imager such as used in the SMS project lead by Dr. J. Thomas). Doppler makes a simple rapid method stop major bleeds without even the use of the ultrasound imager.
We have established a protocol to sweep short-duration, high-amplitude pulses produced by the dynamic focusing transducer to treat large areas rapidly without complications from cavitation. This includes sealing exposed lung from blood and air leakage. These findings expand our trauma care capabilities, improve therapy efficiency, and minimize the power draw required by the device. When two frequencies are mixed, the enhancement is even greater. Bleeds stop 25 percent quicker. In addition, since heating and greater, higher volume bleeds can likely be stopped. Lastly, since the heated region is broader, likely larger vessels can be treated than were previously possible.
We can use the same dual frequency system to treat kidney stones. Renal Stone Formation is Risk 12 on the Critical Path Roadmap, and the device we are currently building may be a method to comminute renal calculi that do form in space. Stone comminution is part of our renewed grant.
Thus, a practical flexible HIFU system for space use is nearing reality, and simultaneously, The University of Washingtons Center for Industrial and Medical Ultrasound (CIMU), with NSBRI funding, is one of the leaders making high intensity focused ultrasound an Earth-bound clinical reality. An MRI-guided HIFU device received FDA approval for the treatment of uterine fibroids this year. The company employs a former student who graduated from our group and has made use of CIMUs published work. Devices in China have treated more than 10,000 patients for cancer and are now negotiating exports to selected sites. CIMU has been consulted on these negotiations. Smaller hemostasis devices are being developed by two spin-off companies from CIMU. These new companies are beginning to generate the substantial private funding necessary to overcome the production, regulatory and insurance reimbursement challenges of a new therapeutic modality.
This project's funding ended in 2004