Research Projects
The Lewis Research focuses on novel applications and enhancements of ultrasound in medicine. Our broad range of projects includes areas such as medical diagnostics, drug delivery and healing. We study interactions of ultrasound with cells to the humans and focus on training the next generation of biomedical scientists.
Ultrasound-Assisted Convection Enhanced Delivery
The presence of the blood-brain barrier prevents most substances, including chemotherapeutic drugs, from passing from the bloodstream into the brain. Surgeons have thus resorted to delivering the drugs directly into the brain through wafer implants or infusions. However, the high rate of elimination of these drugs in the brain means that they do not penetrate deep enough into the tissue to reach the cancer cells or remain long enough to destroy them. Our lab is combining the principles of convection and ultrasound to enhance the delivery of these chemotherapeutic drugs to the brain. In particular, we are studying the effects of Time Reversal Acoustics (TRA) to direct the drug to a specified region of interest.
The TRA system comprises external transducers, and a cannula for drug infusion with a beacon at the tip of the needle. TRA overcomes the reflective nature of the skull by recording the distorted ultrasound waves that reflect off the skull walls with a beacon, and then sending out a mirror image of the signal so that they converge around the beacon. We are looking at ways of using TRA focusing to target drug distribution to specific regions of the brain containing cancer cells while sparing healthy regions.
Continuous Low Intensity Therapeutic Ultrasound (LITUS) for Inflammation and Pain
Persistent pain is the number one reason that patients access the healthcare system according to the National Institutes of Health. Pain seriously affects patients’ quality of life and is associated with secondary morbidities such as depression, anxiety, and sleep disturbance. Pharmaceuticals currently dominate the treatment options due to widespread insurance coverage and convenience. However, there are a myriad of public health problems associated with drug use including addiction, medical side effects, and illegal drug use.
We are investigating mechanisms and clinical application of low intensity therapeutic ultrasound (LITUS) for reducing swelling and pain associated with osteoarthritis (OA) and back pain. In vitro we are using 2D and 3D culture systems to evaluate the response of OA synovial fibroblasts to continuous LITUS. In vivo are working with Weill Cornell Medical College to clinically evaluate the effectiveness of daily 2 to 6 hr LITUS therapy in chronic pain associated with knee OA and lower back pain using wearable iPod-sized ultrasound systems.
Ultrasound Electronics and Circuit Design
Ultrasound has been used safely and effectively for years in physiotherapy and diagnostic imaging. Additionally, the mechanical and thermal mechanisms of action in therapeutic ultrasound have been shown to facilitate wound and bone fracture healing, to promote the penetration of pharmaceuticals across the skin and through soft tissues, and found to enhance a variety of healthcare applications.
Despite the potential of ultrasound therapy, the size, price, and mode of delivery has prohibited its broad availability. Traditional ultrasound device architecture and various permutations rely on commercial radio frequency amplifiers and ultrasound transducers with 50 Ω output and 25 Ω and greater, input impedances, respectively. In the traditional regime, ultrasound generation is achieved by impedance matching the amplifier to the transducer, and the use of high voltage (greater than 100 V) alternating current excitation to drive the transducer. Ultralow Impedance Ultrasonic Design (UIUD) offers a unique platform for investigating the application of therapeutic ultrasound from high throughput cellular studies to human clinical trials. By minimizing the electrical and mechanical impedance of ultrasound systems, UIUD reduces the opposition to energy transfer from power source to ultrasonic vibration. By applying UIUD, much lower voltages (less than 4 V) may be used to generate abundant ultrasonic power. In Ultralow Impedance Ultrasonic Design (UIUD) energy transfers efficiently because electrical to mechanical conversion losses are reduced, allowing us to design miniature (iPod- and coin-sized) therapeutic ultrasound devices as well as high power multichannel arrays for biomedical acoustic research.
We are working on the development of innovative module ultrasound systems with ultralow impedance electronics and ultrasound transducers. The ongoing goal is to construct portable, low-cost, efficient and highly adaptable instrumentation to generate therapeutic ultrasound over a range of power levels and frequencies for clinical and research applications. The new designs will meet the needs of the world community to an extent not possible using commercially available therapeutic ultrasound technology. The developments of this research will increase the functionality and throughput of therapeutic ultrasound systems providing us with unique opportunities for testing the efficacy of acoustic applications in basic research and clinical applications.
Ultrasound Beam Scanning and Power Measurements
For many medical applications that require the use of ultrasound, it is often of interest to determine the interference patterns of acoustic emission. Through the use of beam scanning systems one can obtain high resolution profiles to visually and spatially quantify these patterns. The project involves the design and fabrication of a three dimensional transducer scanning system which utilizes a Matlab user interface to precisely control hydrophones receiver connected to a stepper motor system with micron precision.
Ultrasound Drug Delivery Implant for the Brain
Cancerous tumors in the brain can be removed through surgery leaving behind a cavity where the tumor previously existed. However, not all malignant cells get removed through the surgery.
Some of them are left behind which multiply again to develop another tumor in the same cavity which are often more aggressive than the previous one. To prevent the regeneration of the tumor, various drug delivery methods have been used one of them being planting the gliadel wafers with BCNU inside the cavity. But the effect of this drug is limited by the extent to which it can reach the malignant cells in the brain tissue. The aim of our research is to study the effect of ultrasound on drug diffusion inside the brain and configure the parameters that optimize the performance of the ultrasound delivery device inside the brain.
Implantable Ultrasound and Micro Fluidics
We are investigating innovative ways to deliver therapeutics locally and chronically to the damaged brain tissue, to enhance drug infusion and focusing for long-time treatment in the brain. It involves microdevices improvement and ultrasound assistance. Key components of microdevices are optimized, implantable and partly biodegradable microneedles and PLGA scaffolds, through which drugs can be infused directly into damaged area and can penetrate deeper into tissue compared to traditional therapies.
Improving Ultrasound Diagnostic Fetal Monitoring
Uterine contraction monitoring is a vital parameter in obstetric diagnostics. Symptoms of imminent spontaneous preterm birth are signs of premature labor; such signs consist of four or more uterine contractions in one hour before 37 weeks gestation. Presently, there are no available treatments for preterm birth. The key to treatment and prevention is early diagnosis.
Today’s maternal/fetal monitoring lacks the capability to diagnose labor and predict delivery. Moreover, the conventional methods of uterine contraction measurement are invasive in nature and do not yield very convincing results owing to its subjective/indirect nature. This research project focuses on developing novel noninvasive ultrasound based solutions for continuous measurement of the uterine contraction strength and duration.
Phantom Models for Diagnostic and Therapeutic Ultrasound
We are developing Tissue Mimicking Materials (TMMs) to facilitate ultrasound imaging and therapeutic research. There are a wide variety of materials, hard TMMs and soft TMMs that may be used for modeling different tissue layers and organs. Usually the soft tissues are composed of skin, tendons, muscles, adipose, blood vessels and synovial membranes.
Although a wide variety of soft/hard TMMs are commercially available, the real challenge is to develop materials that possess the correct acoustic and mechanical properties near those of the tissues being mimicked. A great deal of work has been done in the lab for the characterization of materials to find the substitutes for mimicking the uterine wall, brain and skull, leg and arteries and the respective surrounding layers. These models are then integrated into our other research thrusts.
Hydrogels for Ultrasound Mediated Therapy and Diagnostics
Conventional ultrasound transmission gel is messy, uncomfortable, dries out when used over long periods of time, and cannot provide a consistent coating. Our lab is developing alternative methods for ultrasound coupling.
We are designing custom hydrogels molded for diagnostic and therapeutic applications to meet the need of our multidisciplinary research.
Ultrasound Assisted Thrombolysis
The purpose of this project is to develop a novel ultrasound image-guided and therapy-assisted catheter to locate and dissolve thromboses. Ultrasound in combination with tissue plasminogen activator (tPA) and other clot-dissolving thrombolytic drugs is more effective than traditional DVT dissolution treatments; however due to limitations in the amount of energy and the coverage area of current commercially available catheter-based ultrasound technology, ultrasound-assisted DVT treatments still remain a slow process.
We are working to develop an approach to improve on a promising DVT treatment by developing a specially designed catheter and ultrasound therapy delivering transducer based on time-reversal acoustics principles to improve the coverage area of ultrasound-assisted tPA delivery. Additionally, we are exploring multi frequency approaches to improve sonothrombolysis.
Ultrasound for Wound Healing
Low-Intensity ultrasound has been used for years for the purpose of healing. Therapeutic ultrasound causes mechanical agitation of the by compression and rarefaction, stimulating cellular physiologic processes which enhance healing and regeneration of tissue. Both thermal and non-thermal effects contribute to the healing process, although the exact mechanisms are poorly understood.
Currently, therapeutic ultrasound is only applied to the patient for short periods of time (5-20 min) about once a week. There is evidence from animal studies that longer-duration, low-intensity ultrasound has additional benefits.
Our lab is developing pocket-sized, wearable ultrasound devices that allow us to bring the beneficial effects of this mode of delivery to people. Additionally, we are parametrically evaluating permutations of frequency, intensity and exposure levels of ultrasound on living tissues to develop safe guidelines for long duration ultrasound exposure.
In Vivo Acoustic Pressure Measurements, Field Mapping and Modeling
The goal of this research is to determine a safe and effective method to maximize the effects of ultrasound-assisted brain drug delivery. We use assumptions regarding the structure of the brain or brain phantom before and after ultrasound treatment CED infusion. We look to quantify the change in hydraulic conductivity, porosity, intracellular and extracellular space, and local transport coupled with acoustic interactions during ultrasound-assisted CED.
Ultrasound Assisted Colonoscopy
Currently in Western nations, colon cancer is the second leading cause of cancer-related deaths. Screening colonoscopy is the most effective preventative measure for colon cancer and is expected to remain the dominant form of colon cancer screening for several years because of its combination of both diagnosis and treatment. Before an individual can undergo a colonoscopy procedure, the individual must first perform a bowel preparation (cleaning) prior to the procedure. Unfortunately, due to the inconvenience and unpleasantness of bowel preparation, incomplete bowel prep has been reported in up to 20% of patients, which has resulted in 6% of colonoscopy procedures being aborted. The inadequate bowel preparation and the aborted procedures wastes both time and money and has shown to increase the overall costs of colonoscopy procedures by 12% to 22%. Current methods are employed wherein the colonic lumen is irrigated with water and the remaining fluids and unwanted debris are suctioned in an attempt to salvage poor bowel prep during colonoscopies; however, these methods are inadequate when facing a poorly prepped patient with solid stool that cannot be aspirated.This project utilizes ultrasound technology to aid in the aspiration of incomplete bowel prep.
Osmotically-Targeted Convection Enhanced Delivery
We are exploring microdialysis, a technique generally used to analyze neuronal tissue function by removing interstitial fluid in small amounts through osmotic gradients, as a suitable alternative for creating low-pressure gradients in brain tissue to control convection enhanced delivery (CED) distribution. Microdialysis relies on osmotic gradients created by pumping dialysate fluid through an osmotic membrane-containing probe. Differential concentration between the dialysate and fluid outside of the membrane causes net removal of fluid from the tissue through the microdialysis probe, creating a low-pressure area. Experimentation using standard tissue phantoms demonstrated bias between osmotically-targeted CED and control samples. Further work is currently underway to validate the technique and determine the effect of parameters as flow rates, positioning, and dialysate composition.
