The use of focused ultrasound for theraputics in medicine

This is my last week here at Weill, and over the immersion thus far I have gotten to see many, many... many different types of surgeries and medical-clinical procedures. With my little blue note book and cell-phone camera I have been taking notes and jotting down ideas.

At first I was going to focus my research project on neurological drug delivery using ultrasound. This was related very closely to my Ph.D. research and fit with my mentor Dr. Riina, but after seeing all that was available to be here at the hospital and the willingness of clinicians to work with me, I have been able to broaden my view and study.

I also admit that after seeing laproscopic bladder and prostate surgeries, and the tools the doctors use I was inspired to think up some new applications of ultrasound in the treatment of diseases.

BACKGROUND

Acoustical techniques have been used in a variety of situations to enhance medical treatments. For example, high intensity focused ultrasound (HIFU) has been used to ablate and liquefy tissues, and past and current studies are being conducted to assess the use of HIFU as a more complete surgical tool for minimally invasive therapy. Focused ultrasound is beginning to be assessed as a feasible way to deliver drugs to neurological tissues via selective disruption and permeablization of the blood brain barrier (BBB). Drugs that once could not cross the BBB because of molecular weight and hydrodynamic radius are now able to permeate into the neurological tissue with the application of ultrasound. Ultrasound has also been used in other applications such as gene therapy and drug activation, and for further information on therapeutic ultrasound one can read the Nature Drug Discovery Article "Healing sound: the use of ultrasound in drug delivery and other therapeutic applications.

The above image shows the enhancing effects of ultrasound on non-invasive drug delivery into tissue. Shown in yellow is the drug perfusion by diffusion mechanisms alone, shown in green is the enhanced delivery of drug with ultrasound The image x-axis is distance into the tissue and y-axis is the amount of drug potentially delivered.

POTENTIAL USES OF THERAPEUTIC ULTRASOUND

My experience from watching surgeries, talking with clinicians, and reviewing literature on PubMed, has created many potential uses for enhanced drug delivery using ultrasound in the clinical setting.

1. Neurosurgery:

a.) After tumor removal drugs are delivered locally, or the space is filled with a gliadel BCNU wafer. The application of ultrasound may potentially enhance drug diffusion from the locally delivered chemotherapy, thus increasing the chemo's effectiveness.

b.) In trying to fix neural aneurysms the most common techniques are either to pinch it off, or filling it with a coil. The use of ultrasound may be able to activate a locally delivered filling agent, or it may be used to target drugs to reduce the growth and shrink the aneurysm.

Things that must be considered to apply this technique are the following: getting the acoustic energy to the specific location, not damaging the tissue in its pathway and developing a re-usable minimally invasive mechanism.

Possible solutions are:

I. To produce an array that attaches to the head and is able to target the specific location (Like the acoustic version of the gamma knife). Existing mapping technology with MRI/image guided procedures could be used to simplify development

II. Use a high-power catheter based acoustic probe e.g. intravenous ultrasound, that may be guided to the place of interest. This however requires the development of new piezoelectric materials, that can produce large acoustic outputs with small surface area.

The above image is a potential acoustic therapeutic helmet.

2. Prostate Surgery:

Removal of the prostate may be