April 22, 2008

Massachusetts General Hospital, Richard B. Simches Research Center, Room 3110

185 Cambridge Street, Boston

4:00 – 6:00PM, Refreshments 3:30PM

Lester Wolfe Workshop in Laser Biomedicine
Shining Light on Melanoma

The rapid increase in the incidence of malignant melanoma and its high associated mortality necessitates improvements in diagnosis and therapy. This workshop will feature the contributions that can be made in managing this disease by biomedical optics. Although melanoma is highly visible macroscopically, non-invasive optical imaging techniques can improve microscopic detection. Laser-induced thermotherapy can give effective local control and at the same time stimulate the host immune response.

Workshop Moderator: Michael R. Hamblin, PhD, Associate Professor of Dermatology, Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital, mhamblin@partners.org

Introduction: Framing the Problem of Melanoma Diagnosis
Arthur J. Sober, MD, Associate Chief of Dermatology, Massachusetts General Hospital, sober@partners.org

Video not available

Photoacoustic Tomography and Melanoma Imaging
Lihong Wang, PhD, Gene K. Beare Distinguished  Professor, Department of Biomedical Engineering, Washington University in St. Louis, lhwang@biomed.wustl.edu

Professor Lihong Wang's lab develops photoacoustic imaging technologies for early-cancer detection and functional imaging by physically combining non-ionizing electromagnetic and ultrasonic waves. Unlike ionizing x-ray radiation, non-ionizing electromagnetic waves, such as optical and radio waves, pose no health hazard and, at the same time, reveal new contrast mechanisms.  Unfortunately, electromagnetic waves in the non-ionizing spectral region do not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution tomography based on non-ionizing electromagnetic waves alone, as demonstrated by confocal microscopy and two-photon microscopy as well as optical coherence tomography, is limited to superficial imaging within about one optical transport mean free path (~1-2 mm) of the surface of biological tissue. Ultrasonic imaging, on the contrary, provides good image resolution but has strong speckle artifacts as well as poor contrast in early-stage tumors. The lab has developed ultrasound-mediated imaging modalities by combining electromagnetic and ultrasonic waves synergistically to overcome the above limitations. The hybrid modalities provide relatively deep penetration at high ultrasonic resolution and yield speckle-free images with high electromagnetic contrast.

In photoacoustic computed tomography, a pulsed broad laser beam illuminates the biological tissue to generate a small but rapid temperature rise, which leads to emission of ultrasonic waves due to thermoelastic expansion. The short-wavelength pulsed ultrasonic waves are then detected by unfocused ultrasonic transducers. High-resolution tomographic images of optical contrast are then formed through image reconstruction. Endogenous optical contrast can be used to quantify the concentration of total hemoglobin, the oxygen saturation of hemoglobin, and the concentration of melanin. Melanoma and other tumors have been imaged in vivo in small animals. Exogenous optical contrast can be used to provide molecular imaging and reporter gene imaging.

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Continued on reverse

In photoacoustic microscopy, a pulsed laser beam is focused into the biological tissue to generate ultrasonic waves. The ultrasonic waves are then detected with a focused ultrasonic transducer to form a depth resolved 1D image directly. Raster scanning yields 3D high-resolution tomographic images.

Thermoacoustic tomography is similar to photoacoustic tomography except that low-energy microwave pulses, instead of laser pulses, are used.  Although long-wavelength microwaves diffract rapidly, the short-wavelength microwave-induced ultrasonic waves provide high spatial resolution. Microwave contrast measures the concentrations of water and ions.

Clinical Imaging of Melanoma
Zeina Tannous, MD, Attending Dermatologist, Massachusetts General Hospital; Chief of Mohs/Dermatologic Surgery, Boston VA hospitals; Associate Program Director, Dermatopathology, Harvard Dermatology Residency Program, ztannous@partners.org

Video not available

Laser Immunotherapy for Melanoma
Mark F. Naylor, MD, Associate Professor, Department of Dermatology, University of Oklahoma Health Sciences Center, Tulsa Campus; Clinical Associate Professor, Department of Surgery, University of Oklahoma Health Sciences Center; Associate Clinical Member, Arthritis & Immunology, Oklahoma Medical Research Foundation

Treatment with topical TLR-agonists stimulates immune responses against cutaneous tumors and can be useful as monotherapy for treating skin cancers including melanoma. Phototherapy with either PDT or laser also has significant immunostimulatory properties. Dr. Mark Naylor's lab combined these two techniques to treat cutaneous metastases from melanoma, a therapy termed in situ photoimmunotherapy or ISPI. The lab is currently conducting a phase I trial of ISPI in stage III and IV melanoma with cutaneous metastases. Initial results of this therapy demonstrate an impressive response rate, exceeding 60% complete initial clearance in regional (stage III). Complete clearance has been seen in early stage IV and it is possible that we may see prolonged survival in subjects with complete initial clearance. Further study is needed to replicate and confirm these preliminary results. ISPI therapy has the potential to become the treatment of choice for stage IIIC melanoma (in transit metastases).

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Lester Wolfe Biography

Lester Wolfe was an inventor with a special interest in optics and photography. He died in 1983 at the age of 86. He was a benefactor of MIT, and his will provided funds "for fellowships for studies in molecular biology and for research using optical methods in the investigation of the structure and properties of matter." Lester was born in Boston in 1897 to a family of modest means. He enrolled at MIT as physics undergraduate and graduated in the class of 1919 -- well before the advent of quantum mechanics, the atomic bomb or lasers! During World War I he served in the armed forces as an inventor, and received a commendation for design of the "fuel quantity gauge", which used a radioactive source to measure the supply of fuel stored in the wings of an airplane. After the war he became active in industry, and he made his fortune in the field of containerized shipping between the United States and Japan. He became an expert in pre-Colombian art and technology, and a collector in this field and several others. Toward the end of his life Lester became interested in furthering research in biology and medicine as well as in the area that he loved most, optics. That is how he developed an interest in the research projects of the Spectroscopy Laboratory.

The Lester Wolfe Workshop in Laser Biomedicine is a series of talks dedicated to a particular aspect in biomedical optics. The panel of speakers of the Workshop is chosen from expert researchers in academia, medical profession and industry. Held twice a year, the Lester Wolfe Workshop is sponsored by the George R. Harrison Spectroscopy Laboratory, MGH Wellman Center for Photomedicine, Harvard—MIT Division of Health Sciences and Technology, and CIMIT (Center for the Integration of Medicine and Innovative Technology). Information obtained from the MIT Spectroscopy Website: http://web.mit.edu/spectroscopy/events/wolfe.html.