Research Summary:

My research interests lie at the intersection of three fields: medicine, biology and physics.

1. Spectroscopic detection of early cancer with scattered light

2. Confocal light absorption and scattering spectroscopic (CLASS) microscopy

My main area of research interests for the past decade has been spectroscopic detection of early cancer on a cellular scale. I became interested in this field when I learned that one of the most effective methods of fighting cancer might be its prevention if detected at an early stage. What is an early stage? It turns out that in the majority of organs cancer originates in the epithelium, a layer of highly cellular tissue covering the inner and outer surfaces of the body, and is confined there for a while before invading underlying tissues. This cellular precancerous stage is often called dysplasia. Unfortunately, many forms of dysplasia are difficult to detect and diagnose using current methods since they are flat and not readily observable. To detect dysplasia multiple, often random, biopsies are taken from the organ of interest, tissue is fixed, stained and microscopically evaluated by a pathologist who is looking for epithelial changes such as nuclear atypia, cellular proliferation and alterations in architecture.

Over the past several years my students and I have been working on development of a novel optical imaging technique, Confocal Light Absorption and Scattering Spectroscopic (CLASS) Microscopy, capable of non-invasively determining the dimensions and other physical properties of single subcellular organelles with ten-nanometer accuracy (Nature Biotech. under review, Applied Optics, 2007). CLASS microscopy combines the principles of light scattering spectroscopy (LSS) with confocal microscopy. LSS is an optical technique that relates the spectroscopic properties of light elastically scattered by small particles to their size, refractive index and shape. The multispectral nature of LSS enables it to measure internal cell structures much smaller than the diffraction limit without damaging the cell (IEEE J. Sel. Top. Quant. Elect. 2003; J. Biomed. Opt. 2005) or requiring exogenous markers, which could affect cell function. Scanning the confocal volume across the sample creates an image. The CLASS microscope, recently developed in my laboratory, provides unique capabilities to study cell interactions with the environment, cell reproduction and growth and other functions of viable cells, which are beyond the capabilities of other techniques. Using the CLASS microscope, we were able to differentiate and monitor functioning cells? individual organelles, such as mitochondria, lysosomes and microscomes, based on their inherent physical-chemical properties (Nature Biotech. under review). Applications for CLASS microscopy in such diverse areas as obstetrics/gynecology, neuroscience and drug discovery are all linked by the potential of this technique to observe functional intracellular processes nondestructively (this project is supported by NIH R33 project grant and DOD grant).

Selected Publications:

Backman V, Wallace M, Perelman LT, et al. Detection of Preinvasive Cancer Cells. Early-Warning Changes in Precancerous Epithelial Cells Can Now be Spotted In Situ. Nature 2000;406,6791:35-36.

Gurjar R, Backman V, Perelman LT, et al. Imaging Human Epithelial Properties with Polarized Light Scattering Spectroscopy. Nature Medicine 2001;7:1245-48.

Perelman LT and Backman V. Chapter XII. Light Scattering Spectroscopy of Epithelial Tissues: Principles and Applications. In: Handbook on Optical Biomedical Diagnostics, Tuchin V, ed., Bellingham: SPIE Press; 2002, p. 675 -724.

Fang H, Ollero M, Vitkin E, Kimerer LM, Cipolloni PB, Zaman MM, Freedman SD, Bigio IJ, Itzkan I, Hanlon EB and Perelman LT, Noninvasive Sizing of Subcellular Organelles with Light Scattering Spectroscopy. IEEE J. Sel. Top. Quant. Elect. 2003;9,267-276.

Schuele G, Vitkin E, Huie P, Palanker D and Perelman LT, Optical detection of the reaction of organelles to cellular stress. J. Biomed. Opt. 2005;10(5):051404-1-8.