Harvard Catalyst Profiles

Three main research programs at the Center for Advanced Biomedical Imaging and Photonics are: 1) in vivo optical detection of preinvasive cancer; 2) studying sub-cellular morphology with confocal light absorption and scattering spectroscopic microscopy and 3) development of optical spectroscopic technique for noninvasive prenatal diagnosis. The Center develops and uses a variety of different tools and platforms for in vivo optical biomedical imaging.

In Vivo Optical Detection of Preinvasive Cancer

The purpose of this program is to develop an optical system which can perform rapid optical scanning and multispectral imaging of the entire epithelial surface of various organs in reproductive and gastrointestinal tracts and present a diagnosis in near real time. This approach is vastly superior to the present strategies of performing random biopsies. Thus, it can provide a powerful tool for screening large populations of patients for early precancerous changes. In its pilot clinical test in the esophagus at BIDMC this instrument, for the first time in the world, successfully guided biopsy detecting and mapping sites of invisible dysplasia missed by the current standard-of-care.

Studying Sub-Cellular Morphology with Confocal Light Absorption and Scattering Spectroscopic Microscopy

Confocal Light Absorption and Scattering Spectroscopic (CLASS) Microscopy developed at the Center is a novel way to use optical imaging techniques for non-invasive monitoring of embryonic cells on the submicron scale with no exogenous labels. The human embryo development and response to environmental factors could be monitored progressively at all critical stages using CLASS microscopy. For example, when cells are in metaphase, CLASS could provide information concerning the number and shape of chromosomes present. Since the CLASS measurement is nondestructive and requires no exogenous chemicals, a given embryo in vitro could be monitored over time before implantation. These kinds of progression studies are not possible with any other currently available techniques.

Optical Spectroscopic Technique for Noninvasive Prenatal Diagnosis

Non-invasive prenatal diagnosis utilizing fetal cells circulating in maternal peripheral blood has received much attention since it poses no risk to the fetus. Although several fetal cell types have been targeted, the search has focused on fetal nucleated red blood cells (fNRBC). Because of the low concentration of fNRBC in maternal blood, and interference by adult nucleated red blood cells (aNRBC), along with the failure to find broadly applicable identifiers that can differentiate fetal from aNRBC, reliable use of viable fNRBC in amounts sufficient for clinical use remains a challenge. We have demonstrated that fNRBC optical properties provide a unique optical biomarker that is based on the light scattering spectroscopic signatures of fNRBC and may enable isolation of these cells from maternal peripheral blood samples. This project can lead to development of a clinical minimally invasive prenatal genetic testing technique.

References:

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. Functional Imaging of Epithelial Tissues with Polarized Light Scattering Spectroscopy. Nature Medicine, 2001;7:1245-48.

Itzkan I, Qui L, Fang H, Zaman MM, Vitkin E, Ghiran IC, Salahuddin S, Modell MD, Andersson C, Kimerer LM, Cipolloni PB, Lim K-H, Bigio IJ, Itzkan I, Freedman SD, Sachs BP, Hanlon EB, & Perelman LT, Confocal Light Absorption & Scattering Spectroscopic (CLASS) Microscopy Monitors Organelles in Live Cells with no Exogenous Labels, Proc. Nat. Acad. Sci. USA, 2007; 104: 17255-17260.

Qiu L, Pleskow D, Chuttani R, Vitkin E, Leyden J, Ozden N, Itani S, Guo L, Sacks A, Goldsmith JD, Modell MD, Hanlon EB, Itzkan I, & Perelman LT. Multispectral Scanning during Endoscopy Guides Biopsy of Dysplasia in Barrett’s Esophagus, Nature Medicine, 2010; 16:603-606.

Vitkin E, Turzhitsky V, Qiu L, Guo L, Itzkan I, Hanlon EB, & Perelman LT. Photon diffusion near the point-of-entry in anisotropically scattering turbid media. Nature Commun. 2011; 2:587.