Award Abstract #0238903
CAREER: Optical Spectroscopy and Imaging for Understanding the Interrelation of Molecular and Ultrastructural Changes in Neoplastic Cells and Early Cancer Detection

NSF Org:	CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems
Initial Amendment Date:	February 12, 2003
Latest Amendment Date:	June 25, 2007
Award Number:	0238903
Award Instrument:	Continuing grant
Program Manager:	Leon Esterowitz CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems ENG Directorate for Engineering
Start Date:	July 1, 2003
Expires:	June 30, 2009 (Estimated)
Awarded Amount to Date:	$400000
Investigator(s):	Vadim Backman v-backman@northwestern.edu (Principal Investigator)
Sponsor:	Northwestern University 633 CLARK ST EVANSTON, IL 60208 847/491-3003
NSF Program(s):	BIOPHOTONICS, IMAGING &SENSING, BIOMEDICAL ENGINEERING
Field Application(s):	0203000 Health
Program Reference Code(s):	OTHR,1187,1045,0000
Program Element Code(s):	7236,5345

ABSTRACT

0238903

Backman

Under this CAREER award, the advances of optical spectroscopy and imaging will be bridged to those of molecular biology to investigate the dynamics of the alterations of the organization of epithelial cells undergoing precancerous and early cancerous transformations. A novel spectroscopic imaging technique that utilizes light elastically scattered by living epithelial cells and enables quantitative characterization of the cell and tissue micro- and nano-architecture without tissue processing will be developed. This technique will be applied to correlate the ultrastructural and morphological changes in the living epithelial cells with specific molecular events associated with the development of neoplasia, to establish how the cell organization and molecular events are interrelated and affect the development of cancer, and to evaluate the usefulness of these findings for the purposes of the detection and diagnosis of precancerous and early cancerous transformations in the colon. In these studies, experimental model of colon carcinogenesis (azoxymethane-treated rats) and human tissues will be utilized. To enable the development of the light scattering spectroscopic imaging, realistic analytical and numerical models of light scattering by inhomogeneous tissue structures will be developed, and the origins of light scattering signatures in the living epithelial cells will be identified. One of the long-term outcomes of this project would be the development of a novel optical technique to risk-stratify patients for colon neoplasia and to non-invasively diagnose colon and, potentially, other types of cancer.

The objective of the educational plan is to integrate the traditional engineering and physical aspects of the medical imaging curriculum with these of the contemporary biology and medicine. To achieve this goal, an innovative component of the medical imaging curriculum will be developed. This component will consist of three new integrative interdisciplinary courses: Optical Imaging and Microscopy, Advanced Physical Optics, and Clinical Experience in Medical Imaging. The curriculum will bridge the physical and engineering principles with the biological and clinical applications of optical imaging and other imaging modalities. Furthermore, students will learn how the medical imaging is used in clinical practice by rotating through various clinical sub-specialties where medical imaging is extensively used.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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H. K. Roy, P. Iversen, J. Hart, Y. Liu, J.L. Koetsier, Y. Kim, D.P. Kunte, M. Madugula, V. Backman, R.K. Wali.  "Downregulation of SNAIL Suppresses MIN Mouse Tumorigenesis: Modulation of Apoptosis, Proliferation and Fractal Dimension,"  Molecular Cancer Therapeutics,  v.3,  2004,  p. 1159.

H. K. Roy, Y. L. Kim, Y. Liu, M. J. Goldberg, V. Turzhitsky, R. E. Brand, N. Hasabou, M. Jameel, and V. Backman.  "Spectral Markers in Preneoplastic Intestinal Mucosa: An Accurate Predictor of Tumor Risk in the MIN Mouse,"  Cancer Epidemiology, Biomarkers & Prevention,  v.14,  2006,  p. 1639.

H. K. Roy, Y. L. Kim, Y. Liu, R. K. Wali, M. J. Goldberg, V. Turhitsky, J. Horwitz, V. Backman.  "Risk-Stratification of Colon Carcinogenesis through Enhanced Backscattering (EBS) Spectroscopy Analysis of the Uninvolved Colonic Mucosa,"  Clinical Cancer Research,  v.19,  2006,  p. 961.

H. Subramanian, P. Prabhakar, Y. Kim, Y. Liu, X. Li, and V. Backman.  "Photon random walk model of low-coherence enhanced backscattering (LEBS) from anisotropic disordered media: a Monte Carlo simulation,"  Applied Optics,  v.45,  2006,  p. 6292.

H.K. Roy, R. Wali R, Y.L. Kim YL, Y. Liu Y, M. Goldberg, and V. Backman.  "Four-Dimensional Elastic Light-Scattering Fingerprints as Preneoplastic Markers in the Rat Model of Colon Carcinogenesis,"  Gastroenterology,  v.126,  2004,  p. 1071.

J. Gong, B. Liu, Y. Kim, X. Li, V. Backman.  "Wavelength Synthesis for Optimizing the Resolution of Optical Coherence Tomography,"  Optics Express,  v.14,  2006,  p. 5909.

K. Chen, Y. Kim, A. Taflove, V. Backman.  "Self-Assembled Patterns of Nanospheres with Symmetries from Submicrons to Centimeters,"  Applied Physics Letters,  v.86,  2005,  p. 033101.

L. A. Marcelino, V. Backman, A. Donaldson, C. Steadman, J. Thompson, S. Pacocha-Preheim, C. Lien, E. Lim, D. Veneziano, M. F. Polza.  "Accurate Identification of Low Abundant Targets Amidst Similar Sequences by Revealing Hidden Correlations in Oligonucleotide Microarray Data,"  PNAS,  v.103,  2006,  p. 13629.

M. P. Siegel, Y. L. Kim, H. Roy, R. Wali, V. Backman.  "Assessment of Blood Supply in Superficial Tissue using Polarization Gated Elastic Light Scattering Spectroscopy,"  Applied Optics,  v.40,  2006,  p. 335.

R. K. Wali, H. K. Roy, Y. L. Kim, Y. Liu, J. L. Koetsier, D. P. Kunte, M. J. Goldberg, V. Turzhitsky, V. Backman.  "Increased Microvascular Blood Content is an Early Event in Colon Carcinogenesis,"  Gut,  v.54,  2005,  p. 654.

S. C. Kong, J. J. Simpson, V. Backman.  "ADE-FDTD Scattered-Field Formulation for Dispersive Materials,"  IEEE Microwave and Wireless Components Letters,  v.18,  2008,  p. 4.

S. Tseng, A. Taflove, D. Maitland, V. Backman.  "PSTD Simulations of Multiple Light Scattering in 3-D Macroscopic Random Media,"  Radio Science,  v.41,  2006,  p. 10.1029.

X. Li, A. Taflove, V. Backman.  "Anomalous Oscillations in the Spectra of Light Backscattered by Inhomogeneous Microparticles,"  Phys Rev E,  v.75,  2007,  p. 037601.

X. Li, A. Taflove, V. Backman.  "Modified FDTD Near-to-Far Field Transformation for Improved Backscattering Calculation of Strongly Forward-Scattering Objects,"  IEEE Antennas and Wireless Propagation Lett,  v.4,  2005,  p. 35.

X. Li, A. Taflove, V. Backman.  "Modified FDTD Near-to-Far Field Transformation for Improved Backscattering Calculation of Strongly Forward-Scattering Objects,"  IEEE Antennas and Wireless Propagation Lett.,  v.4,  2005,  p. 35.

X. Li, A. Taflove, V. Backman.  "Recent progress in exact and reduced-order modeling of light-scattering properties of complex structures,"  IEEE JSTQE,  v.11,  2005,  p. 759.

X. Li, A. Taflove, V. Backman.  "Quantitative analysis of depolarization of backscattered light by stochastically inhomogeneous dielectric particles,"  Optics Letters,  v.30,  2005,  p. 902.

X. Li, Z. Chen, A. Taflove, and V. Backman.  "Equiphase-sphere approximation for analysis of light scattering by arbitrarily-shaped nonspherical particles,"  Applied Optics,  v.43,  2004,  p. 4497.

X. Li, Z. Chen, A. Taflove, V. Backman.  "Novel Analytical Technique for Light Scattering by Stochastically Inhomogeneous Particles,"  Phys. Rev. Lett.,  v.70,  2004,  p. 056610.

X. Li, Z. Chen, A. Taflove, V. Backman.  "Optical Analysis of Nanoparticles via Enhanced Backscattering Facilitated by 3-D Photonic Nanojets,"  Optics Express, 13(2), 526-533 (2005).,  v.13,  2005,  p. 526.


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