title: Spatial frequency analysis of anisotropic drug transport in tumor samples.
abstract: Directional Fourier spatial frequency analysis was used on standard histological sections to identify salient directional bias in the spatial frequencies of stromal and epithelial patterns within tumor tissue. This directional bias is shown to be correlated to the pathway of reduced fluorescent tracer transport. Optical images of tumor specimens contain a complex distribution of randomly oriented aperiodic features used for neoplastic grading that varies with tumor type, size, and morphology. The internal organization of these patterns in frequency space is shown to provide a precise fingerprint of the extracellular matrix complexity, which is well known to be related to the movement of drugs and nanoparticles into the parenchyma, thereby identifying the characteristic spatial frequencies of regions that inhibit drug transport. The innovative computational methodology and tissue validation techniques presented here provide a tool for future investigation of drug and particle transport in tumor tissues, and could potentially be used a priori to identify barriers to transport, and to analyze real-time monitoring of transport with respect to therapeutic intervention.
authors.affiliation: Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire 03755bCity College of New York, Mechanical Engineering Department, New York, New York 10031cCity College of New York, Institute for Ultrafast Spectroscopy and Lasers, Physics Departme.
authors.forename: Stewart
authors.initials: S
authors.lastname: Russell
authors.affiliation: Dartmouth College, Geisel School of Medicine, Department of Surgery, Hanover, New Hampshire 03755.
authors.forename: Kimberley S
authors.initials: KS
authors.lastname: Samkoe
authors.affiliation: Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire 03755.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Gunn
authors.affiliation: Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire 03755eDartmouth College, Geisel School of Medicine, Department of Surgery, Hanover, New Hampshire 03755.
authors.forename: P Jack
authors.initials: PJ
authors.lastname: Hoopes
authors.affiliation: City College of New York, Institute for Ultrafast Spectroscopy and Lasers, Physics Department, New York, New York 10031.
authors.forename: Thienan A
authors.initials: TA
authors.lastname: Nguyen
authors.affiliation: New York Structural Biology Center, New York, New York 10027fCity College of New York, Chemistry Department, New York, New York 10031.
authors.forename: Milo J
authors.initials: MJ
authors.lastname: Russell
authors.affiliation: City College of New York, Institute for Ultrafast Spectroscopy and Lasers, Physics Department, New York, New York 10031.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Alfano
authors.affiliation: Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire 03755eDartmouth College, Geisel School of Medicine, Department of Surgery, Hanover, New Hampshire 03755.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Pogue
mesh_terms: D000818:Animals; D016880:Anisotropy; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001331:Automation; D045744:Cell Line, Tumor; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000166:cytology; D005456:Fluorescent Dyes / Q000737:chemistry; D005583:Fourier Analysis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D017154:Stromal Cells / Q000166:cytology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes