Endogenous Optical Biomarkers of Ovarian Cancer Evaluated with Multiphoton Microscopy

Abstract

Purpose: Among gynecologic cancers, ovarian cancer is the second most common and has the highest mortality. Currently, there is no accurate early diagnostic technique for ovarian cancer. Furthermore, little is understood regarding the early progression of this disease. We have imaged multiphoton interactions of endogenous tissue constituents from normal and abnormal ovarian biopsies that were kept viable during transport from the operating room and microscopy. Experimental Design: The ovarian surface and underlying stroma were assessed with two-photon excited fluorescence (2PEF) and second harmonic generation (SHG). High-resolution, optically sectioned images were analyzed for epithelial morphology based on 2PEF and collagen density and structural integrity based on SHG. Additionally, multiwavelength 2PEF provided an estimation of the cellular redox ratio of epithelial cells.

Fully automated, quantitative, noninvasive assessment of collagen fiber content and organization in thick collagen gels

“…20 Finally, SHG imaging has been used to examine the collagen fiber morphology surrounding tumor cells in vivo and in tumor explants. 12 The latter study clearly illustrated that the matrix reorganizes significantly in areas of cancer cell invasion, so that the collagen fibers align with the cancer cells and facilitate cell motility into the matrix.…”

“…17,18 Finally, the degree of organization and alignment within fibrillar bundles has been found to significantly influence the detected SHG signal. 19 The analytical tools that have been presented so far for characterizing collagen organization relied at least to a certain extent either on user input, 8,12,17,[19][20][21][22] or on computationally intense calculations that confine the region of interest to a limited region. 9 Here, we present the use of an adaptive thresholding approach in combination with Fourier-and a Hough-transform based analysis as a relatively simple and efficient means of acquiring quantitative information on the content, orientation, and local organization of collagen fibrils.…”

Nonlinear optical microscopy and ultrasound imaging of human cervical structure

“…For instance, it can be used to monitor cancer progression and treatment response; Provenzano et al described tumor association collagen signatures and the corresponding changes in collagen with breast cancer progression, 37 and collagen order in ovarian cancer has been investigated with forward and backward collection of SHG. 38,39 Further, SHG imaging has been used to study collagen orientation during wound healing and scar formation, 40 and mechanical aspects of collagen have been studied in arteries 41 and the trachea. 42 Simple SHG techniques have been recently applied to the cervix.…”

Simultaneous characterization of pancreatic stellate cells and other pancreatic components within three-dimensional tissue environment during chronic pancreatitis

“…16,22,23 Using this method, stromal collagen, which is the major source of SHG signals in extracellular matrix, has been recognized from cellular components. [24][25][26] Lymphatic cells have been distinguished from the other gastric tissue types due to a broad emission that possibly originates from phospholipids, known to be a significant component of lymphocytes. 16 Besides, morphological characteristics obtained by nonlinear optical microscopy can also provide information relating to the differentiation of multiple cell types.…”