Assessment and Diagnosis of Human Ovarian and Colorectal Cancer using Optical and Photoacoustic Imaging

Optical imaging modalities have the advantage of high resolution, label free, rapid, low cost imaging for both in vivo and ex vivo diagnosis of biological tissues. Optical scattering, which is the main contrast of optical coherence tomography (OCT), is related to elastic scattering components, mainly stromal collagen. Tissue elasticity has recently emerged as an important diagnostic parameter associated with tumor development and progression and is also related to the distribution of structural components such as tissue collagen. We have used an optical coherence tomography elastography (OCTE) system for characterizing the differences in the micro-mechanical properties of benign and malignant human ovarian tissue and correlated with the corresponding tissue collagen content (chapter 1). Additionally, spatial heterogeneity has also been associated with diagnosis of normal and malignant tissue. Automated image recognition and analysis can be a useful tool for overcoming the limitations of observer-dependent visual identification and discrimination of normal and malignant features of tissue. We developed a high-resolution full field optical coherence tomography (FFOCT) system for classification of the morphological changes associated with the progression of human ovarian cancer (chapter 2). Optical absorption reveals contrast related to the tumor microvasculature and tumor angiogenesis. Absorption information from two or more wavelengths can provide functional information such as total blood hemoglobin as well as blood oxygen saturation, which is related to tumor angiogenesis and tumor hypoxia. Spatial frequency domain imaging (SFDI) is a powerful wide field, label free imaging modality sensitive to both optical absorption as well as scattering, which can be used together for complete assessment of normal and diseased tissues. SFDI was used for multispectral, ex vivo assessment of different types of human ovarian and colon tissue with considerable accuracy (chapter 3). For in vivo optical diagnosis of human ovarian cancer, the main limitation has been the shallow depth of penetration due to intense scattering from the biological tissue, which requires direct contact with the tissue surface and requires invasive procedures. Photoacoustic tomography combined with ultrasound (PAT/US) was used to overcome this limitation by using NIR light combined with diagnostic frequency ultrasound to achieve a depth of up to 5 cm with considerable resolution and correspondingly provide functional information related to tumor angiogenesis and oxygen saturation (chapter 4)

The angular spectrum of the scattering coefficient map reveals subsurface colorectal cancer

Abstract Colorectal cancer diagnosis currently relies on histological detection of endoluminal neoplasia in biopsy specimens. However, clinical visual endoscopy provides no quantitative subsurface cancer information. In this ex vivo study of nine fresh human colon specimens, we report the first use of quantified subsurface scattering coefficient maps acquired by swept-source optical coherence tomography to reveal subsurface abnormities. We generate subsurface scattering coefficient maps with a novel wavelet-based-curve-fitting method that provides significantly improved accuracy. The angular spectra of scattering coefficient maps of normal tissues exhibit a spatial feature distinct from those of abnormal tissues. An angular spectrum index to quantify the differences between the normal and abnormal tissues is derived, and its strength in revealing subsurface cancer in ex vivo samples is statistically analyzed. The study demonstrates that the angular spectrum of the scattering coefficient map can effectively reveal subsurface colorectal cancer and potentially provide a fast and more accurate diagnosis