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Simple Summary: Tubo-ovarian cancers are associated with high mortality as they are often not detected until a late stage. Early diagnosis is associated with better patient outcomes, but there are currently no effective screening measures. We explore whether an optical imaging catheter can detect early or occult lesions in the fallopian tubes. This device collects three-dimensional structural images of tissue through optical coherence tomography (OCT) simultaneously with functional imaging through autofluorescence imaging (AFI). We image ex vivo fallopian tubes from n = 28 patients (n = 7 cancer patients) and explore eleven imaging biomarkers for their ability to distinguish early or occult disease. We find that high-grade serous ovarian carcinomas can be visually distinguished through this approach, and that there are several quantitative changes within the area of lesion and throughout the specimen that can be measured through these imaging biomarkers. We conclude that this approach shows promise and merits further investigation of its diagnostic potential. Background: There are currently no effective screening measures to detect early or occult tubo-ovarian cancers, resulting in late-stage detection and high mortality. This work explores whether an optical imaging catheter can detect early-stage tubo-ovarian cancers or precursor lesions where they originate in the fallopian tubes. Methods: This device collects co-registered optical coherence tomography (OCT) and autofluorescence imaging (AFI). OCT provides three-dimensional assessment of underlying tissue structures; autofluorescence imaging provides functional contrast of endogenous fluorophores. Ex vivo fallopian tubes (n = 28; n = 7 cancer patients) are imaged; we present methods for the calculation of and analyze eleven imaging biomarkers related to fluorescence, optical attenuation, and OCT texture for their potential to detect tubo-ovarian cancers and other lesions of interest. Results: We visualize folded plicae, vessel-like structures, tissue layering, hemosiderin deposits, and regions of fibrotic change. High-grade serous ovarian carcinoma appears as reduced autofluorescence paired with homogenous OCT and reduced mean optical attenuation. Specimens containing cancerous lesions demonstrate a significant increase in median autofluorescence intensity and decrease in Shannon entropy compared to specimens with no lesion. Non-cancerous specimens demonstrate an increase in optical attenuation in the fimbriae when compared to the isthmus or the ampulla. Conclusions: We conclude that this approach shows promise and merits further investigation of its diagnostic potential. [ABSTRACT FROM AUTHOR]