Jiji Zhang

Background: In vivo, non-invasive optical coherence tomography permits high-resolution imaging of tissue surfaces and subsurfaces, with the potential capability for detection and mapping of epithelial pathologies. Purpose: To evaluate the clinical capability of non-invasive in vivo OCT for diagnosing oral dysplasia and malignancy. Experimental Design: In 50 patients with oral lesions, conventional clinical examination was followed by OCT imaging, then standard biopsy and histopathology. Two blinded, pre-standardized investigators separately diagnosed each lesion based on OCT and histopathology. Results: Intra- and inter-observer agreement between diagnoses based on histopathology and imaging data was excellent, with λ values between 0.844 and 0.896. Sensitivity and specificity were also very good. Conclusions: These data demonstrate the excellent capability of in vivo OCT for detecting and diagnosing oral premalignancy and malignancy in human subjects. © 2009 Wiley-Liss, Inc.

Purpose: To assess noninvasive optical coherence tomography and optical Doppler tomography for early detection and evaluation of chemotherapy-induced oral mucositis. Experimental Design: Cheek pouches of 10 Syrian golden hamsters were imaged using OCT/ODT during development of chemotherapy-induced mucositis. I.p. injections of 5-fluorouracil and mechanical irritation induced oral lesions. At 2, 4, 7, and 11 days, one hamster was sacrificed and processed for histopathology. OCT images were visually examined; ODT results were semiquantified. Imaging data were compared with histologic findings. Results: During the development of mucositis, OCT/ODT identified the following events: change in epithelial thickness, loss of surface keratinized layer continuity, loss of epithelial and submucosal integrity, changes in axial blood flow velocity, and changes in blood vessel size. The semiquantitative imaging-based scoring system identified the severity of mucositis as defined by histopathology. The combination of imaging criteria used allowed for the detection of early, intermediate, and late mucositic changes. Imaging data gave higher scores compared with clinical scores early on, suggesting that the imaging-based diagnostic scoring was more sensitive to early mucositic change than the clinical scoring system. Once mucositis was established, imaging and clinical scores converged. Conclusion: OCT/ODT identified chemotherapy-induced oral changes before their clinical manifestation, and the proposed scoring system for oral mucositis was validated for the semiquantification of mucositic change. © 2007 American Association for Cancer Research.

Early detection of cancer and its precursors remains the best way to ensure patient survival and quality of life. Our specific aim is to test a multimodality approach to noninvasive diagnostics of oral premalignancy and malignancy. In the hamster cheek pouch model, in vivo optical coherence tomography and optical Doppler tomography map epithelial, subepithelial, and vascular change throughout carcinogenesis. In vivo multiwavelength multiphoton and second-harmonic generated fluorescence techniques provided parallel data on surface and subsurface tissue structure, specifically collagen presence and structure, cellular presence, and vasculature. Images are diagnosed by two blinded, prestandardized investigators using a scale from 0 to 6 for all modalities. After sacrifice, histopathology is evaluated on a scale of 0 to 6. Imaging data are reproducibly obtained with good accuracy. Carcinogenesis-related structural and vascular changes are clearly visible to tissue depths of 2 mm. Sensitivity and specificity compare well with conventional techniques. Our conclusions are that OCT/ODT and MPM/SHG are promising noninvasive in vivo diagnostic modalities for oral dysplasia and malignancy. © 2005 Society of Photo-Optical Instrumentation Engineers.

We argue that current discussions of criteria for actual causation are ill-posed in several respects. (1) The methodology of current discussions is by induction from intuitions about an infinitesimal fraction of the possible examples and counterexamples; (2) cases with larger numbers of causes generate novel puzzles; (3) “neuron” and causal Bayes net diagrams are, as deployed in discussions of actual causation, almost always ambiguous; (4) actual causation is (intuitively) relative to an initial system state since state changes are relevant, but most current accounts ignore state changes through time; (5) more generally, there is no reason to think that philosophical judgements about these sorts of cases are normative; but (6) there is a dearth of relevant psychological research that bears on whether various philosophical accounts are descriptive. Our skepticism is not directed towards the possibility of a correct account of actual causation; rather, we argue that standard methods will not lead to such an account. A different approach is required. Once upon a time a hungry wanderer came into a village. He filled an iron cauldron with water, built a fire under it, and dropped a stone into the water. “I do like a tasty stone soup” he announced. Soon a villager added a cabbage to the pot, another added some salt and others added potatoes, onions, carrots, mushrooms, and so on, until there was a meal for all.