Zilly Chen

In many research studies, tumor biopsies are an unavoidable requirement for achieving key scientific aims. Yet some commentators view mandatory research biopsies as coercive and suggest they should be optional, or at least optional until further data are obtained regarding their scientific usefulness. Further complicating the ethical picture is the fact that some research biopsies offer a potential for clinical benefit to trial participants. We interviewed and surveyed a convenience sample of participants in phase I clinical trials at a single institution. Our primary aim was to describe phase I participants’ understanding of whether a research biopsy offered them the prospect of medical benefit. We also endeavored to describe participants’ views about biopsies—specifically, the benefits of biopsies, if any, and whether biopsies were acceptable, risky, or discouraged trial participation. Finally, we collected data on demographics and attitudes to see if any strong correlations with misunderstanding, acceptability, or riskiness existed. Overall, the respondents tended to view research biopsies as acceptable, though they did not succeed in identifying the lack of benefit of a research biopsy. These findings call for renewed efforts in consent conversations and documents to carefully describe the benefits, or lack thereof, of research biopsies

Background: Optical Doppler tomography combines laser Doppler flowmetry with optical coherence tomography to obtain high-resolution images of blood flow in human skin in situ and in real time. Observations: We present a case in which ODT was used on a patient with a port-wine stain birth-mark to document the change of blood flow in response to laser therapy. It might be possible to use ODT blood flow measurements in situ to assist in assessing the efficacy of laser PWS therapy. If partial restoration of flow occurs immediately or shortly after laser exposure, indicative of reperfusion due to inadequate blood vessel injury, the PWS can be retreated using higher light dosages. Retreatment is continued until the measured Doppler shift is zero due to a permanent reduction in blood flow, indicative of irreversible microthrombus formation in the PWS vessels. Conclusions: We have demonstrated that ODT may be used for noninvasive imaging of blood vessels in PWS skin. Moreover, ODT will potentially allow laser therapy to be optimized on an individual patient basis by providing a fast, semiquantitative evaluation of the efficacy of PWS laser therapy in situ and in real time.

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.

The Mueller matrix describes all the polarizing properties of a sample and, therefore, the optical differences between noncancerous and precancerous tissue that may be present within the matrix elements. A high-speed polarimetry system that generates 16 full Mueller matrices to characterize tissues is presented. Feature extraction is done on the Mueller matrix elements resulting in depolarization and retardance images by polar decomposition. These are used to detect and classify early oral cancers and precancerous changes in epithelium such as dysplasia. These images are compared with orthogonal polarization images and analyzed in an attempt to identity useful factors for the differentiation between cancerous lesions and their benign counterparts. Our results indicate that polarimetry has potential as a method for the in vivo early detection and diagnosis of oral premalignancy. © 2007 Optical Society of America.

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.

Optical coherence tomography is a catheter-based imaging technology with powerful resolution capable of identifying vulnerable plaques and guiding coronary intervention. However, a significant limitation of intravascular OCT imaging is its attenuation by blood. We propose that the use of an oxygen-carrying blood substitute could potentially optimize OCT image quality. Surgical isolation of the descending thoracic aorta of six rabbits is performed, followed by intravascular OCT imaging of the abdominal aorta. Perfluorodecalin is oxygenated using a bubble-through technique with 100% oxygen. OCT imaging is performed and compared using three different flushing modalities: PFD; saline; and blood. OCT imaging of the rabbit abdominal aorta is successful in all of the subjects. In each of the six studied subjects, flushing with PFD consistently provides dramatically better imaging of the vessel wall tissue structures. OCT image quality is highly dependent on the ability of the flushing modality to remove blood from the imaging field. From this proof-of-concept study, we demonstrate that endovascular flushing with an oxygen-carrying blood substitute is optically superior to saline flushing for intravascular imaging. © 2009 Society of Photo-Optical Instrumentation Engineers.