Esophageal cancer is increasing in frequency in the United States faster than any other cancer. Barrett's esophagus, an otherwise benign complication of esophageal reflux, affects approximately three million Americans and precedes almost all cases of esophageal cancer. If detected as highgrade dysplasia (HGD), most esophageal cancers can be prevented. Standard-of-care screening for dysplasia uses visual endoscopy and a prescribed pattern of biopsy. This procedure, in which a tiny fraction of the affected tissue is selected for pathological examination, has a low probability of detection because dysplasia is highly focal and visually indistinguishable. We developed a system called endoscopic polarized scanning spectroscopy (EPSS), which performs rapid optical scanning and multispectral imaging of the entire esophageal surface and provides diagnoses in near real time. By detecting and mapping suspicious sites, guided biopsy of invisible, precancerous dysplasia becomes practicable. Here we report the development of EPSS and its application in several clinical cases, one of which merits special consideration.Previously we demonstrated that spectroscopic information in light scattered by nuclei could reveal precancer cellular changes 1 . The first application of light-scattering spectroscopy successfully detected dysplasia in Barrett's esophagus 1-5 using a fiber optic probe that illuminated 1 mm 2 of tissue. Searching the entire area of a diseased esophagus with a singlepoint probe is clinically impractical.Correspondence should be addressed to L.T.P. (ltperel@bidmc.harvard.edu). Note: Supplementary information is available on the Nature Medicine website. AUTHOR CONTRIBUTIONSL.Q., E.V., M.D.M., E.B.H., I.I. and L.T.P. developed and evaluated the method; S.I., L.Q. and E.V. contributed codes for instrument control; D.K.P., R.C., J.D.G., J.L., N.O., L.G., L.Q. and A.S. performed clinical procedures; L.Q., D.K.P., R.C., E.B.H., I.I. and L.T.P. contributed to the writing of the manuscript; E.B.H., I.I., D.K.P., R.C. and L.T.P. designed and planned the project. COMPETING FINANCIAL INTERESTSThe authors declare no competing financial interests.Reprints and permissions information is available online at http://npg.nature.com/reprintsandpermissions/. Since then, several new approaches have been explored using high-resolution endoscopy (HRE) combined with narrow band imaging (NBI) 6 , autofluorescence imaging (AFI) 7 , trimodal imaging 8 , which is a combination of the previous three, and confocal laser endomicroscopy 9 . These techniques showed promise in increased detection of dysplasia in Barrett's esophagus, although none has as yet achieved clinical acceptance. NIH Public AccessA clinically useful technique in the detection of dysplasia in Barrett's esophagus must rapidly survey a comparatively large area while simultaneously detecting changes on a cellular scale. We felt we could achieve both goals by combining an endoscopically compatible scanning instrument with polarized light-scattering spectroscopy (PLSS) 5...

Void spot assays (VSA) and cystometry are two of the most common tests performed in mice to assess lower urinary tract function. Assay protocols and methodology vary greatly among laboratories, and little is known about reproducibility of results generated by different laboratories. We performed VSA in four mouse strains, comparing males with females and comparing results between two independent laboratories. Unique aspects of the current study include direct comparison of results of VSA performed in a similar manner in two locations and comparison of cystometry performed using two different rates of infusion in these two laboratories. Both assays were performed in male and female 129S1/SvImJ, C57BL/6J, NOD/ShiLtJ, and CAST/EiJ mice, and cystometry was performed under urethane anesthesia (10/group). Assays were performed and results analyzed as previously described. Results obtained in female mice were compared with previously reported values. Results of lower urinary tract function testing in mice vary in a consistent manner with strain and sex. Variables in husbandry, testing techniques, and analysis of results can significantly affect conclusions, particularly those obtained by cystometry. Although VSA results were remarkably similar between the two laboratories, consistent methods for performing lower urinary tract function testing in mice are required to compare results among studies with confidence.

From astronomy to cell biology, the manner in which light propagates in turbid media has been of central importance for many decades. However, light propagation near the point-of-entry (POE) in turbid media has never been analytically described, until now. Here we report a straightforward and accurate method that overcomes this longstanding, unsolved problem in radiative transport. Our theory properly treats anisotropic photon scattering events and takes the specific form of the phase function into account. As a result, our method correctly predicts the spatially dependent diffuse reflectance of light near the POE for any arbitrary phase function. We demonstrate that the theory is in excellent agreement with both experimental results and Monte Carlo simulations for several commonly used phase functions.