Clinical Validation of Stimulated Raman Histology for Rapid Intraoperative Diagnosis of Central Nervous System Tumors.

Stimulated Raman histology (SRH) is an ex vivo optical imaging method that enables microscopic examination of fresh tissue intraoperatively. The conventional intraoperative method uses frozen section analysis, which is labor and time intensive, introduces artifacts that limit diagnostic accuracy, and consumes tissue. SRH imaging allows rapid microscopic imaging of fresh tissue, avoids tissue loss, and enables remote telepathology review. This improves access to expert neuropathology consultation in both low- and high-resource practices. We clinically validated SRH by performing a blinded, retrospective two-arm telepathology study to clinically validate SRH for telepathology at our institution. Using surgical specimens from 47 subjects, we generated a data set composed of 47 SRH images and 47 matched whole slide images (WSIs) of formalin-fixed, paraffin-embedded tissue stained with hematoxylin and eosin, with associated intraoperative clinicoradiologic information and structured diagnostic questions. We compared diagnostic concordance between WSI and SRH-rendered diagnoses. Also, we compared the 1-year median turnaround time (TAT) of intraoperative conventional neuropathology frozen sections with prospectively rendered SRH-telepathology TAT. All SRH images were of sufficient quality for diagnostic review. A review of SRH images showed high accuracy in distinguishing glial from nonglial tumors (96.5% SRH vs 98% WSIs) and predicting final diagnosis (85.9% SRH vs 93.1% WSIs). SRH-based diagnosis and WSI-permanent section diagnosis had high concordance (κ = 0.76). The median TAT for prospectively SRH-rendered diagnosis was 3.7 minutes, approximately 10-fold shorter than the median frozen section TAT (31 minutes). The SRH-imaging procedure did not affect ancillary studies. SRH generates diagnostic virtual histologic images with accuracy comparable to conventional hematoxylin and eosin-based methods in a rapid manner. Our study represents the largest and most rigorous clinical validation of SRH to date. It supports the feasibility of implementing SRH as a rapid method for intraoperative diagnosis complementary to conventional pathology laboratory methods.

Reliability of photographic analysis of wound epithelialization assessed in human skin graft donor sites and epidermolysis bullosa wounds.

BACKGROUND: In many clinical trials on cutaneous healing, wound closure is the primary endpoint and single most important outcome parameter, making precise assessment of this time point one of utmost importance. The assessment of wound closure can be performed either by subjective clinical inspection or with a variety of methodologies anticipated to provide more objective data. The aim of this study was to examine intra- and interrater variability of blinded photographic analysis of wound closure of human partial thickness wounds, as well as the reliability of remote photographic analysis of wounds with that of direct clinical assessment. METHODS: Two plastic surgeons, a dermatologist, and a maxillofacial surgeon constituted our rater panel. High-resolution images of patient wounds derived from two randomized controlled clinical trials (EU Clinical Trials Register numbers EudraCT 2009-017418-56 (registered 12 January 2010) and EudraCT 2010-019945-24 (registered 13 July 2010)) were individually assessed by the blinded, experienced study raters. The reliability of photographic image analysis was tested using intraclass and interclass correlation. The validity of photographic image analysis was correlated with clinical assessments of documented time to heal from the study centers' files. RESULTS: The results demonstrated that the mean intraclass correlation coefficient of all four examiners was excellent (r = 0.79; 95% confidence interval (CI), 0.61, 1.00)). The interrater correlation coefficient was good (r = 0.67; 95% CI, 0.57, 1.00)) and therefore acceptable. The agreement between remote visual assessment and clinical assessment at the time of healing was good (r = 0.64; 95% CI, 0.52, 0.76)) with an overall difference of about 1 day. CONCLUSIONS: Remote photographic analysis of cutaneous wounds is a feasible instrument in clinical open-label studies to evaluate time to wound closure. We found that it was a reliable method of measuring wound closure that correlated satisfactorily with clinical judgment, bolstering the potential relevance in the current era of evolving application and dependency in the field of telemedicine. TRIAL REGISTRATION: EU Clinical Trials Register EudraCT numbers 2009-017418-56 (date of registration: 12 January 2010) and 2010-019945-24 (date of registration: 13 July 2010).