Harmonization of diagnostic nomenclature used in the pathology analysis of tissues from rodent toxicity studies will enhance the comparability and consistency of data sets from different laboratories worldwide. The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of four major societies of toxicologic pathology to develop a globally recognized nomenclature for proliferative and nonproliferative lesions in rodents. This article recommends standardized terms for classifying changes observed in tissues of the mouse and rat central (CNS) and peripheral (PNS) nervous systems. Sources of material include academic, government, and industrial histopathology databases from around the world. Covered lesions include frequent, spontaneous, and aging-related changes as well as principal toxicant-induced findings. Common artifacts that might be confused with genuine lesions are also illustrated. The neural nomenclature presented in this document is also available electronically on the Internet at the goRENI website (http://www.goreni.org/).

Indocyanine green (ICG) is a fluorescent agent approved for clinical applications by the Food and Drug Administration and European Medicines Agency. This study examined the mechanism of tumor imaging using intravenously administered ICG. The in vivo kinetics of intravenously administered ICG were determined in tumor xenografts using microscopic approaches that enabled both spatio-temporal and high-magnification analyses. The mechanism of ICG-based tumor imaging was examined at the cellular level in six phenotypically different human colon cancer cell lines exhibiting different grades of epithelioid organization. ICG fluorescence imaging detected xenograft tumors, even those < 1 mm in size, based on their preferential cellular uptake and retention of the dye following its rapid tissue-non-specific delivery, in contrast to its rapid clearance by normal tissue. Live-cell imaging revealed that cellular ICG uptake is temperature-dependent and occurs after ICG binding to the cellular membrane, a pattern suggesting endocytic uptake as the mechanism. Cellular ICG uptake correlated inversely with the formation of tight junctions. Intracellular ICG was entrapped in the membrane traffic system, resulting in its slow turnover and prolonged retention by tumor cells. Our results suggest that tumor-specific imaging by ICG involves non-specific delivery of the dye to tissues followed by preferential tumor cellular uptake and retention. The tumor cell-preference of ICG is driven by passive tumor cell-targeting, the inherent ability of ICG to bind to cell membranes, and the high endocytic activity of tumor cells in association with the disruption of their tight junctions.Tumor imaging using exogenous fluorescent tumor-targeting agents is an essential tool in the clinical diagnosis and surgical treatment of tumors and in basic oncology research. 1-4The advantages of this approach include its high specificity and sensitivity, high frame rate, real-time imaging, relatively low cost, portability, the absence of radiation exposure and the option of simultaneous multiplexed imaging using fluorescent agents differing in their wavelengths. 5,6 Fluorescencebased tumor imaging can be applied to endoscopic and laparoscopic systems as well as to open surgery. It is therefore a valuable method in early cancer detection and in minimally invasive image-guided surgical procedures. However, despite the variety of tumor imaging agents that have been developed, many of those intended for use in humans are still in pre-clinical or early-phase clinical trials. 2Indocyanine green (ICG) is a fluorescent contrast agent approved for clinical applications by the Food and Drug Administration and European Medicines Agency. Because intravenously administered ICG is excreted exclusively via the liver, it has been used for decades to assess hepatic function in humans and has an excellent safety profile.7 The clinical applications of ICG include anatomical imaging, also of the vascular and lymphatic systems. Its advantages over other clinically available fluore...

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