Modification of a melanoma discrimination index derived from hyperspectral data: a clinical trial conducted in 2 centers between March 2011 and December 2013.

BACKGROUND: The morphology of pigmented skin lesions (PSLs) is predominantly a result of varying concentrations and distributions of pigmented molecules such as melanin and hemoglobin. Based on these differences and the fact that their information is contained in cutaneous spectra, a hyperspectral imager (HSI) for pigmented melanoma and a single discrimination index derived from the resultant hyperspectral data are proposed. OBJECTIVE: To develop and evaluate a new discrimination index for melanomas, compared to the previous index. METHODS: A HSI, which is convenient for both patients and clinicians, was newly developed and used in a clinical trial conducted in 2 centers with 80 patients with primary lesions and 17 volunteers between March 2011 and December 2013. There were 24 melanomas and 110 other PSLs. A previously proposed discrimination index was used without modifications. A new index, which emphasized the essential features of melanoma, was proposed, and its performance was examined. For each index, a threshold value was set to minimize the average value of the false positive and false negative fractions. The performances of both indices were compared. RESULTS: The sensitivity and specificity of the old index were 75% and 97%, respectively, while those of the new index were 96% and 87%. CONCLUSION: The new index had a higher sensitivity and adequate specificity, indicating that it is more useful than the old index.

Hyperspectroscopic imager for baby fibers.

Hyperspectral imaging system for diagnosing digestive diseases was newly developed in order to obtain information on pathology beyond morphology of lesions. In order to guide light reflected from a lesion, a baby fiber, which can be inserted in a forceps channel of the electronic endoscope, was also developed. The performance of the system was evaluated by animal experiment. Obtained hyperspectral data were found to have sufficient quality endurable to practical use. Harmful phenomena to a living body were not observed within the experiment. It was considered from the animal experiment that the present system could be practically used for humans.

Melanoma screening system using hyperspectral imager attached to imaging fiberscope.

Early detection and proper excision of the primary lesions of melanoma are crucial for reducing melanoma-related deaths. In order to support the early detection of melanoma, melanoma screening systems have been extensively studied and developed. Recently we have proposed a melanoma discrimination index derived from hyperspectral data (HSD) in the visible-near infrared wavelength region. The index represents variegation in spectra over a lesion and works well in discriminating melanoma from other pigmented lesions. However the previous hyperspectral imager did not have an enough allowance for measurement of lesions. To overcome the problem with it, we have developed a hyperspectral imager attached to imaging fiberscope. This equipment has been able to accumulate HSD in a view field of φ40 mm within about 10 seconds, from which the above-mentioned melanoma discrimination index has been calculated. Performance of the system has been studied in nine cases of melanoma and 18 cases of non-melanoma, obtained from patients and volunteers, all of whom were Japanese. The index has achieved a sensitivity of 100 % and a specificity of 94.4 %.

Extensive trans-species mitochondrial polymorphisms in the carabid beetles Carabus subgenus Ohomopterus caused by repeated introgressive hybridization.

To study the potential importance of introgressive hybridization to the evolutionary diversification of a carabid beetle lineage, we studied intraspecific and trans-species polymorphisms in the mitochondrial NADH dehydrogenase subunit 5 (ND5) gene sequence (1083 bp) in four species of the subgenus Ohomopterus (genus Carabus) in central and eastern Honshu, Japan. Of the four species, C. insulicola is parapatric with the other three, and can hybridize naturally with at least two. This species possesses two haplotypes of remote lineages. We classified ND5 haplotypes using polymerase chain reaction-restriction fragment length polymorphism with TaqI endonuclease for 524 specimens, and sequenced 143 samples. Analysis revealed that each species was polyphyletic in its mitochondrial DNA phylogeny, representing a marked case of trans-species polymorphism. Recent one-way introgression of mitochondria from C. arrowianus nakamurai to C. insulicola, and from C. insulicola to C. esakii, was inferred from the frequency of identical sequences between these species and from direct evidence of hybridization in their contact zones. Other intraspecific polymorphisms in the four species may be due to undetected introgressive hybridization (e.g. C. insulicola to C. maiyasanus) or from stochastic lineage sorting of ancestral polymorphisms. This beetle group has a genital lock-and-key system, with species-specific or subspecies-specific genital morphology that may act as a barrier to hybridization. However, our results demonstrate that introgressive hybridization has occurred multiple times, at least for mitochondria, despite differences among, and stability within, morphological characters that distinguish local populations. Thus, hybridization and introgression could have been key processes in the evolutionary diversification of Ohomopterus.

Incongruence of mitochondrial and nuclear gene trees in the Carabid beetles Ohomopterus.

We studied the molecular phylogeny of the carabid subgenus Ohomopterus (genus Carabus), using two mitochondrial (mt) DNA regions (16SrRNA and NADH dehydrogenase subunit 5) and three nuclear DNA regions (wingless, phosphoenolpyruvate carboxykinase, and an anonymous locus). We revisited the previously reported incongruence between the distribution of mtDNA markers and morphologically defined species (Su et al., 1996; J. Mol. Evol. 43:662-671), which those authors attributed to "type switching", a concerted change in many morphological characters that results in the repeated evolution of a particular morphological type. Our mtDNA gene tree obtained from 44 individuals representing all 15 currently recognized species of Ohomopterus revealed that haplotypes isolated from individuals of a single "species" were frequently separated into distant clades, confirming the previous report. The three nuclear markers generally conformed better-with the morphologically defined species than did the mitochondrial markers. The phylogenetic signal in mtDNA and nuclear DNA data differed strongly, and these two partitions were significantly incongruent with each other according to the incongruence length difference test of Farris et al. (1994; Cladistics 10:315-320), although the three nuclear partitions were not homogeneous either. Our results did not support the type-switching hypothesis that had been proposed to fit the morphological data to the mitochondrial gene tree: The incongruence of the mtDNA tree with other nuclear markers indicates that the mtDNA-based tree does not reflect species history any better than the morphological data do. Incongruence of gene trees in Ohomopterus may have been promoted by the complex processes of geographic isolation and hybridization in the Japanese Archipelago that have led to occasional gene flow and recombination between separated entities. The occurrence of reticulate patterns in this group is intriguing, because species of Ohomopterus exhibit extremely divergent genitalic structures that represent a highly efficient reproductive isolation mechanism.