Fluorescence lifetime imaging can provide valuable diagnostic information relating to the functional status of diseases. In this study, a near-infrared (NIR) dye-labeled hexapeptide (abbreviated Cyp-GRD) was synthesized. In vitro, Cyp-GRD internalized in nonsmall cell lung cancer cells (A549) without observable cytotoxic or proliferative effects to the cells at a concentration up to 1x10(-4) M. Time-domain fluorescence intensity and lifetime imaging of Cyp-GRD injected into A549 tumor-bearing mice revealed that the probe preferentially accumulated in the tumor and the major excretion organs. The fluorescence lifetime of the conjugate at the tumor site was mapped, showing the spatial distribution of the lifetime related to its environment. Additionally, fluorescence intensity image reconstruction obtained by integrating the time-resolved intensities enabled the contrast ratios of tumor-to-kidney or liver in slices at different depths to be displayed. The mean lifetime was 1.03 ns for the tumor and 0.80 ns for the liver when averaging those pixels exhibiting adequate signal-to-noise ratio, showing the tumor had a higher lifetime average and reflecting the altered physiopathology of the tumor. This study clearly demonstrated the feasibility of whole-body NIR fluorescence lifetime imaging for tumor localization and its spatial functional status in living small animals.

Infrared spectroscopy, by probing the molecular vibration of chemical bonds, directly indicates tissue biochemistry. An expanding body of literature suggests that infrared spectra distinguish diseased from normal tissue. The authors used infrared spectroscopy to examine basal cell carcinoma to explore distinctive characteristics of basal cell carcinoma versus normal skin samples and other skin neoplasms. Spectra of epidermis, tumor, follicle sheath, and dermis were acquired from unstained frozen sections, and analyzed qualitatively, by t-tests and by linear discriminant analyses. Dermal spectra were significantly different from the other skin components mainly due to absorptions from collagen in dermis. Spectra of normal epidermis and basal cell carcinoma were significantly different by virtue of subtle differences in protein structure and nucleic acid content. Linear discriminant analysis characterized spectra as arising from basal cell carcinoma, epidermis, or follicle sheath with 98.7% accuracy. Use of linear discriminant analysis accurately classified spectra as arising from epidermis overlying basal cell carcinoma versus epidermis overlying nontumor-bearing skin in 98.0% of cases. Spectra of basal cell carcinoma, squamous cell carcinoma, nevi, and malignant melanoma were qualitatively similar. Distinction of basal cell carcinoma, squamous cell carcinoma, and melanocytic lesions by linear discriminant analyses, however, was 93.5% accurate. Therefore, spectral separation of abnormal versus normal tissue was achieved with high sensitivity and specificity, which points to infrared spectroscopy as a potentially useful screening tool for cutaneous neoplasia.

A noninvasive tool for skin tumor diagnosis would be a useful clinical adjunct. The purpose of this study was to determine whether near-infrared spectroscopy can be used to noninvasively characterize skin lesions. In vivo visible- and near-infrared spectra (400--2500 nm) of skin neoplasms (actinic keratoses, basal cell carcinomas, banal common acquired melanocytic nevi, dysplastic melanocytic nevi, actinic lentigines, and seborrheic keratoses) were collected by placing a fiberoptic probe on the skin. Paired t tests, repeated measures analysis of variance and linear discriminant analysis were used to determine whether significant spectral differences existed and whether spectra could be classified according to lesion type. Paired t tests showed significant differences (p < 0.05) between normal skin and skin lesions in several areas of the near-infrared spectrum. In addition, significant differences were found between the lesion groups by analysis of variance. Linear discriminant analysis classified spectra from benign lesions compared with premalignant or malignant lesions with high accuracy. Near-infrared spectroscopy is a promising noninvasive technique for the screening of skin lesions.

After dystrophic damage, the limb muscles of the mdx mouse recover very effectively compared to muscles in Duchenne muscular dystrophy (DMD) patients. Since thyroid hormone is required for muscle development and integrity, we examined whether a deficiency of the hormone, induced by 0.05% propylthiouracil (PTU) in drinking water over 8 weeks, would be deleterious to the myogenesis and muscle repair in control and mdx mice. Measured metabolic and growth parameters confirmed hypothyroidism in PTU-treated mice. Histological and morphometric techniques were used to study myogenesis and the repair of the tibialis anterior muscle (TA) after crush injury in mdx mice and their nondystrophic controls (C57B1/10ScSn). After 8 weeks, PTU-treated TA from mdx mice had larger crush sites and lower myotube density than TA in untreated mdx mice. In unoperated mdx TA, there was a larger proportionate area of active dystrophy and smaller fiber diameter in PUT-treated than in untreated mdx TA, which suggested that PTU increased the activity of dystrophy as well. In contrast, in control TA neither the regeneration of myotubes or fiber diameter were affected significantly by PTU. Therefore, these results suggest that mdx muscle regeneration is more affected by hypothyroidism than normal muscle repair. This may be due to the larger pool of muscle precursors in mdx than control muscle, and a possible impairment of precursor cell proliferation or fusion during myotube formation.

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