Biomedical subjects

David I McLean

Publications and source records attributed to David I McLean.

11 recordsLinked to original sources

PubMed2006

Monte Carlo simulation of cutaneous reflectance and fluorescence measurements--the effect of melanin contents and localization.

Melanin content and distribution in skin were studied by examining a patient with white, brown and blue skin tones expressed on skin affected by vitiligo. Both diffuse reflectance and autofluorescence spectra of the three distinction skin sites were measured and compared. Monte Carlo simulations were then performed to help explain the measured spectral differences. The modeling is based on a six-layer skin optical model established from published skin optical parameters and by adding melanin content into different locations in the model skin. Both the reflectance and fluorescence spectra calculated by Monte Carlo (MC) simulation were approximately in agreement with experimental results. The study suggests that: (1) trichrome vitiligo skin may be an ideal in vivo model for studying the effect of skin melanin content and distribution on skin spectroscopy properties. (2) Based on the skin optical model and MC simulation, the content and distribution of melanin in skin, or other component of skin could be simulated and predicted. (3) Both reflectance and fluorescence spectra provided information about superficial skin structures but fluorescence spectra are capable of providing information from deeper cutaneous structures. (4) The research method, including the spectral ratio method, the method of adding and modifying the melanin content in skin optical models, and MC simulation could be applied in other non-invasive optical studies of the skin.

Computer Simulation↗

PubMed2005

Counting moles automatically from back images.

Density of moles is a strong predictor of malignant melanoma, therefore, enumeration of moles is often an integral part of many studies that look at malignant melanoma. An automatic method of segmenting and counting moles would help standardize studies, compared with manual counting. We have developed an unsupervised algorithm for segmenting and counting moles from two-dimensional color images of the back torso region, as part of a study to evaluate the effectiveness of sunscreen. The method consists of a new variant of mean shift filtering that forms clusters in the image and removes noise, a region growing procedure to select candidates, and a rule-based classifier to identify moles. When this algorithm was compared to an assessment by an expert dermatologist, the algorithm showed a sensitivity rate of 91% and diagnostic accuracy of 90% on the test set, for moles larger than 1.5 mm in diameter.

Algorithms↗

PubMed2004

Laser-induced autofluorescence microscopy of normal and tumor human colonic tissue.

Laser-induced autofluorescence (LIAF) spectroscopy has been found to be a promising tool for early cancer diagnosis in various organs, but the reasons responsible for the spectral differences between normal and diseased tissue are still not well understood. In this study, a microspectrophotometer (MSP) system was used to identify the microscopic origins of tissue autofluorescence in the colon under the excitation of a helium-cadmium laser at 442 nm. Colonic tissue samples (normal: n=8, adenocarcinoma: n=10) were obtained from 12 patients with known or suspected malignancies of the colon. The intrinsic fluorescence spectra and images of fresh tissue sections prepared from normal and tumor colonic tissue were measured by the MSP system. Three distinct tissue layers of the colon were found for fluorescence, the mucosa, the submucosa and the muscularis propria, with submucosa being the most fluorescent. Differences in the spectral shape and intensity of the intrinsic fluorescence originating from different colonic layers indicate that fundamentally different fluorophores may be present in the respective tissue layers. There was no significant difference in the intrinsic fluorescence features of the submucosa between normal and tumor colonic tissue, but the fluorescence intensity of the submucosa in tumor tissue was significantly reduced due to the infiltration of tumor cells into the submucosa. The intrinsic fluorescence spectrum peaking at about 520 nm for tumor stroma appeared more evident than that of normal lamina propria. Limited areas of the lamina propria layer in some adenocarcinoma colon exhibited an emission band at about 635 nm, which was attributed to endogenous porphyrins in tumor. Autofluorescence microscopy revealed that differences in the clinically measured autofluorescence spectra between normal and tumor tissue were mainly due to thickening of the tumor mucosa resulting in a reduced submucosa fluorescence contribution, as well as the increased hemoglobin absorption in tumor tissue. Therefore, investigation of the microscopic origins of tissue autofluorescence and images can provide new insights into morphological structures and biochemical components of tissues, which are vital to improve the implementation of the LIAF technique for non-invasive in vivo tissue diagnostics.

Adenocarcinoma↗

PubMed2003

Near-infrared Raman spectroscopy for optical diagnosis of lung cancer.

Raman spectroscopy is a vibrational spectroscopic technique that can be used to optically probe the molecular changes associated with diseased tissues. The objective of our study was to explore near-infrared (NIR) Raman spectroscopy for distinguishing tumor from normal bronchial tissue. Bronchial tissue specimens (12 normal, 10 squamous cell carcinoma (SCC) and 6 adenocarcinoma) were obtained from 10 patients with known or suspected malignancies of the lung. A rapid-acquisition dispersive-type NIR Raman spectroscopy system was used for tissue Raman studies at 785 nm excitation. High-quality Raman spectra in the 700-1,800 cm(-1) range from human bronchial tissues in vitro could be obtained within 5 sec. Raman spectra differed significantly between normal and malignant tumor tissue, with tumors showing higher percentage signals for nucleic acid, tryptophan and phenylalanine and lower percentage signals for phospholipids, proline and valine, compared to normal tissue. Raman spectral shape differences between normal and tumor tissue were also observed particularly in the spectral ranges of 1,000-1,100, 1,200-1,400 and 1,500-1,700 cm(-1), which contain signals related to protein and lipid conformations and nucleic acid's CH stretching modes. The ratio of Raman intensities at 1,445 to 1,655 cm(-1) provided good differentiation between normal and malignant bronchial tissue (p < 0.0001). The results of this exploratory study indicate that NIR Raman spectroscopy provides significant potential for the noninvasive diagnosis of lung cancers in vivo based on the optic evaluation of biomolecules.

Aged↗

PubMed2003

Restoration of hair growth with topical diphencyprone in mouse and rat models of alopecia areata.

BACKGROUND: The contact sensitizer, diphencyprone (DPCP), is one of the most effective therapies for the more severe forms of alopecia areata (AA). OBJECTIVE: The purpose of this study was to determine the efficacy of topical DPCP on the 2 available rodent models for AA, and to determine the underlying therapeutic mechanisms. METHODS: AA-affected mice and rats were treated unilaterally with topical DPCP on the ventral and dorsal surface, respectively. The opposite sides were treated with vehicle alone. Skin biopsy specimens were collected from both sides for histologic analysis. RESULTS: Hair regrowth was observed on the treated sides in the majority of the animals of both species. Immunohistochemical analyses revealed reduction of intrafollicular CD8(+) lymphocyte infiltrates after successful treatment in mice. CONCLUSION: The AA-like hair disorder of these 2 rodent models can be used as a tool for furthering our understanding of human AA and the therapeutic actions of DPCP.

Administration, Topical↗

PubMed2003

Irregularity index: a new border irregularity measure for cutaneous melanocytic lesions.

One of the important clinical features that differentiates benign melanocytic nevi from malignant melanomas is the irregularity of the lesion border. There are two types of border irregularities: texture irregularities, the small variations along the border, and structure irregularities, the global indentations and protrusions. Texture irregularities are subject to noise, whereas structure irregularities may suggest excessive cell growth or regression of a melanoma. We have designed a new algorithm for measuring the structure irregularities in the border. Our algorithm first locates all the local and global indentations and protrusions and organizes them in a hierarchical structure. Then an area-based index, called the irregularity index, is computed for each indentation and protrusion along the border. From the individual irregularity indices, two important new measures, the most significant irregularity index and the overall irregularity index are derived. These two new indices provide a measure of the degree of irregularity along the lesion border. A double-blinded test was performed to examine the effectiveness of these two new indices. Fourteen experienced dermatologists were asked to evaluate the borders of 40 pigmented lesions. The clinical evaluation result was then compared with the two new indices and other published shape measurements. The user study showed that both of the new indices vastly outperformed the other shape descriptors. Moreover, our algorithm captured the knowledge of expert dermatologists in analysing malignancy of a lesion based on its shape alone, indicating that the new measures may be useful for diagnosing melanomas.

Algorithms↗

PubMed2003

Effect of formalin fixation on the near-infrared Raman spectroscopy of normal and cancerous human bronchial tissues.

Raman spectroscopy is a vibrational spectroscopic technique that can be used to probe molecular changes associated with tissue malignancy. In this report, the effect of formalin fixation on human bronchial tissues was studied by near-infrared (NIR) Raman spectroscopy to determine if the variations of Raman spectra caused by formalin fixation would affect the potential diagnostic ability for lung cancer detection. A rapid dispersive-type NIR Raman system with an excitation wavelength of 785 nm was used for this study. Bronchial tissue samples were obtained from six patients with known or suspected malignancies of the lung. Raman spectra of fresh normal and tumor tissue were compared with spectra of formalin-fixed normal and tumor tissue. Changes of the ratios of Raman intensities at 1445 to 1655 cm(-1) and 1302 to 1265 cm(-1) versus formalin fixing times varying from 2 to 24 h were also examined. The major tissue Raman peaks at 1265, 1302, 1445, and 1655 cm(-1) were found in both fresh and fixed bronchial tissues. However, bronchial tissue preserved in formalin showed a progressive decrease in overall intensities of these Raman peaks. Raman contaminations due to formalin were also found in the 980-1100, and 1480-1650 cm(-1) ranges with notable formalin peaks (1041 and 1492 cm(-1)) appearing in the fixed normal and tumor tissues. The results showed that NIR Raman spectra of human bronchial tissues were significantly affected by formalin fixing and tissue hydration. Diagnostic markers at the 980-1100, and 1500-1650 cm(-1) regions derived from fixed tissues do not appear to be applicable for in vivo lung cancer detection. To yield valid Raman diagnostic information for in vivo applications, fresh tissue should be used. If only fixed tissue is available, thorough rinsing of specimens in phosphate-buffered saline (PBS) before spectral measurements may help reduce the formalin fixation artifacts on tissue Raman spectra.

Adenocarcinoma↗

PubMed2002

Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy has the potential to improve PDT dosimetry with a verteporfin-like photosensitizer.

In current clinical practice, photodynamic therapy (PDT) is carried out with prescribed drug doses and light doses as well as fixed drug-light intervals and illumination fluence rates. This approach can result in undesirable treatment outcomes of either overtreatment or undertreatment because of biological variations between different lesions and patients. In this study, we explore the possibility of improving PDT dosimetry by monitoring drug photobleaching and photoproduct formation. The study involved 60 mice receiving the same drug dose of a novel verteporfin-like photosensitizer, QLT0074, at 0.3 mg/kg body weight, followed by different light doses of 5, 10, 20, 30, 40 or 50 J/cm2 at 686 nm and a fluence rate of 70 mW/cm2. Photobleaching and photoproduct formation were measured simultaneously, using fluorescence spectroscopy. A ratio technique for data processing was introduced to reliably detect the photoproduct formed by PDT on mouse skin in vivo. The study showed that the QLT0074 photoproduct is stable and can be reliably quantified. Three new parameters, photoproduct score (PPS), photobleaching score (PBS) and percentage photobleaching score (PBS%), were introduced and tested together with the conventional dosimetry parameter, light dose, for performance on predicting PDT-induced outcome, skin necrosis. The statistical analysis of experimental results was performed with an ordinal logistic regression model. We demonstrated that both PPS and PBS improved the prediction of skin necrosis dramatically compared to light dose. PPS was identified as the best single parameter for predicting the PDT outcome.

Animals↗

PubMedDate not supplied

Raman spectroscopy of in vivo cutaneous melanin.

We successfully acquire the in vivo Raman spectrum of melanin from human skin using a rapid near-infrared (NIR) Raman spectrometer. The Raman signals of in vivo cutaneous melanin are similar to those observed from natural and synthetic eumelanins. The melanin Raman spectrum is dominated by two intense and broad peaks at about 1580 and 1380 cm(-1), which can be interpreted as originating from the in-plane stretching of the aromatic rings and the linear stretching of the C-C bonds within the rings, along with some contributions from the C-H vibrations in the methyl and methylene groups. Variations in the peak frequencies and bandwidths of these two Raman signals due to differing biological environments have been observed in melanin from different sources. The ability to acquire these unique in vivo melanin signals suggests that Raman spectroscopy may be a useful clinical method for noninvasive in situ analysis and diagnosis of the skin.

Algorithms↗

PubMedDate not supplied

Cutaneous melanin exhibiting fluorescence emission under near-infrared light excitation.

Under ultraviolet and visible light excitation, melanin is essentially a nonfluorescent substance. This work reports our study on near-infrared (NIR) fluorescence properties of melanins, and explores potential applications of NIR fluorescence techniques for evaluating skin disorders involving melanin. The NIR fluorescence spectrum is obtained using a fiber optic NIR spectrometer under 785-nm laser excitation. In vitro measurements are performed on synthetic dihydroxyphenylalanine (DOPA) melanin, melanin extracted from Sepia ink sacs, human hair, animal fur, and bird feathers. Paired spectral comparisons of white and black skin appendages show that melanization of hair, fur, or feathers more than doubles the NIR fluorescence. In vivo NIR autofluorescence of normal dorsal and volar forearm skin of 52 volunteers is measured. Dorsal forearm skin, which is darker than volar skin, exhibits significantly greater NIR fluorescence. Patients with vitiligo (n=4), compound nevus (n=3), nevus of Ota (n=1), superficial spreading melanoma (n=3), and postinflammatory hyperpigmentation (n=1) are also evaluated. NIR fluorescence is greater within the lesion than the surrounding normal skin for all these conditions except vitiligo, where the converse was true. The observed melanin NIR fluorescence provides a new approach to in vitro and in vivo melanin detection and quantification that may be particularly useful for evaluating pigmented skin lesions.

Animals↗

PubMedDate not supplied

Raman spectroscopy in combination with background near-infrared autofluorescence enhances the in vivo assessment of malignant tissues.

The diagnostic ability of optical spectroscopy techniques, including near-infrared (NIR) Raman spectroscopy, NIR autofluorescence spectroscopy and the composite Raman and NIR autofluorescence spectroscopy, for in vivo detection of malignant tumors was evaluated in this study. A murine tumor model, in which BALB/c mice were implanted with Meth-A fibrosarcoma cells into the subcutaneous region of the lower back, was used for this purpose. A rapid-acquisition dispersive-type NIR Raman system was employed for tissue Raman and NIR autofluorescence spectroscopic measurements at 785-nm laser excitation. High-quality in vivo NIR Raman spectra associated with an autofluorescence background from mouse skin and tumor tissue were acquired in 5 s. Multivariate statistical techniques, including principal component analysis (PCA) and linear discriminant analysis (LDA), were used to develop diagnostic algorithms for differentiating tumors from normal tissue based on their spectral features. Spectral classification of tumor tissue was tested using a leave-one-out, cross-validation method, and the receiver operating characteristic (ROC) curves were used to further evaluate the performance of diagnostic algorithms derived. Thirty-two in vivo Raman, NIR fluorescence and composite Raman and NIR fluorescence spectra were analyzed (16 normal, 16 tumors). Classification results obtained from cross-validation of the LDA model based on the three spectral data sets showed diagnostic sensitivities of 81.3%, 93.8% and 93.8%; specificities of 100%, 87.5% and 100%; and overall diagnostic accuracies of 90.6%, 90.6% and 96.9% respectively, for tumor identification. ROC curves showed that the most effective diagnostic algorithms were from the composite Raman and NIR autofluorescence techniques.

Animals↗