A molecular imaging method employing acetic acid dilute solution as a biomarker of cervical neoplasia is described and
the interpretation of the biophysical processes involved determining the in-vivo measured dynamic scattering
characteristics is presented. A compartmental model of the epithelium has been developed for predicting the epithelial
transport phenomena that are expected to be correlated with the dynamic characteristics of the backscattered light.
Model predictions have been compared and confirmed by experimental data obtained from patients with cervical
neoplasia of different grade, with the aid of specially developed imaging system. Results revealed that the dynamic
scattering characteristics and both structural and functional alterations are largely determined by the intracellular proton
concentration kinetics. This highlights the potential of the developed imaging method and technology for the non-invasive
diagnosis, guided therapeutics and screening of cervical neoplasia.
A novel approach to the problem of non-invasive diagnostics is presented, which relay son a combiend optical and chemical excitation of the tissue, by employing white light and topical application of acetic acid solution, respecitvley. Acetic acid-tissue interaction results in a transient alteration in the light scattering properties of the abnormal tissue selectivity. A specially developed Spectral Imaging system was used for the in vivo spectral imaging and analysis of the tissue and for the measurement, as a function of both time and location, of the acetic acid-induced alterations in the tissue scattering properties. Modeling and fitting of the experimental data result in the calculation of the kinetic constants of the marker-tissue interaction process, and spatil distribution of whcih is visualized with the aid of a pseudocolor scale. Clinical evaluation of both methodology and technology in normal, precancerous and cancerous lesions of cervix show that the measured kinetic data contain specific information, which enables the differentiation between cancerous and non-cancerous lesions, as well as between dysplasias of different grade. The calculated map of the kinetic constants provides information for the spatial distribution of the lesion's grades, thus enabling the detection of incipient lesions and the precise localization and classification of pathologic tissue areas.
Hyperspectral imaging of skin combines the spectral information of diffuse reflectance spectroscopy with the spatial information of 2D imaging. Skin chromophore maps can be reconstructed in which features such as pigmented lesions, diffuse and localized erythema, areas of increased blood stasis, etc. could be identified and the relative
parameters quantified. Hyperspectral imaging is the only reliable method to produce a quantitative distribution map of chromophores contributing to the color appearance of the skin.
Topical application of acetic acid solution is routinely used as a marker for the clinical diagnosis of cervical cancer and more specifically to direct biopsy sampling. Abnormal areas are visualized as transient white patches and there are several evidences that acetic acid-tissue interaction kinetics is correlated with the malignancy grade. The visual assessment of this interaction can not be effective and therefore the obtained diagnostic information is limited. In this paper a new method and a multi-spectral imaging system are presented, capable to enhance the contrast between normal and acetic acid responsive tissue areas and to assess quantitatively the kinetics of acetic acid-tissue interaction. The former is achieved by cutting-off the regular reflection, in combination with the selection of the appropriate imaging spectral band. The second is achieved with the dynamic measurement of the intensity of the back-scattered light in any spatial point of the image, after acetic acid application. The obtained quantitative data provide a means for the early detection, and more accurate grading and mapping of the lesion. This method was experimentally implemented to colposcopy and a remarkable improvement of the sensitivity specificity and reproducibility was demonstrated during in initial clinical trials.
Several aspects of the applications of laser technology in cleaning and diagnostics of painted artworks are reviewed. Laser and material parameter studies leading to the optimization of the cleaning process are presented while the use of spectroscopic techniques for obtaining information on the mechanism of the ablation process and probe possible photochemical effects is discussed. Furthermore, holographic interferometric techniques for detecting possible mechanical stress induced by the laser during the cleaning process are employed and preliminary result are shown. Finally, examples of the applications of imaging techniques in artwork diagnostics are presented.
The biological response to PDT depends on the photosensitizer accumulation to the malignant cells, the tumor vasculature, the inherent cell sensitivity to the photodynamic effect, etc. The in-vivo measurement of physical parameters related with these factors can serve in the understanding of the mechanisms involved in the cell death, as well as in the optimization of the treatment procedure. In this paper we demonstrate a modular diffuse reflection and fluorescence emission imaging colorimeter. We have used it for the in-vivo on-line quantitative measurement and mapping the time course fluorescence intensity after ALA application and for the tissue color changes associated with the erythema developed during irradiation. Based on the obtained quantitative data, we investigate the correlation between the photosensitizer accumulation before light irradiation and the hemodynamic changes, revealed as erythema development, occurring during light irradiation. Their relative significance as predicting factors for the photodynamic treatment effectiveness is also evaluated.
Twenty nine skin malignancies, 14 solar keratoses (SK) and 15 basal cell carcinomas (BCC) were treated with ALA-PDT. The overall cure response rate for SK was 85.7% and 66.6% for BCC. Specific histologic findings in sequential histology were indicative of the destructive and restoration mechanisms. A multispectral imaging system (MUSIS) was developed to perform diffuse reflection and fluorescence studies. Most of the lesions developed peak fluorescence 1.5 - 4 hours after ALA application. Hue was the most sensitive parameter to record the kinetics of the photosensitizer concentration in the atypical cells. It was worth noticing that the peak fluorescence differed among patients and this was an indication to start the irradiation more objectively. Erythema inspection and quantification during irradiation and afterwards was achieved by means of MUSIS. Erythema development was shown to include a new peak in the Hue histogram corresponding to a color range between red and violet. Time course erythema elicitation was found to differ between SK and BCC in accordance with recorded histologic difference relative to PDT-destruction mechanisms. Erythema development was shown to correlate significantly with the phototoxic effect and might be considered a reliable predictor of PDT efficacy.
We have developed a machine vision system, which combines imaging and absolute color measurement techniques, for remote, objective, 2D color and color difference measurements. This imaging colorimeter adapted on an endoscope was used to evaluate nasal mucosa color changes induced by the administration of a sympathomimetic agent, with vasoconstrictive properties. The demonstrated reproducible and reliable measurements indicate the efficacy of the described system, for the potent vasoconstriction assessment of different pharmacotherapeutic agents, and suggests that it can also be useful for evaluating individuals, with allergic rhinitis, vasomotor rhinitis, and inflammation disorders of the paranasal sinuses. Machine vision techniques in endoscopy providing objective indices for optical tissue characterization and analysis can serve in understanding the pathophysiology of tissue lesions, and in the objective evaluation of their response to different therapeutic schemes, in several medical fields.
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