Agreement between colposcopic impression and histological diagnosis among human papillomavirus type 16-positive women: a clinical trial using dynamic spectral imaging colposcopy.

OBJECTIVE: To investigate the agreement between conventional colposcopic impression, dynamic spectral imaging (DSI) colposcopy and histology, for human papillomavirus type 16-positive (HPV16(+)) and non-16 high-risk (hr) HPV(+) women. DESIGN: Prospective, comparative, multicentre clinical trial. SETTING: Three colposcopy clinics in the Netherlands. POPULATION: Women (n = 177) aged 18 years or over with an intact cervix, referred for colposcopy. METHODS: The colposcopist graded the lesion by using the DSI colposcope as a regular video colposcope. Subsequently the DSI impression was displayed and biopsies were taken from all abnormal areas as well as from a random (normal) site. A cervical smear was taken for HPV typing. MAIN OUTCOME MEASURES: Histologically confirmed high-grade cervical intraepithelial neoplasia or cancer (CIN2(+)), positive for HPV16 or for any other hrHPV type. RESULTS: The DSI colposcope identified more CIN2(+) cervical lesions among HPV16(+) women than in non-16 hrHPV(+) women (P = 0.032 regardless of final histology and P = 0.009 among women with CIN2(+)). Consequently, the sensitivity of the DSI colposcope for detecting CIN2(+) lesions was higher in HPV16(+) women than in non-16 hrHPV(+) women (97% versus 74%, P = 0.009). No such differences were seen for the colposcopist impression. In addition, mainly smaller cervical lesions are missed by the colposcopist. CONCLUSIONS: The sensitivity of DSI colposcopy for CIN2(+) is higher in HPV16(+) than in non-16 hrHPV(+) women. Furthermore, regardless of HPV16 status, the sensitivity of DSI for CIN2(+) is higher than that of the colposcopist, probably because colposcopists tend to miss smaller cervical lesions.

Dynamic spectral imaging colposcopy: higher sensitivity for detection of premalignant cervical lesions.

OBJECTIVE: to validate the dynamic spectral imaging (DSI) colposcope's colour-coded map in discriminating high- from low-grade cervical lesions and non-neoplastic tissue. DESIGN: prospective, comparative, multicentre clinical trial. SETTING: the colposcopy clinics of three Dutch hospitals. POPULATION: women of 18 years or over with an intact cervix, referred for colposcopy. METHODS: during a 3-minute image acquisition phase, the DSI colposcope was used as a regular video colposcope: the colposcopist located and graded potential lesions based on conventional colposcopic criteria. Subsequently, a colour-coded map was calculated and displayed, representing localisation and severity of the cervical lesion. Biopsies were collected from all atypical sites, as identified by digital mapping and/or conventional colposcopy. Furthermore, one additional biopsy was taken. MAIN OUTCOME MEASURES: histologically confirmed high-grade cervical disease (CIN2+). RESULTS: in total 275 women were included in the study: 183 women were analysed in the 'according-to-protocol' (ATP) cohort and 239 women in the 'intention-to-treat' (ITT) cohort. In the ATP cohort, the sensitivity of DSI colposcopy to identify women with high-grade (CIN2+) lesions was 79% (95% CI 70-88) and the sensitivity of conventional colposcopy was 55% (95% CI 44-65) (P = 0.0006, asymptotic McNemar test). When the DSI colour-coded map was combined with conventional colposcopy, the sensitivity was 88% (95% CI 82-95). CONCLUSIONS: DSI colposcopy has a significantly higher sensitivity to detect cervical lesions than conventional colposcopy. If the colour-coded map is combined with conventional colposcopic examination, the sensitivity increases further.

A novel optical imaging method for the early detection, quantitative grading, and mapping of cancerous and precancerous lesions of cervix.

This paper describes a novel optical imaging method for the in vivo early detection, quantitative staging, and mapping of cervical cancer and precancer. A multispectral imaging system was developed, which is capable of performing time-resolved imaging spectroscopy. The system was used in order to assess quantitatively the alterations in the light scattering properties of the cervix, induced selectively and reversibly in cervical neoplasias, after the application of acetic acid solution. Spectral imaging and analysis of cervix show that the maximum contrast between acetic acid responsive and nonresponsive areas is obtained at 525 +/- 15 nm, which is further enhanced by cutting off the regular component of tissue reflection, with the aid of two linear cross polarizers. Successive snapshot imaging at this spectral band enables the quantitative assessment of the temporal alterations in the intensity of the backscattered light, in any spatial location of the examined area. Initial clinical trials show that optical contrast enhancement results in a notable improvement of the sensitivity in detecting incipient lesions. It was also shown that the measured temporal characteristics of the phenomenon contain specific information, which enables the differentiation between neoplastic and nonneoplastic lesions, as well as between neoplasias of different grade. The demonstrated improved sensitivity and specificity highlight the potential of the method in both clinical research and noninvasive diagnosis.

An imaging colorimeter for noncontact tissue color mapping.

There has been a considerable effort in several medical fields, for objective color analysis and characterization of biological tissues. Conventional colorimeters have proved inadequate for this purpose, since they do not provide spatial color information and because the measuring procedure randomly affects the color of the tissue. In this paper an imaging colorimeter is presented, where the nonimaging optical photodetector of colorimeters is replaced with the charge-coupled device (CCD) sensor of a color video camera, enabling the independent capturing of the color information for any spatial point within its field-of-view. Combining imaging and colorimetry methods, the acquired image is calibrated and corrected, under several ambient light conditions, providing noncontact reproducible color measurements and mapping, free of the errors and the limitations present in conventional colorimeters. This system was used for monitoring of blood supply changes of psoriatic plaques, that have undergone Psoralens and ultraviolet-A radiation (PUVA) therapy, where reproducible and reliable measurements were demonstrated. These features highlight the potential of the imaging colorimeters as clinical and research tools for the standardization of clinical diagnosis and for the objective evaluation of treatment effectiveness.

In vivo fluorescence kinetics and photodynamic therapy efficacy of delta-aminolevulinic acid-induced porphyrins in basal cell carcinomas and actinic keratoses; implications for optimization of photodynamic therapy.

Photodynamic therapy (PDT) with topical d-aminolevulinic acid (ALA) has become a therapeutic option of growing interest for superficial non-melanoma precancerous and malignant lesions. After application of ALA, in situ conversion to endogenous porphyrins is accomplished in a gradual manner. Therefore, the determination of fluorescence kinetics and spatial distribution in vivo versus time is a crucial point for the success of ALA-PDT. Seventeen basal cell carcinomas (BCC) and 20 actinic keratoses (AK) were enrolled in this study. In 5 BCC and 4 AK, in vivo fluorescence kinetics were performed over 24 hrs and for the remaining lesions between 2 and 7 hrs after ALA application. In vivo spatial and quantitative detection of the fluorescence intensity versus time showed considerable variations among tumors of the same type, so light irradiation was performed according to patient individualities. Both BCC and AK showed maximal median fluorescence intensity at 4-6.5 hrs post-application. In the present study, a high cure rate was proven after topical ALA-PDT (70.6% in BCC and 85% in AK). The results of fluorescence studies suggest that optimum irradiation time for BCC is approximately 3.5-5 hrs and for AK 5 hrs after ALA application, when relative maximal fluorescence intensity in correlation with fluorescence selectivity on the lesion, is obtained.

In vivo detection and staging of epithelial dysplasias and malignancies based on the quantitative assessment of acetic acid-tissue interaction kinetics.

A novel approach to the problem of non-destructive detection and staging of tissue lesions is presented. The method relies on the in vivo quantitative assessment of the spatial and temporal alterations of light-scattering properties, induced in epithelial dysplasias and malignancies of the cervix and larynx, after topical application of acetic acid solution. Initial clinical trials show that the method is capable of detecting incipient lesions and that differences in the dysplasia and malignancy grade are clearly manifested in the measured temporal characteristics of the phenomenon.

In vivo detection of human papilloma virus-induced lesions of anogenital area after application of acetic acid: a novel and accurate approach to a trivial method.

Human papilloma virus infection is increasing at an alarming rate. The ability of the virus to establish a subclinical infection and its association with malignancy of the lower genital tract make the statistics even more worrisome. Topical application of acetic acid solution provokes temporal alterations of the light-scattering properties of human papilloma virus-induced lesions of anogenital area. For the in vivo study of the phenomenon, an imaging system has been employed, which performs time-lapse imaging and enables the calculation and display of the kinetics of the provoked alterations in any point within the examined area. Confirmation of diagnosis has been established with conventional histology and polymerase chain reaction. It has been shown that the method provides early detection and staging of skin alteration or transformation due to human papilloma virus infection and enables mapping of the infected area.

Assessment of nasal mucosa blood supply by quantitative endoscopic imaging of the back-scattered light.

In this article we present a method for the objective assessment and monitoring of tissue blood supply using a specially developed endoscopic imaging colorimeter that enables quantitative color modeling of the back-scattered light during endoscopic examination. Tissue blood volume changes in the nasal mucosa, induced by xylometazoline hydrochloride nasal spray, were evaluated with this method. It was found that quantitative imaging provides sensitive, reproducible, and reliable means for the monitoring and mapping of tissue blood supply and is easy to use routinely. The results showed that saturation decreases with time, being the most sensitive color parameter to the vasoconstriction procedure. It appears that objective indexes for optical tissue characterization and analysis may be promising in the understanding of the pathophysiology of tissue changes and in the objective evaluation of their response to different therapeutic schemes.

Viscoelastic response of human hair cortex.

The present study describes a new methodological approach which allows the separate analysis and quantitative determination of the viscous and elastic components of human hair using a computerised experimental system. In a first series of experiments subsequent to the estimation of the cross-sectional surface area of the cuticle, the cortex and the medulla, the viscoelastic response of hair (considered as a homogeneous material) and of its cortex were determined in ten hair specimens derived from the same human subject. Statistically significant differences were found between hair and its cortex with regard to the values of the modulus of elasticity, limit of linearity and post-yield slope. In a second series of experiments the viscoelastic parameters of hair and its cortex were separately determined in 100 hair specimens derived from ten healthy human subjects (ten specimens from each subject). It was found that the dispersion of the values of modulus of elasticity, limit of linearity and post-yield slope of the cortex was significantly reduced compared with that of the hair. Our results indicate that the pattern of the viscoelastic parameters of human hair cortex, which strongly depends on its microstructural features, may be regarded as a more reliable and sensitive diagnostic marker than that of hair in various structural and functional hair disorders.

A statistical riverine litter propagation model.

A statistical riverine litter propagation (RLP) model based on importance sampling Monte Carlo (ISMC) simulation was developed in order to predict the frequency distribution of certain litter types in river reaches. The model was preliminarily calibrated for plastic sheeting by a pilot study conducted on the River Taff, Wales (UK). Litter movement was predominantly controlled by reach characteristics, such as vegetation overhang and water-course obstructions. These affects were modeled in the simulations, by utilizing geometric distributions of river reaches in the time domain. The proposed model satisfactorily simulated the dosing experiments performed at the River Taff. It was concluded from the preliminary calibrations that, the RLP model can be efficiently utilized to portray litter propagation at any arbitrarily selected river site, provided that the stream flows and reach characteristics are calibrated by representative probability distributions of similar sections. Therefore, the RLP model can be considered as a new statistical technique that can predict litter propagation in river sections.

Mechanical parameters of human hair: possible application in the diagnosis and follow-up of hair disorders.

Mechanical analysis of human hair may provide the dermatologists with several markers of considerable diagnostic importance. In the present paper, using a new computerised experimental system, attempts were made firstly to interpret the curves of the elastic and viscous components of the mechanical behavior of human hair and secondly to determine characteristic parameters which correlate well with its structural features. In order to overcome methodological problems due to the inhomogeneous structure of human hair, mechanical parameters were defined which either depend on the cortical microstructure or correlate well with the size of hair medulla.

Trichothiodystrophic hair reveals an abnormal pattern of viscoelastic parameters.

Separate analysis and quantitative determination of the viscous and elastic parameters of hair performed in 5 patients with trichothiodystrophy and in 20 sex- and age-matched control subjects revealed an abnormal pattern of the mechanical behavior of trichothiodystrophic hair. The change of the viscous parameter is probably associated with the profound alterations in the high-sulfur proteins of the interfilamentary matrix; the changes in the elastic parameters may be related to the reduced stability of the irregularly arranged microfibrils of trichothiodystrophic hair caused by the marked reduction of the disulfide cross-links.

A method for the determination of viscoelastic parameters of human hair in relation to its structure.

An analytical model and the corresponding experimental procedure are presented, which make it possible to separately analyze the viscous and elastic components of human hair. Moreover, a computerized experimental system is described with which a standardized quantitative determination of the most important mechanical parameters of human hair can be performed. Comparative investigations of the mechanical behavior of hair specimens obtained from the frontoparietal and occipital scalp regions of 10 healthy human subjects showed no statistically significant differences with regard to their mechanical parameters. Nevertheless, the paired analysis of the mechanical parameters of thin and thick hair specimens revealed that the values of two of these parameters are significantly higher in thin than in thick hair specimens. These findings suggest that there are mechanical parameters of human hair related to gross hair morphology, whereas others depend on hair microstructure.

Brittle and sparse hair with normal cystine content caused by methionine deficiency?

The unusual case of an 8-year-old girl with a hair disorder is presented, characterized by brittle, short and sparse hair. On polarizing microscopy the latter reveals a "tiger tail" pattern, whereas severe cuticular defects are detected on scanning electron microscopy. The patient's hair has a normal cystine content but is completely devoid of methionine and reveals distinct changes of its visoelastic parameters. It is presently unknown whether the lack of methionine may be implicated in the pathogenesis of this hair disorder, which to the best of our knowledge has not been previously described.

Photodynamic treatment of skin malignancies with aminolevulinic acid. Emphasis on anatomical observations and in vivo erythema visual assessment.

BACKGROUND: Photodynamic therapy with delta-aminolevulinic acid is a promising alternative treatment for superficial skin malignancies. OBJECTIVE: Further clinical experience, study of tissue alterations leading to recovery, and correlation/prediction of the therapeutic response through in vivo skin color changes as represented by erythema development. METHODS: The therapeutic procedure, sequential histology and histochemistry, and the development of a remote machine vision system to measure, map, and monitor the erythema development. RESULTS/CONCLUSIONS: A high cure response rate with adequate follow-up was shown. A significant correlation of the clinical-histologic response of tumors subjected to treatment with the erythema measurements implies that erythema inspection and quantitative analysis offer a reliable predictor of the therapeutic outcome and a clue for optimization of this treatment modality.