Costas Balas

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

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/spl plusmn/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.

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.

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. Here, 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.

Dynamic Spectral Imaging: Improving Colposcopy

Purpose: Colposcopy occupies a key role in the prevention of cervical cancer by identifying preinvasive or invasive lesions. However, colposcopy is subjective and is responsible for 52% of screening failures. Dynamic spectral imaging (DSI) is based on the objective, quantitative assessment of the acetowhitening effect. This study compared DSI with colposcopy. Experimental Design: Women referred for colposcopy were examined simultaneously with colposcopy and DSI using a precommercial DySIS model (FPC-03) in an international, multicenter trial. The colposcopy impression and DySIS values were compared with consensus histology reports of biopsies. Subjects were recruited to a training group and subsequently to a test group. Measures were taken to avoid verification bias. Results: The training and test groups comprised 82 and 308 eligible women, respectively. A cutoff value to identify high-grade disease was selected from the results of the training group and data from previous work. Receiver operator curve analysis of the test data showed an area under the curve of 0.844. DySIS detected 62.9% more high-grade cases than colposcopy (57 versus 35, P = 0.0001). DySIS exceeded end points approved by the Food and Drug Administration for similar studies, with increments in the true positive rate of 22/308 (7.1%; lower 95% CL, 4.5% versus 2%) and in the false positive rate of 32/308 (10.4%; upper 95% CL, 14.7% versus 15%). Conclusions: DySIS is more sensitive than colposcopy in detecting high-grade lesions and can provide improved guidance for biopsy. The results are obtained in a user-independent fashion, making it suitable for use by nursing personnel.

In Vivo Molecular Imaging of Cervical Neoplasia Using Acetic Acid as Biomarker

In this paper, a molecular imaging method employing acetic acid dilute solution as a biomarker is described. An interpretation of the biophysical processes that are involved in the biomarker-tissue interaction and are determining the in vivo measured dynamic scattering characteristics is presented. On the basis of this interpretation, a compartmental model of the epithelium is developed for predicting the epithelial transport phenomena that are expected to be correlated with the dynamic characteristics of the backscattered light. The model predictions have been compared with the experimental data obtained from patients with cervical neoplasia of different grade, with the aid of a specially developed imaging system. Comparisons confirmed the validity of the interpretation of the phenomenon, and particularly, the fact that dynamic scattering characteristics are largely determined by the intracellular proton concentration kinetics. In addition, the correlation of the latter with both structural and functional alterations, associated with cervical neoplasia development, has been predicted theoretically and confirmed experimentally. The established correlation enables the derivation of quantitative indices expressing disease-specific microstructural and functional alterations, from the in vivo measured dynamic optical characteristics. This highlights the potential of the developed imaging method and technology for the noninvasive diagnosis, guided therapeutics, and screening of cervical neoplasia.

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

Please cite this paper as: Louwers J, Zaal A, Kocken M, ter Harmsel W, Graziosi G, Spruijt J, Berkhof J, Balas C, Papagiannakis E, Snijders P, Meijer C, van Kemenade F, Verheijen R. Dynamic spectral imaging colposcopy: higher sensitivity for detection of premalignant cervical lesions. BJOG 2011;118:309–318.

A novel spectral microscope system: application in quantitative pathology

A novel spectral microscope system is presented together with a method for the quantitative assessment of the uptake by histologic samples of stains used in pathology to label tissue features of diagnostic importance. The critical component of the microscope is a variable interference filter-based monochromator. The system is capable of performing real-time spectral imaging in a plurality of spectral bands and micro-spectroscopy in any image pixel, in the spectral range 400-1000 nm. The wavelength-tuning step is 2.4-2.6 nm, while the full-width at half maximum in each step is about 1.5% of the operating central wavelength. The developed system integrates algorithms and calibration procedures for the calculation of the stain-uptake by the tissue. The acquired spectra from both stained tissue and calibration stain solutions enable the calculation of the concentration maps of the stains, even if the latter are multiple and overlap spatially and spectrally. The system was used for the quantitative mapping of the expression of estrogen and progesterone receptors in breast cancer cells. In this particular case, model validation shows that although two stains are employed, capturing of their transmittance at more than ten wavelengths is required in order to obtain an acceptable accuracy. These findings highlight the need for the development and implementation of spectral microscopy in pathology and its potential to introduce novel more reliable diagnostic criteria.

Hyperspectral imaging: potential in non-destructive analysis of palimpsests

Palimpsests -twice written manuscripts- are of great interest since they may contain important hidden text underneath the visible one. Hyperspectral imaging may aid the expert to read the old script by enhancing the contrast between the under- and -overwriting. We present a hyperspectral imager (MUSIS), capable of acquiring 34 calibrated spectral bands in the range of 360-1150 nm (extended to 1550 nm when coupled with a photocathode tube). The potential of spectral imaging to improve the readability of manuscripts by employing common spectral analysis techniques is explored. Results on different manuscripts obtained by principal component analysis (PCA) and linear spectral mixture analysis (LSMA) prove that hyperspectral imaging tools has the potential to become an indispensable tool for the analysis of old manuscripts.

Hyperspectral Image Acquisition and Analysis of Skin

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.

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

Please cite this paper as: Zaal A, Louwers J, Berkhof J, Kocken M, ter Harmsel W, Graziosi G, Spruijt J, Balas C, Papagiannakis E, Snijders P, Meijer C, van Kemenade F, Verheijen R. Agreement between colposcopic impression and histological diagnosis among human papillomavirus type 16‐positive women: a clinical trial using dynamic spectral imaging colposcopy. BJOG 2012;119:537–544.