This study describes the process of design, development and validation of phantoms that mimic the optical
properties of human tissue that could be used for performance verification of Diffuse Optical Tomography (DOT) and
Diffuse Optical Spectroscopy (DOS) instruments. The process starts with choosing and qualifying the ingredients
(hosting matrix, scatterers and absorbers) that allow adjusting of the scattering and absorption coefficients
independently and linearly scalable. Results of the evaluation of liquid and solid phantoms are presented.
In addition, the study evaluates the reproducibility and long-term stability of the designed phantoms. The
results show that some of the phantoms could be reliable references for performance assessment and periodic
calibration-validation of the systems, during pre-clinical and clinical stages.
One important challenge for <i>in-vivo</i> imaging fluorescence in cancer research and related pharmaceutical studies is to discriminate the exogenous fluorescence signal of the specific tagged agents from the natural fluorescence. For mice, natural fluorescence is composed of endogenous fluorescence from organs like the skin, the bladder, etc. and from ingested food. The discrimination between the two kinds of fluorescence makes easy monitoring the targeted tissues. Generally, the amplitude of the fluorescence signal depends on the location and on the amount of injected fluorophore, which is limited in <i>in-vivo</i> experiments. This paper exposes some results of natural fluorescence analysis from <i>in-vivo</i> mice experiments using a time domain small animal fluorescence imaging system: eXplore Optix<sup>TM</sup>. Fluorescence signals are expressed by a Time Point Spread Function (TPSF) at each scan point. The study uses measures of similarity applied purposely to the TPSF to evaluate the discrepancy and/or the homogeneity of scanned regions of a mouse. These measures allow a classification scheme to be performed on the TPSF's based on their temporal shapes. The work ends by showing how the exogenous fluorescence can be distinguished from natural fluorescence by using the TPSF temporal shape.
It is expected that the optical signatures of physiological changes are biomarkers reacting faster to breast tumor
evolution than structural changes, meaning that diffuse optical tomography (DOT) could be a promising modality for
monitoring and detecting early changes of the lesion during neoadjuvant treatment. Numerous publications as well as
our preliminary results revealed that the heterogeneity inside the breast and the variability within the population are
challenging for such application. Moreover the sensitivity of the breast physiology to the external pressure applied
during data acquisition is adding a significant variance to the process.
In the present study we evaluate key factors that could make neoadjuvant treatment monitoring, using DOT,
successfully: 1) sensitivity-the clue for earlier detection; 2) repeatability-minimizing the impact of the artificially
induced variance (related with pressure, angle of the view, etc.); 3) accurate co-localization of the ROI within the
sequential measurements performed during the neoadjuvant treatment.
Non-clinical and clinical studies were performed using a multi-wavelength time-domain platform, with
transmission detection configuration, and 3D images of optical and physiological properties were generated using
diffuse propagation approximation. The results of non-clinical studies show that the sensitivity of the system allows
detection and quantification of absorption changes equivalent to less than 1 micromole of blood.
Clinical studies, involving more than 40 patients, revealed that with the appropriate precautions during patient
positioning and compression adjustment, the repeatability of the results is very good and the similarities between the
two breasts are high suggesting that the contra-lateral breast could be used as a reliable reference for DOT as well.
Recent years have seen significant efforts deployed to apply optical imaging techniques in clinical indications. Optical mammography as an adjunct to X-ray mammography is one such application. 3D optical mammography relies on the sensitivity of near-infrared light to endogenous breast chromophores in order to generate in vivo functional views of the breast. This work presents prospective tissue characterization results from a multi-site clinical study targeting optical tomography as an adjunct to conventional mammography. A 2<sup>nd</sup> -generation multi-wavelength time-domain acquisition system was used to scan a wide population of women presenting normal or suspicious X-ray mammograms. Application specific algorithms based on a diffusive model of light transport were used to quantify the breast's optical properties and derive 3D images of physiological indices. Using histopathological findings as a gold standard, results confirm that optically derived parameters provide statistically significant discrimination between malignant and benign tissue in wide population of subjects. The methodology developed for case reviews, lesion delineation and characterization allows for better translation of the optical data to the more traditional x-ray paradigm while maintaining efficacy. They also point to the need for guidelines that facilitate correlation of optical data if those results are to be confirmed in a clinical setting.
Near-infrared (NIR) technology appears promising as a non-invasive clinical technique for breast cancer screening and diagnosis. The technology capitalizes on the relative transparency of human tissue in this spectral range and its sensitivity to the main components of the breast: water, lipid and hemoglobin. In this work we present initial results obtained using the SoftScan® breast-imaging system developed by ART, Advanced Research Technologies inc., Montreal. This platform consists of a 4-wavelength time-resolved scanning system used to quantify non-invasively the local functional state of breast tissue. The different aspects of the system used to accurately retrieve 3D optical contrast will be presented. Furthermore, preliminary data obtained from a prospective study conducted at The Royal Victoria Hospital of the McGill University Health Center in Montreal will be presented. During this study, 65 volunteers with either abnormal or normal mammograms were enrolled. Analysis of the data gathered by SoftScan demonstrated the potential of the technology in discriminating between healthy and diseased tissue.