We present initial evidence of the SOLUS potential for the multimodal non-invasive diagnosis of breast cancer by describing the correlation between optical and standard radiological data and analyzing a case study.
This study aims at evaluating the effect of NeoAdjuvant Chemotherapy (NAC) on the contralateral tumor-free breast tissue through time domain diffuse optical spectroscopy. The breast tissue composition consisting of hemoglobin, water, lipid, and collagen concentrations is quantitatively derived using our seven-wavelength (635-1060 nm) optical mammograph. Preliminary analysis of ten patients' data shows compositional changes occurring in the non-tumor breast in addition to the tumor breast. This includes reduction in breast density and components’ concentrations through the course of the therapy. The final goal is to eventually identify if there is a correlation of these effects with pathological complete response.
A machine learning classification algorithm is applied to the SOLUS database to discriminate benign and malignant breast lesions, based on absorption and composition properties retrieved through diffuse optical tomography. The Mann-Whitney test indicates oxy-hemoglobin (p-value = 0.0007) and lipids (0.0387) as the most significant constituents for lesion classification, but work is in progress for further analysis. Together with sensitivity (91%), specificity (75%) and the Area Under the ROC Curve (0.83), special metrics for imbalanced datasets (27% of malignant lesions) are applied to the machine learning outcome: balanced accuracy (83%) and Matthews Correlation Coefficient (0.65). The initial results underline the promising informative content of optical data.
The purpose of this clinical study is to monitor NeoAdjuvant Chemotherapy through time domain Diffuse Optical Spectroscopy, correlate the optical results with conventional imaging techniques and pathological response and eventually predict the efficacy of NAC in breast cancer patients. Our seven wavelength (635 -1060 nm) optical mammograph is used to perform non-invasive measurements on patients undergoing NAC in this study. The broad spectral range helps us to fully analyze tissue composition, that includes hemoglobin, water lipids and collagen concentration, to track the tumor response during the course of the therapy. In this paper, we present the preliminary results of five patients.
Significance: Multi-laboratory initiatives are essential in performance assessment and standardization—crucial for bringing biophotonics to mature clinical use—to establish protocols and develop reference tissue phantoms that all will allow universal instrument comparison.
Aim: The largest multi-laboratory comparison of performance assessment in near-infrared diffuse optics is presented, involving 28 instruments and 12 institutions on a total of eight experiments based on three consolidated protocols (BIP, MEDPHOT, and NEUROPT) as implemented on three kits of tissue phantoms. A total of 20 synthetic indicators were extracted from the dataset, some of them defined here anew.
Approach: The exercise stems from the Innovative Training Network BitMap funded by the European Commission and expanded to include other European laboratories. A large variety of diffuse optics instruments were considered, based on different approaches (time domain/frequency domain/continuous wave), at various stages of maturity and designed for different applications (e.g., oximetry, spectroscopy, and imaging).
Results: This study highlights a substantial difference in hardware performances (e.g., nine decades in responsivity, four decades in dark count rate, and one decade in temporal resolution). Agreement in the estimates of homogeneous optical properties was within 12% of the median value for half of the systems, with a temporal stability of <5 % over 1 h, and day-to-day reproducibility of <3 % . Other tests encompassed linearity, crosstalk, uncertainty, and detection of optical inhomogeneities.
Conclusions: This extensive multi-laboratory exercise provides a detailed assessment of near-infrared Diffuse optical instruments and can be used for reference grading. The dataset—available soon in an open data repository—can be evaluated in multiple ways, for instance, to compare different analysis tools or study the impact of hardware implementations.
Significance: Diffuse optical tomography is an ill-posed problem. Combination with ultrasound can improve the results of diffuse optical tomography applied to the diagnosis of breast cancer and allow for classification of lesions.
Aim: To provide a simulation pipeline for the assessment of reconstruction and classification methods for diffuse optical tomography with concurrent ultrasound information.
Approach: A set of breast digital phantoms with benign and malignant lesions was simulated building on the software VICTRE. Acoustic and optical properties were assigned to the phantoms for the generation of B-mode images and optical data. A reconstruction algorithm based on a two-region nonlinear fitting and incorporating the ultrasound information was tested. Machine learning classification methods were applied to the reconstructed values to discriminate lesions into benign and malignant after reconstruction.
Results: The approach allowed us to generate realistic US and optical data and to test a two-region reconstruction method for a large number of realistic simulations. When information is extracted from ultrasound images, at least 75% of lesions are correctly classified. With ideal two-region separation, the accuracy is higher than 80%.
Conclusions: A pipeline for the generation of realistic ultrasound and diffuse optics data was implemented. Machine learning methods applied to a optical reconstruction with a nonlinear optical model and morphological information permit to discriminate malignant lesions from benign ones.
We present in vivo tests on healthy women through our optical mammograph in preparation for a clinical validation on neoadjuvant chemotherapy monitoring, and we report preliminary data on the first patient enrolled in the study.
A multimodal instrument for breast imaging was developed, combining ultrasound (morphology), shear wave elastography (stiffness), and time domain multiwavelength diffuse optical tomography (blood, water, lipid, collagen) to improve the non-invasive diagnosis of breast cancer.
Performance assessment and standardization are indispensable for instruments of clinical relevance in general and clinical instrumentation based on photon migration/diffuse optics in particular. In this direction, a multi-laboratory exercise was initiated with the aim of assessing and comparing their performances. 29 diffuse optical instruments belonging to 11 partner institutions of a European level Marie Curie Consortium BitMap1 were considered for this exercise. The enrolled instruments covered different approaches (continuous wave, CW; frequency domain, FD; time domain, TD and spatial frequency domain imaging, SFDI) and applications (e.g. mammography, oximetry, functional imaging, tissue spectroscopy). 10 different tests from 3 well-accepted protocols, namely, the MEDPHOT2 , the BIP3 , and the nEUROPt4 protocols were chosen for the exercise and the necessary phantoms kits were circulated across labs and institutions enrolled in the study. A brief outline of the methodology of the exercise is presented here. Mainly, the design of some of the synthetic descriptors, (single numeric values used to summarize the result of a test and facilitate comparison between instruments) for some of the tests will be discussed.. Future actions of the exercise aim at deploying these measurements onto an open data repository and investigating common analysis tools for the whole dataset.
The use of technologies still under development (Silicon PhotoMultipliers and Time-to-Digital Converter) for the upgrade of our time-resolved optical mammograph highlighted the crucial need for a thorough and progressive instrument characterization (from extensive laboratory tests on phantoms to in vivo measurements), potentially of general interest. Despite satisfying results on phantoms, in vivo tests urged an instrumental change, with the adoption of a just released high-throughput TDC to obtain high-quality breast scans (much wider scan area, better day-by-day reproducibility, improved signal quality, simpler set-up). A clinical study on monitoring of neoadjuvant chemotherapy is now ongoing at the San Raffaele Hospital, Milan.
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