Justin Y. Lo

Cost-effective diffuse reflectance spectroscopy device for quantifying tissue absorption and scattering in vivo

A hybrid optical device that uses a multimode fiber coupled to a tunable light source for illumination and a 2.4-mm photodiode for detection in contact with the tissue surface is developed as a first step toward our goal of developing a cost-effective, miniature spectral imaging device to map tissue optical properties in vivo. This device coupled with an inverse Monte Carlo model of reflectance is demonstrated to accurately quantify tissue absorption and scattering in tissue-like turbid synthetic phantoms with a wide range of optical properties. The overall errors for quantifying the absorption and scattering coefficients are 6.0+/-5.6 and 6.1+/-4.7%, respectively. Compared with fiber-based detection, having the detector right at the tissue surface can significantly improve light collection efficiency, thus reducing the requirement for sophisticated detectors with high sensitivity, and this design can be easily expanded into a quantitative spectral imaging system for mapping tissue optical properties in vivo.

A strategy for quantitative spectral imaging of tissue absorption and scattering using light emitting diodes and photodiodes.

A diffuse reflectance spectroscopy system was modified as a step towards miniaturization and spectral imaging of tissue absorption and scattering. The modified system uses a tunable source and an optical fiber for illumination and a photodiode in contact with tissue for detection. Compared to the previous system, it is smaller, less costly, and has comparable performance in extracting optical properties in tissue phantoms. Wavelength reduction simulations show the feasibility of replacing the source with LEDs to further decrease system size and cost. Simulated crosstalk analysis indicates that this evolving system can be multiplexed for spectral imaging in the future.

A diffuse reflectance spectral imaging system for tumor margin assessment using custom annular photodiode arrays.

Diffuse reflectance spectroscopy (DRS) is a well-established method to quantitatively distinguish between benign and cancerous tissue for tumor margin assessment. Current multipixel DRS margin assessment tools are bulky fiber-based probes that have limited scalability. Reported herein is a new approach to multipixel DRS probe design, which utilizes direct detection of the DRS signal by using optimized custom photodetectors in direct contact with the tissue. This first fiberless DRS imaging system for tumor margin assessment consists of a 4 × 4 array of annular silicon photodetectors and a constrained free-space light delivery tube optimized to deliver light across a 256 mm2 imaging area. This system has 4.5 mm spatial resolution. The signal-to-noise ratio measured for normal and malignant breast tissue-mimicking phantoms was 35 dB to 45 dB for λ = 470 nm to 600 nm.

Wavelength Optimization for Quantitative Spectral Imaging of Breast Tumor Margins

A wavelength selection method that combines an inverse Monte Carlo model of reflectance and a genetic algorithm for global optimization was developed for the application of spectral imaging of breast tumor margins. The selection of wavelengths impacts system design in cost, size, and accuracy of tissue quantitation. The minimum number of wavelengths required for the accurate quantitation of tissue optical properties is 8, with diminishing gains for additional wavelengths. The resulting wavelength choices for the specific probe geometry used for the breast tumor margin spectral imaging application were tested in an independent pathology-confirmed ex vivo breast tissue data set and in tissue-mimicking phantoms. In breast tissue, the optical endpoints (hemoglobin, β-carotene, and scattering) that provide the contrast between normal and malignant tissue specimens are extracted with the optimized 8-wavelength set with <9% error compared to the full spectrum (450–600 nm). A multi-absorber liquid phantom study was also performed to show the improved extraction accuracy with optimization and without optimization. This technique for selecting wavelengths can be used for designing spectral imaging systems for other clinical applications.

Rapid determination of oxygen saturation and vascularity for cancer detection.

A rapid heuristic ratiometric analysis for estimating tissue hemoglobin concentration and oxygen saturation from measured tissue diffuse reflectance spectra is presented. The analysis was validated in tissue-mimicking phantoms and applied to clinical measurements in head and neck, cervical and breast tissues. The analysis works in two steps. First, a linear equation that translates the ratio of the diffuse reflectance at 584 nm and 545 nm to estimate the tissue hemoglobin concentration using a Monte Carlo-based lookup table was developed. This equation is independent of tissue scattering and oxygen saturation. Second, the oxygen saturation was estimated using non-linear logistic equations that translate the ratio of the diffuse reflectance spectra at 539 nm to 545 nm into the tissue oxygen saturation. Correlations coefficients of 0.89 (0.86), 0.77 (0.71) and 0.69 (0.43) were obtained for the tissue hemoglobin concentration (oxygen saturation) values extracted using the full spectral Monte Carlo and the ratiometric analysis, for clinical measurements in head and neck, breast and cervical tissues, respectively. The ratiometric analysis was more than 4000 times faster than the inverse Monte Carlo analysis for estimating tissue hemoglobin concentration and oxygen saturation in simulated phantom experiments. In addition, the discriminatory power of the two analyses was similar. These results show the potential of such empirical tools to rapidly estimate tissue hemoglobin in real-time spectral imaging applications.

A compact, cost-effective diffuse reflectance spectroscopic imaging system for quantitative tissue absorption and scattering

There is clinical utility for a wide-field, spectroscopic imaging device for quantitative tissue absorption and scattering in a number of applications. We present the design of a compact, cost-effective spectroscopic imaging system, which consists of a broadband source with bandpass filters and a light guide for illumination and an inexpensive array of silicon photodiodes for detection. A single-pixel version of the system was tested in liquid phantoms simulating a wide range of human breast tissue and optical properties can be extracted with absorption and reduced scattering errors of 12.6% and 4.7%, respectively. We show proof-of-concept for performing fast, wide-field spectroscopic imaging with a simple design. The design also allows for scaling and expansion into higher pixel number and density in future iterations of custom device design, which includes in-house photodiode array fabrication processes and integration of on-board current amplifier circuits.

Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma.

OBJECTIVES We propose the use of morphological optical biomarkers for rapid detection of human head and neck squamous cell carcinoma (HNSCC) by leveraging the underlying tissue characteristics in aerodigestive tracts. MATERIALS AND METHODS Diffuse reflectance spectra were obtained from malignant and contra-lateral normal tissues of 57 patients undergoing panendoscopy and biopsy. Oxygen saturation, total hemoglobin concentration, and the reduced scattering coefficient were extracted. Differences in malignant and normal tissues were examined based on two different groupings: anatomical site and morphological tissue type. RESULTS AND CONCLUSIONS Measurements were acquired from 252 sites, of which 51 were pathologically classified as SCC. Optical biomarkers exhibited statistical differences between malignant and normal samples. Contrast was enhanced when parsing tissues by morphological classification rather than anatomical subtype for unpaired comparisons. Corresponding linear discriminant models using multiple optical biomarkers showed improved predictive ability when accounting for morphological classification, particularly in node-positive lesions. The false-positive rate was retrospectively found to decrease by 34.2% in morphologically- vs. anatomically-derived predictive models. In glottic tissue, the surgeon exhibited a false-positive rate of 45.7% while the device showed a lower false-positive rate of 12.4%. Additionally, comparisons of optical parameters were made to further understand the physiology of tumor staging and potential causes of high surgeon false-positive rates. Optical spectroscopy is a user-friendly, non-invasive tool capable of providing quantitative information to discriminate malignant from normal head and neck tissues. Predictive models demonstrated promising results for real-time diagnostics. Furthermore, the strategy described appears to be well suited to reduce the clinical false-positive rate.

Diffuse Reflectance Spectral Imaging for Breast Tumor Margin Assessment

Diffuse reflectance spectroscopy has been previously explored as a promising method for providing real-time visual maps of tissue composition to help surgeons determine breast lumpectomy margins and to ensure the complete removal of a tumor during surgery. We present the simple design, validation, and implementation of a compact and cost-effective spectral imaging system for the application of tumor margin assessment. Our new system consists of a broadband source with bandpass filters for illumination and a fabricated custom 16-pixel photodiode imaging array for the detection of diffuse reflectance. The system prototype was characterized in tissue-mimicking phantoms and has an SNR of greater than 40 dB in phantoms, animals, and human tissue. We show proof-of-concept for performing fast, wide-field spectral imaging with a simple, inexpensive design. The strategy also allows for the scaling to higher pixel number and density in future iterations of the system.

A custom wide-field spectral imager for breast cancer margin assessment

A custom imaging array optimized for wide-field diffuse reflectance spectroscopy imaging for breast cancer margin diagnosis has been designed and implemented, with improvements over a previously reported system.

Rapid Determination of Tissue Hemoglobin Concentration and Oxygen Saturation of Head and Neck Cancers for Global Health Applications

A ratiometric method for quantitative estimation of tissue hemoglobin concentration and oxygen-saturation is presented. A 600X speed-up was achieved on clinical diffuse reflectance data relative to an inverse Monte Carlo with comparable accuracy.