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Open Access Publications from the University of California

Scholarly Works (42 results)

  • Article
  • Peer Reviewed
ICTS Publications (2010)

Diffuse optical spectroscopy (DOS), which is used to image tumor metabolic response to neoadjuvant chemotherapy (NAC), shows large changes in tumor functional parameters with significant reductions in oxy- and deoxyhemoglobin for responders versus nonresponders. Although investigational, DOS may provide a cost-effective, risk-free method for optimizing NAC drug and dosing strategies for individual patients.

    Cover page: Imaging breast cancer chemotherapy response with light. Commentary on Soliman et al., p. 2605.Creative Commons 'BY' version 4.0 license
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2010)
    Diffuse optical spectroscopy (DOS), which is used to image tumor metabolic response to neoadjuvant chemotherapy (NAC), shows large changes in tumor functional parameters with significant reductions in oxy- and deoxyhemoglobin for responders versus nonresponders. Although investigational, DOS may provide a cost-effective, risk-free method for optimizing NAC drug and dosing strategies for individual patients.
      Cover page: Imaging Breast Cancer Chemotherapy Response with LightCreative Commons 'BY' version 4.0 license
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2010)
      Diffuse optical imaging (DOI) is a model-based technique used for noninvasive characterization of subsurface tissue function and structure. Compared to more common transmission geometries, reflectance DOI has the advantage of being portable and easily implemented in a clinical setting. However, reflectance measurements are generally not compatible with conventional DOI image reconstruction methods because they typically provide a limited number of unique tissue views. In this paper, we describe a fast and reliable DOI image reconstruction method based on parameterization of tissue and tumor optical contrast, using physiological a priori knowledge. The reconstruction method is formulated within the general Bayesian inversion framework and is capable of handling both model and measurement errors. Simulations are carried out to illustrate the application of this approach, using a limited number of source-detector combinations. It is also shown that parametric reflectance DOI is robust to model misspecifications and measurement noise.
        Cover page: Parametric Diffuse Optical Imaging in Reflectance GeometryCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2006)
        We present noninvasive, quantitative in vivo measurements of methemoglobin formation and reduction in a rabbit model using broadband diffuse optical spectroscopy (DOS). Broadband DOS combines multifrequency frequency-domain photon migration (FDPM) with time-independent near infrared (NIR) spectroscopy to quantitatively measure bulk tissue absorption and scattering spectra between 600 nm and 1,000 nm. Tissue concentrations (denoted by brackets) of methemoglobin ([MetHb]), deoxyhemoglobin ([Hb-R]), and oxyhemoglobin ([HbO2]) were determined from absorption spectra acquired in "real time" during nitrite infusions in nine pathogen-free New Zealand White rabbits. As little as 30 nM [MetHb] changes were detected for levels of [MetHb] that ranged from 0.80 to 5.72 microM, representing 2.2 to 14.9% of the total hemoglobin content (%MetHb). These values agreed well with on-site ex vivo cooximetry data (r2= 0.902, P < 0.0001, n = 4). The reduction of MetHb to functional hemoglobins was also carried out with intravenous injections of methylene blue (MB). As little as 10 nM changes in [MB] were detectable at levels of up to 150 nM in tissue. Our results demonstrate, for the first time, the ability of broadband DOS to noninvasively quantify real-time changes in [MetHb] and four additional chromophore concentrations ([Hb-R], [HbO2], [H2O], and [MB]) despite significant overlapping spectral features. These techniques are expected to be useful in evaluating dynamics of drug delivery and therapeutic efficacy in blood chemistry, human, and preclinical animal models.
          Cover page: Noninvasive in vivo monitoring of methemoglobin formation and reduction with broadband diffuse optical spectroscopyCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (1995)
          We have measured the optical absorption and scattering coefficient spectra of a multiple-scattering medium (i.e., a biological tissue-simulating phantom comprising a lipid colloid) containing methemoglobin by using frequency-domain techniques. The methemoglobin absorption spectrum determined in the multiple-scattering medium is in excellent agreement with a corrected methemoglobin absorption spectrum obtained from a steady-state spectrophotometer measurement of the optical density of a minimally scattering medium. The determination of the corrected methemoglobin absorption spectrum takes into account the scattering from impurities in the methemoglobin solution containing no lipid colloid. Frequency-domain techniques allow for the separation of the absorbing from the scattering properties of multiple-scattering media, and these techniques thus provide an absolute measurement of the optical absorption spectra of the methemoglobin/lipid colloid suspension. One accurately determines the absolute methemoglob in absorption spectrum in the frequency domain by extracting the scattering and absorption coefficients from the phase shift Φ and average light intensity DC (or Φ and the amplitude of the light-intensity oscillations AC) data with relationships provided by diffusion theory, but one determines it less accurately by using the Φ and modulation M (M ≡ AC/DC) data and the diffusion theory relationships. In addition to the greater uncertainty in the absorption and scattering coefficients extracted from the Φ and M data, the optical parameters extracted from the Φ and M data exhibit systematically inaccurate behavior that cannot be explained by random noise in the system. Possible reasons for the systematically lower accuracy of the methemoglobin absorption spectrum obtained from Φ and M data are discussed.
            Cover page: Frequency-domain method for measuring spectral properties in multiple-scattering media: methemoglobin absorption spectrum in a tissuelike phantom.Creative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2008)
            Little is known about the relationship between anatomic and functional contrast derived from intrinsic optical signals. In order to address this relationship, finite-element (FEM) forward simulations were compared to diffuse optical spectroscopy (DOS) reflectance measurements obtained from 10 breast tumor patients. Clinical ultrasound images were used to estimate anatomical tumor size and depth for the FEM simulations. Actual DOS-measured tumor absorption could not be matched by forward model simulations when tumor size was constrained to match ultrasound dimensions. However, agreement was achieved when the lesion was viewed as a distribution of optical properties (i.e., an extended target). This result suggests that the spatial extent of optical contrast in breast tumors may be significantly greater than anatomical dimensions reported by standard imaging modalities. Analysis indicates that invasive breast tumors with anatomical dimensions of 1 cm may still be detectable at depths of 30 mm or more (the center of the lesion to the surface of tissue) using DOS in a reflectance geometry.
              Cover page: Assessing the spatial extent of breast tumor intrinsic optical contrast using ultrasound and diffuse optical spectroscopyCreative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2010)

              Rationale and objectives

              Imaging tumor response to neoadjuvant chemotherapy in vivo offers unique opportunities for patient care and clinical decision-making. Detailed imaging studies may allow oncologists to optimize therapeutic drug type and dose based on individual patient response. Most radiologic methods are used sparingly because of cost; thus, important functional information about tumor response dynamics may be missed. In addition, current clinical standards are based on determining tumor size changes; thus, standard anatomic imaging may be insensitive to early or frequent biochemical responses. Because optical methods provide functional imaging end points, our objective is to develop a low-barrier-to-access bedside approach that can be used for frequent, functional assessment of dynamic tumor physiology in individual patients.

              Materials and methods

              Diffuse Optical Spectroscopic Imaging (DOSI) is a noninvasive, bedside functional imaging technique that quantifies the concentration and molecular state of tissue hemoglobin, water, and lipid. Pilot clinical studies have shown that DOSI may be a useful tool for quantifying neoadjuvant chemotherapy response, typically by comparing the degree of change in tumor water and deoxy-hemoglobin concentration before and after therapy. Patient responses at 1 week and mid-therapy have been used to predict clinical outcome. In this report, we assess the potential value of frequent DOSI monitoring by performing measurements on 19 different days in a 51-year-old subject with infiltrating ductal carcinoma (initial tumor size 60 x 27 mm) who received neoadjuvant chemotherapy (anthracyclines and bevacizumab) over an 18-week period.

              Results

              A composite index, the Tissue Optical Index (TOI), showed a significant ( approximately 50%) decrease over the nearly 18 weeks of chemotherapy. Tumor response was sensitive to the type of chemotherapy agent, and functional indices fluctuated in a manner consistent with dynamic tumor physiology. Final pathology revealed 4 mm of residual disease, which was detectible by DOSI at the conclusion of chemotherapy before surgery.

              Conclusion

              This case study suggests that DOSI may be a bedside-capable tool for frequent longitudinal monitoring of therapeutic functional response to neoadjuvant chemotherapy.
                Cover page: Frequent Optical Imaging during Breast Cancer Neoadjuvant Chemotherapy Reveals Dynamic Tumor Physiology in an Individual PatientCreative Commons 'BY' version 4.0 license
                • Article
                • Peer Reviewed
                ICTS Publications (2011)

                Diffuse optical spectroscopic imaging (DOSI) non-invasively and quantitatively measures tissue haemoglobin, water and lipid. Pilot studies in small groups of patients demonstrate that DOSI may be useful for longitudinal monitoring and predicting breast cancer neoadjuvant chemotherapy pathological response. This study evaluates the performance of a bedside DOSI platform in 34 breast cancer patients followed for several months. DOSI optical endpoints obtained at multiple timepoints are compared with final pathological response. Thirty-six stage II/III breast cancers (34 patients) were measured in vivo with DOSI prior to, in the middle of and after the completion of pre-surgical neoadjuvant chemotherapy. Cancer therapies ranged from standard anthracyclines to targeted therapies. Changes in DOSI-measured parameters at each timepoint were compared against final surgical pathology. Absolute changes in the tumour-to-normal (T/N) ratio of tissue deoxyhaemoglobin concentration (ctHHb) and relative changes in the T/N ratio of a tissue optical index (TOI) were most sensitive and correlate to pathological response. Changes in ctHHb and TOI were significantly different between tumours that achieved pathological complete response (pCR) versus non-pCR. By therapy midpoint, mean TOI-T/N changes were 47±8 versus 20±5 per cent for pCR versus non-pCR subjects, respectively (Z=0.011). Changes in ctHHb and TOI scaled significantly with the degree of pathological response (non-, partial and complete). DOSI measurements of TOI separated pCR from non-pCR by therapy midpoint regardless of drug or dosing strategy. This approach is well suited to monitoring breast tumour response and may provide feedback for optimizing therapeutic outcomes and minimizing side-effects.

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                Cover page: Diffuse optical spectroscopic imaging correlates with final pathological response in breast cancer neoadjuvant chemotherapy.
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2013)
                Abstract Introduction Radiographic density adversely affects the performance of X-ray mammography and can be particularly problematic in younger and high-risk women. Because of this limitation, there is significant ongoing effort to develop alternative cancer screening and detection strategies for this population. This pilot study evaluates the potential of Diffuse Optical Spectroscopic Imaging (DOSI) to image known tumors in dense breast tissue. Methods We performed a retrospective analysis on 24 radiographically dense breast cancer subjects measured with DOSI over a four-year period (Breast Imaging Reporting and Data System - BI-RADS, category 3 and 4, average age = 39 ± 7.6, average maximum size 31 ± 17 mm). Two previously-described DOSI contrast functions, the tissue optical index (TOI) and the specific tumor component (STC), which are based upon the concentrations and spectral signatures of hemoglobin, water and lipids, respectively, were used to form 2D optical images of breast tumors. Results Using TOI and STC, 21 out of 24 breast tumors were found to be statistically different from the surrounding highly vascularized dense tissue and to be distinguishable from the areolar region. For these patients, the tumor to normal contrast was 2.6 ± 1.2 (range 1.3 to 5.5) and 10.0 ± 7.5 (range 3.3 to 26.4) for TOI and STC, respectively. STC images were particularly useful in eliminating metabolic background from the retroareolar region which led to identification of two out of four retroareolar tumors. Conclusions Using both the abundance and the disposition of the tissue chromophores recovered from the DOSI measurements, we were able to observe tumor contrast relative to dense breast tissue. These preliminary results suggest that DOSI spectral characterization strategies may provide new information content that could help imaging breast tumors in radiographically dense tissue and in particular in the areolar complex.
                  Cover page: Assessing tumor contrast in radiographically dense breast tissue using Diffuse Optical Spectroscopic Imaging (DOSI)
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (1997)
                  In recent years researchers have made significant progress in understanding the physics of fluorescence in highly scattering materials such as tissues in the near-infrared. We have quantitatively verified a model which describes fluorescence in ideal (homogeneous and infinite) tissue-like media. Given the quantitative accuracy of this model, one can use measurements of the fluorescence of a tissue with a homogeneous distribution of fluorophore to obtain the quantum yield, lifetime of the probe, and the absorption and scattering coefficients of the tissue at the fluorescent wavelength. We demonstrate that this can be done with a simple measurement of the photon density as a function of source-detector separation at the excitation and emission wavelengths. To verify our approach we present the lifetime, quantum yield of the fluorescent probe (rhodamine B), and the absorption and scattering coefficients of the medium at the emission peak wavelength that are obtained by a fit of the model to experimental measurements.
                    Cover page: Experimental recovery of absorption, scattering, and fluorescence parameters in highly scattering media from a single frequency measurementCreative Commons 'BY' version 4.0 license
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