Research Highlights

Diffuse optical spectroscopy (DOS) and imaging are emerging diagnostic techniques that quantitatively measure the concentration of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctO2Hb), water (ctH2O), and lipid in cm-thick tissues. In early-stage clinical studies, DOS and diffuse optical imaging have been used to characterize breast tumor biochemical composition and monitor therapeutic response in stage II/III neoadjuvant chemotherapy patients. We investigated whether DOS measurements obtained before and 1 week into a 3-month adriamycin/cytoxan neoadjuvant chemotherapy regimen can predict final, postsurgical pathological response. Baseline DOS measurements of 11 patients before therapy revealed statistically significant increases in tumor ctHHb, ctO2Hb, ctH2O, and spectral scattering exponent, and decreases in bulk lipids, relative to normal breast tissue. Tumor concentrations of ctHHb, ctO₂Hb, and ctH₂O dropped 27 ± 15%, 33 ± 7%, and 11 ± 15%, respectively, within 1 week (6.5 ± 1.4 days) of the first treatment for pathology-confirmed responders (n = 6), whereas nonresponders (n = 5) and normal side controls showed no significant changes in these parameters. The best single predictor of therapeutic response 1 week post treatment was ctHHb (83% sensitivity, 100% specificity), while discrimination analysis based on combined ctHHb and ctH₂O changes classified responders vs. nonresponders with 100% sensitivity and specificity. In addition, the pretreatment tumor-to-normal ctO₂Hb ratio was statistically significantly higher in responders (2.82 ± 0.44) vs. nonresponders (1.82 ± 0.49). These results highlight DOS and sensitivity to tumor cellular metabolism and biochemical composition and demonstrate its potential for predicting and monitoring an individual's response to treatment.

Figure 1 Typical DOS measurement geometry, defining the optical linescan taken over a known tumor location. Complete NIR absorption and scattering spectra are measured at each location.

Figure 2 NIR (a) absorption and (b) reduced scattering spectra obtained non-invasively from a 30 mm diameter tumor in the breast of a neoadjuvant chemotherapy subject. The heightened absorption results from a combination of increased hemoglobin and water relative to normal breast tissue (left panel). The sharp spectral decrease in scattering for tumor tissue is likely due to increases in both cellular density and fibrous tissue in tumor tissue relative to normal breast tissue (right panel). Tumor spectra were obtained from the +10 mm position, whereas the normal spectra were taken from the corresponding contralateral position on the normal side. Error bars are the variation from two independent linescans (plotted every 50 nm for clarity).

Figure 3 Linescan results of (a) ctH₂O and (b) ctHHb from the same patient in the previous figure. NIR spectra at each linescan location are used to calculate NIR absorber concentrations at each spatial location. Error bars are the variations between two independent linescans.

Figure 4 Plots of changes in tumor ctHHb, ctO₂Hb, ctH₂O, and stO₂ for ndividual patients, stratified by final pathological response. The plotted value is the average of the DOS parameter within the FWHM. The "Baseline" and "~ 1 Week" points correspond to the measurements taken within 1 week prior and within 1 week after the start of therapy, respectively. Responder changes are distinctive from nonresponders. Error bars for the individual measurements are not presented for clarity (5-10%).

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