The prospective multi-center ACRIN 6691 trial was designed to evaluate whether changes from baseline to mid-therapy in a Diffuse Optical Spectroscopic Imaging (DOSI)-derived imaging endpoint, the Tissue Optical Index (TOI), predict pathologic complete response (pCR) in women undergoing breast cancer neoadjuvant chemotherapy (NAC). DOSI instruments were constructed at the University of California, Irvine and delivered to 6 institutions where 60 subjects with newly-diagnosed breast tumors (at least 2 cm in the longest dimension) were enrolled over a 2-year period. Bedside DOSI images of the tissue concentrations of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctHbO2), water (ctH2O), lipid, and TOI (ctHHb × ctH2O/lipid) were acquired on both breasts up to 4 times during NAC treatment: baseline, one-week, mid-point, and completion. Of the 34 subjects (mean age 48.4 ± 10.7 years) with complete, evaluable data from both normal and tumor-containing breast, 10 (29%) achieved pCR as determined by central pathology review. The percent change in tumor to normal TOI ratio (%TOITN) from baseline to mid-therapy ranged from −82% to 321%, with a median of −36%. Using pCR as the reference standard and receiver-operating characteristic curve methodology, %TOITN AUC was 0.60 (95% CI 0.39 to 0.81). In the cohort of 17 patients with baseline tumor oxygen saturation (%StO2) greater than the 77% population median, %TOITN AUC improved to 0.83 (95% CI 0.63 to 1.00). We conclude that the combination of baseline functional properties and dynamic optical response shows promise for clinical outcome prediction.

Structural changes in water molecules are related to physiological, anatomical and pathological properties of tissues. Near infrared (NIR) optical absorption methods are sensitive to water, however detailed characterization of water in thick tissues is difficult to achieve because subtle spectral shifts can be obscured by multiple light scattering. In the NIR, a water absorption peak is observed around 975nm. The precise NIR peak shape and position is highly sensitive to water molecular disposition. We introduce a Bound Water Index (BWI) that quantifies shifts observed in tissue water absorption spectra measured by broadband Diffuse Optical Spectroscopy (DOS). DOS quantitatively measures light absorption and scattering spectra and therefore reveals bound-water spectral shifts. BWI as a water state index was validated by comparing broadband DOS to Magnetic Resonance Spectroscopy, diffusion-weighted MRI and conductivity in bound water tissue phantoms. Non-invasive DOS measurements of malignant and normal breast tissues performed in 18 subjects showed a significantly higher fraction of free water in malignant tissues (p<0.0001) compared to normal tissues. BWI of breast cancer tissues inversely correlated with Nottingham-Bloom-Richardson histopathology scores. These results highlight broadband DOS sensitivity to molecular disposition of water, and demonstrate the potential of BWI as a non-invasive in-vivo index that correlates with tissue pathology.

Independently driven four-probe method for local electrical characteristics in organic thin-film transistors under controlled channel potential Rev. Sci. Instrum. 82, 093902 (2011); 10.1063/1.3637489 Integration of reduced graphene oxide into organic field-effect transistors as conducting electrodes and as a metal modification layer Appl. Phys. Lett. 95, 023304 (2009); 10.1063/1.3176216 Impact of semiconductor/contact metal thickness ratio on organic thin-film transistor performance Appl. Phys. Lett. 92, 153305 (2008);

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We have studied the coadsorption of NH 3 molecules on the Si͑001͒ surface using scanning tunneling microscopy. Three adsorption patterns are predominantly observed to be attributed to two NH 3 molecules dissociated into NH 2 and H. The most abundant one is a zigzag pattern where the dissociated NH 2 groups reside on the alternating sides of a dimer row, which is followed by a combined adsorption of the on-dimer and the inter-dimer ͑ID͒ configuration. The last one is a linear pattern of the IDs. These observations suggest a substrate-mediated effective repulsion between NH 2 groups.