Sean Merritt

In vivo water state measurements in breast cancer using broadband diffuse optical spectroscopy

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 975 nm. The precise NIR peaks shape and position are 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.

Non-invasive tissue temperature measurements based on quantitative diffuse optical spectroscopy (DOS) of water

We describe the development of a non-invasive method for quantitative tissue temperature measurements using Broadband diffuse optical spectroscopy (DOS). Our approach is based on well-characterized opposing shifts in near-infrared (NIR) water absorption spectra that appear with temperature and macromolecular binding state. Unlike conventional reflectance methods, DOS is used to generate scattering-corrected tissue water absorption spectra. This allows us to separate the macromolecular bound water contribution from the thermally induced spectral shift using the temperature isosbestic point at 996 nm. The method was validated in intralipid tissue phantoms by correlating DOS with thermistor measurements (R=0.96) with a difference of 1.1+/-0.91 degrees C over a range of 28-48 degrees C. Once validated, thermal and hemodynamic (i.e. oxy- and deoxy-hemoglobin concentration) changes were measured simultaneously and continuously in human subjects (forearm) during mild cold stress. DOS-measured arm temperatures were consistent with previously reported invasive deep tissue temperature studies. These results suggest that DOS can be used for non-invasive, co-registered measurements of absolute temperature and hemoglobin parameters in thick tissues, a potentially important approach for optimizing thermal diagnostics and therapeutics.

Tissue bound water studies on breast tumors using diffuse optical spectroscopy

Differences in tissue water state have been measured in normal and malignant breast tissues. Broadband Diffuse Optical Spectroscopy (DOS) has been used to acquire 650-1000 nm absorption spectra of normal and tumor breast tissues from 7 patients in vivo. The absolute values of spectral differences between normalized tissue water spectra and pure water spectra were combined and divided by the number of points in the sum to form the bound water index (BWI). In all subjects, the average BWIs of line scan points were significantly lower in tumor tissues (1.62 ± 0.27 x10-3) than normal tissues (3.06 ±0.51 x10-3, Wilcoxon Ranked Sum Test z= 0.003 and power=0.98). These results imply that the water in tumors behaves more like free water than the water in normal tissue.