SEMINARS IN BIOMEDICAL ENGINEERING

Characterization of Water Molecular State in In-vivo Thick Tissues using Diffuse Optical Spectroscopic Imaging

So Hyun Chung

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 peak’s shape and position are highly sensitive to water molecular disposition. A bound water index (BWI) was developed that quantifies shifts observed in tissue water absorption spectra measured by broadband diffuse optical spectroscopic imaging (DOSI). DOSI 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 BWI measurements of malignant and normal tissues 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 histopathological scores.
The spectral features of a water absorption spectrum are affected by temperature and bound water simultaneously. In order to measure absolute temperature using the absorption spectrum, the bound water effect was corrected using the spectral features found during the BWI development and the NIR temperature isosbestic point at 996nm. As a result, DOSI measures absolute temperature with a difference of 1.10.91C from a thermistor. In-vivo forearms were measured during cold-stress using the developed algorithm, and the DOSI measured temperature was consistent with previously-reported invasively-measured deep tissue temperature.
Finally, the BWI was compared to Apparent Diffusion Coefficient (ADC) of diffusion weighted MRI in 9 breast cancer patients. ADC measures mobility of water molecules, mostly Brownian motion in a voxel. The BWI and ADC correlated (R=0.8, p=0.01) and both parameters decreased as the histopathological scores and bulk water content of the cancer increased. These results communicate that, in more invasive cancer, the diffusion is more restricted although the increased water content exists unbound to macromolecules. The developed BWI showed its potential as a non-invasive in vivo index for pathophysiology of breast cancer tissues.

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sponsored by

The Laser Microbeam and Medical Program (LAMMP)
a NIH biotechnology resource facility at the Beckman Laser Institute