Non-invasive detection and monitoring of tumor pathological grade during neoadjuvant chemotherapy by measuring tissue water state using diffuse optical spectroscopic imaging.
Authors: Chung S , Cerussi A , Mehta R , Hsiang D , Tromberg B 
Published: December 2010

Abstract #803

Background: Changes of tissue water state are related to physiological and pathological properties of breast tissues. For instance, MRI has measured water mobility in order to monitor local micro-structural changes in breast cancer tissues during chemotherapy. Diffuse Optical Spectroscopic Imaging (DOSI) measures water molecular vibrational states associated with macro-molecular complexes in tissues such as proteins. For DOSI measurements, breast tumors are line-scanned and spectral information on each point is spatially mapped to generate an image.&#x2028; Subjects & Methods: DOSI was employed to measure 15 infiltrating ductal carcinoma (IDC) patients before treatment. Five IDC and one infiltrating lobular carcinoma (ILC) tumors were also measured along the course of neoadjuvant chemotherapy. Patient responses were determined from standard pathology: complete (N=2), partial (N=2) and non-responders (N=2). The spectral features of tissue water absorption from 935 nm to 998nm were compared to those of a pure water spectrum measured at body temperature in order to acquire the Bound Water Index (BWI: the residual between tissue and pure water spectra). In spectroscopic images, the Cancer BWI Ratio (CBR) was calculated by counting the fraction of the BWI less than 20% of the BWI range of pre-chemo (baseline) measurement in a primary cancer. Lower BWI means the cancer has more free water. The CBR communicates the changes of tissue water state along the course of therapies in the similar way to Signal Enhanced Ratio (SER) used in contrast enhanced MRI.&#x2028; Results: In our in vivo clinical studies with 15 IDC tumors, a high inverse correlation between BWI and Nottingham Bloom-Richardson histopathological score (R=-0.87) was found. In the neoadjuvant chemotherapy studies, BWI increased during the entire course of the therapy in complete responders while it fluctuated then stayed close to baseline values in partial responders. In non-responders, the change amount of BWI was very small and the BWI values decreased below baseline values. Quantitatively, for complete responders, BWI increased (more bound water) 59% from baseline and CBR decreased (less pixels for cancer) 26.9% and the pixels presenting cancer property disappeared. In partial responders, BWI increased 4.7% and CBR decreased 8.2% whereas, in non-responders, BWI decreased 16.4% and CBR increased 28.7%.&#x2028; Discussion: The high correlation between BWI and histopathological score communicates that water state measurements using DOSI report on disease grades of breast cancer non-invasively. In the neoadjuvant chemotherapy studies, bigger tissue water state changes have been measured in complete than partial responders and the changes to the opposite direction in non-responders. There results demonstrate a potential of tissue water state with DOSI as a non-invasive pathological grade monitor during chemotherapy, which can be used as a substitute for a biopsy at any point during the treatment cycle.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 803.