Combined Optical and MRI Imaging for Breast Cancer

Institution: University of California, Irvine
Investigator(s): Sean Merritt, B.S. -
Award Cycle: 2003 (Cycle IX) Grant #: 9GB-0085 Award: $58,304
Award Type: Dissertation Award
Research Priorities
Detection, Prognosis and Treatment>Imaging, Biomarkers, and Molecular Pathology: improving detection and diagnosis

Initial Award Abstract (2003)
Recent studies have brought questions to the benefits of performing regular mammograms because of their exposure to harmful ionizing radiation and lack of effectiveness. Other problems with current detection techniques include (i) the inability of mammography to penetrate dense breast tissue in younger women, (ii) both ultrasound and mammography provide structural images but no physiological, cancer-associated information of the breast, and (iii) mammography is associated with discomfort due to breast compression. Our laboratory has been exploring a novel optics-based method, called Diffuse Optical Tomography (DOT). This technology allows for the determination of oxy- and deoxy- hemoglobin, water, and fat content within the breast tissue that is probed by light. The probe is non-invasive, hand-held, and does not involve compression. These measurements can also be obtained on denser, pre-menopausal breast tissue.

The aims of this project are to combine the benefits of DOT and ultrasound to provide a more functional image that is not available using either imaging technique alone. The combined DOT/ultrasound probe will be built by attaching a new optical probe directly to an existing ultrasound probe. Software will be developed for the new probe that will provide a two-dimensional image that overlaps directly with the current ultrasound images used in breast cancer imaging. Two separate imaging models for the DOT instrument will be implemented. One is a standard model and the other is a novel technique developed by our collaborators. The two models will be directly compared to determine which is ideal for a clinical environment. Validation of the new instrument and software will be performed on tissue phantoms, which will simulate the optical properties of a tumor imbedded in breast. The final step will be to apply the technology to an actual breast tumor in a human subject. Our group is currently monitoring tumors during chemotherapy treatment, and we plan to phase-in the new instrument to these ongoing clinical trials.

The novel elements of the project are to combine ultrasound with DOT in such a way as to produce a more accurate, functional image of breast tumors. First, localizing the tumor with ultrasound will help produce the highest contrast DOT image. Second, using ultrasound to define the tumor structure will allow for a more accurate reconstructed optical image. We will also be able to produce physiologically relevant images of water and fat in breast tissue and tumors, which other researchers in our field are unable to obtain.

Final Report (2005)
Notes: The CBCRP approved a change in aims for this grant. The original project focused on using ultrasound as the companion technology for optical imaging. However, the PI and laboratory switched to MRI (magnetic resonance imaging) as the new companion technology in the first project year. In 2004, the CBCRP funded a 3-yr translational project to Mr. Merritt's mentor, Dr. Bruce Tromberg, and Dr. Nola Hylton at UCSF to expand the development of the optical-MRI approach.

The overall goal of this project was the continued development of an emerging optical technique, called diffuse optical spectroscopy (DOS), that has great promise as a medical imaging device. Such an instrument will improve early detection by offering a low cost, portable, safe measurement technique that is rich with functional information and can penetrate mammographically dense breast tissue, a characteristic of pre-menopausal women. The optical instrument has been extensively validated in "tissue phantoms", but validation in vivo requires comparison with a medical imaging "gold standard", which is magnetic resonance imaging (MRI).

The funding provided by the CBCRP has produced validation measurements of our DOS instrument through a comparison to MRI by measuring emulsion phantoms that are comprised of water and fat. This was followed in the second year with validation measurements in vivo that compared water and fat measured with both techniques in the lower leg of a human subject. Further development of broadband DOS include new algorithms developed for tissue bound water measurements and deep tissue measurements. Both of these new techniques are applicable to breast cancer characterization. Bound water provides contrast between normal and cancerous tissue through the differences in the water content and provides sensitivity to different tissue water compartments. We measured a “lower bound water fraction” in tumor that in normal breast tissue which was expected from the MRI literature. Finally, the ability to measure tissue temperature is applicable to breast cancer thermal therapies. A non-invasive deep tissue temperature monitor would be valuable as a temperature feedback for microwave treatment during hyperthermia. Using DOS we were able to measure tissue temperature within 1 degree C in an animal model.

Future studies will involve validation of the bound water measurements through a comparison of DOS with MRI. Also, monitoring bound water during therapies may provide an improved method of determining treatment efficacy similar to “diffusion weighted” MRI.

Comparison of Water and Lipid Content Measurements Using Diffuse Optical Spectroscopy and MRI in Emulsion Phantoms Cancer Research & Treatment 2:563-569, Dec. 2003.
Periodical:Technology in Cancer Research and Treatment
Index Medicus:
Authors: Merritt S, Gulsen G, Chiou G, Chu Y, Deng C, Cerussi AE, Durkin AJ, Tromberg BJ, Nalcioglu
Yr: 2003 Vol: 2 Nbr: 6 Abs: Pg:563-9