Functional Breast MRI with BOLD Contrast

Institution: Stanford University
Investigator(s): Rebecca Rakow-Penner, M.S. -
Award Cycle: 2008 (Cycle 14) Grant #: 14GB-0004 Award: $75,994
Award Type: Dissertation Award
Research Priorities
Detection, Prognosis and Treatment>Imaging, Biomarkers, and Molecular Pathology: improving detection and diagnosis



Initial Award Abstract (2008)

Early detection of breast cancer currently stands as one of the best defenses to the disease, with magnetic resonance imaging (MRI) becoming an increasingly more valuable technology. Currently, MRI diagnostic protocols use Dynamic Contrast Enhanced (DCE) MRI, requiring intravenous injection of a contrast agent, such as Gadolinium. This helps distinguish malignant areas of the breast by highlighting unusual morphology and depicting areas with increased perfusion of blood. Unfortunately, MRI is associated with many “false positives” leading to unnecessary biopsies. Beyond DCE-MRI, new approaches, such as functional MRI (fMRI), detect hemodynamic variation in a tissue due to changes in oxygenation using a method called Blood Oxygen Level Dependent (BOLD) contrast. Traditionally, this technique has been used to study the brain, but has the potential to evaluate tumor metabolism and angiogenesis. Variations in oxygenation may give insight on tumor types, predict susceptibility to anti-angiogenic therapeutics, and monitor chemotherapeutics. To date, no major study has been published which evaluates fMRI BOLD contrast in healthy and malignant human breast tissue. We plan to evaluate BOLD contrast in the breast by stimulating tissue oxygenation with a breathing protocol where we can vary the oxygen intake.

To validate our fMRI BOLD contrast breast imaging, we plan to first develop a robust methodology for detecting BOLD contrast in the breasts of healthy volunteers. BOLD contrast has previously been used to evaluate brain function and its application to the breast poses several challenging adaptations. Three of the challenges we plan to address include: (1) determining the best way to stimulate a variation in oxygen flow through the breast, (2) evaluating the effects of menstrual cycle on BOLD contrast in the breast, and (3) separating the glandular tissue and lipid oxygen measurements in the breast. Once a robust method has been developed, we will evaluate the technology on a small cohort of breast cancer patients at Stanford Hospital. This project also involves collaborations with radiologists and medical physics experts at Stanford University and the University of California, San Francisco.

Determining breast tumor oxygen metabolism with BOLD contrast MRI will provide a non-invasive technique that complements MRI’s utility in breast imaging. BOLD contrast MRI in the breast has the potential to improve the specificity of MRI in detecting tumors, predict therapy response, and monitor therapy response.




Final Report (2010)

Blood oxygen level dependent (BOLD) contrast MRI has the potential to non-invasively detect breast tumor oxygenation. This information may help characterize tumors, predict susceptibility to treatment, and monitor chemotherapeutic response. We have developed a robust methodology for detecting BOLD contrast on healthy volunteers and evaluated the method on 3 breast cancer patients.

For this study, we focused on optimizing how to acquire BOLD contrast in the breast and began to understand the results. First, a single shot fast spin echo (SSFSE) sequence was compared to a gradient echo (GRE) pulse sequence for data acquisition. In order to induce changes in oxygenation, it was necessary to alter the systemic oxygenation of the patients and volunteers. Thus, we evaluated 3 hyperoxic stimuli on 15 healthy volunteers to determine the stimulus with the strongest response in the breast: air interleaved with carbogen (95% O2, 5% CO2), air interleaved with oxygen, and oxygen interleaved with carbogen. The stimulus which produced the best results across all the volunteers was then used for the patient study.

Our results indicated that an SSFSE pulse sequence produced significant BOLD contrast results in the breast compared to a GRE pulse sequence and that oxygen interleaved with carbogen yielded the best results in healthy volunteers. We also noted that BOLD contrast in healthy glandular breast tissue positively correlates to carbogen and breast cancer negatively correlates to carbogen. Thus, it is possible to detect changes in breast cancer oxygenation with MRI.

In conclusion, we have developed a robust protocol for detecting changes in breast cancer oxygenation with MRI. Future research involves testing the protocol on a larger population.




Symposium Abstract (2010)

Rebecca Rakow-Penner, MS1, Bruce Daniel, MD1, and Gary H. Glover, PhD1 Stanford University School of Medicine, Department of Radiology

Goal: To detect tumor oxygenation in breast tissue with MRI.

Blood oxygen level dependent (BOLD) contrast MRI has the potential to non-invasively detect breast tumor oxygenation. This information may help characterize tumors, predict susceptibility to treatment, and monitor chemotherapeutic response. We have developed a robust methodology for detecting BOLD contrast on healthy volunteers and evaluated the method on 3 breast cancer patients.

For this study, we focused on optimizing how to acquire BOLD contrast in the breast and began to understand the results. First, a single shot fast spin echo (SSFSE) sequence was compared to a gradient echo (GRE) pulse sequence for data acquisition. In order to induce changes in oxygenation, it was necessary to alter the systemic oxygenation of the patients and volunteers. Thus, we evaluated 3 hyperoxic stimuli on 15 healthy volunteers to determine the stimulus with the strongest response in the breast: air interleaved with carbogen (95% O2, 5% CO2), air interleaved with oxygen, and oxygen interleaved with carbogen. The stimulus which produced the best results across all the volunteers was then used for the patient study.

Our results indicated that an SSFSE pulse sequence produced significant BOLD contrast results in the breast compared to a GRE pulse sequence and that oxygen interleaved with carbogen yielded the best results in healthy volunteers. We also noted that BOLD contrast in healthy glandular breast tissue positively correlates to carbogen and breast cancer negatively correlates to carbogen. Thus, it is possible to detect changes in breast cancer oxygenation with MRI.

In conclusion, we have developed a robust protocol for detecting changes in breast cancer oxygenation with MRI. Future research involves testing the protocol on a larger patient population. Impact: Detecting tumor oxygenation with BOLD MRI may provide a biomarker for evaluating whether a patient will respond to antiangiogenic therapy.



Detecting blood oxygen level-dependent (BOLD) contrast in the breast.
Periodical:Journal of Magnetic Resonance Imaging
Index Medicus: J Magn Reson Imaging
Authors: Rakow-Penner R, Daniel B, Glover GH
Yr: 2010 Vol: 32 Nbr: 1 Abs: Pg:120-9