The I-SPY 1 TRIAL demonstrated that functional tumor volume (FTV) measured by dynamic contrast-enhanced (DCE) MRI during neoadjuvant chemotherapy (NAC) predicts both pathologic complete response (pCR) and recurrence free survival 1,2 . In addition to DCE, the I-SPY 2 TRIAL is testing whether diffusion weighted MRI (DW-MRI), a non-contrast method that characterizes water mobility and cellularity by measuring the apparent diffusion coefficient (ADC), acquired during the same MRI exam as DCE, can provide valuable distinct information about tumor response. We hypothesize that combining FTV and ADC can improve the predictive performance of breast MRI.
Background: Studies of 3D cell cultures have shown that mammary epithelial cell growth and morphogenesis is regulated by extracellular matrix (ECM) stiffness, linking ECM stiffening to malignant transformation. Tumors are consistently stiffer than normal adjacent tissue, and matrix stiffening is caused by ECM cross-linking and increased deposition of collagen. Some evidence suggests that collagen orientation at tumor boundaries can promote tumor metastasis. Measuring the stiffness of the tumor boundaries and adjacent stromal tissue may give additional information 1) about tumor microenvironment and 2) to guide treatment. Diffusion-weighted imaging (DWI) MRI measures the mobility of water in tissue and may be sensitive to this phenomenon. Material and Methods: MRI data was collected on patients with locally advance breast cancer enrolled in an IRB-approved study at UCSF and signed informed consent. In addition to a standard dynamic contrast enhanced (DCE) MRI, a high-resolution diffusion-weighted image (HR DWI) was acquired with an echo planar imaging sequence and the following parameters: TR/TE=4000/64.8 ms, b=0,600, FOV=70×140mm, matrix=28×64, and voxel size=0.55×0.55×4.0mm. Apparent diffusion coefficient (ADC) maps were created. HR DWI images were segmented into tumor and non-enhancing, surrounding stromal tissue. A proximity mapping method was used to measure ADC values at the inner edge of tumor and at increasing distances from the tumor boundary on HR DWI. The mean was calculated for the voxels in 1 mm increments, starting at 5 mm into the tumor (−5 mm) and ending at 2.5 cm away from the tumor (25 mm). Results: The average of the changes per 1 mm shell was largest for the transition of the tumor boundary (Table 1). In Table 1, the −5 to 0 mm, 0 to 5 mm, and 5 to 25 mm columns represent inside the tumor, tumor boundary, and outside the tumor, respectively. In general, ADC values were consistently lower inside the tumor than outside. The greatest changes per 1 mm shell was seen in the transition from inside to outside tumor, although the values varied among tumor types. Each of the three cases analyzed had different patterns of ADC values. Discussion: These preliminary studies show that water mobility measurements change at the tumor boundary, with different patterns observed among individual patients. We are further investigating the influence of density and tumor margin morphology on these ADC measurements. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-09-12.
Background: Diffusion weighted magnetic resonance imaging (DWI) is a non-invasive technique that is sensitive to tissue microstructure. Previous studies have shown that DWI adds positive predictive value in diagnostic studies of breast cancer and it has been shown to predict tumor response to neoadjuvant chemotherapy. While DWI shows promise for evaluating breast cancer, the technique suffers from limitations. Specifically, image distortion is common with the echo planar sequence available for DWI on clinical scanners, and spatial resolution is lower than that of other MRI sequences. Our group has optimized a high-resolution reduced field-of-view DWI acquisition, originally developed for the spine by Saritas et al., for breast imaging. The goal of this work was to compare high resolution (hr)-DWI) to standard resolution (std)-DWI for characterizing breast tumors. Methods: Patients undergoing neoadjuvant chemotherapy were scanned with MRI before, during and after neoadjuvant chemotherapy as part of IRB-approved studies at our institution. Nine women were scanned with both hr-DWI and std-DWI before and after one cycle of chemotherapy. Apparent diffusion coefficient (ADC) maps were calculated from hr-DWI and std-DWI data using previously described methods. One tumor region of interest (ROI) was defined on the hr-DWI slice estimated to contain the largest tumor area. This tumor ROI was then applied to the corresponding slice and location on the std-DWI and hr-DWI ADC maps. Mean tumor ADC as well as 15th, 25th, 50th, 75th, and 90th percentile ADCs were calculated for both DWI acquisitions for all subjects. Results: The mean tumor ADC values measured prior to treatment were similar for the hr-DWI and std-DWI acquisitions, however there was a significant difference between hr- and std-DWI 15th and 25th percentile ADC values (p= 0.0495, p=0.0717) For the early treatment time point, significant differences between the two DWI acquisitions were found for: mean tumor ADC, 15th, 25th, and 50th percentiles (p=0.0302, 0.0075, 0.0212, and 0.0488, respectively), with the most significant difference found for the lowest (15th) percentile measured. Tumor hr-DWI ADCs were consistently lower than std-DWI ADCs. Discussion: These data show that although the mean ADC values calculated from the pre-treatment hr-DWI and std-DWI are similar, the lower percentile (15th, and 25th) ADC values are significantly lower for the hr-DWI acquisition. Our results also showed larger difference in lower percentile ADC values between the two sequences after one cycle of chemotherapy. The differences in the lower percentile ADC values calculated from the hr-DWI are consistent with reduced partial voluming between viable tumor tissue, which is characterized low ADC values, and normal fibroglandular tissue. This may be particularly important for post-treatment ADC measurements where tumor size may decrease, potentially making partial volume effects more pronounced. Continuing studies are evaluating the relationship between low percentile ADC values from hr-DWI and tumor stage and response to treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-08-06.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.