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Apparent Diffusion Coefficient Using Diffusion Weighted MRI and Biochemical Correlates in Human Breast Cancer1Radiological Sciences, UCLA Geffen School of Medicine, Los Angeles, CA, United States, 2Surgery, UCLA Geffen School of Medicine, Los Angeles, CA, United States
Synopsis
Multiparametric MRI has been investigated in breast and prostate cancer, and other tumors. We evaluated diffusion weighted imaging in a pilot cohort of 20 malignant and 11 benign breast cancer patients, and 7 healthy women. MR spectra were recorded using an accelerated version of five dimensional echo-planar correlated spectroscopic imaging (5D EP-COSI). Significant decline in ADC values of malignant breast cancer compared to benign and healthy women. There was a negative correlation of choline with ADC values in malignant cancer patients. Our findings suggest that choline and lipids can be reliable biomarkers in addition to widely used ADC.
Introduction
During the last three decades, multiparametric MR imaging has been widely investigated in breast cancer1-3. Diffusion-weighted imaging (DWI) is one of MRI modalities to differentiate malignant from benign tumors using the DWI metric, namely apparent diffusion coefficient (ADC)4-8. The DWI has been widely investigated in breast cancer before and after neoadjuvant chemotherapy. Non-invasive biochemical characterization of metabolites such as choline and lipids has been accomplished in breast cancer using water suppressed MR Spectroscopy (MRS) and changes of choline and lipids in breast cancer has been investigated also using MRS9-12. In this project, we investigated DWI and multi-dimensional MR Spectroscopic Imaging (MRSI) in malignant and benign breast cancer patients and also in healthy women.Materials and Methods
We recruited 20 malignant (mean age of 53.2 years) and 11 benign (mean age of 36.7 years) breast cancer patients and 7 healthy women (mean age of 38.7 years). A 3T MRI scanner equipped with a 15 channel breast phased-array coil was used for this investigation. The DWI acquisition protocol included the following: 2D spin-echo echo-planar imaging (EPI) sequence (TR/TE of 3800/93ms; data matrix, 192 × 192; signal average, 3; slice thickness, 3 mm; distance factor, 20%) in the axial plane. Sensitizing diffusion gradients in three orthogonal directions with b values of 50 and 800 s/mm were applied. The ADC maps were created automatically by the system from the trace-weighted images with b values of 50 and 800 s/mm. The 5D EP-COSI acquisition parameters were as follows: The 5D EP-COSI sequence was home-developed 13 and 8X acceleration was used along ky, kz and t1 dimensions. TR/TE=1.5s/30ms; Field of view (FOV) along the 3 spatial dimensions were 160mmx160mmx120mm with 16-32 along kx, 16 along ky and 8 along kz; A voxel size of approximately 60x60x50mm3 was localized by three slice-selective RF pulses (900-1800-900). 2D COSY spectra were extracted from a voxel resolution of 1.5ml. The DWI data was analyzed using the manufacturer supplied software and ADC values were quantified for all groups of subjects. A home-developed Matlab code was used to reconstruct the undersampled 5D EP-COSI data using group sparsity14.Results
Shown in Fig.1 are ADC maps derived from the DWI data acquired in a 45 y.o. malignant and 35 y.o. benign breast cancer patients and a 45 y.o. healthy subject. Fig.2 (A) shows mean±SD of ADC values in 15 malignant and 8 benign breast cancer patients, and 7 healthy women. The remaining data in 5 malignant and 3 benign breast cancer patients were excluded due to inferior DWI quality. Fig.2 (B) shows the distribution of ADC values in the three groups. We observed significant reduction of ADC in malignant patients compared to benign (1.1 vs 1.66) and healthy controls (1.1 vs 1.95) with p<0.001. Figure 3 shows ADC values versus A) tumor grades and B) MRI tumor sizes in malignant patients. Shown in Fig.4 are multi-voxel COSY spectra recorded in a 40 y.o. malignant breast cancer patient (grade 3, size of 63mm, KI-67 of 20-30%) with the axial T1-weighted MRI showing the MRSI grids. Table 1 shows excellent correlation between the two metrics, namely ADC and choline.Discussion
Both DWI and 5D EP-COSI data were acquired using the echo-planar read-outs which are sensitive to B0 inhomogeneity leading to artifacts. Our results are in agreement with previous studies on invasive breast cancer15. The ADC values of malignant patients were significantly lower than benign and healthy subjects. 2D COSY spectra were extractable from a voxel size of 1.5ml from the 5D EP-COSI data. Strong correlation of choline measured through 5D EP-COSI shows the reliability of spectroscopic data. 5D EP-COSI has the advantage of better coverage of breast tumors compared to other known spectroscopic sequences enhancing the accuracy. Increased ADC and decreased choline in malignant group reflect the increased cellularity16 of the malignant lesions without the need for the administration of contrast medium. DWI and 5D EP-COSI shows strong potential as an adjunct technique to reduce breast biopsies, and could increase the overall specificity of DCE-MRI.Conclusion
The pilot findings of this study using DWI and 5D WP-COSI are encouraging and provide positive evidence to support 5D EP-COSI and DWI as useful adjuncts to standard breast MRI protocols in assisting with the diagnosis of breast cancer. However, further validation using a larger cohort of breast cancer patients is needed.Acknowledgements
This research was supported by a CDMRP Breakthrough Step I award # W81XWH-16-1-0524.References
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