Increased breast density is a known risk factor for the development of breast cancer. Quantitative MRI methods have the potential to provide accurate, volumetric measures of breast tissue volume and density. A novel, confounder-corrected chemical shift encoded (CSE) MRI technique designed to provide accurate fibroglandular tissue volume and density quantification is validated using a fat and water phantom. The CSE MRI technique provided accurate quantification of water and volumes and was robust to changes in spatial resolution and complexity of fat/water interfaces, indicating this method is expected to produce accurate and robust quantification of fibroglandular and adipose tissue in-vivo.
Women with mammographically dense breasts are known to have an increased risk for developing breast cancer1. Clinical interpretation of mammograms allows for a qualitative assessment of breast density and subjective assignment to one of four categories2. However, mammographic assessment of breast density is subject to inter- and intra-reader variability3. Thus, robust and accurate volumetric, quantitative MRI-based methods for measuring breast density would have important potential advantages for reproducible assessment of breast cancer risk.
We previously demonstrated the feasibility of a quantitative chemical-shift encoded (CSE) MRI technique capable of providing measures of both fibroglandular tissue volume and the overall percentage of fibroglandular tissue4. Here, we further validate this method in a phantom consisting of known volumes of fat and water.
A phantom consisting of three containers with known volumes of peanut oil and water (2% weight by volume agar gel) was constructed. The agar was doped using CuSO4 to have a T1 similar to that of fibroglandular tissue5. True volumes of fat and water in each container are given in Table 1. To simulate increasingly complex interfaces between breast fat and fibroglandular tissue, the agar was cut into increasingly smaller volumes (see Figure 1).
The phantom was imaged on a 1.5T scanner (Signa HDxt, GE Healthcare) using an 8-channel breast coil. Imaging was performed using investigational version of a quantitative CSE sequence (IDEAL IQ, GE Healthcare) with six echoes and an investigational version of a two-point Dixon method (FLEX, GE Healthcare). Images were acquired in the coronal plane with a 28 cm FOV and 14 cm slab. Flip angles and matrix sizes selected for imaging are given in Table 2.
Images were reconstructed offline using the previously described CSE-MRI4 technique or the two-point Dixon method. The voxel water fraction (WF) was calculated as:
$$$Voxel_{WF}=\frac{Voxel_{water}}{Voxel_{water}+Voxel_{fat}}$$$
The volume of the water was calculated as:
$$$Volume_{water}=\sum{Voxel_{WF}\times{Volume_{voxel}}}$$$
Where the summation was performed over the entire volume of the phantom as defined via a noise thresholding operation on the highest resolution CSE-MRI image of each container. Similar measures were made for fat. Overall water fraction was calculated as the total water volume divided by total calculated volume of the container.
Discussion
The CSE-MRI method was able to calculate the overall volume of each container within 2% of the true volume. Increased T1-weighting at higher flip angles led to underestimation of the overall water volume in voxels containing a mix of species types as expected from previously published results6. This effect had the largest impact in container 3 (see Figure 2) due to the increased water-fat interfaces. Consistent water fraction measurements (within 1% of one another) were observed across the three containers (increasing number of interfaces) despite changes in matrix size (Figure 2), indicating the CSE-MRI technique accurately accounts for partial voluming effects to quantify the water fraction on a per voxel basis. The small, baseline overestimation of the water fraction is of yet unexplained.
The two-point Dixon method was also investigated as it can produce fat and water separated images in a fraction of the acquisition time required for quantitative six-echo CSE-MRI, but it does not account for all known confounding factors. Similar results were seen in response to increasing flip angle (Figure 3 A), but baseline overestimation of the water fraction was higher. The impacts of uncorrected bias are seen more clearly in the water fraction results at different resolutions, with increased overestimation of the water fraction with increasing levels of partial voluming, due to additional interfaces and/or decreasing matrix size.
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