The current standard of care in breast cancer imaging, consisting of ultrasound, xray, and MR mammography, only provides a fraction of the total available information that could be obtained diagnostically. It is not surprising then, that there has been considerable effort in identifying new approaches which attempt to improve upon the unsatisfactory specificity [1
] of breast cancer imaging. The ideal approach would add additional contrast to these systems to discriminate malignant tumors from the surrounding benign or healthy tissue [4
]. The integration of optics into standard breast cancer imaging systems is one promising area. Optical imaging provides functional information which should improve lesion characterization, thereby reducing unnecessary breast biopsies. Innovations to improve its capabilities have included better instrumentation, more sophisticated computational algorithms, contrast agents, and more recently, image guided approaches which integrate the higher resolution of a complimentary modality into optical imaging to improve contrast recovery [9
]. While several pilot studies using this method have been carried out [9
], a major factor limiting more comprehensive studies has been the lack of a practical approach to combine these modalities. This paper discusses the latest software tools and methodology which have enabled three-dimensional MR-guided diffuse optical imaging of breast cancer in vivo
to become a practical procedure.
A synergistic multimodal approach is possible when one modality provides good structural feature identification, while the other provides functional or molecular information about the features [12
]. MR imaging has encouraged perhaps more multimodality interest than xray mammography recently because its extremely high sensitivity might enable a complimentary technology to aid in specificity. Diffuse optical tomography (DOT) can fill this need because it gives information about tissue health by providing images of total hemoglobin, hemoglobin oxygen saturation, water content, lipid content, and scattering properties. Breast cancers have been shown in select studies to have higher hemoglobin and water content than normal tissue, and lower lipid content [13
]. This technique has shown varying degrees of success, depending on study protocol [18
], and generally improves upon the specificity of breast characterization. However, the accuracy of optical mammography with small lesions below the resolution limit of
cm is limited, as both larger-scale studies either noted poorer characterization of lesions (< 6mm) [19
], or excluded them altogether [18
]. It has been shown that the inclusion of high resolution spatial guidance from xray or MR improves the spatial resolution and quantification of optical imaging [20
], often by as much as 35%, depending on technique [23
To date, most clinical studies of optical mammography involving the use of multimodality spatial guidance have been focused on planar acquisitions limited to two dimensions for practical reasons. Yet optical imaging in three dimensions is critical because of the more accurate models of light propagation in 3D, and the difficulty in positioning the optical probes directly over the region of interest with planar or sparse data sampling, especially when the lesion is not palpable. Additionally, there is a need to modify 3D visualization tools to appropriately weight the display of optical data to the sensitivity of the measurements, so that clinicians are not mislead about reconstructed tissue contents which may lie far outside the sampling volume.
The main reason for this limitation in technique has to date been the computational burden of volumetric reconstruction, as shown in , and the effects of poorly sampled tissues on the inverse problem. It is clear that when advancing DOT or simultaneous MR-DOT to three dimensions, the number of unknowns grows by orders of magnitude. However, by using the MR to guide the separation of unique tissue types which can be characterized spectroscopically (MRg-NIRS), this modality becomes much more practical, and yet preserves the spatial fidelity of the original MR images. This paper presents the methodology and implementation of reconstruction and visualization of MR-guided NIRS in three dimensions, and results from phantom experiments and female breast tissue in vivo.
Comparison of the number of chromophores to be computed for 2D DOT, 3D DOT, and MR guided DOT.