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“Breast MRI by the Shutter-Speed Method: Elimination of Unnecessary Breast Biopsies"
If you have a question about this talk, please contact Mala Jayasundera.
Abstract: There is growing public health concern over the benefits of X-ray mammography in breast cancer screening. Though it accomplishes early detection with high sensitivity, the consequent large number of false positive readings leads to a high fraction (typically, 70%) of biopsy procedures yielding benign pathology reports. These biopsies, unnecessary in this sense, have negative (morbid) consequences: pain, anxiety, possible harm, and expense (biopsy procedures cost typically ten times more than mammography or sonography). It has long been wished that MRI provide a more accurate diagnosis of breast disease. For 15 years a particular protocol, quantitative (Dynamic-Contrast-Enhanced) DCE -MRI, has held promise because it is a form of generalized “functional MRI ,” focusing on tumor vascular properties. However, DCE -MRI hasn’t proven significantly better than mammography and, since it is also more expensive, has not come into wide practice. The mathematical model generally used for quantitative DCE -MRI analysis was adopted from well-known tracer pharmacokinetic derivations. However, its unedited translation for DCE -MRI has the unreasonable consequence of treating all inter-compartmental equilibrium water exchange processes as effectively infinitely fast. This is because, though the DCE -MRI contrast agent (CA, a monomeric Gd(III) chelate) plays the tracer molecule role, the signal molecule is water, and these have different tissue compartmentalizations. We have modified the model to accommodate well-known water inter-compartmental transfer rate constants. We conduct an analysis designed to detect tumor foci exhibiting precisely water exchange kinetics effects (“shutter-speed” effects) on pharmacokinetic parameters, particularly the CA extravasation rate constant, Ktrans. In a population now reaching 137 positive-screening breast lesions, we have found that malignant tumor capillaries are sufficiently more CA-permeable to trigger focal Ktrans biomarker shutter-speed effects (ΔKtrans) that are essentially zero for benign lesions. The molecular basis for this is quite reasonable. Lesion region-of-interest and pixel-by-pixel ΔKtrans mapping allows complete specificity between biopsy/pathology-proven malignant (32) and benign (105) tumors. The biopsy procedures on the latter could have been avoided, and with cost savings since they are more expensive than MRI . This discrimination is independent of the screening modality, the MRI instrument vendor (platform/software), and the magnetic field strength. A significant sub-population of 95 lesions occurred in 93 high-risk women who were mammographically-negative but positively screened by clinical MRI approaches. Twenty malignant tumors in this population were missed by mammography. The MR shutter-speed is a fundamental concept that applies not only in quantitative MRI studies of many different cancers, but also of other pathologies and of physiological conditions.
This talk is part of the Cambridge Oncology Seminar Series series.
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