Towards a safe non-invasive method for evaluating the carbonate substitution levels of hydroxyapatite (HAP) in micro-calcifications found in breast tissue

摘要

A new diagnostic concept based on deep Raman spectroscopy is proposed permitting the non-invasivendetermination of the level of carbonate substitution in type II calcifications (HAP). The carbonatensubstitution has shown to be directly associated with the pathology of the surrounding breast tissue andndifferent pathology groups can therefore be separated using specific features in the Raman spectra of thencalcifications. This study explores the principle of distinguishing between type II calcifications, found innproliferating lesions, by using the strongest Raman peak from calcium hydroxyapatites (the phosphatenpeak at 960 cmu00021) to act as a surrogate marker for carbonate substitution levels. It is believed thatncarbonate ion substitution leads to a perturbation of the hydroxyapatite lattice which in turn affects thenphosphate vibrational modes. By studying calcifications, with known carbonate content, buried innporcine tissue it has been possible to evaluate the feasibility of using the proposed approach to probe thencomposition of the calcifications in vivo and hence provide pathology specific information non-invasively,nin real time. Using the proposed concept we were able to determine the level of carbonate substitutionsnthrough soft tissue phantom samples (total thickness of 5.6 mm). As the level of carbonate substitutionnhas been previously correlated with mid-FTIR to the lesion type, i.e. whether benign or invasive or in situncarcinoma, the new findings provide a major step forward towards establishing a new capability forndiagnosing benign and malignant lesions in breast tissue in a safe and non-invasive manner in vivo.