학위논문 (박사)-- 서울대학교 대학원 : 의과학과 의과학 전공, 2013. 2. 문우경.Introduction: Much research has been devoted to the development of new breast cancer diagnostic measures, including those involving high-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopic techniques. Previous HR-MAS MR results have been obtained from surgical specimen, which limits their direct clinical applicability.
Methodology/Principal Findings: In the present study, we performed HR-MAS MR spectroscopic studies on 31 breast tissue samples (13 cancer and 18 non-cancer) obtained by percutaneous core needle biopsy. We employed Carr Purcell Meiboom Gill (CPMG) pulse sequence which can selectively suppress signals with short relaxation times, most notably, lipid signals abundant in core needle biopsy samples. Cancer and non-cancer samples were discriminated very well with Orthogonal Projections to Latent Structure-Discriminant Analysis (OPLS-DA) multivariate model on the MR spectra. A subsequent blind test showed 69% sensitivity and 94% specificity in the prediction of the cancer status. A spectral analysis showed that in cancer cells, taurine- (3.43 ppm) and choline- (3.23 ppm) containing compounds are elevated.
Conclusions/Significance: HR-MAS MR metabolomics on intact breast tissues obtained by core needle biopsy may have a potential to be used as a complement to the current diagnostic measures for breast cancers.Table 1. Clinical and histological data on 31samples from 22 patients ----------22
Table 2. Tumor characteristics of the 13 patients -----------------------------------23
Chapter 2
Figure 1. Schematic illustration of HR-MAS MR spectra study ----------------- 24
Figure 2. HR-MAS MR spectra of breast tissue samples --------------------------25
Figure 3. Multivariate discrimination model-----------------------------------------26
Figure 4. Prediction result for cancer status based on OPLS-DA model -------- 27
Figure 5. Signals contributing to differentiation-------------------------------------28
Figure 6. Average spectra and Mann-Whitney U test for marker signals ------- 29
Figure 7. Discrimination based on prognostic markers ----------------------------30
Supplement Figure 1. Multivariate discrimination model--------------------------31
Supplement Figure 2. H&E staining and immunohistochemistry analysis-------32Docto