title: Metabolomics of Breast Cancer Using High-Resolution Magic Angle Spinning Magnetic Resonance Spectroscopy: Correlations with 18F-FDG Positron Emission Tomography-Computed Tomography, Dynamic Contrast-Enhanced and Diffusion-Weighted Imaging MRI.
abstract: OBJECTIVE
  Our goal in this study was to find correlations between breast cancer metabolites and conventional quantitative imaging parameters using high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) and to find breast cancer subgroups that show high correlations between metabolites and imaging parameters.
  
  
  METHODS
  Between August 2010 and December 2013, we included 53 female patients (mean age 49.6 years; age range 32-75 years) with a total of 53 breast lesions assessed by the Breast Imaging Reporting and Data System. They were enrolled under the following criteria: breast lesions larger than 1 cm in diameter which 1) were suspicious for malignancy on mammography or ultrasound (US), 2) were pathologically confirmed to be breast cancer with US-guided core-needle biopsy (CNB) 3) underwent 3 Tesla MRI with dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) and positron emission tomography-computed tomography (PET-CT), and 4) had an attainable immunohistochemistry profile from CNB. We acquired spectral data by HR-MAS MRS with CNB specimens and expressed the data as relative metabolite concentrations. We compared the metabolites with the signal enhancement ratio (SER), maximum standardized FDG uptake value (SUV max), apparent diffusion coefficient (ADC), and histopathologic prognostic factors for correlation. We calculated Spearman correlations and performed a partial least squares-discriminant analysis (PLS-DA) to further classify patient groups into subgroups to find correlation differences between HR-MAS spectroscopic values and conventional imaging parameters.
  
  
  RESULTS
  In a multivariate analysis, the PLS-DA models built with HR-MAS MRS metabolic profiles showed visible discrimination between high and low SER, SUV, and ADC. In luminal subtype breast cancer, compared to all cases, high SER, ADV, and SUV were more closely clustered by visual assessment. Multiple metabolites were correlated with SER and SUV in all cases. Multiple metabolites showed correlations with SER and SUV in the ER positive, HER2 negative, and Ki-67 negative groups.
  
  
  CONCLUSIONS
  High levels of PC, choline, and glycine acquired from HR-MAS MRS using CNB specimens were noted in the high SER group via DCE MRI and the high SUV group via PET-CT, with significant correlations between choline and SER and between PC and SUV. Further studies should investigate whether HR-MAS MRS using CNB specimens can provide similar or more prognostic information than conventional quantitative imaging parameters.
authors.affiliation: Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Haesung
authors.initials: H
authors.lastname: Yoon
authors.affiliation: Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan, Republic of Korea.
authors.forename: Dahye
authors.initials: D
authors.lastname: Yoon
authors.affiliation: Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Mijin
authors.initials: M
authors.lastname: Yun
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Ji Soo
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Vivian Youngjean
authors.initials: VY
authors.lastname: Park
authors.affiliation: Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Joon
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ja Seung
authors.initials: JS
authors.lastname: Koo
authors.affiliation: Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Moon
authors.affiliation: Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan, Republic of Korea.
authors.forename: Suhkmann
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18