title: A Population-Based Gaussian Mixture Model Incorporating 18F-FDG PET and Diffusion-Weighted MRI Quantifies Tumor Tissue Classes.
abstract: The aim of our study was to create a novel Gaussian mixture modeling (GMM) pipeline to model the complementary information derived from(18)F-FDG PET and diffusion-weighted MRI (DW-MRI) to separate the tumor microenvironment into relevant tissue compartments and follow the development of these compartments longitudinally.
  
  
  METHODS
  Serial (18)F-FDG PET and apparent diffusion coefficient (ADC) maps derived from DW-MR images of NCI-H460 xenograft tumors were coregistered, and a population-based GMM was implemented on the complementary imaging data. The tumor microenvironment was segmented into 3 distinct regions and correlated with histology. ANCOVA was applied to gauge how well the total tumor volume was a predictor for the ADC and (18)F-FDG, or if ADC was a good predictor of (18)F-FDG for average values in the whole tumor or average necrotic and viable tissues.
  
  
  RESULTS
  The coregistered PET/MR images were in excellent agreement with histology, both visually and quantitatively, and allowed for validation of the last-time-point measurements. Strong correlations were found for the necrotic (r = 0.88) and viable fractions (r = 0.87) between histology and clustering. The GMM provided probabilities for each compartment with uncertainties expressed as a mixture of tissues in which the resolution of scans was inadequate to accurately separate tissues. The ANCOVA suggested that both ADC and (18)F-FDG in the whole tumor (P = 0.0009, P = 0.02) as well as necrotic (P = 0.008, P = 0.02) and viable (P = 0.003, P = 0.01) tissues were a positive, linear function of total tumor volume. ADC proved to be a positive predictor of (18)F-FDG in the whole tumor (P = 0.001) and necrotic (P = 0.02) and viable (P = 0.0001) tissues.
  
  
  CONCLUSIONS
  The complementary information of (18)F-FDG and ADC longitudinal measurements in xenograft tumors allows for segmentation into distinct tissues when using the novel GMM pipeline. Leveraging the power of multiparametric PET/MRI in this manner has the potential to take the assessment of disease outcome beyond RECIST and could provide an important impact to the field of precision medicine.
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Mathew R
authors.initials: MR
authors.lastname: Divine
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany Max Planck Institute for Intelligent Systems, Tuebingen, Germany; and.
authors.forename: Prateek
authors.initials: P
authors.lastname: Katiyar
authors.affiliation: Institute of Pathology, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Kohlhofer
authors.affiliation: Institute of Pathology, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany bernd.pichler@med.uni-tuebingen.de.
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Disselhorst
mesh_terms: D000818:Animals; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D018450:Disease Progression; D019788:Fluorodeoxyglucose F18; D006801:Humans; D021621:Imaging, Three-Dimensional; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D064847:Multimodal Imaging / Q000379:methods*; D009336:Necrosis / Q000473:pathology; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000145:classification / Q000000981:diagnostic imaging* / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D059016:Tumor Microenvironment
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: 18F-FDG; DWI; Gaussian mixture model; PET/MR