title: A phase I feasibility study of multi-modality imaging assessing rapid expansion of marrow fat and decreased bone mineral density in cancer patients.
abstract: OBJECTIVE
  Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD.
  
  
  METHODS
  We validated DECT in pre-clinical and phase I clinical trials and verified with water-fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in the cadaver vertebrae and compared with DECT and WF-MRI. For a phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12months after treatment. BMD and MF percent and distribution were quantified in the lumbar vertebrae and the right femoral neck.
  
  
  RESULTS
  Measured precision (3mg/cm(3)) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r=0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r=0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p<0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p<0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only 5% by DXA (p<0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment.
  
  
  CONCLUSIONS
  Our study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and BMD cannot be used interchangeably to monitor skeletal health following cancer therapy.
authors.affiliation: Department of Therapeutic Radiology, University of Minnesota, MN, USA; Masonic Cancer Center, University of Minnesota, MN, USA. Electronic address: huixx019@umn.edu.
authors.forename: Susanta K
authors.initials: SK
authors.lastname: Hui
authors.affiliation: Department of Therapeutic Radiology, University of Minnesota, MN, USA.
authors.forename: Luke
authors.initials: L
authors.lastname: Arentsen
authors.affiliation: Department of Obstetrics and Gynecology, University of Minnesota, MN, USA.
authors.forename: Thanasak
authors.initials: T
authors.lastname: Sueblinvong
authors.affiliation: Mindways Software Inc., Austin, TX, USA.
authors.forename: Keenan
authors.initials: K
authors.lastname: Brown
authors.affiliation: Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, MN, USA.
authors.forename: Pat
authors.initials: P
authors.lastname: Bolan
authors.affiliation: Department of Obstetrics and Gynecology, University of Minnesota, MN, USA.
authors.forename: Rahel G
authors.initials: RG
authors.lastname: Ghebre
authors.affiliation: Department of Obstetrics and Gynecology, University of Minnesota, MN, USA.
authors.forename: Levi
authors.initials: L
authors.lastname: Downs
authors.affiliation: Biostatistics Core, Masonic Cancer Center, University of Minnesota, MN, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Shanley
authors.affiliation: Department of Medicine, Division of Rheumatology, University of Wisconsin, Madison, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Hansen
authors.affiliation: Department of Medicine, University of Minnesota, MN, USA.
authors.forename: Anne G
authors.initials: AG
authors.lastname: Minenko
authors.affiliation: Masonic Cancer Center, University of Minnesota, MN, USA.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takhashi
authors.affiliation: Department of Medicine, University of Minnesota, MN, USA; Masonic Cancer Center, University of Minnesota, MN, USA.
authors.forename: Masashi
authors.initials: M
authors.lastname: Yagi
authors.affiliation: Biostatistics Core, Masonic Cancer Center, University of Minnesota, MN, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, University of Minnesota, MN, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Geller
authors.affiliation: Department of Therapeutic Radiology, University of Minnesota, MN, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Reynolds
authors.affiliation: Department of Therapeutic Radiology, University of Minnesota, MN, USA.
authors.forename: Chung K
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Masonic Cancer Center, University of Minnesota, MN, USA; Department of Medicine, University of Minnesota, MN, USA.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Blaes
authors.affiliation: Family Medicine and Community Health, University of Minnesota, MN, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Allen
authors.affiliation: Campus Bio-Medico University, School of Medicine, Rome, Italy.
authors.forename: Bruno Beomonte
authors.initials: BB
authors.lastname: Zobel
authors.affiliation: Department of Biostatistics, University of Minnesota, Minneapolis, USA.
authors.forename: Chap
authors.initials: C
authors.lastname: Le
authors.affiliation: Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, MN, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Froelich
authors.affiliation: Maine Medical Center Research Institute, Scarborough, ME, USA.
authors.forename: Clifford
authors.initials: C
authors.lastname: Rosen
authors.affiliation: Masonic Cancer Center, University of Minnesota, MN, USA; Department of Medicine, University of Minnesota, MN, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Yee
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D015519:Bone Density; D001853:Bone Marrow / Q000000981:diagnostic imaging*; D005223:Fats; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D064847:Multimodal Imaging; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000503:physiopathology*; D014057:Tomography, X-Ray Computed
chemical_list: D005223:Fats
keywords: Dual energy CT; Quantification and visualization of bone marrow; Water–fat MRI