title: Initial validation of equilibrium contrast imaging for extracellular volume quantification using a three-dimensional engineered tissue model.
abstract: BACKGROUND
  To test the principles underpinning equilibrium contrast imaging estimation of tissue extracellular volume (ECV) fraction, using a three-dimensional (3D) engineered tissue model with known cellular and extracellular volumes.
  
  
  METHODS
  Six 3D tissue models (tumoroids) consisting of cell cultures within a collagen containing hydrogel were constructed after culture centrifugation and direct measurement of the cell component volume. Measured tumoroid ECV ranged from 0.89 to 1. ECV was calculated after measuring the T1 relaxation time at 3 Tesla using inversion recovery relaxometry (TI 100-1500 ms) within the tumoroids and surrounding medium before and 375 min after spiking the medium with Gadolinium (to achieve a concentration of 1.4 mM/L). Linear regression model prediction of directly measured ECV (ECVm ) by EQ-MRI measured ECV (ECVeq ); and Bland-Altman agreement between measures was assessed.
  
  
  RESULTS
  The fractional cellular volume measured by EQ-MRI (ECVeq ) within the tumoroids ranged from 0.821 to 0.963. ECVeq was a good predictor of ECVm (R2 = 0.77, P = 0.02). The regression line Y-axis intercept (when X = 0) was 0.045 ± 0.019 with a slope of 1.28 ± 0.35. Bland-Altman comparison demonstrated 95% limits of agreement between -0.002 and 0.114 with a bias (SD) of 0.056 (0.03).
  
  
  CONCLUSIONS
  This study supports the principles of ECV estimation using equilibrium contrast MRI, but future development of this model may allow validation over a wider, more physiological ECV range and a greater understanding of the effect of tissue extracellular protein burden on ECV.
authors.affiliation: UCL Centre for Medical Imaging, University College London.
authors.forename: Steve
authors.identifier: http://orcid.org/0000-0002-4558-288X
authors.initials: S
authors.lastname: Bandula
authors.affiliation: Tissue Repair and Engineering Centre, Institute of Orthopaedics and Musculoskeletal Sciences, UCL Division of Surgery and Interventional Science, Stanmore, United Kingdom.
authors.forename: Tarig
authors.initials: T
authors.lastname: Magdeldin
authors.affiliation: UCL Centre for Medical Imaging, University College London.
authors.forename: Nicola
authors.initials: N
authors.lastname: Stevens
authors.affiliation: UCL Centre for Medical Imaging, University College London.
authors.forename: Jason
authors.initials: J
authors.lastname: Yeung
authors.affiliation: UCL Institute for Cardiovascular Science, University College London.
authors.forename: James C
authors.initials: JC
authors.lastname: Moon
authors.affiliation: UCL Centre for Medical Imaging, University College London.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Taylor
authors.affiliation: Tissue Repair and Engineering Centre, Institute of Orthopaedics and Musculoskeletal Sciences, UCL Division of Surgery and Interventional Science, Stanmore, United Kingdom.
authors.forename: Umber
authors.initials: U
authors.lastname: Cheema
authors.affiliation: UCL Centre for Medical Imaging, University College London.
authors.forename: Shonit
authors.initials: S
authors.lastname: Punwani
mesh_terms: D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D004058:Diffusion; D005682:Gadolinium / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D021621:Imaging, Three-Dimensional / Q000379:methods*; D016018:Least-Squares Analysis; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D009206:Myocardium / Q000473:pathology; D012044:Regression Analysis; D015203:Reproducibility of Results; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D003287:Contrast Media; D020100:Hydrogels; D003094:Collagen; D005682:Gadolinium
keywords: biological model; contrast agents; fibrosis; magnetic resonance imaging