title: A comparative assessment of preclinical chemotherapeutic response of tumors using quantitative non-Gaussian diffusion MRI.
abstract: Diffusion-weighted MRI (DWI) signal attenuation is often not mono-exponential (i.e. non-Gaussian diffusion) with stronger diffusion weighting. Several non-Gaussian diffusion models have been developed and may provide new information or higher sensitivity compared with the conventional apparent diffusion coefficient (ADC) method. However the relative merits of these models to detect tumor therapeutic response is not fully clear.
  
  
  
  Conventional ADC, and three widely-used non-Gaussian models, (bi-exponential, stretched exponential, and statistical model), were implemented and compared for assessing SW620 human colon cancer xenografts responding to barasertib, an agent known to induce apoptosis via polyploidy. Bayesian Information Criterion (BIC) was used for model selection among all three non-Gaussian models.
  
  
  
  All of tumor volume, histology, conventional ADC, and three non-Gaussian DWI models could show significant differences between control and treatment groups after four days of treatment. However, only the non-Gaussian models detected significant changes after two days of treatment. For any treatment or control group, over 65.7% of tumor voxels indicate the bi-exponential model is strongly or very strongly preferred.
  
  
  
  Non-Gaussian DWI model-derived biomarkers are capable of detecting tumor earlier chemotherapeutic response of tumors compared with conventional ADC and tumor volume. The bi-exponential model provides better fitting compared with statistical and stretched exponential models for the tumor and treatment models used in the current work.
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN 37232, USA; Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37232, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: junzhong.xu@vanderbilt.edu.
authors.forename: Junzhong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: R Adam
authors.initials: RA
authors.lastname: Smith
authors.affiliation: AstraZeneca, Alderley Park, MACCLESFIELD, Cheshire SK10 4TG, United Kingdom.
authors.forename: John C
authors.initials: JC
authors.lastname: Waterton
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN 37232, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Does
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN 37232, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: H Charles
authors.initials: HC
authors.lastname: Manning
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN 37232, USA; Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37232, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Gore
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D015233:Models, Statistical; D010755:Organophosphates / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: C520647:2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate; D010755:Organophosphates; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D004121:Dimethyl Sulfoxide
keywords: BIC; Barasertib; Chemotherapeutic response; Diffusion; High b; MRI; Polyploidy; SW620