title: Multi-modal imaging of tumor cellularity and Tryptophan metabolism in human Gliomas.
abstract: BACKGROUND
  To assess gliomas using image-based estimation of cellularity, we utilized isotropic diffusion spectrum imaging (IDSI) on clinically feasible diffusion tensor imaging (DTI) and compared it with amino acid uptake measured by α[(11)C]methyl-L-tryptophan positron emission tomography (AMT-PET).
  
  
  METHODS
  In 10 patients with a newly-diagnosed glioma, metabolically active tumor regions were defined in both FLAIR hyperintense areas and based on increased uptake on AMT-PET. A recently developed independent component analysis with a ball and stick model was extended to perform IDSI in clinical DTI data. In tumor regions, IDSI was used to define tumor cellularity which was compared between low and high grade glioma and correlated with the glioma proliferative index.
  
  
  RESULTS
  The IDSI-derived cellularity values were elevated in both FLAIR and AMT-PET-derived regions of high-grade gliomas. ROC curve analysis found that the IDSI-derived cellularity can provide good differentiation of low-grade from high-grade gliomas (accuracy/sensitivity/specificity of 0.80/0.80/0.80). . Both apparent diffusion coefficient (ADC) and IDSI-derived cellularity showed a significant correlation with the glioma proliferative index (based on Ki-67 labeling; R = 0.95, p < 0.001), which was particularly strong when the tumor regions were confined to areas with high tryptophan uptake excluding areas with peritumoral edema.
  
  
  CONCLUSIONS
  IDSI-MRI combined with AMT-PET may provide a multi-modal imaging tool to enhance pretreatment assessment of human gliomas by evaluating tumor cellularity and differentiate low-grade form high-grade gliomas.
authors.affiliation: Departments of Pediatrics and Neurology, Wayne State University School of Medicine, 3901 Beaubien St., Detroit, MI, 48201, USA. jeongwon@pet.wayne.edu.|PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, MI, USA. jeongwon@pet.wayne.edu.
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Jeong
authors.affiliation: Departments of Pediatrics and Neurology, Wayne State University School of Medicine, 3901 Beaubien St., Detroit, MI, 48201, USA. juhasz@pet.wayne.edu.|PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, MI, USA. juhasz@pet.wayne.edu.|Karmanos Cancer Institute, Detroit, MI, USA. juhasz@pet.wayne.edu.
authors.forename: Csaba
authors.initials: C
authors.lastname: Juhász
authors.affiliation: Karmanos Cancer Institute, Detroit, MI, USA. smittal@med.wayne.edu.|Departments of Neurosurgery and Oncology, Wayne State University School of Medicine, Detroit, MI, USA. smittal@med.wayne.edu.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Mittal
authors.affiliation: Departments of Pediatrics and Neurology, Wayne State University School of Medicine, 3901 Beaubien St., Detroit, MI, 48201, USA. drbosnyakedit@gmail.com.|PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, MI, USA. drbosnyakedit@gmail.com.
authors.forename: Edit
authors.initials: E
authors.lastname: Bosnyák
authors.affiliation: Departments of Pediatrics and Neurology, Wayne State University School of Medicine, 3901 Beaubien St., Detroit, MI, 48201, USA. promeoso@hotmail.com.|PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, MI, USA. promeoso@hotmail.com.
authors.forename: David O
authors.initials: DO
authors.lastname: Kamson
authors.affiliation: Karmanos Cancer Institute, Detroit, MI, USA. gbarger@med.wayne.edu.|Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA. gbarger@med.wayne.edu.
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Barger
authors.affiliation: Karmanos Cancer Institute, Detroit, MI, USA. robinetn@karmanos.org.|Department of Radiology, Wayne State University School of Medicine, Detroit, MI, USA. robinetn@karmanos.org.
authors.forename: Natasha L
authors.initials: NL
authors.lastname: Robinette
authors.affiliation: Karmanos Cancer Institute, Detroit, MI, USA. wkupsky@med.wayne.edu.|Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA. wkupsky@med.wayne.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Kupsky
authors.affiliation: Departments of Pediatrics and Neurology, Wayne State University School of Medicine, 3901 Beaubien St., Detroit, MI, 48201, USA. dchugani@pet.wayne.edu.|PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, MI, USA. dchugani@pet.wayne.edu.
authors.forename: Diane C
authors.initials: DC
authors.lastname: Chugani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002480:Cellulase; D056324:Diffusion Tensor Imaging; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D049268:Positron-Emission Tomography; D012372:ROC Curve; D014364:Tryptophan
chemical_list: D014364:Tryptophan; D002480:Cellulase