title: Rapid-Steady-State-T1 signal modeling during contrast agent extravasation: toward tumor blood volume quantification without requiring the arterial input function.
abstract: OBJECTIVE
  This study demonstrates how to quantify the tumor blood volume fraction (BVf) using the dynamic Rapid-Steady-State-T1 (RSST1 )-MRI method despite contrast agent (CA) leakage and without arterial input function (AIF) determination.
  
  
  METHODS
  For vasculature impermeable to CAs, the BVf is directly quantified from the RSST1 signal amplitude. In case of CA extravasation, we propose a two-compartment model to describe the dynamic RSST1 signal increase. We applied the mathematical model in a pilot-study on a RG2-glioma model to compare extravasation of two Gd-based CAs. The BVf quantification using the mathematical model in a C6-glioma model (n = 8) with the clinical CA Gd-DOTA was validated using a ΔR2 *-steady-state MRI method with an USPIO and by immunohistochemical staining of perfused vessels labeled with Hoechst-33342 dye in the same rats.
  
  
  RESULTS
  BVf in tumor and in healthy brain tissues (0.034 ± 0.005 and 0.026 ± 0.004, respectively) derived from the dynamic RSST1 signal were confirmed by ΔR2 *-steady-state MRI (0.036 ± 0.003 and 0.027 ± 0.002, respectively, correlation coefficient rS = 0.74) and by histology (0.036 ± 0.003 and 0.025 ± 0.004 respectively, rS = 0.87).
  
  
  CONCLUSIONS
  Straightforward tumor BVf quantification without AIF determination is demonstrated in presence of CA leakage. The method will facilitate angiogenesis assessment in longitudinal neuro-oncologic studies in particular when monitoring the response to antiangiogenic therapies.
authors.affiliation: Université Joseph Fourier, Grenoble Institut des Neurosciences, Institut National de la Santé et de la Recherche Médicale INSERM-U836, Bâtiment Edmond J. Safra, Chemin Fortuné Ferrini, Grenoble, France; CLINATEC, Commissariat à l'énergie atomique et aux énergies alternatives, MINATEC Campus, Grenoble, France; Université Saint Joseph-Faculté des sciences, Département de physique, campus des sciences et technologies, Mar Roukos, Mkallès, Lebanon.
authors.forename: Michel
authors.initials: M
authors.lastname: Sarraf
authors.forename: Adriana Teodora
authors.initials: AT
authors.lastname: Perles-Barbacaru
authors.forename: Marie France
authors.initials: MF
authors.lastname: Nissou
authors.forename: Boudewijn
authors.initials: B
authors.lastname: van der Sanden
authors.forename: François
authors.initials: F
authors.lastname: Berger
authors.forename: Hana
authors.initials: H
authors.lastname: Lahrech
mesh_terms: D000818:Animals; D001810:Blood Volume; D001811:Blood Volume Determination / Q000379:methods; D001932:Brain Neoplasms / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D003198:Computer Simulation; D003287:Contrast Media / Q000493:pharmacokinetics; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology*; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
keywords: C6-glioma model; RSST1-MRI method; quantitative magnetic resonance imaging; tumor blood volume fraction; two-compartment model; vascular permeability