title: Magnetic resonance imaging properties of convective delivery in diffuse intrinsic pontine gliomas.
abstract: OBJECTIVE
  Coinfused surrogate imaging tracers can provide direct insight into the properties of convection-enhanced delivery (CED) in the nervous system. To better understand the distributive properties of CED in a clinical circumstance, the authors analyzed the imaging findings in pediatric diffuse intrinsic pontine glioma (DIPG) patients undergoing coinfusion of Gd-DTPA and interleukin-13-Pseudomonas exotoxin (IL13-PE).
  
  
  METHODS
  Consecutive patients undergoing CED (maximal rates of 5 or 10 μl/minute) of Gd-DTPA (1 or 5 mM) and IL13-PE (0.125 μg/ml or 0.25 μg/ml) for DIPG were included. Real-time MRI was performed during infusions, and imaging results were analyzed.
  
  
  RESULTS
  Four patients (2 males, 2 females; mean age at initial infusion 13.0 ± 5.3 years; range 5-17 years) underwent 5 infusions into DIPGs. Brainstem infusions were clearly identified on T1-weighted MR images at 1-mM (1 infusion) and 5-mM (4 infusions) coinfused Gd-DTPA concentrations. While the volume of distribution (Vd) increased progressively with volume of infusion (Vi) (mean volume 2.5 ± 0.9 ml; range 1.1-3.7 ml), final Vd:Vi ratios were significantly reduced with lower Gd-DTPA concentration (Vd:Vi for 1 mM of 1.6 compared with a mean Vd:Vi ratio for 5 mM of 3.3 ± 1.0) (p = 0.04). Similarly, anatomical distribution patterns were affected by preferential flow along parallel axial fiber tracts, into prior infusion cannula tracts and intraparenchymal air pockets, and leak back around the infusion cannula at the highest rate of infusion.
  
  
  CONCLUSIONS
  Magnetic resonance imaging of a coinfused Gd-DTPA surrogate tracer provided direct insight into the properties of CED in a clinical application. While clinically relevant Vds can be achieved by convective delivery, specific tissue properties can affect distribution volume and pattern, including Gd-DTPA concentration, preferential flow patterns, and infusion rate. Understanding of these properties of CED can enhance its clinical application. Part of clinical trial no. NCT00880061 ( ClinicalTrials.gov ).
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke;
authors.forename: Prashant
authors.initials: P
authors.lastname: Chittiboina
authors.forename: John D
authors.initials: JD
authors.lastname: Heiss
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Warren
authors.forename: Russell R
authors.initials: RR
authors.lastname: Lonser
mesh_terms: D020295:Brain Stem Neoplasms / Q000175:diagnosis*; D057785:Catheters; D002648:Child; D003287:Contrast Media / Q000008:administration & dosage*; D018481:Convection; D004867:Equipment Design; D005098:Exotoxins / Q000008:administration & dosage; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage; D005910:Glioma / Q000175:diagnosis*; D006801:Humans; D018793:Interleukin-13 / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011149:Pons / Q000473:pathology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage
chemical_list: D003287:Contrast Media; D005098:Exotoxins; C521502:IL13-PE38; D018793:Interleukin-13; D011993:Recombinant Fusion Proteins; D019786:Gadolinium DTPA