Magnetic resonance imaging properties of convective delivery in diffuse intrinsic pontine gliomas

Abstract

Object: 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 ).

Fig. 1

Case 1. Intraparenchymal air effects on infusate distribution. A–F: Serial axial T1-weighted MR images obtained every 100 minutes, demonstrating the impact of intraparenchymal air (hypointensity) introduced at the start of the infusion after removal of an internal stylet. While there was a small decrease in the volume of air over time, the serial images demonstrate the restriction of anteromedial spread of infusate (hyperintensity) by the air in the parenchyma.

Fig. 2

Case 3. Preferential infusate flow along parallel white matter tracts. A–D: Serial axial T1-weighted MR images acquired every 50 minutes, demonstrating preferential infusate flow in the white matter tracts of the brainstem in the axial plane. The serial images demonstrate preferential spread of infusate along the horizontal fibers of the pons that initially preserve the perpendicularly oriented corticospinal tracts.

Fig. 3

Case 3. Preferential infusate flow into a previous infusion cannula tract. The previous infusion cannula tract is visualized (white arrows) on sagittal T1-weighted MR image. Once the leading edge of the second infusion (black arrows) encounters the previous cannula tract, the infusate preferentially flows into the prior tract (arrowheads).

Fig. 4

Case 4. Infusate leak back along the cannula at highest rate of infusion. Sagittal T1-weighted MR image demonstrating infusate leak back (arrowheads) along the cannula at 10 μl/minute.