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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 ?l/minute) of Gd-DTPA (1 or 5 mM) and IL13-PE (0.125 ?g/ml or 0.25 ?g/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 ).

SUBMITTER: Chittiboina P

PROVIDER: S-EPMC4294184 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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

Chittiboina Prashant P Heiss John D JD Warren Katherine E KE Lonser Russell R RR

Journal of neurosurgery. Pediatrics 20140110 3

<h4>Object</h4>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).<h4>Methods</h4>Consecutive patients undergoing CED (maximal rates of ...[more]

PMID: 24410126

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Project description:PurposeDiffusion tensor imaging for evaluation of white matter tracts is used with magnetic resonance spectroscopy (MRS) to improve management of diffuse intrinsic pontine glioma (DIPG). Changes in the apparent diffusion coefficient (ADC), fractional anisotropy (FA), and tumor metabolite ratios have been reported after initial radiation for DIPG, but these markers have not been studied sequentially in patients undergoing reirradiation for progressive DIPG. Here, we report a case series of 4 patients who received reirradiation for progressive DIPG on a prospective clinical trial in which we evaluated quantitative changes in FA, ADC, and tumor metabolites and qualitative changes in white matter tracts.Methods and materialsThe median reirradiation dose was 25.2 Gy (24-30.8 Gy). Fiber tracking was performed using standard tractography analysis. The FA and ADC values for the corticospinal and medial lemniscus tracts were calculated before and after reirradiation. Multivoxel MRS was performed. Findings were correlated with clinical features and conventional MRI of tumors.ResultsAll patients had an initial response to reirradiation as shown by a decrease in tumor size. In general, FA increased with disease response and decreased with progression, whereas ADC decreased with disease response and increased with progression. At second progression, the FA fold change relative to values during disease response decreased in both patients with available imaging at second progression. Visualization of tracts demonstrated robust reconstitution of previously disrupted paths during tumor response; conversely, there was increased fiber tract disruption and infiltration during tumor progression. The MRS analysis revealed a decrease in choline:creatinine and choline:N-acetylaspartate ratios during tumor response and increase during progression.ConclusionsDistinct changes in white matter tracts and tumor metabolism were observed in patients with DIPG undergoing reirradiation on a prospective clinical trial. Changes related to tumor response and progression were observed after 24 to 30.8 Gy reirradiation.

Dataset Information

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

Publications

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

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