Tracking accuracy of T2- and diffusion-weighted magnetic resonance imaging for infusate distribution by convection-enhanced delivery

Laboratory investigation

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Object

Because convection-enhanced delivery relies on bulk flow of fluid in the interstitial spaces, MR imaging techniques that detect extracellular fluid and fluid movement may be useful for tracking convective drug distribution. To determine the tracking accuracy of T2-weighted and diffusion-weighted MR imaging sequences, the authors followed convective distribution of radiolabeled compounds using these imaging sequences in nonhuman primates.

Methods

Three nonhuman primates underwent thalamic convective infusions (5 infusions) with 14C-sucrose (MW 342 D) or 14C-dextran (MW 70,000 D) during serial MR imaging (T2- and diffusion-weighted imaging). Imaging, histological, and autoradiographic findings were analyzed.

Results

Real-time T2- and diffusion-weighted imaging clearly demonstrated the region of infusion, and serial images revealed progressive filling of the bilateral thalami during infusion. Imaging analysis for T2- and diffusion-weighted sequences revealed that the tissue volume of distribution (Vd) increased linearly with volume of infusion (Vi; R2 = 0.94, R2 = 0.91). Magnetic resonance imaging analysis demonstrated that the mean ± SD Vd/Vi ratios for T2-weighted (3.6 ± 0.5) and diffusion-weighted (3.3 ± 0.4) imaging were similar (p = 0.5). While 14C-sucrose and 14C-dextran were homogeneously distributed over the infused region, autoradiographic analysis revealed that T2-weighted and diffusion-weighted imaging significantly underestimated the Vd of both 14C-sucrose (mean differences 51.3% and 52.3%, respectively; p = 0.02) and 14C-dextran (mean differences 49.3% and 59.6%; respectively, p = 0.001).

Conclusions

Real-time T2- and diffusion-weighted MR imaging significantly underestimate tissue Vd during convection-enhanced delivery over a wide range of molecular sizes. Application of these imaging modalities may lead to inaccurate estimation of convective drug distribution.

Abbreviations used in this paper: AADC = aromatic l-amino acid decarboxylase; AAV2 = adeno-associated virus serotype 2; CED = convection-enhanced delivery; IL13-PE = interleukin-13 Pseudomonas exotoxin; QAR = quantitative autoradiography; Vd = volume of distribution; Vi = volume of infusion.

Article Information

Address correspondence to: Russell R. Lonser, M.D., Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 3D20, Bethesda, Maryland 20892-1414. email: lonserr@ninds.nih.gov.

Please include this information when citing this paper: published online June 10, 2011; DOI: 10.3171/2011.5.JNS11246.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Coronal T2-weighted MR images obtained in a primate brain after infusion of 15 μl (A), 30 μl (B), and 60 μl (C) of 14C-dextran. Infusion of 14C-dextran solution provides a distinct region of T2-weighted hyperintensity in each thalamus compared with surrounding noninfused parenchyma.

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    Coronal diffusion-weighted MR images obtained in a primate brain after infusion of 15 μl (A), 30 μl (B), and 60 μl (C) of 14C-dextran. Infusion of 14C-dextran solution provides a distinct region of diffusion-weighted hyperintensity in each thalamus compared with surrounding noninfused parenchyma.

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    Graph demonstrating a linear relationship (R2 = 0.94) between Vd with T2-weighted MR imaging and Vi in primates infused with 14C-sucrose and 14C-dextran. The mean Vd/Vi ratio was 3.6 ± 0.5 (mean ± SD).

  • View in gallery

    Graph demonstrating a linear relationship (R2 = 0.91) between Vd with diffusion-weighted MR imaging and Vi in primates infused with 14C-sucrose and 14C-dextran. The mean Vd/Vi ratio was 3.3 ± 0.4 (mean ± SD).

  • View in gallery

    Coronal T2-weighted (A) and diffusion-weighted (B) MR images obtained after CED of 88 μl of radiolabeled 14C-dextran into the right thalamus. The insets show the corresponding autoradiograms of 14C-dextran distribution and demonstrates the spatial inaccuracy and underestimation of T2-weighted and diffusion-weighted MR imaging volumes of distribution compared with drug distribution determined by autoradiography.

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    Autoradiographic analysis of 14C-dextran concentration across the infused region. The concentration profile, based on specific activity, was square-shaped with a steep drop-off at the margins indicative of a relatively uniform concentration over the infused region.

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