Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1414, USA.
J Neurosurg. 2011 Sep;115(3):474-80. doi: 10.3171/2011.5.JNS11246. Epub 2011 Jun 10.
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.
Three nonhuman primates underwent thalamic convective infusions (5 infusions) with (14)C-sucrose (MW 342 D) or (14)C-dextran (MW 70,000 D) during serial MR imaging (T2- and diffusion-weighted imaging). Imaging, histological, and autoradiographic findings were analyzed.
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; R(2) = 0.94, R(2) = 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 (14)C-sucrose and (14)C-dextran were homogeneously distributed over the infused region, autoradiographic analysis revealed that T2-weighted and diffusion-weighted imaging significantly underestimated the Vd of both (14)C-sucrose (mean differences 51.3% and 52.3%, respectively; p = 0.02) and (14)C-dextran (mean differences 49.3% and 59.6%; respectively, p = 0.001).
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.
由于对流增强递送依赖于间质空间中的流体的体流动,因此可能会检测细胞外液和流体运动的 MR 成像技术有助于跟踪对流药物分布。为了确定 T2 加权和扩散加权 MR 成像序列的跟踪准确性,作者在非人类灵长类动物中使用这些成像序列跟踪放射性标记化合物的对流分布。
三只非人类灵长类动物在连续 MR 成像(T2 加权和扩散加权成像)期间接受了(14)C-蔗糖(MW 342 D)或(14)C-葡聚糖(MW 70,000 D)的丘脑对流输注(5 次输注)。分析了成像、组织学和放射自显影结果。
实时 T2 加权和扩散加权成像清楚地显示了输注区域,并且连续图像显示在输注过程中双侧丘脑逐渐充满。T2 加权和扩散加权序列的成像分析表明,组织体积分布(Vd)与输注体积(Vi)呈线性增加(R2 = 0.94,R2 = 0.91)。磁共振成像分析表明,T2 加权(3.6 ± 0.5)和扩散加权(3.3 ± 0.4)成像的平均 ± SD Vd / Vi 比值相似(p = 0.5)。虽然(14)C-蔗糖和(14)C-葡聚糖在输注区域内均匀分布,但放射自显影分析表明,T2 加权和扩散加权成像显著低估了(14)C-蔗糖(平均差异分别为 51.3%和 52.3%;p = 0.02)和(14)C-葡聚糖(平均差异分别为 49.3%和 59.6%;分别为,p = 0.001)的 Vd。
在大范围的分子尺寸范围内,实时 T2 加权和扩散加权 MR 成像在对流增强递送期间显著低估了组织 Vd。这些成像方式的应用可能导致对流药物分布的不准确估计。