Department of Neurosurgery, Chang-Gung University and Memorial Hospital, Taoyuan, Taiwan.
AJNR Am J Neuroradiol. 2013 Jan;34(1):115-20. doi: 10.3174/ajnr.A3150. Epub 2012 Jun 21.
FUS-induced BBB opening is a promising technique for noninvasive and local delivery of drugs into the brain. Here we propose the novel use of a neuronavigation system to guide the FUS-induced BBB opening procedure and investigate its feasibility in vivo in large animals.
We developed an interface between the neuronavigator and FUS to allow guidance of the focal energy produced by the FUS transducer. The system was tested in 29 swine by more than 40 sonication procedures and evaluated by MR imaging. Gd-DTPA concentration was quantitated in vivo by MR imaging R1 relaxometry and compared with ICP-OES assay. Brain histology after FUS exposure was investigated using H&E and TUNEL staining.
Neuronavigation could successfully guide the focal beam, with precision comparable to neurosurgical stereotactic procedures (2.3 ± 0.9 mm). A FUS pressure of 0.43 MPa resulted in consistent BBB opening. Neuronavigation-guided BBB opening increased Gd-DTPA deposition by up to 1.83 mmol/L (a 140% increase). MR relaxometry demonstrated high correlation with ICP-OES measurements (r(2) = 0.822), suggesting that Gd-DTPA deposition can be directly measured by imaging.
Neuronavigation provides sufficient precision for guiding FUS to temporally and locally open the BBB. Gd-DTPA deposition in the brain can be quantified by MR relaxometry, providing a potential tool for the in vivo quantification of therapeutic agents in CNS disease treatment.
FUS 诱导的 BBB 开放是一种有前途的非侵入性和局部递药技术。在这里，我们提出了一种新的使用方法，即利用神经导航系统来引导 FUS 诱导的 BBB 开放程序，并在大型动物体内研究其可行性。
我们开发了一种神经导航仪和 FUS 之间的接口，以允许引导 FUS 换能器产生的聚焦能量。该系统在 29 头猪中进行了超过 40 次的超声处理测试，并通过磁共振成像进行了评估。通过磁共振成像 R1 弛豫定量法在体内定量测定 Gd-DTPA 浓度，并与 ICP-OES 测定法进行比较。用 H&E 和 TUNEL 染色法研究 FUS 暴露后的脑组织学变化。
神经导航可以成功地引导聚焦光束，精度可与神经外科立体定向手术相媲美（2.3 ± 0.9 mm）。FUS 压力为 0.43 MPa 可导致一致的 BBB 开放。神经导航引导的 BBB 开放可使 Gd-DTPA 沉积增加高达 1.83 mmol/L（增加 140%）。磁共振弛豫测量法与 ICP-OES 测量法高度相关（r² = 0.822），表明 Gd-DTPA 沉积可通过成像直接测量。
神经导航为 FUS 提供了足够的精度，可实现时间和局部 BBB 开放。通过磁共振弛豫测量法可定量测定脑内 Gd-DTPA 沉积，为 CNS 疾病治疗中治疗剂的体内定量提供了一种潜在工具。
