Jafri M Samir, Tang Rebecca, Tang Cha-Min
Research Service, Department of Veterans Affairs Medical Center, Baltimore, MD, United States.
J Neurosci Methods. 2009 Jan 30;176(2):85-95. doi: 10.1016/j.jneumeth.2008.08.038. Epub 2008 Sep 17.
The delivery of therapeutic agents directly to targets deep within the brain is becoming an important tool in the treatment of a variety of neurological disorders. Currently, the standard method to accomplish this is by using stereotactic procedures. While this existing method is adequate for many experimental situations, it is essentially a blind procedure that cannot provide real-time feedback on whether the actual location deviated from the intended location or whether the therapeutic agent was actually delivered. Here we describe an optical guidance technique that is designed to work in conjunction with existing stereotactic procedures to provide the needed real-time feedback for therapeutic delivery in live animals. This real-time feedback is enabled by a technology called catheter-based optical coherence tomography (OCT). In this study we show that OCT can provide real-time position feedback based on microanatomic landmarks from the live rodent brain. We show that OCT can provide the necessary guidance to perform microsurgery such as the selective transection of the Schaffer collateral inputs to the CA1 region of the hippocampus with minimal perturbation of overlying structures. We also show that OCT allows visual monitoring of the successful delivery of viral vectors to specific subregions of the hippocampus.
将治疗药物直接输送到大脑深处的靶点正成为治疗多种神经疾病的重要工具。目前,实现这一目标的标准方法是使用立体定向手术。虽然这种现有方法在许多实验情况下是足够的,但它本质上是一种盲操作,无法提供关于实际位置是否偏离预期位置或治疗药物是否实际输送的实时反馈。在此,我们描述一种光学引导技术,该技术旨在与现有的立体定向手术相结合,为活体动物的治疗药物输送提供所需的实时反馈。这种实时反馈由一种名为基于导管的光学相干断层扫描(OCT)的技术实现。在本研究中,我们表明OCT可以基于活体啮齿动物大脑的微观解剖标志提供实时位置反馈。我们表明,OCT可以提供必要的引导以进行显微手术,例如对海马体CA1区的Schaffer侧支输入进行选择性横断,同时对覆盖结构的扰动最小。我们还表明,OCT允许对病毒载体成功输送到海马体特定亚区域进行视觉监测。