MRI Analysis of Coil Position to Improve the rTMS Treatment of Depression

描述(由申请人提供)： 目前这项提议的目的是通过研究改变干预效果的关键变量来补充脑刺激治疗重度抑郁症患者的临床试验。重复经颅磁刺激(RTMS)是FDA最近批准的一种治疗难治性重度抑郁症(TRMD)的方法，即对多种药物无效的患者。CSP 556是一项九点临床试验，已获得资助以评估rTMS在VA系统中的有效性。为了实施治疗，rTMS刺激产生设备(线圈)被放置在患者的头部以刺激大脑的背外侧前额叶皮质区域(DLPFC)。这种刺激诱导焦点磁场使离散皮质区域的神经元去极化。将线圈放置在正确的大脑区域并实施足够的刺激强度是其抗抑郁效果的关键(Herbsman等人，2009；George等人，2010)。这项建议的目的是通过研究线圈定位中已知的改变这两个变量的关键变量(靶向DLPFC的准确性和刺激强度)，最大化从CSP 556获得的知识。这些线圈位置变量与治疗结果直接相关。这项提案的结果可能会导致TMS交付的优化，并改善对抑郁退伍军人的护理。我们选择关注线圈位置的两个关键方面来改变抗抑郁药物的反应：A)线圈沿头皮的位置，它决定了大脑位置的准确性；B)线圈到底层皮质的距离，或头骨到皮质的距离(SCD)，它与目标脑区的磁场强度成正比。我们将根据MRI图像计算SCD，并将该值与汉密尔顿抑郁量表(HRSD)的变化相关联。由于VA患者有皮质萎缩的风险因素，包括高龄、血管风险(如吸烟)，这种SCD可能比平民人群更大，TMS的刺激强度可能不足以到达他们的皮质。关于第一个变量，即沿头皮的位置，目前的临床实践标准是将TMS线圈放置在相对于刺激引起拇指抽动的点前面5厘米的位置。先前对线圈位置的MRI研究表明，在1/3的患者中，这条5厘米的规则不足以达到DLPFC(Herbsman等人，2009年；George等人，2010年)。事实上，抑郁症状的改善程度(由HRSD的变化定义)与弹簧圈放置在前方的程度有关。CSP 556通过将线圈放置在距TMS使拇指抽动的位置6厘米而不是5厘米的位置，改进了当前的临床实践。我们建议通过检查线圈位置和HRSD之间的关系是否继续存在来正式测试6厘米规则的有效性。这将是先前在接受5厘米规则治疗的患者中进行的研究的扩展(Herbsman等人，2009年；George等人，2010年)。将在CSP 556中收集120名患者的MRI，并在MRI上显示TMS线圈在治疗过程中的位置。这些图像将被数字扭曲到一个标准空间，以实现前后线圈位置与HRSD变化之间的关联。我们预测，这种关系将存在于活跃的患者中，而不是假患者中。标准的临床规则也可能不足以进行靶向刺激，6厘米的规则也可能不准确，可能需要MRI来提高准确性。因此，我们将通过比较HRSD的变化与刺激线圈到结构和功能MRI定义的DLPFC的距离，来探索更具创新定义的线圈定位的潜在好处。最后，CSP 556的任务之一是制定rTMS何时具有成本效益的决策规则(Naimark、Krahn、Naglie、Redelmeier和Detsky，1997)。该建议还通过开发何时添加MRI以评估线圈位置将是经济有效的决策规则来增强CSP 556。

DESCRIPTION (provided by applicant): The aim of the current proposal is to supplement a clinical trial of brain stimulation for the treatment of patients with major depression by studying key variables that alter the effectiveness of the intervention. Repetitive transcranial magnetic stimulation (rTMS) is a treatment which was recently approved by the FDA for treatment resistant major depression (TRMD), i.e. patients who've failed to respond to multiple medications. CSP 556 is a nine site clinical trial that has been funded to evaluate rTMS effectiveness in the VA system. In order to administer the treatment, the rTMS stimulus generating equipment (coil) is placed over the patient's head to stimulate the dorsolateral prefrontal cortex region (DLPFC) of the brain. This stimulation induces focal magnetic fields to depolarize neurons in discrete cortical areas. Positioning the coil over the correct brain region and administering adequate stimulation intensity are critical for its antidepressant efficacy (Herbsman et al., 2009; George et al., 2010). The aim of this proposal is to maximize the knowledge gained from CSP 556 by studying key variables in coil positioning known to alter both these variables (accuracy in targeting DLPFC and intensity of stimulation). These coil position variables have been directly related to treatment outcomes. Results from this proposal could lead to an optimization of TMS delivery and improved care of depressed veterans. We chose to focus on two key aspects of coil position that alter antidepressant response: A) coil position along the scalp, which determines accuracy of brain location, B) distance of the coil from the underlying cortex, or skull to cortex distance (SCD), which is proportional to the magnetic field strength at the target brain region. We will calculate SCD based on the MRI image and correlate this value with change in the Hamilton Rating Scale for Depression (HRSD). Because VA patients have risk factors for cortical atrophy including advanced age, vascular risks (e.g. smoking), this SCD may be larger than in the civilian population and the stimulation intensity of the TMS may be inadequate to reach their cortex. With respect to the first variable, position along the scalp, the current standard of clinical practice is to position the TMS coil 5 cm anterior relative to the point at which stimulation induces a thumb twitch. A previous MRI study of coil position suggested that this 5 cm rule was not sufficiently anterior to reach DLPFC in 1/3 of the patients (Herbsman et al., 2009; George et al., 2010). In fact, the size of improvement in depressive symptoms (defined by a change in the HRSD) was associated with the degree to which the coil was placed anteriorly. CSP 556 improved upon prevailing clinical practices by positioning the coil 6 cm, and not 5 cm, from the location where TMS makes the thumb twitch. We propose to formally test the effectiveness of the 6 cm rule by examining whether a relationship between coil position and HRSD continues to exist. This would be an extension of the previous study conducted in patients treated with the 5 cm rule (Herbsman et al., 2009; George et al., 2010). MRI's will be collected on 120 patients in CSP 556 along with a marker to indicate on the MRI where the TMS coil was positioned during treatment. These images will be digitally warped to a standard space that will enable the correlation between anterior/posterior coil position and change in HRSD. We predict that this relationship will exist in the active and not the sham patients. It is also possible that a standar clinical rule will be inadequate to target stimulation and the 6 cm rule may also be inaccurate and MRI may be needed to improve accuracy. We will thus explore the potential benefit of more innovatively defined approaches to coil positioning by comparing change in HRSD to the distance of the stimulating coil from structural and functional MRI defined DLPFC. Finally, one of the missions of CSP 556 is to develop decision rules for when rTMS is cost effective (Naimark, Krahn, Naglie, Redelmeier, & Detsky, 1997). This proposal also augments CSP 556 by developing a decision rule for when adding MRI to assess coil position would be cost effective.