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

MRI 分析线圈位置以改善 rTMS 治疗抑郁症

• 批准号: 8970689
• 负责人: ALLYSON C ROSEN
• 金额: --
• 依托单位: VETERANS ADMIN PALO ALTO HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8970689
• 关键词: Address; Adopted; Aftercare; Age; Amnesia; Anterior; Antidepressive Agents; Area; Atrophic; Blood Vessels; Brain; Brain region; Caring; Clinical; Clinical Trials; Confusion; Decision Modeling; Depressed mood; Economics; Effectiveness; Effectiveness of Interventions; Elderly; Electroconvulsive Therapy; Equilibrium; Equipment; FDA approved; Functional Magnetic Resonance Imaging; Funding; General Anesthesia; Hamilton Rating Scale for Depression; Head; Hospitalization; Hospitals; Image; Individual Differences; Inpatients; Knowledge; Lead; Location; Magnetic Resonance Imaging; Major Depressive Disorder; Medical; Memory Loss; Mental Depression; Methods; Minor; Mission; Neurons; Outpatients; Patients; Pharmaceutical Preparations; Placebos; Population; Positioning Attribute; Prefrontal Cortex; Procedures; Psychotherapy; Resistance; Risk; Risk Factors; Safety; Savings; Scalp structure; Series; Site; Smoking; Stimulus; System; Testing; Thumb structure; Treatment outcome; Veterans; Work; active method; alternative treatment; base; cerebral atrophy; clinical practice; cost; cost effective; cost effectiveness; cranium; depressive symptoms; improved; magnetic field; novel; repetitive transcranial magnetic stimulation; response; symptomatic improvement; treatment group; treatment response

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.

描述（由申请人提供）： 当前提案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方法，用于治疗难治性重度抑郁症 (TRMD)，即对多种药物均无反应的患者。 CSP 556 是一项九个站点的临床试验，已获得资助以评估 VA 系统中 rTMS 的有效性。为了进行治疗，将 rTMS 刺激发生设备（线圈）放置在患者头部上方，以刺激大脑的背外侧前额叶皮层区域 (DLPFC)。这种刺激会引起焦点磁场，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给予足够的刺激强度对于其抗抑郁功效至关重要（Herbsman 等，2009；George 等，2010）。该提案的目的是通过研究已知可改变这两个变量（针对 DLPFC 的准确性和刺激强度）的线圈定位中的关键变量，最大限度地利用从 CSP 556 获得的知识。这些线圈位置变量与治疗结果直接相关。该提案的结果可能会优化 TMS 的交付并改善对抑郁退伍军人的护理。我们选择关注改变抗抑郁反应的线圈位置的两个关键方面：A）沿头皮的线圈位置，这决定了大脑位置的准确性，B）线圈与底层皮层的距离，或颅骨到皮层的距离（SCD） ，与目标大脑区域的磁场强度成正比。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 患者存在皮质萎缩的危险因素，包括高龄、血管风险（例如吸烟），因此这种 SCD 可能比平民更大，并且 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，当前的临床实践标准是将 TMS 线圈定位在相对于刺激引起拇指抽搐的点前方 5 厘米处。之前对线圈位置的 MRI 研究表明，对于 1/3 的患者，这条 5 cm 的尺子不够靠前，无法到达 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）与线圈置于前方的程度相关。 CSP 556 通过将线圈定位在距 TMS 使拇指抽搐的位置 6 厘米（而不是 5 厘米）的位置上，对流行的临床实践进行了改进。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。这将是之前在接受 5 厘米规则治疗的患者中进行的研究的延伸（Herbsman 等人，2009 年；George 等人，2010 年）。将在 CSP 556 中收集 120 名患者的 MRI 数据，并在 MRI 上显示 TMS 线圈在治疗过程中所处的位置。这些图像将以数字方式扭曲到标准空间，从而实现前/后线圈位置与 HRSD 变化之间的相关性。我们预测这种关系将存在于主动患者而非假患者中。标准临床规则也可能不足以实现目标刺激，6 厘米规则也可能不准确，可能需要 MRI 来提高准确性。因此，我们将通过比较 HRSD 的变化与刺激线圈与结构和功能 MRI 定义的 DLPFC 的距离，探索更具创新性定义的线圈定位方法的潜在好处。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）。该提案还通过制定决策规则来增强 CSP 556，以确定何时添加 MRI 来评估线圈位置将具有成本效益。