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: 9794747
• 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 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9794747
• 关键词: 3-Dimensional; 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; Equipment; FDA approved; Functional Magnetic Resonance Imaging; Funding; General Anesthesia; Hamilton Rating Scale for Depression; Head; Hospital Costs; 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; Structure; System; Testing; Thumb structure; Treatment outcome; Use Effectiveness; Veterans; Work; active method; alternative treatment; base; cerebral atrophy; clinical practice; clinical research site; cost; cost effective; cost effectiveness; cranium; depressive symptoms; digital; improved; innovation; magnetic field; novel; patient response; placebo group; repetitive transcranial magnetic stimulation; response; secondary analysis; 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）： 当前建议的目的是通过研究改变干预措施有效性的关键变量来补充大脑刺激的临床试验，以治疗严重抑郁症患者。重复的经颅磁刺激（RTMS）是一种治疗方法，最近获得了FDA批准用于治疗的耐药性抑郁症（TRMD），即未能对多种药物做出反应的患者。 CSP 556是一项九个站点临床试验，已资助以评估VA系统中的RTMS有效性。为了进行治疗，将RTMS刺激产生设备（COIL）放在患者的头上，以刺激大脑的背外侧前额叶皮层区域（DLPFC）。这种刺激引起了局灶性磁场，以使离散皮质区域的神经元去极化。将线圈定位在正确的大脑区域并施用适当的刺激强度对于其抗抑郁药的功效至关重要（Herbsman等，2009； George等，2010）。该建议的目的是通过研究已知可以改变这两个变量的线圈定位中的关键变量来最大化从CSP 556获得的知识（靶向DLPFC和刺激强度的准确性）。这些线圈位置变量已与治疗结果直接相关。该提案的结果可能导致对TMS的优化和改善对抑郁症的退伍军人的护理。我们选择专注于改变抗抑郁剂反应的线圈位置的两个关键方面：a）沿头皮的线圈位置，该位置决定了大脑位置的准确性，b）线圈与基础皮层的距离，或颅骨到皮质距离（SCD）（SCD） ，它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评级量表的变化相关联（HRSD）。由于VA患者具有皮质萎缩的危险因素，包括高龄，血管风险（例如吸烟），因此该SCD可能比平民大，而TMS的刺激强度可能不足以达到其皮层。关于第一个变量，沿头皮的位置，临床实践的当前标准是将TMS线圈前置5 cm的位置相对于刺激诱导拇指抽搐的点。先前对线圈位置的MRI研究表明，该5 cm规则在1/3的患者中不足以达到DLPFC（Herbsman等，2009; George等，2010）。实际上，抑郁症状改善的大小（由HRSD的变化定义）与线圈前方放置的程度有关。 CSP 556通过将线圈6 cm（而不是5 cm）放置在TMS使拇指抽搐的位置，改善了临床实践。我们建议通过检查线圈位置与HRSD之间是否继续存在的关系来正式测试6 cm规则的有效性。这将是对接受5 cm规则治疗的患者进行的先前研究的扩展（Herbsman等，2009； George等，2010）。 MRI将在CSP 556中的120名患者中收集，并在MRI上指示TMS线圈在治疗期间放置的MRI。这些图像将被数字扭曲到标准空间，该空间将使前/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活跃的患者而不是假患者中。标准的临床规则也可能不足以实现目标刺激，而6 cm规则也可能不准确，并且可能需要MRI以提高准确性。因此，我们将通过比较HRSD的变化与刺激线圈与结构和功能性MRI定义的DLPFC的距离来探讨更具创新定义的线圈定位方法的潜在益处。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年）。该提案还通过制定决策规则来增加CSP 556，以添加MRI评估线圈位置将是具有成本效益的。