256导联高密度脑电源定位技术在癫痫外科的临床应用研究

发布时间：2018-04-29 22:08

本文选题：256导联高密度脑电源定位 + 难治性癫痫　；参考：《复旦大学》2014年博士论文

【摘要】：头皮脑电源定位(ESI)是一种利用头皮脑电记录到的癫痫样放电定位颅内电位分布的技术手段,在国外已有较多研究,但在国内相关研究比较滞后。最近,具有高空间分辨率的256导联高密度脑电源定位技术(256-ch dESI)在难治性癫痫术前评估领域已经崭露头角,尽管国内的相关研究尚属空白,但国外已有一些相关的临床研究,均在不同程度上证实了其应用价值。相比现有的难治性癫痫术前无创评估手段如结构相核磁共振(MRI)、正电子发射计算机断层显像(PET)、传统头皮脑电图(cEEG)、发作症状学评估(semiology)、脑磁图(MEG)等,256-ch dESI具备较多优势。它同时具备高时间和空间分辨率、无创性、无毒副作用等优点,且能够进行长程记录,对被试者的配合能力要求不高,对深部致痫区的检测亦很敏感,在难治性癫痫的无创术前评估领域大有应用前景。本研究利用在本单位接受手术治疗的难治性癫痫病例,通过科学手段探讨了256-ch dESI对难治性癫痫的术前评估价值以及不同源定位结果(“源”,sources)模式(pattern)对预后的影响,并且通过基于个体解剖数据的高分辨率个体头模以及影像融合手段探讨了基于个体头模的256导联高密度脑电源定位(256-ch dESI IHM)技术在术前评估中的应用及价值。本研究实现了国际、国内范围内的多个创新。第一部分：256导联高密度脑电源定位技术对难治性癫痫的术前评估价值研究本部分利用53例难治性癫痫病例探讨了256-ch dESI的术前评估价值。所有病例均在我科接受包括256-ch dESI在内的多种无创致痫区评估工具检查,继而接受Ⅰ期切除性手术治疗。将预后良好患者的手术切除区域定义为致痫区范围,以亚脑叶水平和脑叶水平两种标准评价多种工具的定位价值。标准1(亚脑叶水平)：评估工具的定位结果位于切除范围内则定义为准确,接受评价的工具包括256-ch dESI. PET和MRI；标准2(脑叶水平)：评估工具的定位结果与手术切除区域位于同一脑叶,则定义为准确,接受评价的工具包括256-ch dESI, PET,MRI,发作症状学和cEEG。此外,我们根据MRI、发作症状学及cEEG结果筛选出14例明确诊断的颞叶内侧癫痫(mTLE),以颞叶底面及内侧结构作为致痫区评估标准,评价256-ch dESI和PET对mTLE的评估价值。本研究还利用统计学方法对源定位结果(“源”)模式等因素与预后的关系进行了分析。结果显示,无论采取哪种评价标准,256-ch dESI均拥有最高的敏感度和特异度。在14例mTLE病例中,256-ch dESI提示的致痫区在78.6%的病例中完全位于颞叶内侧及底面,而PET仅有36.4%,提示256-ch dESI较PET能够提供更加精确的定位信息(p0.05,Fisher精确检验)。根据源定位结果(“源”)为单一性或多灶性将53例病例分为“单源”和“多源”两组：利用Kaplan-Meier生存分析,结果显示“单源”组术后癫痫缓解的可能性显著性优于“多源”组(p0.05,Log Rank);根据“源”是否被切除将病例分为两组：利用Kaplan-Meier生存分析,结果显示“源”被切除组术后癫痫缓解的可能性较未被切除者更高(p0.05,Log Rank)。采用Cox回归多因素分析方法,结果显示“源”被切除与良好预后相关。256-ch dESI同时具备高空间和高时间分辨率,较其它传统工具具有独特的优势。增加的电极数量和面颊、颈等处的电极覆盖使得其对颞叶内侧、底面等处的放电检测更为敏感。关于源定位结果(“源”)模式的研究显示“单源”病例可能较“多源”病例更适合接受Ⅰ期切除性手术,且切除“源”可能与良好预后相关,这同时也提示反复出现发作间期癫痫样放电(IEDs)的区域(激惹区)与致痫区有较好的关联性；“多源”病例则可能需要考虑先进行颅内电极埋置手术以利用颅内电极脑电图(icEEG)明确致痫区范围。发作期脑电因信噪比低等原因并不适合256-ch dESI,但我们的初步探索显示该技术是可行的,值得进一步开展相关研究。目前发作期脑电的获取仍主要依赖cEEG。第二部分：PET阳性、MRI阴性颞叶癫痫的外科治疗以及256导联高密度脑电源定位技术对其术前评估价值的研究本中心的回顾性研究探讨了PET阳性、MRI阴性颞叶癫痫(PET+MRI-TLE)的外科治疗。从发作症状学、人口统计学、外科治疗以及预后评估的角度,我们利用41例海马硬化型颞叶癫痫(HS+TLE)和18例良性病灶性颞叶癫痫(L+TLE)对比分析了19例PET+MRI-TLE的临床特点、外科治疗及预后。数据分析显示,PET+MRI-TLE组的预后(Engle Ⅰ级：68.4%,Engle Ⅰ+Ⅱ级：84.2%)与HS+TLE组(Engle Ⅰ级：68.3%,Engle Ⅰ+Ⅱ级：80.5%)没有显著差异(p0.05)。分析还显示,PET+MRI-TLE组和HS+TLE组的热性惊厥史比例和继发强直阵挛发作比例有显著差异(p0.05)。一定程度上,PET+MRI-TLE可能是异于HS+TLE的临床疾病,而非HS+TLE的一种亚型。总的来说,经正确评估和筛选的PET+MRI-TLE可以考虑接受Ⅰ期切除性手术。PET虽然是定位颞叶致痫区的有力工具,然而,它具有特异度低、定位范围广泛等缺点。256-ch dESI作为较新出现的无创定位工具,同时拥有高时间、空间分辨率,我们设计了相关研究将其应用于PET+MRI-TLE的术前评估,探讨了其定位价值。通过入选和排除标准,我们选定了12例PET+MRI-TLE病例,利用手术切除区域结合预后来定义致痫区范围,即在预后良好的病例中(9例),如某种工具的定位结果包含在切除区域以内(标准1,亚脑叶水平)或与切除区域在同一脑叶(标准2,脑叶水平),则定义为准确。采用标准1,256-ch dESI的定位准确度为7/9=77.8%,2例“不准确”者的结果为：源定位结果(“源”)位于中、后颞叶、颞枕交界区；PET的准确度为7/9=77.8%,2例“不准确”的结果为：低代谢范围广泛,累及后颞叶、颞枕交界区等处。采用标准2,定位于同侧颞叶即定义为准确,则256-ch dESI的准确度提升至8/9=88.9%,1例“不准确”的结果为：“源”位于颞枕交界区。PET则准确定位所有病例,发作症状学评估的准确度为3/9=33.3%,cEEG的准确度为5/9=55.6%。根据“源”是否位于前颞叶进行分组,结果显示,具有前颞叶“源”病例的预后要显著性优于具有非前颞叶“源”的病例(100%VS 40%,p0.05,Fisher精确检验)。本研究在国际范围内第一次将256-ch dESI应用于PET+MRI-TLE的术前评估并对其应用价值做出探索,结果显示,256-ch dESI是一种有前景的、可用于MRI阴性癫痫精确定位的方法。根据本研究结果,对于PET+MRI-TLE来说,如果256-ch dESI定位于前颞叶,则病例适合进行Ⅰ期前颞叶切除手术；如果256-ch dESI定位于非前颞叶处如后颞叶或颞枕交界等部位,则需谨慎行Ⅰ期切除性手术。这个特点对于此类难治性癫痫病例的选择有一定指导意义。发作期脑电数据并不适合进行256-ch dESI,但依赖cEEG获取的发作期脑电应是MRI阴性癫痫术前评估的重要组成部分。对于MRI阴性癫痫,手术方案决不能盲目依据单一评估手段确定,而应是综合多种评估手段的结果,必要时需考虑进行颅内电极脑电图(icEEG)检查以明确致痫区所在。第三部分：基于高分辨率个体头模的256导联高密度脑电源定位技术及其与颅内电极脑电图的影像融合研究目前,关于高密度脑电源定位(dESI)研究的正演模型一般均基于公共头模(AHM),另外有少数研究基于融入个体头颅MRI的改良头模(SMAC),但其本质仍为球形头模,只是将平均MRI影像替换为个体MRI影像。本研究结合临床病例,利用多模态影像融合技术,将基于高分辨率个体头模的256导联高密度脑电源定位技术(256-ch dESI IHM)应用于难治性癫痫术前评估,并探讨其在致痫区定位方面的理论与临床应用价值,属国内首次,国际领先。在获取3D-SPGR序列MRI(从头顶扫描至下颌)和256导联高密度脑电数据后,通过计算机及手工处理得到256-ch dESI IHM结果。接受颅内电极埋置手术的病例在术后次日获取全脑薄层CT平扫,继而通过计算机与手工处理与个体头模融合。本研究通过两种标准评价致痫区定位工具。标准1：将预后良好病例的手术切除区域定义为致痫区范围,若某工具所定义的致痫区在此切除范围以内,则为准确；标准2：以颅内电极脑电图(icEEG)为致痫区定位标准,若某工具所定义的致痫区与icEEG吻合,则定义为准确。接受icEEG检查的病例接受此标准评价。7例患者接受标准1评价,准确度如下：256-ch dESI IHM 7/7=100%,基于公共头模的256-ch dESI (256-ch dESI AHM) 6/7=85.7%, PET 3/7=42.9%和MRI 5/7=71.4%。仅256-ch dESI IHM准确定位所有病例的致痫区。4例PET结果“不准确”均因其显示的低代谢范围较为广泛。2例MRI结果“不准确”均因其缺乏有意义的局灶性病变。1例“不准确”的256-ch dESI AHM结果位于切除区域附近。采用标准2即以icEEG为标准对病例1进行评价,256-ch dESI IHM与icEEG高度吻合,而256-ch dESI AHM, PET和MRI均出现不吻合处。256-ch dESI AHM虽然精准度稍欠缺,但其能够方便快捷的融入难治性癫痫的无创综合评估流程,是传统工具的有益补充。利用个体MRI重建颅脑几何形态、根据真实皮层方向分布有向偶极子、设定各组织合理的电传导率并获取高密度脑电数据后,高精准度的256-ch dESI IHM技术已具备可行性,并且它可以将包括icEEG在内的多种评估工具的结果融合在同一视图,有利于更精确的制定术前规划及手术方案。本研究率先将256-ch dESI IHM技术应用于难治性癫痫术前评估,并开展了256-ch dESI IHM与“金标准”icEEG的影像融合研究,验证了256-ch dESI IHM的精准度,证实了它的应用前景。我们再次证实经准确识别的、反复出现的IEDs的产生区(激惹区)与致痫区有很好的关联性。但激惹区与其余分区如症状产生区,发作起始区,致痫病灶和功能缺失区都只能在一定程度上代表了致痫区的范围,任何一种分区都不能完全等同于致痫区。因此,外科手术方案必须是综合了多种定位方法的结果。256-ch dESI AHM/IHM不能够取代其它工具(尤其是目前256-ch dESI技术主要基于发作间期癫痫样放电,而发作期脑电的获取在大部分情况下仍需依赖cEEG甚至icEEG),但该技术的优势和对致痫区定位的指导意义是不容忽视的。属性不符
[Abstract]:Scalp brain power location (ESI) is a technical means to locate the distribution of intracranial potential using the epileptiform discharge from the scalp electroencephalogram (EEG). There have been many studies abroad, but the related research in China is lagging behind. Recently, the high spatial resolution 256 lead high-density brain location technique (256-ch dESI) has been used to evaluate the treatment of intractable epilepsy. The field of estimation has come to the fore. Although domestic related studies are still blank, some related clinical studies abroad have proved its application in varying degrees. Compared with existing non invasive methods such as structural phase nuclear magnetic resonance (MRI), positron emission computed tomography (PET), traditional scalp brain Electrogram (cEEG), paroxysmal symptom assessment (semiology), magnetoencephalogram (MEG), and so on, 256-ch dESI have many advantages. It has the advantages of high time and spatial resolution, noninvasive, non-toxic side effects, and can carry out long range records, the ability to cooperate with the subjects is not high, the detection of the deep epilepsy area is also very sensitive, in the refractory epilepsy. The field of noninvasive preoperative assessment is promising. This study explored the preoperative evaluation value of 256-ch dESI for intractable epilepsy and the effect of different source localization results ("source", sources) model (pattern) on the prognosis of intractable epilepsy in this unit by means of scientific means. The high resolution individual head model and image fusion method of the anatomic data are used to discuss the application and value of the 256 lead high density brain power location (256-ch dESI IHM) technology based on the individual head mode in the preoperative assessment. This study has achieved international and domestic innovation. Part one: the 256 lead high density brain power location technology Preoperative assessment value of refractory epilepsy study in this part of 53 cases of intractable epilepsy to explore the value of preoperative assessment of 256-ch dESI. All cases were examined in our department for a variety of non invasive zone assessment tools including 256-ch dESI, and then accepted stage I resection hand surgery. The region is defined as the area of the epileptic zone, evaluating the location value of a variety of tools with two criteria of Subcerebral lobe level and lobar level. Standard 1 (sublobar level): the assessment tool's positioning results are defined within the range of excision, and the tools for evaluation include 256-ch dESI. PET and MRI; standard 2 (lobe level): assessment tool's determination 256-ch dESI, PET, MRI, paroxysmal symptoms, and cEEG. were defined as the accuracy of the position and the surgical area in the same lobes. We screened 14 clearly diagnosed medial temporal epilepsy (mTLE) based on MRI, paroxysmal symptoms and cEEG results. The temporal lobe and medial structure were used as the assessment of the epileptic zone. Evaluate the value of 256-ch dESI and PET for the assessment of mTLE. This study also analyzed the relationship between factors such as source localization results ("source") patterns and prognosis using statistical methods. The results showed that 256-ch dESI had the highest sensitivity and specificity regardless of which criteria were taken. In 14 cases of mTLE, 256-ch dESI was suggested. The eclampsia area was completely located in the medial and bottom of the temporal lobe in 78.6% of the cases, while PET was only 36.4%, suggesting that 256-ch dESI could provide more accurate positioning information (P0.05, Fisher accurate test). 53 cases were divided into "single source" and "multi source" two groups according to the source localization results ("source"), which were divided into "single source" and "multi source" groups: using Kaplan-Meie. R survival analysis showed that the possibility of postoperative epilepsy remission in the "single source" group was significantly better than that of the "multisource" group (P0.05, Log Rank). According to whether the "source" was removed, the cases were divided into two groups: using Kaplan-Meier survival analysis, the results showed that the possibility of epileptic remission in the "source" group was higher than that of the non resected group (P0.05, Lo). G Rank). Using the Cox regression multifactor analysis, the results showed that the source was excised and the good prognosis related to.256-ch dESI had high spatial and high temporal resolution. It had a unique advantage over other traditional tools. The number of electrodes increased and the electrode cover at the cheek and neck made it detect the discharge of the inside and bottom of the temporal lobe. The study of the source location results ("source") model showed that the single source case may be more suitable for a stage I resection than the "multisource" case, and the removal of "source" may be associated with good prognosis, which also suggests that the region (irritable area) that repeated episodes of interictal epileptic discharge (IEDs) is more than that in the epileptic zone. Good correlation; "multi source" cases may need to consider intracranial electrode embedding first to make use of the intracranial electrode electroencephalogram (icEEG) to clear the area of epilepsy. 256-ch dESI is not suitable for the onset of EEG due to low signal to noise ratio, but our preliminary exploration shows that the technique is feasible and worthy of further research. Current seizures of EEG still depend mainly on cEEG. second parts: PET positive, surgical treatment of MRI negative temporal lobe epilepsy and the value of 256 lead high-density brain power location technology for its preoperative evaluation. The retrospective study of the center is a retrospective study on PET positive, MRI negative temporal lobe epilepsy (PET+MRI-TLE) surgery. The clinical characteristics, surgical treatment and prognosis of 19 cases of PET+MRI-TLE were compared and analyzed in 41 cases of hippocampal sclerosis type temporal lobe epilepsy (HS+TLE) and 18 cases of benign temporal lobe epilepsy (L+TLE). The data analysis showed that the prognosis of group PET+MRI-TLE (Engle grade I: 68.4%, Engle I). + class II: 84.2%) there was no significant difference from group HS+TLE (Engle I: 68.3%, Engle I + II: 80.5%). The analysis also showed that the proportion of thermal convulsions in PET+MRI-TLE and HS+TLE groups was significantly different from that of secondary tonic clonic seizures (P0.05). To a certain extent, PET+MRI-TLE may be a clinical disease that is different from HS+TLE, not HS+TLE. In general, the PET+MRI-TLE, which is correctly evaluated and screened, can consider the acceptance of stage I excision operation.PET, although it is a powerful tool for locating the temporal lobe epilepsy area, however, it has the disadvantages of low specificity and wide range of location, such as.256-ch dESI as a newer non-invasive positioning tool, with high time and spatial resolution. Rate, we have designed a related study to apply it to the preoperative assessment of PET+MRI-TLE and explore its positioning value. Through the selection and exclusion criteria, we selected 12 cases of PET+MRI-TLE, using the surgical excision area combined with the pre definition of the area of the epileptic zone, that is, in the well prognosis cases (9 cases), such as the positioning results of some kind of tool. In the excision area (standard 1, sublobular level) or in the same lobes (standard 2, lobar level), the accuracy was defined. The accuracy of the standard 1256-ch dESI was 7/9=77.8%, and the result of 2 cases of "inaccurate" was that the source location ("source") was located in the middle, posterior temporal lobe, and the temporal occipital junction; the accuracy of PET was 7/9 =77.8%, 2 cases of "inaccurate" results were: a wide range of low metabolism, involving the posterior temporal lobe and the temporal occipital junction. Using standard 2, located in the ipsilateral temporal lobe was defined as accurate, the accuracy of 256-ch dESI was raised to 8/9=88.9%, and 1 cases of "inaccurate" results were that the "source" located in the temporal occipital junction.PET accurately locates all cases, hair The accuracy of the symptomatic assessment was 3/9=33.3%, and the accuracy of the cEEG was 5/9=55.6%. based on whether the source was located in the anterior temporal lobe. The results showed that the prognosis of the "source" case with the anterior temporal lobe was significantly better than that of the non anterior temporal lobe (100%VS 40%, P0.05, Fisher accurate test). This study was the first in the world. 256-ch dESI is applied to the preoperative assessment of PET+MRI-TLE and its application value. The results show that 256-ch dESI is a promising method for accurate localization of MRI negative epilepsy. According to the results of this study, if 256-ch dESI is located in the anterior temporal lobe, the case is suitable for the first phase of the anterior temporal lobe. Except for the operation, if 256-ch dESI is located in the non anterior temporal lobe, such as the posterior temporal lobe or the temporal occipital junction, we should be careful with the stage I excision operation. This characteristic is of certain guiding significance for the selection of such cases of intractable epilepsy. The seizure period EEG data is not suitable for 256-ch dESI, but the seizure period of EEG dependent on cEEG should be MR The important component of preoperative assessment of I negative epilepsy. For MRI negative epilepsy, the operation scheme must not be determined blindly according to a single evaluation method, but should be the result of a comprehensive variety of evaluation methods. The intracranial electrode electroencephalogram (icEEG) examination should be considered when necessary. The third part: Based on the high resolution individual head model. The 256 lead high-density brain power source localization technology and the image fusion with the intracranial electrode electroencephalogram (EEG), the forward model of the high density brain power location (dESI) research is generally based on the common head model (AHM), and a few studies are based on the modified head die (SMAC) based on the individual head MRI, but the essence is still spherical head model, only The average MRI image was replaced by an individual MRI image. Combined with clinical cases, the 256 lead high-density brain power location technique (256-ch dESI IHM) based on high resolution individual head model was applied to the preoperative assessment of intractable epilepsy combined with clinical cases, and the theoretical and clinical value of its application in the localization of epileptogenic area was discussed. Value, international lead. After obtaining the 3D-SPGR sequence MRI (from the head scan to the mandible) and the 256 lead high-density EEG data, the results of 256-ch dESI IHM are obtained by computer and manual processing. The case of intracranial electrode embedding surgery is obtained on the next day after the operation, and then the whole brain thin layer CT plain scan is obtained, and then the computer and manual processing and manual processing are carried out. Individual head model fusion. The present study evaluated the epileptic zone positioning tools by two criteria. Standard 1: the surgical area of a good prognosis case was defined as the area of the epileptogenic area. If a tool defined the eclampsia area within this area, it was accurate; standard 2: intracranial electrode electroencephalogram (icEEG) as the location standard for epileptogenic area, if a worker The defined epileptic zone was consistent with icEEG and was defined as accurate. The case accepted by icEEG was evaluated by the standard 1, and the accuracy was as follows: 256-ch dESI IHM 7/7=100%, 256-ch dESI (256-ch dESI AHM) based on the common head model. .4 PET results in the eclampsia area of all cases were "inaccurate" because of their low metabolic range of.2 MRI results "inaccurate" because of their lack of meaningful focal lesions,.1 cases of "inaccurate" 256-ch dESI AHM results were located near the excision area. Standard 2 was used to evaluate case 1 with icEEG as the standard, 25 6-CH dESI IHM and icEEG are highly consistent with icEEG, while 256-ch dESI AHM, PET and MRI all do not coincide with.256-ch dESI AHM, although the accuracy is slightly deficient, but it is a useful supplement to traditional tools. 256-ch dESI IHM technology with high precision has been feasible after setting a dipole, setting reasonable transmission rate and obtaining high density EEG data, and it can integrate the results of a variety of assessment tools including icEEG to the same view, which helps to make the pre operation planning and operation plan more accurate. First, 256-ch dESI IHM technology was applied to the preoperative assessment of intractable epilepsy, and the image fusion of 256-ch dESI IHM and "gold standard" icEEG was carried out. The accuracy of 256-ch dESI IHM was verified and its application prospects were confirmed. Good correlation. However, the irritable zone and the other regions, such as symptom producing areas, seizure initiation area, epileptogenic focus and functional deletion area, can only be one.

【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R742.1

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