1、 Glioma : Diffusion kurtosis MR Imaging in grading Purpose：To assess the diagnostic accuracy of diffusion kurtosis magnetic resonance imaging parameters in grading gliomas 目的：评价磁共振参数扩散峰度成像在诊断脑胶质瘤分级中的准确性。Materials and methods: The institutional review board approved this prospective study, and inform
2、ed consent was obtained from all patients.材料与方法：学术机构审查委员会批准了这项前瞻性研究，并获得知情同意的患者。Diffusion parametersmean diffusivity (MD),fractional anisotropy (FA), mean kurtosis, and radial and axial kurtosiswere compared in the solid parts of 17 high-grade gliomas and 11 low-grade gliomas (P0.5 significance level
3、, Mann-Whitney-Wilcoxon test, Bonferroni correction).扩散参数包括平均扩散率（MD），各向异性分数（FA），平均峰度，径向峰度和轴向峰度。 这些参数在17例高级实体胶质瘤和11例低级实体胶质瘤中作比较，通过Mann-Whitney秩和检验，Bonferroni校正来进行数据分析，当P 0.5，差异有统计学意义。MD, FA, mean kurtosis, radial kurtosis, and axial kurtosis in solid tumors were also normalized to the corresponding v
4、alues in contralateral normal-appearing white matter (NAWM) and the contralateral posterior limb of the internal capsule (PLIC) after age correction and were compared among tumor grades.经过年龄校正后，参照对侧正常白质（NAWM）和对侧内囊后肢（PLIC）的相应值，将实体肿瘤的MD、FA、平均峰度、径向峰度与 轴向峰度标准化，并与肿瘤等级对照。Results: Mean, radial, and axial k
5、urtosis were significantly higher in high-grade gliomas than in low-grade gliomas (P = .02, P = .015, and P = .01, respectively) FA and MD did not significantly differ between glioma grades. . All values, except for axial kurtosis, that were normalized to the values in the contralateral NAWM were si
6、gnificantly different between high-grade and low-grade gliomas (mean kurtosis,P = .02; radial kurtosis, P = .03; FA, P = .025; and MD, P = .03). 结果：高级胶质瘤平均、径向峰度和轴向峰度都高于低级胶质瘤（分别为P=0.02、P=0.015 和 P=0.01）。 不同等级的胶质瘤FA和MD差异无统计学意义。 除 轴向峰度外，高 级与低级胶质瘤的所有参数值参照对侧 NAWM参数值标准化后均有差异。 （平均峰度，P =0.02；径向峰度，P =0.03；各项
7、特异性P =0.025；平均扩散率P =0.03 ）。When values were normalized to those in the contralateral PLIC, none of the considered parameters showed significant differences between high-grade and low-grade gliomas. 但是所有参数值参照对侧 PLIC参数值标准化后，高级别与低级别胶质瘤的参数值间均无差异。The highest sensitivity and specificity for discriminating
8、 between high-grade and low-grade gliomas were found for mean kurtosis (71% and 82%, respectively) and mean kurtosis normalized to the value in the contralateral NAWM (100% and 73%, respectively). 鉴别高级脑胶质瘤和低级脑胶质瘤，最敏感最特异性的指标是平均峰度值(分别是100% 和73%)和对侧NAWM标准化后的平均峰度值 (分别是100%和73%)。Optimal thresholds for me
9、an kurtosis and mean kurtosis normalized to the value in the contralateral NAWM for differentiating high-grade from low-grade gliomas were 0.52 and 0.51, respectively. 最合适的平均峰度 值阈值是 0.52，最合适的对侧 NAWM标准化后的平均峰度值的阈值是 0.51。Conclusion : There were significant differences in kurtosis parameters between hig
10、h-grade and low-grade gliomas; hence, better separation was achieved with these parameters than with conventional diffusion imaging parameters.结论： 成像的参数在高级胶质瘤和低级胶质瘤之间存在显著差异。因此，与传统的扩散参数成像相比， DKI 成像可更好地区分两种级别的肿瘤 。Gliomas are the most common primary brain tumors in adults, with an incidence of four to
11、seven per100000 per year. They cover a broad range of lesions of different cellular origins and with distinct differences in malignancy. 胶质瘤是最常见的原发性脑肿瘤在成年人中，发病率是4-7100000每年。它们涵盖广泛的不同细胞起源的有明显差异的恶性病变。 The 4th edition of the World Health Organization classification of tumors of the central nervous syst
12、em currently serves as the most important reference for guiding therapy and assessing overall prognosis in patients with brain tumors.。The World Health Organization classification guidelines state that adequate grading of gliomas prior to treatment is, among clinical findings such as age and tumor l
13、ocation, of utmost importance in predicting response to treatment and outcome. 第四版世界卫生组织中枢神经系统肿瘤分类对脑肿瘤患者的指导治疗和总体预后评估有重要的参考作用世界卫生组织分类准则规定，治疗之前的神经胶质瘤依据临床表现如年龄、肿瘤位置进行的分级，在预测治疗反应和预后评估上起重要作用。 Diffusion magnetic resonance (MR) imaging has proven to be of additional value in glioma grading. However, diffus
14、ion weighted (DW) imaging and diffusion tensor (DT) imaging still lack sensitivity and specificity for monitoring cellular changes related to malignant progression . Histologic examination still remains the standard of reference to obtain a definitive diagnosis in brain neoplasms and is required in
15、current oncologic practice to start adjuvant therapy. 扩散磁共振成像已经被证明在胶质瘤分级上有额外的价值。然而，扩散加权（DW）成像和弥散张量成像（DT）对于监测与恶性进展相关的细胞的变化仍然缺乏敏感性和特异性。在脑肿瘤中，组织学检查仍然是获得一个明确的诊断的标准参考。目前，当 肿瘤学实践需要启动辅助治疗时，必须要进行组织学检查。DW and DT imaging measure the mobility of water molecules, assuming a process of random, unrestricted but p
16、otentially hindered, diffusion. The diffusion probability distribution function (PDF), the chance of a particular proton diffusing from one location to another in a given time, is thus considered a Gaussian PDF, with the standard deviation relating to the apparent diffusion coefficient. DW 和 DT 成像测量
17、水分子的流动,假设的是一个随机的过程,但有可能受阻,无限制的扩散。扩散概率分布函数(PDF)描述的是一个特定的质子在一个给 定的时间内从一个位置扩散到另一个位置的概率。,因此高斯 PDF 被认为有一个与表观扩散系数相关的标准偏差。However, the complexity of the biologic cytoarchitecturedetermined by, for example, cell membranes, intracellular organelles, and the rapid exchange of protons between different compart
18、mentswill inhibit random Brownian motion and thus causes water diffusion to deviate from strict Gaussian behave or This is referred to as “restricted” diffusion. 然而，细胞膜、胞内 细胞器,不同间隙的质子快速交换决定生物细胞结构的复杂性，这将抑制随机的布朗运动,从而导致水扩散偏离严格高斯分布，或者，这就是“ 限制” 扩散。 The actual PDF will appear more peaked compared with a G
19、aussian PDF, and therefore, the apparent diffusion coefficient is inadequate to describe proton diffusion properly. The degree of deviation from a Gaussian PDF can be quantified by a dimensionless metric, the apparent excess kurtosis coefficient (AKC). Kurtosis is a dimensionless statistical measure
20、 to describe the non-Gaussian nature of an arbitrary probability distribution. 实际的 PDF 比高斯PDF 将出现更多的峰值,因此,表观扩散系数是不足以正确描述质子扩散。偏离高斯 PDF 的程度可以被一个无量纲指标量化,这个无量纲的指标是表观过度峰值系数(AKC)。峰值是一个无量纲的统计工具，用于描述任意分布概率的非高斯本质。Diffusion kurtosis (DK) imaging, an extension of the DT imaging model, allows the simultaneous e
21、stimation of apparent diffusion coefficient and AKC on a direction-dependent basis . By measuring apparent diffusion coefficient and AKC in at least 15 nonlinear directions, the Gaussian and non-Gaussian components of three-dimensional water mobility are quantified by the DT and the DK tensor, respe
22、ctively. 扩散峰度成像（DKI ），是 DT成像模型的一个扩展，允许在一个方向基础上同时估计表观扩散系数（ADC）和AKC。 通过在至少15个非 线性方向上测量ADC和AKC，分别用DT、 DK量化高斯和非高斯三 维水成分流 动性。 From both tensors, several scalar measures can be derived, such as all conventional DT parameters (fractional anisotropy FA, radial diffusivity, axial diffusivity, and mean diffus
23、ivity MD) and several kurtosis parameters (radial, axial, and mean kurtosis) .从这几个张量，派生出几个标量，如所有的 传统 DT 参数（各向异性分数，径向 扩散系数，轴向扩散系数，和平均扩散MD）和几个峰度参数（径向， 轴向和平均峭度）。 Analog to the directional diffusivity measures in DT imaging, axial kurtosis is defined as the AKC measured along the direction parallel to t
24、he principal diffusion direction the first diffusion eigenvector, whereas radial kurtosis is defined as the average AKC measured in the plane perpendicular to the first eigenvector. ean kurtosis is the average of the AKC along all directions of a densely sampled sphere . Non-Gaussian diffusion is de
25、monstrated in both gray and white matter, with higher mean kurtosis in white matter indicating a generally higher degree of diffusion complexity and restriction in white matter structures. 轴向峰度定义为沿平行于主扩散方向测得的 AKC，第一扩散特征向量，而径向峰度定义为在垂直于第一特征向量的平面测量的平均 AKC。M 平均峰度是在一个采样密集非高斯扩散的球形区域的 AKC 平均值，这个模型适用于灰质和白质，
26、具有较高的平均峰度的白质表明其结构的复杂性和扩散程度限制性。Wu and Cheung were able to show that the main contributor to higher mean kurtosis in white matter is radial kurtosis. 吴 Axial diffusivity and kurtosis are believed to reflect the axonal integrity and density of fiber bundles, whereas radial diffusion metrics are assumed
27、 to reflect myelin integrity and axonal density. 和陈已经证明，决定白质平均峰度的主要因素是径向峰度。轴向扩散系数和峰度被认为反映轴突完整性和纤维丛的密度，而径向扩散指数被认为是反映了髓鞘的完整性和轴突密度。Although the physical meaning of DK, essentially the translation to cell properties and histologic details, is still being debated, it is assumed that the deviation from Ga
28、ussian diffusion is assigned to the assembly of diffusion signals of protons in different compartments. In biologic tissue, this encompasses the intra- and extracellular space in the most widely used model. Differences in DK are believed to arise from diffusion restricted by barriers, such as cell m
29、embranes and organelles, as well as the presence of distinct water compartments with varying diffusion properties or varying component sizes from the intra-or extracellular space . 尽管物理意义的 DK,是翻译成细胞特性还是组织学的细节仍在讨论,假定高斯扩散的偏离被分配到不同间隔的质子的扩散信号的组装。在生物组织,在使用最广泛的模型中，这包含了内部和细胞外空间。 DK 上的差异被认为是因为受到障碍限制的扩散,如细胞膜
30、和细胞器,以及有不同扩散属性的不同间隙的存在或者从内部或细胞外部空间可变的组份的大小。Because gliomas display specific cytoarchitectural alterations related to biologic aggressiveness , we believe that DK imaging can be of particular interest in noninvasively providing insights in glioma grading. In this study, we evaluated the diagnostic ac
31、curacy of DK imaging parameters in grading gliomas. 由于胶质瘤显示生物攻击性相关的特异性细胞结构的改变，我们相信DKI在胶质瘤分级中可以无创性的提供见解。 在这项研究中，我 们评估了DKI在诊断胶质瘤分级中的准确性。Advances in Knowledgeadvances in knowledge（知识的进步）Compared with conventionally used diffusion imaging techniques, diffusion kurtosis imaging provides additional inform
32、ation on microstructure and microdynamics in gliomas by exploringnon-Gaussian diffusion properties. 与常规使用的扩散成像技术相比， 扩散峰度成像在胶质瘤组织和微观动力学提供额外的信息，通过探索非高斯扩散特性。Diffusion kurtosis imaging can help better distinguish low-grade from high-grade gliomas than conventional diffusion-weighted imaging and diffusio
33、n tensor imaging.扩散峰度成像比传统的扩散加权成像和弥散张量成像可以帮助更好的区分低级胶质瘤和高级胶质瘤。Implication for patient care（对病人的暗示）Mean kurtosis is a more accurate metric for differentiating between high-grade and low grade gliomas than mean diffusivity, fractional anisotropy, and morphologic imaging parameters.鉴别高级和低级胶质瘤，相比比平均扩散率，各
34、向异性，和形态学成像参数，平均峰度是更精确的度量标准。Materials and methods Patient PopulationThe institutional review board of the University Hospitals of Leuven (Leuven, Belgium) approved this study. Written informed consent was obtained from every patient before participation. Patient recruitment and imaging were performed
35、 between May 2010 and January 2011. Thirty consecutive patients who were suspected of having cerebral glioma on the basis of conventional radiologic findings were enrolled in this prospective study prior to any treatment (nine women, 21 men; age range, 2076 years; average age, 53 years). All patient
36、s were seen and treated afterward by a neurosurgeon鲁汶大学医院的机构审查委员会（鲁汶，比利时）批准了这项研究。从每一个病人在参与前获得书面知情同意。2010五月和2011一月间进行的病人招募和成像。三十例怀疑在常规影像学结果的基础上，具有脑胶质瘤患者在这项前瞻性研究之前未接受任何治疗（九为女性，21为男性；年龄范围，2076年；平均年龄，53岁）。所有患者事后均由神经外科医生治疗处理。. Patients with recurrent tumors were excluded. The minimum age to participate w
37、as 18 years, in conformity with the local jurisdiction regarding the age of majority and the local institutional board definition of “adult” patients. None of the included patients had neurologic disorders other than primary neoplasm. Three (10%) of the 30 patients were ultimately excluded from this
38、 study because they were found to have lesions other than gliomas at histologic examination (one patient had ahem angioblastoma, and two patients had focal cortical dysplasia) 复发性肿瘤的患者被排除在外。参与的最低年龄为18岁，符合当地的管辖权对于年龄的人和地方机构委员会定义的“成人” 的病人。所有患者除了有原发性肿瘤外没有其它的神经性疾病。30例患者中的三（10%）最终被排除在这项研究中，因为发现他们，在组织学检查上除
39、了有脑胶质瘤病变外还有其它损伤。（一个病人有成血管细胞瘤，2例有局灶性皮质发育不良）. The final study group consisted of 27 patients (eight women, 19 men; age range, 20 76 years; average age, 54 years). We enrolled 16 patients (59% of the study group) with high-grade glioma; of the patients in this group, 15 had a grade IV glioma (glioblast
40、oma multiforme), and one patient had a grade III glioma. Ten patients with low-grade gliomas were enrolled (37% of the study group). One patient had a grade II glioma with focal progression to a grade III glioma (4% of the study group). Hence, 17 high-grade lesions and 11 low-grade lesions were incl
41、uded in the study sample. Histopathologic confirmation was obtained in all patients with high-grade gliomas, in six patients with low-grade gliomas, and in the patient with low-grade glioma and focal progression (85% of the study group). 最终的研究组包括 27例患者（八名女性，19名男性；年龄范围，20 76年；平均年龄，54岁）。我们招募了16例患者（研究组
42、的59%）有高级别胶质瘤；本组患者中，15例级胶质瘤（胶质母细胞瘤），和一个病人有一个三级胶质瘤。十例脑胶质瘤患者（研究组37%）。一个病人有局灶性进展为 级胶质瘤的级胶质瘤（4%研究组）。因此，17高档病变和11个低度病变的研究样本。在所有高级别胶质瘤患者，在低级别胶质瘤六例，并在低级别胶质瘤和局灶性进展的患者（研究组85%）获得病理组织学证实。In the group of six patients with low-grade gliomas and a histopathologic diagnosis, one patient was diagnosed with a grade I
43、I diffuse fibrillary glioma, one patient had a grade II pilocytic astrocytoma, two patients had a grade II oligodendroglioma, and two patients had a grade II oligoastrocytoma. All lesions were classified according to grade by using the World Health Organization classification (1). The time lapse bet
44、ween the MR imaging examinations and surgery was a maximum of 28 days. 在低级别胶质瘤，病理诊断六例患者组中，1例患者被确诊为弥漫纤维胶质瘤 级，一个病人有II级毛细胞型星形细胞瘤，2例级少突胶质细胞瘤，2例为级少突星形细胞瘤。所有病变均按等级采用世界卫生组织分类（1）。MR影像学检查和手术之间的时间间隔是一个最大的28天。 The remaining four patients with low-grade gliomas were considered to have low-grade gliomas on the b
45、asis of findings at clinical and radiologic follow-up and imaging features at O-(2-fluorine 18 fluoroethyl)- l-tyrosine (FET) positron emission tomography (PET). PET imaging with radiolabeled amino acids has been used for metabolic studies of intracerebral tumors because protein metabolism is increa
46、sed in brain tumors to meet the requirements of maintaining a high degree of protein synthesis for rapid growth and continuous proliferation. 其余四例低级别胶质瘤被认为在临床和影像学随访和正电子发射断层扫描（FET-PET）影像学特征的基础上为有低级别胶质瘤。放射性标记的氨基酸的PET成像已被用于研究脑肿瘤代谢研究是因为脑肿瘤内的蛋白质代谢的增加以满足蛋白质合成高度，为了快速增长和不断增殖。Dynamic imaging with FET-PET is
47、advocated as the technique of choice in grading gliomas with nuclear medicine imaging techniques. It has been shown that the kinetic behavior of FET uptake differs significantly between low-grade and high-grade gliomas (13). Of the four patients with low-grade gliomas without histopathologic confirm
48、ation, two were followed up for 2 and 7 years and have shown during this follow-up time until the present no clinical or radiologic evidence of progression. One other patient first received a diagnosis of glioma and preferred not to undergo biopsy or surgery. Until the present time, 1 year after fir
49、st diagnosis, the lesion in this patient has shown no changes at conventional MR imaging and no evidence of clinical progression. The fourth patient showed an increase in tumor volume at follow-up imaging after 6 months and consequently underwent biopsy. Histopathologic examination at that time revealed a grade II pilocytic astrocytoma fet-pet动态成像与核医学成像技术被提倡为在胶质瘤的分级中的精选技术。它已被证明，在低和高级别胶质瘤间FET的吸收动力学行为变化显著（ 13）。对没有组织病理学认证的四例脑胶质瘤患者，两个随访2年和7年期间，已经证明这至今没有临床或放射学证据的进展。另一个病人被诊断脑胶质瘤，不愿意接受活检或手术。直到现在，1年后第一次诊断，在这个患者病变已在常规 MRI无变化，无临床进展的证据。第四例患者后6个月在随诊的影像摄片上显示肿瘤体积的增大，因此接受
