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INC美国Mitchel Berger教授:高级别胶质瘤复发和治疗后的不同MR特征

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Abstract Background:Differentiating treatment-induced injury from recurrent high-grade glioma is an ongoing challenge in neuro-oncology in part due to lesion heterogeneity.This study aimed to determine whether different MR features were rel...


  Background:Differentiating treatment-induced injury from recurrent high-grade glioma is an ongoing challenge in neuro-oncology in part due to lesion heterogeneity.This study aimed to determine whether different MR features were relevant for distinguishing recurrent tumor from the effects of treatment in contrast-enhancing(CEL)and non-enhancing lesions(NEL).

  Introduction:Tumor recurrence in patients with high-grade glioma(HGG)is difficult to diagnose because treatment-induced injury often appears identical on conventional anatomic magnetic resonance(MR)imaging.It is estimated that 25 to 35 percent of patients who undergo standard of care radiation and chemotherapy in the form temozolomide for HGG experience treatment-related injury,1–3 and its appearance is even more common with the recent advent of immuno-and other targeted therapies in clinical trials.If recurrence is incorrectly diagnosed,a patient may be removed from an effective therapy,which could invalidate the results of a clinical trial or expose a patient to unnecessary surgical intervention.To mitigate these risks,identifying the exact location and extent of treatment related changes within newly enlarging lesions is critical.To overcome the complications introduced by tissue heterogeneity in ROI-based studies,one strategy is to use image-guided tissue samples of known coordinates to directly map MRI characteristics to histopathology.In 2002,Rock et al.pioneered this technique in distinguishing radiation necrosis from recurrent disease using metabolite ratios derived from 1H MR spectroscopic Imaging(MRSI)at the location of sampled tissue17.Their findings suggested that the ratios of choline and lactate/lipid to creatine could differentiate samples with pure necrosis and tumor,but not those with mixed pathology.In 2009,Hu et al.utilized this technique in conjunction with Dynamic Susceptibility Contrast(DSC)perfusion-weighted imaging to distinguish post-treatment radiation effect from recurrent tumor with high sensitivity and specificity using relative cerebral blood volume(rCBV)values from 13 patients.The goal of this study was to determine whether different MR characteristics were relevant for distinguishing pathological features of recurrent tumor from the effects of treatment in the contrast enhancing and non-enhancing lesions of recurrent high-grade gliomas by leveraging a unique dataset of image-guided tissue samples of known coordinates to avoid complications of tissue heterogeneity that confounds most lesion-level analyses.Based on prior literature,we expect that samples comprised of recurrent tumor will have increased blood volume and abnormal metabolism,with decreased diffusion compared to samples containing treatment-effect.We also hypothesize that:1)this difference would be more pronounced in diffusion and perfusion metrics for samples within the contrast enhancing lesion(CEL),while metabolic measures would be equally effective at differentiating recurrent tumor from treatment effect in both the contrast enhancing and nonenhancing lesions(NEL);and 2)the addition of multiparametric physiologic and metabolic MRI in conjunction with tissue sample level analyses will provide increased sensitivity and specificity in distinguishing recurrent tumor from the effects of treatment in both types of lesions compared to anatomical imaging.

  Methods:This prospective study analyzed 291 tissue samples(222 recurrent tumor;69 treatment-effect)with known coordinates on imaging from 139 patients that underwent preoperative 3T MRI and surgery for a suspected recurrence.8 MR parameter values from perfusion-weighted,diffusion-weighted,and MR spectroscopic imaging at each tissue sample location were tested for association with histopathological outcome using generalized estimating equation models for CEL and NEL tissue samples.Individual cutoff values were evaluated using ROC-Curve analysis with 5-fold cross-validation.

  Results:In tissue samples obtained from the CEL,elevated relative cerebral blood volume(rCBV)was associated with the presence of recurrent tumor pathology(p<0.03),while increases in normalized choline(nCho)and choline-to-NAA index(CNI)were associated with the presence of recurrent tumor pathology in NEL tissue samples(p<0.008).A mean CNI cutoff value of 2.7 had the highest performance,resulting in mean sensitivity and specificity of 0.61 and 0.81 for distinguishing treatment-effect from recurrent tumor within the NEL.

  Conclusion:Although our results support prior work that underscores the utility of rCBV in distinguishing the effects of treatment from recurrent tumor within the contrast enhancing lesion,we found that metabolic parameters may be better at differentiating recurrent tumor from treatment-related changes in the NEL of high-grade gliomas.







  关于美国Mitchel Berger教授


  Mitchel Berger教授来自美国神经外科医院排名第三、世界闻名的神经外科疾病研究和治疗机构UCSF医学中心。Mitchel Berger教授是全美公认的成人及儿童脑肿瘤治疗知名专家,在任职UCSF神经外科主席之前,他还担任过美国神经外科协会主席、美国神经学医师协会主席、美国癌症研究协会州立法委员会主席、北太平洋神经及神经外科和精神病学会主席,在神经外科疾病临床诊疗、癌症研究和基因治疗等方面有突出贡献。目前,Mitchel Berger教授是UCSF医学中心SPORE脑肿瘤项目的首席研究员,也是美国国家“癌症登月”计划蓝带小组专家。

  除了在美国享誉盛名,Mitchel Berger教授更是世界神经外科领域内清醒开颅手术、脑功能监测技术方面的知名专家,尤其在脑部术中建图方面拥有非常丰富的专业知识,能够准确识别运动、感觉和语言功能的部位,从而避免在手术过程中伤及重要神经,能在很大程度上保障手术的精准性和安全性。由Mitchel Berger教授发明的超声引导手术器械方法获得了美国专利商标局(USPTO)授予的专利,目前已在神经外科领域广泛推广使用。