Imaging as a Biomarker for Diffuse Intrinsic Brainstem Gliomas

非侵入性监测脑干生物或代谢活动的理想方法尚未建立。现有的评估脑组织的方法(例如PET)在应用于脑干时存在局限性。目前正在研究新的非侵入性成像方法。我们正在使用动态磁化率对比MR灌注、动态增强MRI、质子核磁光谱成像和FDG PET来进一步研究桥脑胶质瘤的成像特征。目前有四项临床试验属于该项目。几乎所有患有中枢神经系统肿瘤的儿科患者都至少在其中一项研究中接受了广泛的成像。在过去的几年里，我们已经证明了在临床试验中使用标准MRI来定义反应的困难，并根据这些结果提出了对这些患者的临床益处的新定义。治疗反应和新GIMT的疗效通常是根据世卫组织的标准使用二维肿瘤测量来衡量的，或者最近使用RECIST标准来衡量。RECIST标准尚未被证实用于儿童中枢神经系统肿瘤的测量，二维测量仍然是联合试验的标准。我们比较了四个独立的盲读取器对弥漫性桥脑固有胶质瘤的1D、2D和3D测量结果。结果表明，所有测量结果都有显著的变异性(0-197%)，因此肿瘤大小的变化不是临床试验反应的一个很差的指标。我们还对全国的儿科肿瘤学家和神经肿瘤学家进行了电子调查，以确定肿瘤测量的标准实践。我们的结果表明，在这些病变的测量中没有标准的测量方法。我们已经发表了一份报告，建议使用FLAIR图像来测量DIPG，并将其与研究中的最佳响应扫描进行比较。图像应该一张一张地比较。还建议对涉及DIPG的临床试验进行中央审查。我们正在继续评估其他MR序列的实用性，包括灌注成像和光谱成像，试图确定特定成像技术(如光谱学、PET)在这些患者中的作用。最近，我们使用质子光谱成像技术证明了最大CHO：NAA比率随时间的变化可以预测预后。这是在国际儿科神经肿瘤学学会上提出的，并已提交了一份手稿。此外，我们还证明，任何时间点的血流灌注增加都是一个不良的预后因素。在ISPNO(Viena 2010)上也介绍了这一点。

The ideal method for non-invasive monitoring of biological or metabolic activity in the brainstem has not yet been established. Existing methods for evaluating cerebral tissue (e.g. PET) have limitations when applied to the brainstem. New noninvasive imaging methods are currently being studied. We are using dynamic susceptibility contrast MR perfusion, dynamic enhanced MRI, proton nuclear magnetic spectroscopic imaging, and FDG PET to further investigate the imaging characteristics of pontine gliomas. There are four clinical trials which currently fall under this project. Nearly all pediatric patients with CNS tumors undergo extensive imaging on at least one of these studies. Over the past several years, we have demonstrated the difficulty in using standard MRI for definition of response in clinical trials and have proposed a new definition of clinical benefit for these patients based on these results. Response to treatment and therefore efficacy of new gents is typically measured using two-dimensional tumor measurements following WHO criteria, or more recently, using RECIST criteria. RECIST criteria have not been validated for the measurement of pediatric CNS tumors and two-dimensional measurements continue to be the standard in consortium trials. We compared the 1D, 2D and 3D measurements of diffuse intrinsic pontine gliomas by four separate blinded readers. The results show that there is significant variability (0-197%) in all measurements and change in tumor size is therefore a poor indicator of response for clinical trials. We have also electronically surveyed pediatric oncologists and neuro-oncologists across the country to determine the standard practice of tumor measurement. Our results show that there is no standard measurement method being used in the measurement of these lesions. We have published a report recommending the use of FLAIR images to measure DIPG and comparing these with the best response scans on study. Images should be compared side by side. Central review was also recommended for clinical trials involving DIPG. We are continuing to evaluate the utility of additional MR sequences, including perfusion and spectroscopic imaging in an attempt to define the role of specific imaging techniques (e.g. spectroscopy, PET) in these patients. Recently, we have demonstrated that changes in maximum CHO:NAA ratios over time using proton spectroscopic imaging were prognostic of outcome. this was presented at the International Society of Pediatric Neuro-Oncology and a manuscript has been submitted. In addition, we demonstrated that increased perfusion at any time point was a poor prognostic factor. This was also presented at ISPNO (Viena 2010).