Imaging as a Biomarker for Diffuse Intrinsic Brainstem Gliomas

脑干中生物或代谢活动的非侵入性监测的理想方法尚未建立。用于评估脑组织的现有方法（例如PET）在应用于脑干时具有局限性。目前正在研究新的非侵入性成像方法。我们使用动态磁敏感对比MR灌注、动态增强MRI、质子核磁波谱成像和FDG PET来进一步研究脑桥胶质瘤的成像特征。目前有四项临床试验属于该项目。几乎所有患有CNS肿瘤的儿科患者都在至少一项这些研究中进行了广泛的成像。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定义缓解的困难，并根据这些结果提出了这些患者临床获益的新定义。对治疗的反应以及因此新药剂的功效通常使用遵循WHO标准的二维肿瘤测量或最近使用RECIST标准来测量。RECIST标准尚未被验证用于儿童CNS肿瘤的测量，二维测量仍然是联盟试验的标准。我们比较了四个独立的盲读的弥漫性桥脑胶质瘤的1D，2D和3D测量。结果显示，所有测量结果均存在显著变异性（0-197%），因此肿瘤大小的变化是临床试验反应的不良指标。我们还通过电子方式调查了全国的儿科肿瘤学家和神经肿瘤学家，以确定肿瘤测量的标准实践。我们的研究结果表明，没有标准的测量方法被用于测量这些病变。我们发表了一份报告，建议使用FLAIR图像测量DIPG，并将其与研究中的最佳反应扫描进行比较。图像应该并排比较。还建议对涉及DIPG的临床试验进行中心审查。我们将继续评估其他MR序列的效用，包括灌注和光谱成像，以确定特定成像技术（例如光谱、PET）在这些患者中的作用。最近，我们已经证明，随着时间的推移，最大CHO：NAA比率的变化，使用质子光谱成像的预后结果。此外，我们证明了在任何时间点增加灌注是一个不良的预后因素。这些结果现已公布。

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 agents 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. In addition, we demonstrated that increased perfusion at any time point was a poor prognostic factor. These results have now been published..