qCEST: Quantitative Chemical Exchange Saturation Transfer MR imaging of brain tumors at 7 Tesla

CEST磁共振成像被认为是生物医学成像领域的一个令人兴奋的课题。它的主要优点是可以成像生理和分子信息，空间分辨率与常规MRI相当。CEST信号与蛋白质含量、蛋白质结构、代谢物浓度和细胞内pH的相关性使CEST成为肿瘤研究的一种有趣的成像手段：蛋白质含量是肿瘤侵袭过程中细胞密度增加的量度；此外，pH梯度与肿瘤转移之间存在相关性。然而，最近的研究揭示了需要改进的技术来适当地分离通常所称的CEST对比的不同贡献者，例如饱和的酰胺质子交换或蛋白质的脂肪质子交换。由于高频率分辨率，在超高场强(B0=7T)下分离这些单独的CEST效应是可能的。在以前对模型溶液和动物的研究中，我们可以证明CEST数据也必须针对水质子弛豫性质的变化进行校正。这在胶质母细胞瘤的成像中特别重要，因为水松弛参数在这些肿瘤中是改变的。因此，需要一种定量CEST方法(QCEST)来充分发挥CEST成像的潜力，以提供蛋白质含量和pH图。CEST MRI的第二个挑战是相对较长的扫描时间，这阻碍了其临床应用。为了在人类患者中推广常规的QCEST成像，我们打算在两个方向上发展这项技术：(I)开发一种能够深入了解CEST基本参数并提供参考方法的定量CEST序列；(Ii)开发一种快速临床CEST序列并将其引入临床应用。首先，在之前的动物工作之后，将为CEST MRI在人类身上建立重要的纠正步骤。根据以前工作中可获得的序列，将开发能够定量获取蛋白质含量和pH的方法。在用模型溶液进行实验验证后，将在健康受试者身上进行体内评估。同时，将开发扫描时间优化的临床CEST序列。在这里，k空间采集、饱和和读出分割、视图共享和压缩传感技术将针对CEST MRI数据的特定特征进行优化。利用定量CEST序列的结果，这一临床CEST序列将在模体和志愿者研究中得到验证和进一步优化。与扩散加权成像和31P磁共振波谱相比，可以分析qCEST与细胞密度和pH的相关性。最后，将在7T对胶质母细胞瘤患者和较低级别脑肿瘤患者进行检查。通过与标准MR对比，可以评估定量CEST的临床益处。

CEST MRI is regarded as an exciting topic in the field of biomedical imaging. Its major advantage is imaging of physiological and molecular information with spatial resolution comparable to that of conventional MRI. Correlations of CEST signals with protein content and protein structure, metabolite concentration, and intracellular pH have made CEST an interesting imaging modality for studies of cancer: Protein content is a measure of increased cellularity during tumor infiltration; furthermore there is a correlation between gradients in pH and tumor migration. However, recent studies have revealed the need for improved techniques to properly isolate different contributors to what is commonly called a CEST contrast, such as exchange of saturated amide protons or aliphatic protons of proteins. Separation of these individual CEST effects is possible at ultra-high field strength (B0 = 7 T) due to the high frequency resolution. In previous studies with model solutions and animals we could show that CEST data must also be corrected for changes in the relaxation properties of water protons. This is of particular importance in imaging of glioblastoma, since water relaxation parameters are altered in these tumors. Hence, a quantitative CEST approach (qCEST) is required to develop the full potential of CEST imaging to provide protein content and pH maps.A second challenge of CEST MRI is a comparatively long scanning time which impedes its clinical application. To promote routine qCEST imaging in human patients, we intend to advance the technique in two directions: (i) Development of a quantitative CEST sequence that yields insights into the fundamental CEST parameters and provides a reference method, and (ii) development of a fast clinical CEST sequence and its introduction into clinical use. First, important correction steps, following previous animal work, will be established for CEST MRI in humans. Based on the sequence available from prior work, methods that enable quantitative access to protein content and pH will be developed. After their validation in experiments with model solutions, in vivo evaluation in healthy subjects will be performed. Simultaneously, a scanning-time-optimized clinical CEST sequence will be developed. Here, k-space acquisition, saturation and readout segmentation, view-sharing, and compressed sensing techniques will be optimized with respect to the specific features of CEST MRI data. Using the results of the quantitative CEST sequence, this clinical CEST sequence will be validated and further optimized in studies with phantoms and volunteers. Comparison with diffusion-weighted imaging and 31P MR spectroscopy will allow analysis of correlations of qCEST with cellularity and pH. Finally, examinations will be performed at 7 T in patients with glioblastoma and patients with lower grade brain tumors. Comparison with standard MR contrasts will permit the assessment of the clinical benefit of quantitative CEST.