qCEST: Quantitative Chemical Exchange Saturation Transfer MR imaging of brain tumors at 9.4 T
Chemical Exchange Saturation Transfer (CEST) MRI is an indirect molecular imaging method with access to 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 = 9.4T) 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 (see Figure 1).
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 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 9.4T 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.
qCEST: Quantitative Chemical Exchange Saturation Transfer MR imaging of brain tumors at 9.4 T PI: M. Zaiss
Funding: EUR 232.750 for 3 years