Chemical exchange saturation transfer (CEST) and chemical exchange sensitive spinlock (CESL) were shown to have potential to provide molecular information for diagnosing a wide range of diseases. However, the lack of standardized acquisition protocols and freely available post-processing software prohibited the widespread application of these promising techniques until now. In this work, we present a modularly designed CEST/CESL preparation block that is easy to operate and can be used with arbitrary MRI readouts. Further, we developed and provide a C++ based open-source software that offers many CEST/CESL specific functionalities for the post-processing of the acquired data.
CE sensitive MRI sequences are composed of a magnetization preparation and a data acquisition part. The simplest RF preparation in CEST-MRI is a rectangular pulse that is applied for several seconds. However, safety issues and technical limitations of whole-body MR scanners require the use of more advanced preparation approaches consisting of several shorter pulses of more sophisticated shapes.2 The development of such advanced preparation blocks is quite complex and time-consuming.
The asymmetry analysis (MTRasym)3 is the simplest and most commonly utilized CEST metric. Yet, it already requires the normalization and correction for B0-inhomogeneities of the data. More sophisticated CEST metrics like the apparent exchange-dependent relaxation (AREX)4 and/or additional correction algorithms (e.g. for spatial variations of B1) further require the acquisition of B1 and/or T1 maps.5
The pulse sequence was developed within the Integrated Development Environment for MR Applications (IDEA) of Siemens (Siemens Healthcare, Germany). The preparation part was designed in a modular manner and consists of a sequence building block (SBB) and a user interface (UI). The following parameters can be adjusted in the UI: number, duration, distance, power and shape of the saturation pulses, number of offsets and sampling type (e.g. ′regular distance′, ′read txt-file′), recovery times, spoiling options and the parameters of the adiabatic pulses, which are used for spinlock6 and T1 measurements. Due to its modular design, the preparation part can be merged with almost any readout sequence with just little modifications (Fig. 1).
Processing of the resulting images was done with the Medical Imaging Interaction Toolkit (MITK)7. MITK is a C++ based library and application framework. It provides a suite of tools for many common image processing needs such as segmentation, image registration, fitting functionality and read/write support for a wide variety of image formats. It also provides specialized functionality for specific MR applications such as diffusion-weighted MRI8. It was extended to support the presented CEST/CESL sequence and provide CEST/CESL specific features.
The developed preparation block was successfully merged with various readout sequences. These were checked for functionality on several Siemens MR-systems operated under software versions between IDEA VB17 and VE11. The sequences allow the acquisition of arbitrary CEST/CESL contrasts and all relevant parameter maps. This includes the simultaneous acquisition of B0 and B1 maps by means of WASABI9 and the acquisition of T1 maps using adiabatic inversion or saturation recovery. Further, the implemented basic-mode allows switching between these and other predefined preparation-types easily (Fig. 2).
The developed analysis and visualization software MITK-CEST extends the general MITK workbench with several CEST/CESL features and a specific UI that was designed in cooperation with radiologists. MITK-CEST enables the intuitive visualization and interactive exploration of frequency- (e.g. CEST, WASABI) or time-dependent (e.g. T1, dynamic glucose-enhanced CEST/CESL) data and derived information (Fig. 3). Other CEST/CESL functionalities are amongst others normalization, B0-correction, fitting (e.g. T1, WASABI, Multi-Lorentzian) and the calculation and visualization of different contrasts like MTRasym or AREX.
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