Joint Annual Meeting ISMRM-ESMRMB 2014 10-16 May 2014 Milan, Italy



3149-3169 CEST & MT Contrast 

CEST & MT Contrast

Thursday 15 May 2014
Traditional Poster Hall  13:30 - 15:30

3149.   The exchange pathways of NOE-CEST as revealed by NMR study
Haifeng Zeng1,2, Nirbhay N. Yadav1,2, Xiang Xu1,2, Kannie W.Y. Chan1,2, Guanshu Liu1,2, Michael T. McMahon1,2, Peter C.M. van Zijl1,2, and Jiadi Xu1,2
1Kirby Center, Kennedy Krieger Institute, Baltimore, MD, United States, 2Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Amide Proton Transfer (APT) and relayed NOE CEST (rNOE-CEST) images of endogenous mobile protein in vivo can be used to detect pH changes as well as tumors. However, the precise mechanisms underlying the magnetization transfer contributions among water, amide protons and aliphatic protons in mobile proteins is still under debate. Using a series of NMR experiments on egg white, we confirmed that the magnetization transfer from water to aliphatic protons is relayed through amide protons.

3150.   3D Fast Spin-Echo Amide Proton Transfer MR with Intrinsic Field Homogeneity Correction for Neuro-Oncology Applications
Jochen Keupp1, Mariya Doneva1, Julien Sénégas1, Silke Hey2, and Holger Eggers1
1Philips Research Europe, Hamburg, Germany, 2Philips Healthcare, Best, Netherlands

Amide proton transfer (APT), an endogenous saturation transfer contrast, has recently gained attention as a molecular imaging approach in oncology and neurology. For clinical applications, 3D coverage of the whole tumor or whole brain within acceptable acquisition time as well as a robust field homogeneity correction is essential. In this work, we combined previous approaches for fast-spin echo APT MRI with radial phase encoding and intrinsic 3-point spin-echo Dixon B0 mapping and homogeneity correction. The volunteer study (N=9) demonstrates the ability to obtain homogeneous and high SNR 3D APT images in the brain using a single examination in less than 5 minutes.

3151.   Amide Proton Transfer Imaging of the Head and Neck at 3T: A Feasibility Study and preliminary results
Jing Yuan1, Ann D King1, Shuzhong Chen1, Kunwar S Bhatia1, Qinwei Zhang1, Tom Wing Cheung Yuen1, Yi-Xiang J Wang1, David Ka Wai Yeung1, Juan Wei2, and Jinyuan Zhou3
1Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, 2Philips Research China, Shanghai, China, 3Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

This study for the first time explored the use of APT-MRI for the head and neck (HN) at 3T, which is challenging due to tissue heterogeneity, pronounced susceptibility and various motions. We successfully demonstrated the feasibility of APT-MRI for the HN at clinical field strengths by adopting various approaches for image acquisition and data processing to mitigate the technical challenges. Z-spectra and of magnetization transfer ratio asymmetry of HN tissues were recorded. Preliminary results of APT-MRI on HN tumor patients showed that APT effect would be promising to be used as a sensitive biomarker for tumor delineation and characterization.

3152.   Multi-pool CEST imaging of glioblastoma at 7 T
Jan-Eric Meissner1, Johannes Windschuh1, Moritz Zaiss1, Daniel Paech2,3, Alexander Radbruch2,3, and Peter Bachert1
1Department of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany, 2Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany, 3Neurooncologic Imaging, Department of Radiology, German Cancer Research Center, Heidelberg, Germany

Chemical Exchange Saturation Transfer (CEST) enables indirect imaging of metabolites in vivo via magnetization transfer between exchanging protons of functional groups and water protons. We propose and evaluate a 2D-CEST sequence with high spectral sampling which allows for pixel-wise detection and separation of NOE-, amides-, and amine-mediated CEST effects and MT simultaneously by the use of a multi Lorentzian fit. Especially isolated amide and NOE mapping allowed insights into glioblastoma substructure.

3153.   High Throughput Screening of Contrast Agents by Ultrafast CEST Imaging
Xiang Xu1,2, Jiadi Xu1,2, Nirbhay N. Yadav1,2, Craig K. Jones1,2, Michael T. McMahon1,2, Alexej Jerschow3, and Peter C. M. van Zijl1,2
1Radiology Department, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States, 3Chemistry Department, New York University, New York, NY, United States

Recently we reported an ultrafast method to obtain a Z-spectrum over a large range of frequency offsets from only two signal excitations. In this study we extend the spectroscopic method into imaging that enables screening multiple samples at the same time. Furthermore, by interleaving a number of saturation and readout periods within the TR, a series of images with different saturation times can be acquired allowing quantification of the exchange rates using variable saturation time (QUEST) approach. Since only two images are needed, the method reduces time required to acquire Z-spectra and enables high throughput screening of CEST contrast agents.

3154.   NOE-CEST and amine–proton exchange imaging of mouse brain with suppression of MTC effects
Jiadi xu1,2, Kannie W. Y. Chan1,2, Xiang Xu1,2, Nirbhay Yadav1,2, Guanshu Liu1,2, Michael T. McMahon1,2, and Peter C. M. van Zijl1,2
1Radiology Department, Johns Hopkins University, Baltimore, MD, United States, 2Kennedy Krieger Institute, Baltimore, MD, United States

A new CEST scheme was developed using the variable delay multi-pulse train CEST (VDMP-CEST) in which the semi-solid magnetization transfer contrast (MTC) contribution was removed based on its exchange rate. The scheme requires acquisition of two images: one at zero inter-pulse delay and a second with an inter-pulse delay at which the MTC signal is comparable to that at zero delay. Consequently, subtracting the two images removes MTC. In addition, direct saturation is reduced, while CEST contrast in different exchange rate regimes remains preserved. The new method is demonstrated on phantoms and on normal mouse brain.

Hybrid frequency encoding/water relaxation method for detecting exchangeable solute protons with increased sensitivity and specificity
Nirbhay N Yadav1,2, Jiadi Xu1,2, Xiang Xu1,2, Michael T McMahon1,2, and Peter C M van Zijl1,2
1Radiology, The Johns Hopkins University, Baltimore, MD, United States, 2FM Kirby Research Center, Kennedy Krieger Institute, Baltimore, MD, United States

Measurement of chemical exchange is important for characterizing many biological processes. Current methods for detecting exchange in spectroscopy are classified based on whether exchange is slow, intermediate, or fast on the NMR time scale. Here we demonstrate a pulse sequence with solute proton frequency encoding and water detection that has the ability to distinguish exchange contributions over a large range of exchange rates (slow-intermediate-fast). When exchange is slow-intermediate, solute protons are labeled and detected with enhanced sensitivity. At higher exchange rates, changes in the water line shape are detected. This principle is demonstrated for the metabolites creatine, myo-inositol, and glutamate.

3156.   UCEPR: Ultrafast Localized CEST Spectroscopy with PRESS
Zheng Liu1,2, Ivan E. Dimitrov2,3, Robert E. Lenkinski1,2, and Elena Vinogradov1,2
1Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States, 2Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, 3Philips Medical Systems, Highland Heights, Ohio, United States

Chemical Exchange Saturation Transfer often utilizes acquisition of multi-point Z-spectra, which can be time consuming. Recently an ultrafast Z-spectroscopy method was introduced, employing frequency-encoding gradient during saturation and readout-gradient, thus collecting the whole data with two scans. Here we combine the method with PRESS to achieve localized ultrafast Z-spectroscopy (UCEPR). The sequence is straightforward to implement on clinical scanner and provides CEST effects comparable to the standard Z-spectra UCERP provides localized CEST information on a time scale currently unattainable and we anticipate that it will complement conventional imaging and spectroscopy methods in-vivo.

3157.   Using CEST to Detect Glycogen-depleting Exercise-Induced Changes In Vivo
Ying Cheng1,2, Kilian Weiss3, Peter van Zijl1,4, Kathleen Zackowski5,6, and Craig Jones1,4
1Neurosection, Div. of MRI Research, Dept. of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Dept. of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3Dept. of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States,4F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 5Motion Analysis, Kennedy Krieger Institute, Baltimore, MD, United States, 6Dept. of Physical Medicine & Rehab, Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Magnetic resonance spectroscopy (MRS) techniques have been applied to study skeletal muscle energetics. However they suffer from poor spatial resolution and low sensitivity. Chemical exchange saturation transfer (CEST) is a new MRI method that can indirectly detect endogenous cellular substances (e.g. creatine, glycogen) and proteins and metabolites through their exchangeable protons. Here, we applied the CEST technique in human calf muscle at 3T to a previously described exercise regime reported to be glycogen depleting only without a change in phosphocreatine. We demonstrate the potential of detecting exercise-induced changes in CEST signal, which could include glycogen, creatine, and/or T2 changes.

3158.   Spin-lock MRI of glucose and deoxyglucose concentration changes in brain
Tao Jin1, Hunter Mehrens1, and Seong-Gi Kim1,2
1Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 2Center for Neuroscience Imaging Research, Department of Biological Sciences, SKKU, Suwon, Korea

With chemical exchange dependent saturation transfer (CEST) MRI, recent animal studies administering natural D-glucose demonstrated results comparable to PET, and showed wide potential applications in diseases such as cancer. However, this gluco-CEST approach has low sensitivity, low temporal resolution, and is highly susceptible to B0 shifts. Furthermore, the CEST signal is strongly affected by other relaxation effects such as T1, T2 and magnetization transfer, and lacks a reliable means to quantify glucose concentration. In this study we showed that spin-lock MRI is highly sensitive to the administration of D-glucose and 2-deoxy-D-glucose, and is able to quantify concentration changes.

Simultaneously Measuring Glycogen and Lipid Levels Using Localized CEST Spectroscopy at 3T
Stephen J Bawden1, Olivier Mougin1, Karl Hunter2, Luca Marciani3, and Penny Gowland1
1SPMMRC, University of Nottingham, Nottingham, United Kingdom, 2Unilever Discover, Bedford, United Kingdom, 3NDDC Biomedical Research Unit, University of Nottingham, Nottingham, United Kingdom

Glycogen and Lipid levels are measured simultaneously using localised GlycoCEST proton MRS. Phantoms with glycogen, glucose and coconut milk were scanned using frequency stepped pre-saturation pulses and PRESS localization for MRS acquisition. Individual spectra were averaged in saturated and non-saturated regions to determine lipid-to-water peak ratios, and the asymmetry of off-resonance saturation water peak heights used to determine the CEST effect. This sequence was tested in vivo in the liver for varying off resonance saturations, and for varying pulse powers. This pilot study offers a promising new technique for reducing study time and costs whilst simultaneously measuring multiple metabolic pathways.

3160.   Monitoring extracelluar pH, spatial heterogeneity and contrast agent uptake in lymphoma tumor growth with acidoCEST MRI
Liu Qi Chen1, Christine M. Howison2, Amanda F. Baker3, and Mark D. Pagel2
1Chemistry & Biochemistry, University of Arizona, Tucson, AZ, United States, 2Biomedical Engineering, University of Arizona, Tucson, AZ, United States, 3The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, United States

Extracelluar pH (pHe) is a hallmark for tumor microenvironment. A non-invasive MRI method, term “acidoCEST MRI”, was used to accurately measure pHe and assess tumor acidosis. The pixel-wise pHe mapping allows us to access spatial heterogeneity and also contrast agent uptake. We have applied acidoCEST MRI to monitor effects of tumor growth in lymphoma tumor model, Raji, Ramos and Granta519. Our results showed mildly acidic pHe in all 3 tumor models. Granta519 pHe decreased over the course of 3 weeks. The % contrast agent uptake evaluated using acidoCEST MRI correlated with ex vivo VEGF-A score.

3161.   Bicarbonate as a theragnostic CEST agent for glioma models
Francisco Torrealdea1, Marilena Rega1, Joanne Lau1, Jessica Broni1, Sebastian Brandner1, Simon Walker-Samuel2, David L Thomas1, and Xavier Golay1
1Institute of Neurology, UCL, London, London, United Kingdom, 2Centre for Advance Biomedical Imaging, UCL, London, London, United Kingdom

Upregulated aerobic glycolysis in tumours causes acidic extracellular pH. Changes in pH can be detected in-vivo by CEST MRI. The goal of this study is to assess the CEST signal response of brain gliomas following the administration of an intra-peritoneal (IP) bolus of sodium bicarbonate. This preliminary study shows the potential of bicarbonate as a theragnostic CEST agent for the treatment and early assessment of gliomas.

Generating Quantitative pH Maps in Hyper-acute Stroke Patients Using Amide Proton Transfer (APT) Imaging
Yee Kai Tee1, George Harston2, Nicholas Blockley3, Thomas Okell3, Jacob Levman1, Martino Cellerini4, Fintan Sheerin4, Peter Jezzard3, James Kennedy2, Stephen Payne1, and Michael Chappell1
1Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Oxford, Oxfordshire, United Kingdom, 2Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, Oxfordshire, United Kingdom, 3FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxfordshire, United Kingdom, 4Department of Neuroradiology, Oxford University Hospitals NHS Trust, Oxfordshire, United Kingdom

Amide proton transfer (APT) imaging is a variant of chemical exchange saturation transfer (CEST) that has potential for assessing ischemic tissue at risk for infarction. In this study, APT data in healthy subjects and hyper-acute stroke patients within 6 hours of onset were acquired. A quantitative model-based analysis, where the modified Bloch equations were fitted to measured data using Bayesian algorithm, was used to quantify the APT effect. Based on the quantified APT effect and a previously published pH versus amide proton exchange rate relationship, quantitative pH maps in healthy subjects and stroke patients were generated.

3163.   MR imaging of protein folding employing Nuclear–Overhauser–mediated saturation transfer
Patrick Kunz1, Moritz Zaiss2, Steffen Goerke2, Alexander Radbruch3,4, and Peter Bachert2
1Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Dept. Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 3Dept. of Neuroradiology, University of Heidelberg, Heidelberg, Germany, 4Section Neuro–oncologic Imaging, German Cencer Research Center (DKFZ), Heidelberg, Germany

Urea–dependent unfolding of BSA, which can be monitored by fluorescence spectroscopy, affects saturation transfer between water and aliphatic protons of the protein mediated by dipole–dipole couplings (NOE). We show that the NOE imaging contrast of the BSA solution is a function of protein structure and propose that, besides concentration, temperature, and pH, protein folding/unfolding generates an additional contrast mechanism of CEST MR imaging. First outcomes of application in human glioblastoma patients are presented and discussed.

3164.   Imaging brain microenvironments of glial restricted precursor cells in injectable growth-factor supplemented hydrogels using CEST MRI
Kannie WY Chan1,2, Antje Arnold1,3, Ali Fatemi4, Michael Porambo4, Peter CM van Zjil1,2, Jeff WM Bulte1,3, Piotr Walczak1,3, and Michael T McMahon1,2
1Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Kennedy Krieger Institute, Baltimore, MD, United States, 3Institute for Cell Engineering, MD, United States, 4Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD, United States

Cell therapy has shown promise for treating neurological disorders, e.g. stroke, spinal cord injury and multiple sclerosis. Primary challenges include protection and support of cell grafts after transplantation, along with methods to determine cell functionality. These would be important in refinement of treatments, allowing early evaluation of the success of cell therapy for restoring the lost function. Hydrogels have been used to protect and support therapeutic cells in such therapies, here, we show that CEST MRI allow imaging of the microenvironments, including pH, for specific injectable hydrogels suited for glial restricted precursor cells (GRPs).

3165.   Direct 31P Magnetic Resonance Imaging Applying the Nuclear Overhauser Effect
Kristian Rink1, Moritz C. Berger1, Andreas Korzowski1, Peter Bachert1, and Armin M. Nagel1
1German Cancer Research Center (DKFZ), Heidelberg, Germany

Phosphorus plays a crucial role in the energy metabolism of the human body but in comparison to 1H MRI the in-vivo signal is four orders of magnitude smaller. In this work phosphocreatine images of the human calf muscle at 3T were acquired using a frequency selective 3D imaging sequence amplified by Nuclear Overhauser Effect (NOE) pulses. Implementing the NOE yields an SNR gain of up to 1.4 in-vivo and 1.7 in phantom studies with an isotropic resolution of 1cm (TA=33min).

3166.   Indirect MRI Detection of Myelin Water Based on Water Exchange Properties
Xu Jiang1, Peter van Gelderen1, Jacco A de Zwart1, and Jeff H Duyn1
1AMRI, LFMI, NINDS, National Institutes of Health, Bethesda, MD, United States

A novel approach is presented to indirectly image brain myelin content. The proposed method is based on a pulsed saturation transfer experiment, in which water with short T2 (including myelin water) is selectively saturated, after which the delayed effect on long T2 water is studied. Experiments performed at 7T confirm sensitivity and specificity of the method.

3167.   A B1 Insensitive qMT Protocol
Mathieu Boudreau1, Nikola Stikov1, and G. Bruce Pike1,2
1Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, 2Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

Quantitative magnetization transfer (qMT) requires several additional measurements to correct for instrumental biases (B0, B1) and to constrain parameters in the fitting model (T1). When using variable flip angle (VFA) T1 maps, B1 is used twice before fitting the qMT parameters: to correct T1, and the MT saturation powers. Inaccuracies in B1 would propagate to the fitting of the qMT parameters through two pathways – through errors in T1 and MT saturation powers. This work demonstrates that for the Sled and Pike qMT model, certain qMT parameters (F, T2f) are insensitive to a large range of B1 inaccuracies when using VFA.

3168.   Investigation of White Matter Characteristics using Interslice Magnetization Transfer Ratio and Asymmetry at High Field
Jae-Woong Kim1, Janggeun Cho2, Chulhyun Lee2, and Sung-Hong Park1
1Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea, 2Korea Basic Science Institute, Ochang, Korea

Imaging myelin is important for studies related to white matter (WM) diseases. We investigated the feasibility of mapping WM characteristics using interslice MT asymmetry and MT ratio using a recent method termed Alternate Ascending/Descending Directional Navigation (ALADDIN). The WM contrast (compared to gray matter and muscle) was much higher in MT asymmetry images than in MT ratio images, and the two images showed slightly different WM information in subcortical regions, indicating that combination of MT ratio and MT asymmetry may be a promising tool for better understanding of WM characteristics.

3169.   Accelerated In Vivo 3D Chemical Exchange Saturation Transfer (CEST) Imaging using dynamic Compressed Sensing
Juyoung Lee1, Paul Kyu Han1, Seung-Hong Choi2, Sung-Hong Park1, and Jong Chul Ye1
1Department of Bio and Brain Engineering, KAIST, Daejeon, Yuseong-gu, Korea, 2Department of Radiology, Seoul National University Hospital, Seoul, Korea

CEST can be combined with 3D gradient echo imaging to minimize distortion and avoid slice-dependent saturation frequency variations, but the spatial coverage may be limited. One potential approach to overcome this limitation is to use compressed sensing (CS). In this study, we successfully obtained in vivo 3D CEST images using k-t FOCUSS at 3T. Experimental results show that CS acceleration by a factor of 4 works well for both 3D CEST-bSSFP and 3D CEST-FISP and improves the z-spectrum compared to parallel imaging method, which confirms that combination of CS may be a good solution for 3D- CEST imaging.