ISMRM 21st Annual Meeting & Exhibition 20-26 April 2013 Salt Lake City, Utah, USA

Saturation Transfer: New Frontiers & Application
Wednesday 24 April 2013
Room 255 EF  10:00 - 12:00 Moderators: Gil Navon, Peter van Zijl

10:00 0419.   
Ultra-Fast One-Shot Z Spectrum Acquisition
Xiang Xu1, Jae-Seung Lee1,2, and Alexej Jerschow1
1Chemistry Department, New York University, New York, NY, United States, 2Radiology Department, New York University, New York, NY, United States

We propose a fast one-shot method for obtaining complete Z-spectra for studying MT and CEST phenomena in homogeneous system. The method exploits gradient fields to irradiate a given system and acquire the z-polarization of water protons simultaneously at many frequency offsets. The new method can be useful for fast screening of imaging phantoms and paraCEST contrast agents under different experimental conditions.

10:12 0420.   
Correlation of Exercise Induced Changes in Cr CEST and 31P MRS in Human Calf Muscles
Feliks Kogan1, Mohammad Haris1, Anup Singh1, Kejia Cai1, Catherine DeBrosse1, Ravi Prakash Reddy Nanga1, Hari Hariharan1, and Ravinder Reddy1
1Center for Magnetic Resonance and Optical Imaging (CMROI), University of Pennsylvania, Philadelphia, PA, United States

Creatine, a key component of muscle energy metabolism, exhibits a chemical exchange saturation transfer effect (CrCEST) between its amine group and bulk water. We characterized CrCEST for the spatial mapping of free creatine in imaging muscle energy metabolism. In healthy human subjects, following mild plantar flexion exercise, increases in CrCEST were observed in the posterior compartment of the leg which recovered exponentially back to baseline. This technique exhibited good spatial resolution and was able to differentiate differences in muscle utilization among subjects. CrCEST results were compared with 31P MRS results showing good agreement in the recovery kinetics of CrCEST and PCr signal following exercise.

10:24 0421.   CytoCEST: Cells as CEST Agents -permission withheld
Giuseppe Ferrauto1, Daniela Delli Castelli1, Enza Di Gregorio1, Enzo Terreno1, Holger Gruell2, and Silvio Aime1
1Molecular Biotecnology & helath Sciences, Molecular Imaging Center, torino, Italy, 2Eindhoven University of Technology, Eindhoven, Netherlands

CEST agents are able to generate a frequency-encoded contrast allowing the simultaneous detection of multiple agents in the same voxels. Unfortunately they suffer for a low sensitivity. Since sensitivity depends on the number of equivalent mobile protons irradiated, systems bearing huge numbers of exchanging protons have been developed. In this work we report a labeling procedure allowing to exploit the huge number of intracellular water protons to generate CEST contrast. The separation between the NMR signal of “bulk” and intracellular water protons is provided by entrapping inside the cell a paramagnetic shift reagent. This new system has been named cytoCEST.

10:36 0422.   
Development of CEST Liposomes for Monitoring Nanoparticle-Based Cancer Therapies -permission withheld
Kannie W.Y. Chan1,2, Tao Yu3,4, Yuan Qiao5, Guanshu Liu1,6, Ming Yang4, Jeff W.M. Bulte2,7, Peter C.M. van Zijl1,6, Justin S. Hanes3, and Michael T. McMahon1,6
1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Baltimore, MD, United States, 3Center for Nanomedicine, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 4Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 5The Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute and Sidney Kimmel Cancer Center, Baltimore, MD, United States, 6F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 7Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States

Nanoparticle-based local drug treatment has potential for chemotherapy for cancers, but there is a need for real time in vivo imaging of the particle delivery to monitor therapeutic efficacy. We used Chemical Exchange Saturation Transfer (CEST), a molecular MRI contrast mechanism, to monitor the delivery of liposomes loaded with both a diaCEST agent (barbituric acid) with a resonance at 5.0 ppm from water) and drug (Doxorubicin) to colon tumors. The CEST contrast was used to image the spatial distribution of the particles after administration and over a period of 24-h in vivo.

10:48 0423.   
Amide Proton Transfer Imaging of High Intensity Focused Ultrasound-Treated Tumor Tissue
Stefanie J.C.G. Hectors1, Igor Jacobs1, Gustav J. Strijkers1, and Klaas Nicolay1
1Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands

The effects of HIFU treatment on tumor APT intensity were assessed in a murine tumor model. Regions with decreased APT intensity were observed after HIFU treatment. These regions correlated spatially to areas of non-viable, necrotic tumor tissue observed in histology. Analysis of the tumor APT intensity distribution showed a pronounced shift towards lower APT intensity values after HIFU. The fractions of pixels within the defined HIFU-related APT intensity range (-10 to -2%) significantly increased by HIFU treatment. These results suggest that APT imaging may serve as a new biomarker for identification of HIFU-treated tumor tissue.

11:00 0424.   
GlucoCEST for the Detection of Human Xenografts Glioblastoma at Early Stage.
Francisco Torrealdea1, Marilena Rega1, Angela Richard-Loendt1, Sebastian Brandner1, David L. Thomas1, Simon Walker-Samuel2, and Xavier Golay3
1Institute of Neurology, UCL, London, Greater London, United Kingdom, 2Centre for Advanced Biomedical Imaging, UCL, London, Greater London, United Kingdom, 3Institute of Neurology, University College London, London, Greater London, United Kingdom

GlucoCEST has been shown to detect exogenously administrated glucose in tumours and to correlate with FDG PET. In this study we investigate the feasibility of the technique for the detection of xenograft human glioblastoma. Comparison of glucoCEST measurements with histology and T2weighted images, suggests that the technique is sensitive enough to detect brain tumours at an early stage, before the disruption of tissue microestructure has occurred. It also allows dynamic measurements of tumour metabolism which could potentially be used for the characterization of glial tumour grade.

11:12 0425.   
Chemical Exchange Saturation Transfer (CEST) MRI of 2DG and FDG as a Tool for Molecular Imaging of Tumors and Metastases
Michal Rivlin1, Uzi Eliav1, Judith Horev2, Ilan Tsarfaty2, and Gil Navon1
1School of Chemistry, Tel-Aviv University, Tel-Aviv, Israel, 2Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

The two glucose analogs 2-deoxy-D-glucose (2DG) and 2-fluoro-2-deoxy-D-glucose (FDG) are preferentially taken up by cancer cells, undergo phosphorylation and accumulated in the cells. Owing to their exchangeable protons on their hydroxyl residues they exhibit significant CEST effect. Here we report for the first time CEST-MRI on a mouse implanted with DA3 xenograph mammary tumors, which was i.v. injected with 2DG (20 mg/kg). The tumor exhibited a CEST effect of about 10%, while the concentration used was much lower than the approved therapeutic treatment for human. Thus 2DG/FDG CEST MRI has the potential to replace FDG-PET for the detection of tumors and metastases.

11:24 0426.   
Molecular CEST Imaging of Mucins with Different Glycosylation Levels
Xiaolei Song1,2, Raag D. Airan1,2, Dian R. Arifin1,2, Amnon Bar-Shir2,3, Lea Miranda1,2, Deepak K. Kadayakkara1,2, Guanshu Liu1,4, Assaf A. Gilad2,3, Peter C.M. van Zijl1,4, Michael T. McMahon1,4, and Jeff W.M. Bulte2,3
1Division of MR Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, 2Cellular Imaging Section, Institute for Cell Engineering, The Johns Hopkins University, Baltimore, MD, United States, 3Division of MR Research, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, 4F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

Tumor-associated glycosylation changes regulate tumor proliferation, metastasis, and angiogenesis. Underglycosylated mucin-1 (uMUC-1) antigen is overexpressed in many adenocarcinomas (e.g. colon, breast and ovarian cancers). Using CEST imaging, we were able to discriminate deglycosylated from untreated mucin proteins, with the deglycosylated samples showing >80% reduction in the –OH peak. Using cell lines with different levels of MUC-1 glycosylation, a striking differential CEST contrast could be obtained between 0.5 and 4 ppm. These results suggest that CEST imaging may be used as a surrogate marker to non-invasively assess mucin glycosylation and tumor malignancy.

11:36 0427.   Application of Chemical Exchange Saturation Transfer (CEST) MRI in Acute Human Stroke Patients Demonstrates New Potential for Visualization of Tissue Acidosis and Infarction Risk
Manus J. Donahue1, Anna Tietze2,3, Irene Klaerke Mikkelsen2, Leif Ostergaard2, Megan Strother1, Seth Smith1, and Jakob Blicher2,4
1Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, 2Center for Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus, Denmark,3Neuroradiology, Aarhus University Hospital, Aarhus, Denmark, 4Hammel Neurorehabilitation and Research, Aarhus University Hospital, Hammel, Denmark

The purpose of this study is to apply a pH-sensitive CEST protocol in acute (≤4.5 hrs post-onset) and subacute (4.5-24 hrs post-onset) stroke patients to understand the extent to which amide proton transfer (APT) contrast may be used to identify metabolically-impaired tissue at highest risk for infarction. CEST provides unique contrast compared to DWI and PWI in tissue that progresses to infarction by one-month follow up. We also discuss ongoing limitations of CEST in the acute stroke setting and provide an outline of technical hurdles that must be overcome before CEST may be applied routinely in this important patient population.

11:48 0428.   NOE Imaging in the Human Brain at 7T
Craig K. Jones1,2, Alan Huang1,2, Jiadi Xu1,2, Richard Anthony Edward Edden2,3, Michael Schär4,5, Jun Hua1,2, Nikita Oskolkov1,2, Michael T. McMahon1,2, and Peter C.M. van Zijl1,2
1Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 3Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD, United States, 4Philips Medical Systems, Highland Heights, OH, United States, 5Keller Center for Imaging Innovation, Barrow Neurological Institute, Phoenix, AZ, United States

CEST is a magnetization transfer (MT) technique to indirectly detect pools of exchangeable protons through the water signal. Low power RF pulses can slowly saturate protons with minimal interference of conventional semi-solid based MT contrast (MTC). When doing so saturation-transfer signals are revealed upfield from water in the CEST spectrum, which is in the frequency range of non-exchangeable aliphatic and olefinic protons. The visibility of such upfield signals indicates the presence of a transfer mechanism to the water signal, while their finite width indicates that these signals are likely due to mobile solutes.