Room 255 EF

10:00 - 12:00

Moderators:

Gil Navon, Peter van Zijl

Xiang Xu¹, Jae-Seung Lee^1,2, and Alexej Jerschow^1
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.

Feliks Kogan¹, Mohammad Haris¹, Anup Singh¹, Kejia Cai¹, Catherine DeBrosse¹, Ravi Prakash Reddy Nanga¹, Hari Hariharan¹, and Ravinder Reddy^1
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.

Giuseppe Ferrauto¹, Daniela Delli Castelli¹, Enza Di Gregorio¹, Enzo Terreno¹, Holger Gruell², and Silvio Aime^1
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.

Kannie W.Y. Chan^1,2, Tao Yu^3,4, Yuan Qiao⁵, Guanshu Liu^1,6, Ming Yang⁴, Jeff W.M. Bulte^2,7, Peter C.M. van Zijl^1,6, Justin S. Hanes³, and Michael T. McMahon^1,6
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.

Stefanie J.C.G. Hectors¹, Igor Jacobs¹, Gustav J. Strijkers¹, and Klaas Nicolay^1
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.

Francisco Torrealdea¹, Marilena Rega¹, Angela Richard-Loendt¹, Sebastian Brandner¹, David L. Thomas¹, Simon Walker-Samuel², and Xavier Golay^3
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.

Michal Rivlin¹, Uzi Eliav¹, Judith Horev², Ilan Tsarfaty², and Gil Navon^1
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.

Xiaolei Song^1,2, Raag D. Airan^1,2, Dian R. Arifin^1,2, Amnon Bar-Shir^2,3, Lea Miranda^1,2, Deepak K. Kadayakkara^1,2, Guanshu Liu^1,4, Assaf A. Gilad^2,3, Peter C.M. van Zijl^1,4, Michael T. McMahon^1,4, and Jeff W.M. Bulte^2,3
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.

Manus J. Donahue¹, Anna Tietze^2,3, Irene Klaerke Mikkelsen², Leif Ostergaard², Megan Strother¹, Seth Smith¹, and Jakob Blicher^2,4
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.

Craig K. Jones^1,2, Alan Huang^1,2, Jiadi Xu^1,2, Richard Anthony Edward Edden^2,3, Michael Schär^4,5, Jun Hua^1,2, Nikita Oskolkov^1,2, Michael T. McMahon^1,2, and Peter C.M. van Zijl^1,2
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.