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

Moving Magnetization in Milano: NOE, APT & CEST

Thursday 15 May 2014
Red 1 & 2  10:30 - 12:30 Moderators: Guanshu Liu, Ph.D., Ravinder Reddy, Ph.D.

10:30 0760.   
Imaging astrocyte reactivity using gluCEST - permission withheld
Julien Flament1, Maria-Angeles Carrillo-de Sauvage2,3, Julien Valette2,3, and Carole Escartin2,3
1U986 Inserm, MIRCen - CEA/Inserm, Fontenay-aux-Roses, France, 2CEA-MIRCen, Fontenay-aux-Roses, France, 3CNRS URA 2210, Fontenay-aux-Roses, France

This study describes the possibility to image spatial extension of astrocyte reactivity using gluCEST. A model of selective astrocyte activation was used by overexpression of the cytokine ciliary neurotrophic factor (CNTF) in rat striatum. The model was first characterized by NMR spectroscopy, showing a decrease of glutamate (18%, n=9). GluCEST images were acquired on 5 rats and showed decrease of MTRasym reflecting glutamate variation. Interestingly, the area of lower gluCEST contrast matched well with the area containing activated astrocytes (vimentin positive area in postmortem studies). These results suggest that glutamate decrease could be a surrogate marker of astrocyte reactivity.

10:42 0761.   Evaluation of chemoresistance on human GBM by amide proton transfer (APT) imaging in mice
Masaya Takahashi1,2, Koji Sagiyama1, Osamu Togao1, Tomoyuki Mashimo3,4, Shanrong Zhang1, Vamsidhara Vemireddy4,5, Kimmo J. Hatanpaa6, Elizabeth A. Maher3,4, A. Dean Sherry1,2, and Robert M. Bachoo4,5
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, 2Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States, 3Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States, 4Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, 5Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, United States, 6Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, United States

Amide proton transfer (APT) imaging shows increasing interest in characterization of the brain tumor. The objective of our study is to investigate whether APT imaging can provide useful biomarker to determine treatment responses or resistance of the glioblastoma multiforme (GBM) in chemotherapy. In the present study, we compared two human GBM cell lines derived from the same patient that have same genotype, which is a unique and powerful system to compare directly the APT signal in the setting of temozolomide sensitivity and resistance.

10:54 0762.   
In Vivo Monitoring of Liver Glycogen by Chemical Exchange Saturation Transfer Imaging (GlycoCEST) in Live Mice
Koji Sagiyama1, Shanrong Zhang1, Ivan Dimitrov1,2, A. Dean Sherry1, and Masaya Takahashi1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, 2Philips Medical Systems, Cleveland, Ohio, United States

GlycoCEST imaging is one subset of the chemical exchange saturation transfer (CEST) imaging methods which refers specifically to detecting tissue glycogen, which may enable investigation of both normal physiology and various liver diseases. In the present study, we performed phantom and in vivo glycoCEST imaging to detect glycogen and to monitor temporal changes of tissue glycogen concentration in the liver in mice before and after fasting. Our results showed the potential of glycoCEST to study glycogenolysis in vivo.

11:06 0763.   
Serial pH-weighted imaging using amide proton transfer in acute ischemic stroke
George William John Harston1, Yee Kai Tee2, Nicholas Blockley3, Thomas Okell3, Jacob Levman2, Fintan Sheerin4, Martino Cellerini4, Peter Jezzard3, Michael Chappell2, Stephen Payne2, and James Kennedy1
1Radcliffe Department of Medicine, University of Oxford, Oxford, Oxfordshire, United Kingdom, 2Department of Engineering Science, University of Oxford, Oxford, Oxfordshire, United Kingdom, 3Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, Oxfordshire, United Kingdom,4Oxford University Hospitals NHS Trust, Oxford, Oxfordshire, United Kingdom

Measurement of amide proton transfer using chemical exchange saturation transfer techniques can be used to generate an intracellular pH-weighted image of the brain. In experimental models of cerebral ischemia pH is known to fall prior to irreversible infarction. Thus pH-weighted imaging may be useful to assess the metabolic state of potentially viable, but at risk, tissue during stroke, allowing a better understanding of disease processes within individual patients. These data demonstrate the natural history of pH-weighted imaging in patients with acute ischemic stroke and demonstrate different patterns of acidosis in reperfused and non-reperfused brain tissue.

11:18 0764.   Amide Proton Transfer Imaging in Grading Diffuse Gliomas: Comparison with Contrast-enhanced and Diffusion-weighted MR Imaging
Osamu Togao1, Takashi Yoshiura1, Jochen Keupp2, Akio Hiwatashi1, Koji Yamashita1, Kazufumi Kikuchi1, Yuriko Suzuki3, Koji Sagiyama4, Masaya Takahashi4, and Hiroshi Honda1
1Clinical Radiology, Graduate School of Medical Science, Kyushu University, Fukuoka, Fukuoka, Japan, 2Philips Research Europe, Hamburg, Germany,3Philips Electronics Japan, Tokyo, Japan, 4Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States

APT imaging is a specific type of endogenous CEST imaging technique. We reported that APT imaging successfully predicted histopathological grades of diffuse gliomas in patients. Since APT is a newly developed technique, a further verification by comparing with conventional MRI methods is required. In this study, we assessed the diagnostic performance of APT imaging for grading of diffuse gliomas by comparisons with contrast-enhanced and diffusion-weighted imaging. APT imaging showed high diagnostic performance to in grading gliomas compared with contrast-enhanced and diffusion-weighted imaging. APT has an additive value to other MR methods and is useful in accurate glioma grading.

11:30 0765.   
MTC free APT and rNOE-CEST Images of Human Brain at 7T
Xiang Xu1,2, Nirbhay N. Yadav1,2, Craig K. Jones1,2, Haifeng Zeng1,2, Jinyuan Zhou1,2, Peter C. M. van Zijl1,2, and Jiadi Xu1,2
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

The Variable Delay Multi-Pulse (VDMP) CEST method can image slow exchange processes such as Amide Proton Transfer (APT) and exchange relayed Nuclear Overhauser Enhancement (rNOE) without the need for a full Z-spectrum by subtracting signals acquired at two pulse delays. Here we examine the use of the VDMP-CEST sequence to the human brain, where the inter-pulse delay is optimized to remove conventional magnetization transfer contrast (MTC), allowing MTC free APT and rNOE images to be obtained. The results show similar rNOE effects in gray and white matter, while APT effects are higher in gray matter than in white matter.

11:42 0766.   Inverse Z-spectrum analysis for clean NOE and amide CEST-MRI – application to human glioma
Moritz Zaiss1, Johannes Windschuh1, Jan-Eric Meissner1, Daniel Paech2,3, Alexander Radbruch2,3, and Peter Bachert1
1Dept. Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Dept. of Neuroradiology, University of Heidelberg, Heidelberg, Germany, 3Section Neuro–oncologic Imaging, German Cancer Research Center (DKFZ), Heidelberg, Germany

We present NOE and APT-CEST imaging data of glioma patients measured at 7 T. Clean CEST evaluation was achieved by multi-Lorentzian fitting in combination with the recently proposed AREX evaluation, based on the inverse metric of Z-spectra. The spillover, MT and T1 corrected AREX-maps of isolated APT and NOE show very different contrast compared to uncorrected CEST data of three glioblastoma patients.

11:54 0767.   
Nuclear Overhauser Enhancement (NOE) Mediated Chemical Exchange Saturation Transfer (CEST) Imaging At 7 Tesla In Glioblastoma Patients
Daniel Paech1,2, Jan Eric Meissner3, Johannes Windschuh3, Benedikt Wiestler4, Jan Oliver Neumann5, Heinz Peter Schlemmer6, Wolfgang Wick4, Armin Nagel3, Marc Ladd3, Martin Bendszus1, Peter Bachert3, Moritz Zaiss3, and Alexander Radbruch1,2
1Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, BW, Germany, 2Neurooncologic Imaging, Department of Radiology, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Heidelberg, BW, Germany, 3Department of Medical Physics in Radiology, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Heidelberg, BW, Germany, 4Department of Neurooncology, University of Heidelberg Medical Center, Heidelberg, BW, Germany, 5Department of Neurosurgery, University of Heidelberg Medical Center, Heidelberg, BW, Germany,6Department of Radiology, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Heidelberg, BW, Germany

Chemical Exchange Saturation Transfer (CEST) offers a contrast sensitive to endogenous mobile proteins and changes in pH. In our clinical prospective study we investigated Nuclear Overhauser Enhancement (NOE) mediated CEST on a 7T whole body MRI scanner in 11 newly diagnosed and histologically proven glioblastoma patients. Three-dimensional CEST data was co-registrated and compared with contrast enhanced T1-weighted (ce-T1) and T2-weighted sequences. CEST enabled imaging of hot spots within the tumor that were not visible on ce-T1 or T2-weighted images and displayed a surrounding tumor edema significantly smaller than on T2-weighted images.

12:06 0768.   On the origins of chemical exchange saturation transfer (CEST) contrast in tumors at 9.4T
Junzhong Xu1, Mortiz Zaiss2, Zhongliang Zu1, Hua Li1, Jingping Xie1, Daniel F Gochberg1, Peter Bachert2, and John C Gore1
1Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, United States, 2German Cancer Research Center, Heidelberg, Germany

A new three-offset 1/Z method was proposed to correct spillover, MT and R1 (the longitudinal relaxation rate) effects in chemical exchange saturation transfer (CEST) imaging. The corrected APT in tumors was found not significantly different from normal tissues, but corrected NOE effects in tumors showed significant decreases compared with normal tissues. These results are consistent with biochemical measurements suggesting that there is no significant enhancement of protein contents in the tumors. Our results may assist better understanding the contrast depicted by CEST imaging in tumors, and the development of improved APT and NOE measurements for cancer imaging.

12:18 0769.   Overhauser-enhanced MRI as a non invasive probe of BBB breakdown and redox state following ischemia/reperfusion
Matthew S. Rosen1,2, Mathieu Sarracanie1,2, Brandon D. Armstrong1,2, Fanny Herisson3,4, Najat Salameh1,5, and Cenk Ayata3,4
1Department of Radiology, MGH/Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, 2Department of Physics, Harvard University, Cambridge, MA, United States, 3Department of Radiology, MGH/Neurovascular Research Lab, Charlestown, MA, United States, 4Department of Radiology, Harvard Medical School, Boston, MA, United States, 5Institut de Physique des Systèmes Biologiques, EPFL, Lausanne, Vaud, Switzerland

A new method to probe hyperacute BBB breakdown following ischemic stroke in a rodent model using Overhauser-MRI (OMRI) in conjunction with an injected stable free radical, TEMPOL, is described. We present OMRI images of TEMPOL crossing the BBB following ischemia/reperfusion in vivo. The use of OMRI in conjunction with TEMPOL as an exogenous imaging agent for stroke is a new and novel approach, and suggests that TEMPOL may be a suitable probe for observing early BBB breakdown following reperfu-sion in rodent I/R models. We hypothesize that temporally resolved OMRI may be used to indicate the redox status of ischemic tissue.