Moving Magnetization in Milano: NOE, APT & CEST

Thursday 15 May 2014

Julien Flament¹, Maria-Angeles Carrillo-de Sauvage^2,3, Julien Valette^2,3, and Carole Escartin^2,3
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.

Masaya Takahashi^1,2, Koji Sagiyama¹, Osamu Togao¹, Tomoyuki Mashimo^3,4, Shanrong Zhang¹, Vamsidhara Vemireddy^4,5, Kimmo J. Hatanpaa⁶, Elizabeth A. Maher^3,4, A. Dean Sherry^1,2, and Robert M. Bachoo^4,5
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.

Koji Sagiyama¹, Shanrong Zhang¹, Ivan Dimitrov^1,2, A. Dean Sherry¹, and Masaya Takahashi^1
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.

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 Kennedy^1
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.

Osamu Togao¹, Takashi Yoshiura¹, Jochen Keupp², Akio Hiwatashi¹, Koji Yamashita¹, Kazufumi Kikuchi¹, Yuriko Suzuki³, Koji Sagiyama⁴, Masaya Takahashi⁴, and Hiroshi Honda^1
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.

Xiang Xu^1,2, Nirbhay N. Yadav^1,2, Craig K. Jones^1,2, Haifeng Zeng^1,2, Jinyuan Zhou^1,2, Peter C. M. van Zijl^1,2, and Jiadi Xu^1,2
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.

Moritz Zaiss¹, Johannes Windschuh¹, Jan-Eric Meissner¹, Daniel Paech^2,3, Alexander Radbruch^2,3, and Peter Bachert^1
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.

Daniel Paech^1,2, 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 Radbruch^1,2
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.

Junzhong Xu¹, Mortiz Zaiss², Zhongliang Zu¹, Hua Li¹, Jingping Xie¹, Daniel F Gochberg¹, Peter Bachert², and John C Gore^1
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.

Matthew S. Rosen^1,2, Mathieu Sarracanie^1,2, Brandon D. Armstrong^1,2, Fanny Herisson^3,4, Najat Salameh^1,5, and Cenk Ayata^3,4
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.