ISMRM 24th Annual Meeting & Exhibition • 07-13 May 2016 • Singapore

Scientific Session: Molecular & Cellular Imaging

Thursday, May 12, 2016
Room 334-336
16:00 - 18:00
Moderators: David Cormode, Erik Shapiro

A zinc-sensitive MRI contrast agent differentiates healthy from cancerous prostate in a transgenic prostate cancer model
Veronica Clavijo Jordan 1, Su-Tang Lo1, Christian Preihs1, Sara Chirayil1, Wen-Hong Li1, Neil M Rofsky1, and Dean Sherry1,2
1UT Southwestern Medical Center, Dallas, TX, United States, 2UT Dallas, Richardson, TX, United States
The prostate has the highest levels of Zn(II) in the organism and there are marked differences in content between the healthy, malignant, and benign hyperplastic prostate. Given that accurate differential diagnosis between these conditions is difficult non-invasively, we introduce prostate Zn(II) as a MRI imaging biomarker. In this work we use a Gd-based zinc sensor that can sensitively detect glucose-stimulated intracellular release of Zn(II) in the healthy, and malignant mouse prostate using a transgenic adenocarcinoma model.  

Assessment of abdominal aortic aneurysm progression using a novel tropoelastin-specific MR contrast agent
Alkystis Phinikaridou1, Sara Lacerda1, Begoña L Plaza1, Marcelo Andia2, Silvia G Lorrio1, and René M Botnar1
1Biomedical Engineering, King's College London, London, United Kingdom, 2Radiology, Pontificia Universidad Católica de Chile, Santiago, Chile
The extracellular matrix proteins, elastin and collagen, are the most important structural components of the vessel wall that provide tensile strength and stability. During abdominal aortic aneurysm (AAA) formation there is both, progressive degradation and synthesis of new elastin fibers that disrupts the structural integrity of the vessel wall until it becomes unable to accommodate the high intraluminal hemodynamic forces [1-4]. AAA formation is characterized by dilation of the lumen area and thinning of the vessel wall. Possible rupture of the AAA may have fatal consequences. Rupture of aortic aneurysms is the third most common cause of sudden death after myocardial infarction and stroke. We have developed a tropoelastin-binding MR contrast agent (TESMA) and sought to investigate if it can be used as a novel biomarker to assess AAA development and the risk of rupture, beyond aneurysmal diameter.

Direct Quantitative 13C-Filtered 1H Magnetic Resonance Imaging of Pegylated Biomacromolecules In Vivo
Rohan Alvares1, Justin Lau2,3, Peter Macdonald1, Charles Cunningham2,3, and R. Scott Prosser1
1Department of Chemistry, University of Toronto, Toronto, ON, Canada, 2Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, 3Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada
We demonstrate a new platform technology in which macromolecular constituents, such as proteins and drug delivery systems, are observed directly and quantitatively in vivo using 1H MRI of 13C-labeled polyethylene glycol (13C-PEG) tags. The 28 kDa 13C-PEG tags are non-immunogenic, and each bears approximately 2500 spectroscopically equivalent 1H nuclei appearing at a single resonance position.  By filtering the 1H PEG signal through the directly coupled 13C nuclei, background water and fat signals are largely eliminated. We demonstrate the approach by monitoring in real-time the distribution of 13C-PEG and 13C-pegylated albumin injected into the hind leg of a mouse.

Label-free CEST MRI detection of self-assembly anticancer drug-peptide nanofibers
Yuguo Li1,2, Lye Lin Lock3, Renyuan Bai4, Xinpei Mao3, Verena Staedtke5, Peter C.M Van Zijl1,2, Honggang Cui3,6, and Guanshu Liu1,2
1The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 3Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, United States, 4Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, United States, 5Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States, 6Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, United States
A new injectable and CEST MRI-detectable nanofiber hydrogel has been developed for image-guided drug delivery of anticancer drug Pemetrexed (Pem). Such a drug delivery system is composed of only drug (Pem) and peptide (FFEE) and the MRI detectability stems on the inherent CEST signal of Pem. In the present study, PemFE nanofiber hydrogel was first constructed and characterized. Then, the CEST MRI detection of the constructed hydrogel in vivo was demonstrated in an orthotopic brain tumor mouse model. Our study clearly demonstrated the ability of using CEST MRI to monitor drug delivery of PemFE hydrogel. 

Assessment of Thrombus Stage by ‘Multicolor’ 19F MRI
Sebastian Temme1, Christoph Jacoby2, Christoph Owenier1, Christoph Grapentin3, Xiaowei Wang4, Rolf Schubert3, Karlheinz Peter4, Jürgen Schrader1, and Ulrich Flögel1,2
1Molecular Cardiology, University of Düsseldorf, Düsseldorf, Germany, 2Department of Cardiology, Pneumology and Angiology, University Hospital Düsseldorf, Düsseldorf, Germany, 3Pharmaceutical Technology and Biopharmacy, University of Freiburg, Freiburg i. Br., Germany, 4Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, Victoria, Australia
The present study was aimed at developing a non-invasive approach for direct assessment of thrombus stage by ‘multicolor’ 19F MRI. To this end, we used ligands binding specifically during different phases of thrombosis and coupled them to perfluorocarbons (PFCs) with indvidual spectral signatures. Discrimination of the targeted agents was achieved by a novel multi chemical shift selective imaging technique for simultaneous, artifact-free detection of different PFCs. The results show that this technique holds the potential to differentiate thrombi in the acute, subacute and chronic phase and may also be used for in situ labeling of a variety of other targets.

In vivo imaging of cell fate decisions in cardiac cell therapy using cardioCEST MRI.
Ashley Pumphrey1, Zhengshi Yang2, Shaojing Ye2, Ahmed Abdel-Latif2, and Moriel Vandsburger3
1CVRC, University of Kentucky, Lexington, KY, United States, 2University of Kentucky, Lexington, KY, United States, 3Physiology, University of Kentucky, Lexington, KY, United States
We developed a cardiac specific chemical exchange saturation transfer pulse sequence and applied it to the tracking of cell survival/proliferation or rejection in murine models of cardiac cell therapy. 

Quantitative Evaluation of Tumour Associated Macrophages in Breast Cancer: Fluorine-19 versus Iron Oxide Nanoparticles
Ashley V Makela1,2, Jeffrey M Gaudet1,2, and Paula J Foster1,2
1Medical Biophysics, Western University, London, ON, Canada, 2Robarts Research Institute, London, ON, Canada
Tumour associated macrophages (TAMs) are correlated with an aggressive tumour type and poor outcomes. This study is the first time iron and fluorine-19 (19F) based MRI cell tracking methods have been compared for the detection and quantification of TAMs in an orthotopic model of breast cancer. Imaging was performed at 4 days and 3 weeks post cell implantation. Both cell tracking methods showed a much higher TAM density at 4 days; no other imaging study has examined this at such an early time point. 19F MRI provided quantitative information about TAM density and tumoural distribution that was not possible with iron.

Age-related changes in anterograde transport, axonal integrity and visuomotor function in the DBA/2J mouse model of chronic glaucoma
Xiao-Ling Yang1,2, Yolandi van der Merwe1,3, Leon C. Ho1,4, Ian P. Conner2,3, Seong-Gi Kim1,5, Kira L. Lathrop2, Gadi Wollstein2,3, Joel S. Schuman2,3, and Kevin C. Chan1,2
1NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, PA, United States, 2UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, United States, 3Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, United States, 4Department of Electrical and Electronic Engineering, University of Hong Kong, Pokfulam, Hong Kong, 5Center for Neuroscience Imaging Research, Institute for Basic Science, Sungkyunkwan University, Suwon, Korea, Republic of
Glaucoma is the leading cause of irreversible blindness worldwide and is a slowly progressing neurodegenerative disease of the visual system. While elevated intraocular pressure (IOP) and age are major risk factors, their effects on glaucoma pathogenesis remain incompletely understood. In this study, we determined the onset of glaucomatous changes and their progression in a chronic inherited glaucoma model using DBA/2J mice. Our results indicate that elevation of IOP may accelerate the deterioration of structure, physiology and function of the visual system in the DBA/2J mice across age. Comparatively, the visual system in C57BL/6J mice appeared intact across the same ages.

Characterizing Iron Oxide NanoParticles using 4D Spectroscopic SWIFT
Jinjin Zhang1, Hattie L. Ring1, Michael Garwood1, and Djaudat Idiyatullin1
1Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, United States
The ability to accurately and sensitively quantify the bio-distribution of iron oxide nanoparticles is essential for their use as both diagnostic and therapeutic agents in theranostics. In this study, a 4D spectroscopic SWIFT technique was applied and optimized to characterize the distribution of IONPs in mouse invivo up to high concentration (>1.0 mg Fe/g of tissue). The frequency shift due to susceptibility variation and T2* shortening (down to 20 μs) caused by IONPs were detected in mice organs depositing IONPs. The acquired T2* map which provide quantitative information about IONP bio-distribution makes the 4D spectroscopic SWIFT a promising tool in nanoparticle-based theranostics. 

The framework and AnalytiCally Represented Oxygen-17 BrAin Tumor (ACROBAT) phantom for optimization of CMRO2 quantification protocols in dynamic 17O-MRI.
Dmitry Kurzhunov1, Robert Borowiak1,2, Axel Krafft1,2, and Michael Bock1
1University Medical Center Freiburg, Dept. of Radiology - Medical Physics, Freiburg, Germany, 2German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany
Direct dynamic 17O-MRI allows quantification of the cerebral metabolic rate of oxygen consumption (CMRO2). The influence of acquisition parameters on the precision of CMRO2 quantification needs to be investigated for routine application, but the costly and rare 17O gas prohibits extensive imaging studies. Thus, in this work a flexible, Fourier domain-based simulation framework is presented and analytical tumor and numerical 17O MRI brain phantoms are utilized based on experimental 17O relaxation times and signal-to-noise ratios. Precision of CMRO2 quantification is evaluated and optimal acquisition parameters are given.

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