Veronica Clavijo Jordan ¹, Su-Tang Lo¹, Christian Preihs¹, Sara Chirayil¹, Wen-Hong Li¹, Neil M Rofsky¹, and Dean Sherry^1,2
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.  

Alkystis Phinikaridou¹, Sara Lacerda¹, Begoña L Plaza¹, Marcelo Andia², Silvia G Lorrio¹, and René M Botnar^1
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.

Rohan Alvares¹, Justin Lau^2,3, Peter Macdonald¹, Charles Cunningham^2,3, and R. Scott Prosser^1
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.

Yuguo Li^1,2, Lye Lin Lock³, Renyuan Bai⁴, Xinpei Mao³, Verena Staedtke⁵, Peter C.M Van Zijl^1,2, Honggang Cui^3,6, and Guanshu Liu^1,2
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. 

Sebastian Temme¹, Christoph Jacoby², Christoph Owenier¹, Christoph Grapentin³, Xiaowei Wang⁴, Rolf Schubert³, Karlheinz Peter⁴, Jürgen Schrader¹, and Ulrich Flögel^1,2
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.

Ashley Pumphrey¹, Zhengshi Yang², Shaojing Ye², Ahmed Abdel-Latif², and Moriel Vandsburger^3
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. 

Ashley V Makela^1,2, Jeffrey M Gaudet^1,2, and Paula J Foster^1,2
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.

Xiao-Ling Yang^1,2, Yolandi van der Merwe^1,3, Leon C. Ho^1,4, Ian P. Conner^2,3, Seong-Gi Kim^1,5, Kira L. Lathrop², Gadi Wollstein^2,3, Joel S. Schuman^2,3, and Kevin C. Chan^1,2
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.

Jinjin Zhang¹, Hattie L. Ring¹, Michael Garwood¹, and Djaudat Idiyatullin^1
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. 

Dmitry Kurzhunov¹, Robert Borowiak^1,2, Axel Krafft^1,2, and Michael Bock^1
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.