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

Scientific Session: Molecular Probes, DNP & Hyperpolarisation

Tuesday, May 10, 2016
Room 300-302
16:00 - 18:00
Moderators: Moriel Vandsburger, René In 't Zandt

Nanodiamond Imaging with Room Temperature Dynamic Nuclear Polarization
David E J Waddington1,2,3, Mathieu Sarracanie2,3,4, Huiliang Zhang3,5, Torsten Gaebel1, David R Glenn3,5, Ewa Rej1, Najat Salameh2,3,4, Ronald L Walsworth3,5, David J Reilly1, and Matthew S Rosen2,3,4
1School of Physics, University of Sydney, Sydney, Australia, 2A.A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, 3Department of Physics, Harvard University, Cambridge, MA, United States, 4Harvard Medical School, Boston, MA, United States, 5Harvard-Smithsonian Center for Astrophysics, Cambridge, MA, United States
Overhauser-enhanced MRI (OMRI) is a double resonance technique that has been developed to image free radicals in vivo.   Here, we use an ultra-low field MRI scanner with a highly efficient b-SSFP OMRI protocol to image synthetic nanodiamonds (NDs) in water at room temperature.  Surprisingly, we find that high contrast can be generated via the Overhauser effect due to paramagnetic impurities in the ND.   Given the already established application of ND as a biocompatible platform for drug delivery, these results are encouraging for applications based on the non-invasive tracking of nanoparticles using MRI.

Imaging Spermine using LnDOTP5-Towards a Noninvasive Staging of Prostate Cancer
Abiola Olatunde1, Taylor Fuss1, Phillip Zhe Sun1, Leo L Cheng1, and Peter Caravan1
1Massachusetts General Hospital, Boston, MA, United States
Prostate cancer (PCa) is the most frequently diagnosed malignancy in men worldwide. Previous studies have indicated the utility of spermine as a potential biomarker for prostate cancer; however, quantifying spermine using MRS is difficult due to overlapping chemical shifts of spermine with other metabolites. We used LnDOTP5-, an anionic lanthanide macrocyclic complex, to form a stable ternary complex with positively-charged spermine to selectively shift spermine MR resonances. Here we report the affinity of different LnDOTP5- complexes for spermine and the effect of complex formation on spermine MR resonances in both D2O and serum solutions and intact human prostate tissue. 

Molecular imaging of inflammation and extracellular matrix remodelling after myocardial infarction
Isabel Ramos1,2, Markus Henningsson1, Maryam Nezafat1, Begoña Lavin1,2, Pierre Gebhardt1, Andrea Protti1,2, Sara Lacerda1,2, Silvia Lorrio1,2, Alkystis Phinikaridou1,2, Ulrich Flögel3, Ajay M. Shah2, and René M. Botnar1,2
1Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom, 2Cardiovascular Division, The British Heart Foundation Centre of Excellence, King's College London, London, United Kingdom, 3Department of Molecular Cardiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Optimal post-MI healing relies on a suitable degree of inflammation and its timely resolution, which is directly related to a well-orchestrated degradation and deposition of extracellular matrix (ECM) proteins, leading to cardiac remodeling. Here we explored the merits of multinuclear 1H/19F MRI for the simultaneous assessment of cardiac inflammation and subsequent remodelling in a murine model of MI. To investigate inflammatory cell recruitment into injured myocardium, a 19F containing nanoparticle that is avidly taken up by macrophages was used1. To evaluate changes of elastin content in the ECM post-MI, a small molecular weight gadolinium-based elastin-specific MR contrast agent was investigated2.

Correlation of Hyperpolarized 13C-Lactate Measurements and Ex Vivo NMR using a [3-13C]Pyruvate Injection
Casey Y. Lee1,2, Justin Y. C. Lau1,2, Albert P. Chen3, Yi-Ping Gu2, and Charles H. Cunningham1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, 2Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, 3GE Healthcare, Toronto, ON, Canada
Lactate has been proposed as a potential marker to non-invasively predict cancer progression and monitor response to the therapy. Previously, hyperpolarized [1-13C]pyruvate have been used to study the metabolic properties of tumor through measuring the rapid conversion of pyruvate to lactate. However, the fate of the 13C-lactate, following the hyperpolarized experiment, has been less understood due to the fast, irreversible decay of the hyperpolarized signal. In this work, lactate concentrations (total, 13C1- and 13C3-lactate) has been estimated in rat tumor extracts following the injection of hyperpolarized [1-13C]pyruvate and non-hyperpolarized [3-13C]pyruvate in rats.

Velocity-Selective Tip-Back Excitation for Hyperpolarized [13C] Urea Cardiac Perfusion Imaging
Maximilian Fuetterer1, Julia Busch1, Constantin von Deuster1,2, Christian Binter1, Nikola Cesarovic3, Miriam Lipiski3, Christian Torben Stoeck1,2, and Sebastian Kozerke1,2
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, 2Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom, 3Division of Surgical Research, University Hospital Zurich, Zurich, Switzerland
A velocity-selective excitation scheme with bipolar slice-select gradients for hyperpolarized cardiac perfusion imaging is presented. Using the approach, an excitation ratio of >5 of myocardial signal to left-ventricular blood pool signal can be achieved based on differences in blood and tissue velocities. Thereby increased myocardial signal and reduced left-ventricular signal spilling is obtained. Dynamic perfusion images acquired with hyperpolarized [13C]urea in pigs show higher SNR and less signal leakage in the myocardium relative to a conventional excitation approach.   

Investigating in vivo cardiac ketone bodies metabolism using hyperpolarized 13C acetoacetate
Way Cherng Chen1, Xing Qi Teo1, and Teck Hock Philip Lee1
1Laboratory of metabolic imaging, Singapore Bioimaging Consortium, Singapore, Singapore
The use of hyperpolarized 3-13C acetoacetate to probe in vivo cardiac ketone bodies metabolism was investigated. Preliminary results showed the successful detection of 1-13C citrate and 1-13C acetylcarnitine after hyperpolarized acetoacetate delivery. Specifically, a significant increase in citrate with a corresponding decrease in acetylcarnitine was observed in the rat heart in vivo after 24hrs of fasting.

Dynamic Nuclear Polarization of Biocompatible 13C-Enriched Carbonates for In vivo pH Imaging
David E Korenchan1,2, Robert Flavell1, Renuka Sriram1, Celine Baligand1, Kiel Neumann1, Subramaniam Sukumar1, Daniel B Vigneron1,2, Henry VanBrocklin1, David M Wilson1, and John Kurhanewicz1,2
1Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, CA, United States, 2Bioengineering, University of California at Berkeley, Berkeley, CA, United States
Although large gains in hyperpolarized 13C-bicarbonate signal are obtainable for extracellular pH imaging, toxicity becomes a concern for clinical implementation of current methods. We report an approach in which a precursor molecule, 1,2-glycerol carbonate, is hyperpolarized and decomposed to form bicarbonate, CO2, and glycerol using base-catalyzed hydrolysis. This technique enables concentrations and polarizations similar to those previously reported, and its application to pH imaging, both in phantom experiments and in vivo in a mouse model of prostate cancer, is demonstrated. 

Towards High Resolution Chemical Shift Imaging of the Lungs using Hyperpolarized Carbon-13
Mehrdad Pourfathi1,2, Stephen J. Kadlecek1, Harrilla Profka1, Sarmad M. Siddiqui1,3, Heather Gatens1, and Rahim R. Rizi1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, PA, United States, 3Bioengineering, University of Pennsylvania, Philadelphia, PA, United States
We present the utility of a under-sampled single-shot turbo spin-echo (TSE) sequence for high resolution T2 mapping and imaging of the lungs using hyperpolarized carbon-13 agents. We then demonstrate the possibility of using this sequence selectivity excite different carbon-13 species via a minimum-phase frequency-selective excitation pulse.

Heteronuclear cross- relaxation and polarization transfer effects enable spectroscopic measurements of enzymatic activity by hyperpolarized proton NMR.
Piotr Dzien*1, Anne Fages*2, Kevin Michael Brindle3, Markus Schwaiger1, and Lucio Frydman2
1Nuklearmedizinische Klinik und Poliklinik Klinikum rechts der Isar der TUM, Technische Universität München, Munich, Germany, 2Chemical Physics, Weizmann Institute of Science, Rehovot, Israel, 3CRUK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
Disolution DNP increases the sensitivity of 13C MR sufficiently to allow real time measurements of 13C- labelled substrates and products of their metabolism in vivo. While advantages could also result from hyperpolarized observations based on 1H MR, the fast relaxation times of 1H resonances prevent in vivo applications of this kind.  Here we demonstrate, in vitro, that a substantial enhancement of the 1H resonance of [1-1H, 2,2,2-2H3,1-13C] acetaldehyde, produced in situ by solutions containing purified yeast Pyruvate Decarboxylase (yPDC) from 13C - hyperpolarized [U-2H3,2-13C] pyruvate, can be achieved.  This enhancement can arise from either spontaneous or INEPT-driven 13C --> 1H polarization transfers.

Functionalized Cryptophane-129Xe MRI Biosensor for Biothiols Detection through Thiol-addition Reaction
Shengjun Yang1, Weiping Jiang1, Qing Luo1, Qianni Guo1, and Xin Zhou1
1Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, China, People's Republic of
Biothiols such as cysteine, homocysteine and glutathione play an important role in regulating the vital functions of living organisms. Here, we report a biosensor for biothiol detection and imaging using nuclear spin resonance of 129Xe. The 129Xe biosensor consists of cryptophane-A cage encapsulating xenon atom and acrylate group. The latter serves as a reactive site to covalently bond biothiols through thiol-addition reaction. The selectivity of the biosensor enables discrimination of Cys from Hcy and GSH through the chemical reaction rate. Our results indicate that this biosensor is a promising strategy for the real-time imaging of biothiol distributions.

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