David E J Waddington^1,2,3, Mathieu Sarracanie^2,3,4, Huiliang Zhang^3,5, Torsten Gaebel¹, David R Glenn^3,5, Ewa Rej¹, Najat Salameh^2,3,4, Ronald L Walsworth^3,5, David J Reilly¹, and Matthew S Rosen^2,3,4
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.

Abiola Olatunde¹, Taylor Fuss¹, Phillip Zhe Sun¹, Leo L Cheng¹, and Peter Caravan^1
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 LnDOTP^5-, 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 LnDOTP^5- complexes for spermine and the effect of complex formation on spermine MR resonances in both D₂O and serum solutions and intact human prostate tissue. 

Isabel Ramos^1,2, Markus Henningsson¹, Maryam Nezafat¹, Begoña Lavin^1,2, Pierre Gebhardt¹, Andrea Protti^1,2, Sara Lacerda^1,2, Silvia Lorrio^1,2, Alkystis Phinikaridou^1,2, Ulrich Flögel³, Ajay M. Shah², and René M. Botnar^1,2
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.

Casey Y. Lee^1,2, Justin Y. C. Lau^1,2, Albert P. Chen³, Yi-Ping Gu², and Charles H. Cunningham^1,2
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.

Maximilian Fuetterer¹, Julia Busch¹, Constantin von Deuster^1,2, Christian Binter¹, Nikola Cesarovic³, Miriam Lipiski³, Christian Torben Stoeck^1,2, and Sebastian Kozerke^1,2
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.   

Way Cherng Chen¹, Xing Qi Teo¹, and Teck Hock Philip Lee^1
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.

David E Korenchan^1,2, Robert Flavell¹, Renuka Sriram¹, Celine Baligand¹, Kiel Neumann¹, Subramaniam Sukumar¹, Daniel B Vigneron^1,2, Henry VanBrocklin¹, David M Wilson¹, and John Kurhanewicz^1,2
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. 

Mehrdad Pourfathi^1,2, Stephen J. Kadlecek¹, Harrilla Profka¹, Sarmad M. Siddiqui^1,3, Heather Gatens¹, and Rahim R. Rizi^1
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.

Piotr Dzien*¹, Anne Fages*², Kevin Michael Brindle³, Markus Schwaiger¹, and Lucio Frydman^2
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.

Shengjun Yang¹, Weiping Jiang¹, Qing Luo¹, Qianni Guo¹, and Xin Zhou^1
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.