Rolf F Schulte¹, Enrico Chiavazza^2,3, Axel Haase², Silvio Aime³, Marion I Menzel¹, Markus Schwaiger², and Markus Durst^1,2
1GE Global Research, Munich, Germany, ²Technische Universität München, Munich, Germany, ³Università di Torino, Turin, Italy

An experimental setup for 15N was established on a clinical 3T whole-body scanner, in order to measure perfusion with an ultra-long T1 15N compound. The substance α-trideuteromethyl[15N]glutamine was synthesised, polarised and injected into healthy rats to study the perfusion of the kidneys. With a T1 time in vivo of 146s, it was possible to acquire perfusion images for over 5 minutes.

Angus Zoen Lau^1,2, Jack Miller^2,3, and Damian J Tyler^1,2
1Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom, ²Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom, ³Department of Physics, Clarendon Laboratory, Oxford, United Kingdom

Intracellular pH can be measured in vivo by taking the ratio between hyperpolarized HCO₃^- and CO₂ produced from [1-¹³C]pyruvate, but to date, low CO₂ signal has limited this method to whole-heart assessment. We propose a 3D imaging approach using spectrally-selective excitation which exploits the rapid exchange between HCO₃^- and CO₂ to produce in vivo myocardial pH_i maps. The intracellular pH_i is found to be 7.15±0.04 in the healthy rodent heart. Increased cardiac workload via continuous dobutamine infusion resulted in a decreased intracellular pH of 6.90±0.06.

Celine A.J. Baligand¹, Irene Marco-Rius¹, Zhen Jane Wang¹, Daniel B. Vigneron¹, John Kurhanewicz¹, and Michael Ohliger^1
1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States

The branched-chain α-keto acid dehydrogenase (BCKDH) is an important regulator of branched chain amino acid (BCAA) catabolism.  In several diseases including liver cirrhosis, decreased BCKDH activation results in increased BCAA breakdown through the branched-chain amino transferase (BCAT) and subsequent protein and energy deficiency. We show that both hyperpolarized Leucine and HCO3- signals can be detected in liver in vivo at 14.1 T as byproducts of [1-¹³C]KIC metabolism. This provided information on BCAT/BCKDH activities in mouse liver and kidney, consistent with literature values. Assessing the effect of BCAA supplementation on liver cirrhosis has the potential to impact patient monitoring and treatment.

Philip Lee¹, Xing Qi Teo¹, and Way Cherng Chen^1
1FUNCTIONAL METABOLISM GROUP, SINGAPORE BIOIMAGING CONSORTIUM, Singapore, Singapore

Complex reprogramming of cellular metabolism to support tumorigenesis & survival is a hallmark of cancer. Recently Ericksen et al observed that the suppression of branched-chain amino acids (BCAA) catabolic enzymes is a unique signature in human hepatocellular carcinomas (HCC), and the degree of downregulation correlates strongly with tumor grades and survival outcomes1. Specifically the metabolic activity of the branched-chain keto-acid dehydrogenase (BCKDH) complex was significantly reduced. We hypothesize that this modulation can be measured in vivo by tracking the metabolism of hyperpolarized carbon-13 ketoisocaproate.

Jae Mo Park¹, Ralph E Hurd², Shie-Chau Liu¹, and Daniel M Spielman^1
1Radiology, Stanford University, Stanford, CA, United States, ²Applied Sciences Laboratory, GE Healthcare, Menlo Park, CA, United States

Intracellular [lactate]:[pyruvate] is an important biomarker of cytosolic redox-state, directly reflecting free cytosolic [NADH]:[NAD⁺]. Hyperpolarized [1-¹³C]alanine, which can be also transported across the plasma membrane, is useful to measure relative concentrations of intracellular pyruvate and lactate. In this work, we propose a simple method to assess in vivo cytosolic redox-state using hyperpolarized [1-¹³C]alanine, and demonstrate the ethanol-induced redox change in rat liver. 

Mehrdad Pourfathi^1,2, Yi Xin¹, Stephen J Kadlecek¹, Maurizio Cereda³, Harrilla Profka¹, Sarmad M Siddiqui^1,4, Hooman Hamedani^1,4, and Rahim R Rizi^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, PA, United States, ³Anesthesiology and Critical Care, University of Pennsylvania, Perlman School of Medicine, Philadelphia, PA, United States, ⁴Bioengineering, University of Pennsylvania, Philadelphia, PA, United States

Ventilator induced lung injury (VILI) results from mechanical trauma and secondary inflammatory responses. Previous imaging studies focused on the effects of ventilator settings on structural or functional changes; however, no MRI studies have been conducted to elucidate the metabolic changes during VILI. In this study, the potential of HP [1-¹³C]-pyruvate and its conversion to [1-¹³C]-lactate as a marker for the lung inflammation was investigated in a two-hit model of acid aspiration and VILI.

Christian Hundshammer^1,2, Stephan Düwel¹, Malte Gersch³, Benedikt Feuerecker¹, Axel Haase⁴, Markus Schwaiger¹, Steffen J. Glaser³, and Franz Schilling^1
1Department of Nuclear Medicine, Klinikum rechts der Isar, München, Germany, ²Department of Chemistry, Technische Universität München, München, Germany, ³Department of Chemistry, Technische Universität München, Garching, Germany, ⁴Department of Medical Engineering, Technische Universität München, Garching, Germany

[1,5-¹³C₂] Zymonic acid is derived from carbon 13 labelled pyruvic acid and can be easily deuterium enriched for spin lattice relaxation time prolongation. The molecule exhibits pH dependent NMR shifts and can be used for pH in vivo mapping. Phantom measurements on human blood on a 7T preclinical MRI system indicate that [1,5-¹³C₂] ZA is a suitable pH sensor for pre-clinical and potentially also for clinical applications. 

Nicholas Drachman¹, Stephen J. Kadlecek¹, Yi Xin¹, and Rahim R. Rizi^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States

We have shown that the kinetic rate of the production of bicarbonate from pyruvate is heavily pH dependent. An increase in the rate by a factor of ~10 can be achieved by maintaining the pH of the reaction always above 10.3, the pKa of bicarbonate. This discovery will allow researchers to quickly produce hyperpolarized bicarbonate to be used for in vivo pH mapping experiments. 

Jeremy W Gordon¹, Hecong Qin¹, Renuka Sriram¹, Robert Bok¹, Peder EZ Larson¹, Daniel B Vigneron¹, and John Kurhanewicz^1
1Radiology & Biomedical Imaging, University of California - San Francisco, San Francisco, CA, United States

Dissolution DNP provides a 10,000-fold signal enhancement to carbon-13 nuclei and enables real-time metabolic imaging. In addition to the Warburg Effect, many malignant cancers overexpress MCT4, the monocarboxylate transporter responsible for lactate efflux and extracellular acidification. Because of microenvironmental differences, diffusion weighted imaging (DWI) with hyperpolarized substrates may provide unique information on lactate efflux and MCT4 expression. Here we show that DWI with hyperpolarized substrates is sensitive to changes in MCT4 expression, as lactate ADC is increased by >40% in late-stage TRAMP tumors. This technique may potentially provide a novel way to assess metabolite compartmentalization and transporter expression in malignant disease.

Haiyun Qi¹, Thomas Stokholm Nørlinger¹, Per Mose Nielsen¹, Lotte Bonde Bertelsen¹, Yafang Xu¹, Fredrik Palm², Hans Stødkilde-Jørgensen¹, and Christoffer Laustsen^1
1MR Research Centre, Aarhus University, Aarhus N, Denmark, ²Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden

To investigate the essential intrarenal electrolyte gradients in early diabetic kidneys, hyperpolarized 13C urea was applied to measure urea and sodium gradients. No differences in either intrarenal urea or sodium gradients were observed in early diabetes compared to healthy controls. These results indicate that the early metabolic and hypertrophic changes occurring in the diabetic kidney prelude the later functional alterations in diabetic kidney function, thus driving the increased metabolic demand commonly occurring in the diabetic kidney.

Patrick Wespi¹, Jonas Steinhauser¹, Grzegorz Kwiatkowski¹, and Sebastian Kozerke^1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

Hyperpolarized metabolic imaging of the heart suffers from limited spatial specificity in current protocols. In this work two algorithms, k-t PCA and k-t SPARSE, that allow accelerated metabolic imaging are compared in simulations and used to acquire in-vivo metabolic maps in rats at one millimeter in-plane resolution.

Sui-Seng Tee¹, Valentina Digialleonardo¹, Hannah Nikki Aldeborgh¹, Julio Alvarez¹, Alex Poot¹, and Kayvan Rahimi Keshari^1
1Radiology, MSKCC, New York, NY, United States

Hyperpolarized MRI quantifies metabolic fluxes non-invasively. One limitation is the rapid loss of polarized signal, decaying according to its longitudinal relaxation (T₁) time. We propose the use of a permanent, 1 Tesla spectrometer to lengthen T₁s. We show longer T₁ values across different functional groups. Scalar couplings were also visible and these advantages were translatable to biologically-relevant settings using perfused bioreactors. As more clinical trials are performed, it is essential to understand the behavior of HP molecules at field strengths similar to hospital magnets. Sampling HP substrates using permanent magnets is simple and cost-effective and will directly benefit clinical imaging.  

Keita Saito¹, Shingo Matsumoto², Deepak Sail³, Shun Kishimoto¹, Hellmut Merkle⁴, Marcelino Bernardo⁵, Rolf Swenson³, James B. Mitchell¹, and Murali C. Krishna^1
1Radiation Biology Branch, National Cancer Institute, Bethesda, MD, United States, ²Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Japan, ³Imaging Probe Development Center, National Heart, Lung, and Blood Institute, Rockville, MD, United States, ⁴National Institute of Neurological Disorder and Stroke, Bethesda, MD, United States, ⁵Molecular Imaging Program, National Cancer Institute, Bethesda, MD, United States

5,5-Dimethyl-1-pyrroline-N-oxide (DMPO) is a spin trap agent used to detect reactive oxygen species (ROS). We synthesized ¹³C-labeled DMPO, and investigated feasibility of hyperpolarized ¹³C-DMPO to detect ROS generated in living animals. Hyperpolarized ¹³C-DMPO gave us a single peak at 76 ppm on the ¹³C-spectrum, and ¹³C-DMPO was distributed through the mouse body immediately after intravenous injection. The results indicate hyperpolarized ¹³C-DMPO provided sufficient magnitude of the ¹³C signal to be detected in the mouse body, and can be applied to some disease models to evaluate the capability for detection of ROS in vivo. 

Gwang-Woo Jeong^1,2, Chang-Hyun Oh³, Gwang-Won Kim², Chung-Man Moon², Xiao-Li Song¹, Yun-Hyeon Kim¹, Kyu-Youn Ahn⁴, and Heoung-Keun Kang^1
1Department of Radiology, Chonnam National University Medical School, Gwang-ju, Korea, Republic of, ²Research Institute of Medical Imaging, Chonnam National University Medical School, Gwang-ju, Korea, Republic of, ³Department of Electronics and Information Engineering, Korea University, Gwang-ju, Korea, Republic of, ⁴Department of Anatomy, Chonnam National University Medical School, Gwang-ju, Korea, Republic of

Non-alcoholic fatty liver is an increasing common liver disease in world population. Recent hyperpolarized 13C magnetic resonance spectroscopy (HP 13C MRS) studies revealed the cellular metabolite changes associated with the various liver diseases in animals. However, a study for high-fat diet(HFD)-induced obesity using HP 13C MRS in animal model has not yet been performed until now. The purpose of this study was to investigate the time-course metabolic changes based on HP 13C MRS in HFD-induced obesity in rats and their correlations with serum enzyme levels.

Chung-Man Moon¹, Gwang-Won Kim¹, Heoung-Keun Kang², Yun-Hyeon Kim², Kyu-Youn Ahn³, and Gwang-Woo Jeong^1,2
1Research Institute for Medical Imaging, Chonnam National University Hospital, Gwangju, Korea, Republic of, ²Radiology, Chonnam Natioanl University Medical School, Gwangju, Korea, Republic of,³Anatomy, Chonnam Natioanl University Medical School, Gwangju, Korea, Republic of

Hepatic ischemia reperfusion injury (IRI) induces cellular damage and causes cell death. It can lead to acute liver failure accompanied with biochemical changes, microcirculatory disturbances and/or histopathologic changes. Early detection of impaired liver function is vital for effective therapeutic interventions and thus prevents its progression to liver failure. However, an in vivo study of hepatic IRI model in combination with hyperpolarized ¹³C magnetic resonance spectroscopy (¹³C MRS) and diffusion-weighted imaging (DWI) has not yet been attempted until now. The purpose of this study was to investigate the cellular metabolite change, diffusion of water molecules and microcirculation of blood in rat model with hepatic IRI and their correlations with enzyme levels.

Benjamin L Cox^1,2,3, Joseph M Szulczewski⁴, Kai D Ludwig¹, Erin B Adamson¹, David R Inman⁴, Stephen A Graves¹, Justin J Jeffery⁵, Jason D McNulty⁶, Patricia J Keely⁴, Kevin W Eliceiri^2,3,7, and Sean B Fain^1,7,8
1Medical Physics, University of Wisconsin at Madison, Madison, WI, United States, ²Morgridge Institute for Research, Madison, WI, United States, ³Laboratory for Optical and Computational Instrumentation, University of Wisconsin at Madison, Madison, WI, United States, ⁴Cell and Regenerative Biology, University of Wisconsin at Madison, Madison, WI, United States, ⁵UW Carbone Cancer Center, Madison, WI, United States, ⁶Mechanical Engineering, University of Wisconsin at Madison, Madison, WI, United States, ⁷Biomedical Engineering, University of Wisconsin at Madison, Madison, WI, United States, ⁸Radiology, University of Wisconsin at Madison, Madison, WI, United States

A system and workflow for spatially registered in vivo optical microscopy, MRI, and PET of breast tumor metabolism is described. The system is coupled with a bioreactor designed to compare cellular metabolism in vitro using both optical microscopy and MR spectroscopy with the behavior of tumor cells in the in vivo tumor microenvironment. Results from enzyme reactions are shown, demonstrating the temperature control capabilities of the bioreactor. A proof of concept in vivo experiment is also described, with optical microscopy data of a mammary tumor acquired in conjunction with MRI and PET data, on the same animal.

Markus Plaumann¹, Thomas Trantzschel¹, Joachim Bargon², Ute Bommerich¹, and Johannes Bernarding^1
1Department for Biometrics and Medical Informatics, Otto-von-Guericke University Magdeburg, Magdeburg, Germany, ²Institute for Physical and Theoretical Chemistry, University of Bonn, Bonn, Germany

¹⁹F containing substrates serve as attractive reporter molecules for NMR and MRI studies. Applications for in vivo studies are limited by low spin densities due to restricted concentrations. Using hyperpolarization techniques, such as Chemically Induced Dynamic nuclear Polarization (CIDNP), this constrained can be overcome. So far, ¹⁹F hyperpolarization generated in D₂O, which is a prerequisite for an in vivo application, could only be documented using laser photo-CIDNP. In this study the successful hyperpolarization of a ¹⁹F nucleus in in 3-fluoro-DL-tyrosine in its free and a complexed form using D₂O as a solvent is presented using a simple LED photo-CIDNP device.

Stephen J. Kadlecek¹, Mehrdad Pourfathi^1,2, Harrilla Profka¹, and Rahim R. Rizi^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, PA, United States

Hyperpolarized imaging sequences  are subject to potential bias and spread of apparent signal to neighboring voxels due to the time-dependence of magnetization as RF pulses are applied and as polarization is lost through spin-lattice relaxation.  In this abstract, we discuss a method to detect and correct for artifacts and demonstrate it using chemical shift imaging.  The method utilizes periodic resampling of nonselective spectra to correct for signal dynamics.  We show that this technique results in a higher fidelity, "de-blurred" image.

Esben Søvsø Szocska Hansen^1,2, Rasmus Stilling Tougaard^1,3, Emmeli Mikkelsen¹, Thomas Stokholm Nørlinger¹, Lotte Bonde Bertelsen¹, Steffen Ringgaard¹, Hans Stødkilde-Jørgensen¹, and Christoffer Laustsen^1
1MR Research Centre, Aarhus University, Aarhus N, Denmark, ²Danish Diabetes Academy, Odense, Denmark, ³Cardiology, Aarhus University Hospital, Aarhus N, Denmark

Cardiac metabolism has gained considerable attention worldwide lately, both as a diagnostic and prognostication tool, as well as a novel target for treatment. As human trials involving hyperpolarized MR in the heart are imminent, we employed a clinically relevant, large animal model, and sought to evaluate the general feasibility to detect an imposed shift in metabolic substrate utilization during metabolic modulation with glucose, insulin and potassium (GIK) infusion. This study demonstrates that hyperpolarized ¹³C-pyruvate, in a large animal, is a feasible method for cardiac studies, and, in combination with GIK intervention; that it is able to detect imposed metabolic shifts.

Stefan Glöggler¹, Alex Grunfeld², Jeff McCormick², Yavuz Ertas², Phillipp Schleker³, Shawn Wagner⁴, and Louis-Serge Bouchard^2
1University of Southampton, Southampton, United Kingdom, ²University of California Los Angeles, Los Angeles, CA, United States, ³RWTH Aachen University, Aachen, Germany, ⁴Cedars Sinai Medical Center, Los Angeles, CA, United States

We present new amino acid derivatives that can be hyperpolarized with the Para-Hydrogen Induced Polarization method (PHIP). Furthermore, we report on the highest achieved polarization of amino acid derivatives in biocompatible medium (water) to date with relevance for in vivo applications. Moreover, the first heterogeneous catalyst for PHIP in water will be presented that leads to significant levels of polarization. This poses the possiblity of a quick filtration step to yield clean PHIP-polarized contrast agents for future in vivo studies.

Frederike Euchner¹, Rainer Ringleb¹, Joachim Bargon², Ute Bommerich¹, Johannes Bernarding¹, and Markus Plaumann^1
1Department for Biometrics and Medical Informatics, Otto-von-Guericke University Magdeburg, Magdeburg, Germany, ²Institute for Physical and Theoretical Chemistry, University of Bonn, Bonn, Germany

Quaternary ammonium substrates are of huge interest in the pharmaceutical field. Here, the hyperpolarization of new fluorinated pyridinium ions was examined. The effect of the positive charged nitrogen relating to the polarization transfer inside the molecule was proven and compared with the ¹H, ¹³C and ¹⁹F hyperpolarization examinations of 2-(3-fluoro-phenyl)-3-buten-2-ol. The observed effect can be used for localization of polarization and for the synthesis of extened MR signal  enhancements.

Jiazheng Wang¹, Alan Wright¹, De-en Hu¹, Richard Hesketh¹, and Kevin M. Brindle^1,2
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom, ²Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom

We have developed a single-shot 3D sequence for hyperpolarized ¹³C MRI, with a spatial-spectral (SpSp) pulse for excitation and a stack-of-spirals acquired in interleaved fashion during two spin echoes. The sequence achieved a resolution of 1.25x1.25x2.5 mm³ in vivo on a 7T animal system, where hyperpolarized [1-¹³C]pyruvate and [1-¹³C]lactate were imaged alternately at a frame rate of 2 s per metabolite. Variations are allowed in the design of the acquisition train to balance the in-plane and through-plane resolutions. This sequence allows higher temporal resolution and less RF depletion of the polarization than pulse sequences described previously.

Kristin L Granlund^1,2, Elizabeth A Morris³, Hebert A Vargas³, Serge K Lyashchenko⁴, Phillip J DeNoble⁴, Virgilio A Sacchini⁵, Ramon A Sosa³, Matthew A Kennedy³, Duane Nicholson³, YanWei W Guo³, Albert P Chen⁶, James Tropp⁷, Hedvig Hricak^2,3, and Kayvan A Keshari^2,3
1Radiology, Memorial Sloan Kettering, New York, NY, United States, ²Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ³Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ⁴Radiochemistry & Imaging Probes (RMIP) Core, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ⁵Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ⁶GE Healthcare, Toronto, ON, Canada, ⁷GE Healthcare, Fremont, CA, United States

This is a first-in-woman study of hyperpolarized (HP) pyruvate to study in vivo cancer metabolism. A patient with biopsy-proven breast cancer has been scanned with a 2D dynamic hyperpolarized pyruvate protocol. This study aims to evaluate the feasibility and repeatability of HP breast cancer imaging. HP pyruvate imaging may be useful for evaluating treatment response before and after targeted as well as chemo-therapy or radiation treatment.

Peng Cao¹, Xiaoliang Zhang¹, Ilwoo Park¹, Chloe Najac¹, Sarah J. Nelson¹, Sabrina Ronen¹, and Peder E. Z. Larson^1
1Department of Radiology, University of California at San Francisco, San Francisco, CA, United States

This study aimed to develop a lump-element double-tuned common-mode-differential-mode (CMDM) radiofrequency (RF) surface coil with independent frequency tuning capacity for MRS and MRI applications. This CMDM coil maintained intrinsically decoupled magnetic fields, which provided sufficient isolation between the two resonators. The results from in vivo experiments demonstrated high sensitivity of both the ¹H and ¹³C resonators.

Miaomiao Chen¹, Xiaolei Zhang¹, Yanzi Chen¹, Zhiwei Shen¹, Wei Hu¹, Xilun Ma¹, and Renhua Wu^1
1Radiology Department, Second Affiliated Hospital, Shantou University Medical College, Shantou, China, People's Republic of

We have developed a CEST MRI method that can measure pH using ioversol, a contrast agent that is clinically approved for X-ray imaging and has been repurposed for CEST MRI studies. Using ioversol as a CEST agent, we have measured pH over a range of 6.0 - 7.8 pH units by a novel ratiometric pH MRI method, in a concentration-independent manner. We also have used this agent and CEST MRI method to measure the extracellular pH (pHe) within the liver of healthy SD rats.

Haifeng Zeng^1,2, Jiadi Xu^1,2, Nirbhay N Yadav^1,2, Michael T McMahon^1,2, Bradley Harden³, Dominique Frueh³, and Peter C.M van Zijl^1,2
1Russell H. Morgan Department of Radiology and Radiological Science, 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, ³Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, United States

A two-step heteronuclear enhancement approach to magnify ¹⁵N MRI signal through indirect detection of water is described. Chemical Exchange Saturation Transfer (CEST) works by continuously perturbation of the spin magnetization of the exchangeable spins, and then through chemical exchange to accumulate this perturbation on water proton for signal magnification. This perturbation is mainly limited to saturation or excitation pulse on the exchangeable protons. In this work, the signal of ¹⁵N is detected indirectly through the water signal by first inverting selectively protons scalar-coupled to ¹⁵N in the urea molecule, followed by chemical exchange of the amide proton to bulk water.

Aman Khurana¹, Fanny Chapelin¹, Hongyan Xu¹, Partick McConville², Quyen Nguyen³, and Eric Ahrens^1
1Radiology, University of California, San Diego, San Diego, CA, United States, ²Molecular Imaging Inc. La Jolla, San Diego, CA, United States, ³Head & Neck Surgery, University of California, San Diego, San Diego, CA, United States

Head and neck carcinoma is a source of significant mortality worldwide, two prevalent subtypes include double and single hit tumors. We aimed to evaluate the role of infiltrating immune cells in worse clinical outcomes with double-hit tumor patients. A novel 19-Fluorine containing perfluorocarbon (PFC) emulsion was used to tag macrophages with high specificity and sensitivity and no background. The average number of 19F spins within the double hit tumors were approximately double compared to the single hit group. This quantifies the tumor associated macrophage burden of head and neck cancer using a PFC emulsion and proton/19F MRI.

Cheng-He Li¹, Zi-Min Lei¹, Sheng-Min Huang¹, Chin-Tien Lu¹, Kung-Chu Ho², and Fu-Nien Wang^1
1Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan, ²Nuclear Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

This study tried to simultaneously trace blood perfusion and glymphatic passage by applying two-compartment parallel model (2CPM) on D₂O perfusion using the new imaging strategy. Six rats were injected with D₂O, and both F₁ and F₂ were quantified from 2CPM. The results show that F₁ is highly coordinated with cerebral blood flow, while F₂ is much irrelevant. Only regions near several arteries show significant F₂ values, which is speculated as the paravascular pathway of CSF regulated by glymphatic system. Therefore, using 2CPM for tracing D₂O might noninvasively reveal the information of both blood and CSF dynamics.

Laura Szkolar-Sienkiewicz¹, Christiane Mallett², and Erik M Shapiro^1
1Radiology, Michigan State University, East lansing, MI, United States, ²Michigan State University, East lansing, MI, United States

It was demonstrated that enzymatically degradable cellulose triacetate particles offer a novel approach to contrast modulation. The use of such materials as smart contrast agents has been discussed and evidence of cellular uptake and relaxivity modification shown.

Manasmita Das^1,2, Esteban Oyarzabal¹, Heather Decot¹, Xiopeng Zong¹, Neal Shah¹, Sung Ho Lee¹, Jonathan Edward Frank¹, Nazar A Filnov³, and Yen-Yu Ian Shih^1,2
1Biomedical Research Imaging Center, UNC Chapel Hill, Chapel Hill, NC, United States, ²Department of Neurology, University of North Carolina Chapel Hill, Chapel Hill, NC, United States, ³SOP-CNDD, UNC Chapel Hill, Chapel Hill, NC, United States

We have developed a simple, inexpensive method to synthesize high-performance intravascular SPION in house. We were able to tune the relaxivity and PK profile of our home-made SPION via careful surface functionalization control and came up with an optimal formulation that offered very robust and stable contrast for high resolution cerebromicroangiography and steady state CBV functional imaging. Our future studies will focus on developing novel MR-detectable inflammation markers using our home-made iron oxide as the platform material.

Xiaolu Tang¹, Hong Zhang¹, Xuna Zhao^2,3, Jinyuan Zhou², and Yun Peng^1
1Imaging Center, Beijing Children’s Hospital, Capital Medical University, Beijing, China, People's Republic of, ²Neurosection, Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, ³Philips Healthcare, Beijing, China, People's Republic of

Amide proton transfer weighted (APTw) imaging is a novel molecular MRI technique that can noninvasively detect cytosolic endogenous mobile proteins and peptides in myelination process. However it is not well known to brain developments in children with developmental delay using APTw MRI. The aim of our work is to explore the brain development in children with developmental delay (DD) using APTw MRI. The final conclusion shows that APTw MRI is a promising technique to assess children with DD at a molecular level.

Kai Cao¹, Ruirui Qiao², and Huimin Wei^3
1Radiology, Changhai Hospital, Shanghai, China, People's Republic of, ²Chemistry, Chinese Academy of Sciences, Beijing, China, People's Republic of, ³Clinic and Translational Medicine Center, Changhai Hospital, Shanghai, China, People's Republic of

Construction of the specific pancreatic cancer probe based on upconversion nanoparticles. The probes taking biocompatibility upconversion nanoparticles with unique magnetic properties as a carrier, conjugated with ATF peptide specifically targeting the uPAR. Then, its effect of detection of tumor and lymph node metastasis would be further validated in an orthotopic human pancreatic cancer xenograft model by pathology and dual-modal imaging.

 

Yu-Shin Ding^1,2, Shaunak Ohri¹, Jean Logan¹, Thomas Koesters¹, James Babb¹, and Orrin Devinsky^3
1Radiology, NYU School of Medicine, New York, NY, United States, ²Psychiatry, NYU School of Medicine, New York, NY, United States, ³Neurology, NYU School of Medicine, New York, NY, United States

Our results suggest that 1) simultaneous PET/MR imaging provides a useful imaging tool to identify regional abnormalities; 2) more information can be rendered from dynamic PET data; 3) SUVmean_late and cortical thickness are independent biomarkers for epilepsy. In general, Freesurfer and SPM are more robust in orientation and segmentation than FSL.

Po-Wah So¹, Maral Amrahli², Michael Wright², Miguel Centelles², Wladyslaw Gedroyc³, Andrew Miller², and Maya Thanou^2
1Neuroimaging, King's College London, London, United Kingdom, ²Institute of Pharmaceutical Sciences, King's College London, London, United Kingdom, ³Experimental Medicine, Imperial College London, london, United Kingdom

We have designed and synthesised a novel liposome formulation, capable of releasing encapsulated drug on targeting/heating by focussed ultrasound (FUS) for cancer therapy and being visualised by MRI due to the incorporation of gadolinium chelates.  We show the novel liposomes are targeted to tumours by FUS and MRI-visible in vivo and thus, suitable for theranostic applications in cancer.

Chaohsiung Hsu¹, Zhao Li¹, Ryan Quiroz¹, Raymond Ngo¹, and Yung-Ya Lin^1
1Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA, United States

Early detection of pancreatic cancers using enhanced MRI techniques increases not only the treatment options available, but also the patients’ survival rate. This can be achieved with antibody-conjugated superparamagnetic iron oxide (SPIO) nanoparticles capable of binding to early stage pancreatic cancer cells to improve imaging specificity and innovation methods that can sensitively detect SPIO to improve imaging sensitivity. The enhanced contrast from SPIO can then be used to visually assess the distribution and magnitude of SPIO-targeted tumor cells. In vivo subcutaneous and orthotopic xenografts mouse models validated the superior contrast/sensitivity and robustness of this approach towards early pancreatic cancers detection.

Paul Thomas Winnard Jr¹, Santosh Bharti¹, Marie-France Penet¹, Radharani Marik¹, Yelena Mironchik¹, Flonne Wildes¹, Anirban Maitra², and Zaver M Bhujwalla^1
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²MD Anderson Cancer Center, Houston, TX, United States

Therapeutic options for cancer-induced cachexia are limited and therefore, efforts to identify signs of precachexia in cancer patients are necessary for early intervention. Here, we generated a myoblast cell line expressing a dual dTomato:GFP construct that was grafted onto the muscle of mice bearing human pancreatic cancer xenografts to provide noninvasive live imaging of events associated with cancer-induced cachexia (i.e., weight loss). ¹H MRS revealed that weight loss in cachectic animals was associated with a depletion of plasma lipid, cholesterol, and valine, and decreased skeletal muscle alanine levels, which may provide informative biomarkers of cachexia.

Kai D. Ludwig¹, Erin B. Adamson¹, Christian M. Capitini^2,3, and Sean B. Fain^1,4,5
1Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, ²Pediatrics, University of Wisconsin-Madison, Madison, WI, United States, ³Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, United States, ⁴Radiology, University of Wisconsin-Madison, Madison, WI, United States, ⁵Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States

Several MRI data acquisition methods have been used for fluorine-19 (19F) MRI cell tracking and optimizing the image SNR helps mitigate low sensitivity. An optimization workflow is presented for three 19F pulse sequences based upon relaxation parameters measured in a 19F reference phantom.  Bloch simulations reveal signal differences between the reference phantom and pure 19F cellular label for SNR-optimized bSSFP, FSE, and FLASH. The simulated relative errors in 19F signal suggest SNR optimization can compromise signal quantification and thus in vivo cell quantification but could provide insight for improved methods to balance the degree of spin-density weighting and SNR.

Dandan Zheng¹, Wenjia Liu², Bing Wu¹, and Lin Ma^2
1MR Research China, GE Healthcare, Beijing, China, People's Republic of, ²Radiology Department, Beijing Military General Hospital, Beijing, China, People's Republic of

Cerebrospinal fluid fraction, CBF and T2 decay have been reported to be related with hypoxia caused by high altitude in previous studies. All these biomarkers maybe associate with tissue homogeneous magnetism changes, which may result in the magnetic susceptibility changes. Quantitative susceptibility mapping (QSM) is a novel technique that allows mapping of tissue magnetic susceptibility. It has the potential to be more sensitive with respect to magnetic tissue properties than conventional magnitude-based techniques such as transverse relaxation rates. This study was designed to reveal the effect of exposure in hypoxia environment on magnetic susceptibility in human brain assessed by QSM.

Kofi Deh¹, Andrew Gorman², Caspar Schwiedrzik³, Pascal Spincemaille¹, Martin Prince¹, and Yi Wang^1
1Weill Cornell Medical College, New York, NY, United States, ²Tri-Institutional Training Program in Laboratory Animal Medicine and Science, New York, NY, United States, ³The Rockefeller University, New York, NY, United States

An observation of signal loss on functional MRI images of primates following repeated administration of ultra-small super-paramagnetic iron oxide (USPIO) particles, led us to test a hypothesis of iron accumulation in the brain by performing weekly quantitative susceptibility mapping (QSM) of rats receiving daily USPIO injections for 9 weeks.  We observed rapid increase in the susceptibility values in brain ventricles and choroid plexus confirmed by serum iron measurements and histology. In light of a similar report in the literature, we recommend monitoring patients receiving iron therapy with a susceptibility imaging technique such as QSM.

Jae-Hyeok Lee¹, Sun-Yong Baek², YoungKyu Song³, Sujeong Lim³, Hansol Lee³, Minh Phuong Nguyen⁴, Eun-Joo Kim⁵, Gi Yeong Huh⁶, Se Young Chun⁴, and HyungJoon Cho^3
1Department of Neurology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea, Republic of, ²Department of Anatomy, Pusan National University School of Medicine, Yangsan, Korea, Republic of, ³Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Korea, Republic of,⁴Department of Electrical and Computer Engineering, Ulsan National Institute of Science and Technology, Ulsan, Korea, Republic of, ⁵Department of Neurology, Pusan National University Hospital, Busan, Korea, Republic of, ⁶Department of Forensic Medicine, Pusan National University School of Medicine, Yangsan, Korea, Republic of

 Selective iron deposition in the substantia nigra (SN) along with the gradual loss of neuromelanin cell (NMC) is known to be associated with neurodegenerative diseases, such as Parkinson's disease. Postmortem 40-year-old male and 70-year-old female SN tissues were scanned at various spatial resolutions with 7T MRI. The association of T2* and QSM-derived susceptibility values with quantitative NMC and iron from Perl's Prussian blue staining were investigated with precise co-registration of MRI and histology. We identified that T2* and susceptibility values for NMC and iron regions, which were segmented from histology were significantly different from corresponding values of background tissue area.

Susanne Tewes¹, Marcel Gutberlet¹, Van Dai Vo Chieu¹, Dagmar Hartung¹, Sebastian Rauhut², Matti Peperhove¹, Frank Wacker¹, Faikah Gueler², and Katja Hueper^1
1Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany, ²Clinic for Nephrology, Hannover Medical School, Hannover, Germany

Diclofenac is a nonsteroidal anti-inflammatory drug that is frequently prescribed to reduce inflammation and pain. It reduces the prostaglandin-synthesis and may consequently have an effect on renal perfusion. We investigated whether arterial spin labeling can detect reduction of renal perfusion after oral and topical application of diclofenac compared to baseline measurements. Ten healthy subjects underwent functional MRI of the kidney. After oral application of diclofenac renal perfusion was reduced compared to baseline measurements (321±13 vs. 345±16 ml/(min*100g), p<0.01). No significant changes were found after topical application. In conclusion, ASL can detect discreet changes of renal perfusion that occur after application of diclofenac.

Christina R Haeuser¹, Alfred Ross¹, Markus von Kienlin¹, and Basil Künnecke^1
1Roche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland

Drug treatment of vision impairing diseases often involves intraocular drug injection into the vitreous humour, a highly viscous gel-like matter. Drug transport within the vitreous humour has remained rather elusive although transport processes are acknowledged to play a pivotal role for treatment efficacy and adverse effects in the target tissue. Here, we devised a potentially translational approach based on contrast-enhanced 1H-MRI and 19F-MRS to quantitatively ascertain intravitreal drug distribution kinetics at the macro-scale. We provided proof-of-concept for the small drug-like molecule trifluoroethanol in isolated porcine eyes.

Isaac Mawusi Adanyeguh¹, Emilie Poirion¹, Daniel García-Lorenzo², Marie-Stephane Aigrot¹, Brahim Nait-Oumesmar¹, Boris Zalc¹, Alexandra Petiet^1,2, and Bruno Stankoff^1,3
1Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Brain and Spine Institute, ICM, F-75013, Paris, France, Paris, France, ²Center for NeuroImaging Research (CENIR), Brain and Spine Institute, 75013 Paris, France, Paris, France, ³AP-HP, Saint Antoine Hospital, Department of Neurology, 184 bd Faubourg Saint Antoine, 75012 Paris, Paris, France

Endogenous remyelination can potentially restore rapid axonal-conduction and confer neuroprotection in chronic demyelinating diseases such as multiple sclerosis. We used T₂ mapping to evaluate the ability of two candidate pharmacological agents to promote remyelination in cuprizone-demyelinated mice. Demyelination was associated with increase in signal intensity and T₂ values in the corpus callosum and external capsules. T₂ values showed spontaneous recovery after discontinuation of cuprizone treatment, an effect accelerated following administration of the two compounds tested.  This study confirms that in vivo MRI can be used to select pharmacological agents for their therapeutic potential on remyelination.

Cheongsoo Park^1,2, Eun-Hye Park³, Jongeun Kang^1,4, Kiyuk Chang³, and Kwan Soo Hong^1,4,5
1Korea Basic Science Institute, Cheongju, Korea, Republic of, ²The Catholic University of Korea, Seoul, Korea, Republic of, ³Seoul St. Mary’s Hospital and College of Medicine, Seoul, Korea, Republic of,⁴Chungnam National University, Daejeon, Korea, Republic of, ⁵University of Science and Technology, Daejeon, Korea, Republic of

Myocardial infarction (MI) is the major cause of sudden death in most industrialized society. Imaging of early disease progression and investigation of relationship between myocardial necrosis and successive inflammatory response are needed for optimal treatment of MI. We conducted cardiac MR imaging of disease progression in acute MI by using three different MRI methods of Gd (LGE), Mn (ME), and iron oxide nanoparticles (MNP)-based MRI for estimation of infarcted and inflammatory regions.

Ayan Debnath¹, Prativa Sahoo², Pradeep Gupta³, Rakesh Gupta³, and Anup Singh^1
1Centre for Bio-Medical Engineering, Indian Institute of Technolgy Delhi, Delhi, India, ²Philips India Limited, New Delhi, India, ³Radiology, Fortis Memorial Research Institute, New Delhi, India

In the current study, Amide Proton Transfer (APT) and T1-weighted DCE perfusion MRI  was performed on patients with intra-cranial mass lesions(low and high grade tumors, CNS tuberculoma, CNS lymphoma) at 3T MRI. APT maps provided a significant difference between lesion and its contra-lateral side. From the preliminary study it was observed that APT contrast was low in infection lesion followed by tumor and lymphoma.  APT values showed a significant (P<0.01) difference between low and high grade tumors. A weak Inter-class correlation was observed between APT and perfusion parameters (like cbf, cbv, Ktr, Kep, ve). Therefore, APT mapping might improve diagnostic value either alone or in combination with other MRI parameters.  

Tang Xiangyong¹, Dai Zhuozhi¹, Shen Yuanyu¹, Hu Wei¹, Zhang Zhiyan¹, and Wu Renhua^1
12nd Affilicated Hospital, Shantou University Medical College, Shantou, China, People's Republic of

Nuclear Overhauser Enhancement (NOE) mediated Chemical Exchange Saturation Transfer (CEST) imaging in glioma with different progression at 7T

Roberto Colotti¹, Jean Delacoste¹, Giulia Ginami¹, Maxime Pellegrin², Tobias Kober^1,3,4, Yutaka Natsuaki⁵, David Grodzki⁶, Ulrich Flögel⁷, Matthias Stuber^1,8, and Ruud B. van Heeswijk^1
1Department of Radiology, University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland, ²Division of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland,³Advanced Clinical Imaging Technology, Siemens Healthcare IM BM PI, Lausanne, Switzerland, ⁴LTS5, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ⁵Siemens Medical Solutions, NAM USA DI MR COLLAB WE, Los Angeles, CA, United States, ⁶Siemens Healthcare GmbH, HC DI MR R&D PLH, Erlangen, Germany, ⁷Department of Cardiovascular Physiology, Heinrich Heine University, Düsseldorf, Germany, ⁸Center for Biomedical Imaging (CIBM), Lausanne, Switzerland

Fluorine-19 (¹⁹F) MRI of perfluorocarbon emulsions (PFCs) with multiresonant spectra is challenging due to destructive phase interference that leads to short T₂ relaxation times (<10 ms). Pulse sequences with very short echo times (≤ 100 µs) can be used to overcome this challenge. In this study, in vitro and in vivo ¹⁹F MRI obtained with both UTE and PETRA were acquired and quantitatively compared.

Hyungseok Jang^1,2, Hyung-Jun Im¹, Arman Rahmim³, Steve Y Cho¹, and Alan B McMillan^1
1Department of Radiology, University of Wisconsin, Madison, WI, United States, ²Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI, United States, ³Department of Radiology, Johns Hopkins University, Baltimore, MD, United States

In this study we investigate the feasibility of FDG PET/MR as a platform for whole body dynamic quantitative PET imaging. The ability of PET/MR systems to provide truly simultaneous imaging is advantageous compared to PET/CT for serial whole body PET acquisitions in that simultaneously acquired MR images can provide additional information to PET data, such as the application of motion parameters estimated from MR images to PET images to correct for misregistration which is not possible with PET/CT. Further improvements in workflow can allow integration of multiple MR contrasts, making dynamic whole body PET/MR a highly feasible and compelling methodology.