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

Electronic Poster Session: Molecular Imaging

3668 -3691 Hyperpolarized MR (non-gaseous)
3692 -3715 Molecular Imaging & Contrast Agents

Exhibition Hall 

10:00 - 11:00

    Computer #

1 Measuring Perfusion with a Hyperpolarised Ultra-Long T1 15N Glutamine Compound
Rolf F Schulte1, Enrico Chiavazza2,3, Axel Haase2, Silvio Aime3, Marion I Menzel1, Markus Schwaiger2, and Markus Durst1,2
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.


2 In vivo 3D mapping of intracellular pH using hyperpolarized [1-13C]pyruvate in the rodent heart
Angus Zoen Lau1,2, Jack Miller2,3, and Damian J Tyler1,2
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 pHi maps. The intracellular pHi 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.


3 Branched-chain a-keto acid decarboxylation and transamination assessment in mouse liver and kidney using hyperpolarized a-keto[1-13C]isocaproate MRS
Celine A.J. Baligand1, Irene Marco-Rius1, Zhen Jane Wang1, Daniel B. Vigneron1, John Kurhanewicz1, and Michael Ohliger1
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.


4 Hyperpolarized Carbon-13 Ketoisocaproate Reveals Dysfunction in Branched-Chain Amino Acid Metabolism in Liver Cancer
Philip Lee1, Xing Qi Teo1, and Way Cherng Chen1
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.


5 Noninvasive in vivo assessment of cytosolic redox-state in rat liver using hyperpolarized [1-13C]alanine
Jae Mo Park1, Ralph E Hurd2, Shie-Chau Liu1, and Daniel M Spielman1
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. 


6 In-vivo Assessment of Lung Injury Using Hyperpolarized Carbon-13 MRI in a Two-hit Model of Acid Aspiration and VILI
Mehrdad Pourfathi1,2, Yi Xin1, Stephen J Kadlecek1, Maurizio Cereda3, Harrilla Profka1, Sarmad M Siddiqui1,4, Hooman Hamedani1,4, and Rahim R Rizi1
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.


7 Zymonic acid - a novel 13C enriched biosensor for in vivo pH-imaging
Christian Hundshammer1,2, Stephan Düwel1, Malte Gersch3, Benedikt Feuerecker1, Axel Haase4, Markus Schwaiger1, Steffen J. Glaser3, and Franz Schilling1
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. 


8 pH Dependent Kinetics of the Decarboxylation of Pyruvate for pH Mapping Experiments
Nicholas Drachman1, Stephen J. Kadlecek1, Yi Xin1, and Rahim R. Rizi1
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. 


9 In Vivo Hyperpolarized 13C Diffusion Weighted MRI Measures Lactate Efflux and Changes in MCT4 Expression in Prostate Cancer
Jeremy W Gordon1, Hecong Qin1, Renuka Sriram1, Robert Bok1, Peder EZ Larson1, Daniel B Vigneron1, and John Kurhanewicz1
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.


10 Early diabetic kidney maintains the cortico-medullary urea and sodium gradient
Haiyun Qi1, Thomas Stokholm Nørlinger1, Per Mose Nielsen1, Lotte Bonde Bertelsen1, Yafang Xu1, Fredrik Palm2, Hans Stødkilde-Jørgensen1, and Christoffer Laustsen1
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.


11 Accelerating hyperpolarized metabolic imaging of the rat heart using k-t PCA and k-t SPARSE
Patrick Wespi1, Jonas Steinhauser1, Grzegorz Kwiatkowski1, and Sebastian Kozerke1
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.


12 Sampling Hyperpolarized Substrates using a 1 Tesla Permanent Magnet.
Sui-Seng Tee1, Valentina Digialleonardo1, Hannah Nikki Aldeborgh1, Julio Alvarez1, Alex Poot1, and Kayvan Rahimi Keshari1
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.  


13 Hyperpolarized 13C-labeled 5-5-dimethyl-1-pyrroline-N-oxide for in vivo detection of reactive oxygen species
Keita Saito1, Shingo Matsumoto2, Deepak Sail3, Shun Kishimoto1, Hellmut Merkle4, Marcelino Bernardo5, Rolf Swenson3, James B. Mitchell1, and Murali C. Krishna1
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. 


14 Time-course metabolic changes in high-fat diet-induced obesity in rats: hyperpolarized 13C MRS - Permission Withheld
Gwang-Woo Jeong1,2, Chang-Hyun Oh3, Gwang-Won Kim2, Chung-Man Moon2, Xiao-Li Song1, Yun-Hyeon Kim1, Kyu-Youn Ahn4, and Heoung-Keun Kang1
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.


15 Noninvasive biomarkers for the diagnosis of hepatic ischemia reperfusion injury: A real-time in vivo hyperpolarized 13C MRS and IVIM-DWI
Chung-Man Moon1, Gwang-Won Kim1, Heoung-Keun Kang2, Yun-Hyeon Kim2, Kyu-Youn Ahn3, and Gwang-Woo Jeong1,2
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.


16 Multi-modal and multi-scale measurement of metabolism in breast cancer cells both in vitro and in vivo
Benjamin L Cox1,2,3, 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 Eliceiri2,3,7, and Sean B Fain1,7,8
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.


17 LED induced 19F-MR-signal enhancement at 7T
Markus Plaumann1, Thomas Trantzschel1, Joachim Bargon2, Ute Bommerich1, and Johannes Bernarding1
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.


18 A Method to Identify and Correct for Blurring Artifacts in Hyperpolarized Metabolic Imaging
Stephen J. Kadlecek1, Mehrdad Pourfathi1,2, Harrilla Profka1, and Rahim R. Rizi1
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.


19 Hyperpolarized 1-13C Pyruvate Imaging of Porcine Cardiac Metabolism shift by GIK Intervention
Esben Søvsø Szocska Hansen1,2, Rasmus Stilling Tougaard1,3, Emmeli Mikkelsen1, Thomas Stokholm Nørlinger1, Lotte Bonde Bertelsen1, Steffen Ringgaard1, Hans Stødkilde-Jørgensen1, and Christoffer Laustsen1
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.


20 Para-Hydrogen Induced Polarization: Advances in Amino Acid Polarization and Hyperpolarization in Heterogeneous Phase - Permission Withheld
Stefan Glöggler1, Alex Grunfeld2, Jeff McCormick2, Yavuz Ertas2, Phillipp Schleker3, Shawn Wagner4, and Louis-Serge Bouchard2
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.


21 First hyperpolarization of quaternary pyridinium salts using PHIP
Frederike Euchner1, Rainer Ringleb1, Joachim Bargon2, Ute Bommerich1, Johannes Bernarding1, and Markus Plaumann1
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.


22 Hyperpolarized [1-13C]pyruvate and [1-13C]lactate observed using a single shot 3D pulse sequence in vivo
Jiazheng Wang1, Alan Wright1, De-en Hu1, Richard Hesketh1, and Kevin M. Brindle1,2
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.


23 First-in-woman study of in vivo breast cancer metabolism using hyperpolarized [1-13C] pyruvate
Kristin L Granlund1,2, 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 Hricak2,3, and Kayvan A Keshari2,3
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.


24 1H-13C Independently Tuned RF Surface Coil Applied for In vivo Hyperpolarized MRI
Peng Cao1, Xiaoliang Zhang1, Ilwoo Park1, Chloe Najac1, Sarah J. Nelson1, Sabrina Ronen1, and Peder E. Z. Larson1
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.
Exhibition Hall 

10:00 - 11:00

    Computer #

25 Imaging in vitro and in vivo pH with ioversol by CEST MRI
Miaomiao Chen1, Xiaolei Zhang1, Yanzi Chen1, Zhiwei Shen1, Wei Hu1, Xilun Ma1, and Renhua Wu1
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.


26 15N Heteronuclear Chemical Exchange Saturation Transfer MRI Imaging
Haifeng Zeng1,2, Jiadi Xu1,2, Nirbhay N Yadav1,2, Michael T McMahon1,2, Bradley Harden3, Dominique Frueh3, and Peter C.M van Zijl1,2
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.


27 Quantification of macrophage recruitment in double and single hit head and neck cancer using fluorine-19 MRI
Aman Khurana1, Fanny Chapelin1, Hongyan Xu1, Partick McConville2, Quyen Nguyen3, and Eric Ahrens1
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.


28 Simultaneously Trace Blood Perfusion and Glymphatic Passage by Analyzing Deuterium Oxide Perfusion Imaging with a Two-Compartment Parallel Model
Cheng-He Li1, Zi-Min Lei1, Sheng-Min Huang1, Chin-Tien Lu1, Kung-Chu Ho2, and Fu-Nien Wang1
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.


29 Cellulose-triacetate Nanoparticles as Smart Contrast Agents for Single Cell Detection.
Laura Szkolar-Sienkiewicz1, Christiane Mallett2, and Erik M Shapiro1
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.


30 Development of intravascular SPION with tunable pharmacokinetics and relaxivity for preclinical fMRI and micro-MRA
Manasmita Das1,2, Esteban Oyarzabal1, Heather Decot1, Xiopeng Zong1, Neal Shah1, Sung Ho Lee1, Jonathan Edward Frank1, Nazar A Filnov3, and Yen-Yu Ian Shih1,2
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.


31 Assessment of brain development in children with developmental delay using amide proton transfer weighted (APTw) MRI - Video Not Available
Xiaolu Tang1, Hong Zhang1, Xuna Zhao2,3, Jinyuan Zhou2, and Yun Peng1
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.


32 Magnetic/Upconversion Fluorescent Nanoparticle-Based Dual-Modal Molecular Probes for Imaging of  Lymph Node Metastasis From Pancreatic Cancer in vivo
Kai Cao1, Ruirui Qiao2, and Huimin Wei3
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.



33 Dynamic PET and cortical thickness comparison between healthy controls and epilepsy patients using simultaneous PET/MR
Yu-Shin Ding1,2, Shaunak Ohri1, Jean Logan1, Thomas Koesters1, James Babb1, and Orrin Devinsky3
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.


34 MRI-Guided Thermosensitive Liposomal Drug Delivery for Cancer Therapy
Po-Wah So1, Maral Amrahli2, Michael Wright2, Miguel Centelles2, Wladyslaw Gedroyc3, Andrew Miller2, and Maya Thanou2
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.


35 Towards Early Detection of Pancreatic Cancers by Active Feedback MR Molecular Imaging - Permission Withheld
Chaohsiung Hsu1, Zhao Li1, Ryan Quiroz1, Raymond Ngo1, and Yung-Ya Lin1
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.


36 Real Time Detection of Pancreatic Cancer-induced Cachexia using a Fluorescent Myoblast Reporter and 1H MRS Metabolic Analysis
Paul Thomas Winnard Jr1, Santosh Bharti1, Marie-France Penet1, Radharani Marik1, Yelena Mironchik1, Flonne Wildes1, Anirban Maitra2, and Zaver M Bhujwalla1
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.


37 The effect of SNR optimization on cell quantification accuracy for fluorine-19 MRI sequences: bSSFP, FSE, and FLASH
Kai D. Ludwig1, Erin B. Adamson1, Christian M. Capitini2,3, and Sean B. Fain1,4,5
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.


38 Effect of exposure in hypoxia environment caused by high altitude on magnetic susceptibility in human brain assessed by quantitative susceptibility mapping
Dandan Zheng1, Wenjia Liu2, Bing Wu1, and Lin Ma2
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.


39 Iron accumulation in rat brain with frequent USPIO administration
Kofi Deh1, Andrew Gorman2, Caspar Schwiedrzik3, Pascal Spincemaille1, Martin Prince1, and Yi Wang1
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.


40 Comparison Study between T2*, Quantitative Susceptibility Mapping (QSM), and Histology for Postmortem Human Substantia Nigra
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 Cho3
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.


41 Arterial spin labeling can detect discreet changes of renal perfusion after oral application of the pain medication diclofenac in healthy subjects
Susanne Tewes1, Marcel Gutberlet1, Van Dai Vo Chieu1, Dagmar Hartung1, Sebastian Rauhut2, Matti Peperhove1, Frank Wacker1, Faikah Gueler2, and Katja Hueper1
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.


42 Drug Distribution Kinetics in the Eye assessed by 1H-MRI and 19F-MRS
Christina R Haeuser1, Alfred Ross1, Markus von Kienlin1, and Basil Künnecke1
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.


43 Ultra-high field MRI enables the in vivo quantification of the efficacy of candidate promyelinating molecules in the cuprizone mouse model
Isaac Mawusi Adanyeguh1, Emilie Poirion1, Daniel García-Lorenzo2, Marie-Stephane Aigrot1, Brahim Nait-Oumesmar1, Boris Zalc1, Alexandra Petiet1,2, and Bruno Stankoff1,3
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.


44 MRI Assessment of Acute Pathologic Process after Myocardial Infarction: Role of Magnetic Nanoparticle-based MRI - Permission Withheld
Cheongsoo Park1,2, Eun-Hye Park3, Jongeun Kang1,4, Kiyuk Chang3, and Kwan Soo Hong1,4,5
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.


45 APT MRI of Intracranial Mass Lesions at 3T and Comparison with DCE Perfusion Parameters
Ayan Debnath1, Prativa Sahoo2, Pradeep Gupta3, Rakesh Gupta3, and Anup Singh1
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.  


46 Nuclear Overhauser Enhancement (NOE) mediated Chemical Exchange Saturation Transfer (CEST) imaging in glioma with different progression at 7T
Tang Xiangyong1, Dai Zhuozhi1, Shen Yuanyu1, Hu Wei1, Zhang Zhiyan1, and Wu Renhua1
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


47 A Comparison between the UTE and PETRA Pulse Sequences for Fluorine-19 MRI at 3 Tesla
Roberto Colotti1, Jean Delacoste1, Giulia Ginami1, Maxime Pellegrin2, Tobias Kober1,3,4, Yutaka Natsuaki5, David Grodzki6, Ulrich Flögel7, Matthias Stuber1,8, and Ruud B. van Heeswijk1
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.


48 On the Feasibility of Quantitative Dynamic Whole Body PET/MR Imaging
Hyungseok Jang1,2, Hyung-Jun Im1, Arman Rahmim3, Steve Y Cho1, and Alan B McMillan1
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.

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