ISMRM 23rd Annual Meeting & Exhibition • 30 May - 05 June 2015 • Toronto, Ontario, Canada

Electronic Poster Session • Molecular Imaging
4591 -4612 Hyperpolarized MR
4661 -4682 Molecular Imaging

Note: The videos below are only the slides from each presentation. They do not have audio.

Thursday 4 June 2015
13:30 - 14:30

  Computer #  
4591.   1 Comparison of FDG-PET and Hyperpolarized Pyruvate in Assessing Response to an Isoform-specific PI3K inhibitor in Breast Cancer
Aaron K Grant1, Gopal Varma1, Hai Hu2, Xiaoen Wang1, Ashish Juvekar2, Soumya Ullas2, and Gerburg Wulf2
1Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States, 2Hematology and Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States

Phosphoinositide 3-Kinase (PI3K) is known to influence several steps in glycolysis. We compare the effects of an inhibitor of the α isoform of PI3K on FDG uptake and hyperpolarized 13C spectroscopy in a mouse model of breast cancer. Although pan-PI3K inhibitors have been shown to yield sizable reductions in FDG uptake in this model, we find that the isoform specific inhibitor of PI3Kα results in only modest reductions. This inhibitor has larger effects on hyperpolarized 13C spectroscopy of pyruvate and its metabolites. These results indicate that hyperpolarized pyruvate may have greater sensitivity to metabolic effects of isoform-specific PI3Kα inhibition.

4592.   2 High resolution hyperpolarized metabolic imaging with three-dimensional spectral-spatial EPI at 7T
Jack J. Miller1,2, Angus Z. Lau1,3, and Damian J. Tyler1,3
1Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom, 2Department of Physics, University of Oxford, Oxford, United Kingdom, 3Department of Cardiovascular Medicine, OCMR, University of Oxford, Oxford, United Kingdom

Hyperpolarised metabolic imaging has the potential to revolutionise the treatment and management of heart disease. We present here a novel sequence for the 3D imaging of hyperpolarised pyruvate and its metabolic products in the rat heart at 7T. The sequence has excellent spatiotemporal resolution (1x1x2 mm3 after zerofilling by two, ~1.8s) and good coverage (64x32x45 mm FOV). We demonstrate its sensitivity to probe cardiac metabolism by imaging animals who have had their PDH flux modulated by being fasted, fed, or fed and administered the PDK inhibitor dichloroacetate, and observe significantly different images of metabolism in each state.

4593.   3 Effect of acetate concentration on its cerebral metabolism studied by hyperpolarized 13C MRS
 - permission withheld
Elise Vinckenbosch1, Mor Mishkovsky1, Arnaud Comment2, and Rolf Gruetter1,3
1Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 2Institute Of Physics Of Biological Sytems, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 3Department of Radiology, Université de Lausanne et de Genève, Lausanne and Geneva, Switzerland

Hyperpolarized [1-13C]acetate enables for in vivo detection of 2-oxoglutarate (2OG), a tricarboxylic acid (TCA) cycle intermediate, in intact brain. We investigate the effect of acetate concentration on its cerebral metabolism using both Hyperpolarized 13C MRS and 1H MRS at high field. We found that using lower acetate concentration improves physiological results as well as the dynamics range between substrate and its metabolites. The different kinetics of the 2OG as compared to Ace and its dependence on substrate concentration supports its assignment. We conclude that optimized sample formulation combined with lower hyperpolarized substrate dose improves cerebral studies of oxidative pathway.

4594.   4 Magnetic field dependence of singlet state lifetimes and implications for hyperpolarized magnetic resonance
Thomas Theis1, Matthew Morgan1, Kevin Claytor2, Ryan Davis3, Zijian Zhou1, and Warren Warren4
1Chemistry, Duke University, Durham, NC, United States, 2Physics, Duke University, Durham, NC, United States, 3BME, Duke University, Durham, NC, United States, 4Chemistry, Physics, Radiology and BME, Duke University, Durham, NC, United States

The biggest limitation of hyperpolarized magnetic resonance is fast signal decay upon injection of a hyperpolarized metabolite. Over the past decade, long lived singlet states have been developed to store hyperpolarization on much longer timescales than accessible when relying on the normal T1 decay, promising hyperpolarized MR on biological timescales. Here we show, that many interesting motifs such as 15N2-diazirine, show significantly longer singlet lifetimes at low magnetic fields and discuss our findings in light of the fact that with hyperpolarization signal-to-noise is largely independent of the magnetic field concluding that low field hyperpolarized experiments are promising for future research.

4595.   5 Time evolution of [1,2-13C]Pyruvate doublet asymmetry in hyperpolarized 13C MRS
Keshav Datta1 and Daniel Spielman2
1Dept. of Electrical Engineering, Stanford University, Stanford, CA, United States, 2Dept. of Radiology, Stanford University, Stanford, CA, United States

In-vivo hyperpolarized 13C Magnetic Resonance Spectroscopy (MRS) allows the interrogation of multiple key metabolic pathways, with applications in studying cancer metabolism, cardiovascular pathologies and other metabolic disorders. Absolute quantitation is desirable for fully interpreting in-vivo hyperpolarized metabolic imaging data, and a necessary parameter is the liquid-state polarization of the injected substrate. Asymmetry of the C2 doublet, arising from 1% naturally abundant [1,2-13C]Pyr in any hyperpolarized [1-13C]Pyr, has been suggested to be directly related to, and used for measuring the instantaneous C1polarization. The unexpected finding was that the time evolution of the asymmetry parameter seemed to evolve independently of the eventual thermal equilibrium value given by the residual JCC coupling. Here we present a more complete theory in which the combination of dipolar coupling of carbon and adjacent protons, dipolar coupling of carbon nuclei and Chemical Shift Anisotropy (CSA) interactions fully account for the observed time evolution of asymmetry.

4596.   6 In vivo T2 mapping of hyperpolarized [1-13C] pyruvate using an indirect method
Eunhae Joe1, Joonsung Lee2, Hansol Lee1, Seungwook Yang1, Young-suk Choi3, Eunkyung Wang3, Ho-Taek Song3, and Dong-Hyun Kim1
1School of Electrical and Electronic Engineering, Yonsei University, Seoul, Korea, 2Severance Biomedical Science Institute, Yonsei University, Seoul, Korea,3Department of Radiology, Yonsei University College of Medicine, Seoul, Korea

T2 relaxation time is an important consideration in metabolic imaging. However, in vivo T2 relaxation time of 13C metabolites in hyperpolarized 13C study is still not well investigated. Recently, apparent in vivo T2 relaxation times of hyperpolarized [1-13C] pyruvate and its downstream metabolites were reported in several studies, but they measured T2 values from a whole slice or a single voxel using spin-echo based methods. In this work, we propose a T2 estimation method for hyperpolarized 13C metabolites which utilizes the T2¡¯ information of water proton and T2* of the 13C metabolites from a conventional chemical shift image (CSI).

4597.   7 Hyperpolarized 1-13C pyruvate metabolism as marker of inflammation and progression of lung injury
Hoora Shaghaghi1, Yi Xin1, Sarmad Siddiqui1, Stephen Kadlecek1, Mehrdad Pourfathi1, Maurizio Cereda2, Harrilla Profka1, Hooman Hamedani1, and Rahim R. Rizi1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA, United States

Mechanical ventilation is an essential component of the care of patients with acute respiratory distress syndrome to improve gas exchange and minimize any additional hypoxic damage. However mechanical ventilation itself can further injure damaged lungs. The metabolic changes of acid-aspiration lung injury were studied during a protective ventilation strategy using hyperpolarized 13C-MRS. Blood cytokine analysis stabilized after one hour of ventilation. Analysis of hourly CT did not show any changes in lung weight and edema when using the protective ventilation strategy but HP-lactate signal increased during protective ventilation after lung injury and shows the progress of inflammation and neutrophil infiltration.

4598.   8 Voxel-by-voxel signal correlations between carbon-13 metabolic and perfusion agents in a rat breast cancer xenograft model by co-polarization of pyruvic acid and HP001
Justin Y.C. Lau1,2, Albert P. Chen3, Yiping Gu2, William Dominguez-Viqueira2, and Charles H. Cunningham1,2
1Dept. of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 2Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, 3GE Healthcare, Toronto, Ontario, Canada

Pyruvic acid and perfusion agent HP001 were co-polarized and injected into a breast cancer xenograft model in rats. A voxel-by-voxel analysis of pyruvate, lactate, and HP001 showed a statistically significant (p < 0.05) correlation between pyruvate and HP001 in the kidney in all 5 animals. In the tumour, lactate SNR correlated with perfusion, but the correlation between lactate and HP001 was stronger than that between lactate and pyruvate. Normalization of lactate signal using the HP001 response may be reasonable if rapid metabolic conversion to lactate precludes observation of pyruvate signal.

4599.   9 Development of High Resolution 3D Hyperpolarized 13C Imaging Techniques
Eugene Milshteyn1, Cornelius von Morze1, Galen D. Reed2, Hong Shang1, Peter J. Shin1, Zihan Zhu1, John Kurhanewicz1, Robert Bok1, and Daniel B. Vigneron1
1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, 2HeartVista, Menlo Park, CA, United States

Hyperpolarized 13C MRI enables detection of metabolic and physiological information noninvasively with 50,000+ fold signal enhancement. Previous studies involving hyperpolarized pyruvate, lactate, and urea have used spatial resolutions of ~0.05cm3, but here we developed a specialized 3D bSSFP sequence to achieve 1.5mm isotropic (0.003cm3) resolution, leading to dramatic improvements in MR molecular imaging.

4600.   10 Hyperpolarized 1-13C pyruvate metabolism of inflamed lung via pulmonary delivery: A preliminary study
Hoora Shaghaghi1, Stephen Kadlecek1, Mehrdad Pourfathi1, Sarmad Siddiqui1, Harrilla Profka1, Hooman Hamedani1, Maurizio Cereda2, Yi Xin1, and Rahim R. Rizi1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA, United States

Inhaled drug delivery is often preferred because it enables local treatment of asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and acute lung injury while avoiding systemic drug effects. In this study, the uptake of hyperpolarized (HP)-[1-13C] pyruvate by the inflamed lung alveolar is investigated as a potential imaging method to monitor pulmonary drug delivery. The metabolite signal from hyperpolarized pyruvate shows alveolar uptake even in healthy cohorts. Enhancement of lactate signal in the injury model also shows the possibility of using hyperpolarized 13C-MRI for monitoring the arrival of the drug at the site of lung inflammation.

4601.   11 ParaHydrogen Induced Polarization via Side Arm Hydrogenation (PHIP-SAH) allows hyperpolarization of acetate and [1-13C] pyruvate. - video not available
Francesca Reineri1, Tommaso Boi2, and Silvio Aime3
1Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy, 2Bracco Imaging Spa, Italy, 3Molecular Biotechnology and Health Sciences, Universitty of Torino, Torino, Italy

Hyperpolarization techniques led to very important results in the field of Metabolic Magnetic Resonance Imaging. Dynamic Nuclear Polarization (DNP) is the most widely used method and hyperpolarized metabolites such as [1-13C]-pyruvate are shown to report on status of tumors. Parahydrogen Induced Polarization (PHIP) is a chemistry-based technique, easier-to-handle and much less expensive in respect to DNP. Its main limitation is the availability of unsaturated precursors for the target substrates. Herein is reported a method that allows to achieve hyperpolarization on molecules such as acetate, pyruvate and other biologically relevant substrates that cannot be obtained by direct incorporation of parahydrogen.

4602.   12 Observing Gluconeogenesis in Real-Time in the Zucker Rat Using Hyperpolarized [2-13C]Dihydroxyacetone
Karlos Moreno1, Jian-Xiong Wang2, Leila Fidelino3, A. Dean Sherry3, Craig Malloy3, and Matthew E Merritt2
1UT Southwestern Medical Center, Dallas, TX, United States, 2AIRC, UT Southwestern Medical Center, Dallas, TX, United States, 3AIRC, UT Southwestern Medical Center, TX, United States

Hyperpolarized [2-13C]dihydroxyacetone has been shown to be an effective imaging agent for the detection of glycolysis and gluconeogenesis in perfused mouse liver. Here its use in vivo is demonstrated in the Zucker rat liver. A slice selective spectroscopy protocol records its metabolism with 3 s time resolution. DHA is rapidly metabolized to products of both gluconeogenesis and glycolysis. Future experiments will seek to correlate these measures with an independent assessment of gluconeogenesis in the liver.

4603.   13 Strategies to simplify and generalize hyperpolarization of heteronuclei invoking the cost-efficient SABRE method
Thomas Theis1, Milton Truong2, Eduard Chekmenev3, and Warren Warren4
1Chemistry, Duke University, Durham, NC, United States, 2Radiology, Vanderbilt University, Nashville, TN, United States, 3Radiology and BME, Vanderbilt University, Nashville, TN, United States, 4Chemistry, Physics, Radiology and BME, Duke University, Durham, NC, United States

We introduce methods to hyperpolarize nitrogen-15 and likely other heteronuclei cost efficiently and with ease. Heteronuclei are the preferred targets in hyperpolarized magnetic resonance because they are associated with long hyperpolarized signal lifetimes and don’t have to compete with background signals from water. A particularly cost efficient hyperpolarization method is “Signal Amplification By Reversible Exchange” (SABRE) which uses parahydrogen as the source of hyperpolarization; but SABRE has primarily been used to hyperpolarize protons. We demonstrate 1) above 10% nitrogen-15 polarization by conducting SABRE in a magnetic shield and 2) RF based methods to create nitrogen-15 hyperpolarization directly in the magnet.

4604.   14 Hyperpolarized [U-2H, U-13C]glucose reports on glycolytic and pentose phosphate pathway activity in EL4 tumors and glycolytic activity in yeast cells.
Kerstin N Timm1,2, Johannes Hartl1, Markus Keller1, De-En Hu1,2, Alan J Wright2, Mikko I Kettunen1,2, Tiago B Rodrigues2, Susana Ros2, Markus Ralser1,3, and Kevin M Brindle1,2
1Department of Biochemistry, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, 2CRUK Cambridge Institute, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, 3MRC National Institute for Medical Research, London, United Kingdom

A resonance at ~181 ppm in the 13C spectra of tumors injected with hyperpolarized [U-2H, U-13C]glucose was assigned to 6-phosphogluconate (6PG) in a recent study, as in previous studies in yeast, whereas in breast cancer cells in vitro this resonance was assigned to 3-phosphoglycerate (3PG). These peak assignments were investigated and clarified here using measurements of 6PG and 3PG 13C-labeling with liquid chromatography tandem mass spectrometry (LC-MS/MS). We found that the resonance at ~181 ppm in 13C MR spectra following injection of hyperpolarized [U-2H, U-13C]glucose originates predominantly from 6PG in EL4 tumors and 3PG in yeast cells.

4605.   15 Ramp-Sampled, Symmetric EPI for Rapid Dynamic Metabolic Imaging of Hyperpolarized 13C Substrates on a Clinical MRI Scanner
Jeremy W Gordon1, Sonam Machingal1, John Kurhanewicz1, Daniel Vigneron1, and Peder Larson1
1Radiology & Biomedical Imaging, UCSF, San Francisco, CA, United States

Hyperpolarization has enabled non-invasive metabolic imaging, but dynamic data is required to provide quantitative metabolite maps. In this work, we implement a symmetric, ramp-sampled EPI trajectory with a partial Fourier reconstruction to reduce the TE and improve SNR for HP 13C imaging. The ramp-sampled, symmetric EPI implemented here provides a fast and clinically efficacious method to acquire dynamic 13C data with human-sized FOVs.

4606.   16 Gadoxetate-Attenuated Hyperpolarized 13C MRI for Selective Assessment of Liver Metabolism
Michael Abram Ohliger1, Cornelius von Morze1, Jeremy Gordon1, Robert Bok1, Jane Z Wang1, Peter Shin1, John Kurhanewicz1, and Daniel Vigneron1
1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States

We propose to combine the anatomic specificity of gadoxetate, a hepatocyte-specific gadolinium contrast agent, with the metabolic information provided by hyperpolarized 13C imaging to better isolate signal arising from hepatocytes. The metabolism of hyperpolarized [1-13C]pyruvate was measured by MRS in the liver and kidneys of rats prior to and after the administration of gadoxetate in the hepatobiliary phase. Hyperpolarized [1-13C]alanine production in the liver consistently decreased after gadoxetate infusion, while production in the kidney was unchanged. Because alanine is chiefly produced inside cells, this suggests that intracellular gadoxetate is causing a hepatocyte-specific reduction in the hyperpolarized MR signal.

4607.   17 A novel Bloch-McConnell simulator for perfused hyperpolarized substrates
Christopher M Walker1 and James Bankson1
1Department of Imaging Physics, UT MD Anderson Cancer Center, Houston, TX, United States

The transient and non-renewable nature of hyperpolarized (HP) substrates necessitates that acquisition strategies be carefully optimized to maximize accuracy and reproducibility. We describe a software environment for simulation of HP studies that couple the Bloch equations with models for label exchange and pharmacokinetic delivery. With this simulator we can explore the effects of sequence parameters on the accuracy of measurements compared to a known numerical phantom. Initial studies show that the impact of sequence parameters differs substantially between assumption of a “closed system” involving only chemical conversion and a “perfused system” with the HP substrate arriving over time.

4608.   18 Characterization of Glycolytic Activity and Perfusion in a Renal Cell Carcinoma Model During Sunitinib Treatment and Resistance with Hyperpolarized 13C MRI
Leo L Tsai1, Xiaoen Wang1, Gopal Varma1, David Alsop1, and Aaron K Grant1
1Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States

h13C-pyruvate MRI provides vivo assessment of glycolytic activity and perfusion within an RCC model, correlating to treatment response and resistance. This method has translational potential for clinical tumor monitoring in patients

4609.   19 On the Utility of Propionate as a Probe of Myocardial Energy Metabolism Using Hyperpolarization – Effects on Anaplerotic Flux and Substrate Preference
Mukundan Ragavan1, Xiaorong Fu1, Shawn C Burgess1, and Matthew E Merritt1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States

Propionyl-CoA obtained from degradation of amino acids undergoes conversion to succinyl-CoA and provides an anaplerotic flux into the TCA cycle. In this work, sodium propionate is used as a probe of energy metabolism in the heart in conjunction with hyperpolarization. Propionate alters the pool sizes of 4 – carbon TCA cycle intermediates and glutamate without affecting cardiac function. In a hyperpolarized experiment, when injected with pyruvate, propionate significantly increases the pyruvate dehydrogenase flux. These results demonstrate the utility of propionate as a probe for studying myocardial energy metabolism.

4610.   20 Assessing tumor microenvironment in rat glioma model using hyperpolarized 13C MRSI with a sliding window
Jae Mo Park1, Ralph E Hurd2, Dirk Mayer3, Lawrence D Recht4, and Daniel M Spielman1
1Radiology, Stanford University, Stanford, CALIFORNIA, United States, 2Applied Sciences Laboratory, GE Healthcare, Menlo Park, California, United States,3Diagnostic Radiology & Nuclear Medicine, University of Maryland, Baltimore, Baltimore, MD, United States, 4Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States

In vivo characteristics of hyperpolarized 13C-substrates are often critical in the design of optimized pulse sequence as well as in the data analysis. By far, T1 has received most attention since the observation window of hyperpolarized 13C MR signals are T1-limited. T2 and T2* are also useful to understand tissue characteristics and create unique image contrasts, providing information for alternative MR acquisition strategies. In this study, we propose a method that measures T2* using a sliding window spiral chemical shift imaging and calculate (1) in vivo T2* maps of hyperpolarized 13C-substrates and (2) B0 maps from glioma-implanted rat.

4611.   21 Quantification of TAE-induced Alterations in Tumor Metabolism using Hyperpolarized 13C-MRSI
Mehrdad Pourfathi1, Terence Gade1, Stephen Hunt1, Stephen Pickup1, Anthony Mancuso1, Stephen Kadlecek1, Neil Harrison1, Gregory Nadolski1, Rahim R. Rizi1, Mitchell Schnall1, Michael Soulen1, and Simon Celeste2
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Cell and Developmental Biology, University of Pennsylvania, PA, United States

Alteration in tumor metabolism was probed using hyperpolarized pyruvate MRSI before and after Transatertial Embolization (TAE) in hepatocellular carcinoma rat model (HCC). Pre and post embolization data suggests reduced lactate production due to reduced in oxygen consumption of the surviving cancerous tissue.

4612.   22 SNR Comparison of EPI and Spiral 3D Time Resolved Imaging of Hyperpolarized [1-13C]Pyruvate and [1-13C]Lactate
Benjamin J. Geraghty1,2, Justin Y.C. Lau1,2, Albert P. Chen3, William Dominguez-Viqueira1, and Charles H. Cunningham1,2
1Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, 2Dept. of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 3GE Healthcare, Toronto, Ontario, Canada

One of the major challenges facing the clinical translation of metabolic MRI using 13C substrates is limited sensitivity. Acquisition schemes that are reproducible, robust and maximize the attainable SNR are vital. In this work, we provide an SNR comparison for time resolved 3D spiral and echo-planar hyperpolarized [1-13C]pyruvate and [1-13C]lactate imaging. In order to control for inter-experiment variability regarding polarization, metabolism, perfusion and injection timing, we’ve developed an experimental paradigm that alternates the readout trajectory during a single in vivo experiment. Results suggest ~75% increase in SNR attainable using Spiral rather than EPI.

Thursday 4 June 20155
14:30 - 15:30

  Computer #  
4661.   1 Biodistribution of lanthanide-based MRI contrast agents assessed by BIRDS - video not available
Yuegao Huang1, Peter Herman1, Daniel Coman1, Samuel Maritim2, and Fahmeed Hyder1,2
1Diagnostic Radiology, Yale University, New Haven, CT, United States, 2Biomedical Engineering, Yale University, New Haven, CT, United States

Lanthanide-based MRI contrast agents are used in molecular imaging. But biodistribution studies are needed prior to in vivo scans, which are usually examined with radioactive lanthanide ions instead of paramagnetic ions within the complexes. We propose that biodistribution of paramagnetic lanthanide complexes can be examined by biosensor imaging of redundant deviation in shifts (BIRDS), in which proton intensities of the complexes themselves are measured and thus the tissue concentrations of the complexes can be evaluated. We infused TmDOTP5- with three different infusion protocols (i.e., agent only, probenecid treated, and renal ligation) to find variable distributions in different organs.

4662.   2 Fe2O3/AgI Core/Shell Nanoparticles for Dual Modal Computed Tomography and Magnetic Resonance Imaging Applications. - permission withheld
Anamaria Orza1, Xiangyang Tang1, Yi Yang1, Hui We1, Run Lin1, Liya Wang1, and Hui Mao1
1Radiology and Imaging Sciences, Emory University, Atlanta, Georgia, United States

It has been shown that nanoparticle based imaging contrast agents offer high contrast effect and slow clearance as well as potential for targeted imaging once functionalized. Herein, we report a convenient and valuable way to fabricate a high performance targeted dual CT/MRI contrast agent made of AgI/Fe2O3 core/shell nanostructure. We synthesized the AgI/Fe2O3 core/shell nanoparticles by controlling the nucleation and growth kinetics of the metal precursors (KI and AgNO3)on the surface of already prepared iron oxide nanoparticles (IONPs) using a dual reduction agent-ascorbic acid. The prepared dual modal nanoparticles were stabilized with an amphiphilic diblock polymer and then further functionalized with ligands targeting transferrin receptor. Spectroscopic (XPS, UV-VIS, EDX), imaging (TEM, HR-TEM) and in vitro biocompatibility and targeting capability were investigated. Prepared core/shell nanoparticles showed excellent biocompatibility, targeting capability and high CT and MRI contrast enhancement, demonstrating that the present AgI/Fe2O3 platform has a great potential for targeted CT and MRI applications.

4663.   3 Fast relaxing contrast agent for fluorine MRI
Vít Herynek1, Andrea Gálisová1, Jan Blahut2, Jan Kotek2, and Milan Hájek1
1Institute for Clinical and Experimental Medicine, Prague, Czech Republic, 2Faculty of Science, Charles University, Prague, Czech Republic

A novel nickel complex bearing six equivalent fluorine ions with short relaxation was synthesized and characterized. The nickel complex reached T1=4.2 ms, T2=1.8 ms, and T2*=1.1 ms, whereas empty ligand had T1=1100 ms, T2=11 ms and T2*=3.1 ms. Substantial shortening of the fluorine relaxation times enables shortening of measurement time in combination with a suitable fast sequence, or increasing of sensitivity by accumulation of more acquisitions. The complex shortens also proton relaxation times, therefore it is traceable on both proton and fluorine images and might be potentially utilisable for both systemic administration and cell labelling.

4664.   4 Physical Principles of Transient T1-Lengthening by Hemodilution: Applications to Perfusion MRI with Normal Saline Injections (NSI)
Hernan Jara1, Osamu Sakai1, Asim Z Mian1, Stephan Anderson1, Jorge A Soto1, and Alexander M Norbash1
1Boston University, Boston, Massachusetts, United States

Purpose: Work in the context of perfusion-MRI using normal saline as dynamic contrast agent. Purpose is to model the magnetization dynamics of blood and perfused tissues during and after transient hemodilution resulting from an injection of normal saline (NS). Methods: Equations describing the MR signal intensity changes are expressed in terms of the transient inversion recovery signal and the injection temporal profile. Results: Presented theory, which is based on the two-compartment model with rapid exchange, predicts T1 lengthening by hemodilution. Conclusion: Developed theory further supports the viability of NS as a T1-legthning MR contrast agent.

4665.   5 Dual functional graphene quantum dots for targeted multimodal imaging and therapy
Shizhen Chen1, Yuqi Yang1, Qing Luo1, and Xin Zhou1
1National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Wuhan, Hubei, China

We developed a multifunctional nanoprobe incorporating graphene quantum dots, Gd3+ and a typical anticancer drug doxorubicin for magnetofluorescent bioimaging and drug delivery purposes

4666.   6 A novel CEST-MRI ratiometric approach for in vivo pH imaging
Dario Livio Longo1, Phillip Zhe Sun2, Lorena Consolino3,4, Filippo Michelotti5, Fulvio Uggeri6, and Silvio Aime3,4
1Institute of Biostructure and Bioimaging, CNR, Torino, Italy, 2MGH and Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Cherlestown, Massachusetts, United States, 3Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy, 4Molecular Imaging Center, University of Torino, Torino, Italy, 5Department of Preclinical Imaging and Radiopharmacy, University of Tubingen, Tubingen, Germany,6Bracco Imaging SpA, Milano, Italy

A novel ratiometric pH MRI method based on the analysis of CEST effects under different radiofrequency irradiation power levels was developed. The proposed method has been demonstrated using iobitridol, an X-ray contrast agent analog of iopamidol but containing a single set of amide protons, both in vitro and in vivo.

4667.   7 Imaging developing neural structures in chick embryo using novel Gd2O3 contrast agent
Gary R. Stinnett1, Nasim Taheri2, Stacey M. Glasgow3, Benjamin Deneen4, Vicki L. Colvin2, and Robia G. Pautler5
1Baylor College of Medicine, Houston, TX, United States, 2Chemistry, Rice University, Houston, TX, United States, 3Ctr Stem& Regen, Baylor College of Medicine, Houston, TX, United States, 4Neuroscience, Baylor College of Medicine, Houston, TX, United States, 5Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, United States

Using a novel T1 gadolinium oxide based contrast agent we have imaged developing neural structures in a chick embryo.

4668.   8 Developing Hyperpolarized Silicon Micro and Nanoparticles for Targeted Molecular Imaging of Ovarian Cancer
Nicholas Whiting1, Jingzhe Hu1,2, Niki Zacharias Millward1, Rajesha Rupaimoole3, David Gorenstein4, Anil Sood3, and Pratip Bhattacharya1
1Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, 2Department of Bioengineering, Rice University, Houston, Texas, United States, 3Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, 4Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center at Houston, Houston, TX, United States

Hyperpolarized silicon particles hold great promise as targeted molecular imaging agents due to their overall biocompatibility and long-lasting enhanced MRI signals. We performed dynamic nuclear polarization on silicon nano- and micro-particles that were functionalized with thioaptamers that target ovarian cancer and conducted in vivo studies in orthotopic mouse models using a variety of particle administration methods. Early results show large microparticles lack the mobility to migrate to tumor sites; ongoing studies are developing smaller (<100 nm) particles for molecular imaging. The goal is to create a noninvasive nano-platform for targeted diagnostic and therapeutic interventions.

4669.   9 Motexafin Gadolinium (MGd)-Enhanced Molecular MR and Optical Imaging of Rat Gliomas for Potential Intraoperative Determination of Tumor Margins
Longhua Qiu1,2, Feng Zhang1, Yaoping Shi1, Zhibin Bai1, Jianfeng Wang1, Donghoon Lee1, Xiaoyuan Feng2, and Xiaoming Yang1
1Image-Guided Biomolecular Intervention Research, Department of Radiology, University of Washington School of Medicine, Seattle, Washington, United States, 2Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China

Malignant glioma is an extremely aggressive neoplasm known for its highly infiltrative growth and dissemination. Identification of the real tumor margin during surgery plays a pivotal role in ensuring the complete eradication of tumors. The aim of this study was to investigate the possibility of using motexafin gadolinium (MGd)-enhanced molecular MR imaging and optical imaging to identify the genuine margins of rat gliomas.

4670.   10 MRI of liver fibrosis with a fibrin-specific probe
Iliyana Atanasova1, Lan Wei2, Helen Day3, Boris Keil3, Francesco Blasi3, Bryan C Fuchs2, and Peter Caravan3
1Madrid-MIT MVision Consortium, MIT, Cambridge, MA, United States, 2Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, United States, 3A. A. Martinos Center for Biomedical Imagin, Massachusetts General Hospital, Charlestown, MA, United States

We investigate whether liver MRI with a fibrin-targeted contrast agent (EP-2014R) could be used to detect abnormal fibrin deposition in vivo in a rat model of moderate liver fibrosis. Fibrosis was generated by administration of diethylnitrosamine. Control animals received PBS. T1-weighted imaging was performed prior to and following contrast injection. Our results indicated that MRI with a fibrin-specific probe could be used to characterize earlier stages of liver fibrosis as the method can differentiate moderate fibrosis from healthy tissue and is also sensitive to acute effects of liver injury.

4671.   11 A comparison of [11C]-(R)PK11195 tracer kinetics and MRI-based vascularity-related parameters in gliomas
Chao Li1,2, Zhangjie Su1, Ka-Loh Li1, Alex Gerhard1, Gerard Thompson1, Xiaoping Zhu1, Rainer Hinz1, Federico Roncaroli3, Karl Herholz1, and Alan Jackson1
1Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, United Kingdom, 2Department of Neurosurgery, Shanghai First People's Hospital, Shanghai, China, 3“John Fulcher” Neuro-Oncology Lab, Imperial College London, London, United Kingdom

Our previous PET study in human gliomas has shown the tracer kinetics of [11C]-(R)PK11195 and the potential to detect malignant transformation of non-enhancing gliomas. This study compared the MRI-based vascularity-related parametric maps and the PET-based tracer kinetics maps. We demonstrated close relationship between MRI-based parameters, rCBF, MTT etc, and the PET-based parameters, BPND and RI, where the change of vascularity and neuroinflammation was unrecognized on the conventional 3D contrast enhanced MRI. A combination of advanced MRI and PET techniques could provide more information about the nature of the tumor, which would be useful in planning of targeted biopsy and treatment.

4672.   12 Magnetic brain cell stimulation using an MRI contrast agent: superparamagnetic iron oxide nanoparticles (SPIONs)
Yichao Yu1, Chris Payne1, Vitaliy Kasymov2, Bernard Siow1, Quentin Pankhurst3, Alexander Gourine2, and Mark F Lythgoe1
1Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom, 2Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom, 3Institute of Biomedical Engineering, University College London, London, United Kingdom

The ability to manipulate a selective group of cells in vivo is highly desirable and currently optogenetics is the go-to method for this functionality. Here we describe a novel and less invasive technology which uses magnetic field and iron oxide particles to remotely stimulate calcium spikes in astrocytes. We present proof-of-concept results showing stimulation of astrocytes with force created by magnetic fields acting on iron oxide particles attached to the cells, and explore the feasibility of using an MRI system as a source for the magnetic field, so that imaging and actuation could be done in a single system.

4673.   13 MEMRI and Tumors: a method for the evaluation of the contribution of Mn(II) ions in the intra- and extra-cellular compartments - video not available
Eliana Gianolio1, Francesca Arena1, Enza Di Gregorio1, Roberto Pagliarin2, Martina Delbianco2, Gabriella Baio3, and Silvio Aime1
1Molecular Biotecnologies and Health Sciences, University of Torino, Torino, Italy, Italy, 2Chemistry, University of Milano, MIlano, Italy, Italy, 3Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, Scotland, United Kingdom

A method able to differentiate between intra- and extra-cellular Mn(II) MR-signal in vivo is presented. This task was pursued by sequestering the Mn2+ ions in the extracellular compartment into a highly stable chelate (Mn-DO2A) characterized by very low relaxivity (“MRI silent”). The in vivo validation of the method was preceded by the in vitro relaxometric characterization and by studies of the internalization efficiency in B16F10 cells. It was found that, 2 hours after the administration of MnCl2, in the tumor region, 45% and 25% of the observed SE% is due to manganese distributed into the intra- and extra-cellular compartments, respectively.

4674.   14 Manganese-enhanced MRI (MEMRI) enables measurement of regional myocardial viability and to evaluate the regenerative effects by human induced pluripotent stem cell derived cardiomyocytes (iCMs)
Atsushi Tachibana1, Morteza Mahmoudi1, Yuka Matsuura1, Rajesh Dash1, Eric Rulifson1, and Phillip Yang1
1Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States

Human induced pluripotent stem cell derived cardiomyocytes (iCMs) have a possibility to regenerate and restore the myocardium. Manganese-enhanced MRIfs (MEMRI) ability to detect myocardial viability may delineate the regional regeneration by iCM engraftment to explain for enhanced LVEF. This study investigates the iCMsf regenerative changes in the murine model of myocardial injury. The LVEF and MEMRI of iCM-treated myocardium demonstrate enhanced function and viability, which correlate significantly with the BLI signal of iCM engraftment. These findings suggest that the iCMs regenerate the injured myocardium.

4675.   15 Functional Imaging of Brown Fat in mouse - permission withheld
Hussein SROUR1 and Kai Hsiang CHUANG1
1Singapore BioImaging Consortium, Singapore, Singapore, Singapore

The brown adipose tissue (BAT) is a type of fat that modulates both basal and inducible energy expenditure in mammals. Its presence in adult humans has recently gained tremendous interest due to its implication in the development of obesity [1,2,3] and as a potential target for treatments [2]. Compared to white adipose tissue (WAT), BAT has numerous mitochondria and uncoupling protein 1 (UCP-1), and is highly metabolically active. However, despite their importance and implications in obesity, BAT detection is challenging due to the lack of specific marker in vivo. Most imaging of BAT has been done by radioactive fluorodeoxyglucose (FDG) PET, which is limited by its low resolution and radioactivity. Recently BOLD and blood volume-based fMRI was proposed for imaging active BAT [4,5], though their susceptibility-based contrast may suffer from artifacts in body imaging. Previously, we proposed Manganese Enhanced MRI (MEMRI) to map active BAT in the mouse in vivo [6]. Here we evaluated whether MEMRI enters BAT through Ca2+ channel or perfusion.

4676.   16 Evaluation of PET/DWI registration quality in PET/MR hybrid scanner: zoomed DWI vs. conventional DWI
Koji Sagiyama1, Yuji Watanabe2, Ryotaro Kamei1, Shingo Baba1, Takuro Isoda1, Osamu Togao1, Michinobu Nagao2, Satoshi Kawanami2, Akihiro Nishie1, and Hiroshi Honda1
1Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan, 2Department of Molecular Imaging and Diagnosis, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan

Zoomed DWI (z-DWI) can reduce FOV along the phase-encoding direction by exploiting spatially-selective RF pulse and is expected to reduce image distortion by shortening the EPI echo train. In the present study, we optimized imaging parameters for z-DWI in phantom study and compared z-DWI with conventional DWI in the evaluation of PET/DWI registration quality in patient study. Our result indicates that zoomed DWI is useful to obtain more accurate registration of PET/DWI fusion imaging in PET/MR hybrid system by reducing susceptibility artifact and image distortion.

4677.   17 Metabolic imaging to differentiate aggressive versus indolent prostate cancer
Niki Zacharias Millward1, Christopher McCullough1, Youngbok Lee2, Jingzhe Hu1,3, Prasanta Dutta1, David Piwnica-Worms1, and Pratip Bhattacharya1
1Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, United States, 2Department of Applied Chemistry, Hanyang University, Korea, 3Rice University, TX, United States

Many prostate cancers (PCa) detected by screening are indolent however, 90% of patients will receive immediate treatment such as surgery or radiation therapy. There is a pressing need in the clinic for determining the aggressiveness of PCa that allows the whole prostate to be examined and resolving therapeutic dilemma. Employing ex vivo MRS, we have determined that concentration changes in metabolites- succinate, glutamine and phosphocholine correlate well with aggressiveness of PCa and not lactate production. We are now using the chemical reaction multi-molecular polarization (CRIMP) technique and hyperpolarized metabolic imaging to determine the aggressiveness of PCa in transgenic animal models.

4678.   18 Monitoring the pancreatic islets implantation in the subcutaneous polymeric scaffolds by DCE-MRI and optical imaging
Andrea Gálisová1, Daniel Jirák1, Eva Fábryová2, Vít Herynek1, Lucie Kosinová2, Jan Kříž2, and Milan Hájek1
1MR Unit, Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, 2Center of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Subcutaneous polymeric scaffolds supported by stem cells have been tested as an alternative transplant site for pancreatic islets. We supposed that improvement of vascularization and graft survival induced by stem cells should minimize the number of islets needed for normoglycaemia achievement. Functionality of the model was assessed by multimodal approach using MRI, Dynamic Contrast Enhanced MR and optical imaging. MR images showed a cavity in the scaffolds intended for islets transplantation. We observed an increase in perfusion and optical signal after stem cells implantation. Our results indicate promising model functionality, what was also confirmed by recurrence of normoglycaemia.

4679.   19 Improvements of quantitative oxygenation levels in venous blood (Yv) measurements based on QUIXOTIC
Klaus Möllenhoff1 and Nadim Jon Shah1,2
1Institute of Neuroscience and Medicine - 4, Forschungszentrum Jülich GmbH, Jülich, NRW, Germany, 2Faculty of Medicine, Department of Neurology, JARA, RWTH Aachen University, Aachen, NRW, Germany

CMRO2 is a quantitative measurement of a healthy brain. QUIXOTIC is a promising method to access these values in wich we improved acquistion time and resolution.

4680.   20 Optimization of pulsed CEST imaging using genetic algorithm
Eriko Yoshimaru1, Edward Randtke1, Mark D Pagel1, and Julio Cárdenas-Rodríguez1
1Biomedical Engineering, University of Arizona, Tucson, Arizona, United States

The genetic algorithm was used to optimize pulsed CEST RF pulse waveforms and parameters to maximize the CEST effect.

4681.   21 Tri-modal in vivo imaging of the rodent pancreatic islets transplanted in the subcutaneous site
Sayuan Liang1, Karim Louchami1,2, Bryan Holvoet1, Rein Verbeke3, Bella Manshian1, Willy J Malaisse2, Abdullah Sener2, Ine Lentacker3, and Uwe Himmelreich1
1Department of Imaging & Pathology, KU Leuven, Leuven, Flemish Brabant, Belgium, 2Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Brussels, Belgium, 3Laboratory for General Biochemistry and Physical Pharmacy, Ghent University, Ghent, East Flanders, Belgium

As it is important to use non-invasive imaging techniques to monitor the fate of transplanted islets for treatment of type I diabetes disease, the feasiblity of using tri-modal imaging modalities including bioluminescence imaging, fluorescent imaging and 19F MRI has been demonstrated. This multi modal imaging platform could potentially overcome the limitations in sensitivity, resolution and specificity of the individual method

4682.   22 Normal Saline Injections with Dynamic Inversion Recovery Pulse Sequences: Dynamic Parameter Mappings with Signal Polarity Correction
Hernan Jara1, Asim Z Mian1, Osamu Sakai1, Stephan Anderson1, Jorge A Soto1, and Alexander M Norbash1
1Boston University, Boston, Massachusetts, United States

Purpose: Work in the context of perfusion-MRI using normal saline as contrast agent. Purpose was to develop algorithms that take into account the polarity of the signal changes for generating accurate maps of the dynamic parameters: maxENH, AUC, TTP, and MTTP. Methods: Developed algorithms form 1D time vectors for each pixel and use Boolean conditions to identify and map each parameter. Results: Good image quality maps were generated for all patients. Processing took 3-5min depending on 4D-dataset size. Conclusion: Difficulties associated with inversion-recovery signal polarity can be corrected. This work could be instrumental for quantifying tissue perfusion with normal saline injections.Purpose: Work in the context of perfusion-MRI using normal saline as contrast agent. Purpose was to develop algorithms that take into account the polarity of the signal changes for generating accurate maps of the dynamic parameters: maxENH, AUC, TTP, and MTTP. Methods: Developed algorithms form 1D time vectors for each pixel and use Boolean conditions to identify and map each parameter. Results: Good image quality maps were generated for all patients. Processing took 3-5min depending on 4D-dataset size. Conclusion: Difficulties associated with inversion-recovery signal polarity can be corrected. This work could be instrumental for quantifying tissue perfusion with normal saline injections.