Hyperpolarized MR
 

Thursday 4 June 2015

Aaron K Grant¹, Gopal Varma¹, Hai Hu², Xiaoen Wang¹, Ashish Juvekar², Soumya Ullas², and Gerburg Wulf^2
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.

Jack J. Miller^1,2, Angus Z. Lau^1,3, and Damian J. Tyler^1,3
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.

Elise Vinckenbosch¹, Mor Mishkovsky¹, Arnaud Comment², and Rolf Gruetter^1,3
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.

Thomas Theis¹, Matthew Morgan¹, Kevin Claytor², Ryan Davis³, Zijian Zhou¹, and Warren Warren^4
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.

Keshav Datta¹ and Daniel Spielman^2
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 J_CC 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.

Eunhae Joe¹, Joonsung Lee², Hansol Lee¹, Seungwook Yang¹, Young-suk Choi³, Eunkyung Wang³, Ho-Taek Song³, and Dong-Hyun Kim^1
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).

Hoora Shaghaghi¹, Yi Xin¹, Sarmad Siddiqui¹, Stephen Kadlecek¹, Mehrdad Pourfathi¹, Maurizio Cereda², Harrilla Profka¹, Hooman Hamedani¹, and Rahim R. Rizi^1
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.

Justin Y.C. Lau^1,2, Albert P. Chen³, Yiping Gu², William Dominguez-Viqueira², and Charles H. Cunningham^1,2
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.

Eugene Milshteyn¹, Cornelius von Morze¹, Galen D. Reed², Hong Shang¹, Peter J. Shin¹, Zihan Zhu¹, John Kurhanewicz¹, Robert Bok¹, and Daniel B. Vigneron^1
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.

Hoora Shaghaghi¹, Stephen Kadlecek¹, Mehrdad Pourfathi¹, Sarmad Siddiqui¹, Harrilla Profka¹, Hooman Hamedani¹, Maurizio Cereda², Yi Xin¹, and Rahim R. Rizi^1
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.

Francesca Reineri¹, Tommaso Boi², and Silvio Aime^3
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.

Karlos Moreno¹, Jian-Xiong Wang², Leila Fidelino³, A. Dean Sherry³, Craig Malloy³, and Matthew E Merritt^2
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.

Thomas Theis¹, Milton Truong², Eduard Chekmenev³, and Warren Warren^4
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.

Kerstin N Timm^1,2, Johannes Hartl¹, Markus Keller¹, De-En Hu^1,2, Alan J Wright², Mikko I Kettunen^1,2, Tiago B Rodrigues², Susana Ros², Markus Ralser^1,3, and Kevin M Brindle^1,2
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.

Jeremy W Gordon¹, Sonam Machingal¹, John Kurhanewicz¹, Daniel Vigneron¹, and Peder Larson^1
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.

Michael Abram Ohliger¹, Cornelius von Morze¹, Jeremy Gordon¹, Robert Bok¹, Jane Z Wang¹, Peter Shin¹, John Kurhanewicz¹, and Daniel Vigneron^1
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.

Christopher M Walker¹ and James Bankson^1
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.

Leo L Tsai¹, Xiaoen Wang¹, Gopal Varma¹, David Alsop¹, and Aaron K Grant^1
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

Mukundan Ragavan¹, Xiaorong Fu¹, Shawn C Burgess¹, and Matthew E Merritt^1
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.

Jae Mo Park¹, Ralph E Hurd², Dirk Mayer³, Lawrence D Recht⁴, and Daniel M Spielman^1
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.

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 Celeste^2
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.

Benjamin J. Geraghty^1,2, Justin Y.C. Lau^1,2, Albert P. Chen³, William Dominguez-Viqueira¹, and Charles H. Cunningham^1,2
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.

Molecular Imaging
 

Thursday 4 June 20155

Yuegao Huang¹, Peter Herman¹, Daniel Coman¹, Samuel Maritim², and Fahmeed Hyder^1,2
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 TmDOTP^5- with three different infusion protocols (i.e., agent only, probenecid treated, and renal ligation) to find variable distributions in different organs.

Anamaria Orza¹, Xiangyang Tang¹, Yi Yang¹, Hui We¹, Run Lin¹, Liya Wang¹, and Hui Mao^1
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.

Vít Herynek¹, Andrea Gálisová¹, Jan Blahut², Jan Kotek², and Milan Hájek^1
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.

Hernan Jara¹, Osamu Sakai¹, Asim Z Mian¹, Stephan Anderson¹, Jorge A Soto¹, and Alexander M Norbash^1
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.

Shizhen Chen¹, Yuqi Yang¹, Qing Luo¹, and Xin Zhou^1
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

Dario Livio Longo¹, Phillip Zhe Sun², Lorena Consolino^3,4, Filippo Michelotti⁵, Fulvio Uggeri⁶, and Silvio Aime^3,4
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.

Gary R. Stinnett¹, Nasim Taheri², Stacey M. Glasgow³, Benjamin Deneen⁴, Vicki L. Colvin², and Robia G. Pautler^5
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.

Nicholas Whiting¹, Jingzhe Hu^1,2, Niki Zacharias Millward¹, Rajesha Rupaimoole³, David Gorenstein⁴, Anil Sood³, and Pratip Bhattacharya^1
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.

Longhua Qiu^1,2, Feng Zhang¹, Yaoping Shi¹, Zhibin Bai¹, Jianfeng Wang¹, Donghoon Lee¹, Xiaoyuan Feng², and Xiaoming Yang^1
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.

Iliyana Atanasova¹, Lan Wei², Helen Day³, Boris Keil³, Francesco Blasi³, Bryan C Fuchs², and Peter Caravan^3
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.

Chao Li^1,2, Zhangjie Su¹, Ka-Loh Li¹, Alex Gerhard¹, Gerard Thompson¹, Xiaoping Zhu¹, Rainer Hinz¹, Federico Roncaroli³, Karl Herholz¹, and Alan Jackson^1
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.

Yichao Yu¹, Chris Payne¹, Vitaliy Kasymov², Bernard Siow¹, Quentin Pankhurst³, Alexander Gourine², and Mark F Lythgoe^1
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.

Eliana Gianolio¹, Francesca Arena¹, Enza Di Gregorio¹, Roberto Pagliarin², Martina Delbianco², Gabriella Baio³, and Silvio Aime^1
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.

Atsushi Tachibana¹, Morteza Mahmoudi¹, Yuka Matsuura¹, Rajesh Dash¹, Eric Rulifson¹, and Phillip Yang^1
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.

Hussein SROUR¹ and Kai Hsiang CHUANG^1
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.

Koji Sagiyama¹, Yuji Watanabe², Ryotaro Kamei¹, Shingo Baba¹, Takuro Isoda¹, Osamu Togao¹, Michinobu Nagao², Satoshi Kawanami², Akihiro Nishie¹, and Hiroshi Honda^1
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.

Niki Zacharias Millward¹, Christopher McCullough¹, Youngbok Lee², Jingzhe Hu^1,3, Prasanta Dutta¹, David Piwnica-Worms¹, and Pratip Bhattacharya^1
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.

Andrea Gálisová¹, Daniel Jirák¹, Eva Fábryová², Vít Herynek¹, Lucie Kosinová², Jan Kříž², and Milan Hájek^1
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.

Klaus Möllenhoff¹ and Nadim Jon Shah^1,2
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.

Eriko Yoshimaru¹, Edward Randtke¹, Mark D Pagel¹, and Julio Cárdenas-Rodríguez^1
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.

Sayuan Liang¹, Karim Louchami^1,2, Bryan Holvoet¹, Rein Verbeke³, Bella Manshian¹, Willy J Malaisse², Abdullah Sener², Ine Lentacker³, and Uwe Himmelreich^1
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

Hernan Jara¹, Asim Z Mian¹, Osamu Sakai¹, Stephan Anderson¹, Jorge A Soto¹, and Alexander M Norbash^1
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.