Curtis L Johnson¹, Danchin D Chen¹, Armen A Gharibans¹, William C Olivero^2,3, Bradley P Sutton^3,4, and John G Georgiadis^1,3
1Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ²Department of Neurosurgery, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ³Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁴Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States

A spin-echo sequence with interleaved spiral readouts is implemented for Magnetic Resonance Elastography (MRE) of the brain. This novel sequence allows for high-resolution acquisitions with significantly reduced scan times in order to improve subject comfort. To our knowledge, this is the first implementation of such a sequence, and its performance is demonstrated with both phantom and in vivo brain experiments. This sequence will allow for acquisition of data sets necessary for more sophisticated MRE inversion algorithms while maintaining reasonable acquisition times.

Ralph Sinkus¹, Sverre Holm², Bojan Guzina³, Sven Peter Näsholm², Philippe Garteiser¹, Sabrina Doblas¹, Bernard E. Van Beers¹, and Valérie Vilgrain^1
1Dept. of Radiology, CRB3, Hôpital Beaujon (U773), INSERM, Clichy, France, ²Dept. of Informatics, University of Oslo, Norway, ³Department of Civil Engineering, University of Minnesota, Minneapolis, United States

At present, the origin of the power-law behaviour of the tissues’ complex shear modulus in the frequency domain is not understood. Multiple-scattering theories do provide a physical explanation for this phenomenon but require that very-short-delay multiple reflections do occur. We demonstrate via in-vivo transient MR-Elastography for the first time that that very-short-delay multiple reflections are present in liver tissue and that they are absent in a silicon phantom. This sets the basis for further research investigating whether the predicted link between the spatial distribution of reflection coefficients and the observed dispersive behaviour of G* indeed holds.

Kerstin Riek¹, Isabell Hamann², Jason Millwald³, Caspar Pfueller³, Sebastian Hirsch¹, Dieter Klatt³, Jürgen Braun⁴, Carmen Infante-Duarte³, and Ingolf Sack^1
1Department of Radiology, Charité University Medicine, Berlin, Germany, ²Cecilie-Vogt-Klinik für Neurologie, Charité University Medicine, ³Charité University Medicine, ⁴Institute of Medical Informatics, Charité University Medicine, Berlin, Germany

In multiple sclerosis (MS), diffuse brain parenchymal damage exceeding focal inflammation is increasingly recognized as a major cause of clinical disability. Experimental Autoimmune Encephalitis (EAE) is an animal model of MS that enables researchers to study neuronal tissue affected by chronic inflammatory. In this study, cerebral MRE of mice is used to study the relationship between brain viscoelasticity and degree of tissue degradation during EAE. Both symptomatic and asymptomatic EAE mice presented with a significant decrease in the storage modulus with age (p<0.05). In contrast there was no correlation between examination time and complex modulus in healthy controls.

Ramin Sebastian Sahebjavaher¹, Ali Baghani¹, Ralph Sinkus², and Septimiu E Salcudean^1
1Electrical and Computer Engineering, University of British Columbia, Vancouver, British Columbia, Canada, ²Laboratoire Ondes et Acoustique, ESPCI, Paris, France

The diagnostic importance of elasticity for prostate cancer is well established; therefore, viscoelastic information acquired from in-vivo prostatic tissue using MR Elastography (MRE) is expected to provide valuable clinical information. A second harmonic MRE approach was performed on healthy subjects in supine position with the transducer applied at the perineum. Initial results show that the waves sufficiently penetrate into the prostate. Applying the mechanical excitation to the perineum is comfortable for the patients even for extended imaging examinations. The reconstructed viscoelastic values visually show a significant correspondence to the anatomy. This study shows that trans-perineal 2nd harmonic MRE is feasible.

Deirdre Maria McGrath¹, Warren D Foltz¹, and Kristy K Brock^1,2
1Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario, Canada, ²Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

Validation of medical imaging for disease detection and localization is achieved by correlation with the ‘gold-standard’ of histopathology. For accurate 3D biomechanical registration of the histopathology volume with the imaging volume, the effect of pathology fixation on biomechanical ex vivo tissue properties must be incorporated. A quasi-static MRE method at 7 tesla was applied to measure the progressive effects of formalin fixation in preclinical and clinical prostate tissue, and increases in Young’s modulus with fixation were correlated with decreases in T₁, T₂ and ADC. This will allow the formulation of predictive models of material property changes using standard MRI parameters.

Kevin Mattheus Moerman^1,2, Andre M.J. Sprengers², Ciaran Knut Simms¹, Anneloes E Bohte², Rolf M. Lamerichs³, Ralph Sinkus⁴, and Aart J. Nederveen^2
1Trinity Centre for Bioengineering, University of Dublin, Trinity College, Dublin, Ireland, ²Radiology Department, Academic Medical Centre, Amsterdam, Netherlands, ³Philips Research, Eindhoven, Netherlands, ⁴Radiology Department, CRB3, Hôpital Beaujon (U773), INSERM, Clichy, France

The MRI based non-invasive analysis of soft tissue mechanical properties has been the focus of many fields of research. MR Elastography (MRE) allows for the estimation of shear elasticity and viscosity properties and has been shown to be beneficial in the study of liver fibrosis and breast lesions. However, this technique has mainly been limited to microscopic strain levels. Using indentation of a silicone gel soft tissue phantom the current study presents the combination of a fast SPAMM tagged MRI sequence and MRE for the analysis of the large strain mechanical behavior of soft tissue.

Anthony Joseph Romano¹, Michael Scheel², Sebastian Hirsch³, Juergen Braun⁴, and Ingolf Sack^3
1Physical Acoustics, Naval Research Laboratory, Washington, DC, United States, ²Department of Radiology, Charite Universitatsmedizin, Berlin, Germany, ³Department of Radiology, Charite-Universitatsmedizin, Berlin, Germany, ⁴Institute of Medical Informatics, Charite-Universitatsmedizin, Berlin, Germany

We apply Waveguide Constrained MR Elastography to evaluate the anisotropic properties of white matter tracts in the human brain. Diffusion Tensor Imaging is used to evaluate the pathways of the Cortico Spinal Tracts, and MR Elastography is implemented to measure the dynamic displacements within the same brain. A spatial-spectral filter is applied to the data which provides only those waves which are traveling along the white matter tracts as if they act as zero-order waveguides. A sliding window spatial Fourier transform is applied to this data to provide dispersion analysis and yield local anisotropic shear stiffness values of the tracts.

John Zhang¹, Michael Green^1,2, Ralph Sinkus³, and Lynne Bilston^1,4
1Neuroscience Research Australia, Randwick, NSW, Australia, ²University of NSW, Sydney, NSW, Australia, ³Centre de Recherches Biomédicales Bichat-Beaujon, INSERM U773, CRB3, Paris, France,⁴Prince of Wales Clinical School, University of NSW, Sydney, NSW, Australia

The mechanical properties of the cerebellum have never been measured previously, despite the cerebellum's importance in both neurological disease and trauma. This study presents the first measurements of cerebellum viscoelastic properties, made using MR elastography in human volunteers. The results show that the cerebellum is significantly softer than the cerebral hemispheres.

Dieter Klatt¹, Kerstin Riek², Hassan Nuzha¹, Susanne Müller³, Ingolf Sack¹, and Jürgen Braun^2
1Radiology, Charité - Universitätsmedizin Berlin, Berlin, Berlin, Germany, ²Medical Informatics, Charité - Universitätsmedizin Berlin, Berlin, Berlin, Germany, ³Neurology, Charité - Universitätsmedizin Berlin, Berlin, Berlin, Germany

Magnetic resonance elastography (MRE) reveals information about biomechanical properties related to mechanical connectivity and micromechanical order in tissue. To develop MRE towards an in vivo rheometry technique an extension of the range of mechanical excitation and a modelling of tissue properties is mandatory. Therefore wide-range modulus-dispersion MRE is introduced and applied to biological tissue samples. A powerlaw simplification was used to model the dispersion function of the complex shear modulus. In this context, brain and liver tissue show very similar viscoelastic properties, while fibrotic liver displays distinctly higher shear modulus values, similar to the anisotropic elastic constants of excised muscle.

Deirdre Maria McGrath¹, Warren D Foltz¹, Navid Samavati¹, Jenny Lee¹, Michael A Jewett², Theodorus H van der Kwast³, Cynthia Ménard¹, and Kristy K Brock^1,4
1Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario, Canada, ²Department of Surgical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada, ³Department of Pathology, University Health Network, Toronto, Ontario, Canada, ⁴Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

Magnetic resonance elastography (MRE) holds enormous potential as a tool to guide prostate intervention for cancer, such as targeted radiation therapy, MRI-guided biopsy or high dose rate (HDR) brachytherapy. However, to assist in vivo method development quantitative data on the relative increase in biomechanical stiffness of prostate cancer above that of normal tissue is required. A high resolution quasi-static MRE method at 7 tesla has been applied to prostatectomy tissue for which the disease burden was assessed using whole-mount histology. The results revealed a high sensitivity of Young’s modulus to cancer and a strong correlation with pathology.

Tomokazu NUMANO¹, Yoshihiko KAWABATA², Toshikatsu WASHIO³, Kazuyuki MIZUHARA⁴, Naotaka NITTA³, and Kazuhiro HOMMA^3
1Radiological Science, Tokyo Metropolitan University, Arakawa, Tokyo, Japan, ²Takashima seisakusho Co.,Ltd., Hino, Tokyo, Japan, ³National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan, ⁴TOKYO DENKI UNIVERSITY, Tokyo, Japan

In this work we report on the development of a new technique for MRE vibrator based upon air ball-vibrator. It is compact vibrator that generated powerful centrifugal force vibration in the high-speed revolution of the internal-ball by compressed air. Vibration frequency and centrifugal force are freely changeable by operation of air flow volume, and replacement of internal ball. From performance test, even though the vibration frequency increase, the amount of displacement did not decrease. From agarose-gel phantom experiment, this vibrator can be used to make MR elastogram. This work shows that the use of ball-vibrator for MRE is feasible and can improve MRE image resolution by maintains adequate amount of displacement with high frequency vibrations.

Dieter Klatt¹, Patrick Asbach¹, Carsten Kamphues², Sebastian Hirsch¹, Sebastian Papazoglou¹, Jürgen Braun³, and Ingolf Sack^1
1Institute of Radiology, Charite - University Medicine, Berlin, Germany, ²Dept Gen Visceral & Transplantat Surg, Charite - University Medicine, Berlin, Germany, ³Institute of Medical Informatics, Charite - University Medicine, Berlin, Germany

In single shot MR elastography (MRE) a short transient mechanical excitation burst is sufficient for the acquisition of an entire wave image. Single shot MRE of the liver, however, suffers from susceptibility artifacts and low SNR due to fast signal relaxation. Therefore, parallel imaging is combined with single shot MRE which improves image quality and resolution compared to previously used single-shot techniques. The new method was used to assess fibrosis in liver transplant patients. Hepatic fibrosis was diagnosed in four patients. MRE has the potential to replace biopsy for the monitoring of fibrotic changes within liver grafts.

Sebastian Papazoglou¹, Sebastian Hirsch¹, Dieter Klatt¹, Jürgen Braun², and Ingolf Sack^1
1Department of Radiology, Charité University Medicine, Berlin, Berlin, Germany, ²Institute of Medical Informatics, Charité University Medicine, Berlin, Berlin, Germany

In magnetic resonance elastography shear elasticity of soft tissues is traditionally determined on basis of measured displacement wave data. Especially in strongly heterogeneous tissues such as the brain, standard inversion techniques may miss diagnostically valuable structural information. In contrast to the displacement field, the information content of intensity is related to characteristic length scales of shear wave scattering. In this study we demonstrate that 3D shear wave scattering MRE based on the distribution of shear wave intensity in gel phantoms is capable of revealing structural information even when wave inversion suggests similar elastic properties.

Kevin Mattheus Moerman^1,2, Andre M.J. Sprengers², Ciaran Knut Simms¹, Rolf M Lamerichs³, Jaap Stoker², and Aart J. Nederveen^2
1Trinity Centre for Bioengineering, University of Dublin, Trinity College, Dublin, Ireland, ²Radiology Department, Academic Medical Centre, Amsterdam, Netherlands, ³Philips Research, Eindhoven, Netherlands

Current SPAMM methods typically construct data from many repeated motion cycles. However discomfort and health issues may preclude a large number of repetitions. The current study presents the validation of a novel fast SPAMM sequence for the measurement of dynamic 3D soft tissue deformation following just 3 repeated motion cycles. The techniques were validated using marker tracking in a silicone gel phantom and demonstrated a mean displacement difference of 0.07mm (standard deviation 0.6mm). Since only 3 motion cycles are required the presented methods are the fastest currently available for the dynamic measurement of non-linear 3D soft tissue deformation.

Matthew C Murphy¹, Kevin J Glaser¹, Bradley D Bolster, Jr.², Daniel V Litwiller³, Scott A Kruse¹, and Richard L Ehman^1
1Department of Radiology, Mayo Clinic, Rochester, MN, United States, ²MR R&D Collaborations, Siemens Healthcare, Rochester, MN, United States, ³Global Applied Science Laboratory, GE Healthcare, Rochester, MN, United States

MRE is a phase-contrast MRI technique for noninvasively measuring tissue stiffness. MRE of the brain is currently under investigation for its potential to aid in the diagnosis of brain diseases. A robust brain MRE exam should be reproducible even when performed on different MR platforms. The purpose of this work was to assess the reproducibility of MRE of the brain on two platforms manufactured by GE and Siemens. The results indicate that the two platforms yield significantly correlated stiffness measurements, and that the mean measurements on each platform do not differ from each other.

Crystal Harrison¹, Ralph J. DeBerardinis^2,3, Chendong Yang², Ashish K. Jindal¹, A. Dean Sherry^1,4, and Craig R. Malloy^1,5
1Advanced Imaging Research Center, UT Southwestern, Dallas, TX, United States, ²Pediatrics, UT Southwestern, Dallas, TX, United States, ³McDermott Center for Human Growth and Development, UT Southwestern, Dallas, TX, United States, ⁴Chemistry, UT Dallas, Richardson, TX, United States, ⁵Veterans Affairs, North Texas Health Care System, Dallas, TX, United States

Combining data collected by hyperpolarization (HP) and mass spectrometry (MS) in identical model systems allows greater insight into the metabolic exchange of pyruvate and lactate through lactate dehydrogenase (LDH). Glioblastoma cells were investigated with these two techniques following addition of [1-¹³C]pyruvate or [3-¹³C]pyruvate. Various first-order models were investigated utilizing the pyruvate C2 and lactate C1 HP signals acquired with selective excitations and the intracellular and extracellular lactate labeling provided by MS. A three-pool bidirectional model is an accurate description of pyruvate metabolism in these cells; however the initial flux through LDH can be measured accurately regardless of the model chosen.

Tian Cheng¹, Mor Mishkovsky^1,2, and Arnaud Comment^1,2
1Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Department of Radiology, Université de Lausanne, Lausanne, Switzerland

In vivo hyperpolarized MR via dissolution DNP necessitates the transfer of the hyperpolarized solutions from the DNP polarizer to the imager prior to in vivo measurements. This process leads to unavoidable losses in polarization which are difficult to evaluate once the solution is infused into the animal. We propose a method to measure the polarization of the hyperpolarized solutions inside the imager bore at the time of the infusion. This in situ calibration allows to decouple potential problems linked to the hyperpolarization and transfer processes from in vivo acquisition issues and can lead to accurate analyses of in vivo SNR.

Dirk Mayer^1,2, Yi-Fen Yen³, Ralph Hurd³, Sonal Josan^1,2, Jae Mo Park², Adolf Pfefferbaum^1,4, and Daniel Spielman^2
1Neuroscience Program, SRI International, Menlo Park, CA, United States, ²Radiology, Stanford University, Stanford, CA, United States, ³GE Healthcare, ⁴Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States

The feasibility of both polarizing [1-¹³C]-lactate and detecting its metabolic conversion in vivo has previously been demonstrated. As lactate serves as an important energy source for the heart, hyperpolarized lactate could potentially be used as an alternative to pyruvate for probing heart metabolism. The aim of this work was to apply hyperpolarized [1-¹³C]-lactate to the measurement of cardiac metabolism and compare it to [1-¹³C]-pyruvate as a substrate. The presented data demonstrate that bicarbonate as a secondary product of hyperpolarized [1-¹³C]-lactate can be detected in the heart.

Michael Batel¹, Marcin Krajewski², Kilian Weiss², Oliver With¹, Alexander Däpp¹, Andreas Hunkeler¹, Martin Gimersky³, Matthias Ernst¹, and Sebastian Kozerke^2
1Laboratory of Physical Chemistry, ETH Zürich, Zürich, Switzerland, ²Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland, ³Laboratory for Electromagnetic Fields and Microwave Electronics, ETH Zürich, Zürich, Switzerland

A multi-sample dissolution DNP system compatible with commercial wide-bore magnets is presented. The system is designed to accommodate up to six samples on a revolver-style sample changer permitting exchange at liquid Helium temperatures. The system includes EPR and NMR capabilities for monitoring purposes. 13-C DNP enhancements for pyruvic acid with the trityl radical OX63 are reported. In the solid-state 21% polarization is reached and in the dissolved liquid-state the enhancement factor measured is more than 12000 at 7 T.

Cornelius von Morze¹, Galen Reed¹, Peter J Shin¹, Peder E Larson¹, Robert Bok¹, Simon Hu¹, and Daniel B Vigneron^1
1Department of Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States

We describe a new method for metabolic imaging of multiple hyperpolarized ¹³C compounds based on frequency encoding of a single echo. This approach capitalizes on the large chemical shifts between ¹³C resonances to achieve comparable or faster speeds than previous fast MRSI approaches, while avoiding complex acquisition and reconstruction methods. The method was tested in application to metabolic imaging studies of [1-¹³C]pyruvate and its metabolic products lactate and alanine in preclinical normal and transgenic murine models of prostate cancer. Elevated lactate signals were observed in the prostatic regions of the tumor mice corresponding to regions of T2-weighted signal changes.

Ashish K Jindal¹, Lloyd Lumata¹, Yixun Xing², Matthew E Merritt¹, Piyu Zhao², Craig R Malloy¹, A Dean Sherry^1,2, and Zoltan Kovacs^1
1Advanced Imaging, UT Southwestern Medical Center, Dallas, Texas, United States, ²Department of Chemistry, University of Texas at Dallas, Richardson, Texas, United States

The extremely long T₁ (up to 10 minutes) and T ₂ (up to 15 seconds) of ⁸⁹Y, coupled with 100% natural abundance, ½ spin, and narrow linewidth, make it an attractive nucleus for hyperpolarized in vivo imaging. Here we present accurate T₁ measurements of hyperpolarized ⁸⁹Y – DTPA, DOTA, EDTA, and deuterated EDTA complexes. Results suggest that substitution of low-gamma nuclei on the ligand backbone as opposed to that of the solvent most effectively increase the ⁸⁹Y T₁. These results are encouraging for in vivo applications as the presence of bound water may not dramatically affect the T₁.

Jan Falk Dechent^1,2, Lisandro Buljubasich², Laura Maria Scheiber¹, Hans Wolfgang Spiess², and Kerstin Münnemann^2
1Section of Medical Physics, Johannes Gutenberg University Medical Center, Mainz, Germany, ²Max Planck Institute for Polymer Research, Mainz, Germany

A major challenge in molecular imaging is the detection of tiny amounts of interesting molecules. Hyperpolarization can overcome the problem of low sensitivity in Nuclear Magnetic Resonance (NMR) or Magnetic Resonance Imaging (MRI). For the most widely used nucleus ¹H, however, this strategy is limited due to the high number of background protons inside the body. By using the antiphase character of Parahydrogen Induced Polarization we developed a novel ¹H NMR contrast. It allows for the selective detection of a small number of hyperpolarized protons with antiphase NMR/MRI signal in the presence of a large number of thermally polarized protons.

Daniel Ball¹, Marie Schroeder¹, George Radda¹, Kieran Clarke¹, and Damian Tyler^1
1Department of Physiology, Anatomy and Genetics, Oxford University, Oxford, Oxfordshire, United Kingdom

Hyperpolarized 13C-pyruvate is widely used in assessing cardiac metabolism in the perfused rat heart. Typically large concentrations are infused (~2mM) when compared to physiological levels (~60µM). This is done to achieve sufficient signal-to-noise in the acquired spectra. Given that pyruvate is used as a real-time measure of enzymatic flux, it is important to understand the effect of high pyruvate concentrations on the kinetics observed. The aim of this study was to assess varying concentrations of pyruvate to determine when enzyme kinetics become unrepresentative of the physiological state and to find a suitable compromise between high signal and accurate metabolic assessment.

Simon Hu¹, Hikari Yoshihara¹, Robert Bok¹, Peder E Larson¹, John Kurhanewicz¹, and Daniel B Vigneron^1
1Dept. of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, CA, United States

The most commonly used in vivo agent in hyperpolarized ¹³C metabolic imaging thus far has been [1-¹³C]pyruvate. In preclinical studies, not only is its uptake detected but also its intracellular enzymatic conversion to metabolic products including [1-¹³C]lactate. However, the ratio of ¹³C-lactate/¹³C-pyruvate measured in this data does not accurately reflect cellular values since much of the [1-¹³C]pyruvate is extracellular depending on timing, vascular properties and extracellular space and monocarboxylate transporter activity. In order to measure the relative levels of intracellular pyruvate and lactate, in this project we hyperpolarized [1-¹³C]alanine and monitored the in vivo conversion to [1-¹³C]pyruvate and [1-¹³C]lactate.

Jeremy Gordon¹, Ian Rowland^1,2, Eric Peterson³, and Sean Fain^1,2
1Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, ²Department of Radiology, University of Wisconsin-Madison, Madison, WI, United States,³Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States

Gadolinium has been previously reported to increase the solid-state polarization of 1-¹³C pyruvate. However, gadolinium is a potent relaxation agent in the liquid state, decreasing the time available for imaging experiments for polarized nuclei. This work studies the effects of doping pyruvate solutions with lanthanides on the solid-state polarization, buildup time, and liquid-state T₁. Holmium, another paramagnetic lanthanide, was found to increase the solid-state polarization at low (0.5mM) concentrations with favorable relaxation properties in the liquid state.

Justin Yat Cheong Lau^1,2, Albert P Chen³, Jianfeng Zhu⁴, Gang Wu⁴, and Charles H Cunningham^1,2
1Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, ²Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, ³GE Healthcare, Toronto, Ontario, Canada, ⁴Department of Chemistry, Queen's University, Kingston, Ontario, Canada

A current challenge with tracking C₁ polarization by selective small tip angle excitation of C₂ in 1,2-[¹³C]₂-pyruvate is the observed evolution of the C₂ doublet beyond AB asymmetry. We hypothesize that cross coupling between the dipolar field and chemical shift anisotropy (CSA) may, at least in part, be responsible for this behaviour. This study shows that solution pH has an effect on the relaxation mechanism that currently interferes with polarization measurement using C₂ asymmetry of 1,2-[¹³C]₂-pyruvate, suggesting that the C₂ CSA of the protonated form may be less effective at coupling with the dipolar field.

Benjamin M. Pullinger¹, Stephen J. Kadlecek¹, Nicholas N. Kuzma¹, and Rahim R. Rizi^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States

The effects of bovine serum albumin (BSA) on the T₁ relaxation of DNP-hyperpolarized [1-¹³C]Pyruvate are studied as a function of magnetic field at varying concentrations of BSA and the DNP radical OX063 trityl. At low fields of 27.0 and 15.8 gauss the carbon-13 relaxation times are shortened by factors of 3 and 4 after addition of only 3% BSA. Our data suggests that caution should be taken in transporting hyperpolarized [1-¹³C]Pyruvate in the presence of albumin.

Michael Samuel Dodd¹, Beat Schuler¹, Vicky Ball¹, Daniel Ball¹, George K Radda¹, Houman Ashrafian², Hugh Watkins², Kieran Clarke¹, and Damian J Tyler^1
1Physiology, Anatomy and Genetics, Oxford University, Oxford, United Kingdom, ²Cardiovascular Medicine, Oxford University, Oxford, United Kingdom

Alterations in cardiac metabolism underlie many diseases of the heart. The advent of cardiac hyperpolarized magnetic resonance spectroscopy, via dynamic nuclear polarization, has enabled a greater understanding of the in vivo metabolic changes seen as a consequence of heart disease. This study demonstrates for the first time a slice selective approach to investigate the in vivometabolism of [1-¹³C]pyruvate in the murine heart. There is a significant 64% reduction in PDH flux in the fasted murine heart, similar to previous findings in the rat. This work validates the method for detecting changes in transgenic murine models of cardiovascular disease.

Eric T Peterson¹, Jeremy W Gordon², Sean B Fain², and Ian J Rowland^2
1Biomedical Engineering, University of Wisconsin - Madison, Madison, WI, United States, ²Medical Physics, University of Wisconsin - Madison, Madison, WI, United States

Hepatic metabolism studies using hyperpolarized ¹³C pyruvate often yield additional resonances associated with pyruvate and pyruvate hydrate. To investigate the origin of these additional resonances, we have used spectrally sensitive imaging and intravenous gadolinium-based contrast agent. Spectral information strongly suggested that the additional resonances derive from the vena cava. This is attributed to bulk magnetic susceptibility effects due to alignment parallel with B₀. Intravenous contrast diminished the additional high field but not the low field resonances, supporting the conclusion that the additional peaks arise predominantly from an intravascular compartment.

Mark Van Criekinge¹, Kayvan R. Keshari², Daniel Vigneron², and John Kurhanewicz^2
1UCSF, San Francisco, CA, United States, ²UCSF

An important consideration for performing hyperpolarized (HP) 13C-MR studies is matching the T1 relaxation time of the HP 13C-labeled probe with the time scale of the metabolic process being investigated. By evolving the hyperpolarized spins in low field (<0.1T), a dramatic increase in [1-13C]pyruvate relaxation rate was indirectly observed as a 50% increase in residual polarization. For in vivo studies, it is possible that hyperpolarized spins could be allowed to evolve inside of animals at low field, in the fringe field of the magnet, and subsequently transport them into the magnet at a later time to observe slower enzyme kinetics.

Eric T Peterson¹, Matthew R Smith², Joseph J Grudzinski², Jeremy W Gordon², and Sean B Fain^1,2
1Biomedical Engineering, University of Wisconsin - Madison, Madison, WI, United States, ²Medical Physics, University of Wisconsin - Madison, Madison, WI, United States

Hyperpolarized carbon metabolic imaging and spectroscopy have been shown to non-invasively probe in vivo metabolic and transport parameters. This work presents a method which can be used to determine the optimal sampling times and flip angles for any symbolically represented parametric model, or any model where the Fisher Information Matrix may be calculated, in order to maximize the parametric SNR of the acquisition. This allows a substantial increase in the parametric SNR for any imaging or spectroscopy sequence.

David G Gadian¹, Kuldeep S Panesar², Angel J Perez Linde³, Waldemar Senczenko³, Anthony J Horsewill², Walter Kockenberger³, and John R Owers-Bradley^2
1Imaging & Biophysics Unit, UCL Institute of Child Health, London, United Kingdom, ²School of Physics & Astronomy, University of Nottingham, Nottingham, United Kingdom, ³Sir Peter Mansfield MR Centre, School of Physics & Astronomy, University of Nottingham, Nottingham, United Kingdom

There is increasing interest in the development of techniques for hyperpolarising nuclei, with a wide range of potential applications, both in vivo and in vitro. Here, we show that high-field cryogenics (ie the so-called brute-force approach), when applied in conjunction with relaxation switches and low-field thermal mixing, can be used to generate large increases in nuclear polarisation on a realistic timescale. Among the technical advantages of this approach, the polarisation process does not involve any resonance phenomena or radiofrequency irradiation. In addition, the process is completely broadband; thus a wide range of nuclear species could be polarised simultaneously.

William Dominguez-Viqueira¹, Angus Z Lau^1,2, Albert P Chen³, and Charles H Cunningham^1,2
1Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, ²Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, ³GE Healthcare, Toronto, Ontario, Canada

Hyperpolarized-¹³C substrates has become a promising tool to study real-time cardiac-metabolism in-vivo. For such fast imaging it is important to optimize the RF-coils to obtain the best signal-to-noise ratio possible. A single-channel transmit/receive surface-coil for hyperpolarized-¹³C was characterized with benchtop and in-vivo measurements. SNR of up to 40 units was measure in-vivo, and further improvement throughout the volume of interest can be achieved by using the dual-channel surface-coil simulated in this work. This will allow imaging of the different metabolite signals even in the posterior regions of the myocardium, which is not possible at this moment with the single-channel surface-coil.

Ute Bommerich¹, Thomas Trantzschel², Joachim Bargon³, Gerd Buntkowsky⁴, and Johannes Bernarding^2
1SLNIB, Leibniz Institute for Neurobiology, Magdeburg, Germany, ²IBMI, University of Magdeburg, Magdeburg, Germany, ³Institute of Physical Chemistry, University of Bonn, Bonn, ⁴Eduard-Zintl-Institute for Inorganic and Physical Chemistry, Technical University Darmstadt

The generation of hyperpolarized substrates for sensitivity enhancement in MRI and MRS investigations is an emerging field. Hyperpolarization methods lead to a strong signal enhancement enabling the detection of even low concentrated substrates. As 19F nuclei do not appear in soft tissue, hyperpolarized 19F reporter molecules can provide optimal contrast for MR examinations. PHIP (ParaHydrogen Induced Polarization) is successfully applied for sensitivity enhancement but so far only a few substances are proven to exhibit 19F hyperpolarization. In this contribution we present spectra of hyperpolarized 19F nuclei detected from the first hydrogenation step to a biocompatible substrate.

Rolf F Schulte¹, Jonathan I Sperl¹, Axel Haase², Marco Irkens³, Michael Manglberger³, Eliane Weidl⁴, Guido Kudielka¹, Markus Schwaiger⁴, and Florian Wiesinger^1
1GE Global Research, Munich, Germany, ²IMETUM, Technische Universitaet Muenchen, Munich, Germany, ³Rapid Biomedical, Würzburg, Germany, ⁴Department for Nuclear Medicine, Technische Universitaet Muenchen, Munich, Germany

Metabolic imaging of hyperpolarised [1-3C]pyruvate and its downstream metabolites requires efficient encoding methods. Parallel imaging is widely applied to 1H MRI, but not yet to hyperpolarised MRI. In this work, IDEAL spiral CSI was combined with parallel imaging and advanced reconstruction methods. CG SENSE and SPIRiT were compared to gridding reconstruction and regular SENSE unfolding. Results in kidney show high quality dynamic data with improved SNR for SPIRiT and CG SENSE.

Steven Sourbron¹, and David L Buckley^1
1Division of Medical Physics, University of Leeds, Leeds, United Kingdom

The Tofts models have long been regarded as a standard approach to tracer-kinetic analysis of DCE-MRI, but recent technological advances have improved DCE-MRI data quality to a point where more complex models are required. Several alternatives have been proposed, but analytical solutions are either not available or too complex to offer much physical insight. Here, a generalisation is proposed which offers a transparent way of representing the architecture of existing alternatives, and constructing approximations with any desired accuracy. In addition, it allows modelling of more realistic tissues intermediate between the ideals of a compartment or a plug-flow model.

Daniel Wilson^1
1Medical Physics, Leeds Teaching Hospitals, Leeds, West Yorkshire, United Kingdom

Hepatic arterial fraction is often measured from dynamic contrast enhanced MRI data collected using a 3D spoiled gradient echo sequence. Errors in hepatic arterial fraction measurements as a consequence of flip angle and pre contrast T1 measurement errors are minimized if higher flip angles are used. The small errors found suggest that if a flip angle of 30° is prescribed then it is possible to use an assumed T1 rather than measure it.

Jieun Kim¹, Nancy Berman², and Phil Lee^1
1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States, ²Department of Anatomy & Cell Biology, University of Kansas Medical Center, Kansas City, KS, United States

We have overcome the difficulty of measuring blood-brain barrier (BBB) permeability in mice longitudinally by combining T1 mapping and using i.p. administration of Gd-DTPA. We have successfully quantified BBB permeability from the signal changes associated with uptake of Gd-DTPA following traumatic brain injury for 2weeks using T1 map. Results show that significant entry of Gd-DTPA into the brain was evident in the injury site at P3&P7 but almost return to normal level at P14. This study demonstrates that the technique can be employed in longitudinal study of BBB permeability in mice brain in vivo.

Kang Wang¹, Mark Schiebler², Christopher Francois², Alejandro Munoz Del Rio^1,2, Frank Korosec¹, Sean Fain¹, and Scott Nagle^2
1Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, ²Radiology, University of Wisconsin-Madison, Madison, WI, United States

Cardiac motion is a common source of artifact on MR images of the thorax. Traditionally, ECG-gating has been employed to minimize these artifacts, at the expense of decreased scan efficiency and increased complexity in patient set-up. This trade-off is application-specific, with some imaging techniques more sensitive to cardiac motion artifacts than others. The purpose of this study was to determine whether or not ECG-gating improves image quality for pulmonary perfusion MRI using a recently developed pulmonary perfusion method that results in high isotropic spatial resolution, high temporal resolution, and whole chest coverage.

Maximilian N Voelker¹, Jan M Burg², Peggy Schlupp³, Ulf Maeder², Alexander M Koenig¹, and Johannes T Heverhagen^1
1Diagnostic Radiology, Philipps University Marburg, Marburg, Hessen, Germany, ²Institute of Medical Physics and Radiation Protection, University of Applied Sciences Giessen-Friedberg, Giessen, Germany, ³Institute of Biopharmaceutical Technology, University of Applied Sciences Giessen-Friedberg, Giessen, Germany

The penetration of MRI contrast agents into the skin can be measured directly by MRI. With a submicron emulsion as carrier system the efficiency and the dynamics of a Drug Carrier System on the penetration of a topically applied contrast agent can be assessed. Skin penetrating contrast agents could be a new diagnostic tool for the staging of skin tumours or can also be useful as a marker for topically applied drugs

Steven Sourbron^1
1Division of Medical Physics, University of Leeds, Leeds, United Kingdom

A physically intuitive approach is presented for generating approximations to multi-compartment models for DCE-MRI, and illustrated by application to the two-compartment exchange model. Using this method, the analytical solution for arbitrary multi-compartment models can be written out to any desired accuracy simply by listing in order the paths that a tracer particle can follow through the system. The method increases the physical insight into the behaviour of more complicated compartmental models, and will allow more freedom and flexibility in the design of advanced compartment models for particular applications.

Kevin Murphy¹, Ashley D Harris¹, Ana Diukova¹, Christopher John Evans¹, David J Lythgoe², Fernando Zelaya², and Richard G Wise^1
1CUBRIC, School of Psychology, Cardiff University, Cardiff, Wales, United Kingdom, ²King’s College London, Institute of Psychiatry, Centre for Neuroimaging Sciences, DeCrespigny Park, Denmark Hill, London, United Kingdom

Pulsed ASL is likely to find a place in clinical trials and, in particular, the investigation of the action of pharmaceutical agents on neural activity. This study determines the sample sizes necessary to detect regional changes in CBF in common types of clinical trial design: between groups, a two period crossover and within-session. Power calculations suggest that comparatively small cohorts, for example, 7-15 subjects in a crossover can be used to detect a 15 % increase or decrease in CBF. Such sample sizes make feasible the use of CBF measurements in clinical trials of drugs in small cohorts.

Colleen Bailey^1,2, Firas Moosvi^1,2, and Greg J Stanisz^1,2
1Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ²Medical Biophysics, University of Toronto, Toronto, ON, Canada

Intracellular-extracellular water exchange is an important marker of apoptotic cell death. In this study, the feasibility of measuring exchange in nude rats was examined. Data from three separate steady-state gadodiamide concentrations and an SPGR sequence with at four flip angles were fit to a two-pool model with exchange. The ² value was 55% lower than a similar model with the same number of parameters that assumed fast exchange. The exchange value in muscle, 0.24 ± 0.10 s^-1, was consistent with that found in previous studies.

Lauren Jean Bains^1,2, Josephine H Naish^1,2, and David L Buckley^3
1Imaging Sciences Research Group, University of Manchester, Manchester, Greater Manchester, United Kingdom, ²Biomedical Imaging Institute, Manchester, Greater Manchester, United Kingdom, ³Division of Medical Physics, University of Leeds, Leeds, United Kingdom

In this study, a T₁ weighted dynamic contrast enhanced (DCE) MRI acquisition with two bolus injections and two flip angles (30° and 5°) was used to create a DCE timecourse with varying sensitivity to water exchange. The results from using a two compartment model of tracer kinetics incorporating water exchange effects (the WX-2CXM) to fit these data showed that the low flip angle portion of the timecourse had significantly greater sensitivity to water exchange than the 30° portion. The acquisition was sufficiently sensitive to water exchange to provide preliminary estimates of the residence times of water in three tissue compartments.

Andrew Brian Gill^1,2, Andrew N Priest², Richard T Black¹, David J Bowden², Martin J Graves², and David J Lomas^2
1Medical Physics, Addenbrooke's Hospital, Cambridge, United Kingdom, ²Radiology, University of Cambridge, Cambridge, United Kingdom

[Gd] base-line discrepancies in liver DCE-MRI data have been recorded when using a dual acquisition, saturation-prepared fast gradient echo sequence at 3T, recording images in two separate slice orientations in each heartbeat. Pre-contrast discrepancies in [Gd] are thought to be due to flip-angle variation in the saturation pulses. A theoretical correction is derived to estimate the flip-angle at each region of interest and hence determine the true [Gd] curve. Volunteer data has been analysed using a dual-input pharmacokinetic model. Results show correction of the base-line discrepancy, consistent values for pharmacokinetic indices and improved values for the tissue arrival times.