Category Archives: MRI

In Vivo Hyperpolarized 13C MRS and MRI Applications #DNPNMR

Marco-Rius, Irene, and Arnaud Comment. “In Vivo Hyperpolarized 13C MRS and MRI Applications,” 7:12, 2018.

https://doi.org/10.1002/9780470034590.emrstm1592

The tremendous polarization enhancement afforded by dissolution dynamic nuclear polarization (DNP) can be taken advantage of to perform molecular and metabolic imaging. Following the injection of molecules that are hyperpolarized via dissolution DNP, real-time measurements of their biodistribution and metabolic conversion can be recorded. This technology therefore provides a unique and invaluable tool for probing cellular metabolism in vivo in a noninvasive manner. It gives the opportunity to follow and evaluate disease progression and treatment response without requiring ex vivo destructive tissue assays. Seven sites across the globe are currently performing human studies using hyperpolarized 13C-pyruvate, and several other institutions are on the brink of being ready to inject their first patients. The most promising fields of application of this technology are in oncology and cardiology, and the aim of this article is to provide an overview of some of the current in vivo preclinical and clinical applications of hyperpolarized 13C magnetic resonance spectroscopy and imaging. Some new approaches and potential future developments to improve the hyperpolarized 13C technology are also presented and discussed.

A portable ventilator with integrated physiologic monitoring for hyperpolarized 129Xe MRI in rodents

Virgincar, Rohan S., Jerry Dahlke, Scott H. Robertson, Nathann Morand, Yi Qi, Simone Degan, Bastiaan Driehuys, and John C. Nouls. “A Portable Ventilator with Integrated Physiologic Monitoring for Hyperpolarized 129Xe MRI in Rodents.” Journal of Magnetic Resonance 295 (October 2018): 63–71.

https://doi.org/10.1016/j.jmr.2018.07.017

Hyperpolarized (HP) 129Xe MRI is emerging as a powerful, non-invasive method to image lung function and is beginning to find clinical application across a range of conditions. As clinical implementation progresses, it becomes important to translate back to well-defined animal models, where novel disease signatures can be characterized longitudinally and validated against histology. To date, preclinical 129Xe MRI has been limited to only a few sites worldwide with 2D imaging that is not generally sufficient to fully capture the heterogeneity of lung disease. To address these limitations and facilitate broader dissemination, we report on a compact and portable HP gas ventilator that integrates all the gas-delivery and physiologic monitoring capabilities required for high-resolution 3D hyperpolarized 129Xe imaging. This ventilator is MR- and HP-gas compatible, driven by inexpensive microcontrollers and open source code, and allows for precise control of the tidal volume and breathing cycle in perorally intubated mice and rats. We use the system to demonstrate data acquisition over multiple breath-holds, during which lung motion is suspended to enable high-resolution 3D imaging of gas-phase and dissolved-phase 129Xe in the lungs. We demonstrate the portability and versatility of the ventilator by imaging a mouse model of lung cancer longitudinally at 2-Tesla, and a healthy rat at 7 T. We also report the detection of subtle spectroscopic fluctuations in phase with the heart rate, superimposed onto larger variations stemming from the respiratory cycle. This ventilator was developed to facilitate duplication and gain broad adoption to accelerate preclinical 129Xe MRI research.

Temperature-Dependent Nuclear Spin Relaxation Due to Paramagnetic Dopants Below 30 K: Relevance to DNP-Enhanced Magnetic Resonance Imaging #DNPNMR

Chen, Hsueh-Ying, and Robert Tycko. “Temperature-Dependent Nuclear Spin Relaxation Due to Paramagnetic Dopants Below 30 K: Relevance to DNP-Enhanced Magnetic Resonance Imaging.” The Journal of Physical Chemistry B 122, no. 49 (December 13, 2018): 11731–42.

https://doi.org/10.1021/acs.jpcb.8b07958.

Dynamic nuclear polarization (DNP) can increase nuclear magnetic resonance (NMR) signal strengths by factors of 100 or more at low temperatures. In magnetic resonance imaging (MRI), signal enhancements from DNP potentially lead to enhancements in image resolution. However, the paramagnetic dopants required for DNP also reduce nuclear spin relaxation times, producing signal losses that may cancel the signal enhancements from DNP. Here we investigate the dependence of 1H NMR relaxation times, including T1ρ and T2, under conditions of Lee–Goldburg 1H–1H decoupling and pulsed spin locking, on temperature and dopant concentration in frozen solutions that contain the trinitroxide compound DOTOPA. We find that relaxation times become longer at temperatures below 10 K, where DOTOPA electron spins become strongly polarized at equilibrium in a 9.39 T magnetic field. We show that the dependences of relaxation times on temperature and DOTOPA concentration can be reproduced qualitatively (although not quantitatively) by detailed simulations of magnetic field fluctuations due to flip-flop transitions in a system of dipole-coupled electron spin magnetic moments. These results have implications for ongoing attempts to reach submicron resolution in inductively detected MRI at very low temperatures.

[NMR] Two PhD positions at Technical University of Munich in hyperpolarized and diffusion MRI

Two PhD positions (TV-L E13, 75 %) at Technical University of Munich in hyperpolarized and diffusion MRI 

Job Description

The Technical University of Munich (TUM) is seeking applications from highly motivated candidates for two PhD positions in magnetic resonance imaging. The PhD positions are embedded within the Emmy Noether Junior Research Group “Combined biochemical and biophysical imaging biomarkers for characterization of tumor metabolism and response to therapy” led by Dr. Franz Schilling and part of the DFG-funded Collaborative Research Center (SFB 824, www.sfb824.de) entitled “Imaging for Selection, Monitoring and Individualization of Cancer Therapies”.

The successful candidates will develop novel non-invasive magnetic resonance (MR) imaging biomarkers of unprecedented sensitivity for the characterization of tumor metabolism and response to therapy. They will focus on previously unexplored pH-sensitive hyperpolarized molecules and advanced diffusion MRI techniques that provide novel information currently not accessible with existing methods. Imaging biomarkers enable a comprehensive characterization of tissue providing functional, physiological, metabolic, cellular and molecular information beyond anatomical structures. For cancer patients, specific non-invasive imaging strategies for early-stage detection, tumor phenotyping and evaluation of response to therapy are not available at a satisfactory level, creating a pressing need for these advanced imaging technologies.

The preclinical imaging core located at the Department of Nuclear Medicine (www.nuk.mri.tum.de) and the Center for Translational Cancer Research (TranslaTUM, www.translatum.tum.de) provides state-of-the-art imaging instrumentation and consists of a group of scientists working on applications and specific improvements of multimodal imaging. 

Background

Recent research articles from our group on these topics are

  • Düwel et al. “Imaging of pH in vivo using hyperpolarized 13C-labeled zymonic acid.” Nature Communications (2017), 8:15126. 

  • Schilling et al. “MRI measurements of reporter-mediated increases in transmembrane water exchange enable detection of a gene reporter.” Nature Biotechnology (2017) 35(1): 75-80. 


Qualification

We invite applications from candidates having a M.Sc. or equivalent degree in physics, chemistry, bioengineering, or other related subjects. Previous experience in biomedical imaging is beneficial. Team spirit, capability of independent self-motivated work, as well as very good English and communication skills are required. Good computer skills and proficiency in at least one programming language (e.g. MATLAB) are required.

Our offer

The doctoral candidates will be employed by TUM (75 % TV-L E13) for a total duration of three years. Successful applicants will be enrolled within the TUM Graduate School receiving a structured doctoral training (https://www.gs.tum.de/en/doctorate-at-tum/).

Application details

Applications should include a curriculum vitae, certificates and transcripts of academic degrees, a letter of motivation detailing the applicant’s research interests, and contact information for at least 2 references. Please send your application within one PDF-document to bewerbung.nuklearmedizin@mri.tum.de but no later than January 31st 2018.

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Continuous-flow DNP polarizer for MRI applications at 1.5 T

Denysenkov, V., et al., Continuous-flow DNP polarizer for MRI applications at 1.5 T. 2017. 7: p. 44010.

http://dx.doi.org/10.1038/srep44010

Here we describe a new hyperpolarization approach for magnetic resonance imaging applications at 1.5 T. Proton signal enhancements of more than 20 were achieved with a newly designed multimode microwave resonator situated inside the bore of the imager and used for Overhauser dynamic nuclear polarization of the water proton signal. Different from other approaches in our setup the hyperpolarization is achieved continuously by liquid water flowing through the polarizer under continuous microwave excitation. With an available flow rate of up to 1.5 ml/min, which should be high enough for DNP MR angiography applications in small animals like mice and rats. The hyperpolarized liquid cooled to physiological temperature can be routed by a mechanical switch to a quartz capillary for injection into the blood vessels of the target object. This new approach allows hyperpolarization of protons without the need of an additional magnet and avoids the losses arising from the transfer of the hyperpolarized solution between magnets. The signal-to-noise improvement of this method is demonstrated on two- and three-dimensional phantoms of blood vessels.

[NMR] Multiple postdoc positions in Hyperpolarized 13C MR

From the Ampere Magnetic Resonance List

Multiple Postdoctoral Research Fellowship Positions in Hyperpolarized 13C Metabolic Imaging

The University of Maryland School of Medicine has expanded its molecular imaging and interventional research capabilities by establishing the Center for Metabolic Imaging and Therapeutics. The center houses a GE SpinLabTM dynamic nuclear polarizer suitable for preclinical and clinical applications, a GE 3T 750w MR scanner, and an MR Solutions MRS 3017 Preclinical Benchtop MR scanner. The GE MR scanner is also integrated with two Insightec 1024-element high-intensity focused ultrasound (HIFU) systems for image-guided interventions. Our goal is to facilitate both basic science and clinical research by exploring novel molecular imaging agent-based technologies for screening, early disease detection and treatment response, and real-time image-guided interventions.

Multiple postdoctoral research fellowship positions are available in the metabolic imaging group led by Dr. Dirk Mayer. Specific areas of research include optimized acquisition and reconstruction techniques, kinetic modeling for quantitative analysis, and new probe development. These methods will be applied to animal models (e.g., traumatic brain injury, cancer, liver disease) with translation to patients scheduled for summer 2017. This is an exciting opportunity to work at one of the first sites that will do translational/clinical hyperpolarized 13C MRI/MRS.

The candidate should have a Ph.D. (or equivalent degree) in engineering, physics, physical chemistry, or similar fields. The ideal candidate has a strong background in NMR physics with particular emphasis on in vivo imaging and/or spectroscopy, data acquisition and signal/image processing/analysis. Experience in pulse sequence programming (ideally on GE and/or MR Solutions scanners), knowledge of computer languages, such as C++, Matlab and IDL, and experience in performing small animal imaging is also desirable. Qualified applicants should also have a track record of peer-reviewed publications.

Interested individuals should send a letter detailing their research interests, an updated CV and contact information for at least two references to Dirk Mayer, Ph.D. (dmayer@som.umaryland.edu).

Dirk Mayer, Dr. rer. nat.

Associate Professor

Diagnostic Radiology & Nuclear Medicine

University of Maryland School of Medicine

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Simultaneous PET/MRI with (13)C magnetic resonance spectroscopic imaging (hyperPET): phantom-based evaluation of PET quantification

Hansen, A.E., et al., Simultaneous PET/MRI with (13)C magnetic resonance spectroscopic imaging (hyperPET): phantom-based evaluation of PET quantification. EJNMMI Phys, 2016. 3(1): p. 7.

https://www.ncbi.nlm.nih.gov/pubmed/27102632

BACKGROUND: Integrated PET/MRI with hyperpolarized (13)C magnetic resonance spectroscopic imaging ((13)C-MRSI) offers simultaneous, dual-modality metabolic imaging. A prerequisite for the use of simultaneous imaging is the absence of interference between the two modalities. This has been documented for a clinical whole-body system using simultaneous (1)H-MRI and PET but never for (13)C-MRSI and PET. Here, the feasibility of simultaneous PET and (13)C-MRSI as well as hyperpolarized (13)C-MRSI in an integrated whole-body PET/MRI hybrid scanner is evaluated using phantom experiments. METHODS: Combined PET and (13)C-MRSI phantoms including a NEMA [(18)F]-FDG phantom, (13)C-acetate and (13)C-urea sources, and hyperpolarized (13)C-pyruvate were imaged repeatedly with PET and/or (13)C-MRSI. Measurements evaluated for interference effects included PET activity values in the largest sphere and a background region; total number of PET trues; and (13)C-MRSI signal-to-noise ratio (SNR) for urea and acetate phantoms. Differences between measurement conditions were evaluated using t tests. RESULTS: PET and (13)C-MRSI data acquisition could be performed simultaneously without any discernible artifacts. The average difference in PET activity between acquisitions with and without simultaneous (13)C-MRSI was 0.83 (largest sphere) and -0.76 % (background). The average difference in net trues was -0.01 %. The average difference in (13)C-MRSI SNR between acquisitions with and without simultaneous PET ranged from -2.28 to 1.21 % for all phantoms and measurement conditions. No differences were significant. The system was capable of (13)C-MRSI of hyperpolarized (13)C-pyruvate. CONCLUSIONS: Simultaneous PET and (13)C-MRSI in an integrated whole-body PET/MRI hybrid scanner is feasible. Phantom experiments showed that possible interference effects introduced by acquiring data from the two modalities simultaneously are small and non-significant. Further experiments can now investigate the benefits of simultaneous PET and hyperpolarized (13)C-MRI in vivo studies.

Finite element modeling of (129)Xe diffusive gas exchange NMR in the human alveoli

Stewart, N.J., J. Parra-Robles, and J.M. Wild, Finite element modeling of (129)Xe diffusive gas exchange NMR in the human alveoli. J Magn Reson, 2016. 271: p. 21-33.

https://www.ncbi.nlm.nih.gov/pubmed/27526397

Existing models of (129)Xe diffusive exchange for lung microstructural modeling with time-resolved MR spectroscopy data have considered analytical solutions to one-dimensional, homogeneous models of the lungs with specific assumptions about the alveolar geometry. In order to establish a model system for simulating the effects of physiologically-realistic changes in physical and microstructural parameters on (129)Xe exchange NMR, we have developed a 3D alveolar capillary model for finite element analysis. To account for the heterogeneity of the alveolar geometry across the lungs, we have derived realistic geometries for finite element analysis based on 2D histological samples and 3D micro-CT image volumes obtained from ex vivo biopsies of lung tissue from normal subjects and patients with interstitial lung disease. The 3D alveolar capillary model permits investigation of the impact of alveolar geometrical parameters and diffusion and perfusion coefficients on the in vivo measured (129)Xe CSSR signal response. The heterogeneity of alveolar microstructure that is accounted for in image-based models resulted in considerable alterations to the shape of the (129)Xe diffusive uptake curve when compared to 1D models. Our findings have important implications for the future design and optimization of (129)Xe MR experiments and in the interpretation of lung microstructural changes from this data.

Assessment of a Heuristic Model for Characterization of Magnetic Nanoparticles as Contrast Agent in MRI

Félix-González, N., et al., Assessment of a Heuristic Model for Characterization of Magnetic Nanoparticles as Contrast Agent in MRI. Concepts in Magnetic Resonance Part A, 2015. 44A(5): p. 279-286.

http://dx.doi.org/10.1002/cmr.a.21361

In magnetic resonance imaging (MRI), the use of magnetic nanoparticles (MNPs) as contrast agent (CA) greatly enhances the possibility to identify several diseases hardly diagnosed by other means. The efficacy of a new CA is described by the longitudinal and transverse relaxivity. Nuclear Magnetic Relaxation Dispersion (NMRD) profiles represent the evolution of relaxivities with magnetic field. Many efforts have been taken to develop theoretical models to depict water proton relaxation in presence of magnetic compounds. The use of theoretical models in junction with NMRD profiles has become a powerful tool to characterize MNPs as CA. In this work, a heuristical theoretical model was implemented, verified and assessed with different magnetic materials. It has been demonstrated that the model works well when using iron cores but fails with other magnetic compounds. A weighting factor associated with Langevin function was introduced to the model. This extra calibration enables the model to be used with other magnetic compounds to characterize new CAs in MRI.

[NMR] Preclinical MRI Staff Scientist Position at The Weizmann Institute

From the Ampere Magnetic Resonance List

The Weizmann Institute of Science, Israel, seeks candidates for the position of a tenure-track staff scientist in Magnetic Resonance Imaging. The scientist will be in charge of the Institute’s central core MRI/MRS preclinical facilities which include a state-of-the-art 15.2 T preclinical animal imaging magnet, one of the first of its kind worldwide, as well as a 400 MHz wide-bore and 4.7 T magnets. 

About The Work

The work spans a wide range of skills, including: (1.) Working closely with experimental groups at the Institute; setting up and carrying out animal imaging protocols. (2.) Collaborating with Institute scientists in developing new pulse sequences and analysis methodologies for studying in-vivo metabolism, anatomy and physiology. (3.) Overseeing the imaging facilities and ensuring their integrity and viability. 

Candidates should ideally have both a strong quantitative background in magnetic resonance, as well as experience in MRI and animal imaging. However, motivated and outstanding people are encouraged to apply even if they lack some of the necessary prerequisites. 

To Apply

To apply, please email your CV to Dr. Assaf Tal, assaf.tal@weizmann.ac.il.

About The Institute.

The Weizmann Institute provides an outstanding intellectual environment within a beautiful campus. It is internationally renown and has played a major role in magnetic resonance. It currently houses multiple labs studying diverse phenomena ranging from electron paramagnetism of proteins to solid state NMR, hyperpolarization techniqeus, in-vivo spectroscopy and imaging in animal models and in humans. Weizmann has recently made unprecedented investments in magnetic resonance, including hiring of multiple new faculty members, and purchasing a 1 GHz NMR liquid state spectrometer, 15.2 T preclinical MRI and 7 T human MRI, among others.

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