Category Archives: Imaging

Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1 #DNPNMR

Granlund, Kristin L., Sui-Seng Tee, Hebert A. Vargas, Serge K. Lyashchenko, Ed Reznik, Samson Fine, Vincent Laudone, et al. “Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1.” Cell Metabolism 31, no. 1 (January 2020): 105-114.e3.

https://doi.org/10.1016/j.cmet.2019.08.024

Metabolic imaging using hyperpolarized magnetic resonance can increase the sensitivity of MRI, though its ability to inform on relevant changes to biochemistry in humans remains unclear. In this work, we image pyruvate metabolism in patients, assessing the reproducibility of delivery and conversion in the setting of primary prostate cancer. We show that the time to max of pyruvate does not vary significantly within patients undergoing two separate injections or across patients. Furthermore, we show that lactate increases with Gleason grade. RNA sequencing data demonstrate a significant increase in the predominant pyruvate uptake transporter, monocarboxylate transporter 1. Increased protein expression was also observed in regions of high lactate signal, implicating it as the driver of lactate signal in vivo. Targeted DNA sequencing for actionable mutations revealed the highest lactate occurred in patients with PTEN loss. This work identifies a potential link between actionable genomic alterations and metabolic information derived from hyperpolarized pyruvate MRI.

Slice selection in low-temperature, DNP-enhanced magnetic resonance imaging by Lee-Goldburg spin-locking and phase modulation #DNPNMR

Chen, Hsueh-Ying, and Robert Tycko. “Slice Selection in Low-Temperature, DNP-Enhanced Magnetic Resonance Imaging by Lee-Goldburg Spin-Locking and Phase Modulation.” Journal of Magnetic Resonance 313 (April 2020): 106715.

https://doi.org/10.1016/j.jmr.2020.106715

Large enhancements in nuclear magnetic resonance (NMR) signals provided by dynamic nuclear polarization (DNP) at low temperatures have the potential to enable inductively-detected 1H magnetic resonance imaging (MRI) with isotropic spatial resolution on the order of one micron, especially when low temperatures and DNP are combined with microcoils, three-dimensional (3D) phase encoding of image information, pulsed spin locking during NMR signal detection, and homonuclear dipolar decoupling by Lee-Goldburg (LG) irradiation or similar methods. However, the relatively slow build-up of nuclear magnetization under DNP leads to very long acquisition times for high-resolution 3D images unless the sample volume or field of view (FOV) is restricted. We have therefore developed a method for slice selection in low-temperature, DNP-enhanced MRI that limits the FOV to about 50 m in one or more dimensions. This method uses small-amplitude phase modulation of LG irradiation in the presence of a strong magnetic field gradient to invert spin-locked 1H magnetization in the selected slice. Experimental results are reported, including effects of radio-frequency field inhomogeneity, variations in the amplitude of phase modulation, and shaped phase modulation.

In vivo melanoma imaging based on dynamic nuclear polarization enhancement in melanin pigment of living mice using in vivo dynamic nuclear polarization magnetic resonance imaging #DNPNMR

Hyodo, Fuminori, Tatsuya Naganuma, Hinako Eto, Masaharu Murata, Hideo Utsumi, and Masayuki Matsuo. “In Vivo Melanoma Imaging Based on Dynamic Nuclear Polarization Enhancement in Melanin Pigment of Living Mice Using in Vivo Dynamic Nuclear Polarization Magnetic Resonance Imaging.” Free Radical Biology and Medicine 134 (April 2019): 99–105.

https://doi.org/10.1016/j.freeradbiomed.2019.01.002

Melanin is a pigment that includes free radicals and is widely distributed in living animals. Malignant melanoma is one of the most progressive tumors in humans with increasing incidence worldwide, and has shown resistance to chemotherapy, resulting in high mortality at the metastatic stage. In general, melanoma involves the abnormal accumulation of melanin pigment produced by malignant melanocytes. Electron paramagnetic resonance (EPR) spectroscopy and imaging is a powerful technique to directly visualize melanomas using endogenous free radicals in the melanin pigment. Because melanin radicals have a large linewidth, the low spatial resolution of EPR imaging results in blurred images and a lack of anatomical information. Dynamic nuclear polarization (DNP)-MRI is a noninvasive imaging method to obtain the spatio-temporal information of free radicals with MRI anatomical resolution. Proton signals in tissues, including free radicals, can be dramatically enhanced by EPR irradiation at the resonance frequency of the free radical prior to applying the MRI pulse sequence. However, the DNP effects of free radicals in the pigment of living organisms is unclear. Therefore, if endogenous free radicals in melanin pigment could be utilized as a bio-probe for DNP-MRI, this will be an advantage for the specific enhancement of melanoma tissues and might allow the separate noninvasive visualization of melanoma tissues without the need for probe administration. Here, we report that biological melanin pigment induced a in vivo DNP effect by interacting with water molecules. In addition, we demonstrated in vivo melanoma imaging based on the DNP effects of endogenous free radicals in the melanin pigment of living mice.

Dynamic hyperpolarized 13C MR spectroscopic imaging using SPICE in mouse kidney at 9.4 T #DNPNMR

Song, Jae Eun, Jaewook Shin, Hansol Lee, Young‐Suk Choi, Ho‐Taek Song, and Dong‐Hyun Kim. “Dynamic Hyperpolarized 13C MR Spectroscopic Imaging Using SPICE in Mouse Kidney at 9.4 T.” NMR in Biomedicine, December 19, 2019.

https://doi.org/10.1002/nbm.4230.

This study aims to investigate the feasibility of dynamic hyperpolarized 13C MR spectroscopic imaging (MRSI) using the SPectroscopic Imaging by exploiting spatiospectral CorrElation (SPICE) technique and an estimation of the spatially resolved conversion constant rate (kpl). An acquisition scheme comprising a single training dataset and several imaging datasets was proposed considering hyperpolarized 13C circumstances. The feasibility and advantage of the scheme were investigated in two parts: (a) consistency of spectral basis over time and (b) accuracy of the estimated kpl. The simulations and in vivo experiments support accurate kpl estimation with consistent spectral bases. The proposed method was implemented in an enzyme phantom and via in vivo experiments. In the enzyme phantom experiments, spatially resolved homogeneous kpl maps were observed. In the in vivo experiments, normal diet (ND) mice and high-fat diet (HFD) mice had kpl (s−1) values of medullar (ND: 0.0119 ± 0.0022, HFD: 0.0195 ± 0.0005) and cortical (ND: 0.0148 ±0.0023, HFD: 0.0224 ±0.0054) regions which were higher than vascular (ND: 0.0087 ±0.0013, HFD: 0.0132 ±0.0050) regions. In particular, the kpl value in the medullar region exhibited a significant difference between the two diet groups. In summary, the feasibility of using modified SPICE for dynamic hyperpolarized 13C MRSI was demonstrated via simulations and in vivo experiments. The consistency of spectral bases over time and the accuracy of the estimated kpl values validate the proposed acquisition scheme, which comprises only a single training dataset. The proposed method improved the spatial resolution of dynamic hyperpolarized 13C MRSI, which could be used for kpl estimation using high signal-to-noise ratio spectral bases.

Improved reconstruction stability for chemical shift encoded hyperpolarized 13C magnetic resonance spectroscopic imaging using k‐t spiral acquisitions

Macdonald, Erin B., Gregory P. Barton, Benjamin L. Cox, Kevin M. Johnson, Roberta M. Strigel, and Sean B. Fain. “Improved Reconstruction Stability for Chemical Shift Encoded Hyperpolarized 13 C Magnetic Resonance Spectroscopic Imaging Using K‐t Spiral Acquisitions.” Magnetic Resonance in Medicine, December 9, 2019, mrm.28122.

https://doi.org/10.1002/mrm.28122

Purpose: A multiecho, field of view (FOV)-oversampled k-t spiral acquisition and direct iterative decomposition of water and fat with echo asymmetry and least-squares estimation reconstruction is demonstrated to improve the stability of hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) in the presence of signal ambiguities attributed to low-SNR (signal-to-noise-ratio) species, local uncertainties in metabolite peaks, and echo-to-echo signal inconsistencies. Theory: k-t spiral acquisitions redistribute readout points to be more densely spaced radially in k-space by acquiring an FOV and matrix that are oversampled by η. These more densely spaced spiral turns constitute effective intraspiral echoes and can supplement conventional interspiral echoes to improve spectral separation and reduce spectral cross-talk to better resolve 13C-labeled species for spectroscopic imaging.

Methods: Digital simulations and imaging phantom experiments were performed for a range of interspiral echo spacings and η using multiecho, k-t spiral acquisitions. Image spectral cross-talk artifacts were evaluated both qualitatively and quantitatively as the percent error in measured metabolite ratios. In vivo murine experiments evaluated the feasibility of multiecho, k-t spiral [1-13C]pyruvate MRSI to reduce spectral cross-talk for 3 scenarios of different expected reconstruction stability.

Results: Digital simulations and imaging phantom experiments both demonstrated reduced or comparable image spectral cross-talk and percent errors in measured metabolite ratios with increasing η and better choices of echo spacings. In vivo images displayed markedly reduced spectral cross-talk in lactate images acquired with η = 7 versus η = 1.

Conclusion: The precision of hyperpolarized 13C metabolic imaging and quantification in the presence of low-SNR species, local uncertainties in metabolite

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.

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.

Biomolecular imaging of (13)C-butyrate with dissolution-DNP: Polarization enhancement and formulation for in vivo studies

Flori, A., G. Giovannetti, M. F. Santarelli, G. D. Aquaro, D. De Marchi, S. Burchielli, F. Frijia, V. Positano, L. Landini, and L. Menichetti. “Biomolecular Imaging of (13)C-Butyrate with Dissolution-DNP: Polarization Enhancement and Formulation for in Vivo Studies.” Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy 199 (June 15, 2018): 153–60.

https://doi.org/10.1016/j.saa.2018.03.014

Magnetic Resonance Spectroscopy of hyperpolarized isotopically enriched molecules facilitates the non-invasive real-time investigation of in vivo tissue metabolism in the time-frame of a few minutes; this opens up a new avenue in the development of biomolecular probes. Dissolution Dynamic Nuclear Polarization is a hyperpolarization technique yielding a more than four orders of magnitude increase in the (13)C polarization for in vivo Magnetic Resonance Spectroscopy studies. As reported in several studies, the dissolution Dynamic Nuclear Polarization polarization performance relies on the chemico-physical properties of the sample. In this study, we describe and quantify the effects of the different sample components on the dissolution Dynamic Nuclear Polarization performance of [1-(13)C]butyrate. In particular, we focus on the polarization enhancement provided by the incremental addition of the glassy agent dimethyl sulfoxide and gadolinium chelate to the formulation. Finally, preliminary results obtained after injection in healthy rats are also reported, showing the feasibility of an in vivo Magnetic Resonance Spectroscopy study with hyperpolarized [1-(13)C]butyrate using a 3T clinical set-up.

ESR line width and line shape dependence of Overhauser-enhanced magnetic resonance imaging #DNPNMR

Meenakumari, V., Hideo Utsumi, A. Jawahar, and A. Milton Franklin Benial. “ESR Line Width and Line Shape Dependence of Overhauser-Enhanced Magnetic Resonance Imaging.” Magnetic Resonance in Chemistry 54, no. 11 (2016): 874–79.

https://doi.org/10.1002/mrc.4489

Electron spin resonance and Overhauser-enhanced magnetic resonance imaging studies were carried out for various concentrations of 14N-labeled 3-carbamoyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl in pure water. Overhauser-enhancement factor attains maxima in the range of 2.5–3 mm concentration. The leakage factor showed an asymptotic increase with increasing agent concentration. The coupling parameter showed the interaction between the electron and nuclear spins to be mainly dipolar in origin. The electron spin resonance parameters, such as the line width, line shape and g-factor, were determined. The line width analysis confirms that the line broadening is proportional to the agent concentration, and also the agent concentration is optimized in the range of 2.5–3 mm. The line shape analysis shows that the observed electron spin resonance line shape is a Voigt line shape, in which the Lorentzian component is dominant. The contribution of Lorentzian component was estimated using the winsim package. The Lorentzian component of the resonance line attains maxima in the range of 2.5–3 mm concentration. Therefore, this study reveals that the agent concentration, line width and Lorentzian component are the important factors in determining the Overhauser-enhancement factor. Hence, the agent concentration was optimized as 2.5–3 mm for in vivo/in vitro electron spin resonance imaging and Overhauser-enhanced magnetic resonance imaging phantom studies. Copyright © 2016 John Wiley & Sons, Ltd.

A radiofrequency system for in vivo hyperpolarized (13) C MRS experiments in mice with a 3T MRI clinical scanner

Giovannetti, G., et al., A radiofrequency system for in vivo hyperpolarized (13) C MRS experiments in mice with a 3T MRI clinical scanner. Scanning, 2016. 38(6): p. 710-719.

https://www.ncbi.nlm.nih.gov/pubmed/27059822

Hyperpolarized carbon-13 magnetic resonance spectroscopy (MRS) is a powerful tool to explore tissue metabolic state, by permitting the study of intermediary metabolism of biomolecules in vivo. However, a number of technological problems still limit this technology and need innovative solutions. In particular, the low molar concentration of derivate metabolites give rise to low signal-to-noise ratio (SNR), which makes the design and development of dedicated radiofrequency (RF) coils a fundamental task. In this article, the authors describe the simulation and the design of a RF coils configuration for MR experiments in mice, constituted by a (1) H whole body volume RF coil for imaging and a (13) C single circular loop surface RF coil for performing (13) C acquisitions. After the building, the RF system was employed in an in vivo experiment in a mouse injected with hyperpolarized [1-(13) C]pyruvate by using a 3 T clinical MR scanner. SCANNING 38:710-719, 2016. (c) 2016 Wiley Periodicals, Inc.

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