Zepeng Wang^1,2 and Fan Lam^1,2,3
1Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ²Beckman Institute for Advanced Science and Technology, Urbana, IL, United States, ³Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, United States

Diffusion-weighted MRSI (DW-MRSI) is a unique quantitative molecular imaging modality that can potentially provide exclusive cell-type and compartment-specific microstructural information in vivo. However, DW-MRSI studies have been largely limited to single voxels or very low resolutions in basic science and clinical applications due to several fundamental technical challenges. Here, we further enhanced the performance and robustness of the recently proposed subspace imaging method by synergizing improved acquisition and data processing strategies. Higher b-value DE and 3D metabolite mean diffusivity mapping more immune to physiological motions at a 6.9x6.9x8 mm³ nominal resolution were achieved in less than 20-mins.

Brice Albert¹, Joseph W Plummer², Matthew M Willmering¹, Diana M Lindquist^3,4,5, Laura L Walkup^1,2,6,7, and Zackary I Cleveland^1,2,6,7
1Center for Pulmonary Imaging Research, Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ²Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States, ³Imaging Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ⁴Department of Pediatrics, University of Cincinnati, Cincinnati, OH, United States, ⁵Department of Radiology, University of Cincinnati, Cincinnati, OH, United States, ⁶Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ⁷Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

Many single-site studies, and increasingly multi-site clinical trials, employ hyperpolarized ¹²⁹Xe MRI to assess lung structure and function. The lack of reliable imaging ¹²⁹Xe standards hampers image quantification and rigorous comparisons across research sites. This is particularly true for ¹²⁹Xe imaging of pulmonary gas-exchange, which must detect the large gaseous resonance and the two, 50-fold-smaller ¹²⁹Xe dissolved resonances, corresponding to ¹²⁹Xe dissolved in red bloods cells and adjacent plasma/parenchymal barrier tissues. This work demonstrates the feasibility of constructing practical, thermally-polarized, dissolved-phase ¹²⁹Xe phantoms that mimic in-vivo resonances and will enable multi-site studies of gas-exchange imaging to be harmonized.

David Guarin Bedoya^1,2, Erin Elizabeth Hardy¹, Anna Samoilenko³, Sameer Joshi³, Jason Stockmann¹, Jan Henrik Ardenkjaer-Larsen^2,4, Matthew S. Rosen^1,5,6, Boyd M. Goodson⁷, Thomas Theis⁸, Eduard Y Chekmenev^3,9, and Yi-Fen Yen^1
1Radiology Department, Athinoula A. Martinos Center for Biomedical Imaging, Massachusttes General Hospital, Boston, MA, United States, ²Polarize ApS, Frederiksberg, Denmark, ³Department of Chemistry, Wayne State University, Detroit, MI, United States, ⁴Department of Electrical Engineering, Technical University of Denmark, Kongens Lyngby, Denmark, ⁵Radiology Department, Harvard Medical School, Boston, MA, United States, ⁶Physics Department, Havard University, Boston, MA, United States, ⁷School of Chemical and Biomolecular Sciences, Southern Illinois University, Carbondale, IL, United States, ⁸Department of Chemistry, North Carolina State University, Raleigh, NC, United States, ⁹Russian Academy of Sciences, Moscow, Russian Federation

In this work, we developed a DNP hyperpolarized 15N-labeled metronidazole contrast agent. The formulation of the sample and the DNP process were optimized to reduce the build-up time constant down to 22 min while reaching liquid state signal enhancements of 10⁴. The T1 relaxation times were measured in liquid-state, and found to be minutes long. Due to the high enhancement and long T1, MNZ hyperpolarized 15N signal could be monitored for several minutes. The contrast agent was tested with MRS in-vivo, in a rat brain. The hyperpolarized MNZ signal remained above the noise level for more than a minute. 

Jia Xu¹, Sarah E Ernst², Erin E Reasoner³, Stephen A Cross³, Alivia N Brinker³, Cameron A Keomanivong⁴, Zach Elias⁴, Daniel R. Thedens¹, Nandakumar Narayanan⁴, Jordan L Schultz³, Michael J Welsh², and Vincent A Magnotta^1
1Radiology, University of Iowa, Iowa City, IA, United States, ²Internal Medicine, University of Iowa, Iowa City, IA, United States, ³Psychiatry, University of Iowa, Iowa City, IA, United States, ⁴Neurology, University of Iowa, Iowa City, IA, United States

Terazosin is an FDA-approved medicine that has been used primarily for men and data for women are missing. For the first time, the target engagement of Terazosin in neurodegenerative diseases was assessed for both sexes. We chose the βATP/Pi ratio as a biomarker to study the brain energy metabolism and found strong correlations between the in vivo brain ATP levels to whole blood ATP levels. We observed clear sex differences in response to different TZ doses in both mice and humans. Our data suggest that the optimal dose for females may need to be lower as compared to males. 

Abdullah S. Bdaiwi^1,2, Mariah L. Costa^1,2, Joseph W. Plummer^1,2, Matthew M. Willmering¹, Laura L. Walkup^1,2,3,4, and Zackary L. Cleveland^1,2,3,4
1Center for Pulmonary Imaging Research, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States, ²Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States, ³Department of Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States, ⁴Department of Pediatrics, University of Cincinnati, Cincinnati, OH, United States

Hyperpolarized ¹²⁹Xe MRI can non-invasively measure regional ventilation by mapping the spin-density of inhaled gas, thus providing insights into regional disease pathophysiology. However, the quantitative accuracy of ¹²⁹Xe ventilation imaging is reduced by B₁-inhomogeneity causing spatial variations in both coil sensitivity and nonequilibrium magnetization decay. These can cause lung function impairment to be either over or underestimated. We demonstrate these artifacts can be mitigated by generating flip angle maps from paired 2D-spiral images acquired in the same held breath. This yields quantitatively comparable results to those obtained with a conventional, 2D gradient recalled echo sequence in substantially reduced acquisition times.

Abdullah S. Bdaiwi^1,2, Joseph W. Plummer^1,2, Matthew M. Willmering¹, David J. Roach¹, Jason C. Woods^1,3,4, Laura L. Walkup^1,2,3,4, and Zackary L. Cleveland^1,2,3,4
1Center for Pulmonary Imaging Research, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States, ²Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States, ³Department of Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States, ⁴Department of Pediatrics, University of Cincinnati, Cincinnati, OH, United States

Advances hyperpolarized ¹²⁹Xe production, data acquisition and image analysis have allowed ¹²⁹Xe MRI to emerge as a leading pulmonary imaging modality. As the number of sites capable of ¹²⁹Xe MRI and quantitative image-derived metrics grow, the need for an intuitive, organized analysis tool increases. Here, we provide a user-friendly application, designed as MATLAB language-based interface, to analyze HP ¹²⁹Xe data. This open-source, research tool enables standardized analysis of hyperpolarized ¹²⁹Xe calibration, ventilation, diffusion, and gas-exchange data. Furthermore, the modular design allows developers to easily implement additional functions and analysis procedures, providing a framework for growth and sharing of analysis techniques.

Elnaz Parniyany¹, Elise Woodward ¹, Tingting Wu¹, Matthew S Fox^1,2, and Alexei Ouriadov^1,2,3
1Physics and Astronomy, The University of Western Ontario, London, ON, Canada, ²Lawson Health Research Institute, London, ON, Canada, ³School of Biomedical Engineering, Faculty of Engineering, The University of Western Ontario, London, ON, Canada

Hyperpolarized ¹²⁹Xe  lung MRI is an efficient technique used to investigate and assess pulmonary diseases.  However, the longitudinal observation of the emphysema progression using hyperpolarized gas MRI-based ADC can be problematic, as the disease-progression can lead to increasing unventilated-lung areas, which likely excludes the largest ADC estimates.  One solution to this problem is to combine static-ventilation and ADC measurements following the idea of ³He MRI ventilatory ADC (vADC).  We have demonstrated this method adapted for ¹²⁹Xe MRI to help overcome the above-mentioned shortcomings and provide an accurate assessment of the emphysema progression. 

Atsushi M. Takahashi¹, David Guarin^2,3, Erin E. Hardy³, Julie Miller⁴, Hiroaki Wakimoto⁵, Daniel P. Cahill⁵, and Yi-Fen Yen^3
1Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, United States, ²Polarize ApS, Frederiksberg, Denmark, ³Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ⁴Department of Neurology, Massachusetts General Hospital, Boston, MA, United States, ⁵Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, United States

We report an inductively coupled floating coil designed for hyperpolarized ¹³C MR spectroscopic imaging of mouse brain, with emphases on the simplicity of the circuit design, the ease of use, whole-brain coverage, and high SNR obtained. The floating coil is designed to “crown” the mouse head for a snug fit to achieve full coverage of the brain with good sensitivity. Here, we demonstrated the coil’s performance in normal mouse and glioblastoma multiforme mouse model at 4.7 T using a next-generation hyperpolarizer. High signal to noise ratio exceeding 70:1 was obtained in the brain with good spatial resolution (1.53mm x 1.53mm).

Xiao Liang¹, Muhammad G Saleh¹, Steve Roys¹, Rao P Gullapalli¹, and Jiachen Zhuo^1
1Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States

It is desirable to measure GABA, glutamate, and GSH in the thalamus for understanding pathological and pharmacokinetic changes. In this study, we study the feasibility of simultaneous measurements of these metabolites in the thalamus using HERMES. HERMES data were acquired on 20 healthy adult volunteers with and without saturation bands. HERMES data were processed in Gannet with and without spectral alignment. The results demonstrated the feasibility of using HERMES for simultaneous measurements of GABA, Glx and GSH in the thalamus. HERMES combined with saturation bands and retrospective spectral alignment yields high SNR spectra and reproducible measurements in the thalamus.

Wen Jin^1,2, Yibo Zhao^1,2, Rong Guo^1,2, Yudu Li^1,2, Jie Luo³, Yao Li³, and Zhi-Pei Liang^1,2
1Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ²Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ³School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China

With the increasing use of MRSI in research and clinical applications, we have seen a surge in the use of low-rank models for denoising MRSI data. This paper presents a novel method for robust denoising of MRSI data corrupted by both Gaussian noise and nuisance signals. The proposed method has been validated using both simulated and in vivo data, producing impressive results. This method will further enhance the practical utility of low-rank denoising.

Jun Chen¹, Junjie Ma¹, James Ratnakar¹, Shawn C Burgess^2,3, Craig R Malloy^1,4,5, and Jae Mo Park^1,4,6
1AIRC, UT Southwestern Medical Center at Dallas, Dallas, TX, United States, ²Center for Human Nutrition, UT Southwestern Medical Center at Dallas, Dallas, TX, United States, ³Pharmacology, UT Southwestern Medical Center at Dallas, Dallas, TX, United States, ⁴Radiology, UT Southwestern Medical Center at Dallas, Dallas, TX, United States, ⁵Internal Medicine, UT Southwestern Medical Center at Dallas, Dallas, TX, United States, ⁶Electrical and Computer Engineering, University of Texas at Dallas, Richardson, TX, United States

Obesity is associated with insulin resistance and chronic inflammation, both of which are known to affect skeletal muscle metabolism. However, studies in the impact of obesity on metabolism mainly focus on adipose tissue, instead of skeletal muscle. This study analyzes the in vivo pyruvate metabolism in the skeletal muscle of obese volunteers with hyperpolarized [1-¹³C]pyruvate. The results indicate increased lactate production and decreased pyruvate dehydrogenase activity in the skeletal muscle of obesity.

Rong Guo^1,2, Yudu Li^1,2, Yibo Zhao^1,2, Sina Tafti^2,3, Aaron Anderson², Brad Sutton^1,2,4, and Zhi-Pei Liang^1,2
1Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ²Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ³Siemens Medical Solutions, Inc., Urbana, IL, United States, ⁴Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States

Metabolic imaging of the whole brain is desirable in many neuroscience studies and some clinical applications. This work demonstrates whole-brain MRSI (FOV = 240×240×160 mm³) at 7T using a special SPICE-based data acquisition and processing scheme. Experimental results showed that whole brain metabolic imaging at 3.0×3.0×3.2 mm³ resolution could be obtained in an 8-minute scan at 7T.

Li An¹, Jennifer Wai Evans¹, Courtney Burton¹, Jyoti Tomar¹, Maria Ferraris Araneta¹, Carlos A Zarate¹, and Jun Shen^1
1National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States

Unlike weakly coupled spin systems, the signal strength of Glu H4, Gln H4, and GSH glutamyl H4 is affected by the timing of refocusing pulses for a fixed total TE. Using full density matrix simulations, it was found that glutamate H4, glutamine H4, and glutathione glutamyl H4 peak amplitudes can be significantly increased by shortening the echo time of the first spin echo (TE₁) in PRESS from a previously reported 69 ms to 16 ms. The improved sequence was tested in vivo and validated using Monte Carlo simulations.

Julie M Joyce^1,2,3,4, Marilena DeMayo^1,2,3,5,6, Chantel T Debert^2,3,4,7, and Ashley D Harris^1,2,3,4
1Department of Radiology, University of Calgary, Calgary, AB, Canada, ²Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada, ³Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada, ⁴Integrated Concussion Research Program, University of Calgary, Calgary, AB, Canada, ⁵Department of Psychiatry, University of Calgary, Calgary, AB, Canada, ⁶Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada, ⁷Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada

Metabolite concentrations vary across brain regions. What remains unclear is the degree to which this variation is due to inherent regional differences or if it is driven by the composition of the underlying tissue. Using magnetic resonance spectroscopy, we show that apparent ‘regional differences’ in metabolite concentrations are driven by tissue composition for glutamate and glutathione. Furthermore, we provide evidence to suggest a need for a tissue correction for glutamate, glutathione and N-acetyl-aspartate that appropriately addresses differences in voxel gray matter and white matter content.

Felizitas Charlotte Wermter¹, Wolfgang Dreher¹, and Christian Bock^2
1in-vivo MR, University Bremen, Bremen, Germany, ²Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research, Bremerhaven, Germany

Magnetic resonance spectroscopy (MRS) allows non-invasive pH measurements via the chemical shift difference between a pH-dependent resonance and a reference. We studied the pH dependence of taurine chemical shifts in ¹H MRS for a wide range of pH and temperature. At 37°C and in the physiological range (pH ~7.3), the chemical shifts show a bijective dependence on pH. This approach was evaluated by measurements on taurine phantoms using solutions with different pH and temperatures, demonstrating the possibility of absolute pH determination via the chemical shift of taurine.

Anja Maria Fischer^1,2, Petros Martirosian¹, and Fritz Schick^1
1Section on Experimental Radiology, University Hospital Tübingen, Tübingen, Germany, ²Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany

This method allows for the calculation of pixel-wise FID spectra based on a 3D spiral UTE imaging sequence. Images were acquired for 36/72 TE and extrapolated. The method is advantageous for rapidly decaying 1H signals such as those of collagen in tendons or fibrotic tissue. A phantom (6 collagen solutions) served for evaluation. Resulting spectra are comparable to a standard non-localized FID spectrum and show positive correlation between collagen concentration and signal. First in-vivo results recorded in the subcutaneous adipose tissue exhibit the typical fat resonances. The presented UTE-FID spectroscopy seems feasible for spatially resolved applications of rapidly decaying signals.

Theresia Ziegs¹, Loreen Ruhm¹, Andrew Wright¹, and Anke Henning^1,2
1High-Field MR Center, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, ²Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

Glutamate is the major excitatory neurotransmitter in the brain and malfunction of glutamatergic metabolism is associated with various neurological disorders. Respective metabolic rates can be determined via direct ¹³C or indirect ¹H-[¹³C] MRS after intake of ¹³C labelled tracers. In this work, labeling effects after oral intake of [¹³C-1]glucose are observed in human brain using a ¹H-FID-MRSI sequence at 9.4T. Spectral time series of GM and WM voxels as well as metabolite maps show regionally distinct and tissue type specific labelling induced changes of Glu and Gln spectral pattern that allow for the determination of ¹³C label uptake rates.

Agilo L Kern^1,2, Marcel Gutberlet^1,2, Regina Rumpel³, Inga Brüsch³, Jens M Hohlfeld^2,4,5, Frank Wacker^1,2, and Bennet Hensen^1
1Institute of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany, ²Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany, ³Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany, ⁴Department of Clinical Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany, ⁵Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany

Thermometry using the proton resonance frequency (PRF) is challenging in inhomogeneous, fatty tissues and moving organs. Purpose of this study was to develop and test a combined free induction decay (FID)/spin-echo chemical shift imaging sequence for accurate hyperpolarized ¹²⁹Xe MR thermometry in rats exposed to hypothermia. Significant changes of ¹²⁹Xe lipid chemical shift and good agreement with core body temperature are observed. Bland–Altman analysis shows narrower limits of agreement and reduced mean difference for spin-echo acquisitions, suggesting improved precision and accuracy in fatty tissues. The method may be valuable as reference standard for development of more accurate ¹H MR thermometry.

Agilo L Kern^1,2, Marcel Gutberlet^1,2, Jens M Hohlfeld^2,3,4, Frank Wacker^1,2, and Jens Vogel-Claussen^1,2
1Institute of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany, ²Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany, ³Department of Clinical Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany, ⁴Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany

A rapid chemical shift saturation recovery (CSSR) pulse sequence is developed for reconstructing CSSR uptake curves in different cardiac phases by employing retrospective gating. The sequence is tested in a study with 6 healthy volunteers and compared to conventional CSSR. A significant difference in septal wall thickness between trough and crest of the pulse wave in lung tissue is found. Results from rapid and conventional CSSR are strongly correlated and show good absolute agreement. The proposed rapid CSSR pulse sequence may provide valuable new insights into normal lung function, improve precision of CSSR results and may have clinical applications.

Andrew Martin Wright^1,2 and Anke Henning^1,3
1MRZ, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, ²IMPRS for Cognitive and Systems Neuroscience, Eberhard-Karls University of Tübingen, Tübingen, Germany, ³Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

Very short TR (TR < 300) MRSI is a popular method that enables fast acquisition of spectroscopic imaging data; however, raw metabolite signals following short TR acquisitions are influenced by strong T₁-weighting. In order to gather more accurate images and to be able to relate MRSI results to SVS studies, it is valuable to correct for T₁-weighting and to quantify MRSI images. This study presents results that utilize a voxel-specific, T₁-correction method which is an advancement from more traditional methods that utilized average T₁-corrections for metabolites. Fully sampled, single-slice ¹H MRSI metabolite maps are presented for 12 metabolites.