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

J-resolved 1H-MRSI offers several unique advantages but suffers from long acquisition time and lmited SNR, especially for longer TEs. Leveraging the recent progress on constrained MRSI reconstruction using learned nonlinear low-dimensional representations, we propose here a new method for SNR-enhancing reconstruction from rapidly generated, noisy J-resolved data, that can computationally efficiently enforce an accurate nonlinear low-dimensional representation of high-dimensional J-resolved spectroscopic signals through a learned network-based project as well as complementary spatial constraints. The proposed method has been shown to improve the SNR significantly for in vivo J-resolved 1H-MRSI of the brain.

Hooman Hamedani¹, Faraz Amzajerdian¹, Stephen Kadlecek¹, Ryan Baron¹, Kai Ruppert¹, Ian Duncan¹, Mostafa Ismail¹, Yi Xin¹, Tahmina Achekzai¹, Luis Loza¹, and Rahim Rizi^1
1University of Pennsylvania, Philadelphia, PA, United States

Bronchoscopic lung volume reduction (LVR) using endobronchial valves has proven effective at improving lung function and quality of life in certain severely emphysematous patients. Successful lung volume reduction of the target lobe shifts ventilation and perfusion to the healthier ipsilateral lobe and improves breathing mechanics. Functional imaging with spatially-resolved metrics using inhaled hyperpolarized ¹²⁹Xe (HXe) may provide a deeper understanding of the physiology underlying clinical benefit. 

Xiaopeng Zhou¹, Ulrike Dydak^1,2, and Pallab K. Bhattacharyya^3
1School of Health Sciences, Purdue University, West Lafayette, IN, United States, ²Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States, ³Imaging institute, Cleveland Clinic, Cleveland, OH, United States

Frequency drift from EPI-based sequences prior to MRS scans is a known issue. Running MRS scans ‘from cold’ is suggested for the greatest scanner stability, with some equilibration period for systems with overnight energy-saving mode. Running MRS scans before scanner reaches an equilibration period can result in large frequency drifts. Under these conditions, the effect of running fMRI scans seem to be negligible. Applying frequency and phase correction can make the final spectrum appear to be qualitatively similar between scans with big and negligible drift.  

Xiaoxi Liu¹, Shuyu Tang², Robert Bok¹, Hsin-Yu Chen¹, Changhua Mu¹, Romelyn Delos Santos¹, Avantika Sinha¹, Zhen J. Wang¹, and Peder E.Z. Larson^1
1University of California San Francisco, San Francisco, CA, United States, ²HeartVista, Los Altos, CA, United States

MRI of hyperpolarized 13C-labeled compounds is an emerging tool to non-invasively detect metabolic processes, and hyperpolarized [1-13C]pyruvate has been used in clinics for assessing cancer and cardiac metabolism. However, due to nonrenewable and progressively depleted magnetization, hyperpolarized 13C has a limitation to achieve both high spatial resolution and temporal resolution with high SNR. This study proposes a novel bicarbonate-specific 3D bSSFP sequence with stack-of-spiral readout to improve the SNR of dynamic bicarbonate imaging in hyperpolarized [1-13C]pyruvate studies. Compared to a metabolite-specific GRE sequence, the proposed MS-3DbSSFP sequence showed a 3X SNR improvement for bicarbonate imaging in rat heart and kidneys.

Xiaoxi Liu¹, Di Cui¹, Shuyu Tang², Robert Bok¹, Changhua Mu¹, Hsin-Yu Chen¹, Romelyn Delos Santos¹, Avantika Sinha¹, Jeremy Gordon¹, and Peder E.Z. Larson^1
1University of California San Francisco, San Francisco, CA, United States, ²HeartVista, Los Altos, CA, United States

Hyperpolarized 13C-labeled compound is an emerging technique in biomedical imaging to non-invasively detect metabolic processes and has been translated in clinical for cancer and cardiac metabolism studies. However, hyperpolarized MRI signal is limited by high spatial and temporal resolution and high SNR. This work describes a novel rotated Echo-planar imaging (EPI) trajectory with a half scan acquisition that shortens echo time to reduce the T2* effect in metabolic imaging. Compared to the standard full sampled EPI trajectory, the proposed trajectory has the advantage of gaining higher signal intensity, and is less sensitive to motion artifacts, distortion artifacts and aliasing artifacts.

Jun Chen¹, Terry Gemelli², Pradeep Mammen², and Jae Mo Park^1,3
1AIRC, UT Southwestern Medical Center at Dallas, Dallas, TX, United States, ²Internal Medicine, UT Southwestern Medical Center at Dallas, Dallas, TX, United States, ³Radiology, UT Southwestern Medical Center at Dallas, Dallas, TX, United States

Pyruvate metabolism in skeletal muscle plays an essential role for energy production and development of muscular dystrophy (MD). However, investigation of the metabolism of MD has been focused on myocardium due to its vital importance, rather than skeletal muscle. This study presents preliminary results that demonstrate the feasibility of assessing altered pyruvate metabolism in the skeletal muscle of Becker MD patient with hyperpolarized [1-¹³C]pyruvate. In parallel, the metabolic profile of MD skeletal muscle was analyzed by NMR using a Duchenne MD mouse model after [U-¹³C₃]pyruvate infusion. This study indicates that pyruvate metabolism is altered in skeletal muscle with MD.

Eduard Y Chekmenev¹, Patrick TomHon², Mohammad S. H. Kabir³, Shiraz Nantogma³, Mustapha Abdulmojeed², Iuliia Mandzhieva², Jessica Ettedgui⁴, Rolf E. Swenson⁴, Murali C. Krishna⁵, Thomas Theis², Boyd M. Goodson⁶, and Isaiah Adelabu^3
1Chemistry and Oncology, Wayne State University, Detroit, MI, United States, ²Chemistry, North Carolina State University, Raleigh, NC, United States, ³Chemistry, Wayne State University, Detroit, MI, United States, ⁴National Heart, Lung, and Blood Institute, Bethesda, MD, United States, ⁵National Cancer Institute, Bethesda, MD, United States, ⁶Southern Illinois University Carbondale, Carbondale, IL, United States

This presentation covers the recent advances in spin physics and instrumentation of Signal Amplification By Reversible Exchange (SABRE) in SHield Enables Alignment Transfer to Heteronuclei (SHEATH). Order unity ¹³C polarization for [1-¹³C]pyruvate was demonstrated for catalyst-bound species by SABRE-SHEATH, which becomes possible due to favorable ¹³C relaxation dynamics in a microtesla magnetic field. The magnetic field, temperature and co-solvents heavily modulate the attainable ¹³C polarization, providing an opportunity for optimization to deliver highly polarized [1-¹³C]pyruvate quickly and cheaply for biomedical applications. The design of clinical-scale hyperpolarizer is described for production of [1-¹³C]pyruvate and other metabolically relevant hyperpolarized contrast agents.

Xiaoxi Liu¹, Shuyu Tang², Di Cui¹, Sule Sahin¹, Nicholas Dwork¹, Zhen J. Wang¹, and Peder E.Z. Larson^1
1University of California San Francisco, San Francisco, CA, United States, ²HeartVista, Los Altos, CA, United States

In the previous work, 3D balanced steady state free precession (bSSFP) sequence have been used to improve SNR for hyperpolarized 13C lactate imaging. In this study, we proposed a 3D bSSFP stack-of-spiral with golden angle rotation sequence for lactate imaging to furtherly accelerate lactate imaging. At the same time, we designed a regularized reconstruction method for the undersampled data that did not degrade image quality.

Hooman Hamedani¹, Faraz Amzajerdian¹, Stephen Kadlecek¹, Ryan Baron¹, Kai Ruppert¹, Ian Duncan¹, Mostafa Ismail¹, Yi Xin¹, Tahmina Achekzai¹, Luis Loza¹, and Rahim Rizi^1
1University of Pennsylvania, Philadelphia, PA, United States

In order to image function in the free breathing lung with high temporal and special resolution, we have developed a passive, mechanically controlled MR-friendly gas delivery device capable of real time dosimetry and end-tidal gas measurements that can be used in combination with a non-rigid image registration technique. These dynamic images can thus be translated into comprehensible quantitative maps of lung ventilation and gas exchange. In order to image the lung continuously during normal breathing, we have also developed a fast-acquisition pulse sequence that uses diaphragm position to facilitate image reconstruction. 

Collin J. Harlan^1,2, Joshua S. Niedzielski³, Keith A. Michel ², Yunyun Chen⁴, Gary V. Martinez², Philip L. Lorenzi⁵, Lin Tan⁵, Matthew E. Merritt⁶, Mukundan Ragavan⁶, Vlad C. Sandulache⁷, Stephen Y. Lai^4,8,9, and James A. Bankson^2
1The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, United States, ²Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ³Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ⁴Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ⁵Department of Bioinformatics and Computational Biology and The Proteomics and Metabolomics Core Facility, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ⁶Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States, ⁷Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, United States, ⁸Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ⁹Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States

Metabolic imaging of hyperpolarized pyruvate can provide new insight into cancer progression and therapeutic response. Pharmacokinetic modeling can be used to determine k_PL, the apparent rate constant for conversion of hyperpolarized pyruvate into lactate. Quantitative evaluation of signal evolution in vivo can be challenging due to nonstationary signal and multiple barriers between the intravascular precursor and its intracellular conversion into lactate. In this work, we evaluated intracellular k_PL using suspensions of anaplastic thyroid cancer and prostate cancer cells. A pharmacokinetic model with two physical compartments and two chemical pools was utilized for quantitative analysis.

Thomas Theis¹, Patrick TomHon¹, Soeren Lehmkuhl¹, Boyd Goodson², Yi-Fen Yen³, Matthew Rosen³, and Eduard Chekmenev^4
1Chemistry, North Carolina State University, Raleigh, NC, United States, ²Chemistry, Southern Illinois University, Carbondale, IL, United States, ³Martinos Center for Biomedical Imaging, Harvard Medical School, Charlestown, MA, United States, ⁴Chemistry, Wayne State University, Detroit, MI, United States

We describe recent advances with Parahydrogen Induced Polarization (PHIP) to establish easy-to-use, inexpensive hyperpolarizers with potential for translation into preclinical and clinical practice. We show that more than 10% polarization of [1-13C]-Pyruvate can be established by SABRE-SHEATH. With those polarization levels, we demonstrate hyperpolarized MRI at 1.5 T of a cryogen-free MRI system. We also describe a PHIP reactor that provides continuous hyperpolarization and achieves RASER (Radio-wave Amplification by Stimulated Emission of Radiation), which  gives 100% background free, high resolution MR signals. By combining PHIP methods with low-field MRI, an affordable yet highly sensitive molecular imaging approach may emerge. 

Sule Sahin^1,2, Nicholas Dwork¹, Shuyu Tang³, Xiaoxi Liu¹, Zhen Jane Wang¹, and Peder E.Z. Larson^1
1Radiology, University of California, San Francisco, San Francisco, CA, United States, ²UC Berkeley - UCSF Graduate Program in Bioengineering, Berkeley, CA, United States, ³HeartVista, Los Altos, CA, United States

Using a metabolite-specific bSSFP sequence for hyperpolarized [1-¹³C]pyruvate MRI has been shown to increase SNR significantly, yet specialized k_PL methods have not been developed for  this sequence. A k_PL fitting method for bSSFP lactate acquisition was developed and voxel-wise k_PL fitting was performed on four renal cell carcinoma subjects. The k_PL values and maps were compared to and showed agreement with lactate over pyruvate AUC ratio maps and spoiled gradient echo k_PL values and maps.

Vira Grynko^1,2, Yurii Shepelytskyi^2,3, Tao Li³, Hannah Aalto⁴, Iulian Constantin Ruset⁵, and Mitchell S Albert^2,3,6
1Chemistry and Materials Science Program, Lakehead University, Thunder Bay, ON, Canada, ²Thunder Bay Regional Health Research Institute, Thunder Bay, ON, Canada, ³Chemistry Department, Lakehead University, Thunder Bay, ON, Canada, ⁴Applied Life Science Program, Lakehead University, Thunder Bay, ON, Canada, ⁵Xemed LLC, Durham, NH, United States, ⁶Northern Ontario School of Medicine, Thunder Bay, ON, Canada

Cucurbit[6]uril (CB6) is a well-known hyperpolarized ¹²⁹Xe (HP ¹²⁹Xe) MRI contrast agent. Although in-vivo biodistribution detection of CB6 has already been achieved, no studies have been performed on optimization of the saturation pre-pulse train in order to maximize CB6 performance. In the present work, we demonstrate that utilization of sinusoidal saturation pulses for ¹²⁹Xe HyperCEST MRI, instead of using conventional three-lobe sinc pulses, yields substantial improvement of CB6 HyperCEST performance and a significant increase in HyperCEST MRI sensitivity. In addition, lower detectable CB6 concentrations are reported for both types of saturation pre-pulses at 3T using a whole-body scanner.

Maksym Sharma^1,2, Harkiran K Kooner^1,2, Marrissa J McIntosh^1,2, David G McCormack³, and Grace Parraga^1,2,3,4
1Department of Medical Biophysics, Western University, London, ON, Canada, ²Robarts Research Institute, Western University, London, ON, Canada, ³Division of Respirology, Department of Medicine, Western University, London, ON, Canada, ⁴School of Biomedical Engineering, Western University, London, ON, Canada

Texture analysis may be used to extract quantitative information from hyperpolarized ³He MR ventilation images to help explain clinically-relevant outcomes and disease progression. We aimed to combine texture analysis with machine-learning to generate classification models for predicting worsening quality-of-life in ex-smokers with and without COPD. We identified six texture feature contributors, which outperformed standard imaging and clinical variables, with the top machine-learning model achieving a classification accuracy of 80.2% at predicting worsening quality-of-life within 2-3 years. These pilot results suggest that ³He MRI texture features may provide additional prognostic information to predict clinically-relevant changes in quality-of-life in ex-smokers.

Leon Sergey Khalyavin¹ and Jae Mo Park^1
1University of Texas at Dallas, Richardson, TX, United States

This study aims to reconstruct 13C spectrum from FID that is corrupted by signal overflow. As the corruption often occurs in the beginning of the FID, an uncorrupted section can be reconstructed as a time-delayed version of the FID. The T2*, M0, and frequency of metabolite peaks can be calculated from the reconstructed spectrum of the uncorrupted FID signal. Since the T2* is an innate property of the compound, it can be used to extrapolate the M0 of the original signal using a mono-exponential function for each peak. The method was tested with dynamic hyperpolarized 13C MRS data.