Bastiaan Driehuys¹ and Elianna Ada Bier^2
1Radiology, Duke University, Durham, NC, United States, ²Biomedical Engineering, Duke University, Durham, NC, United States

In quantitative ¹²⁹Xe gas exchange MRI, the RBC/barrier ratio is emerging as a robust and important functional metric. However, it depends strongly on how it is measured, specifically on flip angle and repetition time. Moreover, we don’t yet have a clear understanding of its expected range in healthy subjects. Here, we demonstrate that by combining a physical diffusion model of ¹²⁹Xe signal recovery with the recently introduced concept of flip angle to TR-equivalence, we can estimate the “structural limit” for the maximum RBC/barrier ratio expected in healthy adult subjects at any TR and flip angle.  

Elianna Ada Bier¹, David G Mummy², Junlan Lu³, and Bastiaan Driehuys^2
1Biomedical Engineering, Duke University, Durham, NC, United States, ²Radiology, Duke University, Durham, NC, United States, ³Medical Physics Graduate Program, Duke University, Durham, NC, United States

¹²⁹Xe MRS has the potential to detect and characterize cardiopulmonary disease; however, clinical use demands a better understanding of the repeatability of these measurements. We studied the within-session repeatability of ¹²⁹Xe MR static and dynamic spectroscopy of 117 pairs of scans with matched heart rates and adequate quality in both scans. Repeatability of each spectroscopic measurement was quantified using the coefficient of repeatability (CR), coefficient of variation (CV), and the intraclass correlation coefficient (ICC). All measurements had very little bias between the two scans and significant ICCs. The CRs for RBC:barrier and RBC amplitude oscillation were 0.07 and 4.2%, respectively.

Ozkan Doganay¹, Minsuok Kim², and Fergus Gleeson^3
1Ege University, Izmir, Turkey, ²Loughborough University, Loughborough, United Kingdom, ³University of Oxford, Oxford, United Kingdom

Hyperpolarized Xenon-129 MRI ventilation and gas exchange imaging and computational modelling provide a way to quantitatively assess gas ventilation and gas exchange parameters. This new imaging and modelling technique can be used to assess pulmonary diseases including COPD and emphysema and promises to be sensitive to variation in healthy subjects due to age, and/or early phases of pulmonary gas exchange impairment.

Luis Loza¹, Tahmina Achekzai¹, Stephen Kadlecek¹, Hooman Hamedani¹, Ian Duncan¹, and Rahim R. Rizi^2
1University of Pennsylvania, Philadelphia, PA, United States, ²Radiology, University of Pennsylvania, Philadelphia, PA, United States

Fractional ventilation, a metric denoting per-breath pulmonary gas replacement, has been shown to be sensitive to disease-induced alterations in ventilation in diseases such as emphysema. We have developed two discrete techniques for measuring FV using hyperpolarized 129Xe MR imaging and demonstrated their acquisition in a rat. Although the two techniques yield different FV maps, these two techniques offer both a quick and cost-effective method and a longer, robust method for probing pulmonary ventilation.

Mariah L. Costa^1,2, Peter J. Niedbalski³, Matthew M. Willmering¹, and Zackary I. Cleveland^1,2,4
1Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ²Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States, ³Internal Medicine, University of Kansas Medical Center, Kansas City, KS, United States, ⁴Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

Advances in hyperpolarization (HP) technology have expanded the translation and clinical utility of HP media MR. Unfortunately, HP images suffer from artifacts and inaccuracies due to magnetization decay. To mitigate decay, we introduced a method to map magnetization dynamics via Bloch-equation modeling and keyhole reconstruction. Here we extend the approach to include optimization via uncertainty propagation. As proof-of-principle, we compared a linear and interleaved keyhole to map HP decay in digital phantoms and 129Xe ventilation images. Linear keyhole yielded uniform decay values, while interleaved keyhole generated physically improbable distributions, demonstrating the utility of analytical optimization in radial-keyhole decay correction.

Yiwen Qian¹, Kai Ruppert¹, Faraz Amzajerdian¹, Yi Xin¹, Hooman Hamedani¹, Luis Loza¹, Tahmina S Achekzai¹, Ryan J Baron¹, Ian F Duncan¹, Stephen Kadlecek¹, and Rahim R Rizi^1
1University of Pennsylvania, Philadelphia, PA, United States

Measurement of the apparent alveolar septal wall thickness (SWT) via chemical shift saturation recovery (CSSR) with hyperpolarized xenon-129 is emerging as a robust and sensitive technique for detecting lung disease. However, the extracted pulmonary physiological values are obtained by fitting theoretical gas uptake curves that are based on assumptions of an unrealistically symmetric alveolar anatomy to the measurement data. In this work, we investigated the impact of asymmetric septal walls on the fitting parameters using numerically simulated CSSR measurement data. Our simulations predict potentially large errors in all fitting parameters other than the total septal wall thickness.

Vira Grynko^1,2, Yurii Shepelytskyi^1,2, Tao Li³, Ayman Hassan^4,5, Karl Granberg⁴, and Mitchell S. Albert^2,3,5
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, ⁴Thunder Bay Regional Health Sciences Centre, Thunder Bay, ON, Canada, ⁵Northern Ontario School of Medicine, Thunder Bay, ON, Canada

Hyperpolarized (HP) ¹²⁹Xe magnetic resonance imaging (MRI) of the brain can be used to evaluate cerebral perfusion. Currently, all HP ¹²⁹Xe brain imaging techniques were only performed for single slice imaging. To further develop clinical applications of functional HP ¹²⁹Xe brain imaging, multi-slice acquisitions are necessary. In this work, we demonstrate the capability of multi-slice human brain imaging with HP ¹²⁹Xe using 3D gradient echo imaging with a Cartesian readout. This will allow further progress in various HP ¹²⁹Xe functional brain imaging applications such as perfusion evaluation and hemodynamic response detection.

Vladislav Ivantaev¹, Stephan Berner^1,2,3, Henri de Maissin¹, Jan-Bernd Hövener ⁴, Jürgen Hennig¹, Dominik v. Elverfeldt¹, Valerij G. Kiselev¹, and Andreas B. Schmidt^1,2,3
1Department of Radiology, Medical Physics, Medical Center, University of Freiburg, Faculty of Medicine, Freiburg, Germany, ²German Consortium for Cancer Research (DKTK), partner site Freiburg, Freiburg, Germany, ³German Cancer Research Center (DKFZ), Heidelberg, Germany, ⁴Section Biomedical Imaging, Department of Radiology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany

Parahydrogen induced polarization (PHIP) allows providing hyperpolarized (HP) agents for metabolic MRI within seconds and at negligible cost. Recently, we demonstrated PHIP inside of an MRI system using spin-order transfer (SOT) sequences and showed direct in-vivo administration of the agent without transport. Here, we show that molecular translational motion in the inhomogeneous field of the MRI during SOT can strongly corrupt the HP yield. While we already demonstrated signal enhancement of ¹³C of 40.000-fold at 7 Tesla with our method, we suggest that the HP can be further improved by a better field homogeneity and reduced motion during the SOT.

Johanne Haahr Knudsen¹ and Lotte Bonde Bertelsen^1
1The MR Research Centre, Department of Clinical Medicine, The Faculty of Health Sciences, Aarhus University, Aarhus, Denmark

Deoxy-D-glucose (2-DG) is a synthetic glucose analog, which inhibits the first step in the glycolysis by inhibiting the enzyme hexokinase. It has been shown to increase chemosensitivity in some cancers and to reverse glucocorticoid resistance in acute lymphoblastic leukemia. This could have potential for treatment in other leukemia diseases. The present study investigates whether hyperpolarized ¹³C-MR can be used to explore into the effect of 2-DG and lactate on cell metabolism in acute myeloblastic leukemia cells.

Keith Michel¹, Collin Harlan¹, Trevor Mitcham¹, Matthew Merritt², Richard Bouchard¹, and James Bankson^1
1Imaging Physics, UT MD Anderson Cancer Center, Houston, TX, United States, ²Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States

Longitudinal relaxation time constants of hyperpolarized [1-¹³C]pyruvate, [¹³C,¹⁵N₂]urea and [2-¹³C]dihydroxyacetone in whole bovine blood were measured via low excitation angle dynamic pulse-acquire NMR spectroscopy at 7T. A small lactate signal was produced in scans of pyruvate, corresponding to <1% of the pyruvate precursor signal. All three ¹³C agents demonstrated shorter T₁ relaxation time constants in blood with arterial oxygen content than in blood with venous oxygenation, and the greatest oxygen-accelerated relaxation effect was observed for pyruvate.

Geoffrey J. Topping¹, Irina Heid², Marija Trajkovic-Arsic^3,4, Lukas Kritzner², Martin Grashei¹, Christian Hundshammer¹, Maximilian Aigner¹, Jason G. Skinner¹, Rickmer Braren², and Franz Schilling^1
1Department of Nuclear Medicine, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, ²Diagnostic and Interventional Radiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, ³German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany, ⁴Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), West German Cancer Center, University Hospital Essen, Essen, Germany

A narrow-bandwidth alternating-frequency multi-frame slice-selective-excitation FID spectroscopy sequence was implemented with minimal pulse sequence modification by prescribing spatially offset slices. This sequence was used to measure hyperpolarized [1‑¹³C]lactate and its downstream metabolite [1‑¹³C]pyruvate in a xenograft rat model of human pancreatic cancer (PSN1). Broad bandwidth excitation has difficulty separating the smaller pyruvate peak from the larger peak of injected lactate, when analyzed with magnitude spectra, phased complex spectra, or spectral fitting with the AMARES algorithm, particularly for multi-frame data. Narrow bandwidth excitation spectroscopy is simpler and more consistent to analyze, by achieving the spectral separation during acquisition.

GUANNAN ZHANG¹, Kofi Deh¹, Avigdor Leftin², and Kayvan R. Keshari^1,3
1Memorial Sloan Kettering Cancer Center, New York, NY, United States, ²GE Healthcare, New York, NY, United States, ³Weill Cornell Graduate School, New York, NY, United States

Hyperpolarized MRI using [1-¹³C] pyruvate is a novel technique that has been safely performed in humans for cancer studies. Here, we present preliminary work on acquiring dynamics of hyperpolarized [1-¹³C] pyruvate images using a custom-built ¹³C jacket coil, demonstrating the applicability of the method to image patients with metastatic cancer in the abdomen. The jacket coil provides coverage and RF excitation over the whole abdominal area, allowing to detect the spread of the metastatic cancer. The hyperpolarized ¹³C images acquired by a spiral sequence show a good quality, demonstrating the feasibility of the method for future hyperpolarization studies in patients. 

Albert P Chen¹, Kayvan R Keshari², and Charles H Cunningham^3
1GE Healthcare, Toronto, ON, Canada, ²Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ³Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada

The effect of deuterium enrichment on T1 relaxation was investigated for hyperpolarized [2-13C]pyruvate.  The T1 increased by 10s at 3T with deurterium enrichment on the sample molecule.  The T1 further increased by almost 30s when the hyperpolarized sample was dissolved using D2O instead of H2O.  Deuterium enrichment of the substrate and the dissolution media has the potential to significantly increase the available non-equilibrium polarization available at the time of injection for dissolution DNP experiments. 

Thanh Phong Lê^1,2, Andrea Capozzi^2,3, and Jean-Noël Hyacinthe^1,4
1Geneva School of Health Sciences, HES-SO University of Applied Sciences and Arts Western Switzerland, Geneva, Switzerland, ²Laboratory of Functional and Metabolic Imaging, EPFL (Swiss Federal Institute of Technology in Lausanne), Lausanne, Switzerland, ³Department of Health Technology, Center for Hyperpolarization in Magnetic Resonance, Technical University of Denmark, Kongens Lyngby, Denmark, ⁴Image Guided Intervention Laboratory, University of Geneva (UNIGE), Geneva, Switzerland

Hyperpolarized MR studies of localized animal disease models, specifically our studies of cerebral metabolism after transient ischemia in a mouse model of stroke, are greatly improved by implementation of spatially resolved measurements. The latter allows unfolding specific metabolic alterations in core, penumbra and peripheral tissues taking place after ischemia. To achieve higher specificity, the performances of a DNP polarizer were improved by installing a custom fluid path dissolution system to achieve higher polarization levels. In parallel, we implemented a dynamic spiral acquisition sequence to enable time-resolved MR metabolic imaging. Herein, we present our preliminary in-vivo proof of principle.

Henri de Maissin¹, Stephan Berner², Vladislav Vladislav Ivantaev³, Jan Hövener⁴, Jürgen Hennig⁵, Dominik von Elverfeldt⁵, and Andreas Schmidt^6
1Radiology, Uniiklinik Freiburg, Freiburg, Germany, ²radiology, Uniklinik Freiburg, Freiburg, Germany, ³radiology, Uniklinik freiburg, freiburg, Germany, ⁴hyperpolarization, Kiel university, Kiel, Germany, ⁵radiology, Uniklinik Freiburg, freiburg, Germany, ⁶Radiology, Uniklinik Freiburg, freiburg, Germany

Para-Hydrogen Induced Polarization (PHIP) is a promising cost- and time-efficient technique for highly-sensitive metabolic MRI. We recently demonstrated PHIP with ¹³C-polarizations of 25% inside MRI systems at high field using spin-order transfer (SOT) sequences. Here, we show that SOT is extremely sensitive to limited proton-RF bandwidth available in MRI setups. This effect is crucial for hyperpolarization of metabolic agents like acetate and pyruvate; and for PHIP in human MRI setups, dedicated hardware may be required. Still, high-field PHIP is promising as the setup is inexpensive and simple and requires no transport of the agents to the MRI system is needed.

Catriona H.E. Rooney¹, Jack J.J.J. Miller^1,2,3, and Damian J. Tyler^1,3
1Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom, ²Department of Physics, University of Oxford, Oxford, United Kingdom, ³Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, United Kingdom

Silicon nanoparticles (SiNPs) retain enhanced polarization for several hours following hyperpolarization due to their long nuclear T1 relaxation time and are therefore attractive candidates for use as MRI contrast agents. However, “bare” SiNPs show low signal enhancement and require the addition of exogenous radicals to reach sufficient signal enhancements for MRI. Here, the addition of two radicals (Finland trityl and TEMPO) and the effect of their concentration on SiNP build-up and decay properties were investigated. Optimising SiNP polarization characteristics is necessary if their clinical translation as targeted hyperpolarized contrast agents is to be achieved.

José Santiago Enriquez^1,2, Shivanand Pudakalakatti¹, Prasanta Dutta¹, Florencia McAllister^2,3, and Pratip Bhattacharya^1,2
1Cancer Systems Imaging, UT MD Anderson Cancer Center, Houston, TX, United States, ²UT MD Anderson UT Health GSBS, Houston, TX, United States, ³Clinical Cancer Prevention, UT MD Anderson Cancer Center, Houston, TX, United States

Early detection and prevention of pancreatic cancer is a modern-day challenge and there is an unmet need for non-invasive imaging markers that help identify the aggressive sub-type(s) of pancreatic ductal adenocarcinoma (PDAC) at diagnosis Our objective is to address this knowledge gap by  combining hyperpolarized metabolic imaging with Artificial Intelligence (AI). 

Arianna Ferrari¹, Josh Philipp Peters¹, Mariia Anikeeva¹, Frowin Ellermann¹, Andrey Pravdivtsev¹, Kolja Them¹, and Jan-Bernd Hövener^1,2
1SBMI Rad. UKSH, Kiel, Germany, ²Emmy Noether Group Molecular and Metabolic MRI - M3, Freiburg, Germany

The setup of a cryogen-free device for dissolution dynamic nuclear polarization (dDNP) in an imaging facility is described. Fully automated procedures were used to calibrate the system and to perform hyperpolarization of pyruvic acid. Polarizations exceeding 30 % were achieved routinely within an experiment duration of less than an hour. Pitfalls are discussed and solutions proposed.

James T. Grist^1,2,3, Juan Diego Sanchez⁴, Nikolaj Bøgh⁵, Esben Søvsø Szocska Hansen⁵, Jan Henrik Ardenkjær-Larsen⁶, Damian J. Tyler^1,2, and Christoffer Laustsen^5
1Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom, ²Oxford Centre for Magnetic Resonance, University of Oxford, Oxford, United Kingdom, ³Radiology, Oxford NHS Foundation Trust, Oxford, United Kingdom, ⁴Health Technology, Danish Technical University, Copenhagen, Denmark, ⁵Aarhus University, Aarhus, Denmark, ⁶Danish Technical University, Copenhagen, Denmark

Multi-channel acceleration of hyperpolarised 13C MRI is hindered by a lack of prior coil sensitivity profile knowledge. Here we harness a 13C tuned flexible multi-channel array to provide subject specific coil sensitivity measurements from 23Na and subsequent SENSE reconstruction of under-sampled hyperpolarised imaging data.

Reshmi J. S. Patel¹, Collin J. Harlan¹, and James A. Bankson^1,2
1Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ²The University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, TX, United States

Hyperpolarized [1-¹³C]-pyruvate MRI is an emerging imaging method that offers unprecedented spatiotemporal resolution for monitoring tumor metabolism in vivo. To establish a robust imaging biomarker, we must characterize phenomena that may modulate the apparent conversion rate of pyruvate into lactate (k_pl). We sought to investigate the potential effect of diffusion on pyruvate-to-lactate conversion. HP signal evolution, as calculated by finite-difference time domain simulation of a 2D tissue model, was fit to a two-compartment pharmacokinetic model. Results indicate for low intracellular k_pl, diffusion has a minimal impact, but pyruvate diffusion can reduce the apparent rate of conversion at high intracellular k_pl.