Harvey D. Lee^1,2, Connor J. Grady^1,2, Christiane L. Mallett^1,3, Md Nafiujjaman^1,2, Nathan M. Good⁴, N. Cecilia Martinez-Gomez⁴, Taeho Kim^1,2, Erik M. Shapiro^1,3, and Assaf A. Gilad^1,2,3
1Department of Biomedical Engineering, Michigan State University, East Lansing, MI, United States, ²Division of Synthetic Biology, Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI, United States, ³Department of Radiology, Michigan State University, East Lansing, MI, United States, ⁴Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA, United States

Sustainable products are becoming an integral part of our daily lives - in this study, we biosynthetically produced an MRI contrast agent from E.coli with an r1 of 6.0 (per-gadolinium, 7T field strength, room temperature) that provides the user with optical feedback through a jump in green fluorescence upon binding free gadolinium in solution. We anticipate this will reduce the amount of resources spent on quality control (in assessing the amount of unchelated gadolinium that could otherwise introduce toxicity), whereas its compatibility with lyophilization is expected to improve storage conditions in terms of longevity, stability, and transportation costs. 

Sadi Loai^1,2, Daniel A. Szulc^1,2, and Hai-Ling Margaret Cheng^1,2,3
1Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada, ²Translational Biology & Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada, ³The Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada

3D bioprinted scaffolds are one of the most novel and promising tissue regenerative therapeutics currently in development (e.g. to repair damaged cardiac tissue). Validation of correct scaffold placement and retention post-implantation is essential, but it is challenging to visualize scaffolds in-vivo given their similar material properties to native tissue. In this study, a T1-reducing contrast agent, MnPNH₂, was utilized to create an MR-trackable, bioprinted scaffold. In-vitro and in-vivo results confirmed the novel scaffold provided an environment conducive to cell growth and offered significant bright contrast for post-implantation scaffold monitoring in rats.        

Ryan Hall¹, Jing-Can Qin¹, Victoria Laney¹, and Nadia Ayat^1
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States

MRI is increasingly utilized for the diagnosis of liver disease and focal liver lesions. While liver-targeted gadolinium-based contrast agents (GBCAs) have high efficacy, they are shadowed by safety concerns regarding tissue retention. We have developed a liver-targeted manganese alternative – Mn-EOB-PC2A – that uses a liver-targeted ethoxybenzyl modified macrocyclic pyclen diacetate platform. Relaxivity measurements for Mn-EOB-PC2A suggest comparable performance to the GBCA alternatives, and in vitro characterization suggests strong uptake in hepatocytes with minimal toxicity. MRI with Mn-EOB-PC2A demonstrated strong liver-specific enhancement at a clinically relevant dose, underscoring the potential for Mn-EOB-PC2A as an alternative to traditional liver-targeted Gd-based platforms.

Ashrith Jacob¹, Ludger Starke¹, Christian Prinz¹, Jason M Millward¹, Paula Ramos Delgado¹, Ariane Fillmer², Thoralf Niendorf¹, and Sonia Waiczies^1
1Berlin Ultrahigh Field Facility, MDC, Berlin, Germany, ²Physikalisch - Technische Bundesanstalt (PTB) Braunschweig and Berlin, Berlin, Germany

Modifications to the CF₃ side-group of teriflunomide were made to improve its detection by ¹⁹F MRI. Pentafluorosulfanyl (SF₅) was shown to be a superior alternative to CF₃. The SNR efficiency of three ¹⁹F MRI methods showed that within a biological environment, SF₅-substitutions gave the highest SNR efficiency in combination with an ultrashort echo-time (UTE) MRI method. Chemical modifications did not hamper biological activity but SF₅-TF was more effective to inhibit T cell proliferation, indicating better anti-inflammatory activity. This study proposes SF₅ as a novel superior ¹⁹F MR reporter group for the drug teriflunomide.

Simonetta Geninatti Crich¹, Sabrina Geninatti Elkhanoufi², Diego Geninatti Alberti², Eric Thiaudiere³, Rachele Stefania¹, Elodie Parzy³, Philippe Mellet³, Philippe Massot³, and Silvio Aime^1
1University of Torino, Torino, Italy, ²University of torino, Torino, Italy, ³University of Bordeaux-CNRS, Bordeaux, France

New stable organic radicals probes have been proposed in this study to perform Molecular Imaging by monitoring by Overhauser Magnetic Resonance Imaging (OMRI) the enzymatic activity. The  radicals used are Tempo-containing esters forming stable micelles that are practically EPR silent. The hydrolysis of the ester bond catalyzed by Carboxyl esterases generates a narrow and intense EPR signal as a consequence of the release of the nitroxide radical from the micelle. Thus we have prepared a off/on probe responsive to the carboxylesterase activity that can be detected quantitatively in the OMR image.

Ludger Starke^1,2, Mariya Aravina¹, Jason M. Millward¹, Thoralf Niendorf^1,3, and Sonia Waiczies^1
1Berlin Ultrahigh Field Facility, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany, ²Digital Health Center, Hasso Plattner Institute, Potsdam, Germany, ³Experimental and Clinical Research Center (ECRC), A Joint Cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany

Siponimod is a fluorinated drug approved for treatment of secondary progressive multiple sclerosis. We detect ¹⁹F-MR signal in the liver, brain, kidneys, and thymus, and achieve the first ¹⁹F-MR images of a disease modifying drug, both in the liver and brain ex vivo and in a proof-of-concept in vivo experiment. Clear concentration differences between lobes of the liver or regions of the CNS can be observed. We have demonstrated the feasibility of using ¹⁹F-MRI to study the distribution of disease modifying drugs and improve our understanding of pharmacokinetics or guide therapeutic decisions.

Leif Schröder¹ and Jan Oliver Jost^1
1Translational Molecular Imaging, Deutsches Krebsforschungszentrum, Heidelberg, Germany

MRI reporters for hyperpolarized ¹²⁹Xe CEST need further improvement in order to sufficiently outcompete the intrinsic loss of hyperpolarization appearing under in vivo conditions.  This study opens up a possibility by accelerating the CEST build-up for the well-known Xe host CrA-ma by two orders of magnitude.  We designed a liposome decorated with a CrA-lipopeptide. To avoid inefficiency from back exchange, the lipopeptide fraction should be kept relatively low (e.g., 2 mol%). Complete saturation transfer could be easily achieved for maximum possible image contrast in ¹²⁹Xe MRI scans. This study pinpoints a large flexibility for designing  powerful HyperCEST agents.

Christian T McHugh^1,2, Phillip G Durham³, Michele Kelley^1,2, Nicholas J Bryden^1,2, Paul A Dayton^2,4, and Rosa T Branca^1,2
1Physics & Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, ²Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, ³Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, ⁴Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

Recently, it was shown that hyperCEST enables detection of microbubbles at clinically relevant ultrasound doses. Nanodroplets filled with low-boiling point perfluorocarbons are precursors of microbubbles. Because the chemical shift of xenon in liquid-phase perfluorocarbon nanodroplets is different than that in gas-phase microbubbles, hyperCEST detection of these nanodroplets could enable MR detection of their phase-change upon ultrasound activation. To this end, here we investigate if perfluorocarbon nanodroplets can be used as hyperCEST agent, first in vitro and then in vivo.

Patrick Michael Lehmann¹, Mads Andersen^2,3, Anina Seidemo¹, Xiang Xu^4,5, Xu Li^5,6, Nirbhay Yadav^5,6, Ronnie Wirestam¹, Patrick Liebig⁷, Frederik Testud⁸, Pia Sundgren^3,9,10, Peter C. van Zijl^5,6, and Linda Knutsson^1,5,6
1Department of Medical Radiation Physics, Lund University, Lund, Sweden, ²Philips Healthcare, Copenhagen, Denmark, ³Lund University Bioimaging Centre, Lund University, Lund, Sweden, ⁴BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ⁵Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁶F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ⁷Siemens Healthcare GmbH, Erlangen, Germany, ⁸Siemens Healthcare AB, Malmö, Sweden, ⁹Department of Radiology, Lund University, Lund, Sweden, ¹⁰Department of Medical Imaging and physiology, Skåne University hospital, Lund, Sweden

D-glucose is proposed as a cheap biodegradable alternative to gadolinium-based contrast agents. By performing glucoCEST imaging during and after administration of glucose, an approach referred to as dynamic glucose-enhanced (DGE) MRI, information about glucose delivery and uptake can be obtained. However, the small DGE signal changes at 3 T can easily be corrupted by motion. Furthermore, standard retrospective motion correction may erroneously alter true DGE signal, which may lead to misinterpretation. We designed a numerical head phantom that can be used for validation of motion correction and providing insight into the corresponding effects in vivo. 

Karl Ludger Radke¹, Daniel Benjamin Abrar¹, Miriam Frenken¹, Lena Marie Wilms¹, Matthias Boschheidgen¹, Patrick Liebig^2,3, Alexandra Ljimani¹, Sven Nebelung^1,4, Hans-Jörg Wittsack¹, and Anja Müller-Lutz^1
1University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Düsseldorf, Germany, ²Cent. of Med. Phys. and Biomed. Eng., Friedrich-Alexander-Univ. Erlangen-Nürnberg, Erlangen, Germany, ³Siemens Healthcare GmbH, Erlangen, Germany, ⁴Department of Diagnostic and Interventional Radiology, University Hospital Aachen, Aachen, Germany

Quantification of altered lactate concentrations with non-invasive MR imaging is of diagnostic interest in a broad spectrum of diseases and further analysis of athletic activity. In this context, chemical exchange saturation transfer (CEST) is an increasingly validated contrast mechanism in MRI. However, successful application of CEST requires efficient selective saturation of the exchanging lactate protons. In this study, we successfully optimized and investigated the application of intramuscular lactate CEST imaging (LATEST) supported by numerical simulations and were able to apply LATEST for the first time in-vivo at 3.0 T.

Chan Hong Moon¹, Carolyn Anderson^1,2,3,4,5, Sina Tavakoli ^5,6, Tiffany Pham ⁶, Lydia Perkins⁵, Lynda Little-Ihrig⁵, Neal Mason¹, Xiaoyuan Chen⁷, Charles Laymon^1,2, Mark Gladwin⁵, and Enrico Novelli ^3,5
1Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States, ²Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States, ³Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, United States, ⁵Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States, ⁶Gilead Sciences, Foster City, CA, United States, ⁷National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, United States

Sickle cell disease (SCD) causes vaso-occlusion, ischemia, and end-organ infarction that causes acute pain episodes, also known as vaso-occlusive crises (VOC). Understanding the mechanism underlying VOC is critical to identify patients at risk and for accurate diagnosis while in VOC. PET imaging with the probe ⁶⁸Ga-PRGD2 that binds integrin αvβ3 identified areas of increased binding of  sickle RBC to the endothelium in VOC. Simultaneous PET-MR imaging could provide additional information on tissue changes associated with VOC. Thus, we imaged a patient with SCD with ⁶⁸Ga-PRGD2 in combination with MRI by using PET-MR 3T scanner.