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Dayang Wang¹, Srivathsa Pasumarthi¹, and Ryan Chamberlain^1
1Subtle Medical Inc., Menlo Park, CA, United States

Keywords: Simulations, Data Acquisition, MRI Dose Simulation

In Gadolinium-based contrast agents (GBCAs) assisted MRI scans, dose simulation is a significant task that enables understanding of the perfusion process. In this work, we propose a new transformer-based iterative model to generate MRI images with arbitrary contrast dosages. By using datasets where only 0%, 10%, and 100% dose images are available, the proposed model can synthesize quantitatively and qualitatively accurate MRI images of varying dosages. The simulated images can be used for other downstream tasks like developing reduced-dose acquisitions and finding the minimum dose needed for a given pathology.

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Yinghao Li^1,2,3, Adrian Paez^2,3, Di Cao^1,2,3, Chunming Gu^1,2,3, Kaihua Zhang^2,3, Xinyuan Miao^2,3, Jay Pillai^4,5, Peter M van Zijl^3,6, Christopher Earley⁷, Xu Li^2,3, and Jun Hua^2,3
1Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ³Neurosection, Division of MRI Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁵Department of Neurology, Johns Hopkins University School of Medicine, Baltimtore, MD, United States, ⁶F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimtore, MD, United States, ⁷Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Keywords: Contrast Agent, Blood vessels

Iron Dextran is a widely used FDA-approved ultra-small-superparamagnetic-iron-oxides (USPIO) to treat iron deficiency anemia in patients. Here, we evaluate the feasibility of using Iron Dextran as an MRI contrast agent for imaging arterial and venous blood vessels using multi-echo susceptibility weighted imaging (SWI) MRI at 7T. Phantom experiments were performed to measure relaxivity values (r1 and r2) for Iron Dextran in blood. Pre- and post-infusion MRI images were acquired in human subjects from which maps of arteries and veins were extracted. The post-contrast SWI images showed enhanced susceptibility difference between blood and the surrounding tissue in both arteries and veins.

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Daniëlle van Dorth¹, Ahmad Alafandi², Krishnapriya Venugopal², Aurélien Delphin³, Dirk H. J. Poot², Thomas Christen³, Marion Smits^2,4,5, Jeroen de Bresser⁶, Juan Hernandez Tamames², and Matthias J. P. van Osch^1,4
1C. J. Gorter MRI Center, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands, ²Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, Netherlands, ³University Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences, Grenoble, France, ⁴Medical Delta, Delft, Netherlands, ⁵Brain Tumor Center, Erasmus MC Cancer Institute, Rotterdam, Netherlands, ⁶Radiology, Leiden University Medical Center, Leiden, Netherlands

Keywords: Simulations, DSC & DCE Perfusion

In quantitative DSC-MRI, the concentration-time course is obtained from the MR signal changes following a bolus injection of contrast agent. The generally assumed linear relationship between ΔR₂^* and contrast agent concentration is not always valid. In this study a realistic 3D simulation model was used to establish the characteristics of this relationship in whole-blood and brain tumor tissue. The results show an improved performance of the 3D simulation model compared to its 2D version. In addition, the relationship between ΔR₂^* and contrast agent concentration appeared to be dependent on the B₀ direction and MR sequence.

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Nikorn Pothayee¹, Stephen Dodd¹, Li Liu¹, Gary Zabow², and Alan Koretsky^1
1National Institutes of Health, Bethesda, MD, United States, ²National Institute of Standards and Technology, Boulder, CO, United States

Keywords: Contrast Agent, Cell Tracking & Reporter Genes

In this study, gold coated microfabricated gold-coated iron particles are used for in vitro and in vivo labeling of immune cell and neural precursors, respectively for MRI. These particles have a pure iron core and protective layer of gold and exhibit extremely high magnetic moment relative to more commonly used, chemically synthesized, iron-oxide based particles. Following in situ labeling of neural precursor cells, we show that the migration of a large pool of individual cells can be visualized in time-lapse and longitudinal MRI.

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Yeon Ji Chae¹, Mi-hyun Kim^2,3, Chul-Woong Woo⁴, Sang-Tae Kim⁴, Do-Wan Lee⁵, Hwon Heo¹, Monica Young Choi⁴, Yoonseok Choi⁶, Kyung Won Kim^1,4, and Dong-Cheol Woo^1,4
1Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of, ²Department of Radiation Science & Technology, Jeonbuk National University, Jeonbuk, Korea, Republic of, ³Trial Informatics. Inc, Seoul, Korea, Republic of, ⁴Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea, Republic of, ⁵Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of, ⁶Medical Research Institute, Gangneung Asan Hospital, Gangneung-si, Gangwon-do, Korea, Republic of

Keywords: Contrast Agent, Contrast Agent, Magnetic resonance lymphography, Iron-oxide-based T1 contrast agent

The novel iron-oxide-based T1 contrast agent may be an optimal contrast agent for MR lymphangiography, because it enhances the lymphatics only without venous contamination for more than 1 hour. It can overcome the limitations of gadolinium-based contrast agents such as venous contamination and rapid washout.

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Stephen Dodd¹, Natalia Gudino¹, O Zadorozhnii², M Staňo², J Hajduček², J. A. Arregi², Vojtech Uhlíř², H. Doug Morris³, Mladen Barbic⁴, and Alan Koretsky^1
1Laboratory of Functional and Molecular Imaging, NINDS, National Institutes of Health, Bethesda, MD, United States, ²Ceitec Magnetism, Central European Institute of Technology, Brno, Czech Republic, ³Uniformed Services University of the Health Sciences, Bethesda, MD, United States, ⁴NYU Langone Health - Tech4Health Institute, New York, NY, United States

Keywords: Contrast Agent, Cell Tracking & Reporter Genes, Magnetocaloric material

We present progress towards smaller magnetocaloric samples, that drastically change magnetic moment and hence T2* contrast when switched with external magnetic field or temperature, with the eventual goal of achieving a size appropriate for cell tracking.  To that end a FeRh sample was microfabricated with a thickness of 200 nm, and patterned with varying linear dimensions from 500 micron down to 1 micron square.  We demonstrate that this sample may be switched with temperature and with external field through imaging at 4.7 and 11.7T and with the application of pulsed B0 insert coil.

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Sean William McRae¹, Michael Cleary², Francisco Martinez³, Ying Xia³, Peter Caravan², Eric Gale², John Ronald³, and Timothy Scholl^3
1Medical Biophysics, Western University, London, ON, Canada, ²Massachusetts General Hospital, Boston, MA, United States, ³Western University, London, ON, Canada

Keywords: Contrast Agent, Molecular Imaging

This work investigated the performance of a novel class of Mn(II) T1 contrast agents made from a commercially available chelator with various lipophilic targeting moieties added to promote uptake through the human derived OATP1B1 and OATP1B3 transporters. Agent performance was assessed in vitro using cells engineered to express the human OATPs, and in vivo by assessing liver uptake in mice where other OATP isoforms are present. In vitro measurements suggested targeting of agents to human OATPs where in vivo imaging revealed strong contrast enhancement in murine livers, with no evident toxicity at a 0.1 mmol/kg dose.

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Ece Su Sayin¹, Vittorio Stumpo², Jacopo Bellomo², Julien Poublanc³, Marco Piccirelli⁴, James Duffin¹, Vepeson Wijeya ³, Athina Pangalu⁴, Andrea Bink⁴, Bence Nemeth ⁴, Zsolt Kulcsar⁴, David John Mikulis³, Joseph Arnold Fisher¹, Olivia Sobcyzk ³, and Jorn Fierstra ^2
1Physiology, University of Toronto, Toronto, ON, Canada, ²Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland, ³University Health Network, Toronto, ON, Canada, ⁴Department of Neuroradiology, University Hospital Zurich, Zurich, Switzerland

Keywords: Contrast Agent, Perfusion

Dynamic susceptibility contrast perfusion imaging is clinically acquired using Gadolinium based contrast agents (GBCA), however, there remain many drawbacks. We show that in patients with steno-occlusive disease perfusion imaging using hypoxia-induced dOHb have a high degree of similarity to those obtained using GBCA. 

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Hamidreza saeidi ^1,2, Morteza Mozaffari², Serhat Ilbey¹, Jochen Leupold¹, and Michael Bock^1
1Division of Medical Physics, Department of Radiology, University Medical Center Freiburg, Freiburg, Germany, ²Faculty of Physics, University of Isfahan, Isfahan, Iran (Islamic Republic of)

Keywords: Contrast Agent, Relaxometry, Relaxometery, longitudinal Relaxation Time

Magnetic resonance imaging (MRI) contrast agents with both intrinsic high r₁ and r₂ relaxivities are desirable in medical diagnosis to achieve highly accurate and ambiguity-free MR images. Here, we report synthesis and MRI tests of Europium doped Mn-Zn ferrite (EuMZF) nanoparticles at different magnetic field strengths. EuMZF nanoparticles showed significant improvement in both positive (T1) and negative (T2) contrasts. The results showed that by increasing magnetic field, r₁ relaxivity decreased while r₂ increased so that the EuMZF is suitable as a dual-mode contrast at 1.5 and 3T but it is a T2 agent at 7 and 9.4T.

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Patrick Werner^1,2, Matthias Taupitz², Sophia Ber³, and Leif Schröder^1
1German Cancer-research center (DKFZ), Heidelberg, Germany, ²Charite Berlin, Berlin, Germany, ³Universität Heidelberg, Heidelberg, Germany

Keywords: Contrast Agent, Relaxometry, GBCA, gadolinium, long-term deposition, GAGs, dextran sulfate

Detailed biochemical information on the long-term deposition of Gd³⁺ in the body after administration of GBCAs is still missing. Glycosaminoglycans should be considered as chelators of released Gd³⁺. We used dextran-sulfate to study the effect of polysaccharides with different molecular weights on the observable relaxivity. Chelation was observed through an increase in relaxation. Moreover, a molecular weight-specific shielding revealed by subsequent reduced R₁ occurs at higher polysaccharide/Gd-ion ratios. This coincided with observations of Gd-induced aggregation. Similar shielding of re-chelated Gd³⁺can lead to an underestimation of deposited Gd-ions in the body and requires further research.

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Khallil Taverna Chaim¹, Mayara Klimuk Uchiyama^1,2, Robson Raphael Guimaraes², Koiti Araki², and Claudia da Costa Leite ^1
1School of Medicine - Radiology, University of Sao Paulo, Sao Paulo, Brazil, ²Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil

Keywords: Contrast Agent, Contrast Agent, nanoparticles

MRI is one of the best imaging techniques in clinical analysis because it is non-invasive and has high resolution. Contrast agents are used to further improve these images, as they increase the level of soft tissue detail, differentiating regions of interest. Currently, Gd-based contrast agents have important precautions. In this work we present a new nanoparticle based on iron oxide, with 4 nm and positive contrast (T1-weighted). Thus, effects similar to gadoteric acid, with reduced signal persistence and partial renal excretion, indicating great stability, this new paramagnetic nanoparticle has great potential to be applied as a contrast agent in MRI.

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Tapas Bhattacharyya¹, Jeremy M.-L. Hix¹, Christiane L. Mallett¹, and Erik M. Shapiro^1
1Radiology and Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI, United States

Keywords: Molecular Imaging, Cell Tracking & Reporter Genes

Hepatic OATPs are a promising molecular imaging reporter gene for MRI yet its translation for human studies is limited by the reported extremely high dose of contrast agent required (>40x clinical dose) for robust detection of engineered cells in vivo. Here we describe studies that culminated in the in vivo MRI detection of OATP-overexpressing cells using standard clinical doses. OATP-overexpression was accomplished by lentiviral transduction of tumor cells, followed by MRI screening to determine the best performing OATPs.  In vivo MRI of OATP-overexpressing tumors was accomplished using a combination of both T1-weighted and dynamic contrast enhanced (DCE-) MRI.

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Calin Nicolescu¹, Da Sun¹, Songqi Gao¹, and Zheng-Rong Lu^1,2
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, United States

Keywords: Molecular Imaging, Cancer, Breast

Developing new molecular targeted therapies for triple negative breast cancer remains an obstacle. MANCR is a long noncoding RNA overexpressed in TNBC that sustains aggressive breast cancer growth. Silencing its expression with siRNA nanoparticles suppresses tumor growth, and treatment efficacy can be assessed by MRMI with a targeted contrast agent, MT218. Reduction in contrast-to-noise ratio following treatment confirmed effectiveness of siRNA therapy and allowed regular monitoring of tumor inhibition. RNA therapy shows promise as a new approach for treating aggressive breast cancer, and MRMI with the targeted contrast agent is a non-invasive imaging tool for TNBC detection and therapeutic surveillance.

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Geoffrey J. Topping¹, Salma Mansi², Kilian M. A. Müller², Zahid Hussain³, Sarah Dummert³, Carolin Rickert⁴, Sebastian P. Schwaminger⁵, Younzhe Zou², Diana M. Rojas-González², Sonja Berensmeier⁵, Oliver Lieleg⁴, Roland Fischer³, Petra Mela², and Franz Schilling^1
1Department of Nuclear Medicine, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, ²Medical Materials and Implants, Department of Mechanical Engineering, TUM School of Engineering and Design, & Munich Institute of Biomedical Engineering, Technical University of Munich, Garching, Germany, ³School of Natural Sciences and Catalysis Research Center, Technical University of Munich, Garching, Germany, ⁴Biomechanics, Department of Materials Engineering, TUM School of Engineering and Design, Technical University of Munich, Garching, Germany, ⁵Chair of Bioseparation Engineering, School of Engineering and Design, Technical University of Munich, Garching, Germany

Keywords: Contrast Mechanisms, Preclinical, Tissue Engineering

Polycaprolactone scaffolds were melt electrowritten with and without included metal-organic frameworks (MOF) or nanoparticles (USPIO). MR images and relaxation rate (R1, R2, R2*) maps were acquired of scaffolds in agar and blood. Pure polycaprolactone showed weak or no contrast. Addition of MOF or USPIOs produced strong T2* contrast. Tensile properties were preserved up to 0.2 w/w% USPIOs. MOFs produced strong w/w% dependent antibacterial effects when included in scaffolds.

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Elizabeth Jane Fear^1,2, Antonella Antonelli¹, Pasant Abdalla¹, Elisa Zamboni³, Marie-Christine Labarthe-Last², Victoria Annis², Simon Benedict Duckett², Mauro Magnani¹, and Aneurin James Kennerley^2,4
1Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy, ²Centre for Hyperpolarisation in Magnetic Resonance (CHyM), Chemistry, University of York, York, United Kingdom, ³Psychology, University of York, York, United Kingdom, ⁴Sport and Exercise Science, Institute of Science, Manchester Metropolitan University, Manchester, United Kingdom

Keywords: Contrast Agent, Contrast Agent, red blood cells, Super Paramagnetic Iron Oxide Nanoparticles

We have developed a next generation, safe, personalised iron-based contrast agent (CA) for empowering functional Magnetic Resonance Imaging (fMRI). Our proprietary method uses state-of-the-art red blood cell (RBC) encapsulation technology to engineer biocompatible super-paramagnetic CAs able to withstand rapid clearance from the bloodstream by macrophages (as part of the mononuclear phagocytic/reticuloendothelial system). The agent is validated in a multi-modal (concurrent fMRI and intrinsic optical imaging) preclinical rat model as a novel CA for the mapping of cerebral blood volume (CBV) in response to somatosensory stimulation, providing a non-BOLD alternative for accurate, high-resolution mapping of brain function.

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Hamidreza saeidi ^1,2, Morteza Mozaffari², Serhat Ilbey¹, and Michael Bock^1
1Division of Medical Physics, Department of Radiology, University Medical Center Freiburg, Freiburg, Germany, ²Faculty of Physics, University of Isfahan, Isfahan, Iran (Islamic Republic of)

Keywords: Contrast Mechanisms, Contrast Agent, Relaxometery, longitudinal Relaxation Time

MRI contrast agents have gained extensive attention for providing contrast between normal and abnormal tissue. However, single-mode contrast agents do not always provide the required contrast enhancement for disease detection. One effective strategy for avoiding ambiguous images is to design MRI contrast agents with simultaneous T1 and T2 shortening effects. The purpose of this work is to synthesize rare earth ions doped Mn-Zn ferrite (ReMZF) nanoparticles and characterize them with a 1.5T MRI scanner in vitro. The ReMZF exhibited high r₁ and r₂ relaxivities but moderate r₂/r₁ which make them suitable to be used as dual-mode contrast agents.

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Chih-Hsien Tseng¹, Martijn Nagtegaal¹, Jaap Jaspers², Alejandra Mendez Romero², Piotr Wielopolski³, Marion Smits^3,4, Matthias J.P. van Osch^4,5, and Frans Vos^1,3,4
1Imaging Physics, Delft University of Technology, Delft, Netherlands, ²Radiation Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, Netherlands, ³Radiation and Nuclear Medicine, Erasmus MC, University Medical Center, Rotterdam, Netherlands, ⁴Medical Delta, Delft, Netherlands, ⁵Radiology, C.J. Gorter MRI center, Leiden University Medical Center, Leiden, Netherlands

Keywords: Contrast Mechanisms, DSC & DCE Perfusion

Both inflow and partial volume effects (PVE) are sources of error when measuring the arterial input function (AIF) in DCE-MRI. We proposed a method that estimated the perceived pulse number of spins, and then corrected with these such that both effects were simultaneously compensated. Simulation data demonstrated that the reconstructed AIFs showed only marginal bias. In addition, the algorithm yielded highly correlated reconstructed curves over a wide range of PVEs in clinical data. Our findings show that the PVE can be compensated by considering it as part of the inflow correction as it exhibits similar confounding effects when measuring DCE-AIFs.

Zhongling Wang¹, AN CHEN¹, Hongwei Lu², and Xiance Zhao^3
1Shanghai General Hospital，School of Medicine ，Shanghai jiaotong University, Shanghai, China, ²Lthink Medical Institute, Guangzhou, China, ³Philips Healthcare, Shanghai, China

Keywords: Molecular Imaging, Multimodal

 We developed a novel nanoplatform-based MMP9-responsive T2–T1 switching MRI contrast agent, which can be used not only for non-invasive visualization and quantitative analysis of MMP9 activity, but also as a carrier in photothermal sensitization chemotherapy. The nanoplatform acts as a T2 contrast agent in physiological conditions ,then transform  into a T1 contrast agent by MMP9 stimulus. We have demonstrated that the changes R1 and R2/R1 values are MMP9 concentration dependent  in tumors. The combination of PMPSD with laser irradiation was more effective than single chemo-/photothermal therapy, and up-regulation of MMP9 in the tumor could eanhance the nanoplatform’s therapeutic effect.

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Sheng Shen¹, David E. J. Waddington², Marie Zhang³, and Matthew S. Rosen^1,4,5
1MGH/A. A. Martinos Center for Biomedical Imaging, Boston, MA, United States, ²The University of Sydney, Sydney, Australia, ³Imagion Biosystems, Ltd, San Diego, CA, United States, ⁴Department of Physics, Harvard University, Cambridge, MA, United States, ⁵Harvard Medical School, Boston, MA, United States

Keywords: Contrast Agent, Modelling

Characterization of the parameters of superparamagnetic iron oxide nanoparticles (SPIONs) can guide synthesis of optimized particles for use in magnetic resonance imaging (MRI). With a goal of application of SPIONs in ultra-low field (ULF) MRI, we investigated the properties of SPIONs, and conducted imaging on a 6.5 mT MRI scanner. Specifically, we measured the NMR relaxivity and susceptibility of different SPIONs sample, both dominated by the core size of SPIONs. We also implemented susceptibility imaging using an bSSFP sequence to obtain positive contrast images of SPION phantoms, and present here a method to optimize the ULF susceptibility MRI images.