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Deepti Upadhyay¹, Shubhangi Agarwal¹, Jinny Sun¹, Robert A Bok¹, Rahul Aggarwal², Donna M Peehl¹, John Kurhanewicz¹, and Renuka Sriram^1
1Radiology and Biomedicla Imaging, University of California, San francisco, San Francisco, CA, United States, ²University of California, San francisco, San Francisco, CA, United States

Keywords: Cancer, Metabolism, Models, metastasis, tumor, microenvironment

Metabolic plasticity due to cell intrinsic properties, its inherent dependence on organ of origin as well as its interaction with microenvironmental factors are considered key to establishment of metastases and is believed to be heterogenous. This in turn has a significant impact and differential response to the treatment of choice making this a lethal disease. Here, we investigate using magnetic resonance imaging and spectroscopy the biochemical profile of the same patient derived xenografts of small cell neuroendocrine prostate cancer, an aggressive phenotype, implanted in two different sites, liver and bone that are associated with reduced survival.

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Xiuhong Guan¹, Yue Zhao¹, Xin Huang², Zhiyong Wang³, and Ruimeng Yang^4
1Department of Radiology, First Affiliated Hospital of Jinan University, Guangzhou, China, ²Guangzhou Medical University, Guangzhou, China, ³School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, China, ⁴Department of Radiology, Guangzhou First People’s Hospital, Guangzhou, China

Keywords: Molecular Imaging, Cancer, tumor, dual-modality imaging, STING pathway, Immunotherapy

Due to the high incidence and mortality rate, breast cancer has become the major cause of cancer death among females. This study reports a kind of functional nanocomposite, which was designed to comprises Pluronic F127 to self-assembly manganese carbonyl (MnCO) and IR780 dyes into one system, exhibiting NIR-II and MR dual-modal imaging guided STING pathway and anti-tumor immunity against triple-negative breast cancer.

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Keyu Zhuang^1,2, Rocco Romagnuolo³, Daniel A. Szulc^1,2, Hai-Ying Mary Cheng^4,5, Michael A. Laflamme^3,6,7, and Hai-Ling Margaret Cheng^1,2,8
1Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada, ²Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada, ³McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada, ⁴Department of Biology, University of Toronto Mississauga, Mississauga, ON, Canada, ⁵Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada, ⁶Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada, ⁷Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, ⁸The Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada

Keywords: Molecular Imaging, Cell Tracking & Reporter Genes, stem cell

To extend our previously reported bright-ferritin cell tracking platform to monitoring stem cell therapy, we investigated tracking human embryonic stem cells transplanted intramuscularly in immune-compromised mice. With this technology, the stem cells impart a bright, T1-induced contrast. In-vitro assays of viability and pluripotency, and imaging both in vitro on cell pellets and in vivo in mice were performed. Monitoring mice on MRI over two months confirmed the ability to assess cell survival and teratoma formation non-invasively.

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Devin Raine Everalo Cortes^1,2,3,4, Margaret C. Stapleton^2,4, Samuel Wyman^2,4, Kristina E. Schwab^5,6, Noah W. Coulson^2,7, Dalton R West^2,4, Thomas Becker-Szurszewski^5,6, Sean Hartwick^5,6, Anthony G. Christodoulou⁸, and Yijen L Wu^2,3,4,9
1Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States, ²Department of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States, ³Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Rangos Research Center Small Animal Imaging Core, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States, ⁵Rangos Research Center Animal Imaging Core, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States, ⁶Department of Pediatrics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, United States, ⁷Rangos Research Center Small Animal Imaging Core, University of Pittsburgh, Pittsburgh, PA, United States, ⁸Biomedical Imaging Research Institue, Cedars-Sinai Medical Center, Los Angeles, CA, United States, ⁹Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States

Keywords: Contrast Agent, Placenta, Perfusion, PCA, FASD, DCE

Placental development is a dynamic process, and the timing of placental development events is crucial for appropriate fetal development. However, the placenta itself remains critically understudied in the context of fetal development disorders. We propose novel models for correlating DCE-MRI perfusion estimation with biologically relevant compartments and extracting dynamic biomarkers for placental development. We validate this model by demonstrating that placental perfusion is disrupted in a murine model of peri-conceptual alcohol exposure, and that this disruption occurs differently across various compartments from E14.5 to E17.5.

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Behnaz Ghaemi¹, Yuguo Li², Martin Pomper¹, Jeff Bulte¹, Peter van Zijl², and Aline Thomas^1
1Johns Hopkins University, Baltimore, MD, United States, ²Kennedy Krieger Institute, Baltimore, MD, United States

Keywords: Cancer, Preclinical, Prostate Cancer

Increased utilization of glutamine is characteristic of many advanced, aggressive cancers. Established glutamine imaging strategies require the use of labeled probes (positron emission tomography, hyperpolarized spectroscopy) that can limit their accessibility. Here, we investigated the utility of chemical exchange saturation transfer (CEST) MRI upon intravenous injection of unlabeled alanine to monitor differences in cellular glutamine uptake as a potentially complementary imaging biomarker for profiling cancers and monitoring their progression.

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Xiaokai Wang¹, Angela Yee¹, Jiayue Cao¹, Ashley Cornett¹, Fatimah Alkaabi¹, Yushi She¹, Ulrich Scheven¹, and Zhongming Liu^1
1University of Michigan, Ann Arbor, MI, United States

Keywords: Data Acquisition, Animals

Anesthesia has been required for preclinical gastrointestinal MRI but may confound gastric physiology. This study demonstrates, for the first time, the feasibility of gastrointestinal MRI with awake rats, and reports the effects of anesthesia on gastric motor function. Results suggest that awake rats show greater rates of gastric emptying and intestinal filling, and stronger gastric and intestinal motility relative to those anesthetized. Anesthesia with 2.5% isoflurane can entirely stop muscle contraction. The methods and findings reported herein lay the foundation for using awake GI-MRI in preclinical studies of gastrointestinal function or dysfunction.

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Akira Sumiyoshi¹, Takahiro Nomoto², Megumi Iiyama¹, Kensuke Osada¹, Rumiana Bakalova¹, Nobuhiro Nishiyama², and Ichio Aoki^1
1National Institutes for Quantum Science and Technology, Chiba, Japan, ²Tokyo Institute of Technology, Yokohama, Japan

Keywords: Molecular Imaging, Cancer

Here we performed a molecular MR imaging study on patient-derived tumor xenografts (PDX) mouse model. In vivo molecular MR imaging demonstrated that proliferative vs. non-proliferative regions exist in PDX model and highly specific contrast agent such as PEGMnCap (pH-responsive nanoparticle based on Mn) can delineate active and hypoxic regions while small-molecular size contrast agent such as Gd-DOTA (gadoterate meglumine) can delineate non-active tumor regions. These MR image separations were not clearly obtained with a cancer cell line, suggesting more complex microenvironment of PDX model and may provide valid translational feedbacks for clinical practice.

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Andrea Capozzi^1,2, Yupeng Zhao³, Magnus Karlsson³, Esben Søvsø Szocska Hansen⁴, Lotte Bonde Bertelsen⁴, Christoffer Laustsen⁴, Mathilde Hauge Lerche³, and Jan Henrik Ardenkjær-Larsen^3
1IPHYS, EPFL, Lausanne, Switzerland, ²Health Tech, Technical University of Denamrk, Kgs. Lyngby, Denmark, ³Health Tech, Technical University of Denmark, Kgs. Lyngby, Denmark, ⁴Aarhus University Hospital, Aarhus, Denmark

Keywords: New Devices, Hyperpolarized MR (Non-Gas), transportable hyperpolarization

Hyperpolarization via dissolution Dynamic Nuclear Polarization has the potential to revolutionize diagnostic radiology. Nevertheless, the methodology struggles to enter everyday clinical practice. One of the reasons why broad consensus among clinicians is still missing lies in the technical complexity that characterize hyperpolarization via dDNP. Differently from PET, hyperpolarized MR contrast agent cannot be transported and have to be prepared on-site. We developed a robust methodology to change this paradigm. We herein present our latest updates on transportable hyperpolarization technology.

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Rohan S Virgincar¹, Shimrit Avraham², Kai H Barck¹, Joshua Webster³, Jeffrey Hung³, Aaron K Wong⁴, Hans D Brightbill⁴, Patrick Caplazi³, Bill Forrest⁵, Laura Bell⁶, Man Kin Choy¹, Andrey Shaw², Alex J de Crespigny⁶, and Luke Xie^1
1Translational Imaging, Genentech, South San Francisco, CA, United States, ²Research Biology, Genentech, South San Francisco, CA, United States, ³Research Pathology, Genentech, South San Francisco, CA, United States, ⁴Translational Immunology, Genentech, South San Francisco, CA, United States, ⁵Bioinformatics, Genentech, South San Francisco, CA, United States, ⁶Clinical Imaging Group, Genentech, South San Francisco, CA, United States

Keywords: Kidney, Diffusion Tensor Imaging

Voxel-based analysis (VBA) can enable voxel-wise statistical analysis of control and disease images without the need for user-defined regions-of-interest (ROI), but has not been widely used beyond neuroimaging. We demonstrate that VBA can be successfully applied to mouse models of renal fibrosis. Diffusion MRI parametric maps of control and disease groups were registered non-linearly to a common coordinate space and VBA successfully identified distinct regions of fibrosis in two different models, which strongly corresponded to whole-kidney histology. VBA therefore has potential in the clinic to identify regions of fibrosis, where whole-kidney histology cannot be obtained.

Jinhuan Xie¹, Liling Long¹, Chenhui Li¹, and Huiting Zhang^2
1The First Affiliated Hospital of Guangxi Medical University, Nanning, China, ²Siemens Healthineers, Wuhan, China

Keywords: Liver, Diffusion/other diffusion imaging techniques

The purpose of this study was to explore the feasibility of preoperative non-invasive evaluation of immunohistochemical indexes of hepatocellular carcinoma, CK19 and Hep par-1 positive, with Fractional Order Calculus (FROC) model using nude mice model. Results showed that the diffusion coefficient D and fractional order derivative in space β had statistically significant differences and good diagnostic performances between the CK19 and Hep par-1 positive groups. These finding showed that FROC is useful diffusion model and D and β are useful biomarkers in liver cancer with expression of the immunohistochemical indexes CK19 and Hep par-1.

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Victoria Laney¹ and Zheng-Rong Lu^1
1Case Western Reserve University, Cleveland, OH, United States

Keywords: Molecular Imaging, Cancer

PDAC is a highly aggressive malignant cancer and the 3rd leading cause of cancer related deaths in the US. The aggressive nature of PDAC is in part due to the desmoplastic tumor microenvironment, which promotes rapid tumor growth and impedes therapeutic efficacy of conventional therapies. Immune checkpoint inhibitors have showed specific efficacy in PDAC promotes extracellular remodeling for effective treatment of aggressive tumors. In this study we investigated the ability of an MR molecular imaging technology for image guidance and therapeutic monitoring of PD-L1 treated PDAC tumors.  

Rong Zhang¹ and Zhang Hua^1
1Department of Radiology, Affiliated Hospital of Qingdao University, Qingdao, China

Keywords: Molecular Imaging, DSC & DCE Perfusion, Magnetic resonance angiography

Timely evaluating the abundance of vessels and infiltration by noninvasive ways together with synchronous photothermal therapy (PTT) still faces great challenges. A multifunctional and biocompatible nanoprobes (NaBiF4: Gd@PDA@PEG) with high longitudinal relaxation rate  and photothermal conversion efficiency  was designed as promising photosensitizer for tumor PTT and contrast agent for MR imaging. The anatomic decrease and thinning of tumor blood vessels could be observed in real-time using noninvasive MR angiography ( TRICKS and DSC-PWI) during PTT.  We demonstrated that the vascular invasion status of tumor during PTT can be monitored by utilizing our multifunctional nanoprobes, which provide possibility for clinical transformation.

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Qian Wan¹, Hao Peng¹, Feng Liu², Chuanli Cheng¹, Xiaoyi Liu², Changjun Tie¹, Xin Liu¹, Yi Wang², and Chao Zou^1
1Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China, ²Peking University People's Hospital, Beijing, China

Keywords: Contrast Agent, Liver

The early detection of the inflammation and fibrosis grade are important to Nonalcoholic steatohepatitis (NASH) patients. Gadoxetic acid with MRI T1 quantitation is one of promising noninvasive method. However, intracellular hepatocyte lipid is a confounding factor for the accurate T1 quantitation in NASH case. Here, we used a water specific T1 (wT1) mapping with dynamic gadoxetic acid enhanced MRI in a rat NASH model induced by MCD diet.  The results demonstrated that gadoxetic acid was not helpful to differentiate the inflammation and fibrosis severity in the early stage of NASH in rats.

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Ren Li¹, Yong Zhang², and Xiao-Yong Zhang^1
1Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, 200433, Shanghai, China, ²GE. Healthcare, shanghai, China

Keywords: Spectroscopy, Quantitative Imaging, PM2.5

PM2.5 has been shown to be harmful to the central nervous system of mammals. Long term exposure to PM2.5 may cause changes in brain neural metabolites. However, there were few magnetic resonance spectroscopy (MRS) studies in rodents under PM2.5 exposure. In this work, we developed an air enrichment system to concentrate PM2.5. Using 1H-MRS, we successfully observed the brain metabolic profile of olfactory bulb in PM2.5-exposed mice, and found the concentration changes of some key metabolites in the brain, indicating that PM2.5 has a non-negligible impact on brain metabolism.

Dong Liu¹, Lei Pan², Weiyin Vivian Liu³, and Wenzhen Zhu^1
1Department of Radiology, Tongji Hosptial of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China, ²Faculty of Resources and Environmental Science, Hubei University, Wuhan, China, ³MR Research, GE Healthcare, Wuhan, China

Keywords: Liver, Animals, assess fish health

Quantitative methods of fish lipid accumulation have attracted a lot of attention in ecotoxicology. Traditionally, invasive approaches were time-consuming and generally required animal sacrifice, drastically restricting applicability in ecotoxicology. In this study, a noninvasive MRI approach was proposed to quantify lipid accumulation in two represented fish species with IDEAL-IQ and Cube-Flex-T2 sequences. We demonstrated the accuracy of our novel MRI approach in quantifying fish lipid accumulation. In addition, we conducted  cadmium exposure experiment  and observed no significant differences in lipid deposition between MRI and traditional methods. Thus, this MRI method could have a wide range of applications in ecotoxicological research.

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El-Sayed H. Ibrahim¹, Abdul Parchur¹, Srividya Kidambi¹, Mingyu Liang¹, and Allen Cowley^1
1Medical College of Wisconsin, Milwaukee, WI, United States

Keywords: Kidney, Hypertension

T2*-based blood oxygenation level-dependent (BOLD) MRI has been used to investigate renal metabolism in the rat’s kidney, which is typically conducted on high-field small-animal MRI scanners. However, T2* is very small at high-field strength, e.g., 9.4T, which results in borderline signal-to-noise ratio and questions the measurements accuracy. In this study, we investigated the capability of BOLD imaging of the rat’s kidney on a clinical 3T MRI scanner, where T2* is much higher, and compared the results to those acquired on 9.4T small-animal scanner. The results showed the capability for distinguishing different oxygenation levels in the kidney on clinical 3T scanners.

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Jin Zhang¹, Sawwal Qayyum¹, Jonghyun Bae¹, Eddy Solomon¹, and Gene Kim^1
1Weill Cornell Medical College, New York, NY, United States

Keywords: Image Reconstruction, DSC & DCE Perfusion

In this study, we propose a contrast kinetic model-based GRASP (mGRASP) method which can improve the spatial image quality as well as temporal characteristics of DCE-MRI. The proposed mGRASP method was assessed with 9L rat glioma model and GL261 mouse glioma model in an Active Contrast Encoding (ACE)-MRI experiment which simultaneously measures the pre-contrast T₁ and contrast kinetic model parameters including intracellular water lifetime. The results show that mGRASP provides improved image quality and temporal patterns compared to GRASP.

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Antoine Cherix¹, Mohamed Tachount¹, and Jason Lerch^1,2
1Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ²Mouse Imaging Centre (MICe), Hospital for Sick Children, Toronto, ON, Canada

Keywords: Spectroscopy, Animals

³¹P-MRS experiments in mouse brain are scarce and often limited to ultra-high field scanners. We have recently reported that ³¹P-MRS is feasible in mouse brain at 7T as well. We now tested the potential of using saturation transfer experiments in the same setting to measure the creatine kinase rate in mouse brain.

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Elise Cosenza^1,2, Aurélien Trotier¹, Gauthier Massone¹, Emeline J Ribot¹, Laurent Petit², Sylvain Miraux¹, and Valery Ozenne^1
1CNRS, CRMSB, Bordeaux, France, ²CNRS, GIN IMN, Bordeaux, France

Keywords: Data Analysis, Animals, brain parcellation

3D T₁ templates of the mouse brain at 7T and 4.7T were created with a MP2RAGE pulse sequence. The template was next coregistered with the DORR atlas.  The resulting parcellation allows volume and T₁ measurements for each labels. The values obtained can be compared according to the magnetic field, intra and inter individual. Volumes were found in agreement with the literature. The T₁ measurements are reproducible between individuals and significantly different at 4.7T and 7T.

Jamil Nour Eddin¹, Hugo Dorez¹, and Valentina Curcio^1
1HawkCell, Marcy-l'Étoile, France

Keywords: Segmentation, Animals

Brain extraction in an MRI image is the first pre-processing step of a neuroimaging quantification pipeline. Once the brain is extracted, further post-processing becomes faster, more specific, and easier to implement and interpret. Existing brain extraction tools are mostly adapted to work on the human anatomy, or on specific animal species. This gives poor results when applied to animal brain images. We developed an atlas-based Veterinary Images Brain Extraction (VIBE) algorithm that is fully automatized and was successfully tested on different cats and dogs breeds, 3D and 2D MRI images, different contrasts (T1-weighted, T2-weighted and T2 FLAIR) and acquisition planes.