To begin searching the abstracts, please use the search feature above.

Digital Poster - Preclinical
Weekend and Oral

Digital Poster (no CME credit)

ISMRT Education Session

ISMRT Poster Presentations (no CME credit)

Traditional Poster/Educational Exhibit Posters (no CME credit)

Acquisition & Analysis Digital Poster Body Digital Poster Cardiovascular Digital Poster Contrast Mechanisms Digital Poster
Musculoskeletal Digital Poster Neuro Digital Poster Pediatrics Digital Poster Physics & Engineering Digital Poster
Machine Learning Digital Poster Quantitative Imaging Digital Poster YIA Digital Poster  

Preclinical Digital Poster (No CME Credit)
Session Title

The Bench: Preclinical Studies Throughout the Body

Program # 3740 - 3759
Wednesday, 07 June 2023 | 08:15

The Bench: Preclinical Studies Within the Brain

Program # 3914 - 3933
Wednesday, 07 June 2023 | 09:15

The Bench: Preclinical Studies Throughout the Body

Exhibition Halls D/E
Wednesday 8:15 - 9:15
Preclinical

3740
Computer 161
Metabolic similarity of prostate cancer patient-derived xenografts propagated in the bone versus liver
Deepti Upadhyay1, Shubhangi Agarwal1, Jinny Sun1, Robert A Bok1, Rahul Aggarwal2, Donna M Peehl1, John Kurhanewicz1, and Renuka Sriram1

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.

3741
Computer 162
manganese-based nanosystem for dual-modality imaging guided STING pathway with immunotherapy against triple-negative breast cancer
Xiuhong Guan1, Yue Zhao1, Xin Huang2, Zhiyong Wang3, and Ruimeng Yang4

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.

3742
Computer 163
A Novel MRI Platform for Long-term Stem Cell Tracking In Vivo
Keyu Zhuang1,2, Rocco Romagnuolo3, Daniel A. Szulc1,2, Hai-Ying Mary Cheng4,5, Michael A. Laflamme3,6,7, and Hai-Ling Margaret Cheng1,2,8

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.


3743
Computer 164
Modeling Mouse Placental Perfusion Dynamics and Contractions via Dynamic Contrast Enhancement MRI
Devin Raine Everalo Cortes1,2,3,4, Margaret C. Stapleton2,4, Samuel Wyman2,4, Kristina E. Schwab5,6, Noah W. Coulson2,7, Dalton R West2,4, Thomas Becker-Szurszewski5,6, Sean Hartwick5,6, Anthony G. Christodoulou8, and Yijen L Wu2,3,4,9

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.


3744
Computer 165
ALAw-CEST MRI of the ASCT2 transporter in a mouse model of prostate cancer
Behnaz Ghaemi1, Yuguo Li2, Martin Pomper1, Jeff Bulte1, Peter van Zijl2, and Aline Thomas1

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.

3745
Computer 166
Gastrointestinal MRI with Conscious Rats
Xiaokai Wang1, Angela Yee1, Jiayue Cao1, Ashley Cornett1, Fatimah Alkaabi1, Yushi She1, Ulrich Scheven1, and Zhongming Liu1

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.

3746
Computer 167
Distinct contrast patterns in patient-derived tumor xenografts (PDX) mouse model revealed by pH-sensitive MR contrast agent
Akira Sumiyoshi1, Takahiro Nomoto2, Megumi Iiyama1, Kensuke Osada1, Rumiana Bakalova1, Nobuhiro Nishiyama2, and Ichio Aoki1

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.

3747
Computer 168
Rat angiography from far away: design and performance of a small bath cryostat with NMR capability for transport of hyperpolarized samples.
Andrea Capozzi1,2, Yupeng Zhao3, Magnus Karlsson3, Esben Søvsø Szocska Hansen4, Lotte Bonde Bertelsen4, Christoffer Laustsen4, Mathilde Hauge Lerche3, and Jan Henrik Ardenkjær-Larsen3

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.

3748
Computer 169
Voxel-based analysis of renal fibrosis with diffusion MRI in mouse models
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 Xie1

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.

3749
Computer 170
Fractional order calculus model in liver cancer with immunohistochemical indexes CK19 and Hep par-1: a preliminary animal study
Jinhuan Xie1, Liling Long1, Chenhui Li1, and Huiting Zhang2

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.

3750
Computer 171
MR Molecular Imaging of Pancreatic Cancer Reveals Differences in Tumor Microenvironment during Therapeutic Monitoring with Immunotherapy
Victoria Laney1 and Zheng-Rong Lu1

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.  

3751
Computer 172
Dynamic MR Imaging-guided Photothermal Therapy of Solid Tumor and Monitoring of Vascular Invasion
Rong Zhang1 and Zhang Hua1

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.

3752
Computer 173
Can dynamic gadoxetic acid-enhanced MRI combined with water specific T1 mapping predict the early-stage of Nonalcoholic Steatohepatitis in rat?
Qian Wan1, Hao Peng1, Feng Liu2, Chuanli Cheng1, Xiaoyi Liu2, Changjun Tie1, Xin Liu1, Yi Wang2, and Chao Zou1

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.

3753
Computer 174
1H-MRS reveals changes of metabolites in the olfactory bulb of PM2.5-exposed mice
Ren Li1, Yong Zhang2, and Xiao-Yong Zhang1

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.

3754
Computer 175
Three-dimensional CUBE MR imaging accurately quantified lipid accumulation in reflection of longitudinal fish health
Dong Liu1, Lei Pan2, Weiyin Vivian Liu3, and Wenzhen Zhu1

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.

3755
Computer 176
Optimized metabolic imaging of rat’s kidney on clinical MRI scanners. Comparison to small-animal high-field imaging
El-Sayed H. Ibrahim1, Abdul Parchur1, Srividya Kidambi1, Mingyu Liang1, and Allen Cowley1

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.

3756
Computer 177
Contrast Kinetic Model-based GRASP Reconstruction for Small Animal Imaging at 7T
Jin Zhang1, Sawwal Qayyum1, Jonghyun Bae1, Eddy Solomon1, and Gene Kim1

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.

3757
Computer 178
Assessment of mouse brain creatine kinase rate using 31P-MRS at 7 Tesla
Antoine Cherix1, Mohamed Tachount1, and Jason Lerch1,2

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.

3758
Computer 179
In vivo T1-mapping template of the mouse brain at 4.7T and 7T with a MP2RAGE sequence
Elise Cosenza1,2, Aurélien Trotier1, Gauthier Massone1, Emeline J Ribot1, Laurent Petit2, Sylvain Miraux1, and Valery Ozenne1

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.

3759
Computer 180
Automatic brain extraction on multi-contrast dogs and cats MRI images
Jamil Nour Eddin1, Hugo Dorez1, and Valentina Curcio1

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.


The Bench: Preclinical Studies Within the Brain

Exhibition Halls D/E
Wednesday 9:15 - 10:15
Preclinical

3914
Computer 161
Longitudinal simultaneous fMRI and mesoscale calcium imaging in a mouse model of Alzheimer’s disease
Francesca Mandino1, Xilin Shen2, Gabriel Desrosiers-Gregoire3, David O'Connor4, Bandhan Mukherjee5, Kristin DeLuca5, Ali Hamodi4, Ashley Owens5, Yonghyun Ha1, An Qu1, John Onofrey4, Xenophon Papademetris4, Mallar Chakravarty3, Michael C. Crair4, Stephen M Strittmatter5, and Evelyn Lake1

1Radiology, Yale University, New Haven, CT, United States, 2Radiology and bioimaging sciences, Yale University, New Haven, CT, United States, 3Douglas Mental Health University Institute, McGill, Montreal, QC, Canada, 4Yale University, New Haven, CT, United States, 5Neurology and Neuroscience, Yale University, New Haven, CT, United States

Keywords: Alzheimer's Disease, Brain

Multimodal neuroimaging plays an active role in understanding clinically accessible biomarkers of health and disease. Using simultaneous mesoscopic calcium imaging and BOLD-fMRI, we examine spontaneous activity in a GCaMP-positive mouse model of Alzheimer’s disease (AD)—longitudinally—at 4, 6, and 9 months. We find that both imaging modalities show early wide-spread changes in connectivity in AD compared to controls, with diverging trends at 6months. Intriguingly, these neuroimaging changes precede typical behaviour deficits. Further, preliminary evidence of cross-modal uncoupling hints at a complex relationship between excitatory neural activity (calcium imaging data), and the BOLD signal that is affected by AD-related progression.

3915
Computer 162
MRI detection of gene expression in the mammalian brain using the Manganese transporter Zip14
Harikrishna Rallapalli1, Eleanor C McCall1, Nadia Bouraoud1, and Alan P Koretsky1

1Laboratory of Functional and Molecular Imaging, NIH/NINDS, Bethesda, MD, United States

Keywords: Molecular Imaging, Cell Tracking & Reporter Genes, Brain, Neuroscience, Cell-type Imaging, Brain connectivity

We report the use of Zip14, a Manganese transporter, as an MRI-visible gene expression reporter system. Mice were intracranially injected into various brain areas with AAVs carrying a plasmid construct of Synapsin promoter for neuronal-specific expression, Zip14, and histological marker. MRI was performed immediately after, 2 weeks after, and 4 weeks after injection. Significant, large magnitude hyperintensity was observed 2 and 4 weeks after injection, but not immediately after, at the injection site and areas projecting away or towards the injection site. This gene expression reporter system is viable without the use of additional contrast agents or non-standard imaging protocols.

3916
Computer 163
Identifying spreading depression during coma induction with multi-modal fMRI
Yuanyuan Jiang1, Zeping Xie1, Wenchao Yang1, Bei Zhang1, David Hike1, Andy Liu1,2, Brian L. Edlow1,3, and Xin Yu1

1Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, 2Department of Neuroscience, Boston University, Boston, MA, United States, 3Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, United States

Keywords: Stroke, Ischemia, coma, spreading depression

We have demonstrated spreading depression as a key event contributing to coma induction following the ET-1 injection to the brainstem of rats. Multi-modal fMRI enables the whole brain functional mapping to present the spatial dynamic changes during coma induction, in particular, paired with the incidence of SD events. 

3917
Computer 164
Therapeutic response assessment to IDH inhibitor using hyperpolarized [5-12C-1-13C]α-ketoglutarate MRSI in rat models of low-grade glioma
Donghyun Hong1, Yaewon Kim1, Chandrasekhar Mushti2, Noriaki Minami1, Jing Wu2, Murali Krishna Cherukuri2, Rolf E. Swenson3, Daniel B Vigneron1, and Sabrina Ronen1,4

1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, 2National Cancer Institute, NIH, Bethesda, MD, United States, 3National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, United States, 4Brain Tumor Research Center, University of California, San Francisco, San Francisco, CA, United States

Keywords: Hyperpolarized MR (Non-Gas), Treatment, Tumor, Preclinical, Non-proton, Spectroscopy

Hyperpolarized [1-13C]α-ketoglutarate is useful for monitoring 2HG and glutamate production but has limited SNR and the [5-13C]α-ketoglutarate natural abundance peak is within 0.1ppm of 2HG. To address these challenges, this study investigated the utility of HP [5-12C-1-13C]α-ketoglutarate to monitor 2HG and glutamate production as biomarkers of response to treatment with the mutant IDH inhibitor BAY-1436032 in an in vivo rat glioma model using an optimized acquisition strategy. We were able to clearly monitor the dynamic localized production of both 2HG and glutamate in vivo in real-time, and early metabolic changes predicted enhanced survival. 

3918
Computer 165
Agonism/antagonism on cannabinoid 1 receptor reveal opposite cerebral blood volume change: a simultaneous PET/fMRI study on primates
Chi-Hyeon Yoo1 and Hsiao-Ying Wey1

1Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, United States

Keywords: Molecular Imaging, Drug Development

The goal of this study was to detect the changes of cerebral blood volume (CBV) in the non-human primate brain induced by administration of agonist and antagonist of cannabinoid receptor 1 (CB1R) using simultaneous positron emission tomography (PET) and function magnetic resonance imaging (fMRI). After the antagonist injection, a bi-phasic response, fast increase and prolonged decrease of CBV, were identified throughout the brain, while CB1R agonist administration evoked elevation of CBV. Future studies integrating PET-derived receptor occupancy information with the CBV changes will provide deeper understanding on CB1R and brain response.

3919
Computer 166
First neuroimaging experience at 11.7 Tesla on the anaesthetized non-human primate.
Fawzi Boumezbeur1, Alexis Amadon1, Marion Gay1, Franck Mauconduit1, Vincent Gras1, Maxime Roustan1, Frederic Lepretre1, Aurélien Massire2, Cécile Rabrait-Lerman1, Sebastien Mériaux1, Alexandre Vignaud1, and Nicolas Boulant1

1NeuroSpin, CEA, Gif-sur-Yvette, France, 2Siemens Healthcare SAS, Saint-Denis, France

Keywords: Bioeffects & Magnetic Fields, High-Field MRI

After more than 20 years of research and development, the 11.7T Iseult MRI scanner is in the last stage of its commissioning. However, authorization of Human MRI examination at this unprecedented magnetic field strength is still pending. In this context, MRI examinations of healthy anaesthetized non-human primates are being carried out to check on the absence of acute physiological effects following exposure and gain some insights into the opportunities and challenges ahead.

3920
Computer 167
Development and application of dynamic MRSI of an HP neuroprotective agent in an MCAO mouse model of ischemic stroke at 14.1 T
Thanh Phong Lê1,2, Lara Buscemi3, Mario Lepore4, Andrea Capozzi1,5, Lorenz Hirt3, Mor Mishkovsky1, and Jean-Noël Hyacinthe2,6

1Laboratory of Functional and Metabolic Imaging, École polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland, 2Geneva School of Health Sciences, HES-SO University of Applied Sciences and Arts Western Switzerland, Geneva, Switzerland, 3Department of Clinical Neurosciences, Lausanne University Hospital (CHUV), Lausanne, Switzerland, 4CIBM Center for Biomedical Imaging, École polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland, 5Department of Health Technology, Center for Hyperpolarization in Magnetic Resonance, Technical University of Denmark, Kgs Lyngby, Denmark, 6Image Guided Intervention Laboratory, University of Geneva (UNIGE), Geneva, Switzerland

Keywords: Hyperpolarized MR (Non-Gas), Preclinical, Molecular Imaging

Advanced acquisition hardware and sequences boosting the spatiotemporal resolution overcome the existing limitations of HP metabolic MRI in animal disease models, providing new contrasts and opening up new perspectives. Herein, we designed a 1H/13C volume/surface-combined head coil providing full mouse brain coverage with high sensitivity, as well as a high-efficiency acquisition scheme to achieve superior spatial and temporal resolution images. This setup was employed for time-resolved imaging of the cerebral metabolic response to a neuroprotective bolus of hyperpolarized pyruvate in a transient hypoxia/ischemia mouse model. The experiments suggest a distinct metabolism between the ischemic and healthy tissues.


3921
Computer 168
Exercise and Environmental Complexity Superintervention Improves Mechanical Property Recovery in FASD Rodents Measured via MRE
L. Tyler Williams1, Ian F. Smith2, Katrina A. Milbocker2, Diego A. Caban-Rivera1, Samuel Kurtz3,4, Matthew D. J. McGarry5, Elijah E. W. Van Houten4, Anna Y. Klintsova2, and Curtis L. Johnson1,2

1Dept. of Biomedical Engineering, University of Delaware, Newark, DE, United States, 2Dept. of Psychological & Brain Sciences, University of Delaware, Newark, DE, United States, 3Laboratorie de Mécanique et Génie Civil, CNRS, Université de Montpellier, Montpellier, France, 4Département de Génie Mécanique, Université de Sherbrooke, Sherbrooke, QC, Canada, 5Thayer School of Engineering, Dartmouth College, Hanover, NH, United States

Keywords: Elastography, Preclinical

In this longitudinal study, we investigate the effects of fetal alcohol exposure on mechanical properties in the developing rodent brain using magnetic resonance elastography (MRE). Additionally, we test whether behavioral “superintervention,” consisting of combined exposure to wheel running followed by environmental complexity, can mitigate changes to property measures. We found that alcohol exposed rats exhibit lower stiffness than sham intubated rats at baseline but recover stiffness to near baseline levels after superintervention. Furthermore, we confirmed MRE is sensitive to small property variations in rodents which may reflect myelination and microstructural integrity.

3922
Computer 169
In vivo measurement of rat brain water content at 9.4T using super-resolution reconstruction
Dennis C. Thomas1,2, Ana-Maria Oros-Peusquens*1, Michael Schöneck1, Antje Willuweit1, Zaheer Abbas1, Markus Zimmermann1, Jörg Felder1, Avdo Celik1, and N. Jon Shah1,3,4,5

1Institute of Neuroscience and Medicine-4, Forschungszentrum, Jülich, Germany, 2Institute of Neuroradiology, University Hospital Frankfurt, Frankfurt, Germany, 3Institute of Neuroscience and Medicine 11, INM-11, JARA, Forschungszentrum Jülich,, Jülich, Germany, 4JARA - BRAIN - Translational Medicine, Aachen, Germany, Aachen, Germany, 5RWTH Aachen University, Aachen, Germany

Keywords: Quantitative Imaging, Neurofluids, Super-resolution reconstruction, High-field MRI, ex vivo

Animal models have an indisputable role in the investigation of brain pathology. Investigating water content in vivo could lead to a better understanding of pathogenesis and hence, a robust technique to measure water content using MRI would be very beneficial. Here, we adapt a super-resolution-based technique, previously developed for humans, to the rat brain and report in vivo high-resolution (200μm isotropic) water content maps, obtained using a 9.4T MRI scanner. High resolution, isotropic water content maps of the rat brain are demonstrated. The water content values obtained using the proposed MR technique are compared with ex vivo wet/dry methods.

3923
Computer 170
Hyperpolarized [1-13C]pyruvate detects neuronal metabolic impairment in glucose transporter and pyruvate kinase deficient mice
Caroline Guglielmetti1,2, Huihui Li3, Yoshitaka Sei3, Lydia Le Page1,2, Lauren Schields3,4, Brice Tiret1,2, Xiao Gao1,2,5, Iris Lo3, Talya Dayton6, Jeffrey Rathmell7, Matthew Vander Heiden6,8, Ken Nakamura3,4,9,10, and Myriam Chaumeil1,2,4,5

1Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, CA, United States, 2Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 3Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, United States, 4Graduate Program in Biomedical Sciences, University of California San Francisco, San Francisco, CA, United States, 5UCSF/UCB Graduate Program in Bioengineering, University of California San Francisco, San Francisco, CA, United States, 6Koch Institute for Integrative Cancer Research and the Department of Biology, Massachusetts Institute of Technology, Boston, MA, United States, 7Department of Pathology, Microbiology, and Immunology, Vanderbilt Center for Immunobiology, Nashville, TN, United States, 8Dana-Farber Cancer Institute, Boston, MA, United States, 9Department of Neurology, University of California San Francisco, San Francisco, CA, United States, 10Graduate Program in Neuroscience, University of California San Francisco, San Francisco, CA, United States

Keywords: Hyperpolarized MR (Non-Gas), Neuro

We generated mice with deletion of the glucose transporter 3 (GLUT3cKO) or pyruvate kinase 1 (PKM1cKO) in CA1 hippocampal neurons. GLUT3cKO and PKM1cKO mice showed memory impairment. Hyperpolarized (HP) 13C magnetic resonance spectroscopic imaging showed that female, but not male, PKM1cKO mice had increased HP [1-13C]pyruvate-to-lactate conversion, while female GLUT3cKO mice had decreased conversion and brain volume, evaluated by T2-MRI. Fluorine-18-fluorodeoxyglucose ([18F]-FDG) positron emission tomography imaging did not detect changes, highlighting HP [1-13C]pyruvate’s potential to detect downstream alterations in brain glucose metabolism. Altogether, our findings demonstrated that neurons metabolize glucose through glycolysis in vivo, and require glycolysis for normal function.

3924
Computer 171
Metabolic Activity Diffusion Imaging [MADI] of Rat Brain Glioma
Joshua Schlegel1, Eric Baker1, Samantha Holland2, Jared Stoller3, William Packwood4, Xin Li1, Ramon Barajas3, Charles Springer1, and Martin Pike1

1AIRC, OHSU, Portland, OR, United States, 2Neurology, OHSU, Portland, OR, United States, 3Diagnostic Radiology, OHSU, Portland, OR, United States, 4Research Cores and Shared Resources, OHSU, Portland, OR, United States

Keywords: Molecular Imaging, Metabolism, Cancer

We compared the novel DWI MRI-based metabolic activity [MA] imaging approach [MADI] to 18FDG-PET, employing an in vivo rat glioma model. The MADI-derived parameter, kio*V product, is proportional to Na+/K+ ATPase [NKA] activity, the primary cellular energy consumer.  The kioV decreased within the tumor vs. contralateral while 18FDG uptake increased.   This is consistent with the Warburg effect in glioma, which activates glucose uptake but also switches energy production from mitochondrial oxidative phosphorylation to glycolysis, thus reducing overall ATP production and NKA activity.  MADI expands DWI MRI utility, providing a novel, noninvasive MA imaging method, with greater resolution than PET.

 


3925
Computer 172
Feasibility of simultaneous fMRI and optical imaging for head-fixed freely-behaving mice
Wen-Ju Pan1, Harrison Watters1, Lisa Meyer-Baese1, Annabelle Singer1, and Shella Keilholz1

1Emory University/Georgia Institute of Technology, Atlanta, GA, United States

Keywords: Multimodal, Brain

For simultaneous optical imaging and fMRI with freely-behaving mice, head-fixed without body restriction in minimal stress awake state, optimizations were conducted on multiple aspects, including multi-wavelength optical imaging system for both optical intrinsic signals and extrinsic fluorescence studies of genetically encoded calcium indicators (GECI) and voltage indicators (GEVI) mice with tube lens design instead of imaging fiber bundle, transparent cranial window development, integrated quadrature coil in head holder, and the designed belt treadmill/ virtual reality (VR) system to fit a customized rodent cradle in the commonly used 12cm ID gradient for the small animal MRI system.

3926
Computer 173
Improved glutamine detection using diffusion-weighted SPECIAL at 14.1T
Jessie Mosso1,2,3, Dunja Simicic2,3, Bernard Lanz2,3, Rolf Gruetter1, and Cristina Cudalbu2,3

1LIFMET, EPFL, Lausanne, Switzerland, 2CIBM Center for Biomedical Imaging, Lausanne, Switzerland, 3Animal Imaging and Technology (AIT), EPFL, Lausanne, Switzerland

Keywords: Spectroscopy, Diffusion/other diffusion imaging techniques, brain, preclinical, sequence design

Brain glutamine (Gln) is a key biomarker of hepatic encephalopathy (HE). The estimation of its diffusion properties with diffusion-weighted MRS is of high interest in the field but remains challenging due to its low concentration. We propose a new diffusion-weighted MRS sequence, DW-SPECIAL, which enables to reach shorter echo times and is thus beneficial for strongly J-coupled metabolites such as Gln. DW-SPECIAL reduces the uncertainty in Gln diffusion decays and the standard deviation across animals for Gln diffusivity in a homogenous control population and paves the way for an in-depth study of Gln diffusion properties in HE.


3927
Computer 174
9 crossings per 1 bend: Tractography of contra- and ipsilateral connections in mouse optic pathways improved with ODF-Fingerprinting
Patryk Filipiak1, Thajunnisa A. Sajitha2, Timothy Shepherd1, Kamri Clarke1, Dimitris G. Placantonakis3, Jiangyang Zhang1, Kevin C. Chan2, Fernando E. Boada4, and Steven H. Baete1

1Center for Advanced Imaging Innovation and Research (CAI2R), Department of Radiology, NYU Langone Health, New York, NY, United States, 2NeuroImaging and Visual Science Laboratory, Departments of Ophthalmology and Radiology, NYU Langone Health, New York, NY, United States, 3Department of Neurosurgery, Perlmutter Cancer Center, Neuroscience Institute, Kimmel Center for Stem Cell Biology, NYU Langone Health, New York, NY, United States, 4Radiological Sciences Laboratory and Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, Stanford, CA, United States

Keywords: Image Reconstruction, White Matter, tractography, optic pathways, optic tract, optic chiasm, crossing fibers

Reconstruction of rodent optic pathways is particularly challenging for dMRI tractography due to the relatively small size of the crossing area in the optic chiasm and the unbalanced proportion between the contra- and ipsilateral axonal links. In this study, we replace the commonly used Orientation Distribution Function peak finding approach with our dictionary-based technique called ODF-Fingerprinting to improve the reconstruction of crossing fibers and thus correct the proportion of tracts exiting the optic chiasm. Our results from in vivo diffusion-weighted images of 18 mice show significant improvement (p<0.05) in many cases, helping decrease the discrepancies between reconstruction and gold-standard histology.

3928
Computer 175
Imaging the transmembrane pH gradient in gliomas
Sandeep Kumar Mishra1, Jelena Mihailović1, Fahmeed Hyder1,2, and Daniel Coman1

1Radiology & Biomedical Imaging, Yale University, New Haven, CT, United States, 2Biomedical Engineering, Yale University, New Haven, CT, United States

Keywords: Molecular Imaging, Cancer, transmembrane pH

Extracellular acidosis in relation to intracellular milieu is a unique feature of the tumor microenvironment. The difference between intracellular pH (pHi) and extracellular pH (pHe) is much larger in tumors than normal tissue. Measuring the transmembrane pH gradient (ΔpH=pHi–pHe) could provide a tool for assessing tumor aggressiveness, monitoring treatment efficacy, guiding localized drug delivery, and understanding tumor responsiveness. This work establishes transmembrane pH gradient imaging in brain tumors. We observed a significantly higher transmembrane pH gradient in RG2 tumors compared to normal brain. Decreasing transmembrane pH gradient may serve as a functional biomarker for positive therapeutic outcome.


3929
Computer 176
Mapping the effect of oxytocin on the mouse brain using Q2TIPS arterial spin labelling and BOLD fMRI at 9.4T
Eugene Kim1, Davide di Censo1, Zhuoni Li2, Eilidh MacNicol1, Alexandra Hertz2, Michael Craig2, Diana Cash1, and Marija M Petrinovic2

1Department of Neuroimaging, King's College London, London, United Kingdom, 2Department of Forensic and Neurodevelopmental Sciences, King's College London, London, United Kingdom

Keywords: Brain Connectivity, Arterial spin labelling, pharmacological MRI

Currently, standard Bruker protocols for arterial spin labelling (ASL) in mice are limited to single-slice methods. Here, we implemented multi-slice Q2TIPS ASL on a Bruker 9.4T scanner for whole-brain mapping of cerebral blood flow (CBF) in mice. There was good agreement between Q2TIPS and the standard Bruker FAIR ASL. Pharmacological MRI using Q2TIPS ASL and BOLD fMRI revealed that systemic administration of a behaviorally relevant dose of oxytocin caused a global decrease in CBF and increase in functional connectivity in healthy, wildtype mice. These opposing effects corroborate a recent concept of mutual exclusivity between neuronal activity and functional connectivity. 


3930
Computer 177
A water-exchange dynamic contrast-enhanced MRI protocol optimized for AQP4 measurement in glioma
Guangxu Han1, Yinhang Jia1, Zejun Wang1, Yi-Cheng Hsu2, and Ruiliang Bai3,4

1Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China, 2MR Collaboration, Siemens Healthcare, Shanghai, China, 3Zhejiang University School of Medicine, Hangzhou, China, 4College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China

Keywords: Contrast Agent, Tumor

A dynamic contrast-enhanced MRI (DCE-MRI) protocol was optimized to measure transmembrane water exchange rate (kio), which was correlated kio with aquaporin-4 (AQP4) immunohistochemistry results in a rodent subcutaneous glioma model. From the acquired results, a significant correlation was demonstrated between the optimized kio and AQP4, indicating that kio measured by DCE-MRI could reveal the expression of AQP4.

 


3931
Computer 178
Mechanical Stiffness and Anisotropy Measured by MR Elastography during Brain Development in the Minipig
Shuaihu Wang1, Charlotte A Guertler1, Ruth J Okamoto1, Curtis L Johnson2, Matthew DJ McGarry3, and Philip V Bayly1

1Washington University in St. Louis, St. Louis, MO, United States, 2University of Delaware, Newark, DE, United States, 3Dartmouth College, Hanover, NH, United States

Keywords: Elastography, Tissue Characterization

The relationship between brain development and mechanical properties of brain tissue is important but remains incompletely understood. Here we use data from magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI) to estimate anisotropic mechanical properties in six female Yucatan minipigs at ages from 3 to 6 months with a transversely- isotropic nonlinear inversion (TI-NLI) algorithm. Our results show that white matter is more dissipative and anisotropic than gray matter, and reveal effects of brain development on brain stiffness and structural anisotropy. Changes in brain mechanical properties may be a fundamental biophysical signature of brain development.

3932
Computer 179
Bias-Reduced LCModel Quantification of 1H Brain MRS with Baseline-and-MM Removal: Application in a Circulatory Arrest Study using Neonatal Pigs
Meng Gu1, Ralph Hurd1, and Daniel Spielman1

1Radiology, Stanford University, Stanford, CA, United States

Keywords: Data Processing, Spectroscopy, Accurate Quantification

Quantification of in-vivo short-TE MRS using LCModel suffers from biases due to varying baseline and macro-molecule components, especially for metabolites with coupled resonances. This problem exacerbates at low SNR as the baseline estimated becomes less accurate. To improve quantification, baseline and macro-molecule components were estimated from a high SNR line-broadened spectrum and then subtracted from the original spectrum. Using the baseline and macro-molecule removed spectrum, significantly reduced biases for Gln/tCr and GABA/tCr were achieved at different SNRs. Using this method, LCModel quantification revealed a more prominent trend of increasing Gln/tCr and increased GABA/tCr during circulatory arrest in neonatal pig brain.

3933
Computer 180
Correlation Tensor Imaging Enhances Histological Differences Between Mouse Glioblastoma Subtypes
Rafael Neto Henriques1, Rui V Simões1,2, Sara Monteiro1,3, Andrada Ianuş1, Tânia Carvalho1, Sune Jespersen4,5, and Noam Shemesh1

1Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal, 2Institute for Research & Innovation in Health (i3S), University of Porto, Porto, Portugal, 3Institute for Systems and Robotics, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal, 4Center of Functionally Integrative Neuroscience (CFIN) and MINDLab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, 5Department of Physics and Astronomy, Aarhus University, Aarhus, Denmark

Keywords: Diffusion/other diffusion imaging techniques, Diffusion/other diffusion imaging techniques

Correlation Tensor Imaging (CTI) has been recently proposed as a novel methodology for resolving kurtosis sources without relying on strong multi-gaussian component assumptions. Here, CTI is harnessed to decipher kurtosis sources in two different mouse glioblastoma subtypes. Our results reveal that CTI’s kurtosis source separation resolves the underlying microstructural differences between the glioblastoma subtypes and faithfully represents their specific histopathological features. In comparison to previous diffusion MRI approaches, CTI kurtosis maps present enhanced sensitivity towards tumor differences. These first results show the potential of CTI in providing more sensitive and specific future biomarkers for monitoring tumor progression and therapy outcome.