Yue Yuan¹, Congxiao Wang¹, Jia Zhang¹, and Jeff W.M. Bulte^1
1The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Baltimore, MD, United States

Human mesenchymal stem cells (hMSCs) overexpress high-mannose-type (HM) N-glycans on their membrane surface. Taking advantage of the five exchangeable hydroxyl groups on mannose that provide CEST MRI contrast, we present a label-free method for tracking hMSCs in vivo. The mannose-sensitive CEST (manCEST) signal of hMSCs was clearly distinguishable from the surrounding host tissue and stood out against several other transplanted cell lines tested.

Daniel Andrzej Szulc^1,2, Xavier Alexander Lee^2,3, Hai-Ying Mary Cheng^4,5, and Hai-Ling Margaret Cheng^1,2,6
1Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada, ²Translational Biology & Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada, ³Department of Physiology, University of Toronto, Toronto, ON, Canada, ⁴Biology, University of Toronto Mississauga, Toronto, ON, Canada, ⁵Department of Cell & Systems Biology, University of Toronto, Toronto, ON, Canada, ⁶Edward S. Rogers Sr. Department of Electrical & Computer Engineering, University of Toronto, Toronto, ON, Canada

Tissue engineering with transplanted cells has the potential to repair and regenerate almost every tissue and organ of the body. One major obstacle of cell therapies is the inability to longitudinally assess injected cells. Non-invasive imaging with contrast-enhanced MRI is highly suited for this task but is limited with current methods. In this study, we report a novel method for producing bright endogenous cellular contrast through a genetic MRI reporter that results in the formation of in situ ferritin-manganese nanoparticles. The signal produced by these cells is significantly higher than traditional iron labelled ferritin-overexpressing cells and manganese-permeable cell lines.  

Viswanath Pamulakanty Sudarshan^1,2,3, Shenpeng Li⁴, Anthony Fernandez¹, Phillip Ward^4,5, Sharna Jamadar^4,5, Gary Egan^4,5, Suyash Awate³, and Zhaolin Chen^4
1Monash University, Clayton, Australia, ²IITB Monash Research Academy, Mumbai, India, ³Indian Institute of Technology, Bombay, Mumbai, India, ⁴Monash Biomedical Imaging, Clayton, Australia, ⁵Turner Institute for Brain and Mental Health, Clayton, Australia

Simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) provide complementary structural and functional information. Recent developments in continuous infusion functional PET (fPET) have shown promising results to track dynamic changes in brain metabolism. Although fPET provides opportunities to investigate functional metabolism in the brain, the temporal resolution still remains a major challenge compared to functional MRI (fMRI). In this work, we use anatomical MRI information modeled as a Bowsher prior to improve the sensitivity of fPET at higher temporal resolution. We validate our MRI-assisted fPET analysis framework using both in-silico and in-vivo experiments.

Phillip G.D. Ward^1,2,3, Xingwen Liang¹, Gary F Egan^1,2,3, and Sharna D Jamadar^1,2,3
1Monash Biomedical Imaging, Monash University, Melbourne, Australia, ²Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Melbourne, Australia, ³Australian Research Council Centre of Excellence for Integrative Brain Function, Melbourne, Australia

Metabolic connectivity measured using FDG-PET has been proposed as a biomarker for disease, however static FDG-PET cannot provide subject-level measures of connectivity. We applied constant infusion functional FDG-fPET to measure subject-level metabolic connectivity simultaneously with BOLD-fMRI connectivity. Group-average FDG-fPET and BOLD-fMRI connectivity profiles showed similarities and differences. FDG-fPET and BOLD-fMRI connectivity was most similar in superior cortex, and least similar in subcortical regions. Group-average FDG-fPET within-subject connectivity showed little similarity with static FDG-PET connectivity. Our new method opens up the opportunity for new metabolic neuroimaging biomarkers for disease, as well as approaches for multimodality MR-PET imaging.  

Justine Debatisse^1,2, Omer Eker^3,4, Oceane Wateau⁵, Tae-Hee Cho^1,6, Marlene Wiart¹, Nicolas Costes⁷, Ines Merida⁷, Christelle Leon¹, Jean-Baptiste Langlois⁷, Thomas Troalen², Christian Tourvielle⁷, Thibault Iecker⁷, Didier Le Bars⁷, Sophie Lancelot⁷, Norbert Nighoghossian^1,6, Michel Ovize^1,8, Hugues Contamin⁵, Francois Lux⁹, Olivier Tillement⁹, and Emmanuelle Canet Soulas^1
1CarMeN lab, U1060 INSERM, University of Lyon, Lyon, France, ²Siemens Healthcare SAS, Saint-Denis, France, ³Interventional Neuroradiology, Hospices Civils de Lyon, Lyon, France, ⁴CREATIS lab, UMR CNRS 5220, INSERM U1206, INSA, University of Lyon, Villeurbanne, France, ⁵Cynbiose SAS, Marcy l'Etoile, France, ⁶Neurology, Hospices Civils de Lyon, Lyon, France, ⁷CERMEP, Lyon, France, ⁸Cardiology, Hospices Civils de Lyon, Lyon, France, ⁹ILM, CNRS UMR5306, University of Lyon, Villeurbanne, France

Quantification of blood-brain barrier (BBB) leakage is of main interest in the stroke field to identify patients susceptible to develop hemorrhage and to identify the therapeutic window for neuroprotective drugs administration. We used small (Gd-DOTA) and medium size (nanoparticles AGuIX) contrast agents (CA) to quantify BBB permeability 60-to-90 minutes post-recanalization in a model of stroke using dynamic contrast-enhanced (DCE) MRI. We confirmed 1) Early BBB leakage with both CA and 2) BBB opening to nanoparticles at post-recanalization provides opportunity for selective neuroprotection drug delivery. 

Gabriel Richard¹, Christophe Noll¹, Mélanie Archambault¹, Luc Tremblay¹, Serge Phoenix¹, Samia Ait-Mohand¹, Réjean Lebel¹, Brigitte Guérin¹, André C. Carpentier¹, and Martin Lepage^1
1Université de Sherbrooke, Sherbrooke, QC, Canada

Brown adipose tissue (BAT) oxidative metabolism can be measured by ¹¹C-acetate PET with a 3-tissue pharmacokinetic model. However, this model can have trouble distinguishing between increased oxidation and increased blood volume, both of which occur in active BAT. A sequential DCE-MRI and ¹¹C-acetate PET protocol was performed in male Wistar rats with and without BAT activation. DCE-MRI perfusion measures were comparable to those obtained previously with ⁶⁸Ga-DOTA PET. Incorporating the DCE-MRI blood volume information into the ¹¹C-acetate model revealed higher oxidation in activated BAT than indicated by the unconstrained model.

Ryan Hall¹, Nadia Ayat¹, Peter Qiao¹, Amita Vaidya¹, and Zheng-Rong Lu^1
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States

Oral squamous cell carcinoma (OSCC) has maintained poor prognosis due to its aggressive nature and lack of targetable biomarkers for early and accurate detection. We have developed a targeted MRI contrast agent specific to extradomain-B fibronectin (EDB-FN), an extracellular matrix protein closely associated with tumor aggressiveness. Immunohistochemical analysis revealed strong EDB-FN expression in OSCC with minimal expression in normal tongue tissue. MR molecular imaging with our targeted contrast agent demonstrated the ability for differential contrast enhancement of aggressive OSCC tumors, underscoring the potential for using EDB-FN as a targetable biomarker for precision molecular imaging of OSCC.

Nivin N Nyström^1,2, Timothy J Scholl^2,3, and John Andrew Ronald^1,2,4
1Medical Biophysics, University of Western Ontario, London, ON, Canada, ²Medical Imaging Laboratories, Robarts Research Institute, London, ON, Canada, ³Medical Biophysics, Robarts Research Institute, London, ON, Canada, ⁴Lawson Health Research Institute, London, ON, Canada

Organic anion-transporting polypeptide 1b3 (Oatp1b3) is a protein derived from the human liver that is capable of taking up Gd-EOB-DTPA, a clinical contrast agent, into cells. We synthetically express the Oatp1b3 gene on breast cancer cells and are able to track them throughout the bodies of preclinical animal models with high sensitivity and resolution as they metastasize. In the future, we hope to develop Oatp1b3 as a tool to track the activation and location of gene and cellular therapies in patients on MRI.