The Cardiac and Interventional MR section has projects to develop miniaturized MR detectors on guidewires for endoscopic MRI at ≤100μm resolution and precision-guided high-frequency intravascular ultrasound ablation. High-speed intravascular MRI methods for imaging vessel disease at ~10 fr/sec are being developed, along with precision MRI-guided interventional procedures that could treat obesity and cancer. Ongoing MR spectroscopy (MRS) studies of cardiac energetics in heart failure patients are underway in collaboration with investigators in the Division of Cardiology.
The Cellular Imaging Section is located in the Institute for Cell Engineering. We engineer cells so they can be detected with non-invasive imaging techniques such as magnetic resonance imaging and magnetic particle imaging. Our primary mission is to develop new magnetic tracers and cell labeling procedures to study the fate of therapeutic stem cells and immune cells after injection, also known as “cell tracking”.
We have been part of several clinical studies performed around the world, using cell labeling techniques developed in our lab. Targets of cell therapy include dysmyelination, multiple sclerosis, cancer, spinal cord injury, stroke, and diabetes. We use cell scaffolds and hydrogels to embed our cells for optimal survival post-transplantation and are able to visualize the biodegradation of these gels in vivo, with applications in regenerative medicine. Finally, we develop novel MRI contrast agents and theranostics with clinical applicability. These include both metallic (i.e. paramagnetic) and non-metallic (i.e. diaCEST) agents, and fluorinated tracers and capsules for 19F MRI and 19F iCEST MRI.
Director of Cellular Imaging, The Johns Hopkins Institute for Cell Engineering, Director of Scientific Communications, Department of Radiology, Professor of Radiology and Radiological Science
Ali Shakeri-Zadeh, Ph.D.
Aline Thomas, Ph.D.
Shreyas Kuddannaya, Ph.D.
Behnaz Ghaemi, Ph.D.
Marzieh Salimi, Ph.D
Chao Wang, Ph.D.
Intracellular self-assembly of OlsaCEST-MRI detectable, DNA methylation-inhibiting theranostic nanoparticles.
The single molecule compound Olsa(green)-CBT (pink)-RVRR (blue) is injected intravenously, passes through the cell membrane with the aid of the cell-penetrating peptide RVRR (representing multiple arginines), and the small peptide substrate RVRR is cleaved by the tumor-associated enzyme furin (purple). The single Olsa-CBT residues are then self-assembled into nanoparticles through a glutathione (GSH) and 2-cyanobenzothiazole (CBT)-mediated biocompatible click condensation reaction followed by π-π stacking.
From: Y. Yuan, J. Zhang, X. Qi, S. Li, G. Liu, X. Song, M.T. McMahon, J.W.M. Bulte. Furin-mediated intracellular self-assembly of olsalazine nanoparticles for enhanced MR imaging and tumor therapy. Nat. Mat. 18, 1376-1383 (2019).
Y. Yuan, P. Raj, J. Zhang, S. Siddhanta, I. Barman, J.W.M. Bulte. Furin-mediated self-assembly of olsalazine nanoparticles for targeted Raman imaging of tumors. Angew. Chem. Int. Ed., doi: 10.1002/anie.202014839.Play Video:
Magnetizing Cells for Tracking | Science: Out of the Box
Although it has great potential for treating cancer, spinal cord injuries, diabetes and many other serious diseases, there are challenges to making stem cell therapy a reality. Watch cell imaging specialist Jeff Bulte explain his pioneering work in tracking stem cells in the body — and how it can help lead to better stem cell treatments by reporting stem cells’ location and whether they are still alive.
MRI Reporter Gene
We developed a new gene construct "CEST reporter" which after its incorporation in glioma cells resulted in the production of magnetic resonance imaging MRI visible proteins. These protein-expressing tumor cells were transplanted into the brain of living mice and allowed to grow. A week after transplantation we imaged these live mice with MRI which enabled us to clearly see the tumor cells growing in the brain. We are now using our new MRI reporter gene technology with cell therapy where we track the survival growth and migration of transplanted stem cells.
The Neuroscience Section is focused on the development of novel MRI technologies and their application to basic science problems and clinical disease, especially in the brain. Methods have and are being developed for MRS and MRS imaging (MRSI); diffusion tensor imaging (DTI) and axonal mapping; physiological imaging (blood flow, blood volume, and blood oxygenation); and for the study of biochemical interactions using magnetization transfer processes.
Other research to improve the understanding of the blood oxygen level-dependent (BOLD) mechanism that underlies functional MRI, and the theory of MR relaxation in blood that underlies it is underway. Several faculty members of this large section are engaged in the development of new technologies for high-field MRI, including novel biodegradable contrast agents (sugar and proteins), molecular imaging markers, and new endogenous contrast agents for distinguishing tumors from healthy tissue.
Kazi Akhter, B.S.
Adnan Bibic, Ph.D.
Joe Gillen, B.S.
Wenbo Li, Ph.D.
Deng Mao, Ph.D.
Feng Xu, Ph.D.
Our Research Labs
The Peter van Zijl Laboratory focuses on developing new methodologies for using MRI and magnetic resonance spectroscopy (MRS) to study brain function and physiology. In addition, we are working to understand the basic mechanisms of the MRI signal changes measured during functional MRI (fMRI) tests of the brain. We are also mapping the wiring of the brain (axonal connections between the brains functional regions) and designing new technologies for MRI to follow where cells are migrating and when genes are expressed. A more recent interest is the development of bioorganic biodegradable MRI contrast agents. Our ultimate goal is to transform these technologies into fast methods that are compatible with the time available for multi-modal clinical diagnosis using MRI.
Research in the Neurofunction Section is focused on the development of novel MRI techniques to evaluate the brain's physiology, function, metabolism, and structure, as well as their clinical applications. Our work spans across humans to animal models and ranges from neonates to elderly individuals. Our central goal is to develop translatable MRI tools as candidate biomarkers in neurologic and psychiatric diseases.
Representative techniques that our team is actively developing include T2-Relaxation-Under-Spin-Tagging (TRUST) to measure oxygenation and oxidative metabolism, cerebrovascular reactivity (CVR) to evaluate the brain’s vascular reserve, water extraction with phase contrast arterial spin tagging (WEPCAST) for non-contrast assessment of BBB permeability, MR fingerprinting arterial spin labeling (MRF-ASL) for multi-parametric hemodynamic imaging, and brain atlases in special populations such as pediatric patients. Our team is looking forward to opportunities of collaboration and welcomes inquiries or requests of our techniques.