|Advances in MRI-Based Cell Tracking|
|High Resolution Imaging of Arterially Delivered
Min Liu1, Qing Yang1, Bijoy Thattaliyath1, Giulio Cossu2, Sean Germain1, Glenn Adam Walter1
1University of Florida, Gainesville, Florida, USA; 2Stem Cell Research Institute, Milan, Italy
Cell based therapies represent a challenge for noninvasive monitoring due to the variability in stem cell incorporation that occurs in the presence of massive cell death. In this work MR based strategies have been developed to track the migration/integration of arterially delivered muscle stem cells into skeletal muscles and the bone marrow of dystrophic mice. Longitudinal MR tracking of mesioangioblasts was achieved following SPIO labeling of cells followed by high-resolution imaging.
|MRI Studies of In-Vitro Perfused Human Pancreatic
Islet Cell Activation
Suraj Serai1, Lara Leoni2, Natalia Pablo1, Muhammad E. Haque2, Brian B. Roman, 12
1University of Illinois at Chicago, Chicago, Illinois, USA; 2University of Chicago, Chicago, Illinois, USA
Many unpredictable variables influence the outcome of human islet isolation, jeopardizing the quantity and quality of islets; and in order to improve outcome in clinical pancreatic islet isolation and functionality, various factors should be investigated thoroughly during the process of islet retrieval. Another variable factor is the number of donors. Manganese enhanced MRI is presented here as a tool to image isolated perfused human pancreatic islets. With our methods we can verify islet functionality with MR related SNR parameters. Once established, the invitro data needs to be correlated with invivo studies for enhancement in pancreas following Mn & glucose infusions.
A Dynamic Process of Macrophage
Infiltration During Tumor Progression
Yi-Hua Hsu1, Chia-Ming Shih1, Sui-Shan Lin2, Kai-Ping Chow3, Chen Chang2
1Academia Sinica, Taipei, Taiwan; 2Academia Sinica , Taipei, Taiwan; 3Chang-Gung University , Taoyuan, Taiwan
The aim of the present study is to provide insights into the role of tumor-associated macrophages (TAMs) by employing superparamagnetic iron oxide (SPIO) nanoparticles-enhanced MRI to longitudinally trace the spatial and temporal evolution of TAM infiltration during tumor progression. Our data demonstrated that TAMs facilitated the tumor neovascularization by incorporating into and/or coordinating the new vessel formation and TAM infiltration was accompanied by in situ tumor mass expansion, implying sequential TAM recruitment resulting in stepwise tumor outgrowth.
Factors Influencing in Vivo MR Imaging of
Transplanted Pancreatic Islets
Natalia Evgenov1, John Pratt1, Pamela Pantazopoulos1, Anna Moore1
1Massachusetts General Hospital, Charlestown, USA
A significant islet loss has been observed immediately after islet transplantation in diabetic patients. Previously we have showed that SPIO-labeled islets could be monitored by MRI. This study focused on both the effect of hyperglycemia and the effect of contaminating non-endocrine tissue on MRI imaging of islet grafts. We found that diabetic animals with transplanted islets showed significantly higher rate of islet death on in vivo MR images than their healthy counterparts. In contrast, transplantation of the islets contaminated with non-endocrine tissue did not have any significant influence on the imaging picture.
Tracking the Fate of Iron-Labeled Cells:
Differentiation Between Live and Dead Cells
Daniel Jirak1, Jan Kriz1, Ayman Oweida1, Jason Townsen2, Ann Chambers2, Brian Rutt1, Paula Foster1, 2
1Robarts Research Institute, London, Canada; 2University of Western Ontario, London, Canada
The use of iron oxides to label cells for their detection by MRI is quite widely used today in MR research. A question often posed about the areas of signal loss caused by iron labeled cells is whether they represent live or dead cells. It is assumed that if an iron-labeled cell dies it will be ‘cleared’ by the immune system and the area of signal loss will disappear. Here we present data from cellular MRI experiments in various models which suggests that whether or not the signal loss remains over time, when cells die, depends on the host tissue.
Self-Refocused Spatial-Spectral Pulse Pair for
Positive Contrast Imaging of Cells Labeled with Superparamagnetic
Iron-Oxide (SPIO) Nanoparticles
Priti Balchandani1, John Pauly1, Philip Yang1, Mayumi Yamada1, Daniel Mark Spielman1
1Stanford University, Stanford, California , USA
We have developed a self-refocused spatial-spectral (SPSP) pulse pair to achieve slice-selective, frequency-selective, short-echo-time, spin-echo imaging. The self-refocused SPSP pulse pair is a phase-matched 90 SPSP pulse and 180 SPSP pulse combined, through a series of approximations, into a single pulse. The pulse pair is suitable for any application requiring spatial and spectral selectivity at short echo times. We utilized the pulse pair to perform slice-selective, positive-contrast imaging of superparamagnetic iron-oxide (SPIO) nanoparticle-labeled cells. Phantom and in vivo data demonstrate that the pulse pair is successful in creating positive-contrast images of SPIO-labeled cells for a selected slice.
Quantitative Tracking of Magnetically Labeled Breast
Cancer Cells in Rat Brain with a Fast T2 Mapping Technique
wei liu1, 2, Julien Senegas3, Ho-Taek Song2, 4, E Kay Jordan2, Hannes Dahnke3, Joseph A. Frank2
1Philips Research North America, Briarcliff Manor, New York, USA; 2National Institutes of Health, Bethesda, Maryland, USA; 3Philips Research Europe, Hamburg, Germany; 4College of Medicine, Yonsei University, Shinchon, Republic of Korea
Since intracellular SPIOs have much longer T2 compared to free SPIOs, measuring both T2 and T2* relaxation times will reduce the interference from free SPIOs for accurate quantification of SPIO labeled cells. T2 maps of the rat brain were acquired with a fast T2 mapping technique through undersampling and k-t reconstruction. Reduction of brain T2 after intracardiac injection of SPIO labeled breast cancer cells was characterized as 3-4% with both regular T2 mapping and fast T2 mapping. This mild reduction in T2 suggests that the significant alteration in brain T2* we observed previously was mainly induced by SPIOs labeled cells.
MRI Detects in Vivo Migration of Rat's Bone Marrow
Derived Mesechymal Stem Cells Towards Quinolinic Acid Lesion
Noam Shemesh1, Ofer Sadan, 12, Daniel Offen, 12, Eldad Melamed, 12, Yoram Cohen1
1Tel Aviv University, Tel Aviv, Israel; 2Laboratory of Neurosciences, FMRC, Rabin Medical Center, Tel Aviv, Israel
Synopsis-The injection of Quinolinic Acid (QA) to the rat striatum is an important animal model of Huntington's disease (HD). Neurotrophic factors producing Mesenchymal stem cells (MSCs) are promising candidates for the treatment of CNS related diseases. The need to determine the implanted cells' viability has led us to test their ability to migrate from the deposition site towards the QA lesion. Our high-resolution 3D gradient echo images clearly show SPIO labeled cells that migrate and accumulate in the lesion. The MRI findings are correlated with immunohistochemistry, thus suggesting the viability of the cells up to 18 days post transplantation.
Magnetic Targeting of Stem Cells to a Site of
Vascular Injury Using an MRI Contrast Agent
Panagiotis Kyrtatos1, Pauliina Lehtolainen1, Manfred J. Ramirez, Anthony N. Price1, Thomas Poulianitis2, Quentin A. Pankhurst2, David G. Gadian, Mark F. Lythgoe1
1Institute of Child Health and Department of Medicine, University College London, London, UK; 2London Centre for Nanotechnology, London, UK
Cellular labelling with MRI contrast agents is becoming an established method of tracking cells in vivo, and it may also be possible to apply an external magnetic force on cells labelled with iron oxide. Endothelial progenitor cells (EPCs) are proliferative cells that can adopt an endothelial-like phenotype and are known to be involved in pathological and physiological processes such as tumour-induced and post-ischaemic neovascularisation. The long term aims of our study are to monitor the homing and retention of EPCs non-invasively using MRI and target them to the site of injury using an externally applied magnetic field, thus enhancing re-endothelialisation.
MRI Transverse Relaxation Rate Correlates with Number
of Viral Particles Expressing H-Ferritin in the CNS
Bistra Iordanova1, Clinton S. Robison1, William F. Goins2, Eric T. Ahrens1
1Carnegie Mellon University, Pittsburgh, Pennsylvania, USA; 2University of Pittsburgh, Pennsylvania, USA
Optimal use of transgenic animals and preclinical development of gene therapy requires methods for non-invasive visualization of gene expression. Our present work describes an indirect method of quantifying a gene expression using heavy-chain ferritin (H-Ft) MR reporter in the mouse the brain. We computed the 3D distribution of MR transverse relaxation rates in a mouse brain after transgene vector inoculation. We established that these relaxation rates correlate significantly to the number of inoculated infectious particles.