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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.