Molecules & Cells: Novel Imaging Methods
Friday 24 April 2009
Room 323ABC 10:30-12:30


Jeff W. M. Bulte and Peter M. Jakob

10:30 802. SWIFT Detection of SPIO Labeled Stem Cells Grafted in the Myocardium
    Rong Zhou1, Djaudat Idiyatullin2, Steen Moeller2, Curt Corum2, Hualei Zhang1, Michael Garwood2
Labotories of Molecular Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA; 2Center for Magnetic Resonance Research , University of Minnesota, Minneapolis, MN, USA
    We demonstrate the feasibility of (SWIFT) based detection of superparamagnetic iron-oxide (SPIO) labeled stem cells in the heart. We show that SWIFT allows 3-dimensional imaging of SPIO labeled cells while simultaneously presenting T1-weighted signal of myocardial wall. Compared to T2*W GRE images, SWIFT magnitude images suppress the susceptibility artifacts leading to better delineation of stem cell distribution while SWFT imaginary images present an enhanced (positive) boundary between regions containing high concentration of SPIOs and the surrounding myocardium.
10:42 803. Fast Positive-Contrast Imaging of SPIO-Labeled Cells with Low-Angle Alternating-TR SSFP
    Tolga Çukur1, Mayumi Yamada2, William R. Overall1, Phillip Yang2, Dwight G. Nishimura1
Electrical Engineering, Stanford University, Stanford, CA, USA; 2School of Medicine, Stanford University, Stanford, CA, USA
    There has been recent interest in positive-contrast MRI methods for tracking cells labeled with super paramagnetic iron oxide (SPIO) nanoparticles. High off-resonant signal can be generated by utilizing the low-angle SSFP response to achieve fast high-resolution imaging. However, the positive contrast is compromised by the limited suppression of on-resonant and fat signals. In this work, we investigate an improved technique based on alternating-TR SSFP to achieve reliable background suppression. Sensitivity measurements are performed, and phantom and in vivo data are presented to demonstrate the reliability of the generated contrast.
10:54 804. UTE Imaging for Single Cell Detection with Positive Contrast
    Clemens Diwoky1, Andreas Reinisch2, Dieter Gross3, Volker Lehmann3, Dirk Strunk2, Rudolf Stollberger1
Inst. of Medical Engineering, TU Graz, Graz, Austria; 2Stem Cell Research Unit, Dept. of Hematology, Univ. Clinic of Internal Medicine, Medical University of Graz, Graz, Austria; 3Dept. of Microimaging, Bruker BioSpin GmbH, Rheinstetten, Germany
    For the detection of single SPIO loaded cells 3D GRE sequences with small isotropic imaging volumes are essential. Unfortunately they are highly time consuming and not applicable in a clinical setup. An alternative are 2D GRE acquisitions with enlarged slices. However, signal variations caused by global SPIO induced field inhomogeneities reduce their usefulness for cell detection. To enhance detectability, we propose the use of 2D UTE sequences with positive SPIO contrast. As a visual benchmark, the outstanding performance of UTE compared to 2D GRE is shown on a new in-vitro model consisting of cell networks build by endothelial progenitor cells.
11:06 805. 3D Radial UTE Imaging for Quantification of Transplanted Iron Oxide Labelled Islet Cells
    Lindsey Alexandra Crowe1, Frederic Ris2, Sonia Nielles-Vallespin3, Peter Speier3, Solange Masson2, Mathieu Armanet2, Domenico Bosco22, Thierry Berney2, Jean-Paul Vallée1,4
Faculty of Medicine  , University of Geneva, Geneva, Switzerland; 2Cell Isolation and Transplant Center, Department of Surgery, Geneva University Hospital, Geneva, Switzerland; 3Siemens AG Medical Solutions, Erlangen, Germany; 4Work supported in part by the Center for Biomedical Imaging (CIBM), Geneva and Lausanne, Switzerland
    Monitoring the fate of transplanted pancreatic Islets of Langerhans into the liver is vital for improvement of treatment for type 1 diabetes. MR provides quantitative, non-invasive imaging for serial examination of iron oxide labelled cells. In-vivo 3D difference ultra-short echo time (dUTE) imaging gives positive, quantifiable contrast from iron labelled islets in rat. Between the ultra-short and ‘long’ echo times the islet cell signal changes but the small vessels and liver constant. Coverage of the whole liver in the absence of cardiac and respiratory motion artifact, and isotropic resolution provides improvement over 2D GRE.
11:18 806. Multi-Color 19F CSI: Simultaneous Detection of Differently Labeled Cells in Vivo
    Thomas Christian Basse-Lüsebrink1,2, Gesa Ladewig1, Thomas Kampf2,3, Gerd Melkus2, Daniel Haddad4, Wolfgang Rudolf Bauer3, Peter M. Jakob2,4, Guido Stoll1
Neurology, University of Würzburg, Würzburg, Germany; 2Department of Experimental Physics 5, University of Würzburg, Würzburg, Germany; 3Medical Clinic and Polyclinic I, University of Würzburg, Würzburg, Germany; 4Research Center for Magnetic Resonance Bavaria (MRB), Würzburg, Germany

19F markers provide unambiguous signal in vivo due to the low natural abundance of fluorine in living organisms. A further advantage of 19F molecular MRI is that fluorine markers possess a unique spectral signal. Therefore, chemical shift imaging (CSI) methods can be used to distinguish between cells labeled with different fluorine markers.

This pilot study demonstrates the feasibility of distinguishing between differently labeled cells in vivo in a PT mouse model. This is possible by using fast and specific multi-color CSI methods.

11:30 807.  Dynamic Manganese-Enhanced MRI Reveals Dominant Modulation of Myocardial L-Type Calcium Channel Flux by Neuronal, Not Endothelial Nitric Oxide Synthase in Mice
    Moriel H. Vandsburger1, Brent A. French1,2, Christopher M. Kramer2,3, Frederick H. Epstein1,2
Biomedical Engineering, University of Virginia, Charlottesville, VA, USA; 2Radiology, University of Virginia, Charlottesville, VA, USA; 3Medicine, University of Virginia, Charlottesville, VA, USA
    Modulation of L-Type Calcium Channel (LTCC) flux plays an important role in calcium cycling and cardiomyocyte contractility. Manganese (Mn2+) enters cardiomyocytes through the LTCC and shorterns T1 proportionatly. Modulation of LTCC flux by neuronal (nNOS) and endothelial (eNOS) isoforms of nitric oxide synthase is unclear. The uptake of Mn2+ was examined in wild type (WT), nNOS-/-, and eNOS-/- mice at baseline and with dobutamine using an ECG-gated saturation recovery pulse sequence with constant repetition time (TR) of 200ms. Whereas baseline LTCC flux was higher in nNOS-/- mice and unchanged with dobutamine, LTCCI increased with dobutamine in WT and eNOS-/- mice.
11:42 808. Assessment of Myocardial Ca2+ Dysregulation Using Mn Enhanced MRI
    Janaka Wansapura1, Doug Millay1, Jeff Molkentin1, Woody Benson1
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
    Accumulated Mn2+ within the myocardial tissue causes signal enhancement. In this study, we infused delta-sarcoglycan null mice, a model for muscular dystrophy with highly purified 20mM, MnCl2.4H2O while TrueFISP images were being obtained in the short axis. Compared to WT, these mice showed significantly low rate of enhancement in the myocardium. It is widely accepted that dystrophic cardiomyocytes show altered Ca2+ influx. Increased [Ca2+] cause decreased Mn2+ uptake by the heart. Thus our results demonstrate the feasibility of assessing Ca2+ dysregulation in the dystrophic heart using Mn enhancement.
11:54 809. High Throughput MRI Method  for in Vitro CEST Agent Screening
    Guanshu Liu1, Assaf A. Gilad2, Jeff W.M. Bulte2, Peter C.M. van Zijl1, Michael T. McMahon1
F.M. Kirby Center, Kennedy Krieger Institute, Baltimore, MD, USA; 2Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    We developed a high throughput MRI method for screening Chemical Exchange Saturation Transfer (CEST) agents. This approach allows simultaneous evaluation of multiple samples in presence of B0 inhomogeneity. Data with and without shimming were comparable in quality. As a first example, we screened a library of 16 samples and were able to obtain high quality CEST spectra with an average acquisition time of 2.6 minutes, which implies the great potential of this method in developing CEST MRI reporter agents.
12:06 810. High Resolution MR Imaging of Brain Lactate Using Selective Saturation Transfer
    Christopher Lascola1,2, Talignair Venkatraman1, Sean Snodgress1, Haichen Wang3
Radiology, Duke University Medical Center, Durham, NC, USA; 2Brain Imaging and Analysis Center, Durham, NC, USA; 3Anesthesiology, Duke University Medical Center, Durham, NC, USA
    Lactate is an important metabolic biomarker for a variety of neurological disease states, and is now also recognized as an essential substrate of neuronal metabolism [1]. An improved MR method for mapping brain lactate would aid the study of this important metabolite in physiologic and pathologic conditions, and provide a clinically relevant diagnostic tool. 13C and 1H MR spectroscopic (MRS) methods have been used previously to measure brain lactate concentrations but have limited temporal and spatial resolution. The purpose of this study is to investigate whether magnetic coupling between lactate methyl and water protons previously reported in MRS studies [2] and in phantoms [3] can be exploited to generate MRI contrast specific localized lactate accumulations. Our initial findings show that selective radiofrequency saturation of lactate methyl protons results in cumulative saturation of dominant water protons via immobilized macromolecules in both protein phantoms and in vivo, increasing the sensitivity of lactate detection in vivo as compared to MRS, and enabling high resolution mapping of subtle lactate changes in brain.
12:18 811. Delta Relaxation Enhanced MR: Experimental Validation
    Jamu K. Alford1, Brian K. Rutt1,2, Timothy J. Scholl1, William B. Handler1, Blaine A. Chronik1
Physics and Astronomy, The University of Western Ontario, London, Ontario, Canada; 2Imaging, Robarts Research Institute, London, Ontario, Canada
    Herein the first experimental validation of a new approach to MRI molecular imaging is described. This method, delta relaxation enhanced MRI (dreMR) uses induced magnetic field perturbations as a means of measuring the binding of molecule-specific MR probes such as Vasovist and EP-2104R to their respective target molecules. It is shown that this approach results in unprecedented specificity to the binding state of the contrast agent and therefore clearly distinguishes samples containing the target molecule from all other samples. This method has significant implications in the areas of molecular imaging, tumor physiology, and detection of disease.