Joint Annual Meeting ISMRM-ESMRMB 2014 10-16 May 2014 Milan, Italy

Molecular Imaging: New Mechanisms & Techniques

Wednesday 14 May 2014
Red 1 & 2  16:00 - 18:00 Moderators: Claudia Calcagno, M.D., Ph.D., Peter Caravan, Ph.D.

16:00 0682.   GluCEST imaging of Tumor Protease Activity
Mohammad Haris1,2, Anup Singh1, Imran Mohammed3, Ranjit Ittyerah4, Kavindra Nath4, Ravi Prakash R Nanga1, Catherine Debrosse1, Feliks Kogan1, Kejia Cai1,5, Harish Poptani4, Damodar Reddy1, Hari Hariharan1, and Ravinder Reddy1
1CMROI, Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 2Research Branch, Sidra Medical and Research Center, Doha, Qatar, 3Department of Pharmacology and Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 4Molecular Imaging, Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 5CMRR 3T Research Program, University of Illinois at Chicago, Chicago, IL, United States

We propose a noninvasive MRI method that is capable of measuring expression of cathepsin proteases in tumors in vivo. Degradation of L-poly glutamate by cathepsins in to glutamate or smaller peptide fragments exposes amine protons, which can be monitored through chemical exchange saturation transfer (CEST) imaging. In the current study, we have shown the feasibility of mapping cathepsins in tumor cells line and rat model of brain tumor using CEST imaging technique.

16:12 0683.   Developing a nanobiosensor for non-invasive visualization of the AKT signaling pathways - permission withheld
Amnon Bar-Shir1,2, Nikita Oskolkov1,3, Galit Pelled1,3, Jeff W.M. Bulte1,2, Michael T McMahon1,3, and Assaf A. Gilad1,2
1Radiology, Johns Hopkins University, Baltimore, MD, United States, 2Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, United States, 3F.M. Kirby Research Center, Kennedy Krieger Institute, Baltimore, MD, United States

The goal of this study is to develop a non-invasive platform to visualize the response to protein kinase inhibitors in brain cancer. For that end, we started with screening for an ideal peptide that will provide high CEST contrast that will be reduced only upon phosphorylation by the enzyme AKT. Three peptides, substrates of the enzyme AKT, generated CEST contrast. Adding phosphorus to the threonine residue resulted in reduction of the contrast. Thus, these finidngs are the first step in optimizing a peptide with the best senstivity and specificity toward AKT.

16:24 0684.   pH-nanosensors for monitoring the cell fate after transplantation into diabetic mice using CEST MRI
Dian R. Arifin1,2, Kannie W.Y. Chan1,2, Peter C.M. van Zijl1,3, Daniel S. Warren4, Zhaoli Sun4, Jeff W.M. Bulte1,2, and Michael T. McMahon1,3
1Russell H. Morgan Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 4Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Imaging the functionality of transplanted islet cells in diabetes is important for proper post-treatment follow-up. Insulin secretion is accompanied by a decrease in pH, and the ability to image pH changes could be used to monitor release of insulin. We investigated the potential of pH-nanosensors incorporated in alginate microcapsules to sense insulin release in diabetic mice using CEST MRI, which detects protons exchanging with water at a rate sensitive to pH. We show that a decrease in CEST contrast of the microcapsules may correspond to an increase in insulin secretion, indicating potential for application to monitoring cell function in diabetes.

16:36 0685.   MRI guidance of Doxorubicin release from liposomes stimulated by pulsed low intensity non-focused Ultrasound in an experimental tumor model
Silvia Rizzitelli1, Pierangela Giustetto1,2, Juan Carlos Cutrin1,3, Marta Ruzza1, Cinzia Boffa1, Daniela Delli Castelli1, Valeria Menchise4, Filippo Molinari5, Silvio Aime1,2, and Enzo Terreno1,2
1Department of Molecular Biotechnology and Health Sciences, Molecular Imaging Center, University of Torino, Torino, Italy, 2Center for Preclinical Imaging, University of Torino, Colleretto Giacosa, Torino, Italy, 3(UBA-CONICET), ININCA, Buenos Aires, Argentina, 4Institute for Biostructures and Bioimages (CNR) c/o Molecular Biotechnology Center, University of Torino, Torino, Italy, 5Biolab, Department of Electronics and Telecommunications, Politecnico di Torino, Torino, Italy

Doxorubicin is one of the most effective antitumoral drugs, which is clinically administered in liposomal form to improve the therapeutic index and reduce side effects. Since liposomes are not able to deeply diffuse in the tumor, several methods to promote the release of the drug at the target site have been proposed. In this contribution, we used pulsed low-intensity non-focused US (pLINFU) as physical trigger to stimulate a mechanic release of the drug from stealth liposomes. The co-encapsulation of the MRI agent Gadoteridol provided a non invasive and efficient MRI guidance to monitor the drug release.

16:48 0686.   Hot-spot 19F imaging of stem cell transplantation into the intrathecal space in a large animal model
Miroslaw Janowski1,2, Guan Wang1, Jiadi Xu3, Monica Pearl1, Gokhuldass Mohandas1, Amnon Bar-Shir1, Monika Barczewska4, Joanna Wojtkiewicz4, Aleksandra Habich4, Wojciech Maksymowicz4, Jeff W.M. Bulte1, Dara Kraitchman1, and Piotr Walczak1,5
1The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, United States, 2NeuroRepair Department, Mossakowski Medical Research Centre PAS, Warsaw, Mazovia, Poland, 3F.M. Kirby Research Center, Kennedy Krieger Institute, Baltimore, Maryland, United States, 4Department of Neurology and Neurosurgery, University of Warmia and Mazury, Olsztyn, Varmia and Masuria, Poland,5Department of Radiology, University of Warmia and Mazury, Varmia and Masuria, Poland

An intrathecal route was found to be a minimally invasive and potentially efficient method of stem cell delivery to the spinal cord. However, that approach is highly challenging due to uncertain cell distribution. Cell tracking with proton imaging proved difficult due to omnipresent magnetic field inhomogeneity. We have shown that suspending stem cells in a hydrogel improves the targeted injection. Labeling of the hydrogel with fluorine nanoparticles enables detailed and quantitative depiction of stem cell distribution. The use of fluorine image-guidance enables a very precise deployment of stem cells within the intrathecal space.

17:00 0687.   Direct cerebral 17O-MRI at a clinical field strenght of 3 Tesla using a Tx/Rx head coil
Robert Borowiak1,2, Jens Groebner3, Dmitry Kurzhunov3, Elmar Fischer3, Iulius Dragonu3, and Michael Bock3
1German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Baden-Württemberg, Germany, 2Radiology - Medical Physics, University Medical Center Freiburg, Freiburg, Baden-Württemberg, Germany, 3Radiology - Medical Physics, University Medical Center Freiburg, Baden-Württemberg, Germany

In this work 17O MRI at natural abundance is presented with a transmit/receive (Tx/Rx) 17O head coil at a clinical field strength of 3 T. Image data sets are acquired of the human brain in an acquisition time of 20 min, and data are co-registered to 1H brain data sets. Data from this preliminary study show that 17O whole brain MRI is possible in a clinical setting.

17:12 0688.   Earth-field magnetic resonance imaging - investigating magnetic nanoparticle contrast in ex vivo liver
Friedrich Wetterling1,2, Eoin K Fox3, Dermot F Brougham3, and Oliviero Gobbo4
1Faculty of Engineering, Trinity College, the University of Dublin, Dublin, Leinster, Ireland, 2Tomometrics Ltd., Dublin, Leinster, Ireland, 3School of Chemical Sciences, Dublin City University, Dublin, Leinster, Ireland, 4School of Pharmacy and Pharmaceutical Sciences and Institute of Neuroscience, Trinity College, the University of Dublin, Dublin, Leinster, Ireland

In the current study, an earth-field magnetic resonance imaging (EFMRI) system was used to firstly examine the effect of magnetic nanoparticles (MNP) on the longitudinal relaxation time in the polarizing field and secondly to acquire images from ex vivo livers containing MNPs. The use of MNPs as contrast agents for relaxation rate enhancement of MRI signal has been previously reported and was confirmed by our EFMRI measurements. 3D image data sets were recorded for control and MNP doped livers. We conclude that earth-field MRI at 50uT provides a promising tool to study MNP concentration changes non-invasively with sufficient spatial resolution as a model system for developing insights into bio-distribution and changes in relaxivity on localisation.

17:24 0689.   Distinguishing magnetic nanoparticles by r2/r1
Veronica Clavijo Jordan1,2 and Kevin M Bennett3
1University of Hawaii at Manoa, Honolulu, HI, United States, 2Arizona State University, Tempe, AZ, United States, 3University of Hawaii at Manoa, HI, United States

In this work we have developed a novel technique to chemically tune the magnetic properties of the iron crystal inside apoferritin. By tuning their properties from paramagnetic to superparamagnetic, we introduce a set of particles with unique r2/r1 combinations. These magnetic signatures can be extracted with a unique scanning technique that result in simultaneous detection of nanoparticle agents and thus of targets at nM concentrations.

17:36 0690.   
Modulating Activity in the Olfactory Bulb Leads to Reversible Changes in Size and Alter Migration of New Neurons
Nikorn Pothayee1, Diana Cummings2, Leonardo Belluscio2, and Alan Koretsky1
1Laboratory of Functional and Molecular Imaging, NINDS, NIH, Bethesda, MD, United States, 2Developmental Neural Plasticity Section, NINDS, NIH, Bethesda, MD, United States

In mammalian, the migrating new neuron precursors play an important role in maintaining neuronal homeostasis in olfactory bulbs (OB). Various techniques based on optical and electron microscopy have been used to study cell migration and neuronal turnover in OB. However, none of these techniques enable longitudinal study of the whole brain within the living subject. We utilized in situ MRI labeling in combination with MRI volumetry to address the question of whether change in olfactory sensory level alter migrating speed and pattern of NPC integration in OB as well as changes in OB sizes in response to alteration of activity deprivation and recovery.

17:48 0691.   Reduced intracellular mobility underlies manganese relaxivity in mouse brain in vivo: MRI at 2.35 and 9.4 T
Takashi Watanabe1, Jens Frahm1, and Thomas Michaelis1
1Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany

One day after systemic administration of manganese, increases of the longitudinal relaxation rate ∆R1 in several brain regions are significantly higher at 2.35 T than at 9.4 T. In contrast, ∆R1 after intraventricular Gd-DTPA administration are not significantly different. The pronounced field dependence of manganese relaxivities indicates a reduced mobility of manganese in vivo by confinement to a viscous fluid compartment and/or due to macromolecular binding. This is further supported by a slow release of manganese from nerve cells post mortem, which occurs despite a high permeability of damaged cellular membranes.