Molecular Imaging: New Mechanisms & Techniques

Wednesday 14 May 2014

Mohammad Haris^1,2, Anup Singh¹, Imran Mohammed³, Ranjit Ittyerah⁴, Kavindra Nath⁴, Ravi Prakash R Nanga¹, Catherine Debrosse¹, Feliks Kogan¹, Kejia Cai^1,5, Harish Poptani⁴, Damodar Reddy¹, Hari Hariharan¹, and Ravinder Reddy^1
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.

Amnon Bar-Shir^1,2, Nikita Oskolkov^1,3, Galit Pelled^1,3, Jeff W.M. Bulte^1,2, Michael T McMahon^1,3, and Assaf A. Gilad^1,2
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.

Dian R. Arifin^1,2, Kannie W.Y. Chan^1,2, Peter C.M. van Zijl^1,3, Daniel S. Warren⁴, Zhaoli Sun⁴, Jeff W.M. Bulte^1,2, and Michael T. McMahon^1,3
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.

Silvia Rizzitelli¹, Pierangela Giustetto^1,2, Juan Carlos Cutrin^1,3, Marta Ruzza¹, Cinzia Boffa¹, Daniela Delli Castelli¹, Valeria Menchise⁴, Filippo Molinari⁵, Silvio Aime^1,2, and Enzo Terreno^1,2
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.

Miroslaw Janowski^1,2, 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 Walczak^1,5
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.

Robert Borowiak^1,2, Jens Groebner³, Dmitry Kurzhunov³, Elmar Fischer³, Iulius Dragonu³, and Michael Bock^3
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.

Friedrich Wetterling^1,2, Eoin K Fox³, Dermot F Brougham³, and Oliviero Gobbo^4
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.

Veronica Clavijo Jordan^1,2 and Kevin M Bennett^3
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.

Nikorn Pothayee¹, Diana Cummings², Leonardo Belluscio², and Alan Koretsky^1
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.

Takashi Watanabe¹, Jens Frahm¹, and Thomas Michaelis^1
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.