0000000000082709
AUTHOR
Laura M. Schreiber
showing 46 related works from this author
Multifunctional superparamagnetic MnO@SiO2 core/shell nanoparticles and their application for optical and magnetic resonance imaging
2012
Highly biocompatible multifunctional nanocomposites consisting of monodisperse manganese oxide nanoparticles with luminescent silica shells were synthesized by a combination of w/o-microemulsion techniques and common sol–gel procedures. The nanoparticles were characterized by TEM analysis, powder XRD, SQUID magnetometry, FT-IR, UV/vis and fluorescence spectroscopy and dynamic light scattering. Due to the presence of hydrophilic poly(ethylene glycol) (PEG) chains on the SiO2 surface, the nanocomposites are highly soluble and stable in various aqueous solutions, including physiological saline, buffer solutions and human blood serum. The average number of surface amino groups available for lig…
Hyperpolarized 1H long lived states originating from parahydrogen accessed by rf irradiation
2013
Hyperpolarization has found many applications in Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI). However, its usage is still limited to the observation of relatively fast processes because of its short lifetimes. This issue can be circumvented by storing the hyperpolarization in a slowly relaxing singlet state. Symmetrical molecules hyperpolarized by Parahydrogen Induced Hyperpolarization (PHIP) provide a straightforward access to hyperpolarized singlet states because the initial parahydrogen singlet state is preserved at almost any magnetic field strength. In these systems, which show a remarkably long 1H singlet state lifetime of several minutes, the conversion of t…
Flip-angle measurement by magnetization inversion: Calibration of magnetization nutation angle in hyperpolarized 3 He magnetic resonance imaging lung…
2010
The aim of this work was to establish a new, fast, and robust method of flip-angle calibration for magnetic resonance imaging of hyperpolarized 3He. The method called flip-angle measurement with magnetization inversion is based on acquiring images from periodically inverted longitudinal magnetization created using the spatial modulation of magnetization technique. By measuring the width of the area where the magnetization was inverted by the spatial modulation of magnetization preparation in phase images, the flip angle can be generated using a simple equation. To validate and establish the limits of the proposed method, flip-angle measurement with magnetization inversion acquisitions were …
Area at Risk and Viability after Myocardial Ischemia and Reperfusion Can Be Determined by Contrast-Enhanced Cardiac Magnetic Resonance Imaging
2008
<i>Background/Aims:</i> Clinical differentiation between infarcted and viable myocardium in the ischemic area at risk is controversial. We investigated the potential of contrast-enhanced cardiac magnetic resonance imaging (ceCMRI) in determining the area at risk 24 h after ischemia. <i>Methods:</i> Myocardial ischemia was induced by percutaneous coronary intervention of the left anterior descending coronary artery in pigs. Coronary occlusion time was 30 min in group A, which caused little myocardial infarction and 45 min in group B, which led to irreversible damage. 24 h after reperfusion ceCMRI was performed at 2 and 15 min after administration of gadolinium-diethyl…
Pushing the Limit – MRI of the Lung Using Hyperpolarized 3-Helium in Conjunction with Parallel Imaging
2009
Imaging of the lung with hyperpolarized 3He became a well known technique in the last decade. Being able to image ventilation and the microstructure of the lung an increase of SNR and a shortage of scan time is eligible. By using a 32-channel phased array the sensitivity was increased dramatically. High resolution 2D-images with a resolution of 1 × 1 mm2 having a 3 mm slice was realized, showing highly detailed images of the lung. By applying parallel imaging techniques the SNR could be increased and scan time was reduced drastically by using a 2D acceleration of R = 4 × 2 with a 3D-protocol covering the whole lung.
Quantitative myocardial perfusion magnetic resonance imaging: the impact of pulsatile flow on contrast agent bolus dispersion.
2011
Myocardial blood flow (MBF) can be quantified using T1-weighted first-pass magnetic resonance imaging (MRI) in combination with a tracer-kinetic model, like MMID4. This procedure requires the knowledge of an arterial input function which is usually estimated from the left ventricle (LV). Dispersion of the contrast agent bolus may occur between the LV and the tissue of interest. The aim of this study was to investigate the dispersion under conditions of physiological pulsatile blood flow, and to simulate its effect on MBF quantification. The dispersion was simulated in coronary arteries using a computational fluid dynamics (CFD) approach. Simulations were accomplished on straight vessels wit…
Magnetic resonance imaging of dissolved hyperpolarized 129Xe using a membrane-based continuous flow system.
2009
Abstract A technique for continuous production of solutions containing hyperpolarized 129Xe is explored for MRI applications. The method is based on hollow fiber membranes which inhibit the formation of foams and bubbles. A systematic analysis of various carrier agents for hyperpolarized 129Xe has been carried out, which are applicable as contrast agents for in vivo MRI. The image quality of different hyperpolarized Xe solutions is compared and MRI results obtained in a clinical as well as in a nonclinical MRI setting are provided. Moreover, we demonstrate the application of 129Xe contrast agents produced with our dissolution method for lung MRI by imaging hyperpolarized 129Xe that has been…
Realization of administration unit for3He with gas recycling
2011
Hyperpolarized (HP) noble gases (3He,129Xe) are used for MR-imaging of the lung. In the majority of case the HP gas is filled in Tedlarbags and directly inhaled by the patients. Starting from an earlier pilot device, an administration unit was built respectively to the Medical Devices Law to administer patients HP noble gas boli in defined quantities and at a predefined time during inspiration with high reproducibility and reliability without reducing MR-quality. The patient's airflows are monitored and recorded. It is possible to use gas admixtures, measure the polarization on-line and collect the exhaled gas for later recycling. The first images with healthy volunteers were taken with thi…
Local transient myocardial liposomal gene transfer of inducible nitric oxide synthase does not aggravate myocardial function and fibrosis and leads t…
2010
Microcirculation (2010) 17, 69–78. doi: 10.1111/j.1549-8719.2010.00002.x Abstract Background: This study was designed to explore the effect of transient inducible nitric oxide synthase (iNOS) overexpression via cationic liposome-mediated gene transfer on cardiac function, fibrosis, and microvascular perfusion in a porcine model of chronic ischemia. Methods and Results: Chronic myocardial ischemia was induced using a minimally invasive model in 23 landrace pigs. Upon demonstration of heart failure, 10 animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection and 13 animals received a sham procedure to serve as control. The efficacy of this iNOS-gene-…
Progression of emphysema evaluated by MRI using hyperpolarized 3he (hp 3he) measurements in patients with alpha-1-antitrypsin (a1at) deficiency compa…
2009
Background: The progression of emphysema is traditionally measured by pulmonary function test, with forced expiratory volume in 1 s (FEV1) being the most accepted and used measurement. However, FEV1 is insensitive in detecting mild/slow progression of emphysema because of low reproducibility as compared to yearly decline. Purpose: To investigate the progression of emphysema over a period of 2 years using diffusion-weighted hyperpolarized (HP) 3He magnetic resonance imaging (MRI) in patients with alpha-1-antitrypsin (A1AT) deficiency. Material and Methods: Nine patients with severe A1AT deficiency were studied over a period of 2 years (baseline, year 1, and year 2) with HP 3He MRI using app…
DNP in MRI: an in-bore approach at 1.5 T.
2011
Abstract We have used liquid state (“Overhauser”) Dynamic Nuclear Polarization (DNP) to significantly enhance the signal to noise ratio (SNR) of Magnetic Resonance Imaging (MRI). For the first time this was achieved by hyperpolarizing directly in the MRI-scanner field of 1.5 T in continuous flow mode and immediately delivering the hyperpolarized substance to the imaging site to ensure maximum contrast between hyperpolarized sample and sample at thermal polarization. We achieve a maximum absolute signal enhancement factor of 98; while the hyperpolarized sample is transported at a flow rate of up to 30 ml/h yielding an average flow speed up to 470 mm/s over a distance of approximately 80 mm. …
Functionalized magnetic nanoparticles for selective targeting of cells
2009
AbstractInitiation of pathways that lead to proliferation and chemoresistance by Toll-like receptors (TLRs) is an important factor in cancer progression. Here, we show the response of human cancer cells to TLR signaling inevitably linked to tumor biology. The approach is based on tailored multifunctional magnetic nanoparticles equipped with pathogen-derived ligands (CpG) functioning as TLR agonists (molecular component) to investigate the impact of transcription factor immune activation on human cancer cells. Magnetic nanoparticles (MnO and bifunctional Au-MnO) particles were covalently coated with a multifunctional polymer, displaying no cytotoxicity, to being able to enter cells while car…
Visualization of inert gas wash-out during high-frequency oscillatory ventilation using fluorine-19 MRI
2010
High-frequency oscillatory ventilation is looked upon as a lung-protective ventilation strategy. For a further clarification of the physical processes promoting gas transport, a visualization of gas flow and the distribution of ventilation are of considerable interest. Therefore, fluorine-19 magnetic resonance imaging of the imaging gas octafluorocyclobutane (C(4) F(8) ) during high-frequency oscillatory ventilation was performed in five healthy pigs. For that, a mutually compatible ventilation-imaging system was set up and transverse images were acquired every 5 sec using FLASH sequences on a 1.5 T scanner. Despite a drop in signal-to-noise ratio after the onset of high-frequency oscillato…
Comparison of the quantitative first pass myocardial perfusion MRI with and without prospective slice tracking: Comparison between breath-hold and fr…
2010
Physiologic motion of the heart is one of the major problems of myocardial blood flow quantification using first pass perfusion-MRI method. To overcome these problems, a perfusion pulse sequence with prospective slice tracking was developed. Cardiac motion was monitored by a navigator directly positioned at heart's basis to overcome no additional underlying model calculations connecting diaphragm and cardiac motion. Additional prescans were used before the perfusion measurement to detect slice displacements caused by remaining cardiac motion between navigator and the perfusion slice readout. The pulse sequence and subsequent quantification of myocardial blood flow was tested in healthy pigs…
Resting myocardial blood flow quantification using contrast-enhanced magnetic resonance imaging in the presence of stenosis: A computational fluid dy…
2015
Purpose: The extent to which atherosclerotic plaques affect contrast agent (CA) transport in the coronary arteries and, hence, quantification of myocardial blood flow (MBF) using magnetic resonance imaging (MRI) is unclear. The purpose of this work was to evaluate the influence of plaque induced stenosis both on CA transport and on the accuracy of MBF quantification. Methods: Computational fluid dynamics simulations in a high-detailed realistic vascular model were employed to investigate CA bolus transport in the coronary arteries. The impact of atherosclerosis was analyzed by inserting various medium- to high-grade stenoses in the vascular model. The influence of stenosis morphology was ex…
Magnetic separation of encapsulated islet cells labeled with superparamagnetic iron oxide nano particles.
2012
Islet cell transplantation is a promising option for the restoration of normal glucose homeostasis in patients with type 1 diabetes. Because graft volume is a crucial issue in islet transplantations for patients with diabetes, we evaluated a new method for increasing functional tissue yield in xenogeneic grafts of encapsulated islets. Islets were labeled with three different superparamagnetic iron oxide nano particles (SPIONs; dextran-coated SPION, siloxane-coated SPION, and heparin-coated SPION). Magnetic separation was performed to separate encapsulated islets from the empty capsules, and cell viability and function were tested. Islets labeled with 1000 μg Fe/ml dextran-coated SPIONs expe…
Magnetic Resonance Imaging and Computational Fluid Dynamics of High Frequency Oscillatory Ventilation (HFOV)
2011
In order to better understand the mechanisms of gas transport during High Frequency Oscillatory Ventilation (HFOV) Magnetic Resonance Imaging (MRI) with contrast gases and numerical flow simulations based on Computational Fluid Dynamics(CFD) methods are performed.
Heparin–polynitroxides: Synthesis and preliminary evaluation as cardiovascular EPR/MR imaging probes and extracellular space-targeted antioxidants
2011
We report here the synthesis of heparin-polynitroxide derivatives (HPNs) in which nitroxide moieties are linked either to uronic acid or glycosamine residues of the heparin macromolecule. HPNs have low anticoagulant activity, possess superoxide scavenging properties, bind to the vascular endothelium/extra-cellular matrix and can be detected by EPR and MRI techniques. As the vascular wall-targeted redox-active paramagnetic compounds, HPNs may have both diagnostic (molecular MRI) and therapeutic (ecSOD mimics) applications.
Measurement of gas transport kinetics in high-frequency oscillatory ventilation (HFOV) of the lung using hyperpolarized 3He magnetic resonance imaging
2010
PURPOSE: To protect the patient with acute respiratory distress syndrome from ventilator associated lung injury (VALI) high-frequency oscillatory ventilation (HFOV) is used. Clinical experience has proven that HFOV is an efficient therapy when conventional artificial ventilation is insufficient. However, the optimal settings of HFOV parameters, eg, tidal volumes, pressure amplitudes and frequency for maximal lung protection, and efficient gas exchange are not established unambiguously. METHODS: In this work magnetic resonance imaging (MRI) with hyperpolarized (3)He was employed to visualize the redistribution of gas within the cadaver pig lung during HFOV. The saturated slice method was use…
Gene therapy with iNOS enhances regional contractility and reduces delayed contrast enhancement in a model of postischemic congestive heart failure
2012
Aims: The purpose of this study was to evaluate the effect of transient local myocardial gene transfer of iNOS on cardiac function in a large mammal animal model of heart failure induced by chronic ischemia. Methods: Chronic myocardial ischemia was induced using a minimally invasive model in 16 landrace pigs. Upon demonstration of heart failure, eight animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection; eight animals received a sham procedure to serve as control. Results: The transmurality of late enhancement (control: 46.4%, iNOS: 35.9%; p < 0.05) was significantly decreased in the ischemic area in the iNOS-treated group. Wall thickness at end-…
Improvement of solubility and biocompatibility of MnO based nanoparticles in aqueous solutions
2011
ABSTRACTMnO nanoparticles were surface modified using two different multifunctional polymers. By introducing a PEG group, the long term stability, MRI applicability and sterile filtration could be greatly improved. Furthermore, PEGylated MnO NPs were less toxic compared to non-PEGylated NPs. The results suggest that these nanoparticles are suitable for in vivo applications.
Synthesis, characterization and functionalization of nearly mono-disperse copper ferrite CuxFe3−xO4 nanoparticles
2011
Magnetic nanocrystals are of great interest for a fundamental understanding of nanomagnetism and for their technological applications. CuxFe3−xO4 nanocrystals (x ≈ 0.32) with sizes ranging between 5 and 7 nm were synthesized starting from Cu(HCOO)2 and Fe(CO)5 using oleic acid and oleylamine as surfactants. The nanocrystals were characterized by high-resolution transmission electron microscopy (HRTEM), electron diffraction (ED), magnetization studies and Mossbauer spectroscopy. The CuxFe3−xO4 particles are superparamagnetic at room temperature 300 K with a saturation magnetization of 30.5 emu g−1. Below their blocking temperature of 60 K, they become ferrimagnetic, and at 5 K they show a co…
CpG-DNA loaded multifunctional MnO nanoshuttles for TLR9-specific cellular cargo delivery, selective immune-activation and MRI
2012
Initiation of pathways that lead to a proliferation and chemoresistance by Toll-like receptors (TLRs) are an important factor in cancer progression. Multifunctional magnetic nanoparticles equipped with a pathogen-derived ligand (CpG) functioning as TLR agonists were used to show the impact of immune activation on human HNSCC (head and neck squamous cell carcinoma) cells. The response of human cancer cells to TLR signaling is linked to tumor biology. The magnetic MnO nanoparticles were coated with a multifunctional polymer, displaying no cytotoxicity and being able to enter cells while carrying foreign DNA (unmethylated CpG) to recognize intracellular TLR9. Both the particle and the nucleic …
A 20-channel receive-only mouse array coil for a 3 T clinical MRI system
2011
A 20-channel phased-array coil for MRI of mice has been designed, constructed, and validated with bench measurements and high-resolution accelerated imaging. The technical challenges of designing a small, high density array have been overcome using individual small-diameter coil elements arranged on a cylinder in a hexagonal overlapping design with adjacent low impedance preamplifiers to further decouple the array elements. Signal-to-noise ratio (SNR) and noise amplification in accelerated imaging were simulated and quantitatively evaluated in phantoms and in vivo mouse images. Comparison between the 20-channel mouse array and a length-matched quadrature driven small animal birdcage coil sh…
Design and evaluation of a 32-channel phased-array coil for lung imaging with hyperpolarized 3-helium
2010
Imaging with hyperpolarized 3-helium is becoming an increasingly important technique for MRI diagnostics of the lung but is hampered by long breath holds (>20 sec), which are not always applicable in patients with severe lung disease like chronic obstructive pulmonary disease (COPD) or α-1-anti-trypsin deficiency. Additionally, oxygen-induced depolarization decay during the long breath holds complicates interpretation of functional data such as apparent diffusion coefficients. To address these issues, we describe and validate a 1.5-T, 32-channel array coil for accelerated 3He lung imaging and demonstrate its ability to speed up imaging 3He. A signal-to-noise ratio increase of up to a factor…
Development of MR active contrast agents via Parahydrogen Induced Polarization
2009
Parahydrogen Induced Polarization provides dramatic MR signal enhancement that can be exploited for molecular imaging. This method allows amongst others for Magnetic Resonance Imaging of 13C and 15N, which is usually constrained by the low MR sensitivity of these nuclei. By combining hydrogenation of barbiturates with parahydrogen under special experimental conditions (PASADENA under pressure) with a polarization transfer sequence we demonstrate the transfer of the initial 1H polarization to 13C. The polarization transfer yields a signal increase for 13C of more than 1000. Hence, the role of certain target compounds such as anesthetics like the barbituric acid derivatives could be investiga…
Au@MnO-“Nanoblumen” - Hybrid-Nanokomposite zur selektiven dualen Funktionalisierung und Bildgebung
2010
In j ngster Vergangenheit hat das Interesse f r die Entwicklung von Hybrid-Nanostrukturen, die sich aus verschiedenen Materialien zusammensetzen, in erheblichem Mase zugenommen. Es wurde berichtet, dass die Zusammenf hrung verschiedener Nanomaterialien, die ihrerseits spezifische optische, magnetische oder elektronische Eigenschaften aufweisen, zu Kompositen aus mehreren dieser Komponenten, deren individuelle Eigenschaften ver ndern oder sogar verbessern k nnen. Durch gezielte Optimierung der Struktur und der Grenzfl chenwechselwirkung innerhalb der Nanokomposite k nnte eine breite Basis f r zuk nftige Technologien geschaffen werden, beispielweise f r die synchrone Biomarkierung, Proteintre…
Quantification of Myocardial Blood Flow Using Magnetic Resonance Imaging with Different accelerated Pulse Sequences
2009
The aim of this study was to compare SRTurboFLASH, SR-TrueFISP, and SR-segEPI pulse sequences using a twofold TSENSE-acceleration with regard to their use in quantification of myocardial blood flow (MBF). Six healthy volunteers were examined at 1.5T by first pass myocardial perfusion MRI at rest using all three TSENSE-accelerated pulse sequences. For absolute quantifi-cation of MBF XSIM software with the MMID4 model has been used. MBF analyses revealed significant MBF differences between SRTurboFLASH and SR-segEPI compared to SR-TrueFISP (p<0.005 and p<0.001, respectively). Differences between SRTurboFLASH and SR-segEPI were not statistically significant. The median MBF values for SR-TurboF…
Quantitative contrast-enhanced myocardial perfusion magnetic resonance imaging: Simulation of bolus dispersion in constricted vessels
2009
Quantification of myocardial blood flow (MBF) by means of T 1 -weighted first-pass magnetic resonance imaging(MRI) requires knowledge of the arterial input function (AIF), which is usually estimated from the left ventricle (LV). Dispersion of the contrast agent bolus may occur between the LV and the tissue of interest, which leads to systematic underestimation of the MBF. The aim of this study was to simulate the dispersion along a simplified coronary artery with different stenoses. To analyze the dispersion in vessels with typical dimensions of coronary arteries, simulations were performed using the computational fluid dynamics approach. Simulations were accomplished on straight vessels wi…
Application unit for the administration of contrast gases for pulmonary magnetic resonance imaging: optimization of ventilation distribution for3He-M…
2014
Purpose MRI of lung airspaces using gases with MR-active nuclei (3He, 129Xe, and 19F) is an important area of research in pulmonary imaging. The volume-controlled administration of gas mixtures is important for obtaining quantitative information from MR images. State-of-the-art gas administration using plastic bags (PBs) does not allow for a precise determination of both the volume and timing of a 3He bolus. Methods A novel application unit (AU) was built according to the requirements of the German medical devices law. Integrated spirometers enable the monitoring of the inhaled gas flow. The device is particularly suited for hyperpolarized (HP) gases (e.g., storage and administration with m…
Phase separated Cu@Fe3O4 heterodimer nanoparticles from organometallic reactants
2011
Cu@Fe3O4 heteroparticles with distinct morphologies were synthesized from organometallic reactants. The shape of the magnetic domains could be controlled by the solvent and reaction conditions. They display magnetic and optical properties that are useful for simultaneous magnetic and optical detection. After functionalization, the Cu@Fe3O4 heterodimers become water soluble. The morphology, structure, magnetic and optical properties of the as-synthesized heterodimer nanoparticles were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), mossbauer spectroscopy, superconducting quantum interference device (SQUID) magnetometry, and dark field imaging. A special a…
Three-dimensional mapping of the B 1 field using an optimized phase-based method: Application to hyperpolarized 3 He in lungs
2010
A novel method is presented for the three-dimensional mapping of the B1-field of a transmit radio-frequency MR coil. The method is based on the acquisition of phase images, where the effective flip angle is encoded in the phase of the nonselective hard pulse excitation. The method involves the application of a rectangular composite pulse as excitation in a three-dimensional gradient recall echo to produce measurable phase angle variation. However, such a pulse may significantly increase the radio-frequency power deposition in excess of the standard acceptable SAR limits, imposing extremely long TRs (>100 msec), which would result in acquisition times significantly greater than a single brea…
Au@MnO nanoflowers: hybrid nanocomposites for selective dual functionalization and imaging.
2010
Recently, the development of hybrid nanostructures consisting of various materials has attracted considerable interest. The assembly of different nanomaterials with specific optical, magnetic, or electronic properties to multicomponent composites can change and even enhance the properties of the individual constituents. Specifically tuning the structure and interface interactions within the nanocomposites has resulted in novel platforms of materials that may lead the way to various future technologies, such as synchronous biolabeling, protein separation and detection, heterogeneous catalysis, and multimodal imaging in biomedicine. Of the various kinds of nanomaterials, gold nanorods show an…
Controlling phase formation in solids: rational synthesis of phase separated Co@Fe2O3 heteroparticles and CoFe2O4 nanoparticles
2011
A wet chemical approach from organometallic reactants allowed the targeted synthesis of Co@Fe(2)O(3) heterodimer and CoFe(2)O(4) ferrite nanoparticles. They display magnetic properties that are useful for magnetic MRI detection.
Proton magnetic resonance imaging with para-hydrogen induced polarization.
2012
A major challenge in imaging is the detection of small amounts of molecules of interest. In the case of magnetic resonance imaging (MRI) their signals are typically concealed by the large background signal of e.g. the body. This problem can be tackled by hyperpolarization which increases the NMR signals up to several orders of magnitude. However, this strategy is limited for (1)H, the most widely used nucleus in NMR and MRI, because the enormous number of protons in the body screens the small amount of hyperpolarized ones. Here, we describe a method giving rise to high (1)H MRI contrast for hyperpolarized molecules against a large background signal. The contrast is based on the J-coupling i…
Pathogen-Mimicking MnO Nanoparticles for Selective Activation of the TLR9 Pathway and Imaging of Cancer Cells
2009
Here, design of the first pathogen-mimicking metal oxide nanoparticles with the ability to enter cancer cells and to selectively target and activate the TLR9 pathway, and with optical and MR imaging capabilities, is reported. The immobilization of ssDNA (CpG ODN 2006) on MnO nanoparticles is performed via the phosphoramidite route using a multifunctional polymer. The multifunctional polymer used for the nanoparticle surface modification not only affords a protective organic biocompatible shell but also provides an efficient and convenient means for loading immunostimulatory oligonucleotides. Since fluorescent molecules are amenable to photodetection, a chromophore (Rhodamine) is introduced …
Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascul…
2012
Novel strategies of cancer therapy combine irradiation and anti-angiogenic active compounds. However, little is known concerning the undesired cellular and molecular effects caused by this novel treatment concept. We used a mouse squamous cell carcinoma (SCC) xenotransplantation model to evaluate the potential undesired effects which compromise the success of this therapeutic combination. SCCs were subcutanously implanted in nude mice. Animals were treated with a fractionated irradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascular endothelial growth factor (VEGF) antibodies. Controls remained untreated. Before and after treatment, resonance imaging (MRI), …
Lung ventilation- and perfusion-weighted Fourier decomposition magnetic resonance imaging: In vivo validation with hyperpolarized3He and dynamic cont…
2012
The purpose of this work was to validate ventilation-weighted (VW) and perfusion-weighted (QW) Fourier decomposition (FD) magnetic resonance imaging (MRI) with hyperpolarized (3)He MRI and dynamic contrast-enhanced perfusion (DCE) MRI in a controlled animal experiment. Three healthy pigs were studied on 1.5-T MR scanner. For FD MRI, the VW and QW images were obtained by postprocessing of time-resolved lung image sets. DCE acquisitions were performed immediately after contrast agent injection. (3)He MRI data were acquired following the administration of hyperpolarized helium and nitrogen mixture. After baseline MR scans, pulmonary embolism was artificially produced. FD MRI and DCE MRI perfus…
Highly soluble multifunctional MnO nanoparticles for simultaneous optical and MRI imaging and cancer treatment using photodynamic therapy
2010
Superparamagnetic MnO nanoparticles were functionalized using a hydrophilic ligand containing protoporphyrin IX as photosensitizer. By virtue of their magnetic properties these nanoparticles may serve as contrast enhancing agents for magnetic resonance imaging (MRI), while the fluorescent target ligand protoporphyrin IX allows simultaneous tumor detection and treatment by photodynamic therapy (PDT). Caki-1 cells were incubated with these nanoparticles. Subsequent exposure to UV light lead to cell apoptosis due to photoactivation of the photosensitizer conjugated to the nanoparticles. This method offers great diagnostic potential for highly proliferative tissues, including tumors. In additio…
Development of a Polarizer and Biocompatible Polarizing Agents for Use in Dynamic Nuclear Polarization DNP-Enhanced NMR and MRI
2009
The application of 13C (or other low γ nuclei) NMR spectroscopy and imaging for clinical diagnosis has been constrained by the extremely long imaging and spectroscopy acquisition times that are required to obtain high SNR under physiological conditions (low natural abundance of 13C, low concentration of 13C-compounds, physiological temperature etc.). However, this obstacle could be overcome by in vitro hyperpolarization of a 13C-containing molecule with long spin lattice relaxation time via dynamic nuclear polarization (DNP) and subsequent injection into the animal or patient of investigation [1, 2]. DNP is achieved by resonant excitation of electron spins of radicals (electron paramagnetic…
How do different surface modification strategies affect the properties of MnO nanoparticles for biomedical applications? Comparison of PEGylated and …
2011
ABSTRACTMnO nanoparticles (NPs) were surface functionalized by two different approaches, (1) using a dopamine-poly(ethylene glycol) (PEG) (DA-PEG) ligand and (2) by encapsulation within a thin silica shell applying a novel approach. Both MnO@DA-PEG and MnO@SiO2 NPs exhibited excellent long-term stability in physiological solutions. In addition, the cytotoxic potential of both materials was comparatively low. Furthermore, owing to the magnetic properties of MnO NPs, both MnO@DA-PEG and MnO@SiO2 lead to a shortening of the longitudinal relaxation time T1 in MRI. In comparison to the PEGylated MnO NPs, the presence of a thin silica shell led to a greater stability of the MnO core itself by pre…
Quantification of pulmonary blood flow (PBF): validation of perfusion MRI and nonlinear contrast agent (CA) dose correction with H(2)15O positron emi…
2009
Validation of quantification of pulmonary blood flow (PBF) with dynamic, contrast-enhanced MRI is still missing. A possible reason certainly lies in difficulties based on the nonlinear dependence of signal intensity (SI) from contrast agent (CA) concentration. Both aspects were addressed in this study. Nine healthy pigs were examined by first-pass perfusion MRI using gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) and HO positron emission tomography (PET) imaging. Calculations of hemodynamic parameters were based on a one-compartment model (MR) and a two-compartment model (PET). Simulations showed a significant error when assuming a linear relation between MR SI and CA dose in the …
Small animal tumour imaging with MRI and the ECAT EXACT scanner: application of partial volume correction and comparison with microPET data.
2010
Objective Partial volume effects caused by limited spatial resolution of conventional positron emission tomography (PET) scanners result in an underestimation of the activity concentration in small tumours. The aim of the study was to evaluate the feasibility of small animal tumour imaging with the clinical PET scanner ECAT EXACT after partial volume correction based on MRI calculations. The same tumour model was examined additionally with the small animal PET system, microPET focus 120. Methods Before the ECAT EXACT studies recovery coefficients for different sphere volumes were generated with phantom experiments. For the following in-vivo study DS-sarcoma cells were implanted on both hind…
Spin‐Labeled Heparins as Polarizing Agents for Dynamic Nuclear Polarization
2010
A potentially biocompatible class of spin-labeled macromolecules, spin-labeled (SL) heparins, and their use as nuclear magnetic resonance (NMR) signal enhancers are introduced. The signal enhancement is achieved through Overhauser-type dynamic nuclear polarization (DNP). All presented SL-heparins show high 1 H DNP enhancement factors up to E=-110, which validates that effectively more than one hyperfine line can be saturated even for spin-labeled polarizing agents. The parameters for the Overhauser-type DNP are determined and discussed. A striking result is that for spin-labeled heparins, the off-resonant electron paramagnetic resonance (EPR) hyperfine lines contribute a non-negligible part…
Ventilation-Perfusion Ratio in Perflubron During Partial Liquid Ventilation
2010
BACKGROUND: Functional magnetic resonance imaging (fMRI) of fluorine-19 allows for the mapping of oxygen partial pressure within perfluorocarbons in the alveolar space (Pao(2)). Theoretically, fMRI-detected Pao(2) can be combined with the Fick principle approach, i.e., a mass balance of oxygen uptake by ventilation and delivery by perfusion, to quantify the ventilation-perfusion ratio (Va/Q) of a lung region: The mixed venous blood and the inspiratory oxygen fraction, which are equal for all lung regions, are measured. In addition, the local expiratory oxygen fraction and the end capillary oxygen content, both of which may differ between the lung regions, are calculated using the fMRI-detec…
Magnetic resonance imaging of (1)H long lived states derived from parahydrogen induced polarization in a clinical system.
2015
Hyperpolarization is a powerful tool to overcome the low sensitivity of nuclear magnetic resonance (NMR). However, applications are limited due to the short lifetime of this non equilibrium spin state caused by relaxation processes. This issue can be addressed by storing hyperpolarization in slowly decaying singlet spin states which was so far mostly demonstrated for non-proton spin pairs, e.g. 13C-13C. Protons hyperpolarized by parahydrogen induced polarization (PHIP) in symmetrical molecules, are very well suited for this strategy because they naturally exhibit a long-lived singlet state. The conversion of the NMR silent singlet spin state to observable magnetization can be achieved by ma…