EMIM 2015 - Session Details

PS 15 | Applications of Novel Imaging Techniques
Type: Parallel Session
Chair:  Adriaan Lammertsma, Thomas Snoeks
Date: March 20, 2015
Time: 8:00 - 9:30
Room: HS 24

For detailed information please click on the respective abstract

8:00
 
#PS 15 / IL Applications of Novel Imaging Techniques (#656)
Jan-Bernd H�vener
Medical Physics, Dept. Radiology University Medical Center Freiburg, Breisacher Stra�e 60a, Freiburg 79098, Germany
 
8:25
 
#PS 15 / 1 Multimodal non-invasive longitudinal studies of imaging biomarkers for the quantification of colon inflammation in a mouse model of colitis (#361)
Anne Beltzer 1, Andrea Bianchi 1, Teresa Bluhmki 1, Tanja Schoenberger 2, Andrea V�gtle 1, David Kind 1, Eric Kaaru 1, Michael Neumaier 1, Birgit Stierstorfer 2, Thomas Kaulisch 1, Detlef Stiller 1
1Boehringer Ingelheim Pharma GmbH & Co. KG Target Discovery Research, In-vivo imaging laboratory, Biberach an der Riss, Germany
2Boehringer Ingelheim Pharma GmbH & Co. KG Target Discovery Research, Target Validation Technologies, Biberach an der Riss, Germany
 
8:37
 
#PS 15 / 2 Phase contrast CT for quantification of structural changes in lungs of asthma mouse models of different severity (#176)
Christian Dullin 1, Emanuel Larsson 2,3,4, Giuliana Tromba 2, Andrea Markus 5, Frauke Alves 5,1,6
1University Medical Hospital Goettingen Diagnostic and Interventional Radiology, Robert Koch Str. 40, 37075 Goettingen, Germany
2Elettra-Sincrotrone Trieste SYRMEP beamline, Strada Statale 14 - km 163,5 in AREA Science Park, 34149 Trieste, Italy
3University of Trieste Architecture and Engineering, 34149 Trieste, Italy
4Link�ping University Physics, Chemistry and Biology, SE-58183 Linkoeping, Sweden
5University Medical Hospital Goettingen Haematology and medical Oncology, Robert Koch Str. 40, 37075 Goettingen, Germany
6Max Plank Institute for experimental Medicine Molecular Biology of neuronal Signals, Hermann-Rein-Str. 3, 37075 Goettingen, Germany
 
Introduction
Lung imaging in mouse disease models is crucial for the assessment of the severity of airway disease but remains challenging due to the small size and the high porosity of the organ. Synchrotron inline free propagation phase contrast CT with its intrinsic high soft-tissue contrast provides the necessary sensitivity and spatial resolution to analyse the mouse lung structure in great detail.
Methods
We analysed the benefit of this technique in combination with single distance phase retrieval to quantify alterations of the lung structure in asthma mouse models of different severity. In order to mimic an in-vivo situation as close as possible, the lungs were inflated with air at a constant physiological pressure. Entire mice were embedded in agarose gel and imaged using inline free propagation phase contrast CT at the SYRMEP beamline (Synchrotron Light Source, �Elettra�, Trieste, Italy).
Results
The quantification of the obtained phase contrast CT data sets revealed an increasing lung soft-tissue content in mice correlating with the degree of asthma severity (Fig. 1). In addition, we found significant changes in the real part of the complex refractive index pointing to a modification of the lung soft tissue composition. Interestingly, these changes differ in between mild and severe acute asthma and therefore may reflect variations in the underlying pathomechanism. Based on these findings, it was possible to successfully discriminate between healthy controls and mice with either mild or severe asthma.
Conclusions
We believe that our approach may have the potential to evaluate the efficacy of novel therapeutic strategies that have effects on the airway remodelling processes in asthma.
Acknowledgement
This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) [DU 1403/1-1] and by the COST MP1207 action. The authors thank Sarah Greco and B�rbel Heidrich for their excellent work of setting up the asthma models used in the study. In addition, we thank the whole team of the SYRMEP beamline which has contributed to this work in many different ways; especially we thank Nicola Sodini for his technical assistance and essential support for the success of the study. Also, we thank the group of Tim Gureyev who provided the software �X-tract�, used to perform the phase retrieval of the data sets.
Fig. 1: VR of a control (CN), mild asthmatic (MAA) and severe asthmatic (SAA) mouse shows increasing soft-tissue content in the lung in correlation with increasing asthma severity.
Fig. 1:
VR of a control (CN), mild asthmatic (MAA) and severe asthmatic (SAA) mouse shows increasing soft-tissue content in the lung in correlation with increasing asthma severity.
8:49
 
#PS 15 / 3 Multiparametric characterization of kidney function and perfusion exploiting a dynamic CEST approach (#37)
Dario Longo 1,2, Lorena Consolino 3,2, Pietro Irrera 3, Juan Carlos Cutrin 3,2, Silvio Aime 3,2
1Institute of Biostructure and Bioimaging - CNR Molecular Biotechnolgy and Health Sciences, Via Nizza, 52, 10126 Torino, Italy
2University of Torino Molecular Imaging Center, Via Nizza, 52, 10126 Torino, Italy
3University of Torino Molecular Biotechnolgy and Health Sciences, Via Nizza, 52, 10126 Torino, Italy
 
9:01
 
#PS 15 / 5 Hyperpolarization using Parahydrogen of biologically relevant substrates: acetate and pyruvate (#450)
Francesca Reineri 1, Tommaso Boi 2, Silvio Aime 1
1University of Torino Molecular biotechnology and health sciences, Via Nizza 52, 10123 Torino, Italy
2Bracco Imaging Spa, CRB, 10010 Colleretto Giacosa (TO), Italy
 
Introduction
Hyperpolarization methods represent a recent break-through in field of diagnostic tools by Magnetic Resonance. The in vivo administration of 13C-labelled metabolites, hyperpolarized by means of DNP (Dynamic Nuclear Polarization), can provide outstanding information about intracellular metabolism. Parahydrogen Induced Polarization (PHIP) is  an alternative route to hyperpolarization that has the advantage of being cheaper and easier to handle. The application of PHIP to bio-medical studies has been limited by the availability of unsaturated precursors. Our work shows how parahydrogen can be used to obtain hyperpolarization on some biologically relevant molecules such as pyruvate and acetate.
Methods
In order to obtain hyperpolarization on the 13C carboxylate signal of carboxylic acids such as acetate and pyruvate, an ester is synthesized in which the unsaturated bond is placed on the alcoholic moiety.
The vinyl ester of acetate, propargyl esters of acetate and pyruvate are used. Parahydrogenation is carried out in both organic solvent and aqueous phase, using a Rh(I) catalyst and 92% enriched parahydrogen. Magnetic field cycling is applied to achieve polarization transfer from parahydrogen spin order to 13C net magnetization. Hydrolysis of the polarized ester is carried out using NaOD (1M).
Results
Parahydrogenation of vinyl and propargyl esters of acetate, followed by magnetic field cycling, allows achieving hyperpolarization of the 13C carboxylate signal. Hydrolysis of the parahydrogenated esters leads to 13C hyperpolarized Sodium acetate (figure 1).
Parahydrogenation of propargylic ester of pyruvate in organic medium (chloroform/methanol mixture) and application of field cycling allows polarization transfer to the 1-13C carboxylate signal. After the polarization transfer step, hydrolysis is carried out by the addition of an aqueous basic solution and [1-13C] hyperpolarized pyruvate is obtained in the aqueous phase (figure 2).
Conclusions
The experimental results show that high polarization level can be obtained on the 13C carboxylate signal of parahydrogenated esters on which parahydrogen is added to the alcoholic moiety. Theoretical studies allow to demonstrate that field cycling allows to obtain a polarization level on the 13C carboxylate signal which is as high as that observed on molecules where parahydrogen is added at adjacent positions to the target 13C nucleus.
The herein presented method, namely ParaHydrogen Induced Polarization by means of Side Arm Hydrogenation (PHIP-SAH), markedly widens the applicability of the PHIP approach for the hyperpolarization of biologically relevant molecules.
Figure 1: a) hyperpolarized carboxylate signal of  parahydrogenated ethyl acetate (naturally abundant 13C); b) after hydrolysis, hyperpolarized Sodium acetate is obtained. Both spectra are single scan. c) thermal signal, 1000 scans, 56h acquisition. Figure 2: a) hyperpolarized 13C signals of parahydrogenated allyl-pyruvate, the asterisk indicates the acetalic form of pyruvate obtained in the organic phase; b) after hydrolysis hyperpolarized Sodium pyruvate is obtained. c) thermal equilibrium 13C NMR spectrum.
Figure 1:
a) hyperpolarized carboxylate signal of parahydrogenated ethyl acetate (naturally abundant 13C); b) after hydrolysis, hyperpolarized Sodium acetate is obtained. Both spectra are single scan. c) thermal signal, 1000 scans, 56h acquisition.
Figure 2:
a) hyperpolarized 13C signals of parahydrogenated allyl-pyruvate, the asterisk indicates the acetalic form of pyruvate obtained in the organic phase; b) after hydrolysis hyperpolarized Sodium pyruvate is obtained. c) thermal equilibrium 13C NMR spectrum.


 

  back to overview