Abstract/Video opens by clicking at the talk title.
Abstract/Video opens by clicking at the talk title.
|12:00 p.m.||PS 17-01||
Introductory Lecture (#675)
1 Ghent University, Gent, Belgium
|12:18 p.m.||PS 17-02||
The SAFIR Prototype PET insert: first high rate measurement results (#240)
Werner Lustermann1, Robert Becker1, Volker Commichau1, Jan Debus1, Lubomir Djambazov1, Afroditi Eleftheriou2, Jannis Fischer1, Peter Fischer3, Mikiko Ito1, Parisa Khateri1, Christian Ritzer1, Michael Ritzert3, Ulf H. Röser1, Charalampos Tsoumpas4, Geoffrey Warnock2, Matthias Wyss2, Agnieszka Zagozdzinska-Bochenek1, Bruno Weber2, Günther Dissertori1
1 ETH Zürich, Institute for Particle Physics and Astrophysics, Zürich, Switzerland
The SAFIR  (Small Animal Fast insert for MRI) collaboration is developing a PET insert for the pre-clinical Bruker BioSpin 70/30 MR system. The speciality of the SAFIR insert is PET imaging at high activities of up to 500 MBq. It allows for precisely resolving the temporal evolution of tracer concentrations with time frames of a few seconds, enabling truly simultaneous PET-MR studies of fast kinetic processes in small rodents.
The prototype detector employs:
The scanner acquires raw data of all hits, which are offline corrected for timing delays, energy calibrated and sorted into coincidences with a coincidence time window of 500 ps and an energy window of 391-601 keV.
The measurement of the static B0-field of the MR system, after shimming and with SAFIR installed revealed an excellent homogeneity in the field of view . The operation of the SAFIR prototype insert reduces the signal-to-noise ratio of the MRI in a homogeneous phantom by 4.9%. Using a 0.65 MBq point source we measured an energy resolution of 13.7 % and a coincidence timing resolution of 194 ps (FWHM) combining all 2880 crystals.
We completed successfully the construction of the SAFIR Prototype PET insert and performed first measurements inside the MRI and at high activity > 100 MBq. The scanner is compatible with the Bruker 70/30 MRI system, permitting simultaneous PET/MR measurements. The first in-vivo mouse images fully satisfy our requirements with respect to spatial resolution and frame based activity concentration resolution.
AcknowledgmentThis work was supported by the ETH Zurich Foundation through ETH Research Grant ETH-30 14-2. Geoffrey Warnock was funded by the Clinical Research Priority Program for Molecular Imaging of the University of Zurich.
 Becker, R., et al., 2017, “The SAFIR experiment: Concept, status and perspectives”, NIM A, vol. 845, pp. 648-651, 2017
 C. Ritzer, et al., 2019, "Compact MR-compatible DC-DC converter module", JINST, vol. 14, Sept. 2019, P09016
 Ritzer, C., et al., 2019, “Initial Characterization of the SAFIR prototype PET-MR Scanner”, submitted to IEEE TRPMS
In-vivo time-activity-curve at normal and high activity (mouse, cardio tracer)
Comparison of time activity curve measurements. The images show the activity in a sphere of 7 mm diameter around the heart of a mouse injected with (a) 7.6 MBq (left) and (b) 108.3 MBq (right) of an 18F labelled cardio tracer, corrected for the decay of the tracer. The first 60 points are reconstructed using 3 s time frames and the last two points using 10 s time frames.
Keywords: PET/MR, PET-MR, high rate PET, SAFIR, preclinical PET insert
|12:30 p.m.||PS 17-03||
The MERMAID Project - PET imaging of small aquatic animals (#345)
Steven Seeger1, Milan Zvolsky1, Leoni de Graaf1, David Weller1, Moritz Schaar1, Christian Schmidt2, Magdalena Rafecas1
1 Universität zu Lübeck, Instititut of Medical Engineering, Lübeck, Germany
MERMAID (Multi-Emission Radioisotopes - Marine Animal Imaging Device) stands for a new approach for high-resolution positron emission tomography (PET) imaging of small aquatic animals. One of our objectives is the development of a dedicated PET scanner. In the biomedical research, such a non-invasive functional imaging tool can provide new insights into the physiology of model organisms, e.g. zebrafish. In the field of aquaculture, a better knowledge of metabolic processes of fish helps to further improve and optimize aquatic environments.
First proof-of-concept (PoC) prototype contains two detectors, which rotate around the object under study in user-defined steps to acquire a full set of projections. Each detector module consists of an 8x8 LYSO scintillation crystal matrix and is directly coupled to a silicon photomultiplier array. The 128 channels of the prototype were calibrated using a 22Na source to clearly identify the photopeaks and assure channel homogeneity. Efficiency of the individual channels was determined with an 18F-FDG filled phantom. In addition to investigations of a two-point source and dedicated phantoms, GATE simulations were performed to evaluate the image quality and improve image reconstruction. For future fish imaging, we have also developed a flow-through chamber including immobilization and care.
Mean energy resolution of 9 % FWHM was obtained at the 511 keV photopeak. The time resolution is about 400 ps FWHM (non optimized). Linearity between count rates and activity was assessed for the range of 15 to 35 MBq. Single crystal efficiencies varied within 20 % relative to each other. Reconstructed images using the MLEM algorithm show that resolution degradation due to crystal penetration can be partially compensated through our optimized system model within the reconstruction. For a radioactive source of 1 mm diameter, we obtained source profiles with 1.1 mm average FWHM. Due to the extremely small field-of-view (FoV) defined by only two rotating modules, truncation artefacts affected the images of extended sources. To overcome this limitation, an extension of the prototype to 8 detector modules is underway; further improvements of the reconstruction are also ongoing.
We have built a first PoC PET prototype and evaluated its performance for the very limited case of only two detector modules. A good energy and timing resolution were obtained. Reconstructed images of point sources and simple phantoms showed the relevance of an optimized system model of crystal penetration in reconstruction and the need to extend the FoV. Fish welfare together with immobilization will be possible with the constructed fish holder.
AcknowledgmentThis project is part of ATTRACT that has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 777222.
Thanks to Cindy Läken (IMT), who helped within several experiments.
Prototype design including immobilisation chamber an detector
The picture shows the prototype design including the two detector modules rotating around the measurement chamber for an zebrafish. This chamber gently immobilizes the fish and supports oxygen rich water and anesthetics over the whole measurement time. This also ensures the drainage of tracer residues, which may have been excreted by the fish, in order to reduce image artifacts. Furthermore, one of the detector modules with the 8x8 crystal matrix and the SiPM coupled to it is shown in detail.
Measured 22-Na Energy spectrum an reconstructed image of two-point sourece
Energy spectrum from one channel of the measured 22Na two-point source with approx. 400 kBq per point (left). Reconstructed image of the 22Na source using a custom MLEM reconstruction algorithm (right). The two points have the correct distance to each other (5mm).
Keywords: small animal PET, zebrafish, in-vivo imaging
|12:42 p.m.||PS 17-04||
In-Vivo Coronary Micro-Computed Tomography Angiography in Mice (#14)
Jan Kuntz1, Carlo Amato1, Laura Klein1, Joscha Maier1, Danielle Franke2, Nicole Gehrke2, Andreas Briel2, Greetje Vande Velde3, Marc Kachelrieß1, Stefan Sawall1
1 German Cancer Research Center (DKFZ), X-Ray imaging and CT, Heidelberg, Germany
Coronary computed tomography angiography is an essential clinical tool in the diagnosis of coronary artery disease and other, potentially life threatening pathologies. In-vivo imaging of coronaries in preclinical research, i.e. in disease models of small animals in general and in rodents in particular, seems impossible due to the high demands on spatial and temporal resolution which cannot be met by current micro–CT systems. We present the first measurements using a novel cardiac micro-CT system illustrating that the in-vivo visualization of coronary arteries is possible using micro-CT.
Five mice were anesthetized via inhalation of isoflurane + O2, i.v.-injected with a blood pool contrast agent (ExiTron nano 12000, nanoPET Pharma) and measured in a custom-build cardiac micro-CT. This system is based on a clinical gantry allowing for the required magnification and is equipped with a micro-focus x-ray source (L10915, Hamamatsu) and a high-speed flat detector (Dexela 2923, Varex). Measurements are performed using a tube voltage of 60 kV at 800 µA and a 4×4 binning mode of the detector resulting in 86 fps. Total scan time amounted to 14 s. Intrinsic gating signals for cardiac and respiratory motion were retrospectively computed. Image reconstruction is performed via a motion compensation method using 8 overlapping respiratory phases and 20 overlapping cardiac phases.
The mice showed respiratory rates of 141±34 rpm and cardiac rates of 338±78 bpm during the measurements. The reconstructions illustrate the complete cardiac cycle and all phases can be easily identified and might be used to compute quantitative values, e.g. the ejection fraction (fig. 1). The course of the left coronary artery can be clearly observed in all cardiac phases. This applies as well to major branches, i.e. the left circumflex (LCX) and obtuse marginal (OMA) arteries. Further branches of these arteries can be followed to the cardiac apex (fig. 2). Best image quality is observed in diastole since the motion velocity is significantly lower compared to systole. The right coronary artery could not be observed in the experiments which might be caused by the higher motion speed compared to the left coronary or a lack of contrast enhancement.
In-vivo micro-CT imaging of coronary arteries in small animals could boost studies of myocardial infarction, (re-)perfusion and other processes in preclinical models of cardiac pathologies.
In-Vivo Coronary Micro-Computed Tomography Angiography in Mice
Top: Axial slices showing cardiac motion over a complete cardiac cycle. Middle: The corresponding coronal reformats illustrate the expansion of aorta and pulmonary trunk in systole. Bottom: A sliding-thin-slab maximum-intensity-projection (STS-MIP) over 0.5 mm in longitudinal direction allows for an assessment of coronary arteries up to several branches (*).
Keywords: micro-CT, contrast media, cardiac imaging, coronary arteries
|12:54 p.m.||PS 17-05||
Synchrotron Radiation Phase Contrast Computed Tomography of porcine lung in a human-scale chest phantom (#508)
Francesca Di Lillo1, Jonas Albers2, Willi L. Wagner3, 4, Felix Wuennemann3, 4, Serena Pacile'1, 5, Fulvia Arfelli6, Diego Dreossi1, Nicola Sodini1, Jürgen Biederer3, 4, Philip Konietzke3, 4, Wolfram Stiller3, 4, Marc O. Wielpütz3, 4, Agostino Accardo5, Marco Confalonieri7, Maria Cova8, Joachim Lotz2, 9, Frauke Alves2, 10, 11, Hans-Ulrich Kauczor3, 4, Giuliana Tromba1, Christian Dullin2, 1, 10
1 Elettra-Sincrotrone Trieste, Basovizza, Trieste, Italy
Phase contrast imaging has proven to provide images with increased contrast-to-noise ratios (CNR) at relatively low doses compared to classical absorption-based radiography. This technique has been shown to be particularly effective for lung imaging in preclinical animal models , .
Freshly excised hearts and lungs from several pigs were placed in the ARTIChest phantom simulating a human-scale chest with near-human physiological conditions. 3% agarose gel, containing a clinical contrast agent with Iodine content of 300 mg/ml was injected into the lung to simulate nodules. SR CT of porcine lungs in the phantom was perfomed in Propagation Based Imaging (PBI) setup at the SYRMEP beamline of ELETTRA (Trieste, Italy) with a monochromatic beam (E=40 keV). CT scans were acquired using a CdTe photon-counting detector, 100-mm pixel size, placed at 2.6 m or 10.7 m from the sample (Fig. 1a,b) with a total entrance air kerma of about 12 mGy. For comparison, samples were also studied with a conventional clinical CT system at 200 mAs and 120 kVp.
We demonstrate that SR PBI acquisitions can be performed on porcine lungs with only a fraction of the x-ray dose of a clinical state-of-the-art high-resolution lung CT providing more than 180 times smaller voxels. This increased spatial resolution allowed a very detailed assessment of lung structure and artificial nodules (Fig. 1c). Individual interlobular septa, which are important anatomical landmarks of many pulmonary diseases, can be clearly delineated.
We report on the first application of Propagation Based phase-contrast CT on a human-scale chest phantom prepared with an inflated fresh porcine lung. Compared with clinical CT systems, PBI images showed an increased visibility of details and anatomical structures at a lower delivered dose.
 Dullin, C., dal Monego, S., Larsson, E., Mohammadi, S., Krenkel, M., Garrovo, C., Biffi, S., Lorenzon, A.,Markus, A., Napp, J., Salditt, T., Accardo, A., Alves, F. & Tromba, G. (2015). J. Synchrotron Rad. 22, 143–155
 Gradl, R., Dierolf, M., Hehn, L., Günther, B., Yildirim, A. Ö., Gleich, B., Achterhold, K., Pfeiffer, F. & Morgan, K. S. (2017). Sci. Rep. 7, 4908
 Wagner, W. L., Wuennemann, F., Pacile’, S., Albers, J., Arfelli, F., Dreossi, D., Biederer, J., Konietzke, P., Stiller, W., Wielpütz, M. O., Accardo, A., Confalonieri, M., Cova, M., Lotz, J., Alves, F., Kauczor, H.-U., Tromba G., and Dullin, C. (2018), J. Synchrotron Rad. 25.
A) phantom with fresh porcine lung mounted at the SYRMEP beamline. B) setup scheme (changes to pilot study in red). b = beam outlet, i = calibrated ionization chamber, f = aluminium filter set (17.55 / 20.15 mm respectively) , p = human chest phantom, h = phantom holder, r = rotary unit and stage, do and dn = position of the detector (2.6 / 10.7 m respectively) C) comparison of the image quality for an artificial lung nodule between PBI and clinical CT - clearly PBI allows better visualization of the nodule at even lower dose.
Keywords: Phase Contrast Imaging, Lung CT, Synchrotron Radiation
|1:06 p.m.||PS 17-06||
Within-breath changes in small airway dimensions assessed in vivo by dynamic synchrotron radiation phase-contrast lung imaging in anesthetized rabbits with acute lung injury (#137)
Eva Solé Cruz1, 2, Luca Fardin1, 3, 4, Ludovic C. Broche1, Anders Larsson4, Gaetano Perchiazzi4, Alberto Bravin3, Sam Bayat1, 2
1 Inserm, UA7 STROBE Laboratory, Grenoble, France
Micromechanical behaviour of individual small airways remain largely unknown in vivo in intact lung, mainly due to the lack of microscopic imaging techniques allowing for sufficient temporal and spatial resolution. We previously developed a time-resolved synchrotron radiation X-ray phase-contrast tomographic technique which allows to image intact lungs in vivo with 20 µm pixel resolution. Here we assessed the changes in small airway dimensions during the breathing cycle in anesthetized and mechanically ventilated rabbits with acute lung injury.
The experiment was performed on 4 anesthetized, tracheotomized, muscle-relaxed and mechanically ventilated rabbits. Lung injury was induced by whole lung lavage followed by injurious ventilation for 2 hours. Projection images were acquired at a constant frame rate at time resolution of 15 ms using a PCO edge 5.5 camera, coupled with optics determining a pixel size of 20 µm, during 30 minutes. Volumetric CT images were reconstructed at various phases of the respiratory cycle, during systole and diastole (at 10 and 150 ms after the ECG R wave, respectively). Small peripheral and terminal airway branches were manually segmented from the reconstructed CT images.
A sample segmented airway and daughter branches is shown in Figure 1. Figure 2 shows sequential measurements averaged along the length of a small bronchus and 2 terminal branches during the breathing cycle upon systole (S) and diastole (D). Airway pressure measured at the tracheal opening, ranged from 5 to 25 cmH2O from end-expiration to end-inspiration, respectively. Our preliminary results demonstrate that both airway pressure variation (p<0.05) and the phase of the cardiac cycle (p<0.001) significantly affected individual terminal airway dimensions, as airway radii were reduced during diastole with cardiac filling.
Using time resolved (4D) synchrotron radiation phase-contrast imaging, we demonstrate for the first time in intact in vivo lung, that both airway pressure and cardiac contractions determine small airway calibre variations in mechanically ventilated rabbits with acute lung injury. These findings bring new insight into the pathophysiology of ventilation-induced lung injury.
AcknowledgmentStudy funded by: The Swedish Reseach Council under grant 2018-02438; ESRF.
Keywords: Pulmonary airways, Acute Respiratory DIstress Syndrome, X-ray computed tomography, synchrotron radiation
|1:18 p.m.||PS 17-07||
Myocardial infarct assessment with super resolution PET/ultrafast ultrasound imaging (#414)
Mailyn Perez-Liva1, 2, Thulaciga Yoganathan1, 2, Joaquin L. Herraiz4, Jonathan Poree3, Mickael Tanter3, Daniel Balvay1, 2, Thomas Viel1, 2, Anikitos Garofalakis1, Jean Provost3, Bertrand Tavitian1, 2
1 Paris-Cardiovascular Research Center at HEGP, INSERM U970, Paris, France
The spatial resolution of PET is improved by increasing spatial sampling through shifts of sub-resolution precision [1,2], ideally using an imaging modality capable to follow anatomical deformation with high temporal and spatial resolution . Imaging modalities commonly associated with PET, such as CT or MRI, do not support acquisition rates of rodents’ heart beat (~300-600 bpm). In contrast, Ultrafast Ultrasound imaging (UUI) can acquire at kHz rates with excellent spatial resolution (~100 µm) . Here, we used UUI for enabling super-resolution cardiac PET imaging in rats.
We simultaneously acquired cardiac fused PET/CT/UUI images of normal and infarcted rat hearts with our non-invasive, in vivo, preclinical scanner PETRUS . Simultaneous ECG-gated 16 frames per cycle PET-UUI sequences were acquired during 30-min in rats (n = 2) after IV injection of 43 MBq [18F]FDG. Dynamic ultrafast B-mode images were used to obtain the anatomical motion vectors field (MVF) of the heart’s deformation along time frames by non-rigid registration. An image-domain variational super resolution (SR) algorithm was applied to the images of each cardiac frame of the PET data. SNR, contrast and spatial resolution were used as image quality estimators.
Figure shows the single-frame (A-C) and the corresponding SR (B-D) images of a healthy rat heart (A, B) and of an infarcted rat heart 2 hours after ligation of the left-descending coronal artery (C, D). SR considerably improved image quality: the myocardial to intraventricular contrast increased by 80%, signal-to-noise ratio by 40% and spatial resolution by 78% (~0.8 mm) with respect to single-frame PET.
Applying the SR algorithm to co-registered, simultaneous acquisition of PET and ultrasonic data drastically enhance the quality of metabolic imaging of the rodent heart. We anticipate that better resolution and more accurate quantification will improve PET characterization of ischemic events and other disorders that induce local glucose dysregulation of the heart.
AcknowledgmentThis project was funded in part by Plan Cancer (ASC16026HSA-C16026HS) and by LABEX WIFI (Laboratory of Excellence ANR-10-LABX-24) within the French program “Investments for the Future” under reference ANR-10-IDEX-0001-02 PSL In vivo imaging was performed at the Life Imaging Facility of Paris Descartes University (Plateforme Imageries du Vivant - PIV), supported by France Life Imaging (grant ANR-11-INBS-0006) and Infrastructures Biologie-Santé (IBISA). It was also funded in part by a CARPEM Siric grant (to BT)
 Kennedy, J. A., et al., (2006). Super-resolution in PET imaging. IEEE transactions on medical imaging, 25(2), 137-147.
 D. Wallach,et al, (2011) "Super-resolution in respiratory synchronized positron emission tomography," IEEE Trans. Med. Imaging, vol. 31, (2), pp. 438-448.
 Nam, W. H., et al., (2013). Motion-compensated PET image reconstruction with respiratory-matched attenuation correction using two low-dose inhale and exhale CT images. Physics in Medicine & Biology, 58(20), 7355.
 M. Tanter and M. Fink, "Ultrafast imaging in biomedical ultrasound," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, vol. 61, (1), pp. 102-119, 2014.
 J. Provost, et al., (2018), "Simultaneous positron emission tomography and ultrafast ultrasound for hybrid molecular, anatomical and functional imaging," Nature Biomedical Engineering, vol. 2, (2), pp. 85.
PET/Ultrafast B-mode fusion data.
A, single-frame PET/Ultrafast B-mode fusion during the cardiac diastole in a normal heart of a rat, B, super resolution image restoration for the normal heart. C, single-frame PET/Ultrafast B-mode fusion 2-hours after left-coronary ligation. D, super resolution image restoration for the infarcted heart
Keywords: imultaneous PET/CT-UUI system, super resolution in cardiac PET, preclinical PET, motion correction