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Laboratory for Preclinical Imaging

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The laboratory for preclinical imaging was founded in 2007:

  • Prerequisites in 2006:

    • Establishment of radiochemistry group for PET tracer synthesis

    • Establishment of a lab for molecular biology

    • Upgrade of the medical imaging infrastructure & group

 

  • September 2007:

    • Reestablishment of pinhole SPECT methodology using a clinical SPECT System

    • Construction of the laboratory space in the clinic basement (U2, Campus Grosshadern)

  • October 2007:

    • Arrival of the Siemens Inveon P120 DPET small animal tomograph

    • First in-vivo small animal scan of a mouse (cardiac viability study, ECG gated)

 

  • December 2007:

    • Installation of individually ventilated cages (IVC) for animal housing

  • 2008:

    • Construction of laboratory for molecular biology

    • Construction of laboratory for PET tracer research

 

Equipment

Data Storage

  • Network Disk Raid Array

    • Operation system: Windows Server, LDAP authentication

    • Hardware: Transtec CALLEO 211L (2 x AMD Dual Opteron, 8 GB RAM, rack mounted), Transtec AG, Tübingen

    • Raid: iSCSI, 16x1TB Raid 5, 1 spare (12 Terrabyte useable volume)

Data Processing

  • Linux cluster

    • Operation system: SuSE Linux Enterprise Server 10sp1, 64 bit

    • 1 master: Transtec CALLEO 314L (2 x AMD Dual Opteron, 8 GB RAM, internal Raid, rack mounted), Transtec AG, Tübingen

    • 7 nodes: Transtec CALLEO 211L (2 x AMD Dual Opteron, 8 GB RAM, rack mounted), Transtec AG, Tübingen

  • Server for remote desktop sessions

    • Operation system: 64 bit SuSE Linux Enterprise Server 10sp1

    • Hardware: Transtec CALLEO 302L (1 x Xeon Quad core, 16 GB RAM, rack mounted)

    • Software:

      • NX server for remote X sessions on Windows Desktop PCs

      • PMOD

      • IDL

      • Amide

      • MRIcro

      • Mipav

      • MINC tools

      • Matlab & SPM

      • Software development (C, C++, Root)

  • Dedcicated workstations

    • 2 Siemens preclinical workstations

 

Tomographs

Small animal PET: Siemens Inveon P120 Dedicated PET

                  Acq. mode:                     Listmode
                  External inputs:               ECG & Respiration
                  Sensitivity:                      approx. 10% (250-750 keV%, 4.1 ns)
                  FOV:                                axial 12 cm, transaxial 10 cm (ø)
                  Resolution:                      transaxial approx. 1.2 to 1.4 mm
                  Reconstruction:              2D OSEM, 3D OSEM/MAP

Pinhole-SPECT: 3-head Picker Prism 3000

                  Collimators:                    3 Picker Pinhole collimators, single hole,
                                                            Det2Apert. = 16 cm
                  Acq. mode:                     120 deg./head, Apert2COR = 4 cm
                  External inputs:               ECG
                  FOV:                                axial max. 16 cm, transaxial 8 cm (ø)
                  Resolution:                      axial & transaxial > 1.6 mm
                  Reconstruction:              OSEM (3D “blob”-based project

Figure: Images of a small (“cold” i.e. non-radioactive) plexiglas cylinder with tracer filled (“hot” i.e. radioactive) rods. Numbers beneath rod groups indicate rod diameters. Top row: Phantom filled with various PET tracers and imaged with the small animal PET. Bottom row: Phantom filled with Tc-99m and imaged with the Pinhole SPECT camera.

Workload

The following figures demonstrate the great workload of the small animal imaging laboratory where more than 1000 in-vivo small animal studies have been performed within less than 1 year.

In-vivo studies

October 2007 to August 2008

Figure: The number of in-vivo animal studies that have been performed with the small animal PET and the pinhole SPECT & conventional scintigraphy devices between October 2007 (foundation of lab. for precl. imag) and August 2008.

Inveon in-vivo PET studies

October 2007 to August 2008

Figure: The number of in-vivo PET studies that have been performed on the small animal PET scanner with different PET tracers between October 2007 (foundation of lab. for precl. imag.) and August 2008.
Since the dept. of nuclear medicine of the LMU currently does not own a cyclotron for the production of short lived radioactive nuclides such as C11, O15 or N13, most of the PET tracers that we used are based on the nuclide F18. The great variety of applicable F18-based tracers can only be provided because of our excellent radiochemistry group.

Study examples

18F-FDG scan of a mouse’s heart

Anesthetized healthy mouse imaged with 18F-FDG in the small animal PET. The high tracer accumulation in the heart wall denotes the high metabolic activity (i.e. energy consumption) of the heart muscle compared to its neighboring areas. The separation of data into multiple phases of the heart beat cycle was achieved by connecting a physiological monitoring system for small animals and deriving an ECG of the animal during acquisition.

Figure: Mouse (24g), 23 MBq 18F-FDG, 30 min scan (60 min. p.i.), ECG (8 gates), OSEM2D. From left to right: heart slices are displayed along horizontal long axis (HLA), short axis (SA) and vertical long axis (VLA).

18F-Fuoride scan of a rat’s skeleton

18F-Fluoride is widely used for bone scans in clinical routine for the diagnosis of bone tumor metastases. To demonstrate the high resolution and high image quality of a dedicated small animal PET we performed this 18F-Fluoride whole body scan of a rat.

Figure: 60 min. 18F-Fluoride scan of a rat’s skeleton (60 min. p.i. of 310 MBq of 18F-Fluoride).

Study of Serotonin receptors in a rat epilepsy model

We participate in the European research project Euripides for the study of neurodegenerative diseases such as e.g. epilepsy. The pathways of medication and the mechanism that inhibit or disturb medical treatment are herein analyzed. Our part is the study of changes in the binding potential of the Serotonin receptor tracer 18F-MPPF in a rat epilepsy model.

“Uptake and Binding of the Serotonin 5-HT1A Antagonist [18F]-MPPF in Brain of Rats; Effects of the Novel P-glycoprotein Inhibitor Tariquidar”, la Fougère et.al., Neuroimaging 2009, submitted.

No animal movement between scans

• Serotonin receptor imaging with MPPF PET
• Anatomical landmarking with FDG PET

Spatial normalization using MNI tools (Montreal Neurological Institute, CA)

• Target is a rat cryo atlas (by Pedro Rosa-Neto)
• Determine normalization transformation using FDG sum
• Application of transformation to MPPF dynamic

Figure: Scan protocol to allow perfectly coregistered data sets of anatomical information (FDG scan) and receptor binding potential study (MPPF scan)

Figure: Fusion of 18F-FDG metabolic scan (sum of 45 min.) for anatomical landmarking and 18F-MPPF Serotonin receptor scan (sum of 5 to 50 min.) of a rat’s brain. Both studies have been acquired in one session without moving the animal. Therefore, the reconstruction of the FDG scan (sum of all 45 minutes) can be used to determine the correct stereotactic normalization transformation for mapping both studies to a standard rat brain atlas. The above movie demonstrates the precise coregistration of both scans by alternate display of the FDG image and a summed image of the MPPF scan (from 5 to 50 minutes post injection to exclude the initial phase of blood flow).

Figure: The above movie shows the kinetics of the 18F-MPPF tracer from its time of administration (00:00 min:sec) until 9 minutes post injection (09:00 min:sec). It nicely demonstrates the pathway of the tracer, being delivered during the first seconds by the vessels and then gradually accumulating to its binding sites (Serotonin receptors, e.g. in hippocampus).

Euripides: 5-HT1A receptor imaging wit 18F-MPPF in a rat epilepsy model

Manual spatial normalization of MPPF by using the FDG sum and a rat cryo-atlas

Figure: Superposition of the FDG sum with the rat atlas (left) and MPPF sum with rat atlas (right) for one rat after applying the same stereotactic normalization transformation to both. Whereas FDG accumulates in all brain areas, the Serotonin receptor ligand MPPF accumulates mainly in the hippocampus.

Euripides: 5-HT1A receptor imaging wit 18F-MPPF in a rat epilepsy model

Pixelwise kinetic modeling (Logan)

Figure: Rat atlas (left row) and mean MPPF binding potential (BP, middle row) of 12 normal rats. Binding potential was assessed by individually normalizing each rat’s FDG data to the stereotactic rat atlas, applying the same transformation to the MPPF dynamic data, performing voxelwise kinetic modeling (Logan plot using PMOD) and averaging the 3D BP maps of all 12 subjects. In the right row, the mean BP map is superimposed onto the rat atlas.

18F-SiFA rat serum albumin

This project of the PET radiochemistry research group of our department demonstrates the successful development of new PET tracers and the simplification of the process of tracer synthesis. Here, a kit like labeling technique was developed to produce F18 labeled rat serum albumin which is suitable for blood pool imaging.

„Kit-Like 18F-Labeling of Proteins: Synthesis of 4-(Di-tert-butyl[18F]fluorosilyl)benzenethiol (Si[18F]FA-SH) Labeled Rat Serum Albumin for Blood Pool Imaging with PET“, Wängler et.al., Biocon. Chem., 2009.

Figure: Dynamic display of tracer accumulation over time. First frame shows path of tracer from injection site (tail vein) into the abdominal aorta. As intended, this tracer did not significantly leave the vessel system.

Figure: VOIs were defined in the above data for various organs and tracer kinetics analyzed. Tracer concentration in blood as indicated by the large left ventricular blood pool VOI is high and constant over time.

Figure: ECG gating was performed and data devided into multiple phases of the heart cycle. Albumin accumulates in intestines, vessels and heart blood pool areas (ventricles and atria) and is metabolized in liver.

Test of the ECG gating setup and analysis using a Fisher Price “beating mouse heart simulator”

In this setup we wanted to achieve a perfectly known object (animal “heart”) with known object motion (“heart beat”) and known data (ECG information). ECG information is automatically stored in the small animal PET acquisition data (listmode stream).

Figure: Fisher Price children toys were used to position a radioactive source (18F-FDG) inside the tomograph. The source rotated in a circular orbit with an adjustable rotation speed simulating different heart beat rates. A light sensitive resistor was used to generate an ECG trigger according to the rotation frequency. This pulse was fed into the tomograph’s list mode coincidence data stream.