The SuperArgus PET/CT from Sedecal is a fully functional integrated system combining modern technologies for both PET and CT providing molecular imaging on a wide variety of pre-clinical animal models. The development of this system is a major breakthrough in high performance functional and molecular imaging technologies for biomedical research. The dual modality configuration delivers faster scan times with superior image resolution, improved localization and quantifiable data. The SuperArgus PET/CT has been designed with a user-friendly operator interface and easy animal positioning.

SuperArgus PET/CT

The SuperArgus PET/CT incorporates state-of-the-art detectors and electronics as the latest evolution of the Argus PET/CT family of scanners.

The core of the new scanner is the unique phoswich PET detector technology, which provides true depth-of-interaction (tDOI), providing resolution (≤1.0mm ) uniformity across the entire field of view, resulting in the largest field of view on the market. These detectors are also some of the most sensitive (11% at 100-700keV), allowing for real-time imaging (up to 2.5msec frame rate if desired).

The SuperArgus system may be configured to be PET-only or PET/CT. There are three models available r – 100mm bore for mice, rats, or marmosets up to 3kg; R – 160mm bore for multi-animal imaging, as well as rabbits up to 6kg; or P – 260mm bore for non-human primates, canine or porcine up to 10kg. Each model can be configured with 2, 4, or 6 PET rings.

Updates to the CT technology have focused on lower doses of radiation, faster scan times, higher resolution images, and advanced applications.

The SuperArgus has been designed to meet the demanding needs of the busy laboratory with improved animal handling, including a multi-animal bed that allows for high throughput imaging on all of the available models.

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The SuperArgus PET/CT system incorporates state-of-the-art detectors as well as the latest advancements in electronics, resulting in one of the most sensitive systems on the market today.

The phoswich detectors are key to the unique features of the system:

  • Provide true depth of interaction (tDOI) information resulting in
    • Highest resolution on the market; ≤1.0mm
    • Uniform resolution across the entire field of view, with the field of view filling the majority of the bore of the system due to the parallax error correction
  • Highest sensitivity on the market; 11% at 100-700keV
  • Real-time imaging; up to 2.5msec frame rate if desired

The advanced electronics allow for the following:

  • Dynamic imaging; possible due to time-stamp acquisition electronics
  • Parallel electronics for acquisition

Combined the phoswich detectors and electronics allow the SuperArgus system to be the first capable of conscious imaging in awake animals; this capability opens up endless possibilities of neuro-cognitive research which has yet to be explored.

In addition to awake animal imaging, the unique features of the SuperArgus system allow for sensorless cardiac imaging, possible on both a single animal but also on multi-animal imaging sessions.

Finally, a research and development consortium spread across Spain and the US has worked to develop Multiplex PET (mPET) capabilities on the SuperArgus system. That is the ability to detect two radiotracers simultaneously during the same imaging session. The software is then able to deconvolve the tracers, displaying the individual reconstructions.

Sedecal has optimized the electronics and algorithms to perform precise image reconstruction very quickly.

These are some of the more common reconstructions available on the system:

  • FBP (Filtered Back Projection) completed in less than 5 seconds
  • 2D OSEM (Ordered Subset Expectation Maximization) completed in less than 1 minutes
  • 3D OSEM completed in less than 2 minutes

Taken as a whole, the SuperArgus systems provide best-in-class image quality, as seen here on an 18F PET bone scan image:

The SuperArgus system may be configured to be PET-only or PET/CT. There are three models available r – 100mm bore for mouse, rats or marmosets up to 3kg; R – 160mm bore for multi-animal imaging, as well as rabbits up to 6kg; or P – 260mm bore for non-human primates, canine or porcine up to 10kg. Each model can be configured with 2, 4, or 6 PET rings. Please review the Tech Spec document for additional information on fields of view.

While Sedecal has invested a great deal of time in developing the phoswich detectors, and updated electronics for PET imaging, they have also focused on updating the CT technology within the SuperArgus systems as well. Updates have focused on lower doses of radiation, faster scan times, higher resolution images and advanced applications. These updates further the systems functionality in longitudinal studies, by minimizing the exposure of the animals to radiation throughout the course of a study.

The SuperArgus systems (r and R models only) have been designed to be self-shielded, meeting the FDA guidelines for CT scanners. This means that there are no special room requirements, or additional shielding required. The SuperArgus systems can easily be placed within existing laboratory environments, imaging core, or within an animal facility.

The animal handling systems of the SuperArgus system have been well thought out and designed to have integrated anesthesia, heating, and physiological monitoring. Multi-animal handling systems are available for all models, and custom configurations are possible.

The key benefits of the SuperArgus PET/CT systems include:

  • State-of-the-art phoswich detectors, providing
    • Provide true depth of interaction (tDOI) information resulting in
      • Highest resolution on the market; ≤1.0mm
      • Uniform resolution across the entire field of view, with the field of view filling the majority of the bore of the system due to the parallax error correction
    • Highest sensitivity on the market; 11% at 100-700keV
    • Real-time imaging; up to 2.5msec frame rate if desired
  • The advanced electronics allow for the following:
    • Dynamic imaging; possible due to time-stamp acquisition electronics
    • Parallel electronics for acquisition
  • First systems capable of conscious imaging in awake animals
  • Optimized reconstruction algorithms
    • FBP (Filtered Back Projection) completed in less than 5 seconds
    • 2D OSEM (Ordered Subset Expectation Maximization) completed in less than 1 minutes
    • 3D OSEM completed in less than 2 minutes
  • Sensorless cardiac imaging on single or multi-animal imaging sessions
  • Multiplex PET (mPET) imaging capabilities
  • Self-shielded design of the CT component, meeting FDA guidelines, reducing infrastructure requirements for installation
  • Multi-animal handling options available on all system models

Oncology is one of the most common applications of PET in preclinical imaging. Used clinically to detect small metastatic lesions throughout the body, preclinical applications of PET imaging are diverse. PET tracers have been developed to study:

  • Cell proliferation
  • Apoptosis
  • Angiogenesis
  • Metastasis
  • Gene expression of specific molecular targets
  • Receptor-ligand interactions
  • Substrate transportation
  • Nutrient metabolism

PET imaging may be used on any type of tumor model, as the radiotracers are typically injected intravenously for distribution to all areas of the body. Specifically, PET imaging may be used on orthotopic and transgenic/spontaneous tumors, as well as xenografts or metastatic lesions.

The above images and data come from a paper published by R.C. Mease et al. in Clinical Cancer Research [2008; 14(10)]. In this study they investigated the time vs. intensity curve of 18F-DCFBC, a radiotracer specifically designed to target prostate-specific membrane antigen. In this study the tumor on the left shoulder of the mouse was PSMA+ while the tumor on the right was PSMA-. This group also studied the activity in other organs such as the blood, kidneys, and liver.

Neurological applications of PET are commonplace both clinically and preclinically. Preclinical PET tracers have been developed to study:

  • Biodistribution of a specific target
  • Cerebral blood flow
  • Cerebral metabolic rate
  • Availability of specific receptors in the brain
  • Dopamine transmission
  • Plasma membrane transporters
  • Receptor binding sites

PET imaging has been used to study the pathological processes, response to therapeutics, and resolution of many disease models, including Parkinson’s Disease, Alzheimer’s Disease, Huntington’s Disease, Stroke, Epilepsy, Traumatic Brain Injury, and Neuropsychiatric disorders.

In the study above, which was featured on the cover of Journal of Neurochemistry [2015. Vol. 133(3)], Dr. Stephanie Kramer’s group studied the biodistribution of a novel metabotropic glutamate receptor 5 (m-Glu-R5) which utilized F-18 rather than C-11. This tracer is important in studying the synaptic plasticity and modulation of neural network activity, which is relevant in a number of psychiatric and neurological disorders. Previously, this work typically used a C-11 tracer; with the development of an F-18 tracer to do similar work the logistics of carrying out such studies becomes increasingly easier due to the longer half-life of F-18 compared to C-11.

Cardiology applications of PET are commonplace both clinically and preclinically. Preclinical PET tracers have been developed to study:

  • Myocardial perfusion to examine the extent of stenosis and severity of obstruction
  • Myocardial metabolism
  • Myocardial viability
  • Infarct assessment
  • Calcium scoring in coronary artery disease
  • Inflammation and plaque development for risk stratification

Many different cardiovascular diseases may be investigated using PET imaging, including coronary artery disease, myocardial infarction, or heart failure.

In addition to standard cardiac imaging using ECG leads, the SuperArgus system is capable of generating sensorless cardiac images, either from a single animal or multiple animals in the same imaging session.

       ECG-Based Gating   Automatic Gating
Systole           Diastole       Systole         DiastoleThe image above shows the accuracy of the automatic, sensorless, cardiac gating compared to that achieved with ECG-gated cardiac imaging. These images were acquired on a rat.

The recent COVID-19 pandemic has brought to the forefront the importance of PET imaging in immunological and infectious disease research. A survey of the literature shows that preclinical PET imaging has been shown to be invaluable in studying the following:

  • Understanding disease progression and pathogenesis
  • Diagnosis of disease, by targeting the specific pathogenic agent
  • Studying therapeutic efficacy of target compounds
  • Optimizing treatment regimens and studying the resolution of infections
  • Understanding the host’s immune response to infection
  • Studying the efficacy of vaccines

Infectious diseases and immunology are not limited to the study of viruses, but rather go well beyond these specific agents to look at models of bacterial, viral, parasite, and prion infections. The only limitation to this type of work is in the PET tracers available to investigate both the infectious agent as well as the host’s response.

Dynamic PET imaging is often used to study the kinetics of a newly developed PET tracer, or to investigate target concentrations, or biodistribution. Time-activity curves are often prepared along with assessments of radiotracer accumulation and biodistribution kinetic modeling.

                                   

In the images and data shown above, the first pass of FDG (flurodeoxy glucose) can be quantified in the tail vein, as well as the subsequent saline flush at approximately 14 seconds.

A variety of bone diseases may be studied using PET imaging, these include but are not limited to osteoporosis, osteomalacia, rickets, or rheumatoid arthritis.

A wide variety of other diseases, including metabolic disorders, can also be studied using PET imaging.

There is truly no limit on the application of PET in preclinical imaging, it is merely dependent on the development of specific and relevant PET tracers.

The above image shows increased metabolic activity in the paws of this arthritic rat model.

Typically, PET imaging is performed under sedation or anesthesia of some type. With the increased sensitivity of the phoswich detectors, as well as the advanced electronics which allow for real-time PET imaging, the possibility of performing conscious imaging on awake animals is now possible.

This capability opens the doors to any number of studies, including but not limited to neurological studies examining the effects of a stimulus, brown fat metabolism, and many others.

The animal is conditioned to the imaging tube, made of translucent red plastic so that the animals remain calm but can still be observed within the tube. The diameter of the tube is selected such that the animal cannot turn around but leaving sufficient room so as to not be compressed. Fiducial markers are glued to either side of the nose and behind each ear, in the case of neurological imaging. Once positioned within the tube the tracer is given either before or during the imaging session, and images are acquired in list mode.

The images above show a conscious rat injected with FDG (fluorodeoxygluocose). The acquisition is replayed at 50 frames per second, followed by a coregistration of the acquired frames into a 3D image covering the entire brain. The acquired data could also be reconstructed to show changes in the PET signal over time within a 3D volume.

Multiplex PET (mPET) imaging on the SuperArgus system was developed through a research and development consortium involving institutes in both Spain and the USA. This technique takes advantage of those radiotracers which commonly have triple coincidence events, as opposed to double coincidence events, such as Idodin-124, Bromine-76, Technesium-94m, Copper-60 etc. In a typical mPET imaging session a standard PET isotope is used in combination with a non-standard isotope, such as those mentioned above causing triple coincidence events on a regular basis. While acquiring an mPET image, the system electronics are set to accept both double and triple coincidence events; the software is then able deconvolve the two signals resulting in an image of each isotope being reconstructed.

In the images above the group was looking to simultaneously study glucose metabolism and dopamine transporters in the striate of the rat brain. FDG (fluorodeoxyglucose) was injected to look at cerebral metabolic activity, while an Iodine-124 CIT tracer was injected to study dopamine transporters.

The SuperArgus system is one of the leading PET/CT systems on the market, with high sensitivity and uniform resolution across the entire field of view. The high-performance capabilities of the system relate to both the unique phoswich detectors as well as the advanced electronics developed by Sedecal.

The spatial resolution of the SuperArgus systems was found to be ≤1.0mm at the center of the field of view, but this was maintained across the entire axial field of view due to the parallax error correction provided by the phoswich detectors, when the 3D-OSEM reconstruction algorithm was used.

In this hot rod study the phantom was inserted into the system with an off set of 1.2cm from the center of the field of view. Between images the phantom was rotated 60 degrees from A through C. When no depth of interaction correction is applied the effects are clear. There is streaking of the rods in most sectors, specifically those that are further from the center of the field of view. Additionally, smallest rods cannot be resolved, and the ring of activity on the outside cannot be seen in its entirety on the outer portions of the field of view. However, when the depth of interaction information is taken into account there is no streaking seen, and the entire outer ring can be seen in all positions. The smallest rods are clearly resolved in all images, even when these are the furthest from the center of the field of view.

In the image above the resolution is shown as a function of offset from the center of the field of view, with results shown for various reconstruction algorithms with and without the depth of interaction information taken into account.

The sensitivity of the 4R (160mm bore, with 10mm fixed trans-axial field of view with 4 rings) model was found to be 8.3% at the center of the FOV in the energy window of 100-700 keV. The graph below shows both the axial and trans-axial sensitivity from a point source as a function of radial offset from the center of the field of view.
The NEC rate of the 4R (160mm bore, with 10mm fixed trans-axial FOV with 4 rings) was found to be >260 kcps at 0.5mCi in a rat phantom, and 1200 kcps (or 1.2 Mcps) at 1.5-1.6mCi in the rat phantom; both measured at 100-700 keV.

The above image shows the NEC rate at a variety of energy windows, these measurements were performed on a rat phantom.

ModelArgus CompactSuperArgus PET/CT 2rSuperArgus PET/CT 4rSuperArgus PET/CT 6rSuperArgus PET/CT 2RSuperArgus PET/CT 4RSuperArgus PET/CT 6RSuperArgus PET/CT 4PSuperArgus PET/CT 6P
AnimalsMice onlyMice, rats and marmosetsMice, rats and marmosetsMice, rats and marmosetsMice, rats, marmosets, rabbits (3 kg)Mice, rats, marmosets, rabbits (3 kg)Mice, rats, marmosets, rabbits (3 kg)Non-human primates; canine; porcine, murine (10 kg)Non-human primates; canine; porcine, murine (10kg)
Dynamic AFOV100 mm220 mm220 mm220 mm350 mm350 mm350 mm650 mm650 mm
Static AFOV100 mm50 mm100 mm150 mm50 mm100 mm151 mm100 mm150 mm
TFOV50 mm80 mm80 mm80 mm120 mm120 mm120 mm210 mm210 mm
Bore size55 mm90 mm90 mm90 mm160 mm160 mm160 mm260 mm260 mm
Detectors322856844896144128192
DOI crystals10816946418928283921622432448486724326464896
ModelBasicAdvancedExtended
RotationContinuosContinuousContinuous
FOV70 x 180 mm120 x 350 mm210 x 650 mm
ZoomNoYesYes
Acquisition time15 s15 s15 s
Spatial resolution50 µm15 µm20 µm
Flat panelCMOS and Cs plateCMOS and Cs plateCMOS and Cs plate
FPS868686
Detector Active Area12 x 15 cm23 x 15 cm29 x 23 cm
Number of pixels1944 x 15363072 x 19443888 x 3072
X Ray Energy peak50 kV130 kV130 kV
Source spot35 µm 7 to 100 µm 7 to 100 µm
Max Power50 W65 W65 W
X Ray ProtectionAuto shielded according FDA