Biospace Lab Photon Imager - Designed for REAL TIME Bioluminescence

The Photon Imager is a modular system for the non-invasive detection, localization and quantification of a dynamic optical signal - bioluminescence or fluorescence – from live animals. A unique photon counting technology makes it extremely sensitive from the very start of image acquisition and enables the unparalleled kinetic recording of dynamic processes without the need for setting acquisition time, or pixel binning prior to imaging. Photon Imager continuously displays the light distribution during an experiment and image acquisition can be stopped at any time. This is a key advantage for REAL TIME bioluminescence imaging and can open new horizons for fluorescence imaging. Unlike other Pre-Clinical Imaging systems, the REAL TIME imaging capability of the Photon Imager delivers impressive performance, whilst its modular design philosophy ensures that the systems capabilities can be extended, as further state-of-the-art imaging technologies become available.

High sensitivity

Photon Imager intensified CCD
1 -> Lenses
2 -> Photocathode
3 -> Multichannel plate
4 -> High voltages
5 -> Phosphor screen

The Photon Imager design incorporates an intensified CCD camera, which makes it highly sensitive from the very first moments of image acquisition. iCCD technology amplifies all light emitted from the specimen by a factor 106; making the Photon Imager one of the most sensitive systems on the market for detection of low signal levels.

The operating principle is described opposite: photons are focused by a series of lenses (1) and are converted to electrons when they reach the photocathode (2). These electrons are then amplified by the microchannel plate (3), and converted back to photons by a phosphorescent screen (5) and the resulting spot of light is then recorded by the CCD camera. By amplifying the signal in this way, thermal noise can easily be removed, since its intensity will always be much lower than the signal resulting from even a single photon amplified by the intensifier tube. As a direct result of this, the CCD camera is able to record and forward the signal at a rapid constant frame rate of 43 Hz. The excellent sensitivity and real time capabilities of the Photon Imager come directly from this design and help provide a unique solution for in vivo whole body optical imaging in small animals.

Outstanding sensitivity and dynamic range

Photon Imager Dynamic Detection Range

The Photon Imager design ensures signal intensification by a factor of 106 and as a consequence, the Photon Imager is the most sensitive system on the market for detection of weak light signals. Furthermore, users of the Photon Imager can rely on an unequalled linear dynamic range: Luminescence expression in tissues can thereby be followed, quantified and compared; from early detection of weak signal, through to later development of higher signal strength.

Unique features of the Photon Imager

• True REAL TIME Bioluminescence(30 frames per second) capture and display
• Unmatched performance with a unique photon counting technology
• Fast and easy automated fluorescence, user friendly hardware and software
• New imaging possibilities. The Photon Imager is the only in vivo whole body imaging instrument that provides fast kinetic results and acquire videos of non sedated, freely moving animals

Easy REAL TIME fluorescence

Continuous selection of the excitation wavelength in the range of 400 nm to 800 nm enables optimal excitation conditions. Auto fluorescence is automatically suppressed.

No more guessing

Acquisition time or pixel binning settings prior to imaging is not necessary. The Photon Imager continuously displays the light distribution during the experiment and can be stopped at any time. Bias linked to reaction kinetics are suppressed.

Disclaimer:
Biospace Lab's Photon Imager may be used in a wide range of imaging applications including in vivo imaging in animals. However, in certain countries such as the United-States and Canada, certain applications may require a license from third parties. Biospace Lab's sale or transfer of its Photon Imager does not convey any right or license under any third party patent. In particular, Institut Pasteur from France believes that it owns or controls Patents with valid claims that cover certain aspects of in vivo imaging. Therefore, users of the Photon Imager in the United States and Canada should seek legal advice to determine whether they require a license under one or more of the following Patent Nos. US 6,800,492 and US 2007/0274923. Also, in the United-States and Canada, Caliper Life Sciences, Inc believes that it owns or controls U.S. and Canadian patents with valid claims that cover specific aspects of in vivo imaging. Therefore, users of the Photon Imager in the United States and Canada should seek legal advice to determine whether they require a license under one or more of the following patents: U.S. Patent Nos. 5,650,135 ; 6,217,847 ; 7,198,774 ; 6,649,143 ; 6,939,533 ; 6,916,462 ; 6,923,951 ; 6,890,515 ; 6,908,605 ; 5,824,468 ; 6,638,752 ; 6,737,245 and 6,867,348; and Canadian Patents and Patent Applications Nos: CA2237983 ; CA2384496 ; CA2407141 ; CA2373747 ; CA2440560 ; CA2384496 ; CA2364017 and CA2355900.

Biospace Lab Gamma Imager

The Gamma Imager is a modular system dedicated to preclinical real-time in vivo nuclear imaging of small animals. The Gamma Imager is a system that can be purchased in different configurations: planar scintigraphy, SPECT, SPECT/CT, 2-head SPECT or SPECT/CT. The system is appreciated for its modularity and its good value for money.

Planar scintigraphy

• Gamma Imager is fast, easy to operate and provides reliable quantitative information
• Powerful hardware and software tools generate high resolution scintigraphic images on which regions of interest can easily be drawn for quantitation purpose
• Full body mouse biodistributions are saved in a list mode file allowing separation of the image contributions of different radioisotopes as well as opening any time frame of interest
• Gamma Imager is compatible with a wide range of radioisotopes, including ¹²⁵I, ⁸¹mKr, ²⁰¹Tl, ⁹⁹mTc, ¹²³I, ¹¹¹In
• Gamma Imager is operated from a notebook computer and the ideal solution for multi sites experiments including small animal facilities

Micro SPECT

• Switching from planar scintigraphy to microSPECT imaging is very easy and convenient
• This cost effective solution has been designed to provide state of the art performance with minimal footprint, compatible with any lab bench-top
• During acquisition, a micro SPECT reconstructed transaxial slice is displayed and refreshed continuously for close experiment monitoring
• Dynamic studies are available in micro SPECT mode with 1 minute time resolution
• Parallel collimation and high resolution pinhole collimation are available

Micro SPECT

• Gamma Imager - SCT hardware and software provide 3D image fusion that combines microCT high resolution anatomical image with microSPECT functional information
• MicroCT large field of view is compatible with large rat imaging as well as full body mouse imaging
• Gamma Imager-SCT performs both micro SPECT and micro CT acquisitions simultaneously
• Fused micro SPECT / microCT images are displayed in real time and refreshed continuously during the experiment

Fast, easy and quantitative biodistributions

Planar scintigraphy: biodistribution of a ¹¹¹In complex functionalized with Glutamine residues in HER-2/neu mouse. Courtesy of Dr. S. Aime, Univ Torino.

True real-time micro SPECT / micro CT registration and display

Screenshot during a micro SPECT / micro CT acquisition. Micro SPECT, micro CT and micro SPECT-CT fusion slices are displayed and refreshed continuously during the experiment.

3D micro SPECT / micro CT registration

Micro SPECT / micro CT ^99mTc-MIBI. Courtesy of Dr. M. Kilbourn, University of Michigan, USA

Sub-millimetric spatial resolution

¹²⁵I pinhole micro SPECT of mouse thyroid. Courtesy of E. Noirault, INSERM U484, Clermont-Ferrand, France.

2D micro SPECT / micro CT registration

Micro SPECT / micro CT ⁹⁹mTc-MIBI. Courtesy of Dr. T.Higuchi, Nuklearmedizinische Klinik, Munich, Germany

Biospace Lab Beta Imager

The Beta Imager is a system for digital autoradiography, with high sensitivity, especially for tritium (3H), and high throughput (large field of view). It cuts down time acquisition by up to 500 compared with films: a few hours compared to a few days or a few weeks. The system is a "must-have" for brain receptor studies, which require large series of acquisitions, and is used by a great number of leading pharmaceutical companies for drug development. Its capabilities to discriminate the contributions of several isotopes from a single acquisition makes it also very interesting for applications in nuclear medicine research.

Tritium detection 500 times faster than film autoradiography

Tritium is an excellent probe for the measurement of biological activity. It may be substituted into virtually any compound at high specific activities and the low energy beta radiation is ideal for autoradiographic imaging. However, detection by way of traditional methods is slow. Film and Storage Phosphor imaging based methods can take days or weeks to deliver results. Now, there is a better way to meet the need for high throughput and quick results: Beta imager cuts tritium imaging from weeks, or days to hours.

A versatile technology

• Ideal for tritium detection
• Detects all other commonly used beta emitting isotopes (¹⁴C, ³²P, ³⁵S, ³³P, ¹²⁵I)
• Detects electrons associated with gamma emitting isotopes
• Detects positrons associated with isotopes commonly used in Positron Emission Tomography

A wide range of applications

• Ex vitro and in vitro receptor binding
• Quantitative Whole Body Autoradiography
• Tissue sections mounted on glass
• Any tissue sections
• TLC plate
• Electrophoresis gels
• Hybridization membranes
• Ex vivo imaging after microSPECT or microPET

The very high sensitivity of the Beta imager cuts tritium imaging from weeks to hours

4 week imaging plate acquisition (left) of rat brain sections using a ³H labeled probe compared to a 5 hour Beta Imager acquisition (right). Courtesy of Aventis Bridgewater, NI, USA

Real-time imaging provides a direct visualization of the signal being acquired at any time during the experiment

Distribution of D1 receptors in the rat striatum with ³H labeling. Courtesy of Janssen Research Foundation

Probe multiplexing for healthy and necrotic cells discrimination

A study of the apoptotic to healthy cells ratio in the rat heart. ²⁰¹Tl is fixed by healthy cells, ⁹⁹mTc-Annexin is fixed by necrotic cells. Courtesy of N. Barthe, INSERM, Bordeaux, France.

Biospace Lab Micro Imager

The Micro Imager is a system for digital autoradiography, with high sensitivity and high resolution. It cuts down time acquisition by up to 50 compared with films, with a resolution down to 15 µm. The system has numerous applications and is used by laboratories on topics as diverse as neurosciences, microbiology, cardiology, oncology and physiology, but also developmental biology, vegetal physiology and marine geochemistry. Like the Beta Imager, the Micro Image is able to discriminate the contributions of several isotopes from a single acquisition, a keay feature for applications in nuclear medicine research.

The Micro Imager: Digital detection - High resolution Fast acquisition - Multiple probe discrimination Finally a digital solution to micro autoradiography

Micro Imager is 50 times faster than fil with tritium labeled samples, allows precise quantitation, and boasts a 15 µm resolution unsurpassed by any other non film technique.

Micro Imager is fast, precise, and easy to operate

• no complex techniques are required
• 15 µm spatial resolution opens new fields for digital micro autoradiography
• real-time display and list mode data file storage avoid risk of over and under exposure
• image registration is available using either direct white light sample illumination or image import from microscope
• an exclusive patent allows simultaneous imaging and discrimination of multiple emitters
• precise quantitation can be performed even at very short acquisition times

Accurate analysis of labeled molecules in tissue sections and other applications

• ex vivo positron and gamma emitter imaging
• in situ hybridization
• receptor-ligand
• binding assays
• metabolic tracer experiments
• BNA arrays
• biochips

The very high resolution of the Micro Imager opens a wide range of applications in Genomics

In situ hybridization study in rat hyppocampus using a ³H labeled probe.

Micro array involving 220 clones at 300 μm pitch on a 5 mm x 5 mm chip. The ³³P probe was prepared from rat brain cells, labeled and hybridized to the corresponding cDNAs on the slide. Courtesy of S. Dumas and J. Mallet, Laboratory of Neurotransmission Molecular Genetics and Neurodegenerative Processes (LGN), la Pitié Salpêtrière Hospital, Paris, France.

Tissue sections

Receptor binding assay: characterization of serotonin receptors on a rat brain section, with ¹²⁵I labeled serotonin-O-carboxymethyl-glycile. The image show an heterogeneous distribution with regions rich in 5-HT 1B and 5HT 1D binding sites. The absence of saturation enables distinguishing all structures in the section. Courtesy of L. Ségu, CNRS URA 339, Bordeaux, France.

Tritium labeled rat kidney section Courtesy of S. Harris, Roche, Welwyn, United Kingdom.

Choroid membrane of a rat eye (¹⁴C label). Couresty of Dr. Delbos, Laboratoires Serviers, Orléans, France

Biospace Lab Beta Microprobe

The Beta Microprobe is a unique fibered system for in vivo local measurements of radioactivities. With its thin fiber tip, the system can be inserted in virtually any location in the animal for a precise and accurate quantification of beta emissions. It provides a very low cost, simple alternative to µ-PET for pharmacokinetics, behavior studies, FDG studies, radiotracer development, and input function measurements among others.

The probe is sensitive to Beta emitters including ¹¹C, ¹⁸F, ³²P, ¹³¹I, and provides a very low cost, simple alternative to µPET for pharmacokinetics, behavior studies, FDG studies, radiotracer development, and input function measurements among others.

Stereotaxically implanted in the animal brain, this unique microprobe allows users to measure kinetics of a Beta labeled molecule on animals anesthetized or not, on short to long timescales, in a well defined brain locus. The probe can also be positioned in an organ, a tumor, or in a blood vessel to measure the input function in a tracer experiment.

Fast, easy and quantitative biodistributions

On line kinetics measurements of ¹¹C-raclopride binding after anaesthesia. Two beta microprobes were implanted stereotaxically before the injection of the tracer. Courtesy of V. Leviel and L. Zimmer, CERMEP, Lyon, France.

Rat brain kinetics after three successive injections of ¹⁸F-FDG (0.5, 1 and 2 mCi). Kinetics are recorded by two probes implanted in the striatum and cerebellum. Courtesy of L. Besret and Ph. Hantraye, SHFJ Orsay, France.

Biospace Lab M³ Vision

Biospace Lab has developped a new software for the analysis of its molecular imaging instruments, the Beta Imager, the Micro Imager, the Photon Imager and the Gamma Imager. The philosophy of the new software relies on two analysis modes: a standard mode for easy, fast yet precise routine analyses; and an advanced mode, with a large number of options and highly specific processes.

Save time with the automated tasks

When you analyze acquisitions, there is a significant number of actions you repeat identically for each image: fuse signal and photographic images, adapt the Look up Table (LUT) min and max to the signal histogram distribution, isolate the signal source with a region of interest for quantification and characterization, discriminate fluorescence and autofluorescence, check kinetics.

After a throrough study of analyses routines, Biospace Lab was able to implement in M3 Vision an easier and more consistent interface for image analysis. Routine tasks are automated or pre setted:

• Images are automatically opened as fusion (signal & photography of acquisitions)
• ROI selection is immediate with the magic wands. The magic wands analyze the LUT min parameter to suggest intelligent thresholds
• Users can get rid of autofluorescence in a few clicks with the semi automated unmixing interface
• Kinetics of images or regions of interest require only a single click to reveal the signal time profile
• Zoom into you signal to detect the significance of even subtle signal variations in autoradiographic images

You analyze, M³ Vision reckons

Biology is too complex to permit approximative interpretation. With M3 Vision, you can spend more time to think on the interpretation of your results and leave the computation time to the software. Quantification with M3 Vision means:

After a throrough study of analyses routines, Biospace Lab was able to implement in M3 Vision an easier and more consistent interface for image analysis. Routine tasks are automated or pre setted:

• Easy drawing of regions of interest: geometric, freehand, automated with magic wands; duplication, editing, fusion features
• Clear and detailed report of ROI signal intensities
• Immediate export of intensities to Excel files or html format of all images analysed in one shot
• Export kinetic curves and spatial profile as easily as the ROI intensities
• Export snapshots of your acquisitions with the quantification figures burned in the images

Multi Modality Molecular Vision - The software includes the expertise of Biospace Lab for the analysis of the different modalities of its instruments: autoradiography, scintigraphy, optical imaging. The standard/advanced mode, and the polymorphism properties of the software enables it to offer, for each modality, a user-friendly interface and optimized processes.

A search engine

We know research is not just about imaging one mouse, but tens, hundreds, thousands or maybe more before your idea turns into an hypothesis and a discovery. M3 Vision gives you the possibility to find back instantaneously the acquisition, among all your files, with which everything started... or any of the 999 other images! The search desktop builds and scans an image base that allows to find images on any possible way: comments, properties, acquisition date... No way you can loose a file now!

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