Optical imaging in visible & nir i

Detect, quantify and monitor biological processes thanks to an unmatched sensitivity and benefits of the kinetics recording.

The non-invasive nature of optical imaging allows the high throughput monitoring of interest, such as disease progression or infection course within the same group of animals. Several subgroups of animals can be analyzed in the context of one experiment, accelerating the studies. Thus, reducing the number of animals needed to generate statistically significant data. In addition, by avoiding the need for invasive sampling procedures, optical imaging can also result in a reduction in the levels of stress and discomfort experienced by animals.

The PhotonIMAGER systems enable the in vivo acquisition of bioluminescence and fluorescence signals in small animals within the visible spectrum, ranging from violet to near infrared.

This system combines high sensitivity, very wide quantification dynamic range and high speed, with the possibility to image up to 10 animals per acquisition.

  • 1- Detect the tiniest biological processes thanks to the unmatched sensitivity of our unique dynamic acquisition technology.

A single photon detected on the entry face of the intensified camera will generate an intense light spot easily detectable and recognizable by the CCD when intensified.

This technology allows to count individually each photon emitted by the signal center. This method of quantification is called photo counting and leads to an almost perfect linearity as it sums each photon detected.

The photo-counting technology combined with the high-dynamic of the optaical chain allow to reach a global linear range over 106 and a linear range within a same image over 104.

The high sensitivity opens way towards bioluminescence detection to few cells’ detection subcutaneous and few hundreds in deep tissues (livers, lungs, pancreas…)

Example of pulmonary metastasis detected in the lungs. Despite the resection, there is a 1,000 factor between the primary tumor and the metastasis.

  • 1- Detect the tiniest biological processes thanks to the unmatched sensitivity of our unique dynamic acquisition technology.

Example of pulmonary metastasis detected in the lungs. Despite the resection, there is a 1,000 factor between the primary tumor and the metastasis.

A single photon detected on the entry face of the intensified camera will generate an intense light spot easily detectable and recognizable by the CCD when intensified.

This technology allows to count individually each photon emitted by the signal center. This method of quantification is called photo counting and leads to an almost perfect linearity as it sums each photon detected.

The photo-counting technology combined with the high-dynamic of the optical chain allow to reach a global linear range over 106 and a linear range within a same image over 104.

The high sensitivity opens way towards bioluminescence detection to few cells’ detection subcutaneous and few hundreds in deep tissues (livers, lungs, pancreas…)

  • 2- Quantify with the greatest accuracy by monitoring the signal kinetics enabled by our real - time acquisition.

Thanks to its high temporal resolution and excellent sensitivity the PhotonIMAGER continuously displays the light distribution from the first seconds of the experiment and can be stopped at any time. The dynamic imaging capability of the PhotonIMAGER system allows the signal kinetics to be followed precisely and independently, even when the signal is weak. It provides precise control over the time-zone selected for the measurement of each ROI, both during and following signal acquisition. The ideal signal measurement window can always be accurately selected for each animal or anatomical region in turn.

Only Real-time acquisition takes into account the kinetic of the luciferase enzymic reaction, and hence allows for accurate quantification. The quantification is performed at the optimal timeline.

The quantification depends on the biodistribution of the Luciferin (i.e.; anesthesia, food intake, circadian cycle … ). For each acquisition, the signal quantification should be done at the time when the enzyme activity is balanced and the signal intensity issued from it is optimal. It is called the “Plateau”.  The kinetic of the signal variating from an animal to another is mainly due to marked cells localization, only real-time acquisitions will allow to control the quantifications on temporal windows wisely chosen on the plate for each emission sites.

Although the kinetics are subjected to equivalent protocols and experimental conditions, we can see that the kinetics from emission sites vary and that a reliable quantification requires an individualized plate control.

Picture above shows the signal kinetic from 3 different mice who received a subcutaneous injection of mesenchymal stem cells transfected with the gene expressing the firefly luciferase (Fluc). Each mouse has also been injected in intra-peritoneal with luciferine just before acquisition:

  • 3- Discover unique insights by visualizing moving animals.

With the real-time technology of the PhotonIMAGER, you can imagine experiments with non-anesthetized, freely moving animals and opens previously unimagined new avenues for research.

Biological phenomena are always dynamic, and so a single observation at a fixed time point often results in an incomplete view of the overall process, which results in misinterpretation of the available data. It results in the loss of information on fast moving dynamic phenomena.

Find out full advantages of imagery of non-anesthetized animals:

  • Anesthesia is a time-consuming step and reduces the throughput of an imaging system.
  • Anesthesia can introduce bias by disturbing the physiology and affecting signal expression, so directly affecting the pathology of an animal model. (cf Anesthesia and other considerations for in vivo imaging of small animals, Hildebrandt et al, ILAR 2008).
  • Imaging an animal in motion is not possible, so monitoring activity in the brain during sleep and wake cycles or observing a bioluminescent signal in a contracting muscle non-invasively in vivo is not possible.
 
 
  • 3- Discover unique insights by visualizing moving animals.

With the real-time technology of the PhotonIMAGER, you can imagine experiments with non-anesthetized, freely moving animals and opens previously unimagined new avenues for research.

Biological phenomena are always dynamic, and so a single observation at a fixed time point often results in an incomplete view of the overall process, which results in misinterpretation of the available data. It results in the loss of information on fast moving dynamic phenomena.

Find out full advantages of imagery of non-anesthetized animals:

  • Anesthesia is a time-consuming step and reduces the throughput of an imaging system.
  • Anesthesia can introduce bias by disturbing the physiology and affecting signal expression, so directly affecting the pathology of an animal model. (cf Anesthesia and other considerations for in vivo imaging of small animals, Hildebrandt et al, ILAR 2008).
  • Imaging an animal in motion is not possible, so monitoring activity in the brain during sleep and wake cycles or observing a bioluminescent signal in a contracting muscle non-invasively in vivo is not possible.
 
 
  • 4- A modular system for all applications. Build your own system adapted to your research.

The modular philosophy of the PhotonIMAGER systems allows you to keep up with the latest developments in imaging technologies – existing optional modules and future options can be added to the basic instrument configuration.

Optical imaging has never been easier: change modules quickly, chose your module and acquisition mode on the touchscreen and start acquisition.

MACROLENS

Many real-life applications, such as studying cell invasion and cell migration in Cancer Research or stem cell implantation experiments, require information gathered at different spatial resolutions. The MacroLens module offers a practical solution to this challenge: track cells non invasively at the macroscopic level throughout an entire animal, assess cell growth, spreading or migration at the level of the organ or at a specific anatomic location, focus on smaller groups of cells at the microscopic level.

The MacroLens module was developed by Biospace Lab to open a new window into the world of bioluminescence microscopy and to build the missing link between macroscopic and microscopic for fluorescence and bioluminescence imaging applications.

Macrolens module for high resolution optical imaging down to 2,5µm ex vivo. Zoom in on specific areas of interest and obtain accurate quantification. Correlate the in vivo to ex vivo.

Many real-life applications, such as studying cell invasion and cell migration in Cancer Research or stem cell implantation experiments, require information gathered at different spatial resolutions. The MacroLens module offers a practical solution to this challenge: track cells non invasively at the macroscopic level throughout an entire animal, assess cell growth, spreading or migration at the level of the organ or at a specific anatomic location, focus on smaller groups of cells at the microscopic level.

The MacroLens module was developed by Biospace Lab to open a new window into the world of bioluminescence microscopy and to build the missing link between macroscopic and microscopic for fluorescence and bioluminescence imaging applications.

Macrolens module for high resolution optical imaging down to 2,5µm ex vivo. Zoom in on specific areas of interest and obtain accurate quantification. Correlate the in vivo to ex vivo.

IN ACTIO

The In Actio module simultaneously records both bioluminescence signal and a bright field video of the animal under infra red illumination for co-registration; thereby extending the the imaging capabilities of the Photon Imager from recording dynamic signal from an anesthetized animal, to recording dynamic signal from a free moving animal. The In Actio module offers the following advantages in circumstances where there is no need for multiple views of the animal, as provided by the 3D Module:

Epilepsy crisis in a 7-day-old mtGA expressing mouse

4 VIEW – 3D

Simultaneous acquisition of the 4 views of the animal The 4 View module helps increasing the analysis accuracy and relevance of your acquisitions. It offers a precise quantification by providing you not only one but several views of your animal (dorsal, ventral, and lateral views) simultaneously and in real time. The 4-View module is an excellent tool for a better localization of optical signals

The 4-View – 3D module for an even better localization and quantification of optical signals.

X-RAY

The X-Ray module for the PhotonIMAGER Optima provides the possibility for overlay of x-ray images and optical signals. With this specific high resolution anatomical information the accurate localization of the optical signals is made easy.

X-Ray module for a better anatomical localization of optical signals. A low dose imaging up to 5 mice.

XRAY

The X-Ray module for the PhotonIMAGER Optima provides the possibility for overlay of x-ray images and optical signals. With this specific high resolution anatomical information the accurate localization of the optical signals is made easy.

X-Ray module for a better anatomical localization of optical signals. A low dose imaging up to 5 mice.

TOMOFLUO

The PhotonIMAGER OPTIMA TomoFluo module was specifically developed for highly precise 3D quantification of fluorescence signals in vivo. It uses fDOT, the next generation of in vivo Fluorescence Tomography algorithms. fDOT (fluorescence Diffusion Optical Tomography) reduces scattering & attenuation artefacts as well as samples boundary problems thanks to its iterative Algebraic Reconstruction Technique (ART). Volumetric Fluoresence data can be ovelayed to a 3D surface reconstruction of the subject or co-registered with CT/PET/SPECT/MRI data

TomoFluo module for Quantifying deep seated tissue signals, obtaining accurate pharmacokinetics and longitudinal quantification.

PHOTONIMAGER OPTIMA & RT

PhotonIMAGER Optima

The PhotonIMAGER Optima system is a fully comprehensive solution for advanced in vivo optical imaging applications and is unequalled in its performance.

All modules are compatible

PhotonIMAGER RT

The PhotonIMAGER RT system is a modular entry level solution for routine in vivo luminescence and fluorescence imaging applications.

Modules : 4views, In action, Macrolens.

Optical imaging in the near infrared II & III (SWIR)

Acquire images with deep penetration, high sensitivity, and high spatial resolution in the short-wave infrared region (SWIR) without interference by autofluorescence, with minimum light absorption by blood and tissue, or scattering.

The PhotonIMAGER SWIR is the world’s first industrial solution for an integrated preclinical application. Biospace Lab leverages 30th years of experience in optical imaging to bring SWIR concept to industrial reality.

Biospace Lab is a part of the NanoTBTech consortium ( “Nanoparticles-based 2D thermal bioimaging technologies” FET-Open EU H2020 801305)  that developed noninvasive solutions to measure tissue temperature for oncology treatment and diagnosis.

Imaging in the shortwave infrared region (900-1700 nm) allows improved tissue penetration and spatial resolution. These features enable unprecedented imaging opportunities with direct aapplications in the field of oncology and high potential for clinical translation

  • Achieve tissue transparency and obtain deep tissue information such as detailed vascular blood flow maps.

Achieving deep photon penetration is one of the main objectives in optical imaging. The NIR II and NIR III regions are characterized by negligible tissue autofluorescence, reduced optical scatter, and lower absorption compared to the near-infrared-I (NIR-I) window (600 to 900 nm). This high spatial resolution capacity of the SWIR in combination of high sensitivity due to the minimization of absorption and autofluorescecne allows for monitoring of smaller and deeper vessels.

  • Study rapid biological processes in greater detail than classic imaging modalities.

The PhotonIMAGER SWIR system is a perfect solution to acquire images in real time due to the high sensitivity that allows high frame rates. Thus contact-free monitoring of respiration and heart rate as well as real time metabolic imaging can be imaged with unprecedent accuracy.

  • Customize your own system to respond to your specific applications field such as temperature sensing with the newly developed nanothermometer probes.

Nano-thermometry is one of the main applications of the SWIR imaging due the spectral signatures of newly developed nanoparticles which are also known as nanothermometers. Nano-thermometry applications include the early detection of cancer, monitoring of enzymatic activity, evaluation of the therapeutic efficiency of drugs and controlling hyperthermia therapy. Temperature sensing rises as a new indispensable biological information.

Contact us to customize your SWIR instrument to your applications of interest. Choose among different lasers, filters, cameras …

 

We are the only company to offer a nanothermometry module which we integrated as an option of our PhotonIMAGER SWIR

Gather further information during your experimentations by monitoring the temperature of your region of interest and by using one the 3 following nanothermometry acquisition modes:

  • Sequential Fluorescence Imaging
  • Dual channel sequential Fluorescence Imaging (Ratiometry)
  • Suppression of Intrinsic tissue autofluoresence to obtain a superior sensitivity, by using the fluorescence lifetime mode

Autoradiography

Acquire ultra-rapidly, quantitatively, without failure the small scale biodistributions of low energy radioisotopes as well as multi-isotopes.

  • 1 - Unique system to detect and quantify both high and low sample concentrations in a single data acquisition with a high sensitivity and resolution.

Linear dynamic range of the BetaIMAGER

Courtesy of Dr Alain Schweizer, Novartis

The BetaIMAGER systems count all emitted particles, regardless of their energy. This direct beta counting technology of the BetaIMAGER systems provides unequalled performance: the BetaIMAGER tRACER system is some 500X more sensitive and the BetaIMAGER dFINE system some 50X more sensitive to tritium than either X-ray film or Storage Phosphor Screen. The BetaIMAGER tRACER system is unique in its ability to detect tritium levels as low as 0.007 cpm/mm2.

The BetaIMAGER systems provide precise localization and quantification of beta emitting radioligands. The advanced image analysis tools of the M3 vision sofware allow for direct analysis of digital data and a better than 1:10,000 linear dynamic range ensures accurate quantification over the widest possible range.

You can detect and quantify both high and low sample concentrations in a single data acquisition.

Biospace Lab develops an exclusive technology for the simultaneous detection and discrimination of multiple radioisotopes.

A single sample can be simultaneously labeled with several radioisotopes and the specific contribution from each detected during a single data acquisition. Discrimination can be based on emission energy (2 radioisotopes), or on radioactive half-life (2 isotopes or more). Examples of dual-detection radioisotope pairs include 3H/14C,3H/35S, 3H/32P or 33P and an example of a multi-label combination would be 99mTc/ 111In/18F.

This unique radioisotope discrimination feature allows the development of more rapid and accurate protocols for recording the distribution of several molecules simultaneously in a single specimen.

You can obtain co-localization of different receptors, or receptors and ligands. Map complex functional activity with pathology or Comparing specific gene expression with a reference gene.

  • 1 - Unique system to detect and quantify both high and low sample concentrations in a single data acquisition with a high sensitivity and resolution.

The BetaIMAGER™ systems count all emitted particles, regardless of their energy. This direct beta counting technology of the BetaIMAGER systems provides unequalled performance: the BetaIMAGER™ tRACER system is some 500X more sensitive and the BetaIMAGER™ dFINE system some 50X more sensitive to tritium than either X-ray film or Storage Phosphor Screen. The BetaIMAGER™ tRACER system is unique in its ability to detect tritium levels as low as 0.007 cpm/mm2

The BetaIMAGER systems provide precise localization and quantification of beta emitting radioligands. The advanced image analysis tools of the M3 vision sofware allow for direct analysis of digital data and a better than 1:10,000 linear dynamic range ensures accurate quantification over the widest possible range.

 

Linear dynamic range of the BetaIMAGER

Courtesy of Dr Alain Schweizer, Novartis

You can detect and quantify both high and low sample concentrations in a single data acquisition.

Biospace Lab develops an exclusive technology for the simultaneous detection and discrimination of multiple radioisotopes

A single sample can be simultaneously labeled with several radioisotopes and the specific contribution from each detected during a single data acquisition. Discrimination can be based on emission energy (2 radioisotopes), or on radioactive half-life (2 isotopes or more). Examples of dual-detection radioisotope pairs include 3H/14C,3H/35S, 3H/32P or 33P and an example of a multi-label combination would be 99mTc/ 111In/18F

This unique radioisotope discrimination feature allows the development of more rapid and accurate protocols for recording the distribution of several molecules simultaneously in a single specimen.

You can obtain co-localization of different receptors, or receptors and ligands. Map complex functional activity with pathology or Comparing specific gene expression with a reference gene.

  • 2- Gain hours or days by acquiring images in real time thanks to our real time detection technology.

The exclusive real-time detection technology used in both systems displays and accumulates counts in real-time:

 

Real-time autoradiography: distribution of D1 receptors in rat brain striatum following tritiated ligand binding

X-Ray film or Storage Phosphor screen based autoradiography requires a two-step blind acquisition process: expose and then scan

The real-time acquisition allows the instantaneous display of the image recorded by the camera and to follow the progression of the reconstitution of the finale image. The display of the finale image is refreshed every 30 seconds for the user to see it during the acquisition.

The unmatched sensitivity cuts your data acquisition time from weeks to hours.

You can see data accumulating in real-time and obtain the first results in minutes.

  • 3- No missed experiments caused by saturation

Disintegrations are detected in real-time and the data display is continuously updated during acquisition, so that under or over exposure of the sample.

Thus, the longer the acquisition is, the better is the image dynamic. The absence of limit on the duration of the acquisition allows the detection of the weak signals and the improvement of resolution.

  • 4- Use minimal amounts of radiolabeled compounds, reduce radioactive waste and minimize experimental costs as you can detect ultra-low level of bounds radiolabeled ligand.

Thanks to its high sensitivity, the BetaIMAGER systems can detect ultra-low levels of bound radiolabeled ligands. You can use minimal amounts of radiolabeled compounds and reduce radioactive waste as well as minimize your experimental costs.

Reduce the number of experiments thanks to the reproducibility of the system.

Non-destructive probe: no slices damaged or destroyed during the measurement.

 
 

BETAIMAGER SYSTEMS

Whatever the autoradiography application, either high speed or high-resolution autoradiography, Biospace Lab has the ideal solution.

BETAIMAGER TRACER

The BetaIMAGER™ TRACER is the system of choice for applications requiring the highest sensitivity and either high throughput, or larger sample sizes. Autoradiography becomes a fast and easy routine.

Tritium is a reliable beta emitter for measurement of biological samples. Problem is, detection is slow. Traditional film and phosphor imaging methods can take weeks to complete. But now, there’s a better way to meet the high throughput needs of your lab: The BetaIMAGER™ TRACER system cuts your tritium imaging time from weeks to hours. Exceptional sensitivity can be obtained even with ultra-low energy tritium emissions: the TRACER system detects tritium levels as low as 0,007 cpm/mm2

With a 200 x 250mm maximum field of view, the Beta Imager can accommodate up to 15 microscope slides, several larger tissue sections, or TLC plates for simultaneous image acquisition.

The sample activity has been calculated on the left figure acquisition because it is the only one containing the whole sample: 7,5.103 hpm (hit per minutes) which is 6,82 nCi.

Tritiated sample. 5h acquisition. Wider visual range than the sample
Tritiated sample. 18h acquisition. Minimal visual range.
  • 1. BetaIMAGER TRACER

The BetaIMAGER™ TRACER is the system of choice for applications requiring the highest sensitivity and either high throughput, or larger sample sizes. Autoradiography becomes a fast and easy routine.

Tritium is a reliable beta emitter for measurement of biological samples. Problem is, detection is slow. Traditional film and phosphor imaging methods can take weeks to complete. But now, there’s a better way to meet the high throughput needs of your lab: The BetaIMAGER™ TRACER system cuts your tritium imaging time from weeks to hours. Exceptional sensitivity can be obtained even with ultra-low energy tritium emissions: the TRACER system detects tritium levels as low as 0,007 cpm/mm2

With a 200 x 250mm maximum field of view, the Beta Imager can accommodate up to 15 microscope slides, several larger tissue sections, or TLC plates for simultaneous image acquisition.

Tritiated sample. 5h acquisition. Wider visual range than the sample
Tritiated sample. 18h acquisition. Minimal visual range.

The sample activity has been calculated on the left figure acquisition because it is the only one containing the whole sample: 7,5.103 hpm (hit per minutes) which is 6,82 nCi.

BETAIMAGER DFINE

The high-resolution digital autoradiography solution     

The BetaIMAGER™ DFINE system is the system of choice for applications involving smaller tissue sections and where the best possible spatial resolution is required. Four samples, up to 24 x 32mm each in size can be loaded onto the automated stage for sequential image acquisition. Spatial resolution as high as 10μm can be achieved with Tritium. The DFINE is the perfect ex-vivo complement to PET and SPECT molecular imaging.

The BetaIMAGER DFINE is 50 times faster than film with tritium labeled samples, allows precise quantitation, and boasts a 10μm resolution for tritiated samples unsurpassed by any other non film technique. No complex techniques or procedures to learn.

 
  • 2 - The BetaIMAGER™ DFINE

The high-resolution digital autoradiography solution     

The BetaIMAGER™ DFINE system is the system of choice for applications involving smaller tissue sections and where the best possible spatial resolution is required. Four samples, up to 24 x 32mm each in size can be loaded onto the automated stage for sequential image acquisition. Spatial resolution as high as 10μm can be achieved with Tritium. The DFINE is the perfect ex-vivo complement to PET and SPECT molecular imaging.

The BetaIMAGER DFINE is 50 times faster than film with tritium labeled samples, allows precise quantitation, and boasts a 10μm resolution for tritiated samples unsurpassed by any other non film technique. No complex techniques or procedures to learn.

 

Software

The IMAGER systems can be driven by the PhotoAcquisition and BetaAcquisition software which control the whole systems and its modules and manage the acquisitions semi-automatically.

The user-friendly interface of the software makes the use of the instrument simple and pleasant.

  • Simplicity and user-friendly Acquisition software

One of the real-time imagery interests is its practicality because it gives a feedback immediately after the beginning of the acquisition. Thus, the user can see the first signals after few seconds and quickly stop the acquisition or sufficiently extend it with the awareness of the accumulated signal quantity.

This real-time feedback allows the automatic and optimized control of some of the acquisition parameters such as the opening of the lens during the acquisition depending on the signal progress. These automatic time optimization capabilities simplify the use without blind configuration of the lens opening, integration time or binning level which must often be determined experimentally on the cooled CCD cameras system.

 
  • Simplicity of the analysis software

This software allows user to visualize 2D and 3D images, to play on the signal display threshold and to quantify depending on the ROIs which we set freely the limits depending on geometrical forms or thresholding made on the signal intensity.

The measurements made on the ROIs will allow a quantification of the total value of the signal, its top intensity, its lowest and its average value.

M3Vision also make time analysis possible which will allow to do quantifications at the plate time for each ROIs. An automatic selection tool of the temporal window to the signal plate allow a quick analysis of each ROI for high speed studies.

All quantifications and time profiles are easily exportable to Excel reports in one single click. For the longitudinal studies, all (the acquisitions linked to a study can be exported in a single Excel folder that includes one tab per acquisition as well as a summary table of all the quantifications.

The software analysis includes numerous functions which will allow automatically to quantify precisely and carefully:

The magic wand will allow to automatically draw the whole of the ROIs which will be determined by a signal intensity threshold: the conditions are then the same for the zone to quantify and the ROIs are automatically drawn in few fractions of seconds by the software.

The automatic temporal analysis: this tool will allow to proceed to the temporal analysis (quantification at the plate on each ROIs) in few seconds thanks to an automated process.

  • Traceability

During the acquisition save, the whole acquisition settings including lens opening, plate position, acquisition time, grid speed as well as date and time are saved. It is also possible to save comments related to imaged animals or notable event that occurred before or during the acquisition. All of this information will be linked to the acquisition folder and will be accessible from the analysis software.

M3Vision is a licensed software.