Equipment List

Select a section from below to learn more about that equipment

CT

What is a CT scan?
X-ray Computed Tomography (CT) uses electronically generated x-rays to create three-dimensional images of an object’s internal structures.

How does it work?
An X-ray CT system consists of an x-ray source (tube) and a corresponding detector, each located on opposite arms of a rotating gantry. As the gantry rotates about its axis, the system acquires a series of two-dimensional x-ray projection images of the object of interest, located at its isocentre. Structures within the object attenuate (by absorbing or reflecting) the x-rays generated by the source, thereby reducing the amount of x-ray energy that reaches the detector. Structures with greater density cause more attenuation than less dense structures. This is the mechanism that creates the contrast in X-ray CT images. After the projection images are acquired, a data processing technique called Back Projection Reconstruction is used to “smear out” each of these projection images along the projection plane, and then combine them to create a volume of X-Ray CT image slices through the object. These images are often scaled to Hounsfield Units, where air = -1000 HU and water = 0 HU.

Why would you use a CT scanner?
As mentioned above, the contrast in an X-ray CT image is directly related to the density of the different tissues or structures within the object being imaged, with high density materials attenuating x-rays to a greater degree than low density materials. For that reason, X-Ray CT is very useful in differentiating and quantifying high density structures such as bone and, for example, would be an effective modality for evaluating trabecular bone density in osteoporosis models.

Contrast between different soft tissue structures is subtle, but still visible in X-Ray CT images. Often large, well-defined tumours can be visualized, and their volumes measured, using a traditional X-ray CT scan. Targeted contrast agents can additionally aid the distinction of smaller or less-defined tumours. At STTARR, iodine-based (highly dense) contrast agents are incorporated into liposomal shells, which are then targeted to tumour biomarkers such that, after injection, they will find and remain at a tumour site for several days. The highly dense contrast agent at the tumour site is easily distinguished on X-Ray CT scans and aids visualization of the tumour itself.
Contrast agents can additionally be used to examine the kinetics of vascular perfusion. These dynamic scans involve simultaneous injection of an iodine-based contrast bolus into the blood stream via tail-vein catheter, as sequential X-ray CT image volumes are acquired over time. The result is a time series of X-ray CT image volumes that visualize the uptake and washout of the contrast bolus within the body. These scans are useful in the study of vascular-related disease such as stroke, and also in the analysis of tumours, which require increased blood supply to grow.

Siemens Inveon CT

The Siemens Inveon MicroCT System at STTARR supports whole-body anatomical imaging of mice in vivo, as well as high resolution studies of small excised samples (e.g. mouse femur, tibia) and non-biological samples.

Inveon CT scanner (Siemens) with a 12-cm bore and 10 x 10 cm field of view is available for high-resolution images (spatial resolution, 15 micron) and is also installed in the facility for specimen CT scanning of small subjects and samples.

Variable Magnification Settings: High, Medium High, Medium, Medium Low, Low
Voxel Size: ~13-100μm (depending on chosen magnification setting)
Anatomical Scan Times: 40-10mins
Maximum transaxial and longitudinal field of views: 25-46mm and 16-31mm respectively

GE

The GE Locus Ultra supports high resolution anatomical imaging of small animals ranging from mice to rabbits, as well as brain imaging of some larger animal models. It is the only CT system at STTARR that additionally supports Dynamic Contrast Enhanced (DCE) scanning, offering a 60s scan (with 1 volume acquired each second) and 3, 5 or 10 minute multiphase scans (with 1 volume acquired each second for the first 30 seconds and then 1 volume acquired every 10 seconds for the remainder of the scan). The BioVet gating system is also available for post-acquisition correction of respiration artifacts in both anatomical and perfusion scans.

Anatomical Scans

Voxel Size: ~150μm
Resolution (measured by MTF): ~350um smallest resolvable feature
Anatomical Scan Times: 4, 8, and 16s
Maximum transaxial field of view (FOV): 14cm
Maximum longitudinal field of view (FOV): 4.5cm/4s scan, 5.4cm/8s scan, and 10.2cm/16s scan

Perfusion Scans
Voxel Size: ~150μm (bin by 3 in longitudinal direction)
Perfusion Scan Times: 60s (1 volume/s), and 3, 5 and 10min (multiphase)
Maximum transaxial field of view (FOV): 14cm
Maximum longitudinal field of view (FOV): 3.6cm/60s scan, 4.1cm/3, 5 and 10min scans

MRI

What is a MRI scan?
A MRI scan uses the magnetization from water protons to generate images in which brightness can reflect not only the density of water protons in tissue but also the interaction of water protons with their local microenvironment.  Commonly used image contrasts are termed proton-density weighted, T2-weighted, and T1-weighted.  More watery tissues are bright in T2-weighted images, while contrast agents tend to accentuate signal in T1-weighted images.

Why would you use a MRI scanner?
MRI is used primarily because it provides superior soft tissue contrast to any other imaging modality, and as such it can be complementary to modalities like CT (predominantly bony tissue contrast) and SPECT/PET radionuclide imaging (density of radiotracers).  MRI also provides the flexibility to acquire images in any plane in 3D space.  MRI is also applied to quantify physiologic/disease processes to support longitudinal or inter-subject comparisions in scientific trials.  These measurements, termed biomarkers, are derived from a direct relation between the MRI signal and biologic processes such as metabolism, tissue perfusion, and water diffusivity changes following tumor cell death or proliferation.

How does it work?
Some atomic nuclei exhibit nuclear magnetism because they contain an odd number of protons and neutrons.  Hydrogen protons found on water molecules are one such nuclei.  When oriented within a strong magnetic field,  a very small proportion of the nuclei will align or polarize.  This net polarization is small yet significant enough to be measured owing to the high proportion of water within biologic tissue.

MRI technology provides the means to spatially map the magnetization arising from water protons.  This technology consists of three main components:

  1. First, a strong magnet is required to polarize the otherwise randomly oriented water protons.  This magnet is often super-conducting and ranging in strength from 1.5 to 3 tesla for clinical studies, and from 4.7 to 11.7 tesla for pre-clinical studies.
  2. Second, RF antennae or coils are required to transmit energy at the resonance frequency of the polarized water protons.  This energy absorption re-orients the water proton magnetization away from the direction of the field of the magnet.  The natural precessional motion of this magnetization then induces a signal in the RF coil.  It is this signal which is reflected in MR images.
  3. Third, gradient coils are used to spatially resolve the emitted signal.  Gradient coils overlay the main magnetic field with a linear field variation.  Because the frequency of the emitted signal is linearly related to the magnetic field strength, the measured signal therefore has a frequency distribution defined by the slope of the gradient field.  As the slope of the gradient field is known, one can directly relate frequency to position.

STTARR-MRI-v2

The STTARR facility provides a 7 tesla pre-clinical MRI system.  By utilizing a range of RF and gradient coil inserts, it can accomodate animal models ranging in scale from ex vivo tissue samples and rodents, through to 5-7 kg animals.  The machine capabilities are model-dependent, but can range from MR microscopy tasks (i.e.  60-micron isotropic voxels, using optimized RF coils and prolonged scanning sessions) through to standard techniques at high resolution for the relevant anatomy (i.e. 100x100x500-micron voxels in time-efficient murine brain scans; 500x500x1500-micron voxels in primates).

The STTARR-MRI machine is designed for MR imaging of individual animals, but with comprehensive physiologic characterization including T1-weighted and T2-weighted imaging, diffusion-weighted imaging at arbitrary b-values and directions, relaxation time mesaurements, MR spectroscopy, dynamic contrast enhancement, magnetization transfer and chemical exchange saturation transfer imaging, angiography, and ultra-short TE imaging.  Each technique can be gated to bulk physiologic motions (e.g. respiration).  The machine has multi-nuclear capabilities for imaging and spectroscopy, using dual-tuned 19F/1H and31P/1H  transmit/receive surface coils.

The STTARR-MRI can also accomodate multi-modal MR/CT/PET imaging in rodents utilizing the Minerve Small Animal Environment System.

Please contact Dr. Warren Foltz for additional information and consultation (warren.foltz@rmp.uhn.on.ca).

7T-MRI Figure 1

Figure 1: Contrast-enhanced MR images.  Panel a. Clearly resolved murine brain glioma in T1-weighted images after Gd-DTPA injection (arrow), despite poor conspicuity in T2-weighted images (125x125x500-µm voxels, 80 s each). Panel b. Endogenous (left) and liposome (right) contrast-enhanced maximum intensity projections through the hind Paws of mice subjected to antibody-induced arthritis 24 h post-injection (3D-FLASH, 125-µm isotropic voxels, 25 min acquisition).  The murine brain glioma model is courtesy of Dr. Gelareh Zadeh.  The murine arthritis model is courtesy of Dr. Eleanor Fish.  The image is published in Foltz WD, Jaffray DA.  Principles of Magnetic Resonance Imaging. Radiat Res 177(4):331-345, 2012. Reproduced with permission of the Radiation Research Society.

7T-MRI Figure 2
Figure 2: Dynamic contrast-enhanced MRI at 7 tesla. The top rows are T2-weighted, 2D-FLASH DCE frames, and late phase high resolution T1-weighted images for both glioma and cervix tumor xenograft models.  Tumor locations are highlighted by arrows in T2-weighted images. The bottom left image displays the set-up for cervix tumor DCE, in which the mouse is lying prone on a murine 4-coil phased array receiver.  The tail vein is cannulated, enabling remote manual injection using a precision Hamilton syringe. [Cervix images courtesy of Dr. Naz Chaudar; brain glioma images courtesy of Dr. Caroline Chung; The image is published in Foltz WD, Jaffray DA.  Principles of Magnetic Resonance Imaging. Radiat Res 177(4):331-345, 2012. Reproduced with permission of the Radiation Research Society.

7T-MRI Figure 3

Figure 3: (a) Sagittal view of a μCT slice of a rat spine with mixed osteolytic /osteoblastic metastatic involvement secondary to ACE1 cancer cell injection; (b) Corresponding slice in a T1-weighted MR image after affine registration (for bone registration); (c) Corresponding slice in a T2-weighted MR after the affine registration (for osteolytic tumor visualization. 3D T1-and T2-weighted MR images of the explanted rat spine were acquired at 60 µm isotropic resolution.  The images are courtesy of Dr. Carrie Whyne, and is taken from Hojjat SP, Foltz W, Wise-Milestone L, and Whyne CM, “Multimodal uCT/uMR based semiautomated segmenta- tion of rat vertebrae affected by mixed osteolytic/osteoblastic metastases.” Med. Phys. 39(5) 2848-2853 (2012). Images are published with permission of the Journal of Medical Physics.

1T-MRI Figure 1

Aspect Imaging’s M3 system is a high performance 1T MRI system capable of a broad range of pulse sequences and applications.  It is well suited for multi-modal applications, and we have experience with 3D registration of the MR data sets to PET (Siemens Focus 220) and BLI (Xenogen Ivis) data sets using the Lumiquant bed system. The M3 is currently used at STTARR for T1 and T2-weighted anatomical imaging, as well as dynamic contrast enhanced (DCE) imaging of tissue perfusion and permeability. The system is equipped with two RF body coils and a RF head coil for murine imaging applications, plus a specialized RF coil which is compatible with the Lumiquant bed.

The images below outline existing use of the 1T system:

1 Tesla MRI_Figure 2Figure 1. T2-weighted image (FSE, 200μm x 200μm x 1mm, 15 slices, 5 min 12 sec acquisition time) of a mouse bearing an intracranial U87 glioma lesion. Photo courtesy of Jinzi Zheng, Kelly Burrell.

1 Tesla MRI_Figure 3Figure 2. T2-weighted image (FSE, 200μm x 200μm x 1mm, 12 slices, 3 min 47 sec acquisition time) of a mouse bearing an orthotopically implanted ME-180 cervical tumor. Photo courtesy of Jinzi Zheng, Nancy Dou.

IMG_5419Siemens’ 1.5T Aera is a leading-edge system for clinical imaging.  At STTARR, it will serve as the platform for development of MR-guided therapeutics, including MR-guided focused ultrasound, and with its 70 cm bore diameter, it allows for imaging in a broad range of animal models.  A selection of RF coils and techniques are provided which are enabling for preclinical imaging applications.

Nuclear

PET is a nuclear medicine imaging modality that detects the emissions of radiolabelled tracers.  Specifically, as positron-emitting isotopes decay, the positrons annihilate with electrons converting their mass into energy (E=mc2) in the form of gamma-rays.  This produces paired gamma-rays (2 x 511 keV photons) that travel in opposite directions.  PET scanners contain a 360° detector ring that allows localization of the initial decay event and therefore the location of the administered tracer.  PET scans are commonly used in cancer, neuroscience, and cardiac imaging applications.  PET tracers are commonly small molecules that have been labelled with one of the isotopes listed below.

Commonly Used Isotopes Half-life (min)
Carbon-11 20
Nitrogen-13 10
Oxygen-15 2
Fluorine-18 110
Copper-64 760

The most commonly used PET tracer is the glucose analogue 18F-FDG. It is used to measure glucose metabolic activity. Tumours and viable myocardium have increased glucose metabolic activity, for instance. Thymidine analogues that measure proliferation (18F-FLT) and radiopharameuticals such as 18F-FAZA and 64Cu-ATSM measure hypoxic regions (oxygen tension) for oncology, neurology, and cardiology applications.

Advantages 
Radionuclide imaging techniques offer the greatest sensitivity of any conventional imaging modality. PET imaging affords approximately a 10-fold greater sensitivity compared to SPECT. This sensitivity advantage allows PET greater temporal resolution, thus making PET the preferred choice for dynamic nuclear medicine imaging studies.

Limitations
Nuclear medicine imaging has lower spatial resolution than conventional techniques so MR and CT are often acquired as reference anatomical scans. PET isotopes are generally shorter lived than those used for SPECT imaging. Therefore studies must be completed in a shorter time and efficient manner.  These isotopes also generally require a cyclotron for production. The short half-life and more involved production methods cause PET imaging to be more expensive and less accessible than SPECT imaging.

PET

Core II houses PET, SPECT and CT pre-clinical scanners that help to provide quantitative non-invasive analysis for a variety of subjects at all depths within tissue.

Molecular (or functional) imaging demonstrates, in a non-invasive way, biochemical, physiological, and pharmacological processes in vivo. Radio-labelled tracers are injected into the subject to be imaged, and the scanners produce images of the concentration of the radioisotope, thereby demonstrating the biological pathways which are followed by the radiotracer. Molecular imaging can provide information about many features of tumour biology: microenvironmental effects such as hypoxia; cellular processes like angiogenesis and apoptosis; and gene expression.

The Core II PET scanner is a Siemens MicroPET Focus 220. The Focus 220 has a large-bore gantry (22 cm) and an axial field of view of 7.7 cm, which allows imaging of animals as large as small primates. It utilizes a full ring of detectors containing 168 detector blocks of LSO with a 12 x 12 array (1.5 x 1.5 x 10 mm each) providing 24,192 detector elements. Positron-emitting radionuclides generate annihilation photons that are detected in coincidence by 2 crystals with a timing window of 6 ns. Utilization of iterative reconstruction methods can provide ~1.3 mm resolution in the transaxial planes at the centre of the field of view. Several 2D and 3D reconstruction techniques are available.

SPECT is a radionuclide imaging technique based on the detection of gamma rays emitted by radioisotopes.  The scanner consists of four gamma camera heads (scintillating sodium iodide crystals doped with thallium) with pinhole collimators that rotate around the subject.  A SPECT scan acquires multiple 2-D images (projections) from multiple angles and a computer algorithm applies a tomographic reconstruction to these generating a 3-D image.  Historically, 2-D planar gamma camera imaging preceded SPECT imaging.  Isotopes useful for SPECT imaging emit gamma rays with energies between ~25 – 250 keV.  Several of the most commonly used isotopes are listed in the table below.  They are high atomic number metals commonly used to label molecules of biological significance.

Commonly Used Isotopes Half-life (hours)
Gallium-67 78
Technetium-99m 6
Indium-111 67
Iodine-123 13
Thallium-201 73

Clinically, 99mTc is incorporated into radiopharmaceuticals and commonly used for bone, brain, and cardiac scans.  123I-MIBG  (metaiodobenzylguanidine) is utilized for tumour and cardiac imaging. 111In-oxine is used to label leukocyctes for imaging infection.

Advantages
Nuclear medicine imaging techniques offer greater sensitivity than conventional imaging techniques, although PET is more sensitive than SPECT.  Importantly, SPECT isotopes generally have a longer half-life than those used for PET imaging.  Longer half-lives allow longer scan times, which can offset sensitivity issues, although biological changes may occur during the scan.  With small-animal scanners, SPECT can  provide somewhat higher spatial resolution that PET but with the tradeoff of longer scan times.  The nanoSPECT at STTARR has a 1.2 mm FWHM resolution compared to 1.4 mm for the Focus 220 microPET at the centre of the FOV.  99mTc can be produced onsite using molybdenum generators, reducing the need for expensive isotope production facilities to be situated close to imaging facilities.  Finally, SPECT offers the potential for dual isotope imaging because detection is dependent on the energy of the gamma rays.  This means that multiple isotopes can be imaged in the same subject at the same time.

Limitations
Long isotope half-lives can be undesirable in human imaging because of the increased radiation exposure to patients.  SPECT does not afford the same sensitivity as PET.  As a result, dynamic scans with kinetic modeling are not very practical with SPECT.

SPECTThe SPECT scanner is Bioscan’s nanoSPECT/CT, a dual–modality scanner with multi-pinhole SPECT detectors.The nanoSPECT uses 36 pinholes (9 pinholes for each of the 4 apertures) and the gamma rays are projected onto 4 NaI (TI) detectors (30 x 215 x 9.5 mm). After a helical scan, an iterative reconstruction algorithm can provide ~0.8 mm resolution in the trans-axial planes.This system combines a CT unit (50 um resolution) to add structural features to the SPECT images. Reconstruction is by ordered-subset expectation maximization (OSEM). The CT scanner is a cone-beam system with 5 cm x 10 cm field of view; 90 kVp x-ray tube, and a spatial resolution of 200 mm.

Optical

Xenogen New_v2

What is Bioluminescence Imaging?
Bioluminescence imaging uses the enzyme and substrate that fireflies use to generate light to track the localization of cells within small animals.  The enzyme, luciferase, can be inserted into the genome of cancer cells, or the cells you are wishing to track.  These cells are then implanted within mice, and a tail vein or intra-peritoneal injection of luciferin delivers the substrate to the cells.  The combination of luciferin and luciferase causes light to be emitted, this light can then be captured using a very sensitive camera, with the mouse supported on a heated stage in an enclosed, light-tight box.  The Xenogen IVIS Spectrum system we have also has the ability to perform spectral fluorescence imaging similar to the CRI Maestro system, allowing the possible use of simultaneous bioluminescence and fluorescence imaging.

Why is this optical imaging technique more useful than alternative methods?  What are the pros vs cons for this technique?
The primary advantage of bioluminescence imaging is its sensitivity.  Since the light is being produced by an enzymatic reaction, and no excitation light is required, the camera can capture all the photons coming from the mouse, with the mouse enclosed within a light-tight box.  Since tissues have very low auto-luminescence, the signal coming from the luciferase-luciferin reaction can be measured very reliably, and can be used for quantitative analysis, allowing the experimenter to possibly determine the number of cells expressing luciferin within the animal (if a proper standard curve is generated).  A disadvantage of this system is that it generates primarily a 2d image of the luminescence coming from the animal, and due to the scattering and absorption of light, deeper-seated tumors will result in less light arriving at the camera than shallow tumors; thus it is important to have animals in the same orientation, with tumors in roughly the same anatomical location, in order to obtain the most quantitative results from the system.

Which specimens / experiments would you typically use the Xenogen system to image?
Xenogen bioluminescence imaging provides the ability to detect luciferase expressing cells with a fairly high degree of sensitivity, making it useful in particular for lower numbers of cells, for which fluorescence imaging may not be sensitive enough to separate signal from background autofluorescence.  The quantitative or semi-quantitative nature of bioluminescence imaging also allows you to track the number of cells (or degree of luciferase expression) over time, with multiple injections of luciferin, lending itself well to applications such as monitoring of tumor burden over time.

PerkinElmer VisEn FMT 2500 LX Quantitative Tomography System
FMT New

What is Fluorescence Tomographic Imaging? 
The FMT2500 system generates a three dimensional map of the location of the fluorescent signal within the mouse, using the information generated from a laser scanned in a grid pattern to determine the amount of scattering and absorption within tissues, followed by capturing the fluorescence excitation within that tissue.  The system allows you to look at up to 4 fixed wavelength fluorophores at once (635, 680, 750 and 800nm excitation), building a three-dimensional map of where the fluorescence signature is located.

Why is this optical imaging technique more useful than alternative methods?  What are the pros vs cons for this technique?
The FMT2500 system provides the ability to do quantitative or semi-quantitative fluorescence imaging, by attempting to correct for the scattering and absorption within tissues using their fluorescence tomography techniques, and also working in the near-infrared spectrum, where tissue autofluorescence, scattering and absorption are much lower than in the visible spectrum.  This technique is very useful for visualizing deep seated tumors, and also allows for the extension to activatable and targeted fluorescent probes.  The mouse sits in a multi-modality chamber, allowing co-registered imaging with other modalities such as micro-CT, PET or MRI imaging.  The main disadvantage of this system is that there are currently no fluorescent proteins that work in the infrared range, so this system is primarily used with exogenous supplied fluorophores.

Which specimens / experiments would you typically use the FMT2500 system to image?
This system is typically used to visualize the 3D localization of injected fluorophores within the experimental animal.  Targeted and activatable probes are available for a wide range of experimental models, including cancer, drug delivery, arthritis, bone remodeling, vascular and heart disease applications.

Machine Capabilities
• Four laser wavelengths:
* 635 nm Channel (Excitation), Emission range = 650 – 670 nm
* 670 nm Channel (Excitation), Emission range = 690 – 740 nm
* 745 nm Channel (Excitation), Emission range = 770 – 800 nm
* 790 nm Channel (Excitation), Emission range = 805+ nm
• Multi-Modality Enabled: Includes DICOM image export
• Includes isoflurane-based anesthesia system
• Voxel  ~1mm3
• 3D – enables depth in fluorescence

Applications
• Small animal scanning (mice) using 3D fluorescence to find macro distribution of
fluorescence qualitatively and semi-quantitatively.
• Serves as a precursor to optical microscopy (macro vs. micro confirmation of
fluorescence distribution.
• Can be used in multimodal imaging with a fixed animal position for easy multimodal
co-registration.

Maestro New_v2What is in vivo Spectral Unmixed Fluorscence Imaging?  
The CRI Maestro system can image fluorescence from animals or samples from blue to infrared wavelengths, making it useful for a wide range of fluorescent proteins or molecules.  Excitation light illuminates the surface of your mouse, and a camera captures the resulting emitted fluorescence light, capturing a series of images for each emission wavelength, spaced 10nm apart.  This “hyperspectral” image can then be “unmixed”, in which a known spectrum is used to extract the fluorescence coming from your fluorophore, away from the presence of other fluorophores in your mouse, including tissue autofluorescence.  This is particularly useful for wavelengths in the visible spectrum, as mouse tissues can have a significant amount of autofluorescence that can make it difficult to interpret your images.  The result is a series of images of each fluorophore present in your mouse, that you can use to relate back to the presence or absence of your fluorophore within the tissue of interest.

Why is this optical imaging technique more useful than alternative methods?  What are the pros vs cons for this technique?
The CRI Maestro system is best suited for imaging transgenic mice containing fluorescent proteins, like GFP or RFP, in tissues close to the mouse surface, such as a subcutaneous tumor.  An advantage of this system relative to others represented here is the ability to scan across any wavelength, allowing you to use either fluorophores that already exist in your system, such as GFP expressing cells, or use custom fluorophores – other systems like the FMT2500 only work with fixed fluorescence wavelengths.  It also does a fairly good job of being able to discriminate the signal coming from your fluorophore from tissue (or gut) autofluorescence, as seen in the image below.  A primary disadvantage of this system is the requirement to have the fluorescence close to the surface of the mouse, particularly for non-infrared imaging applications.  Visible light scatters and is absorbed rapidly within tissues, and GFP will generally not be visible in this system below 1-2mm due to the scattering and absorption of the excitation and emission light.  Another disadvantage is that the image does not reveal the location of the fluorescence in 3 dimensions, you receive a 2d picture, with the fluorescence located on the surface of the skin of the mouse – this fluorescence has scattered and diffused since it left the source within the animal, so the location is not as precise as with the FMT technique.

Which specimens / experiments would you typically use CRI Maestro to image?
The CRI Maestro system is best used with known fluorophores, or transgenic cells expressing a fluorescent protein, growing subcutaneously within mice.  If your experiment requires knowledge of the 3d location, or concentration of the fluorophore, then you would be better off using the FMT2500 system

Instrument Specifications
The Maestro in vivo fluorescence imaging system is a light-tight apparatus that uses a Cermax-type 300 Watt Xenon light source. This provides 5600°K that spans the electromagnetic spectrum from 500–950nm. The CCD is a 16-bit, high-resolution, scientific grade-imaging sensor. Four fiber-optic adjustable illuminator arms yield an even distribution to the subject. The light radiating from the excitation source and filter passes through the sample to the long pass emission filter. The light then passes through the camera lens and through the solid-state liquid crystal tuning element and finally to the CCD. The excitation and emission filter sliders hold two 50 mm diameter longpass filters. The long pass filters removes the band light especially from the excitation source. These filters are color coded to indicate the wavelength they represent. Consult the Maestro Filter Selection Guide in the software section.

Hardware
• Field of View (length x width): 3.4 cm X 2.5 cm to 10.16 cm X 7.62 cm (variable zoom)
• Resolution: 25 to 75 μm (based on zoom lens position)
• Fluence Rate: 4 to 20 mW/cm2 (based upon light position)
• Scan Time: 5 sec to 1 min
• Reconstruction Time: 1 to 30 sec
• Scans needed for 1 mouse (Nose to Rump): 1 scan (at farthest table position) to 3
scans (at nearest table position)
• Maximum Whole Mice per Scan 3
• Maximum Mice per Scan 4

Filter Types Excitation Range Emission Range
Blue 445 to 490 nm 515 nm longpass
Green 503 to 555 nm 580 nm longpass
Yellow 575 to 605 nm 645 nm longpass
Red 615 to 665 nm 700 nm longpass
Deep Red 671 to 705 nm 750 nm longpass
Special NIR 725 to 775 nm 800 nm longpass
NIR 710 to 760 nm 800 nm longpass

Leica FCM 1000The Leica FCM 1000 is a fiber-optic confocal fluorescence microscope adapted to in vivo and in situ animal imaging. The FCM 1000 combines high resolution (1.8-3.9 micron) confocal microscopy imaging with a flexible probes that is easy to use. The probes allow you to visualize live processes (i.e cellular or vascular events) using a ultra-high frame rate for real-time dynamic recording. In addition, the flexible fibered microprobes allows for imaging anywhere in the living animal.

Fore more information, click here for the Leica FCM 1000 brochure.

Ultrasound

What is Ultrasound Imaging?
An ultrasound scan is obtained by applying sound to the body and measuring the echoes from different tissue structures. It is used to perform anatomic imaging  and can detect blood flow in large vessels using a technique called Doppler ultrasound. Additionally, microbubble contrast agents can be used to detect blood flow in small vessels, such as the capillaries.

Ultrasound works by generating a sound wave using a device called a transducer. The transducer is composed of a special material (i.e. has piezoelectric properties) that converts an electric signal into mechanical vibrations. For medical ultrasound the transducer vibrates 1 million to 50 million times a second, producing a sound wave with a frequency (i.e. number of vibrations per second) between 1 MHz to 50 MHz. The sound wave travels through the body and echoes are produced by cells and boundaries between tissue types. The echo is then collected by the same transducer and the amplitude of the sound wave is used to generate an image. The depth of the echo is determined by measuring the time required for it to return to the transducer.

For small animal imaging, high frequency ultrasound (20 to 60 MHz) is used. Increasing the ultrasound frequency improves the spatial resolution, with the penalty of reduced depth of sound penetration. High frequency ultrasound is often referred to as “ultrasound biomicroscopy”, because it is analogous to optical biomicroscopy.

Why would you use Ultrasound?
Ultrasound has many advantages over other imaging techniques such as Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). Ultrasound can generate images of anatomy and blood flow in real time without the use of ionizing radiation. The axial spatial resolution (i.e. parallel to the direction of sound propagation)  is approximately 60 µm at 20 MHz  and 20 µm at 40 MHz. The lateral resolution (i.e. perpendicular to the direction of sound propagation) is approximately 200 µm at 20 MHz and 55 µm at 40 MHz. CT, MRI and PET are not real-time imaging modalities and in the case of CT and PET radiation exposure is a concern. However; ultrasound is limited by the skill of the operator, has a limited field of view, and suffers from poor soft tissue discrimination; meaning it can be difficult to tell the difference between many tissues in the body.

Ultrasound New_v2

The Vevo 2100 ultrasound system operates at frequency (20 to 40MHz) an order of magnitude above what is typically used in the clinic (1 to 5 MHz). Increasing the frequency improves the resolution which is crucial for imaging small structures of a mouse. However, increasing the frequency also reduces the depth of sound penetration.

Machine type/model/basic info: VisualSonics Vevo2100, high frequency ultrasound scanner. Capabilities include: B-Mode, 3D Mode, M-Mode, Pulse Wave Doppler, Color Doppler, Power Doppler, Nonlinear Contrast Imaging, Digital RF Mode, ECG and Respiratory Gating, EKV software and VevoCQ software.

Machines capabilities: We have 2 ultrasound transducers: (1) MS-250 which operates between 13 – 24 MHz . Applications include: large tumour (<23mm), Cardiovascular, and Nonlinear Contrast Imaging; (2) MS550 which operates between 32– 56 MHz . Applications include: Embryo, Abdominal, Vascular, Epidermal Imaging, Tumors (< 13mm), and Ophthalmology.

Photoacoustics

What is Photoacoustic Imaging?
The photoacoustic (PA) effect refers to the generation of acoustic waves from an object being illuminated by pulsed or modulated electromagnetic (EM) radiation, including optical waves. The fundamental principle of the PA effect is based on the thermal expansion resulting from the absorption of EM radiation. The thermal expansion increases the acoustic pressure in the medium. Pulsing or modulating the EM radiation generates an acoustic wave which can be detected using an ultrasound transducer.

Photoacoustics in biomedicine takes advantage of the sensitive optical absorption contrast, the penetration of diffused light, and low acoustic scattering in soft tissue. In addition, optical absorption is highly related to molecular constitution and formation; meaning that PA signals contain a wealth of functional and molecular information.

Why use Photoacoustic Imaging?
Photoacoustics can be used to image the spatio-temporal distribution of any object which has a high optical absorption coefficient.  An important application is measuring haemoglobin oxygen saturation (SO2). The ability to measure SO2 stems from the fact that haemoglobin is the primary absorber in blood and oxygenated (HbO2) has different optical absorption characteristics compared to deoxygenated haemoglobin (Hb).  Therefore, PA may provide an important tool to understand cancer biology in terms of angiogenesis and hypoxia.

Additionally, PA can be used to image a contrast agent with a high optical absorption coefficient (e.g. gold nanoparticles and porphysomes). Molecular imaging is also possible using contrast agents which have differential optical absorption properties based on their state (bound vs unbound).

Photoacoutics
Vevo 2100 System with Integrated Vevo LAZR

Photoacoustic Mode, or ‘PA’ Mode is a integrated feature built onto the Vevo 2100 platform to enhance high-resolution ultrasound-derived images with the sensitivity of optical imaging. The Vevo LAZR system uses a 20Hz tunable laser (680 – 970nm) to image functional hemodynamic and molecular data with a resolution down to 40 µm and a depth of 1cm.

 

Machine type/model/basic info: Vevo LAZR Photoacoustic System. Capabilities include: Tunable laser (680 – 970 nm), 20Hz frame rates, can be combined with the standard ultrasound imaging modes provided by the Vevo2100, OxyZated™  mode for haemoglobin oxygen saturation mode, and HemoMeaZure™  for haemoglobin content measurements.

Machines capabilities: We have 2 ultrasound transducers: (1) LZ-250 which operates between 13 – 24 MHz with integrated light guide; (2) LZ-550 which operates between 32– 56 MHz with integrated light guide. These transducers offer the same functionality as the MS-250 and MS-550 with the addition of PA imaging capabilities.