STTARR Logo Reseach and Innovation Cores Logo

Driving development and research with state-of-the-art imaging resources

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STTARR Logo Reseach and Innovation Cores Logo

Driving development and research with state-of-the-art imaging resources

Get Started

Welcome to STTARR

Spatio-Temporal Targeting and Amplification of Radiation Response

The STTARR Innovation Centre brings together products, services, and technologies to accelerate cutting-edge and multidisciplinary research in oncology, cardiology, metabolic diseases, and many other fields.

Flexible to the needs of our academic and industry clients, STTARR staff provides full support, from study conception to completion, including study design, budgeting, federal and provincial regulatory compliance, histopathology services, and advanced data analysis.

To access our equipment and services, user registration is required; please refer to our manual for a detailed guide on how to create a new user account.

Please contact us at sttarr.general@uhn.ca to discuss your project's needs.

Go to Access

 

6,642 ft 2

Research Space

 

13+

Years of Experience

 

700+

Projects

 

1,800+

Researchers Working with STTARR

Innovation

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Cutting-edge technologies for multidisciplinary research

STTARR's advanced imaging instruments and experimental capabilities include CT, MR, PET, SPECT, ultrasound, photoacoustics, optical, and radiation therapy. The STTARR Correlative Pathology Laboratory is equipped with innovative technology enabling whole-mount pathology, thus preserving the geometric integrity of the sample and ensuring accurate correlation to in vivo imaging in a systematic way.

STTARR also has animal holding rooms and can assist researchers with development of new contrast agents, molecular probes, and radiotracers.

Services

Sttarr offers the services and facilities needed for translational drug development and preclinical research.
Our services include:

For more information on Internal and External rates, please contact us or Naz Chaudary.

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Preclinical Imaging

Multimodal in vivo imaging in small and large animal models

  • Fluorescence and bioluminescence imaging
  • High resolution 3D ultrasound and photoacoustic imaging
  • Small animal 7T MRI
  • Large animal 1.5T MRI
  • MR-guided HIFU at 1.5T and 7T
  • PET-MR, SPECT-CT-PET
  • MicroCT imaging
  • Image-guided, flat-panel cone-beam CT radiation therapy units
  • Veterinary support through the Animal Resources Centre
  • Clinical CT scanner
  • Large animal CT
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Radionuclides and Radiotracers

  • STTARR has expertise in:
    • radiolabeling proteins, antibodies, antibody fragments, liposomes, and other nanoparticles in one of its two Intermediate Level laboratories
    • performing pharmacokinetic and biodistribution studies
    • positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging
  • The STTARR Innovation Centre has a nuclear substances permit to possess, transfer, store and use:
    Ac-225, Au-198, Ba-133, C-11, Co-57, Cs-137, Cu-64, F-18, Ga-67, Ga-68, Hg-197, I-123, I-125, I-129, In-111, Lu-177, Tc-99m, Y-90, Cu-67, Na-22, Pb-203, Tb-155, Tb-161 and Zr-89
  • PET Radiotracers can be obtained from affiliates or commercial sources:
    F-18 FDG, F-18 FAZA, F-18 FCholine, F-18 DCFPyL(PSMA), F-18 Florbetaben, F-18 Sodium Fluoride (NaF), and F-18 FLT, Ga-68 DOTATATE
  • A selection of SPECT radiotracers include, but is not limited to the following: Tc-99m pertechnetate, Tc-99m MDP, Tc-99m HMPAO, Tc-99m DTPA, and Tc-99m MIBI
  • The LabLogic® Logi-CHROME ONE, the integrated all-in-one radio-HPLC system specifically developed for PET/SPECT quality control, providing a small footprint and simple to use solution for radiochemical purity testing.

If your isotope or tracer is not mentioned, please talk to us !

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Histopathology

The STTARR's histopathology core now provides 100+ optimized antibodies for immunohistochemistry/immunofluorescence. The histopathology core now specializes in the special MOVAT stain (highlights the various constituents of connective tissue, especially cardiovascular tissue, by five colors in a single stained slide). The new development of an in-situ hybridization protocol combined with immunofluorescence or human X-Y chromosome assays is now a histopathology service offered at STTARR.

Services include:

▸ Formalin fixed Paraffin embedded (FFPE) tissue services
  • Grossing

    Inspect the samples for fixation statues, trimming harvest tissue to the plain of interest.

  • Tissue processing & embedding (regular and wholemount)

    Regular cassettes size is 30mm x 35mm.
    Supersize cassette for wholemount is 65mmX50mm.

  • Re-embedding

    Melt down paraffin block and re-orient the tissue into the desire cutting plain.

▸ Frozen tissue services
  • Cryo block sectioning

    Sectioning OCT frozen tissue blocks prepared by users.

  • Regular tissue specimen Freezing

    User provide fresh harvested tissue to STTARR Pathology for snap freezing in OCT.

  • Muscle Specimen Freezing

    Special snap freezing technique for muscle tissue prone to freeze artifact.

▸ Microtomy
  • Microtomy

    Sectioning paraffin and frozen section at routine 4um thickness or in special thickness requested by user.

  • Paraffin Microtomy

    Regular slides: 25mmx75mm.
    Wholemount large slide:50mmx75mm.

  • Serial sections

    Paraffin or frozen (per slide) consecutive sections from a ribbon of section mounted on slides labelled with numbers.

  • Specific micro-structure/Precise sectioning

    Look for specific microscopic structures in paraffin/frozen blocks and take sections eg. Mouse aortic arch, aortic root, mouse embryo thyroid glands.

▸ Immunohistochemistry
  • IHC New Antibody Optimization

    Optimization of commercial and/or in house produced antibodies.

  • Immunohistochemistry

    Check out our Pathology Optimized Antibody List for a list of antibodies currently available and optimized at STTARR Pathology. Please note that the list is continuously updated. If the antibody you are interested in is not on the list, please contact us.

  • Multiplex IF staining

    Multiplex of up to 3 target proteins in cells/tissues using flourescent tagged antibodies.

  • Tunel assay

    Detection of DNA fragmentation in last phase of apoptosis (cell death).

▸ In situ hybridization
  • In Situ Hybridization (RNAscope)

    Uitlizing ACDBio System probes and detection systems to detect target mRNA in paraffin embedded sections.

▸ Special Stains
  • Special Stains & Enzyme Histochemistry

    Masson trichrome, Elastic Trichrome, Picrosirius red,Periodic acid Schiff, Cresyl echt violet, Luxol fast blue, Gram stain, von Kossa calcium, Oil O red, Gordon & Sweets Siliver Reticular fiberstain, Safranin O, MOVAT, Prussian blue, Fontana Masson and fast green, TRAP(Tartaric Acid Resistant Phosphotase).
    STTARR Pathology has other histochemistry stain protocols that are available upon request, please inquire if the stain that you are interested is not on the list.

▸ H&E staining

Principle and routine stain used in histopathology perform on paraffin or frozen sections.

▸ Other services
  • Autoradiography

    Sectioning thick sections (3--50microns) for autoradiography, 2 sets of slides each sample. Protocol on sample preparation for autoradiography available upon request.

  • Cell pellet agar embedding

    Centrifuge cell pellet and double embed into agar gel and paraffin.

  • Decalcification- acid

    Formic acid for rapid decalcification or EDTA for tissue to be used for IHC.

  • Full necropsy (Mouse, Rat, guinea pig)

    Havest tissue for toxicology study or specific organ of interest.

  • Tissue microarray construction

    Combining multiple donor tissue parrafin blocks into one for high throughput IHC staining.

TRAP stain for Osteoblast_rabbit bone

Image of TRAP stain for Osteoblast_rabbit bone

Mouse embryo_E15_thyroid

Image of Mouse embryo_E15_thyroid

Pancytokeratin_lymph node metastasis

Image of Pancytokeratin_lymph node metastasis
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Consulting & Education

Scientific consulting & project management, workshops, user training and facility tours available

  • Our scientists provide comprehensive support throughout study conception, project management, method development, and data analysis
  • We offer workshops on molecular imaging, user training sessions and facility tours. Please contact us for personalized workshop and training opportunities
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Translational Infrastructure

  • With the wide range of imaging capabilities as well as proximity to fully equipped operating rooms, STTARR provides the proper infrastructure and support for translational research

Access

Online resources

Equipment

Our equipment is designed to facilitate multidisciplinary collaborations.

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CT

CT (Computed Tomography) combines a series of x-ray images taken from different angles around the subject or animal. Taking advantage of the differences in the x-ray attenuation properties of the various tissues and organs, computer processing creates cross-sectional images (slices) of the internal structures.

▸ Bruker SkyScan 1276
  • The Bruker SkyScan 1276 microCT system, located at UHN's Krembil Discovery Tower and operated by STTARR, supports whole-body anatomical imaging of mice and rats in vivo, as well as high resolution studies of small excised samples (e.g. mouse femur, tibia) and non-biological samples
  • The SkyScan 1276 microCT has a maximum scan field of view that is 80 mm wide and more than 300 mm long. The highest nominal spatial resolution achievable is 2.8 µm pixel size for bone and tissue samples and approximately 10 µm for in vivo mouse studies
  • Physiological monitoring for time-resolved CT imaging (e.g. cardiac and respiratory gating) is available
▸ Mediso CT (As part of the SPECT-CT-PET trimodal system)
  • Mediso nanoScan SPECT-CT-PET is a triple modality system which also supports whole-body anatomical imaging of mice and rats at STTARR. CT scans can be easily co-registered to corresponding SPECT or PET scans
  • A 10 µm isotropic voxel size is the highest resolution possible for small (< 2 cm) field-of-view CT scans
▸ Clinical CT
  • GE Revolution Gen 2 ES (large animals) Spectral (dual-energy) CT allows for soft tissue differentiation without the use of contrast agents. Because of its fluoroscopy capabilities, researchers can perform image-guided biopsies and other interventional procedures.
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MRI

A MRI (Magnetic Resonance Imaging) 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. These images provide an unparalleled soft tissue contrast, enabling both anatomic and functional imaging for monitoring tumor growth and response to therapies.

▸ 7 Tesla MRI (Biospec, Bruker)
  • 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 can also accomodate multi-modal MR/CT/PET imaging in rodents utilizing the Minerve Small Animal Environment System

** The Bruker 7T MRI is now upgraded as of Spring 2023, to the NEO architecture running ParaVision 360, which will provide safer operation, higher throughput imaging, longer hardware lifetimes, and best-in-class fast imaging.

▸ 1.5 Tesla MRI (Aera, Siemens)
  • Siemens' 1.5T Aera is an equivalent MRI system to one that might be found in a clinical radiology department, including a 70 cm bore diameter and a clinically-standard selection of RF coils and MRI pulse sequences
  • At STTARR, it allows for comprehensive imaging in larger animal models, plus it will serve as a platform for development of MR-guided therapeutics, including MR-guided high intensity focused ultrasound
  • STTARR also maintains a research standard level of system access to enable use of custom techniques
▸ MRgHIFU (LabFUS, Image Guided Therapy)
  • STTARR provides MR-guided high intensity focused ultrasound for both the 7 Tesla Bruker Biospec and 1.5 Tesla Siemens Aera MRI systems
  • The small animal MRgHIFU system for the Biospec includes two 25-mm diameter 8-element annular array transducers; a 1.5 MHz transducer suited for blood brain barrier disruption, and a 2.5 MHz transducer appropriate for hyperthermia or ablation applications. The large animal system includes a 145-mm diameter 256-element phased-array transducer operating at 1 MHz
  • For both small animal and large animal platforms, MRgHIFU feedback control based on real-time MR thermometry can be implemented through Proteus software
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Molecular Imaging

The nuclear medicine modalities of PET (Positron Emission Tomography) and SPECT (Single Photon Emission Computed Tomography) rely on injection (or sometimes inhalation) of a radioactive tracer. Nuclear medicine and molecular imaging techniques provide unique insight into the visualization, characterization, and measurement of biological processes at the molecular and cellular levels.

PET is a nuclear medicine imaging modality that detects the emissions of radiolabelled tracers. As positron-emitting isotopes decay, positrons interact with electrons in the subject. When a positron and electron interact, an annihilation event occurs in which the mass of these subatomic particles is converted into energy (E = mc2) in the form of two 511 keV gamma rays emitted at 180° apart from each other. These gamma ray pairs, resulting from annihilation events, are what is detected by the PET scanner.

SPECT is an imaging technique based on the detection of gamma rays emitted by radioactive tracers. The scanner consists of four gamma camera heads (scintillating sodium iodide crystals doped with thallium) with pinhole collimators that rotate around the subject. The SPECT computer reconstructs a 3-D tomographic image from the acquisition of 2-D images at multiple angles (projections). Isotopes useful for SPECT imaging emit gamma rays with energies between ~25 - 250 keV. They are high atomic number metals commonly used to label molecules of biological significance.

▸ PET/MRI – Mediso NanoScan
  • The Mediso NanoScan PET/MRI supports whole-body anatomic and physiological dynamic mouse and rat imaging at STTARR, including cardiac and respiratory gated PET and MRI
  • PET specifications: 0.9 mm spatial resolution (with reconstructed voxel sizes of 0.3, 0.4 or 0.6 mm)
  • MR specifications: 1 Tesla MRI, Gradient strength 450 mT/m, spatial resolution ≤ 100 µm with integrated gradient coil, RF and magnetic shielding
▸ SPECT-CT-PET - Mediso NanoScan
  • The Mediso NanoScan SPECT/CT/PET trimodal system supports whole-body mouse and rat imaging at STTARR. Dual-isotope SPECT imaging as well as gated SPECT and PET acquisitions are possible
  • SPECT parameters: spatial resolution varies depending on selected collimators, e.g. 1.1 mm (mouse - ultra-high sensitivity), 0.6 mm (mouse - ultra-high resolution) and 1 mm for rats
  • PET parameters: 0.9 mm spatial resolution (reconstructed voxel options: 0.3, 0.4 or 0.6 mm)
  • CT parameters: 10 µm minimum voxel size for a small field-of-view (e.g. mouse vertebra). Typically, a whole-body mouse CT takes less than 5 minutes for acquisition and reconstruction
▸ Wallac 1480 Wizard Gamma-Counter - PerkinElmer
  • The Wallac 1480 Wizard gamma-counter is an indispensible instrument for any pharmacokinetic or biodistribution experiment
  • 4π counting geometry for optimum efficiency, i.e. a 3-inch NaI(Tl) crystal surrounded by 3 inches of lead shielding, thus impenetrable to background radiation and crosstalk
  • Perfect for high energy (15 keV - 2 MeV), low activity samples
  • The researcher can count up to 20 mL/sample and up to 1000 samples/run using a library of 51 radionuclides
  • Counting racks can accommodate from 12×75 mm test tubes to 25 mm-diameter liquid scintillation vials
  • 2048-channel multichannel analyzer capable of back-decay and spilldown corrections
▸ HPLC (High-performance liquid chromatography)

This compact HPLC system not only has a UV-Vis detector, but also a NaI scintillation detector for characterizing and quantifying radioligands. It is sensitive enough to read low amounts of radioactivity over a wide range of energies and allows the delivery of up to 4 solvents allowing for maximum flexibility. Using the Laura software, the researcher can create and edit methods, set up sample runs, and view data collection in real time.

▸ Hidex AMG (Automatic Gamma Counter)

Hidex Gamma counter is ideal for nuclear medicine and PET applications, with precise onboard balance, samples can automatically be weighed for preclinical biodistribution studies. It can count up to 230 samples that are 13mm in diameter and 72 samples at 28mm in diameter. It is a compact system with lead shielding to minimize interference as well as detects energies from 15-2000KeV.

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Optical

Fluorescence and Bioluminesence imaging techniques.

▸ PerkinElmer Xenogen IVIS Spectrum Imaging System
  • Xenogen bioluminescence imaging provides the ability to detect luciferase-expressing cells with a high degree of sensitivity, making it particularly useful in 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 the tracking of 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
▸ CRI Maestro System
  • The CRI Maestro system is best used with known fluorophores, or transgenic cells expressing a fluorescent protein, growing subcutaneously within the murine model
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Ultrasound

Real-time images are generated by applying high-frequency sound and then detecting the returning sound waves (echoes) caused by differences in acoustic impedence of the various tissue interfaces within the subject of interest. In addition to 2D B-mode images, anatomical 3D images of a small region can also be obtained. If the ultrasound beam is directed into a blood vessel, the blood flow gradient can be measured by a technique known as the Doppler effect. Visualization of blood flow can be further enhanced by the use of acoustic contrast agents such as microbubbles.

▸ Visualsonics Vevo 2100 System
  • Operates at frequency (20 to 40MHz) an order of magnitude above what is typically used in the clinic (1 to 5 MHz), which improves the resolution which is crucial for imaging small structures of a mouse
  • Features include 2D and 3D imaging, non-linear contrast imaging, M-mode, colour Doppler as well as pulsed-wave and continuous-wave Doppler
  • Transducers for mice and rat interrogation are the MS250 (13-24 MHz) and MS550D (22-55 MHz)
  • Heated mouse platform for regulating temperature and ECG-gating
  • Ultrasound-guided biopsy instrumentation
  • Vevo LAB software for quantifying and characterizing disease progression with specific applications
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PhotoAcoustics

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.

▸ Visualsonics Vevo LAZR Photoacoustic Imaging System
  • A multi-component system which integrates laser light delivery with ultrasound image acquisition to produce photoacoustic image data
  • 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 1 cm
  • Transducers for mice and rat interrogation are the MZ250 (13-24 MHz) and MZ550 (32-55 MHz)
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Small Animal Irradiator

STTARR has installed the new SmART+ system, the small animal irradiator at PMCRT in Nov 2022.

▸ SmART+ system
  • Mimicking clinical radiotherapy imaging and treatments, our Small Animal Radiation Therapy (SmART+) systems bring a highly sophisticated, expandable platform to the field of preclinical research. Together with easy-to-use software and an advanced set of imaging modalities, including Cone-Beam CT, µCT, and Bioluminescence (BLI), this state-of-the-art focal irradiation system is the perfect tool for image-guided radiation research.
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Software and Analysis Workstations

STTARR's Image Analysis Core provides both self-service workstations and dedicated technician analysis of medical images coming from the STTARR facility scanners. Our team can guide you through the available options and provide software training as needed.

▸ Pathology image analysis software
  • Commercial software packages can be used for high-throughput analysis of digitized whole slide images including performing classification of various tissue types and cell counting
  • Definiens TissueStudio and Developer
▸ Radiology image analysis software
  • Siemens Inveon Research Workplace (IRW)
  • InviCRO VivoQuant volumetric analysis software
▸ Pathology analysis software
  • Definiens Tissue Studio and Developer*
  • Aperio Image Scope*
  • QuPath*
  • Image J / Fiji*
  • Viseopharm*
▸ Imaging analysis software
  • Invicro VivoQuant
  • Bruker CTAn
  • Siemens Inveon Research Workplace
  • Mediso Interview Fusion
  • GE AW Server
  • Cardiac MRI-CT CVi42
  • Pilot & SmART-ATP
▸ Other software
  • MATLAB
  • Python Workspaces*

Note: Software marked with an asterisk (*) do not have staff support available. For software without the asterisk, our staff is available to assist you.

Team

Initial of Naz Chaudary

Naz Chaudary, PhD

Core Manager, STTARR Innovation Centre
Staff Scientist

Pre-Clinical Imaging Core

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Warren Foltz, PhD

MRI Lead
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Teesha Komal

Imaging Technologist
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Luke Kwon, PhD

Scientific Associate
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Rita Chen

Research Technician
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Steve Ansell

Computational Consultant
picture of Alberto Cevallos

Alberto Cevallos

Research Technician

Histopathology Core

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Napoleon Law

Histopathology Core Lead
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Feryal Sarraf

Histotechnologist
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Jordi Ros Rodriguez

Histotechnologist
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Catherine Williams

Administrative Assistant
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Simon Zhou

Histotechnologist

Publications

We kindly request for authors who use STTARR resources to include the following acknowledgement in their publication:
“The authors would like to acknowledge the Spatio-Temporal Targeting and Amplification of Radiation Response (STTARR) program and its affiliated funding agencies.”

Select a year to see a listing of articles published.

Workshops

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November 27, 2023

In-Person Event: UHN's first Research Cores Showcase

Date: December 6th, 2023 | 11am to 2pm

Get a closer look at each research core at their dedicated booth. Our expert staff will be available to address your questions and highlight our specialized services and equipment. Dive into cutting-edge technologies and learn how they can enhance your research endeavors.

This is a great opportunity for our research community to discuss and explore how research core facilities can collaborate on your CFI grant applications.

a poster of the event
August 22, 2023

In-Depth Look at SmART+: The Revolutionary Small Animal Radiotherapy System at STTARR

Date: August 23, 2023 | 10:00 – 11:00 AM EST

This webinar showcases the SmART+ system, revolutionizing small animal radiotherapy at the STTARR Core Facility. Learn how this advanced technology is transforming research in the field of radiation oncology, enabling precise treatments for small animal models. Explore its features, benefits, and potential impact on cancer research.

 Click here for webinar

picture of magnetic insight workshop poster
May 12, 2021

Magnetic Particle Imaging: An Introduction and Applications Presentation

Date: May 20, 2021 | 4pm (1 hour)

REGISTRATION FORM HERE

Description: Results from immune cell tracking, in vivo quantitation, drug-delivery monitoring, inflammation quantitation, and localized hyperthermia will be discussed…

Newsletters

Contact Us

STTARR Innovation Centre

The STTARR Innovation Centre is located at:
101 College Street, 7th floor
MaRS Building - East Tower
Princess Margaret Cancer Research Tower
Toronto, Ontario, M5G 1L7
Canada

Phone: (+1) 416-581-7771
Email: sttarr.general@uhn.ca
Homepage: www.sttarr.com
Twitter: https://twitter.com/sttarr_research
Linkedin: https://www.linkedin.com/in/sttarr-innovation-centre

Frequently Asked Questions?

General FAQ

STTARR is accessible to researchers from any organization. To discuss your project requirements, please contact us. If you're looking to initiate a new project or add new users/resources to an existing STTARR number, please fill out our Facility Access Request Form. To access this link, users need an account on Stratocore. If you're a new user, you can set up an account through this link.

Please contact us for a free consultation to discuss your research needs with a member of our expert team. Meeting and discussing your research and goals is the best way for us to ensure the right technology and/or equipment is applied to your project.

Stratocore FAQ

Stratocore PPMS (Pasteur Platform Management System) is a web-based, management software system that increases the administrative efficiency of Core facilities while providing researchers an easy way to reserve instruments, request training, and request services.

  • A STTARR number is a project number that is assigned to you upon submitted a Facility Access Request Form.
  • Once assigned, your STTARR number is linked to your account and can be found on your profile. You can see all projects in which you are a designated researcher under “Project Memberships”.
  • You need to have your PI sign the New User PI Agreement Form and submit an electronic copy to STTARR staff (Rita: rita.chen@uhn.ca).
  • Ensure that your ACK# at the top of the form is included in your email to staff.
  • The New User PI Agreement Form can be found under the Documents tab and the Facility Access Forms can be found under the Requests tab in Stratocore.
  • Project requests are usually processed withins 3 business days. If it takes longer, please send an email to a member of staff (Rita: rita.chen@uhn.ca or Deborah: deborah.scollard@uhn.ca). There could be a variety of reasons for delays in account creation.
  • Please send an email with your AUP number to a member of staff (Rita: rita.chen@uhn.ca)

Sponsors

The STTARR program appreciates the research funding from the following agencies.
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