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Tonya Coulthard, MSc.
Team Leader
Scintica Instrumentation
Phone: +1 (519) 914 5495
tcoulthard@scintica.com
CHANGING HOW
RESEARCHERS THINK
ABOUT MRI:
Utilizing a simple to use, compact,
MRI system to transform preclinical
imaging
• Introduction to MRI, and M-SeriesTM Overview
• Comparison to Conventional High-Field MRI Systems
• Key Research Applications
Topics of Discussion
Introduction to MRI and M-SeriesTM Overview
• Magnetic Resonance Imaging (MRI)
• M-SeriesTM Compact magnet design
• Animal handling system
• Software interface and user experience
• Hardware and software add-ons
• Purchase, operating and maintenance costs
• MRI is the gold standard for soft tissue imaging
• Differentiate various organs, tissue types, and internal structures
• Visualize inflammation, tumors, and other pathological changes
• Contrast agents may be used to enhance the vasculature and other molecular targets
Magnetic Resonance Imaging (MRI)
Note – these images were
not taken with the M-
Series systems
• No use of ionizing radiation to acquire images
• MRI and ultrasound do not require ionizing radiation making them preferable to CT (computed tomography) or
PET (positron emission tomography) for diagnostic imaging where possible
• MRI is the best choice for brain, soft tissue, or tumor imaging
• Ultrasound cannot penetrate bone or air; but is useful on many abdominal organs
MRI vs Other Imaging Modalities
• CT requires the use of ionizing radiation and is ideal for imaging bones, sinuses, and kidney stones.
• Does not resolve soft tissue as well as MRI
• PET requires a radioactive tracer, often FDG (a radioactive derivative of glucose), and is most often used to detect
tissues with high metabolic activity
• Should be co-registered to provide anatomical context to detected signal
MRI vs Other Imaging Modalities
CT vs. MRI
PET vs. MRI
Note – these images were not taken with the M-Series systems
MRI vs Other Imaging Modalities
Sensitivity&MolecularImaging
High/Low High/High
Low/Low Low/High
Resolution & Anatomical Imaging
µPET
µSPECT
MRI
Ultrasound
µCT
Optical
M-SeriesTM Compact Magnet Design
The M-Series systems compact MRI systems
have been designed and manufactured with
the pre-clinical researcher in mind.
These high-performance MRI systems provide
powerful results without the cost, complexity and
technical burden of conventional MRI systems.
M-SeriesTM Compact, High
Performance, MRI Systems from
Aspect Imaging
M3 M7
Bore Opening 50x120 mm (hxw) 220x90 mm (hxw)
Imaging Volume 80x80x35 mm (spheroid) 120x120x70 mm (spheroid)
Animal Size Mice only Mice – large rats
Height 108 cm 132 cm
Width 73.4 cm 79.0 cm
Depth 73.4 cm 95.0 cm
Weight 640 kg 1600 kg
M-SeriesTM Compact Magnet Design• Require no special infrastructure
• Compact and self shielded with minimal external fringe field
• Operate very quietly during image acquisition
• Systems are installed with first images being acquired in less
than 1 day
❖ Installed within an animal facility, or existing
laboratory next to other equipment or furnishings
System Components
• Compact magnet – select either the M3 or M7 magnet;
• Electronics cabinet and User Workstation - is the same for all systems.
• Accessories and add-ons
• Animal handling system with heating and physiological monitoring
• Anesthesia delivery and exhaust gas scavenging
• SimPETTM insert – simultaneous PET/MRI
• VivoFuseTM – co-registration of 3D optical (BLI/FLI) with MR images
• MR-Based histology – high resolution automated ex vivo imaging
• Multi-Nuclear capabilities – for advanced users
Animal Handling System
• Fully integrated animal handling and coil system includes
• Mouse or rat beds to suite varying animal sizes
• Anatomy specific coils, with automatic tuning
• Heating
• Physiological monitoring
• Anesthesia delivery and scavenging
Imaging Coils
Type
Dimensions
Application
Inner Diameter Length
Mouse Head 23 mm 25 mm Neurological imaging in mice
Mouse Body 30 mm 50 mm
Extremity, abdominal, and thoracic cavity imaging
in mice
Mouse Whole Body 30 mm 80 mm Whole body imaging in mice
Large Mouse Body 38 mm 50 mm
Extremity, abdominal and thoracic cavity imaging in
large/obese mice
Rat Head 35 mm 40 mm Neurological imaging in rats
Rat Body 50/60 mm ellipsoid 90 mm
Extremity, abdominal and thoracic cavity imaging in
rats
Large Rat Body 71 mm 90 mm
Extremity, abdominal and thoracic cavity imaging in
large rats
Imaging coils should fit as tightly as
possible to the anatomical target for
high quality images
Physiological Monitoring and
Heating Systems
• Continuous monitoring of ECG, heart rate, respiration
rate, and body temperature
• Allows for ECG and/or respiratory triggering
• Heated water is continuously circulated to
maintain body temperature
Anesthesia System
• Fully integrated with the animal handling system
• 3 delivery points
• knock down chamber
• animal preparation (for example - tail vein cannulation)
• animal bed
• Gas exhaust actively scavenges waste gas
Most measurements and
parameters are functions of
time, so we need waveforms
Most measurements and
parameters are functions of
time, so we need waveforms
• The M-seriesTM systems have an easy to operate, intuitive software
interface to quickly generate reproducible, quantitative results
• No need to have a background in MR physics to operate the systems
• Default sequences have been optimized
• The system also offers the experienced MR user the flexibility and
customization options to tailor the performance of the system to
meet their needs
Software Interface and User Experience
Most measurements and
parameters are functions of
time, so we need waveforms
Software Interface and User Experience
Hardware and Software Add-Ons:
SimPETTM Insert
• The SimPETTM insert expands the capabilities of the M7 system to allow
for simultaneous PET/MR imaging
• MR images compliment the highly sensitive PET images in detecting
functional information, abnormalities, and early disease, providing an
anatomical context
Hardware and Software Add-Ons:
VivoFuseTM
• VivoFuseTM is both a hardware and software add-on allowing
for co-registration of 3D tomographic optical (BLI/FLI)
images with 3D MR images
• Combined images allow the molecular/functional
information to be localized to a specific anatomical location
• Tumor volume and growth could be tracked longitudinally
Hardware and Software Add-Ons:
MR-Based Histology
• The focus with MR-Based histology is to acquire very high
resolution 3D images on ex-vivo samples, i.e. for toxicology
studies
• This hardware and software add-on allows for automated
sample handling of multiple samples
• Images are used to detect, localize, and quantify lesion
number and size
Most measurements and
parameters are functions of
time, so we need waveforms
• Minimal running costs
• No electricity required to create/maintain magnetic field
• No cryogens or water cooling due to the design of the permanent magnet
• Only electricity is for the electronics cabinet and work station during image
acquisition
Purchase, Operating, and Maintenance Costs
MRI is now accessible to
more pre-clinical
researchers.
Research budgets are
preserved and can be used
to focus on science rather
than equipment costs
• There are no ongoing maintenance costs for this system
• A well equipped M3 system starts at $290,000 USD
Comparison to Conventional High-Field Systems
• Image comparison between high and low field systems
• Contrast imaging at 1 Tesla
• Installation requirements
Image Comparison Between
High and Low Field Systems:
Signal to Noise Ratio
(TR/TE=5000/25, FOV=30mm, Matrix=192x192,
NEX=4 , Res 156 µm, Acq. Time 4 min)
Mouse
SNR kidney=65
Vertical bore @ 7 Tesla
(TR/TE=3000/56, FOV=30mm, Matrix=192x192,
NEX=12 , Res 156 µm, Acq. Time 14 min)
Mouse
SNR kidney=17
M-Series @ 1 Tesla
• The laws of physics explain that the Signal to Noise Ratio (SNR)
is linearly proportional to field strength
• How can the SNR be improved?
• Increase acquisition time
• Decrease resolution
• Optimized coil and
system design
Image Comparison Between
High and Low Field Systems:
Signal to Noise Ratio
T2 weighted: FSE (TE/TR=47/6000, FOV=80x30mm, Matrix=512x192, NEX=10, ETL=16, Res.
156um, Acq. Time 14:00 min:sec)
T2 weighted: FSE (TE/TR=52.7/4060, FOV=80x30mm, Matrix=256x96, NEX=10, ETL=16, Res.
312um, Acq. Time 5:24min:sec)
T1 weighted: SE (TE/TR=17/540, FOV=80x30mm, Matrix=512x192, NEX=6, Res. 156um, Acq Time
11:07min:sec)
T1 weighted: SE (TE/TR=9.8/500, FOV=80x30mm, Matrix=256x98, NEX=3, Res. 312um, Acq Time
2:30min:sec)
T2 Weighted
156um 312um
T1 Weighted
156um 312um
T2 Weighted
156um 312um
T1 Weighted
156um 312um
Image
Weighting
Resolution Acquisition Time
T2 Weighted 156um 14:00 min:sec
312um 5:24 min:sec
T1 Weighted 156um 11:07 min:sec
312um 2:30 min:sec
• Image resolution and acquisition time can off-set each other
• Decision should be based on images required to answer
specific biological question
Image Comparison Between High and Low Field Systems
Images courtesy of Prof. G. Allan Johnson at Duke University
Molecules behave differently at 1T than at high fields, this allows for improved sensitivity to contrast agents
as well as to specific disease targets, i.e. orthotopic glioblastoma tumor in the brain
Vertical bore @ 7 Tesla M-Series @ 1 Tesla
T2 weighted: SE (TE/TR-80/2500, FOV = 32, Matrix =
256x256x23, NEX = 6, Res. 125µm, Acq. Time 64 min) Mouse
Image Comparison Between
High and Low Field Systems:
Gadolinium Contrast Agents
MRI of Cells and Mice at 1 and 7
Tesla with Gd-Targeting Agents:
when the low field is better!
Geninatti-Crich S, Szabo I, Alberti D, et al. MRI of cells and mice at 1 and 7
Tesla with Gd-Targeting Agents: when low field is better! Contrast Media Mol.
Imaging. 2011. ePub ahead of print.
In Vivo7T 1T
In Vitro
Increasing concentrations of Gadolinium-loaded cells
showed stronger signal enhancement at 1T than at 7T
5 hours after injection of the Gadolinium contrast
agent, there is a greater enhancement at lower field
than high:
• 1T: 80±9%
• 7T: 30±13%
Image Comparison Between High and Low Field Systems
Images courtesy of Dr. A. Annapragada at Texas Children’s Hospital
100um isotropic resolution
Acqu. Time = 50 minutes
MR Angiography of the mouse cerebrovasculature.
Installation Requirements:
Conventional high-field MRI
Installations
Installation Requirements:
Conventional high-field MRI
Installation Requirements:
M-SeriesTM Compact MRI
Key Research Applications
• Anatomy and morphology
• Neurology
• Cancer biology
• Cardiovascular Biology
• Multi-modal imaging
• Ex vivo imaging
Anatomy and Morphology:
Normal Mouse
T2 weighted: FSE (TE/TR=47/6000, FOV=80x30mm, Matrix=512x192,
NEX=10, ETL=16, Res. 156um, Acq. Time 14:00 min)
T1 weighted: SE (TE/TR=17/540, FOV=80x30mm, Matrix=512x192,
NEX=6, Res. 156um, Acq Time 11:07min:sec)
Kidney
Liver
T2 Weighted
T1 Weighted
Coronal
Kidney
Spinal Cord
Sagittal
T1 Weighted
T2 Weighted
Anatomy and Morphology:
Organ Segmentation
• VivoQuant® is a powerful image analysis platform which can be used to
post-process images from the M-SeriesTM systems
• Image pre-processing and co-registration
• Visualization
• Analysis
Anatomy and Morphology:
Hind Limb Inflammation
• Acute inflammation was induced by topical application of an irritant
• Lesion volume (red) = 486 mm2
• Entire ipsilateral leg volume (blue + red) = 1120 mm2
• Contralateral leg volume (green) = 824 mm2
T2 weighted: SE(TE/TR=50/1500, FOV=60mm, Matrix=256x256, Res. 235um,
Acq. Time 6:24m:s)
Anatomy and Morphology:
Visceral Fat Segmentation
• Images can be automatically segmented based on grey-scale
intensities of connected voxels – in these T1 weighted images
adipose tissue appears very bright
• Volume = 1075 mm3
Neurology:
Normal Mouse
• T2 Weighted images are used to highlight morphology within the brain
T2 weighted: FSE (TE/TR=73.8/3100,
FOV=40x20mm, Matrix=256x128, NEX=20,
ETL=16, Res. 156um, Acq. Time 10 min)
Sagittal
Transverse
Coronal Coronal
Neurology:
Orthotopic Glioblastoma
• Day 4 – normal anatomical structures
T2 weighted: FSE (TE/TR=73.8/3100, FOV=40x20mm, Matrix=256x128,
NEX=20, ETL=16, Res. 156um, Acq. Time 10 min)
4 days post injection
15 days post injection
• Day 15 – tumor is visible, spread throughout the
brain, enlarged ventricles
• Tumor volume = 20 mm3
Neurology:
Traumatic Brain Injury
• TBI caused by percussion injury to the skull
• Injury appears clearly on T2 weighted image due to
the inflammatory lesion
• Effect of preventative measures or therapeutic
response could be evaluated
T2 weighted: FSE (TE/TR=74/2840, FOV=50, Matrix=256x256, Res. 195µm, Acq. Time 13:46 min:sec)
Images courtesy of Prof A. Friedman & S. Lublinsky
Brain Imaging Research Center, Ben-Gurion University of the Negev
Neurology:
Epilepsy
• Epilepsy was induced by intoxication with paraoxone causing
severe cholinergic symptoms
• Significant changes are visible in the cortex 48 hours post
exposure
T2 weighted: FSE (TE/TR=74/3400,
FOV=50, Matrix=256x256, Res.
195µm, Acq. Time 16:30 min:sec)
Images courtesy of Prof A. Friedman & S. Lublinsky
Brain Imaging Research Center, Ben-Gurion University of the Negev
3 hours post PO exposure
48 hours post PO exposure
Neurology:
Stroke
• Stroke was induced by photothrombosis in the rat
brain
• The stroke lesion is clearly visible on T2 weighted
images due to the inflammation in the area
Images courtesy of Prof A. Friedman & S. Lublinsky
Brain Imaging Research Center, Ben-Gurion University of the Negev
T2 weighted: FSE (TE/TR=74/3030, FOV=50, Matrix=256x256, Res. 195µm, Acq. Time 14:41 min:sec)
Cancer Biology:
Xenograft Tumor Model
• Subcutaneous head and neck tumor located on
the hind limb
• Tumor can be identified with clear borders on the
T2 weighted image – images taken 3 weeks post
implantation
• Internal structures, such as cysts and lobes, can
easily be seen
• Tumor volume is easily quantified = 730mm3
T2 weighted: FSE (TE/TR=52.7/3500, FOV=80x30mm,
Matrix=256x96, NEX=8, ETL=16, Res. 312um, Acq. Time
4:40 min)
Model Courtesy of Dr. J. Mahmood, PhD., Radiation Medicine Program, Princess Margaret Cancer Center, UHN
Cancer Biology:
Xenograft Tumor Model
• Subcutaneous lung tumor implanted on the hind limb
• Tumor progression can be monitored in the same animal
over time
Model Courtesy of Dr. J. Mahmood, PhD., Radiation Medicine Program, Princess Margaret Cancer Center, UHN
T2 weighted: FSE (TE/TR=52.7/3500,
FOV=80x30mm, Matrix=256x96, NEX=8,
ETL=16, Res. 312um, Acq Time 4:40 min
Day 10 Day 23
Mouse 1 4.9 mm3 248 mm3
Mouse 2 10 mm3 106 mm3
Mouse 1
Mouse 2
Day 10 Day 23
Cancer Biology:
Orthotopic Cervical Tumor Model
• Therapeutic effect can be monitored over time using
the same animal as it’s own control
T2 weighted: FSE (TE/TR=52.7/3500, FOV=80x30mm, Matrix=256x96, NEX=8, ETL=16, Res. 312um, Acq Time 4:40 min)
T1 weighted: SE (TE/TR=9.8/500, FOV=80x30mm, Matrix=256x96, NEX=3, Res. 312um, Acq Time 2:42min:sec)
Model Courtesy of Drs. Naz Chaudary, Richard Hill & Shawn Stapleton, Princess Margaret Cancer Center
0
50
100
150
200
250
300
350
5.5 Weeks 7 Weeks
TumorVolume(mm3)
Control
Treated
Control (n=4) Treated (n=30)
5.5 weeks 179±46 mm3 93±8.5 mm3
7 weeks 227±64 mm3 134±11 mm3
Control
Treated
Cardiovascular Biology:
CINE Imaging
• Cineloop images can be acquired
• Varying sequence parameters will vary the appearance of the blood
throughout the cardiac cycle
• Surrounding structures are also visible
Cardiovascular Biology:
Cardiac Function
• Cardiac function can be measured from a single slice, or collection of
short and long axis images
• Measurements could include:
• Ejection Fraction
• Volume Measurements – i.e. stroke volume, end-diastolic, and
end-systolic volumes
• Wall Thickness
• Left Ventricular Mass
Multi Modal Imaging:
PET/MRI – Metabolic Research
Images Courtesy of Prof. Robert Lenkinski, Harvard Medical School
• Brown adipose tissue, along with white adipose tissue,
appears brightly on T1 weighted MR images
• FDG-PET was used to detect metabolic activity to
differentiate brown fat from other adipose tissue
• Co-registration of images confirms location of brown fat,
which can be quantified from MR images
MRI PET PET/MRI
Brown Adipose Tissue
Multi Modal Imaging:
PET/MRI – Tumor Imaging
• Tumor showed increase metabolism on FDG-PET compared
to contralateral muscle (ratio = 2.7)
• Central region of tumor showed decreased PET signal,
T2 weighted MR image indicates increased fluid content – possibly a necrotic core
• CT images may provide additional anatomical context
Model courtesy of Dr. R. DeSouza, STTARR (UHN) PET PET + CT + MRIMRI – T1wCT MRI – T2w
Necrotic Core
TumorTumor volume is best
measured on MRI =
410 mm3
Multi Modal Imaging:
3D Optical + MRI
• VivoFuseTM includes an imaging cassette which allows the animal to be moved from the optical imager to the MRI
• 3D Bioluminescence Imaging (BLI) or Fluorescence Lifetime Imaging (FLI) may be used to generate a 3D tomographic
optical image, this is then co-registered with the sequentially acquired 3D MR image
• Optical signal may confirm the lesion seen on MRI is a tumor; volume is quantified from MR image
Imaging cassette in MR
animal handling system
Acquisition of optical +
CT image
Co-registration
using CT and
silhouette
VivoFuse has been developed in collaboration with the team at the MMCT headed by Prof. M Ogris at University of Vienna, Austria
Ex Vivo Imaging:
MR-Based Histology
• High resolution images of an ex vivo fixed rat brain sample
• Exquisite details of the structures within the brain can be
visualized, identified, and quantified
Image Resolution: 83x83x300 µm
Sample Courtesy of Prof. Alan Johnson- Duke University, NC
• Fibrotic changes within the liver can be
visualized on fixed sample
• Images may be used to guide sectioning
for conventional histological analysis
Control Fibrosis
ControlFibrosis
High MagnificationLow Magnification
Ex Vivo Imaging:
MR-Based Histology
Ex Vivo Imaging:
MR-Based Histology
• Toxicology studies rely on a few histological samples taken
throughout an organ to look for lesions, i.e. liver toxicity
• MR-based histology is performed on in tact fixed samples,
providing a full 3D image of an organ
• Lesions are identified, counted, and volume calculated
• MR images may be used to guide tissue sectioning to confirm
lesion characteristics using conventional histology
• M-SeriesTM Features and Benefits
• Comparison to Conventional High-Field MRI Systems
• Key Research Applications
Topics of Discussion
❖ Imagine how your studies could benefit from utilizing
this simple to use, compact, MRI system
Tonya Coulthard, MSc.
Team Leader
Scintica Instrumentation
Phone: +1 (519) 914 5495
tcoulthard@scintica.com
Q&A
SESSION:
To ask a question, click the Q&A
Button, type your question and click
send. Any questions that are not
addressed during the live webinar will
be answered following the event.
Thank you for participating!
Changing how researchers think about MRI:  Utilizing a simple to use, compact, MRI system to transform preclinical imaging

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  • 1. Tonya Coulthard, MSc. Team Leader Scintica Instrumentation Phone: +1 (519) 914 5495 tcoulthard@scintica.com CHANGING HOW RESEARCHERS THINK ABOUT MRI: Utilizing a simple to use, compact, MRI system to transform preclinical imaging
  • 2. • Introduction to MRI, and M-SeriesTM Overview • Comparison to Conventional High-Field MRI Systems • Key Research Applications Topics of Discussion
  • 3. Introduction to MRI and M-SeriesTM Overview • Magnetic Resonance Imaging (MRI) • M-SeriesTM Compact magnet design • Animal handling system • Software interface and user experience • Hardware and software add-ons • Purchase, operating and maintenance costs
  • 4. • MRI is the gold standard for soft tissue imaging • Differentiate various organs, tissue types, and internal structures • Visualize inflammation, tumors, and other pathological changes • Contrast agents may be used to enhance the vasculature and other molecular targets Magnetic Resonance Imaging (MRI) Note – these images were not taken with the M- Series systems • No use of ionizing radiation to acquire images
  • 5. • MRI and ultrasound do not require ionizing radiation making them preferable to CT (computed tomography) or PET (positron emission tomography) for diagnostic imaging where possible • MRI is the best choice for brain, soft tissue, or tumor imaging • Ultrasound cannot penetrate bone or air; but is useful on many abdominal organs MRI vs Other Imaging Modalities • CT requires the use of ionizing radiation and is ideal for imaging bones, sinuses, and kidney stones. • Does not resolve soft tissue as well as MRI • PET requires a radioactive tracer, often FDG (a radioactive derivative of glucose), and is most often used to detect tissues with high metabolic activity • Should be co-registered to provide anatomical context to detected signal
  • 6. MRI vs Other Imaging Modalities CT vs. MRI PET vs. MRI Note – these images were not taken with the M-Series systems
  • 7. MRI vs Other Imaging Modalities Sensitivity&MolecularImaging High/Low High/High Low/Low Low/High Resolution & Anatomical Imaging µPET µSPECT MRI Ultrasound µCT Optical
  • 8. M-SeriesTM Compact Magnet Design The M-Series systems compact MRI systems have been designed and manufactured with the pre-clinical researcher in mind. These high-performance MRI systems provide powerful results without the cost, complexity and technical burden of conventional MRI systems.
  • 9. M-SeriesTM Compact, High Performance, MRI Systems from Aspect Imaging M3 M7 Bore Opening 50x120 mm (hxw) 220x90 mm (hxw) Imaging Volume 80x80x35 mm (spheroid) 120x120x70 mm (spheroid) Animal Size Mice only Mice – large rats Height 108 cm 132 cm Width 73.4 cm 79.0 cm Depth 73.4 cm 95.0 cm Weight 640 kg 1600 kg
  • 10. M-SeriesTM Compact Magnet Design• Require no special infrastructure • Compact and self shielded with minimal external fringe field • Operate very quietly during image acquisition • Systems are installed with first images being acquired in less than 1 day ❖ Installed within an animal facility, or existing laboratory next to other equipment or furnishings
  • 11. System Components • Compact magnet – select either the M3 or M7 magnet; • Electronics cabinet and User Workstation - is the same for all systems. • Accessories and add-ons • Animal handling system with heating and physiological monitoring • Anesthesia delivery and exhaust gas scavenging • SimPETTM insert – simultaneous PET/MRI • VivoFuseTM – co-registration of 3D optical (BLI/FLI) with MR images • MR-Based histology – high resolution automated ex vivo imaging • Multi-Nuclear capabilities – for advanced users
  • 12. Animal Handling System • Fully integrated animal handling and coil system includes • Mouse or rat beds to suite varying animal sizes • Anatomy specific coils, with automatic tuning • Heating • Physiological monitoring • Anesthesia delivery and scavenging
  • 13. Imaging Coils Type Dimensions Application Inner Diameter Length Mouse Head 23 mm 25 mm Neurological imaging in mice Mouse Body 30 mm 50 mm Extremity, abdominal, and thoracic cavity imaging in mice Mouse Whole Body 30 mm 80 mm Whole body imaging in mice Large Mouse Body 38 mm 50 mm Extremity, abdominal and thoracic cavity imaging in large/obese mice Rat Head 35 mm 40 mm Neurological imaging in rats Rat Body 50/60 mm ellipsoid 90 mm Extremity, abdominal and thoracic cavity imaging in rats Large Rat Body 71 mm 90 mm Extremity, abdominal and thoracic cavity imaging in large rats Imaging coils should fit as tightly as possible to the anatomical target for high quality images
  • 14. Physiological Monitoring and Heating Systems • Continuous monitoring of ECG, heart rate, respiration rate, and body temperature • Allows for ECG and/or respiratory triggering • Heated water is continuously circulated to maintain body temperature
  • 15. Anesthesia System • Fully integrated with the animal handling system • 3 delivery points • knock down chamber • animal preparation (for example - tail vein cannulation) • animal bed • Gas exhaust actively scavenges waste gas
  • 16. Most measurements and parameters are functions of time, so we need waveforms
  • 17. Most measurements and parameters are functions of time, so we need waveforms • The M-seriesTM systems have an easy to operate, intuitive software interface to quickly generate reproducible, quantitative results • No need to have a background in MR physics to operate the systems • Default sequences have been optimized • The system also offers the experienced MR user the flexibility and customization options to tailor the performance of the system to meet their needs Software Interface and User Experience
  • 18. Most measurements and parameters are functions of time, so we need waveforms Software Interface and User Experience
  • 19. Hardware and Software Add-Ons: SimPETTM Insert • The SimPETTM insert expands the capabilities of the M7 system to allow for simultaneous PET/MR imaging • MR images compliment the highly sensitive PET images in detecting functional information, abnormalities, and early disease, providing an anatomical context
  • 20. Hardware and Software Add-Ons: VivoFuseTM • VivoFuseTM is both a hardware and software add-on allowing for co-registration of 3D tomographic optical (BLI/FLI) images with 3D MR images • Combined images allow the molecular/functional information to be localized to a specific anatomical location • Tumor volume and growth could be tracked longitudinally
  • 21. Hardware and Software Add-Ons: MR-Based Histology • The focus with MR-Based histology is to acquire very high resolution 3D images on ex-vivo samples, i.e. for toxicology studies • This hardware and software add-on allows for automated sample handling of multiple samples • Images are used to detect, localize, and quantify lesion number and size
  • 22. Most measurements and parameters are functions of time, so we need waveforms • Minimal running costs • No electricity required to create/maintain magnetic field • No cryogens or water cooling due to the design of the permanent magnet • Only electricity is for the electronics cabinet and work station during image acquisition Purchase, Operating, and Maintenance Costs MRI is now accessible to more pre-clinical researchers. Research budgets are preserved and can be used to focus on science rather than equipment costs • There are no ongoing maintenance costs for this system • A well equipped M3 system starts at $290,000 USD
  • 23. Comparison to Conventional High-Field Systems • Image comparison between high and low field systems • Contrast imaging at 1 Tesla • Installation requirements
  • 24. Image Comparison Between High and Low Field Systems: Signal to Noise Ratio (TR/TE=5000/25, FOV=30mm, Matrix=192x192, NEX=4 , Res 156 µm, Acq. Time 4 min) Mouse SNR kidney=65 Vertical bore @ 7 Tesla (TR/TE=3000/56, FOV=30mm, Matrix=192x192, NEX=12 , Res 156 µm, Acq. Time 14 min) Mouse SNR kidney=17 M-Series @ 1 Tesla • The laws of physics explain that the Signal to Noise Ratio (SNR) is linearly proportional to field strength • How can the SNR be improved? • Increase acquisition time • Decrease resolution • Optimized coil and system design
  • 25. Image Comparison Between High and Low Field Systems: Signal to Noise Ratio T2 weighted: FSE (TE/TR=47/6000, FOV=80x30mm, Matrix=512x192, NEX=10, ETL=16, Res. 156um, Acq. Time 14:00 min:sec) T2 weighted: FSE (TE/TR=52.7/4060, FOV=80x30mm, Matrix=256x96, NEX=10, ETL=16, Res. 312um, Acq. Time 5:24min:sec) T1 weighted: SE (TE/TR=17/540, FOV=80x30mm, Matrix=512x192, NEX=6, Res. 156um, Acq Time 11:07min:sec) T1 weighted: SE (TE/TR=9.8/500, FOV=80x30mm, Matrix=256x98, NEX=3, Res. 312um, Acq Time 2:30min:sec) T2 Weighted 156um 312um T1 Weighted 156um 312um T2 Weighted 156um 312um T1 Weighted 156um 312um Image Weighting Resolution Acquisition Time T2 Weighted 156um 14:00 min:sec 312um 5:24 min:sec T1 Weighted 156um 11:07 min:sec 312um 2:30 min:sec • Image resolution and acquisition time can off-set each other • Decision should be based on images required to answer specific biological question
  • 26. Image Comparison Between High and Low Field Systems Images courtesy of Prof. G. Allan Johnson at Duke University Molecules behave differently at 1T than at high fields, this allows for improved sensitivity to contrast agents as well as to specific disease targets, i.e. orthotopic glioblastoma tumor in the brain Vertical bore @ 7 Tesla M-Series @ 1 Tesla T2 weighted: SE (TE/TR-80/2500, FOV = 32, Matrix = 256x256x23, NEX = 6, Res. 125µm, Acq. Time 64 min) Mouse
  • 27. Image Comparison Between High and Low Field Systems: Gadolinium Contrast Agents MRI of Cells and Mice at 1 and 7 Tesla with Gd-Targeting Agents: when the low field is better! Geninatti-Crich S, Szabo I, Alberti D, et al. MRI of cells and mice at 1 and 7 Tesla with Gd-Targeting Agents: when low field is better! Contrast Media Mol. Imaging. 2011. ePub ahead of print. In Vivo7T 1T In Vitro Increasing concentrations of Gadolinium-loaded cells showed stronger signal enhancement at 1T than at 7T 5 hours after injection of the Gadolinium contrast agent, there is a greater enhancement at lower field than high: • 1T: 80±9% • 7T: 30±13%
  • 28. Image Comparison Between High and Low Field Systems Images courtesy of Dr. A. Annapragada at Texas Children’s Hospital 100um isotropic resolution Acqu. Time = 50 minutes MR Angiography of the mouse cerebrovasculature.
  • 32. Key Research Applications • Anatomy and morphology • Neurology • Cancer biology • Cardiovascular Biology • Multi-modal imaging • Ex vivo imaging
  • 33. Anatomy and Morphology: Normal Mouse T2 weighted: FSE (TE/TR=47/6000, FOV=80x30mm, Matrix=512x192, NEX=10, ETL=16, Res. 156um, Acq. Time 14:00 min) T1 weighted: SE (TE/TR=17/540, FOV=80x30mm, Matrix=512x192, NEX=6, Res. 156um, Acq Time 11:07min:sec) Kidney Liver T2 Weighted T1 Weighted Coronal Kidney Spinal Cord Sagittal T1 Weighted T2 Weighted
  • 34. Anatomy and Morphology: Organ Segmentation • VivoQuant® is a powerful image analysis platform which can be used to post-process images from the M-SeriesTM systems • Image pre-processing and co-registration • Visualization • Analysis
  • 35. Anatomy and Morphology: Hind Limb Inflammation • Acute inflammation was induced by topical application of an irritant • Lesion volume (red) = 486 mm2 • Entire ipsilateral leg volume (blue + red) = 1120 mm2 • Contralateral leg volume (green) = 824 mm2 T2 weighted: SE(TE/TR=50/1500, FOV=60mm, Matrix=256x256, Res. 235um, Acq. Time 6:24m:s)
  • 36. Anatomy and Morphology: Visceral Fat Segmentation • Images can be automatically segmented based on grey-scale intensities of connected voxels – in these T1 weighted images adipose tissue appears very bright • Volume = 1075 mm3
  • 37. Neurology: Normal Mouse • T2 Weighted images are used to highlight morphology within the brain T2 weighted: FSE (TE/TR=73.8/3100, FOV=40x20mm, Matrix=256x128, NEX=20, ETL=16, Res. 156um, Acq. Time 10 min) Sagittal Transverse Coronal Coronal
  • 38. Neurology: Orthotopic Glioblastoma • Day 4 – normal anatomical structures T2 weighted: FSE (TE/TR=73.8/3100, FOV=40x20mm, Matrix=256x128, NEX=20, ETL=16, Res. 156um, Acq. Time 10 min) 4 days post injection 15 days post injection • Day 15 – tumor is visible, spread throughout the brain, enlarged ventricles • Tumor volume = 20 mm3
  • 39. Neurology: Traumatic Brain Injury • TBI caused by percussion injury to the skull • Injury appears clearly on T2 weighted image due to the inflammatory lesion • Effect of preventative measures or therapeutic response could be evaluated T2 weighted: FSE (TE/TR=74/2840, FOV=50, Matrix=256x256, Res. 195µm, Acq. Time 13:46 min:sec) Images courtesy of Prof A. Friedman & S. Lublinsky Brain Imaging Research Center, Ben-Gurion University of the Negev
  • 40. Neurology: Epilepsy • Epilepsy was induced by intoxication with paraoxone causing severe cholinergic symptoms • Significant changes are visible in the cortex 48 hours post exposure T2 weighted: FSE (TE/TR=74/3400, FOV=50, Matrix=256x256, Res. 195µm, Acq. Time 16:30 min:sec) Images courtesy of Prof A. Friedman & S. Lublinsky Brain Imaging Research Center, Ben-Gurion University of the Negev 3 hours post PO exposure 48 hours post PO exposure
  • 41. Neurology: Stroke • Stroke was induced by photothrombosis in the rat brain • The stroke lesion is clearly visible on T2 weighted images due to the inflammation in the area Images courtesy of Prof A. Friedman & S. Lublinsky Brain Imaging Research Center, Ben-Gurion University of the Negev T2 weighted: FSE (TE/TR=74/3030, FOV=50, Matrix=256x256, Res. 195µm, Acq. Time 14:41 min:sec)
  • 42. Cancer Biology: Xenograft Tumor Model • Subcutaneous head and neck tumor located on the hind limb • Tumor can be identified with clear borders on the T2 weighted image – images taken 3 weeks post implantation • Internal structures, such as cysts and lobes, can easily be seen • Tumor volume is easily quantified = 730mm3 T2 weighted: FSE (TE/TR=52.7/3500, FOV=80x30mm, Matrix=256x96, NEX=8, ETL=16, Res. 312um, Acq. Time 4:40 min) Model Courtesy of Dr. J. Mahmood, PhD., Radiation Medicine Program, Princess Margaret Cancer Center, UHN
  • 43. Cancer Biology: Xenograft Tumor Model • Subcutaneous lung tumor implanted on the hind limb • Tumor progression can be monitored in the same animal over time Model Courtesy of Dr. J. Mahmood, PhD., Radiation Medicine Program, Princess Margaret Cancer Center, UHN T2 weighted: FSE (TE/TR=52.7/3500, FOV=80x30mm, Matrix=256x96, NEX=8, ETL=16, Res. 312um, Acq Time 4:40 min Day 10 Day 23 Mouse 1 4.9 mm3 248 mm3 Mouse 2 10 mm3 106 mm3 Mouse 1 Mouse 2 Day 10 Day 23
  • 44. Cancer Biology: Orthotopic Cervical Tumor Model • Therapeutic effect can be monitored over time using the same animal as it’s own control T2 weighted: FSE (TE/TR=52.7/3500, FOV=80x30mm, Matrix=256x96, NEX=8, ETL=16, Res. 312um, Acq Time 4:40 min) T1 weighted: SE (TE/TR=9.8/500, FOV=80x30mm, Matrix=256x96, NEX=3, Res. 312um, Acq Time 2:42min:sec) Model Courtesy of Drs. Naz Chaudary, Richard Hill & Shawn Stapleton, Princess Margaret Cancer Center 0 50 100 150 200 250 300 350 5.5 Weeks 7 Weeks TumorVolume(mm3) Control Treated Control (n=4) Treated (n=30) 5.5 weeks 179±46 mm3 93±8.5 mm3 7 weeks 227±64 mm3 134±11 mm3 Control Treated
  • 45. Cardiovascular Biology: CINE Imaging • Cineloop images can be acquired • Varying sequence parameters will vary the appearance of the blood throughout the cardiac cycle • Surrounding structures are also visible
  • 46. Cardiovascular Biology: Cardiac Function • Cardiac function can be measured from a single slice, or collection of short and long axis images • Measurements could include: • Ejection Fraction • Volume Measurements – i.e. stroke volume, end-diastolic, and end-systolic volumes • Wall Thickness • Left Ventricular Mass
  • 47. Multi Modal Imaging: PET/MRI – Metabolic Research Images Courtesy of Prof. Robert Lenkinski, Harvard Medical School • Brown adipose tissue, along with white adipose tissue, appears brightly on T1 weighted MR images • FDG-PET was used to detect metabolic activity to differentiate brown fat from other adipose tissue • Co-registration of images confirms location of brown fat, which can be quantified from MR images MRI PET PET/MRI Brown Adipose Tissue
  • 48. Multi Modal Imaging: PET/MRI – Tumor Imaging • Tumor showed increase metabolism on FDG-PET compared to contralateral muscle (ratio = 2.7) • Central region of tumor showed decreased PET signal, T2 weighted MR image indicates increased fluid content – possibly a necrotic core • CT images may provide additional anatomical context Model courtesy of Dr. R. DeSouza, STTARR (UHN) PET PET + CT + MRIMRI – T1wCT MRI – T2w Necrotic Core TumorTumor volume is best measured on MRI = 410 mm3
  • 49. Multi Modal Imaging: 3D Optical + MRI • VivoFuseTM includes an imaging cassette which allows the animal to be moved from the optical imager to the MRI • 3D Bioluminescence Imaging (BLI) or Fluorescence Lifetime Imaging (FLI) may be used to generate a 3D tomographic optical image, this is then co-registered with the sequentially acquired 3D MR image • Optical signal may confirm the lesion seen on MRI is a tumor; volume is quantified from MR image Imaging cassette in MR animal handling system Acquisition of optical + CT image Co-registration using CT and silhouette VivoFuse has been developed in collaboration with the team at the MMCT headed by Prof. M Ogris at University of Vienna, Austria
  • 50. Ex Vivo Imaging: MR-Based Histology • High resolution images of an ex vivo fixed rat brain sample • Exquisite details of the structures within the brain can be visualized, identified, and quantified Image Resolution: 83x83x300 µm Sample Courtesy of Prof. Alan Johnson- Duke University, NC
  • 51. • Fibrotic changes within the liver can be visualized on fixed sample • Images may be used to guide sectioning for conventional histological analysis Control Fibrosis ControlFibrosis High MagnificationLow Magnification Ex Vivo Imaging: MR-Based Histology
  • 52. Ex Vivo Imaging: MR-Based Histology • Toxicology studies rely on a few histological samples taken throughout an organ to look for lesions, i.e. liver toxicity • MR-based histology is performed on in tact fixed samples, providing a full 3D image of an organ • Lesions are identified, counted, and volume calculated • MR images may be used to guide tissue sectioning to confirm lesion characteristics using conventional histology
  • 53. • M-SeriesTM Features and Benefits • Comparison to Conventional High-Field MRI Systems • Key Research Applications Topics of Discussion ❖ Imagine how your studies could benefit from utilizing this simple to use, compact, MRI system
  • 54. Tonya Coulthard, MSc. Team Leader Scintica Instrumentation Phone: +1 (519) 914 5495 tcoulthard@scintica.com Q&A SESSION: To ask a question, click the Q&A Button, type your question and click send. Any questions that are not addressed during the live webinar will be answered following the event. Thank you for participating!