This presentation highlights the applications and capabilities of the M-Series™ compact MRI systems. Anatomical, functional, and molecular imaging can be performed on the M-Series and are often applied in cancer, cardiac, neuroscience, and multimodal imaging studies. It showcases example data from a variety of papers and training sessions in which the focus is on anatomy, neurobiology, and oncology. The presentation shows data from contrast agents which further enhances the capabilities of the M-Series, providing invaluable insights into tissue/tumor perfusion, myocardial infarction size, and molecular targets.

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M-finite applications of the
M-Series
Compact, Self-Shielded, High
Performance, Small Animal MRI

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Outline
• M-Series Magnet Design and User Experience
• Poll Question
• Application Areas
• Anatomy & Morphology
• Neurology
• Cancer Biology
• Cardiovascular Biology
• Contrast Agents
• Multi-Modal Imaging
• Ex Vivo Imaging
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M-SeriesTM Magnet Design
• Requires no special infrastructure or cooling
• Compact and self-shielded with minimal external
fringe field
• Easily installed within an animal facility, or existing
laboratory next to other equipment or furnishings
• Operates very quietly during image acquisition
• Systems are installed with first images being
acquired in less than 1 day
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M-Series (M5) Components
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• Electronics Cabinet and User
Workstation
• Compact Magnet
• Animal Handling System
• Animal handling systems for
mice and rats

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Animal Handling System
• Fully integrated animal handling and coil
system includes:
• Mouse or rat beds to suite a variety of sized
animals
• Anatomy specific coils
• Animal heating
• Physiological monitoring
• Anesthesia delivery and scavenging
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Animal Preparation and Imaging Set-Up
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Software Interface and User Experience
• The M-Series software is intuitive, and easy to operate;
designed to quickly generate reproducible, and quantitative
results
• No need to have a background in MR physics to operate the
system – default sequences are available and can be further
optimized
• Experienced MR users have full flexibility to customize
options to tailor the performance of the system to meet their
needs
• Software is study based, and optimized protocol sets may be
selected by the user
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M-Series Systems
• The M-Series are designed with the pre-
clinical researcher in mind
• No MRI technician needed
• Streamlined workflow for animal
preparation and positioning
• User-friendly software interface
• Wide variety of applications
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9. Audience Poll

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Key Research Applications
• Anatomy and Morphology
• Neurology
• Cancer Biology
• Cardiovascular Biology
• Contrast Agents
• Multi-Modal Imaging
• Ex Vivo Imaging
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Anatomy and Morphology: Normal Mouse
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T2 weighted FSE on Mouse Abdomen
T1 weighted SE on Mouse Abdomen
400µm resolution
4:54m:s, 7 excitations
420µm resolution
6:12m:s, 11 excitations

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Anatomy and Morphology: Spinal Imaging
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Fixed mouse
T1 weighted imaging
Live mouse
T2 weighted imaging
Live mouse
T2 weighted imaging

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Anatomy and Morphology: Hind Limb Inflammation
• Acute inflammation was
induced by topical application
of an irritant
• Lesion volume (red) =
486mm3
• Entire ipsilateral leg volume
(blue+red) = 1120mm3
• Contralateral leg volume
(green) = 824mm3
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T2 weighted: SE(TE/TR=50/1500, FOV=60mm, Matrix=256x256, Res. 235um, Acq. Time 6:24m:s)

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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 = 1075mm3
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Key Research Applications
• Anatomy and Morphology
• Neurology
• Cancer Biology
• Cardiovascular Biology
• Contrast Agents
• Multi-Modal Imaging
• Ex Vivo Imaging
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Neurology: Normal Mouse
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T2 weighted: FSE Coronal/Sagittal 120um, 12:20m:s; Axial 160um, 16:00m:s

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Neurology: Glioblastoma (UIC training)
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Glioblastoma model with frequent edema
Fluid attenuation T2 weighted imaging
(FLAIR)
T2 weighted imaging T2 weighted imaging
Edema in red Edema in red
Tumor in blue
T2 weighted: FSE Axial 250um, 6:44m:s
Images courtesy of Dr. David Largaespada’s group at University of Minnesota

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Neurology: Orthotopic Glioblastoma
• Day 4 – normal anatomical
structures are visible
• Day 15 – tumor
is visible, spread
throughout the
brain, enlarged
ventricles
• Tumor volume =
20mm3
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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

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Neurology: Traumatic Brain Injury
• TBI caused by percussion
injury to the skull
• Injury appears clearly on a
T2 weighted image due to
the inflammatory lesion
• Effect of preventative
measures or therapeutic
response can be evaluated
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T2 weighted: FSE (TE/TR=74/2840, FOV=50, Matrix=256x256, Res. 195µm, Acq. Time 13:46 min:sec)
Images courtesy of Prov. A. Friedman & S. Lublinsky – Brain Imaging Research Center, Ben-Gurion University of the Negev

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Neurology: Epilepsy
• Epilepsy was induced by
intoxication with
paraoxone causing severe
cholinergic symptoms
• Significant changes are
visible in the cortex 48
hours post exposure
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T2 weighted: FSE (TE/TR=74/3400, FOV=50, Matrix=256x256, Res. 195µm, Acq. Time 16:30 min:sec)
Images courtesy of Prov. A. Friedman & S. Lublinsky – Brain Imaging Research Center, Ben-Gurion University of the Negev
3 hours post PO exposure
48 hours post PO exposure

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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
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T2 weighted: FSE (TE/TR=74/3030, FOV=50, Matrix=256x256, Res. 195µm, Acq. Time 14:41 min:sec)
Images courtesy of Prov. A. Friedman & S. Lublinsky – Brain Imaging Research Center, Ben-Gurion University of the Negev

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Neurology: Stroke
• Stroke volume was calculated in
VivoQuant, and found to be
19.0mm3
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Images courtesy of L. Lacovitti’s lab at Thomas Jefferson University, Hospital for Neuroscience
• Stroke was induced by photothrombosis in the mouse brain
• The stroke lesion is clearly visible on T2 weighted images due to
the inflammation in the area

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Key Research Applications
• Anatomy and Morphology
• Neurology
• Cancer Biology
• Cardiovascular Biology
• Contrast Agents
• Multi-Modal Imaging
• Ex Vivo Imaging
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Cancer Biology: Tumor Detection
Fat-suppressed T2-weighed MRI can be used to monitored
tumour burden over time using the same animal as its own
control
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Fat-suppressed T2 weighted: FSE (TE/TR=10-60/4000ms, Inversion time = 100ms)
Th-MYCN GEMM
2min scan 8min scan
TRAMP GEMM
8min scan
O.t. medulloblastoma
3min scan
KPC GEMM
O.t. Prostate bone marrow metastasis
12min scan
RH-41 xenograft
4min scan

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Cancer Biology: Tumour Response Assessment in GEM model of
neuroblastoma
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Fat-suppressed T2 weighted: FSE (TE/TR=10/4500ms, FOV=60x30mm, slice thickness 1 mm, Matrix=144x72, NEX=2, Inversion time = 100ms, total scan time <2min)
• Rapid screening: Mouse is back in its cage within 5mins
• Reduced bias: Compared to physical palpation
• Reduction in animal used: enhanced statistical power
• Enhanced data curation
• Nijhuis A et al., Nat Commun. 2022
• Poon E et al., J Clin Investig. 2020
• Dubiella C et al., Nat Chem Bio. 2021
• Roeschert C et al., Nat Cancer. 2021
183 mm3 426 mm3 593 mm3 29 mm3
277 mm3 867 mm3 143 mm3 0 mm3

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Cancer Biology: Flank tumor (UIC training)
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T1 weighted imaging T2 weighted imaging
Images courtesy of Dr. David Largaespada’s group at University of Minnesota

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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
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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

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Cancer Biology: Nerve Sheath (UIC training)
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Images courtesy of Dr. David Largaespada’s group at University of Minnesota

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Cancer Biology: Orthotopic Cervical Tumor Model
Therapeutic effect can be monitored over time using
the same animal as it’s own control
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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
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50
100
150
200
250
300
350
5.5 Weeks 7 Weeks
Tumor
Volume
(mm
3
)
Control
Treated
Control (n=4) Treated (n=30)
(n=30)
5.5 weeks
weeks
179±46 mm3 93±8.5 mm3
7 weeks 227±64 mm3 134±11 mm3
Control
Treated

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Cancer Biology: Multi modal detection of orthotopic model of prostate
bone marrow metastasis
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Fat-suppressed T2 weighted: FSE (TE/TR=36/7300ms, FOV=60x30mm, slice thickness 0.8 mm, Matrix=240x120, NEX=8, Inversion time = 100ms, total scan time
12min)
Control Injected (right leg)
Bioluminescence imaging
Maximum intensity projection (MIP) (3 slices)
Control Injected

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Key Research Applications
• Anatomy and Morphology
• Neurology
• Cancer Biology
• Cardiovascular Biology
• Contrast Agents
• Multi-Modal Imaging
• Ex Vivo Imaging
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Cardiovascular Biology: CINE Imaging
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Images courtesy of Erik Blackwood at the Translation Cardiac Research Center
The University of Arizona

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Data from short axis
For the Left Ventricle:
o End Diastole and End Systole LV mass (ED/ED LVM), in g
o End Diastolic Volume (EDV), in ml
o End Systolic Volume (ESV), in ml
o Stroke Volume (SV), in ml
o Ejection Fraction (EF), as %
o Cardiac Output, in l/min, when the user inputs the heart rate
o Heart Rate, in bpm, as input by the user
For the Right Ventricle:
o End Diastole and End Systole LV mass (ED/ED LVM), in g
o End Diastolic Volume (RVEDV), in ml
o End Systolic Volume (RVESV), in ml
o Stroke Volume (RVSV), in ml
o Ejection Fraction (EF), as %

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Strain Analysis-Long Axis (CINE)
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Strain Analysis-Exported data
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Angiography – TOF 2D
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Mouse: Brain Mouse: Cardiovascular system
Mapping of blood vessels in the body without the use of contrast agents

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Key Research Applications
• Anatomy and Morphology
• Neurology
• Cancer Biology
• Cardiovascular Biology
• Contrast Agents
• Multi-Modal Imaging
• Ex Vivo Imaging
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Contrast Agent Imaging
• 50µL Primovist (Gd-EOB-
DTPA), was injected i.v.
through the tail vein
• T1 weighted imaging was
performed pre and post
contrast injection
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Contrast Agent Imaging
• VivoQuant was used to
subtract the pre and post
contrast injection images,
the results were colored
green
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Contrast Agent Imaging: Normal Mouse
• Dynamic Contrast
Enhanced imaging was
performed during the
injection – 1 frame/sec
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Key Research Applications
• Anatomy and Morphology
• Neurology
• Cancer Biology
• Cardiovascular Biology
• Contrast Agents
• Multi-Modal Imaging
• Ex Vivo Imaging
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Multi-Modal Imaging: PET/MRI
• The SimPET 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 anatomical context
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Multi-Modal Imaging: PET/MRI
• Reconstructed images of a hot rod
phantom with rod diameters of 0.75, 1.00,
1.35, 1.70, 2.00, 2.40mm
• Reconstructed using 3D OSEM algorithm with
incorporation of point spread function (a) or
without point spread function (b)
• Example image: effects of tumor associated
macrophages on tumor hypoxia and
aerobic glycolysis (Cancer Research, 2019)
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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
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Model courtesy of Dr. R. DeSouza, STTARR (UHN)
PET PET + CT + MRI
MRI – T1w
CT MRI – T2w
Necrotic Core
Tumor
Tumor volume is best measured on MRI = 410 mm3

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Complimentary Nature of Imaging Modalities
Bioluminescence helps to confirm viability of the tumor cells, as they express luciferase, approximate volumes may be possible
from the BLI signal; anatomical images help to confirm tumor volume - ultrasound (263mm3) or MRI (273mm3)
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Orthotopic Mammary Fat Pad Tumor (MDA-MB-231)
Optical Imaging - BLI Ultrasound
MRI

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Key Research Applications
• Anatomy and Morphology
• Neurology
• Cancer Biology
• Cardiovascular Biology
• Contrast Agents
• Multi-Modal Imaging
• Ex Vivo Imaging
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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
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Sample Courtesy of Prof. Alan Johnson- Duke University, NC
Image Resolution: 83x83x300 µm

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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 intact 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
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Key Research Applications
• Anatomy and Morphology
• Neurology
• Cancer Biology
• Cardiovascular Biology
• Contrast Agents
• Multi-Modal Imaging
• Ex Vivo Imaging
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M-Series Systems
• The M-Series are designed for pre-clinical
researchers
• No MRI technician needed
• Streamlined workflow for animal preparation and
positioning
• User-friendly software interface
• Wide variety of applications that can
contribute to your research
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