In this webinar, we reviewed some of the most commonly used preclinical imaging modalities, including magnetic resonance imaging (MRI), positron emission tomography (PET), computer tomography (CT), ultrasound, photoacoustic, bioluminescence, fluorescence, dual-energy x-ray absorptiometry (DEXA/DXA), and intravital microscopy. For each modality, we spent time reviewing the basics of how each worked, the strengths and considerations of each, and some key application areas and example images. Finally, we discussed the benefits of multimodal imaging and reviewed a few papers utilizing a variety of imaging modalities to help support their research outcomes.
We ended with a very brief introduction to Scintica Instrumentation and our philosophy behind the various products we represented. However, the main focus of the webinar was on education, and not our diverse product portfolio.
(March 13, 2024) Overview of Preclinical Small Animal and Multimodal Imaging
1. Overview of
Preclinical Small Animal
and
Multimodal Imaging
Applications
Tonya Coulthard, MSc.
Senior Account Director, Northeast Region
Scintica
tcoulthard@scintica.com
2. Preclinical Imaging
• In most cases, adaptation of clinical imaging to preclinical research
• Magnetic Resonance Imaging (MRI)
• Positron Emission Tomography (PET)
• Computer Tomography (CT)
• Ultrasound
• Some modalities have gone from preclinical research to the clinic
• Photoacoustic
• While some modalities designed specifically for preclinical research
• Bioluminescence (BLI)
• Intravital Microscopy (IVM)
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3. Benefits vs. in vitro, ex vivo, in situ
• Intact subject involvement of all organs and immune system
• Longitudinal studies Elucidation of disease mechanism over time
Reduced variability - imaging subject used as own control
Supports 3R’s (Replace, Reduce, Refine)
• Multimodal imaging Possible
Preclinical Imaging
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Day 0
Baseline Image
Day 1
Induce Model
Day 2
Imaging Timepoint,
Disease Progression
Day 3
Imaging Timepoint,
Disease Progression
Day 4
End Point Imaging,
Tissue Collection
4. Preclinical Imaging
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• Size of imaging subject and imaging target
increased spatial resolution
• Physiological differences, i.e. heart rate
increased temporal resolution
• Cost of novel target/contrast agents
increased sensitivity
• Animal welfare
integrated anesthesia, heating, physiological
monitoring, etc.
Considerations – “From Mouse to Man”
5. Modality Overview
Overview
• How each modality works
• Strengths vs. weaknesses
• Application areas and example images
Focus
• MRI, PET, CT, Ultrasound, Photoacoustic,
Bioluminescence/Fluorescence, DEXA,
Intravital Microscopy
• Other preclinical imaging modalities
- SPECT, Magnetic Particle Imaging, Raman
Imaging, etc.
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James ML, Gambhir SS. Physiological reviews. 2012
7. Magnetic Resonance Imaging (MRI)
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Images acquired using Aspect Imaging’s M-Series.
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
8. Magnetic Resonance Imaging (MRI)
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Key Strengths
• No limit to depth of penetration
• High spatial resolution
• Excellent soft tissue contrast
• No ionizing radiation
• Quantitative data
• Clinically translatable
Key Limitations/Considerations
• Lower sensitivity to contrast agents
• Can be expensive
• Permanent magnet options at
lower cost, and complexity to
install
• Relatively low temporal resolution
9. Magnetic Resonance Imaging (MRI)
• Anatomical and
morphological
• Neurology
• Cancer Biology
• Cardiovascular
Biology
• Cell Tracking
• Ex vivo Imaging
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Images acquired using Aspect Imaging’s M-Series.
10. Positron Emission Tomography (PET)
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James ML, Gambhir SS. Physiological reviews. 2012 Lancelot S, Zimmer L. Trends in Pharmacological Sciences. 2010
12. Positron Emission Tomography (PET)
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Key Strengths
• No limit to depth of penetration
• Excellent sensitivity
• Quantitative data
• Clinically translatable
Key Limitations/Considerations
• Requires cyclotron/generator
• Relatively expensive
• Ionizing radiation from isotopes
• Limited spatial resolution
• Should be combined with another
modality (i.e. MRI or CT) for
anatomical co-registration
13. Positron Emission Tomography (PET)
• Neurology
• Cancer Biology
• Cardiovascular
Biology
• Bone & Disease
Imaging
• Biodistribution
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Images acquired using Sedecal’s SuperArgus PET.
15. Computed Tomography
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Key Strengths
• No limit to depth of penetration
• High spatial resolution
• Good temporal resolution
• Bone and lung imaging is very strong
• Clinically translatable
Key Limitations/Considerations
• Poor sensitivity
• Primarily anatomical information –
bone and air-filled structures
• Limited soft tissue resolution
• Ionizing radiation
Images acquired using Sedecal’s
SuperArgus CT.
17. Ultrasound
• High-frequency (i.e.
shorter wavelength)
soundwaves are needed
when imaging small
animal models
- High-resolution
- Shallow depth of
penetration
• Select highest frequency
possible to visualize
structure of interest
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Images acquired using S-Sharp’s Prospect T1.
18. Ultrasound
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Key Strengths
• Relatively inexpensive
• Quantitative data
• No ionizing radiation
• Good soft tissue contrast
• High-temporal resolution
• Clinically translatable
Key Limitations/Considerations
• Limited depth of penetration
• Primarily anatomical information
• Expanded with the use of
contrast agents
• Limited to imaging soft-tissue only
(no bone or air structures)
21. Photoacoustic
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Key Strengths
• Superior depth of penetration compared
to other optical techniques
• Good temporal resolution
• Clinically translatable
Key Limitations/Considerations
• Limited to imaging soft tissue only (no
bone or air structures)
• Coupling of instrument to subject
required
• Limited anatomical/structural information
Images acquired using Photosound’s TriTom.
23. Bioluminescence/Fluorescence
BLI
• Imaging target must express
a luciferase enzyme
• Appropriate substrate must
be present
FLI
• Appropriate fluorophore
must be selected
• Imaging target must either
express, or contain, the
fluorophore
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26. Dual Energy X-Ray Absorptiometry (DEXA)
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Figure from Luo, Yunhua. 2017. Chapter 3
Parameter
Unit of
Measure
Description
(available on whole animal, or from each ROI)
BMC g Bone Mineral Contents (Bone Mass)
BMC = bone density x bone area
Fat g Fat mass
Fat Ratio % Fat Ratio = Fat/Total Mass
Lean g Fat free mass
Lean Ratio % Lean Ratio = Lean/Total Mass
Total Mass g Total Mass = Fat + Lean + Bone
BMD g/cm2 Bone Mineral Density
Bone Area cm2 Bone Area in Image
Tissue Area cm2 Tissue Area in Image
27. Dual Energy X-Ray Absorptiometry (DEXA)
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Key Strengths
• Rapid scan times
• Whole body imaging is possible
• Very low ionizing rations levels
per scan – allows for longitudinal
imaging
• Clinically translatable
Key Limitations/Considerations
• Provide only 2D images
• Low soft tissue contrast
Images acquired using Osteosys’s iNSiGHT.
29. Intravital Microscopy
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Key Strengths
• Excellent spatial resolution
• Multiplex capabilities
• Dynamic/real-time information about
microscopic cellular events
• Yields quantitative measures
Key Limitations/Considerations
• Poor depth of penetration - Improved
with two photon over confocal
• Small field of view
• Can require multiple laser excitations
• Surgical preparation of models
Images acquired using IVIM Technology’s IVIM.
30. When to use Which Imaging Modality
Primary Considerations
• Feasibility – cost to purchase equipment + infrastructure costs +
running/maintenance costs
• Type of Information – anatomical, functional, molecular
• Imaging Target, Resolution, and Depth Required
Then ask yourself the following
• Do you need to image over time?
• Do you have the ability to engineer cells, what contrast agents do you
have access to?
• Would multimodal imaging be beneficial?
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31. Multimodal/Multiplex Imaging
• Defined
• Use of two or more complimentary imaging modalities, or
contrast/reporting agents used within a single experiment – may be
simultaneously or sequentially
• Goal
• Acquire as much data as possible to tackle a biological question more
holistically then would be possible with a single modality, as well as to
approach the biological question from multiple scale levels
• Purpose
• Elucidate the various biological mechanisms of disease, as well as to fully
understand the response to therapeutic interventions
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