Preclinical Imaging:
Modalities Overview

Preclinical Imaging Modalities Used in Research

As we begin to explore the idea of multimodal imaging, let’s first start to explore the variety of preclinical imaging modalities that are most commonly used by researchers around the world. Many of the imaging modalities used in the clinic have been adapted for preclinical use with a focus on working with mice, rats, as well as some other species such as guinea pigs, hamsters, rabbits and even zebrafish, birds, ferrets, etc. These imaging modalities include MRI (magnetic resonance imaging), PET (positron emission tomography), CT (computed tomography), ultrasound (US), fluorescence (FLI), and DEXA (dual energy x-ray absorptiometry). While other imaging modalities are focused mostly on preclinical imaging to help understand the underlying mechanisms of disease, but are not necessarily directly translatable to the clinic, including bioluminescence (BLI) and intravital microscopy (IVM). While some still are newer to both clinical and preclinical research, but continue to advance over time, such as photoacoustic imaging (PAI). 

Modality: Sensitivity vs. Resolution

Each modality has its own strengths and weaknesses, and this may also include areas where they are more commonly used in preclinical research. However, in general, the use of more than one complimentary imaging modality would allow researchers to further elucidate molecular and biological mechanisms of disease, and to explore the response to a variety of therapeutic interventions. When considering an imaging modality, one must consider what is being imaged – i.e., soft tissue, bone, endogenous or exogenous contrast agents, etc. Additionally, resolution, radiation exposure, imaging time, and need for genetic manipulation or injection of additional agents are all factors that should be considered when designing an imaging experiment.

Finally, complimentary modalities should be selected as to not provide redundancy, but to augment the information to include as many of the following as possible – anatomical, morphological, functional and/or molecular data. Overall, the goal should be to provide a composite of complimentary information about a specific disease model over time; providing as much spatial and temporal information about a specific process as possible by developing a mechanistic understanding of the model at the whole body, organ, and/or cellular level. 

Modality Summary

Modality Comparision

Modality Resolution Advantages Limitations Applications

MRI

~100µm
– Non-ionizing radiation
– Whole body imaging is possible
– Excellent soft tissue contrast
– Clinical translation
– Some systems are expensive and high maintenance costs
**Note M-Series compact MRI does not have these limitations
– No bone contrast
– Cancer Biology
– Neurology
– Organ Imaging
– Cardiac Imaging
– Contrast Agent Imaging

CT

≤50µm
– Whole body imaging is possible
– Excellent bone imaging
– Clinical translation
– Ionizing radiation
– Low soft tissue contrast
– Bone Imaging
– Anatomical Reference for Other Imaging Modalities

PET

~1mm
– Whole body imaging is possible
– High sensitivity to agents used
– Quantifiable data
– Wide variety of applications, based on imaging agents used
– Clinical translation
– Radioactive agents are required
– Specialized infrastructure required
– Proximity to cyclotron, more important for short half-life molecules
– Cancer Biology
– Neurology
– Cardiac Imaging
– Pharmacokinetics and Pharmacodynamic Imaging

Ultrasound

~30-50µm
– High temporal and spatial resolution
– Good soft tissue contrast
– Non-ionizing radiation
– Clinical translation
– Depth of penetration vs resolution
– Operator dependent
– Cancer Biology
– Organ Imaging
– Cardiac Imaging
– Vascular Imaging
– Developmental Biology
– Contrast Agent Imaging

Optical
Imaging

~1mm
– Non-Ionizing radiation
– Whole body imaging is possible
– High throughput
– Wide variety of applications depending on agent used
– Ease of use
– Limited tissue penetration for some photons
– Low spatial resolution
– Semi-quantitative
– Cancer Biology
– Cell Trafficking
– Gene Expression

Photoacoustic
Imaging
(PAI)

~300um
– Whole body imaging is possible
– Penetration depth
– Endogenous and exogenous contrast
– Anatomical & structural information
– Cancer Biology
– Neurology
– Developmental Biology
– Contrast Agent Imaging
– Angiograph

Intravital Microscopy
(IVM)

~1µm
– Multiplex imaging capabilities
– Microscopic resolution
– Dynamic imaging allowing for live cell and molecule tracking
– Wide variety of applications
– Depth of penetration
– Small field of view
– Surgical preparation to access imaging target
– Cancer Biology
– Neurology
– Cardiac Imaging
– Vascular Imaging
– Organ Imaging
– Musculoskeletal Imaging
– Cell Tracking

DEXA/DXA 

~100µm for DEXA
~30µm for highest magnification digital radiography image
– Rapid scan times
– Whole body imaging is possible
– Bone mineral density/content measurements provided
– Lean vs. fat mass measured
– Very low ionizing radiation level per scan, allowing for longitudinal imaging
– Clinical translation
– Images are 2D
– Low soft tissue contrast
– Bone Imaging
– Body Composition Measurements
– Digital Radiography

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