physics

Preclinical imaging

Preclinical imaging is a physics topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Preclinical imaging rather than just read about it. In short: Preclinical imaging is the visualization of living animals for research purposes, such as drug development. Imaging modalities have long been crucial to the researcher in observing changes, either at the organ, tissue, cell, or molecular level, in animals responding to physiological or environmental changes.

Key takeaways

Preclinical imaging belongs to physics; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Preclinical imaging to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Preclinical imaging from memory before moving on to harder problems.

Reference excerpt

Preclinical imaging is the visualization of living animals for research purposes, such as drug development. Imaging modalities have long been crucial to the researcher in observing changes, either at the organ, tissue, cell, or molecular level, in animals responding to physiological or environmental changes. Imaging modalities that are non-invasive and in vivo have become especially important to study animal models longitudinally. Broadly speaking, these imaging systems can be categorized into primarily morphological/anatomical and primarily molecular imaging techniques. Techniques such as high-frequency micro-ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) are usually used for anatomical imaging, while optical imaging (fluorescence and bioluminescence), positron emission tomography (PET), and single photon emission computed tomography (SPECT) are usually used for molecular visualizations. These days, many manufacturers provide multi-modal systems combining the advantages of anatomical modalities such as CT and MR with the functional imaging of PET and SPECT. As in the clinical market, common combinations are SPECT/CT, PET/CT and PET/MR.

Micro-ultrasound Principle: High-frequency micro-ultrasound works through the generation of harmless sound waves from transducers into living systems. As the sound waves propagate through tissue, they are reflected back and picked up by the transducer, and can then be translated into 2D and 3D images. Micro-ultrasound is specifically developed for small animal research, with frequencies ranging from 15 MHz to 80 MHz. Strengths: Micro-ultrasound is the only real-time imaging modality per se, capturing data at up to 1000 frames per second. This means that not only is it more than capable of visualizing blood flow in vivo, it can even be used to study high speed events such as blood flow and cardiac function in mice. Micro-ultrasound systems are portable, do not require any dedicated facilities, and is extremely cost-effective compared to other systems. It also does not run the risk of confounding results through side-effects of radiation. Currently, imaging of up to 30 μm is possible, allowing the visualization of tiny vasculature in cancer angiogenesis. To image capillaries, this resolution can be further increased to 3–5 μm with the injection of microbubble contrast agents. Furthermore, microbubbles can be conjugated to markers such as activated glycoprotein IIb/IIIa (GPIIb/IIIa) receptors on platelets and clots, αvβ3 integrin, as well as vascular endothelial growth factor receptors (VEGFR), in order to provide molecular visualization. Thus, it is capable of a wide range of applications that can only be achieved through dual imaging modalities such as micro-MRI/PET. Micro-ultrasound devices have unique properties pertaining to an ultrasound research interface, where users of these devices get access to raw data typically unavailable on most commercial ultrasound (micro and non-micro) systems. Weaknesses: Unlike micro-MRI, micro-CT, micro-PET, and micro-SPECT, micro-ultrasound has a limited depth of penetration. As frequency increases (and so does resolution), maximum imaging depth decreases. Typically, micro-ultrasound can image tissue of around 3 cm below the skin, and this is more than sufficient for small animals such as mice. The performance of ultrasound imaging is often perceived as to be linked with the experience and skills of the operator. However, this is changing rapidly as systems are being designed into user-friendly devices that produce highly reproducible results. One other potential disadvantage of micro-ultrasound is that the targeted microbubble contrast agents cannot diffuse out of vasculature, even in tumors. However, this may actually be advantageous for applications such as tumor perfusion and angiogenesis imaging. Cancer Research: The advances in micro-ultrasound has been able to aid cancer research in a plethora of ways. For example, researchers can easily quantify tumor size in two and three dimensions. Not only so, blood flow speed and direction can also be observed through ultrasound. Furthermore, micro-ultrasound can be used to detect and quantify cardiotoxicity in response to anti-tumor therapy, since it is the only imaging modality that has instantaneous image acquisition. Because of its real-time nature, micro-ultrasound can also guide micro-injections of drugs, stem cells, etc. into small animals without the need for surgical intervention. Contrast agents can be injected into the animal to perform real-time tumor perfusion and targeted molecular imaging and quantification of biomarkers. Recently, micro-ultrasound has even been shown to be an effective method of gene delivery.

Functional ultrasound brain imaging Unlike conventional micro-ultrasound device with limited blood-flow sensitivity, dedicated real-time ultra fast ultrasound scanners with appropriate sequence and processing have been shown to be able to capture very subtle hemodynamic changes in the brain of small animals in real-time. This data can then be used to infer neuronal activity through the neurovascular coupling. The functional ultrasound imaging (fUS) technique can be seen as an analogue to functional magnetic resonance imaging (fMRI). fUS can be used for brain angiography, brain functional activity mapping, brain functional connectivity from mice to primates including awake animals.

… excerpt ends here. Continue reading the full article.

Illustrations

Preclinical imaging: High resolution 99mTc-MDP mouse SPECT scan: animated image of rotating maximum intensity projections. — High resolution 99mTc-MDP mouse SPECT scan: animated image of rotating maximum intensity projections.

Worked examples

Example 1 — a first encounter with Preclinical imaging

Start with the simplest possible case. Write down what Preclinical imaging claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In physics, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Preclinical imaging before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Preclinical imaging ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Preclinical imaging

In research: Preclinical imaging appears in physics research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Preclinical imaging in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Preclinical imaging is common in secondary-school and first-year university syllabi. It links to neighbouring topics Imaging, Medical imaging, Medical physics, so understanding it makes those chapters shorter.
In everyday life: Look for Preclinical imaging outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Preclinical imaging in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Preclinical imaging means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Preclinical imaging out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Preclinical imaging in simple terms?

Why does Preclinical imaging matter?

Because it connects several physics ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Preclinical imaging?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Preclinical imaging.