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Imaging techniques present a very popular and easy way of quickly and non-invasively monitoring diseases. In the hospitals, these are often the first tests that physicians prescribe, before concluding on a medical decision.

The main imaging technologies used in clinics are Computed Tomography (CT), Positron Emission Tomography (PET), Single Photon Emission (SPECT), Magnetic Resonance Imaging (MRI) and Ultrasound (US). All these modalities are also used in basic and translational research, where two more methods are added – currently not or very little translated to humans, but able to provide important and straightforward information: Optical Imaging (OI) and Photo Acoustic imaging (PAI). So, how do these technologies work and what do they provide?

A combination of CT and SPECT imaging in basic research: preclinical studies to follow the fate of a novel contrast agent in an organism after intra-muscular injection. The clearance of the substance through the kidneys is monitored anatomically and functionally, and quantified, in a non-invasive way. Image from the nTRACK project.

Computed Tomography (TC) is probably the most popular and fast imaging test. It is based on the different absorption and density that organs present, and this results in black-and-white images with high-resolution anatomical information. Soft tissues are hard to discriminate, but lungs, bone, some tumours and heart diseases or liver masses are demonstrated in an excellent way, especially when contrast agents are also introduced. CT presents a technology with a non-negligible radiation risk, so its use should always be justified.

The second most popular imaging test is Magnetic Resonance Imaging (MRI). Again, this modality provides excellent anatomical images, but this time soft tissues, internal organs and the brain can be differentiated very clearly. In addition, in this modality contrast agents are also used to improve contrast and learn more about the abnormalities or physiological functionalities of certain organs With MRI bone is more challenging to image, as this technique is based on the magnetic alignments of different atoms inside a magnetic field to generate images. An added advantage is that it does not use radiation, so it is a radiation risk-free test.

Positron Emission Tomography (PET) and Single-Photon Emission Tomography (SPECT) are radionuclide-based molecular imaging techniques that can show biochemical alterations and function of diverse organs such as brain, liver, heart, kidney and lung. They provide valuable information in translational research and clinical assessment by using radioactive isotope-labelled compounds addressed to in vivo show specific biological targets, metabolic pathways or cell tracking of cells. Both techniques have limitless depth of penetration, but limited resolution. Their big advantage is the high sensitivity – i.e., even small amounts or structures can be easily traced. Despite these techniques are emerging, currently is a necessary tool for several medical disciplines of cardiology, oncology, neurology and endocrinology, among others as well as in drug discovery and development. 

PET
SPECT

Ultrasound (US) is an imaging tool that exploits the properties of high-frequency sound waves as they travel through biological tissue, to create mostly anatomical images. It is widely used to image soft tissues and its main strength is the high sensitivity, fast imaging and no use of radiation. PAI is the production of sound waves resulting from the absorption of light. It has the potential to facilitate the investigation of anatomical and biochemical features of both normal and disease states in living subjects in a non-invasive way and again mostly for imaging soft tissues. However, this technique has some limitations such as the low penetrability of the waves, their dispersion and the dependence on the radiologist who performs the assessment.

Optical Imaging (OI) allows the visualization of cells and tissues using light in basic research and diagnostic imaging. Detection is possible after recording the light emission from irradiated probes incorporated into a body and addressed to specific biological targets. It involves the detection of low-energy photons, as opposed to high-energy gamma rays detected by PET and SPECT, so it is considered relatively safe. However, the use of low-energy photons means that the depth of penetration is limited. It is widely used in basic cancer research and in drug research, due to its simplicity and fast imaging capability. In clinics, its use is limited to the ophthalmology, dermatology and surgery areas.

The basic features of the dominant imaging technologies. Figure from DOI:10.1088/0031-9155/60/14/R239

From this analysis, it becomes clear that all imaging technologies present both strengths and limitations, especially when used one-a-time. By combining different imaging techniques, collective results can be achieved that present unparallel cumulative strength. The nTRACK project is taking advantage of all these imaging modalities (CT, SPECT, PET and MRI) to allow the visualization and tracking of cell-based therapies. Cell-based therapies are a real and promising therapeutic option to treat many diseases and injuries that conventional therapies cannot heal. However, the prediction of the success or failure of cell therapy is challenged by the current lack of methods to “see” these cells at different time-points: do the cells remain at the injection site? Do the cells move to another location? How long the cells are alive?

The nTRACK project is currently investigating the visualization and longitudinal monitoring of the transplanted stem cells in real time. The nTRACK nanoparticles enhances the various strengths of all mentioned imaging technologies to overcome the limitations of each independent imaging system aiming its clinical translation.

A graphical representation of the nTRACK GNPs, that combine the best properties of CT, MRI and SPECT/PET imaging

For further information on imaging technologies, we recommend the following videos:

How do MRI, PET and CT scans work?

The Evolution of Medical Imaging for Cancer Care (IAEA)

An example of Radionuclide imaging in basic research: