Tracking Exosomes by Computed Tomography

Exosomes are lipid bilayer vesicles released by cells and are natural carriers of intercellular communication. They are 30-150nm and carry biologically active molecules such as proteins, lipids, RNA, and DNA, which play essential roles in many physiological and pathological processes. Research has found that exosomes can be used as biomarkers to diagnose diseases and monitor the effects of treatment.

Figure 1. Pathway of exosome secretion and internalization in the human body for diagnostic and therapeutic purposes. (Lorenc T, et al., 2020)

Imaging of exosomes will help to better understand their biological functions and potential as therapeutic and drug-delivery vehicles. To elucidate exosome-mediated cellular communication and to visualize biodistribution in vivo, various strategies have been developed to label and track exosomes. Among the imaging modalities, optical imaging has been widely used. However, its ability to visualize in depth is limited. In recent years, researchers using computed tomography (CT), a non-invasive imaging method, can take images of deep structures in vivo, which can help in exosome tracking and further understanding of exosome uptake mechanisms, biodistribution, migration, function, and therapeutic properties.

What is the CT Technology?

CT is a computerized X-ray imaging process that uses the absorption properties of samples to obtain structural information about the interior of biological tissues and engineered materials without destroying the sample. During the CT scanning process, a narrow beam of X-rays is aimed at the sample and rotated rapidly, generating signals that are processed by a machine computer to produce cross-sectional images or "slices". ". These tomographic images can provide clinicians with more detailed information than traditional X-rays. Once the computer has collected multiple consecutive slices, the slices can be digitally "stacked" together to form a three-dimensional (3D) image, making it easier to identify underlying structures and possible tumors or abnormalities.

Figure 2. CT scanner systems that are currently available for dual-energy/spectral imaging. (So A, Nicolaou S, 2021)

What is the Imaging Principle of CT?

CT uses X-rays to scan a layer of a certain thickness. The X-rays transmitted through the layer are received by a detector, converted into visible light, and then converted into electrical signals by an analog/digital converter, which is then converted into digital signals and fed into a computer for processing. The selected layer is divided into several rectangles of the same volume, called voxels. The information from the scan is calculated to obtain the X-ray attenuation or absorption coefficient for each voxel, which is then arranged into a digital matrix. The digital matrix is converted by a digital/analog converter into small black-to-white squares, called pixels, which are arranged in a matrix to form the CT image.

Figure 3. Schematic of the imaging principle of CT. (Popov O, et al., 2020)

What are the Components of a CT Device?

1. The scanning part consists of the X-ray tube, detector, and scanning frame.

2. Computer system: Stores and calculates the information data collected from the scan.

3. Image display and storage system: The images processed and reconstructed by the computer are displayed on a TV screen or captured by a multi-frame/laser camera.

What are the Types of CT Scans?

Plain CT scan - A plain CT scan is a normal scan without contrast enhancement or contrast.

Contrast enhancement - Contrast enhancement refers to the method of injecting water-soluble organic iodine through a vein using a high-pressure syringe and then scanning. The increased iodine concentration creates a density difference, which may result in a clearer image.

Contrast scanning - Contrast scanning is a method in which an organ or structure is first visualized and then scanned.

What are the Prerequisites for Using CT to Track Exosomes?

CT is a non-invasive imaging method that can take images of deep structures in the body, which helps in exosome tracking in vivo. However, exosomes cannot be detected directly by CT and must be labeled with a CT contrast agent. The contrast agent contains substances that block X-rays and are more visible in the image. Advances in nanotechnology have made it possible to label exosomes using nanoscale, ultra-small gold nanoparticles (GNPs). GNP are ideal contrast agents for in vivo CT imaging and exosome tracking due to their strong X-ray attenuation, high flexibility in coating and targeting functional groups, non-toxicity in vivo, and biocompatibility.

Advances in Using CT to Track Exosomes

Acute myocardial infarction (MI) is the leading cause of cardiovascular disease. Mesenchymal stem cell-derived exosomes (MSC-Exo) have been reported to improve cardiac function after MI. In vivo imaging can reveal the transport process and biodistribution of exosomes, contributing to a deeper understanding of the communication mechanism and pharmacokinetics of exosomes. MSC-Exo is labeled using glucose-modified GNP and visualized by in vivo CT imaging. The results showed that MSC-Exo is retained in the MI region for a longer period after intramyocardial injection, suggesting that they could be used to improve post-infarction cardiac function.

Figure 4. CT MSC-Exo in vivo CT imaging after injection. (Gong L, et al., 2021)

Spectral Photon Counting Computed Tomography (SPCCT) represents a breakthrough advancement in X-ray imaging technology. Using photon counting detectors, SPCCT accurately counts the number of incident X-ray photons and measures the energy. SPCCT increases the contrast between different tissues, removes electronic noise, and corrects for beam-hardening artifacts, providing valuable insight into the composition, concentration, and distribution of specific elements. SPCCT facilitates the quantitative assessment of elements with specific energy thresholds in the diagnostic energy range. SPCCT has been found to support studies of myocardial blood perfusion and enhance tissue characterization and contrast agent identification in ways not previously possible.

Figure 5. Photon-counting detectors convert X-rays into electrical signals. (Meloni A, et al., 2024)

Our Products

In addition to our one-stop exosome service, we offer a range of high-purity exosome products for clients' research.

As a leading company in the field of biology, Creative Biostructure focuses on providing cutting-edge exosome-tracking services utilizing CT technology. We can provide detailed visualization and tracking of exosomes to facilitate critical research and medical advancements. We strive to provide clients with convenient and high-quality solutions for exosome research. If you are interested in our services and products, please feel free to contact us for a formal quote.

References

1. Lorenc T, et al. Current Perspectives on Clinical Use of Exosomes as a Personalized Contrast Media and Theranostics. Cancers (Basel). 2020. 12(11): 3386.
2. So A, Nicolaou S. Spectral Computed Tomography: Fundamental Principles and Recent Developments. Korean J Radiol. 2021. 22(1): 86-96.
3. Popov O, et al. Quantitative Microstructural Analysis and X-ray Computed Tomography of Ores and Rocks—Comparison of Results. Minerals. 2020. 10(2): 129.
4. Gong L, et al. In vivo CT imaging of gold nanoparticle-labeled exosomes in a myocardial infarction mouse model. Ann Transl Med. 2021. 9(6): 504.
5. Meloni A, et al. Spectral Photon-Counting Computed Tomography: Technical Principles and Applications in the Assessment of Cardiovascular Diseases. Journal of Clinical Medicine. 2024. 13(8): 2359.