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Maisa Kivistö & Katharine Wilding

Introduction

Coronary artery disease (CAD) is the most common national disease in Finland among cancers according to Duodecim (2016). It is a cardiovascular disease which are most burdening the health care. That is why we wanted to focus on the early diagnosis of CAD with non-invasive heart imaging. Furthermore, as using non-invasive imaging methods the patients do not need to undergo invasive procedures which always have greater risks of complications and side-effects. Usually non-invasive methods cost less and are not so risky for the patient.

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The MR contrast agents can have mild side-effects but the radio-isotopes have a rather short half-life so they have hardly any side-effects. Nuclear techniques are for example SPECT (single photon emission computed tomography) and PET (positron emission tomography). In magnetic resolution imaging (MRI) is used contrast agents and this is also the imaging method we are focusing on. These methods are convenient and almost as accurate as the invasive methods and they are constantly developing to become more accurate.


How does it work?

Cardiac Magnetic Resonance Imaging (CMRI) is a well-established form of clinical and functional molecular imaging which is safer for the patient as it is non-invasive and avoids the use of ionizing radiation. Patient lies inside the magnetic resonance tube as the imaging is started. Images are obtained by using a very strong magnetic field, which makes all the hydrogen nuclei (i.e. all protons in the body) react and regulate themselves like tiny magnets. When the protons emit a signal, it is transformed into a visible image with the simultaneous use of radiofrequency pulsations.

A Contrast Agent (CA) can be used to highlight areas of interest. The CA is a fluid containing gadolinium, (an easily magnetized rare metal), which is injected intravenously. Different levels of diffusion of the CA into the cardiac tissue show different areas and stages of damage.

Usability

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and Safety


This technology enables the professionals to see minute structural changes of the heart (eg. inflammatory changes) which aid in the diagnosis. It can be seen if there is an old fibrosis or an ongoing inflammation. In addition to the heart muscle structure the CMRI shows also the condition of heart valves and coronary vessels. As a good image of the heart is seen, the need for an invasive procedure can be re-assessed. However, this machine can be used only in settings which have educated professionals and the machinery is relatively expensive.

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As mentioned previously, one type of iron oxide nanoparticle, Ferumoxytol, (trade name-Feraheme in America, Rienso in Europe) is used as a treatment for anemia in Chronic Kidney Disease and it is thought to be potentially valuable in Cardiac Magnetic Resonance Imaging. However, despite being licensed for use in Europe as Rienso, it was withdrawn from medical use by its manufacturer (Takeda) in 2015, following several serious adverse effects and some deaths. It continues to be administered in America, as Feraheme in its capacity to treat anemia only, but has been subjected to rigorous testing and strongly worded warnings on its packaging.  

Future views and prospects

 

The MRI is based on molecular imaging, where even individual cells or components can be seen. One such cell of interest in cardiac magnetic resonance imaging is the macrophage. Inflammation is found in many cardiovascular conditions such as atherosclerosis, myocardial infarction and heart failure. Macrophages (a type of white blood cell that engulfs and digests anything unrelated to the body in its path) are very important to the inflammatory process, as macrophages both destroy foreign matter in the body and then clear the way for repair work. By imaging macrophages at work, doctors can understand more fully how cardiovascular diseases start, and can also evaluate how severe the condition is in real time. This can aid in diagnostics, prognosis and evaluate efficiency of treatments.

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In relation to cardiac diagnostics and treatment, nanoparticles have several different prospective uses. With the MRI, a large magnetic field can be created which would use the iron oxide nanoparticles to “pull” medication into the cells, a process known as magnetofection. Magnetic targeting, on the other hand, would use the magnetized nanoparticles to break up thrombi (blood clots). The imaging aspect could also make it possible to “track” magnetized cells in the heart in still non-invasive manner and even evaluate cell grafts and cell based therapies. It is also hoped that the medication, Ferumoxytol, may be used to differentiate between acute myocardial inflammation from old myocardial damage, which opens up the possibilities of observing early stages of heart transplant rejection and cardiac tumors.

 

References

 

Alam, S.R., Stirrat, C., Richards, J., Mirsadraee, S., Semple, S.I.,  Tse, G.,  Henriksen, P., Newby, D.E. 2015. Vascular and plaque imaging with ultrasmall superparamagnetic particles of iron oxide. [Review] Journal of Cardiovascular Magnetic Resonance. 17:83, 2015 Sep 18.

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