New magnetic resonance imaging methods to contrast agent free cardiac imaging

The doctoral thesis of Elias Ylä-Herttuala, MSc, demonstrates the feasibility of new magnetic resonance imaging relaxation time methods in the diagnostics of myocardial infarction without contrast agents. New relaxation time methods were able to determine both acute and chronic myocardial infarction from the surrounding myocardium with high contrast. New relaxation time methods were also used to image the effect of the lymphatic system to the myocardial infarction scar without any contrast agents.

The public examination of the doctoral dissertation will be held at Kuopio Campus and online on 26 June 2020 starting at 12 noon.

Cardiovascular diseases and ischemic heart diseases are the leading global causes of death. The most common cardiovascular disease is myocardial infarction (MI), which is caused by the occlusion of the coronary arteries preventing the flow of oxygen-rich blood to the myocardium. MI also leads to changes in the lymphatic system, which collects extracellular fluid from the tissues. The lymphatic system controls tissue fluid homeostasis and thus participates in many physiological and pathological processes. Surprisingly, the role of the lymphatic system in the development of MI has been rarely studied and has remained unclear. However, it has been hypothesized that edema increases after the MI in an insufficient lymphatic myocardium and therefore, this can be detected with medical imaging devices. Potentially, the cardiac lymphatic system may have a much more important role in the development of MI than previously believed.

Magnetic resonance imaging (MRI) is a non-invasive medical imaging modality, whose strength is its high soft tissue contrast with high spatial and temporal resolution without subjecting the patient to ionizing radiation. There are numerous ways to generate good contrast in an MR image. These ways are divided mainly into endogenous and exogenous contrasts. MRI is a versatile tool for imaging the heart since it can provide anatomical, functional and pathological information of the myocardial tissue. Traditionally, these approaches have been achieved by applying T1 based anatomical, T2 based edema imaging and the gadolinium-based late gadolinium enhancement (LGE) method to determine the presence of scar tissue in the myocardium.   

The conventional relaxation times, T1 and T2, differ from rotating frame relaxation times (T1r and T2r), where the relaxation occurs during the RF excitation. Both T1r and T2r, have been shown to be more specific than for a fairly narrow range of slow microscopic molecular motions compared to T2. However, T1r and T2r suffer from high tissue heating, which limits their use in the clinic.

A novel rotating frame relaxation time method called relaxation along a fictitious field (RAFF) was recently developed. Subsequently, RAFF has been extended into higher rotating frames, which is designed as RAFF in the rotating frame of rank n (RAFFn). The main reason to adopt higher rotating frames is to reduce tissue heating during the imaging by the tens of percent’s.

The aim of Ylä-Herttuala’s doctoral thesis was to implement RAFFn in cardiac MRI in vivo and apply T1r and RAFFn methods to characterize MI without the need of contrast agents. This is the first time that RAFFn has been applied in heart imaging. Additionally, by exploiting different mouse models, new knowledge about fibrosis detection, and the role of cardiac lymphatic vessels during MI development has been obtained.

The findings of this thesis demonstrate that the characterization of chronic MI can be achieved with T1r mapping. In addition, the research demonstrated the feasibility of using RAFFn to determine the fibrotic MI area in an MI area close to that measured with LGE in mice in vivo. Therefore, RAFFn has the potential to be used in the evaluation of MI without administration of contrast agents. Additionally, the cardiac lymphatic system was found to have an important role during the development of MI; these findings were confirmed by histology. In the future, these new methods may become routine in the diagnosis and treatment of myocardial infarction in clinical medicine.

The doctoral thesis of Elias Ylä-Herttuala, Master of Science, entitled Characterizing myocardial infarction using novel magnetic resonance imaging tools – a comparison between a normal and an insufficient lymphatic circulation will be examined at the Faculty of Health Sciences. The opponent in the public examination will be Professor Gustav Strijkers of the University of Amsterdam and the Custos will be Adjunct Professor Timo Liimatainen of the University of Oulu.

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