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CMR of molecular changes

Using MRI to track molecular changes holds clinical promise across diverse cardiac pathologies

Non-invasive Imaging: Magnetic Resonance Imaging

Friday’s session on the CMR of molecular changes highlighted the cutting edge of molecular imaging and the diverse possibilities for its application in clinical medicine.

Dr van Heeswijk began with the Flourine - 19 isotope, which can be used as a target molecule for MRI. It is safe, inert and not normally present within the human body, and can be pharmacologically introduced using perflourocarbons.
It is readily taken up by immune cells, thereby allowing a highly specific means of monitoring inflammation over time.
Ligands can be added to liposomes containing PFC which helps direct them to specific cells, like dendritic cells in the brain and human myocardial progenitor cells.
Potential applications include monitoring myocardial changes following infarction, or tracking neoplastic cells, such as in colo
rectal cancer.
The use of newer molecules with higher fluorine loading may offer further potential in the future.

Dr Alam described MR imaging with USPIO (Ultrasmall Superparamagnetic Iron Oxide particles), a non - invasive, quantitative imaging modality which can be used to detect inflammation in infarcted myocardial tissue and in patients following CABG.
He went on to highlight two exciting future studies on the horizon:
- the ‘IRONMAN’ study, using iron nanoparticle enhanced MRI in the assessment of myocardial infarction ; and
- the DECIFER - HEART study, using Ferumoytol to detect cellular inflammation in cases of myocarditis, heart transplant and cardiac sarcoidosis.

Dr Karamitsos introduced the use of oxygenation - sensitive CMR as a novel non-contrast technique that allows the non-invasive assessment of myocardial oxygenation.
Due to changes in proton signals relative to blood oxygen levels, deoxygenated hemoglobin in blood can act as an intrinsic contrast agent.
Increases in O2 saturation increase the BOLD (blood oxygen level) imaging signal (T2 or T2*), whereas decreases diminish it.
Not only has this technique proved valuable in patients with epicardial coronary artery disease but it has also shown interesting insights in micro-vascular coronary dysfunction.
There is still a need to apply this to multicenter trials and to generate meaningful outcome data.

Dr Malloy focused on Carbon-13, a naturally occurring isotope that can be imaged using MRI.
Using a process of hyperpolarization the nuclear spin can be polarized beyond thermal equilibrium, thereby increasing the SNR during MRI and effectively “tagging ” the molecule.
Pyruvate is an important metabolite that can be tagged with
hyperpolarized C13 and used to monitor metabolic processes in the heart.
A major challenge is ensuring a consistent rate of pyruvate uptake by the myocardium despite variations in the patient’s fasting state.
The rate of metabolism of hyperpolarized pyruvate to CO2 relative to lactate may prove to be a useful indicator of mitochondrial function, providing a specific signal of viable myocardium and facilitating the selection of patients who will benefit from intervention.

Dr Sosnovik described how the role of molecular imaging in enhancing the understanding of myocardial injury and repair is rapidly expanding. Apoptosis, necrosis, macrophage infiltration,
myeloperoxidase activity, cathepsin activity, and type 1 collagen have all been imaged in vivo with a magneto fluorescent (MRI and/or fluorescence) approach.
For example Anx-CLIO can be used to target apoptotic cells
at the borderline zone of an infarct and Gd-TO (Thiosyl Orange) can be used as a marker of necrosis.

More widespread use of molecular MRI will be driven by several factors, including the increasing use of cardiovascular MRI in clinical environments, and the development of more complex and individualised therapies for cardiovascular disease that may benefit from specific metabolic monitoring strategies.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.