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BIA-Brukerstyrt innovasjonsarena

Manganese-enhanced MRI in Heart Failure

Alternative title: Mangan som kontrastmiddel for MRI diagnostikk i hjertesvikt

Awarded: NOK 15.6 mill.

Project Number:


Project Period:

2021 - 2025

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IC Targets AS has patented the use of a contrast agent based on Manganese (Mn) for Magnetic Resonance Imaging (MRI). Most MRI contrast agents are based on Gadolinium (Gd), a metal from the Lanthanide family. Both metals must be inserted into a chelate before they can be used in humans to enhance MR signals for better presentations of organs or disease processes. This is necessary to protect the cells in the body against possible side effects that metals may cause. There is a significant difference between Gd and Mn: Gd is completely alien to the human body, while Mn behaves much like Calcium (Ca), present in many organs providing pathways to take care of it once its job is done. Mn-ions can strengthen MRI signals like Gd. Ca plays an important role in the heart where is a key element in the pumping function of the heart. Deterioration of pumping is a key indicator when patients get diseases which increase the work load. This may lead to a condition called Heart Failure (HF). It can be difficult to measure when the heart is beginning to fail due to a slowly increasing workload. Examination by invasive procedures such as catheterization may be required for a conclusive diagnosis. However, diagnosis may be inconclusive even with the catheterization, which may suggest that function is normal. This category of heart disease is often referred to as HFpEF (“HefPef”) or Heart Failure with preserved Ejection Fraction. Pump function is reduced, but it is not visible with current diagnostics. This may be enabled by MRI enhanced with mangafodipir, which is taken up into the cells of the heart via the Ca-channels. Once inside Mn-ions bind to cellular proteins which slow down the tumbling rate of the Mn-ions, thereby increasing the influence on protons which are key signal givers for the MRI scanner. In this RCN supported project IC-T and our partner Oslo University Hospital will carry out a first study in patients to verify that mangafodipir works in patients with HFpEF.

Mangafodipir is the only approved manganese-containing Magnetic Resonance Imaging contrast agent and is a semi-stable entity releasing Mn2+ ions in blood. Mn2+ ions enter cardiomyocytes through L-Type Calcium channels in proportion to calcium flux. IC-T and Oslo University Hospital aim with this project to develop a novel method for tracer kinetic analysis with T1-mapping in MRI for quantitative measurements of the two determinants of myocardial stiffness in patients with Heart Failure with preserved Ejection Fraction (HFpEF); cardiomyocyte calcium uptake and extracellular volume fraction as an indicator of myocardial fibrosis. A proof of concept study will be performed in patients with diabetic and non-diabetic HFpEF. This may allow, for the first time, to characterize different phenotypes of HFpEF and enable selection and monitoring of specific therapies when these become available. This will initiate a paradigm shift in the management of HFpEF patients and open a large new market for contrast enhanced cardiac MRI and create business opportunities for MRI software companies. IC TARGETS (IC-T) has in-licensed intellectual property rights for mangafodipir from GE HealthCare, who has marketed the product under the tradename Teslascan® for liver and pancreas imaging in the past. In addition, IC-T has obtained granted patents for mangafodipir within the cardiac field. HFpEF patients represent an enormous cost for the health care system. The prevalence of HFpEF exceeds 8 % of persons older than 65 years of age and because of the current pandemic of obesity, the prevalence of HFpEF in persons younger than 65 years of age is rising exponentially. The challenge for the future lies in raised awareness of this devastating disease, improved patient stratification and development of stage-specific therapies. IC-T aims with our novel pathology-specific method to meet this societal challenge which is very relevant for UNs 3rd sustainability goal "Good health and well-being".

Funding scheme:

BIA-Brukerstyrt innovasjonsarena