The expertise of the NMR laboratory used to monitor the growth of a patient’s heart

Benjamin Marty is co-leader of the NMR and Spectroscopy Laboratory at the Institute’s  Neuromuscular Investigation Center. Together with Yves Fromes, also a researcher in this NMR lab, they just published an article* in The Lancet, in collaboration with Prof Kamenicky, describing the longitudinal muscular (skeletal and cardiac) exploration of a patient with hypopituitary dwarfism treated by gradual hormone replacement in adulthood. Interview with Benjamin Marty.

How did you come to carry out MRI investigations on this patient?

This patient, a 24-year-old man (1.37 m, 26 kg), was referred to us by Professor Kamenicky. He suffers from hypo-pituitary dwarfism, which means that his pituitary gland does not secrete enough hormones, in particular growth hormone. We met with him to take stock of his muscular and cardiac condition before starting treatment. We observed that he had the heart and muscles of a healthy child under the age of 10, in keeping with his clinical and morphological condition.

The question was whether, by administering hormone treatment, the heart would also grow, bearing in mind that heart cells do not multiply in adulthood. Different hormones** were gradually introduced, with periods of several months between each new hormone, and between each intervention we carried out a cardiac and muscular MRI to see how the heart and muscles reacted.

What methods did you use?

To characterise this patient, we used all the quantitative methods that we have developed over the years in the laboratory and that we apply in our clinical protocols, which tend to focus on neuromuscular diseases.

As far as cardiac exploration is concerned, we have at our disposal the very best that is currently available in the clinic, techniques that are around ten years old but have been in clinical use for the last 4 or 5 years.

Until now, we have carried out cross-sectional studies on cohorts of children and adults, but this is the first time we have carried out a longitudinal investigation on a patient moving from the childhood stage to the adult stage.

What were the results?

We monitored him for 4 years, during this time he grew by 24 centimetres and had a “normal” puberty at the age of 40. We have shown that this patient’s heart developed like a normal heart, growing, enlarging and gaining mass in an extremely linear fashion over the course of his treatment, and that his cardiac function was not altered at all over the 4 years. He grew at an accelerated rate, 25 years behind schedule, while retaining the function he was supposed to have. This is the first time such a situation has been described.

Based on our methods, we looked at the structure of the cardiac tissue using MRI to identify its characteristics and we showed that it was the myocardial cells that had grown. The hypotrophy of the muscle cells was therefore corrected.

We also looked at the muscular skeletal structure. Images taken of the thighs have been appended to the article, which also show an increase in mass and volume. In addition, we observed a reduction in inflammation over the course of the treatment, as well as a normalisation of virtually all the parameters measured by MRI over time.

What did you conclude?

In this study, we demonstrated that the methods we developed for MNM are applicable to other pathologies.

We also demonstrated the sensitivity of our methods to changes due to therapeutic interventions on a single individual. We have variations in most of the parameters that can be measured by MRI, which is the sensitivity to response to treatment.

What are the next steps?

We are constantly refining our methods to examine more specifically, more sensitively and earlier.

Earlier: in MNM, the diseased muscle atrophies and is replaced by fat. This replacement damage is clearly visible on MRI. As we don’t know how to reverse this process, the idea is to develop methods to detect before the muscle deteriorates that something is wrong (e.g. the inflammatory aspect, ion homeostasis, pH deregulation, altered metabolism).

More sensitive: because the parameter we are looking at has to be sensitive to the disease.

More specific: because the parameters measured by NMR are magnetic (relaxation time T1 or T2 which is linked to the mobility of the water molecules in the tissue observed) and therefore relate to the magnetic properties of the tissue. We therefore need to make the link between the magnetic parameters and the alteration in the tissue, and understand what this means from a pathophysiological point of view.

The laboratory is therefore developing a number of increasingly effective methods aimed at characterising the structure of muscle in great detail, whether skeletal or cardiac. The aim is to monitor changes in a patient’s muscular and cardiac condition over time in response to treatment, whatever the disease. We are one of the few laboratories in France able to monitor both skeletal and cardiac muscle.


* Fromes Y, Chasseloup F, Bouvattier C, Creze M, Trabado S, Young J, Chanson P, Marty B, Kamenický P. Growing heart in congenital hypopituitarism treated in adulthood. Lancet. 2023 Oct 28;402(10412):1562-1563. doi: 10.1016/S0140-6736(23)02022-6. PMID: 37898533.


** Treatment consisted of administering hydrocortisone to restore cortisol levels, then levothyroxine to improve thyroid function, then growth hormones to stimulate growth, and finally gonadotropics to trigger puberty.