The year 2007 has been very busy on the new 3T whole-body scanner, with the acceptance tests and, in parallel, the definition and optimisation of a number of protocols for advanced and quantitative NMR imaging of skeletal muscle. This is a crucial step and robust high-quality imaging schemes have to proposed to our clinical partners if NMR imaging is to play a pivotal role in the evaluation of muscular disorders therapeutic trials.
Protocols have been defined and optimized for the entire coverage of the lower limbs, with contiguous slices, using T1-weighted and T2-weighted fat-saturated spin echo sequences. In addition, on a selected 3D slab, quantitative analysis of muscle composition (muscle, fat, fibrosis) based on a series of frequency selective gradient echo acquisitions.
Fat selective (left) and water selective (right) imaging of the thighs in a normal subject
NMR imaging at 3T is currently an integral part of the evaluation tools for the clinical research protocols at the Institute of Myology: the AAV based gene therapy phase one trial of gamma-sarcoglycanopathy patients, the natural history study of Pompe disease.
Grade 3+ fatty replacement
in the legs of a Pompe patient
The GRMD (Golden Retriever Muscular Dystrophy) dog is a most valuable model for pre-clinical investigation of novel therapeutic approaches of Duchenne disease. The NMR characterization of the GRMD dogs is a field of active collaboration with the ENVA (S. Blot, J.L. Thibaud).
Fat-saturated T2-weigthed SE imaging
in a normal (left panel) and in aGRMD dog
(right panel)
A number of NMR imaging indices have been identified that allows non-invasive characterization of muscle involvement in this disease. Preliminary results suggest that these indices might be used as markers of positive response to treatment, as indicated by the first data obtained on dogs treated with AAV mediated exon-skipping in L. Garcia’s group.
Cardiac investigations are also within the scope of our activities. The head of the lab is an expert in cardiovascular NMR lab and strong ties are being established with leading clinical cardiology groups. The focus will be on cardiomyopathies, particularly but not exclusively those developing in muscular dystrophy patients, with the aim of assessing myocardial perfusion, viability and sub-segmental contractility. As an example here below, very high quality images of the cardiac fibro-inflammatory involvement in a case of systemic vascularitis.
On the left image, white arrows pointing to the fibro-inflammatory lesions revealed
by late Gd-enhancement and on the right image, arrow pointing to pericardial effusion.
3-pt Dixon methods
Although routine T1w imaging can give an indication of the presence or absence of muscular fat infiltration, it is difficult to extract fully quantitative data from these images, due to the background signal of normal muscle, as well as image inhomogeneities. It is difficult to compare such images between different centres because of the use of different magnets and radio frequency hardware, and they are also difficult to use in longitudinal studies.
3-point Dixon methods circumvent some of these problems by acquiring three echoes at different echo times, permitting variations in the main magnetic field across the image to be taken into account. The chemical shift between water and fat is exploited to generate separate fat and water images.
