Highlights:

1. Novel imaging MRI techniques to assess bone quality.

2. MR-based methods to image sarcopenia and muscle function.

Target audience: MDs, PhDs and students with interest in bone and muscle research.

Objectives:

The learner will understand the role and limitations of quantitative MR-based techniques for clinical imaging of bone, bone marrow and muscle. These will include high resolution, morphological MRI, UTE, chemical shift-based fat quantification techniques, T2 relaxation time measurements, BOLD MRI and MRS.

Purpose:

1. To present quantitative MRI techniques that measure bone quality and strength and can be used clinically.

2. To provide an overview of novel MR technologies used to characterize muscle structure and function.

Methods:

1. MR Techniques for Assessing Bone Quality and Strength:

While bone mineral density (BMD) measurements are well established they only incompletely capture bone strength. BMD measurements also have shown limitations in monitoring therapy, predicting fracture risk and differentiating individuals with and without fractures. These entities of bone which are not assessed with BMD have been defined as bone quality, a term which was initially coined by the NIH Consensus Development Panel on Osteoporosis Prevention in 2000 (1). In the last 20 years multiple MRI based technologies and sequences to characterize bone quality have been developed. The most important techniques are (a) high resolution MRI to visualize bone architecture, (b) ultra short TE (echo time) (UTE) sequences to quantify cortical bone water and (c) spectroscopic techniques (MRS) to analyze bone marrow composition such as the degree of bone marrow fat.

High resolution MRI

Early clinical studies demonstrated that structure measures derived from high resolution images of the distal radius, distal tibia and calcaneus provided additional information to BMD in differentiating individuals with and without fragility fractures (2-4). In addition to post-menopausal women trabecular bone architecture was studied with MRI in hypogonadal men (5), patients with cardiac and renal transplants (6, 7) as well as patients with renal osteodystrophy (8); all of these studies showed that MRI derived bone structure provided information beyond BMD in assessing bone fragility. Subsequent longitudinal studies demonstrated the feasibility of the technique in monitoring the effect of therapeutic interventions (5, 9). Recent studies analyzing micro-architecture in the proximal femur showed that finite element analysis of proximal femur microarchitecture allowed to differentiate post-menopausal women with and without fragility fractures while BMD measured by DXA did not (10). Moreover it was also demonstrated that MRI was better suited than BMD in detecting detrimental changes in proximal femur microarchitecture and strength in long-term glucocorticoid users (11).

Ultrashort TE

Ultra-short echo time (UTE) imaging techniques allow detection of signal components with T2 relaxation times on the order of only a few hundred microseconds, which are found in highly ordered tissues such as cortical bone and tendons and can not be detected with conventional imaging techniques (12). Techawiboonwong et al (13) validated UTE imaging in bone specimens using an isotope exchange experiment and studied the right tibial midshaft in pre- and post-menopausal females and patients on hemodialysis. The quantitative analysis showed that bone water content was 135% higher in the patients on maintenance dialysis than in the pre-menopausal women and 43% higher than in the post-menopausal women. Interestingly no significant differences were found in tibial volumetric BMD between patients on hemodialysis and pre- and postmenopausal normal controls. This increase in water content was explained by abnormal cortical porosity and microscopic pores being filled with water.

Bone Marrow Composition

Bone marrow fat has been identified as an important contributor to osteoporosis and increased fracture risk (14). Proton magnetic resonance spectroscopy (1H-MRS) has been used clinically to quantify marrow adiposity non-invasively. A number of studies have been performed that showed bone marrow fat measured with MRS to be associated with DXA BMD and to be significantly elevated in postmenopausal females and older men (15-17). It has also been shown that MRS can provide information on different compartments of lipids in marrow, such as saturated lipids versus unsaturated lipids (18). A more recent study linked altered bone marrow fat composition with fragility fractures and diabetes and suggested that MRS of spinal bone marrow fat may serve as a novel tool for BMD-independent fracture risk assessment (19).

2. Quantitative MR Methods to Characterize Muscle:

Disorders of muscles can be structural and/or functional. Dysfunction of the muscular system leads to disability and pain. Quantitative MRI allows to morphologically and structurally probe muscle and its relationship to muscle strength, function and metabolic disorders. These imaging biomarkers may serve as outcome measures for physiotherapy and surgical procedures. They may also help in guiding treatment. In addition functional MRI can evaluate the effect of exercise and exercise training on muscle activity and may provide additional information beyond electromyography (EMG).

Structural assessment

Structural abnormalities include atrophy, fat infiltration and muscle type transformation. One of the early semi-quantitative techniques that was described to assess muscle fatty infiltration on MRI was the Goutallier classification, which was used in a number of clinical studies, i.e. to quantify fatty infiltration of the shoulder rotator cuff (20) and the calf muscles (21). Given the limitations to reproducibly measure fatty infiltration using this technique quantitative techniques were developed using chemical shift-based fat quantification technique, which were successfully used in clinical studies (21, 22).

Quantitative analysis of muscle function

Several techniques have been developed to understand muscle function, these include MR spectroscopy (23), T2 relaxation time measurements (24) and Blood oxygenation-level dependent (BOLD) MRI (25). Most clinical studies using these technologies have investigated volunteers during muscle exercise. A smaller number of studies have focused on muscle dysfunction in the setting of clinical abnormalities such as patients with patellofemoral pain (26) and lumbar back pain (27). Muscle involvement in Duchenne muscular dystrophy has also been studied using MRS and T2 mapping techniques (28-30).

Conclusion:

A number of new MRI technologies are evolving which allow clinically to quantitatively characterize bone and muscle structure and function. Among those techniques analyzing bone quality and strength are high resolution, morphological MRI, UTE and MRS. These techniques have shown promise in clinical studies, providing information beyond bone mineral density. Novel technologies focusing on the assessment of muscle structure and function are chemical shift-based fat quantification techniques, MRS, T2 relaxation time measurements and BOLD MRI, all of which are clinically applicable and were used in investigating pain syndromes and disorders of muscle function.