3.2.1
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is a noninvasive imaging method which uses a powerful magnet to produce high resolution images and is increasingly being used in the evaluation of disease severity in neuromuscular diseases.
Basic Physics of MRI
The signal acquired from MRI systems predominately comes from the hydrogen protons within the body, specifically, those from water and fat. All protons inherently have a nuclear “spin” and a resulting intrinsic magnetic field. In the presence of a strong external magnetic field, the interaction between the external magnetic field and the magnetic field of the proton will cause the proton to precess at a frequency directly related to the strength of the external magnetic field. The protons will also align with the external magnetic field, creating a net longitudinal magnetic vector directed along the axis of the external magnetic field.82,83
A radiofrequency (RF) pulse is then applied which excites the protons to a higher energy level. Simultaneously, there is a gain in the protons’ phase coherence. This produces a loss of longitudinal magnetization and a gain in transverse magnetization, respectively. When the RF pulse is turned off, the excited hydrogen protons undergo relaxation back to their original lower energy level. 84 The relaxation process of the protons back into their equilibrium state occurs by
two mechanisms: longitudinal (T1) and transverse (T2) relaxation. In T1 relaxation, the proton returns to its equilibrium state by transferring energy to the other nuclei in its surroundings, or lattice. This mechanism is also referred to as spin-lattice relaxation, and results in a net increase in longitudinal magnetization. T2 relaxation reflects the loss of phase coherence due to
interactions between spinning protons. Also known as spin-spin relaxation, T2 relaxation leads to a net decrease in transverse magnetization.83
Different tissues will exhibit different T1 and T2 relaxation times. By varying the scanning parameters, images are generated so that the signal is primarily due to the T1 or T2 relaxation times of the tissue. The signal intensity of normal skeletal muscle is similar to that of water, and lower than that of fat on T1-weighted images. In T2-weighted images, the signal of skeletal muscle is lower than that of both water and fat. Table 3.1 summarizes the appearance of muscle, fat, and water in T1- and T2-weighted images. Fat suppressed images can be generated by using short τ inversion recovery (STIR) or by using a pre-saturation pulse to suppress the fat signal. Fat suppressed T2-weighted images are much more sensitive in detecting subtle muscle edema.70,85
Table 3.1: MRI signal characteristics of muscle components
T1-weighted T2-weighted
Water Low to intermediate High
Fat High Intermediate
MRI in DMD
Because healthy skeletal muscle and fat exhibit very different T1 relaxation times, T1- weighted imaging is very sensitive to intramuscular fatty deposition.86 T1 signals have been shown to be significantly higher in the muscles of boys with DMD compared to normal control.86 T1 intensity has also been shown to increase during the course of the disease,
associated with the increasing replacement of muscle by fat.87 However, water has a T1
relaxation time that is similar to normal muscle, thus T1-weighted images are insensitive at detecting increased water in muscle, making T1-weighted images less relevant in young DMD patients. It has been hypothesized that T2-weighted images, which are sensitive to both fat and water, may be more appropriate for evaluating DMD patients early in the course of the disease, before fatty infiltration is significant.88 Acute muscle damage, inflammation, and fat have been
characterized in dystrophic muscle using T2-weighted imaging.89
A number of approaches have utilized MRI to measure muscle size in DMD. Muscle cross- sectional area is a quantitative measurement and can show differential involvement of muscle groups in disease progression. Researchers at the University of Florida have used muscle cross- sectional area to compare boys with DMD to age matched controls.90 They found that muscle
cross-sectional area of the calf muscles were larger in DMD patients compared with controls. In another study by the same group, tissue within the cross-sectional area was classified as
contractile (muscle tissue) and non-contractile (fatty tissue) based on T1 signal intensity. Comparing 28 boys with DMD and 10 control subjects, they showed that the DMD patients had a significantly greater proportion of non-contractile tissue. The proportion of non-contractile tissue in boys with DMD was shown to increase significantly with age.91
Muscle size is typically calculated by manually tracing individual muscles in axial slices from T1- or T2-weighted images. Because this manual assessment is time consuming, muscles are generally only segmented in a limited number of slices. To address this need, the Neuro
Image Research and Analysis Laboratory at the University of North Carolina has recently developed a semi-automated segmentation method for segmenting the full length of individual muscles. They found that utilizing the full volume of muscle resulted in significantly less error and variability in measurements, compared to the standard, limited range, muscle
segmentation.92 Further, they showed that distribution of T2 values could be analyzed in three
dimensions throughout the full muscle to provide information of muscle heterogeneity, and have demonstrated that MRI texture features are capable of distinguishing longitudinal progression between GRMD and normal dogs.93
Overall, MRI is a powerful and sensitive technique for evaluating skeletal muscle
involvement in DMD. The major disadvantages of MRI as a biomarker for disease progression or therapeutic response in clinical trials are associated with the high cost, and the necessity of sedation or anesthesia in young children to prevent motion artifacts.94 This is especially undesirable in this patient population as anesthesia is potentially more hazardous in boys with DMD.95 Furthermore, MRI is not capable of directly measuring fibrosis, which is a critical
characteristic of degenerated dystrophic muscle.96
3.2.2
Ultrasound Imaging
Medical ultrasound, discussed in detail in Chapter 4, provides a safe and relatively inexpensive alternative to the high cost of MRI. Moreover, the rapid acquisition time make ultrasound less susceptible to motion artifacts, eliminating the need for sedation in pediatric patients.