Sensitive ultrasonic detection of dystrophic skeletal muscle in patients with duchenne muscular dystrophy using an entropy-based signal receiver

Abstract

The dystrophinopathies comprise a group of X-linked genetic diseases that feature dystrophin deficiency. Duchenne and Becker muscular dystrophy are characterized by progressive weakness and wasting of skeletal, smooth, and/or cardiac muscle. Duchenne muscular dystrophy (DMD) is the most severe dystrophinopathy, with an incidence of 1:3500 male births. Despite understanding the structural and genetic basis for DMD, the pathogenesis and clinical basis for more severe involvement in specific skeletal muscle groups and the heart are poorly understood. Current techniques, such as strength testing for monitoring progress of disease and therapy in DMD patients, are imprecise and physically demanding for test subjects. Ultrasound is well-suited to detect changes in structure and organization in muscle tissue in a manner that makes low demands on the patient. Therefore, we investigated the use of ultrasound to quantitatively phenotype the remodeling process in patients with DMD. Beam-formed radio-frequency (RF) data were acquired from the skeletal muscles of nine DMD and five normal subjects imaged with a clinical imaging system (HDI5000 w/7 MHz probe applied above left biceps muscle). From these data, images were reconstructed using B-mode (log of analytic signal magnitude) and information-theoretic receivers (H(f)-receiver). H(f) images obtained from dystrophic muscle contained extensive "mottled" regions (i.e., areas with heterogeneous image contrast) that were not readily apparent from the B-Mode images. The 2-D autocorrelation of DMD H(f) images have broader peaks than those of normal subjects, which is indicative of larger scatterer sizes, consistent with pathologic changes of fibers, edema and fatty infiltration. Comparison of the relative peak widths (full width measured at 60% maximum) of the autocorrelation of the DMD and normal H(f) images shows a quantitative difference between the two groups (p < 0.005, student two-tailed paired t-test). Consequently, these imaging techniques may prove useful for longitudinal monitoring of disease progression and therapy.

Fig. 1

Images showing a comparison of backscattered ultrasound in normal (left column) vs. DMD (right column) muscle tissue. The top row are images of the logarithm of the analytic signal magnitude of the backscattered ultrasound, i.e., grayscale B-mode images. The direction of insonification is from top to bottom. The middle row was made by sliding a square window of 2.38μs over the backscattered RF lines in 0.037μs steps and computing the signal energy, E_f in each window (resulting in an image size of 961×256 pixels). Subsequently this image was rescaled to 256×256 pixels for presentation and processing purposes. The bottom row was made using the same window and subsequent rescaling, but the data within each window were used to compute H_f . Each panel represents a spatial region that is 2.94cm×2.3cm. The DMD date are from the subject (nine years old) whose age most closely matches the group mean value.

Fig. 2

Correlation images of the panels shown in Figure (1). Each image shows a bright central region, as expected. The widths of these regions are significantly different when grouped according to whether they are from normal or dystrophic muscle. This suggests that the width might be used to differentiate the two groups. The dashed indicates the position of pixels in the normal and DMD H_f images used to plot the curves shown in Figure (3).

Fig. 3

A cross-sectional slice through the mid-sections of the H_f images shown in Figure (2). The the 60% level is indicated. At this level the widths of the cross-sections are obviously different, reflecting differences in the H_f images shown in Figure (2).

Fig. 4

A comparison of mean width, at the 70% level of the central peaks of log[E] images of normal (N = 5) and dystrophic (N = 9) muscle. The two groups are significantly different (P < 0.02).

Fig. 5

A comparison of mean width, at the 60% level of the central peaks of H_f images of normal (N = 5) and dystrophic (N = 9) muscle. The two groups are significantly different (P < 0.005).