Fat Infiltration and Impaired Muscle Function in COPD
Fat Infiltration and Impaired Muscle Function in COPD
Muscle weakness is a prevalent complication in chronic obstructive pulmonary disease (COPD). Atrophy does not fully explain muscle weakness in this population. The recent focus on fat infiltration and its clinical implications in age and diseased muscles are important because it may further explain the extent of declining muscle strength and mobility seen in COPD.
Purpose: The objectives of this study are to quantify fat infiltration (muscle quality) of lower-limb muscles in people with COPD and healthy older adults using magnetic resonance imaging and proton magnetic resonance spectroscopy, and to explore its relationship with muscle strength and walking capacity in COPD.
Methods: T1-weighted magnetic resonance imaging and proton magnetic resonance spectroscopy were performed in people with COPD (n = 10) and control subjects (n = 10) matched for age, gender, and body mass index. Maximal cross-sectional area (muscle size), isokinetic and isometric muscle peak torques, and 6-min walk distance were also assessed.
Results: In addition to muscle atrophy (mean between-group differences of 20% to 25%, P < 0.05), COPD group presented with fatty infiltration in thigh and calf muscles that were significantly greater than what was observed in their healthy counterparts (mean between-group differences of 74% to 89%, P = 0.001). There was a strong inverse correlation between intramuscular fat infiltration, muscle peak torque, and walking distance (r = -0.6 to -0.8, P < 0.001) in this group as opposed to fair-to-moderate correlations between muscle size and the same outcomes (r = 0.4–0.6, P < 0.01).
Conclusion: Poor muscle quality accompanies atrophy in people with COPD. Intramuscular fat infiltration not only appears to have a strong correlation with impaired function but also is more profound than muscle atrophy in this group. Monitoring both muscle size and quality may enable a more comprehensive assessment of exercise programs in COPD.
Peripheral muscle weakness, particularly of lower limbs, is an important complication of chronic obstructive pulmonary disease (COPD). It is associated with exercises intolerance, increased health care services use, and increased risk of mortality. Although decline in strength is commonly attributable to a decrease in muscle size and cross-sectional area, atrophy alone does not fully explain the extent of muscle weakness observed in people with COPD. In addition to size, changes in muscle composition may play a role in explaining peripheral muscle weakness.
Excessive lipid deposition within the skeletal muscles are usually seen in association with atrophy in aging, inactivity, and chronic disease conditions such as diabetes, muscular dystrophy, spinal cord injury, and stroke. Increased intramuscular fatty infiltration is now identified as a contributor to declining strength and mobility, independent of muscle size. The potential importance of fatty atrophy in age and diseased muscles has also stimulated the application of various imaging approaches such as magnetic resonance imaging (MRI) to assess lipid content within the muscle.
In a previous study by our group, a standard MRI technique (T1-weighted imaging) revealed an unusual pattern of fat infiltration across three major thigh muscle groups in people with COPD. Such technique provides excellent spatial resolution to detect anatomical structures. However, quantification of fat is limited because each voxel comprising the image can contain different tissues (e.g., water, fat, connective tissue) and therefore possess a signal average of all elements. Proton magnetic resonance spectroscopy (H-MRS) is used in conjunction with MRI to quantify lipid fraction within the muscle.H-MRS produces a chemical spectrum of the tissue where the areas of the spectral peaks correlate with the concentration of chemical present measured in parts per million (Fig. 1A and B). It can also be used to measure biophysical properties of the tissue (Fig. 1C and D), the transverse relaxation time (T2). Changes in T2 values are associated with increased water content in muscle due to inflammation and/or edema, reflecting a pathological process. To our knowledge, no studies have used a combination of MRI and H-MRS to assess muscle quality in COPD.
(Enlarge Image)
Figure 1.
Calf muscles of a person with COPD and a matched healthy individual as assessed by spectroscopy. Proton spectra signals from soleus muscles (TR = 6000 ms, TE = 120 ms) of a 70-yr-old COPD female (A) and a 70-yr-old control subject (B); concentrations of lipid determined relative to water and fraction ratio (lipid/total proton) calculated as a measure of lipid infiltration. Soleus T2 relaxation time of a 70-yr-old COPD female (C) and a 70-yr-old control subject (D) determined from the curve fit of the amplitude of the water peak obtained from five TE. A decline in the water peak is observed with longer TE. T2 was calculated using the following equation: signal intensity = ke(1/T2x) + c, where k = 6 × 108.
The recent focus on the clinical implications of intramuscular fat infiltration in chronic diseases is important because it may further explain the degree of strength deficits and mobility limitations seen in COPD. It could also potentially provide insight into the design of exercise protocols to alleviate muscle dysfunction in these individuals. Therefore, we aimed to quantify lipid and water contents (muscle quality) of lower limb muscles in people with COPD using MRI and H-MRS and compare them with matched control subjects. We also examined the relationship between muscle quality and muscle strength and mobility in the COPD group.
Abstract and Introduction
Abstract
Muscle weakness is a prevalent complication in chronic obstructive pulmonary disease (COPD). Atrophy does not fully explain muscle weakness in this population. The recent focus on fat infiltration and its clinical implications in age and diseased muscles are important because it may further explain the extent of declining muscle strength and mobility seen in COPD.
Purpose: The objectives of this study are to quantify fat infiltration (muscle quality) of lower-limb muscles in people with COPD and healthy older adults using magnetic resonance imaging and proton magnetic resonance spectroscopy, and to explore its relationship with muscle strength and walking capacity in COPD.
Methods: T1-weighted magnetic resonance imaging and proton magnetic resonance spectroscopy were performed in people with COPD (n = 10) and control subjects (n = 10) matched for age, gender, and body mass index. Maximal cross-sectional area (muscle size), isokinetic and isometric muscle peak torques, and 6-min walk distance were also assessed.
Results: In addition to muscle atrophy (mean between-group differences of 20% to 25%, P < 0.05), COPD group presented with fatty infiltration in thigh and calf muscles that were significantly greater than what was observed in their healthy counterparts (mean between-group differences of 74% to 89%, P = 0.001). There was a strong inverse correlation between intramuscular fat infiltration, muscle peak torque, and walking distance (r = -0.6 to -0.8, P < 0.001) in this group as opposed to fair-to-moderate correlations between muscle size and the same outcomes (r = 0.4–0.6, P < 0.01).
Conclusion: Poor muscle quality accompanies atrophy in people with COPD. Intramuscular fat infiltration not only appears to have a strong correlation with impaired function but also is more profound than muscle atrophy in this group. Monitoring both muscle size and quality may enable a more comprehensive assessment of exercise programs in COPD.
Introduction
Peripheral muscle weakness, particularly of lower limbs, is an important complication of chronic obstructive pulmonary disease (COPD). It is associated with exercises intolerance, increased health care services use, and increased risk of mortality. Although decline in strength is commonly attributable to a decrease in muscle size and cross-sectional area, atrophy alone does not fully explain the extent of muscle weakness observed in people with COPD. In addition to size, changes in muscle composition may play a role in explaining peripheral muscle weakness.
Excessive lipid deposition within the skeletal muscles are usually seen in association with atrophy in aging, inactivity, and chronic disease conditions such as diabetes, muscular dystrophy, spinal cord injury, and stroke. Increased intramuscular fatty infiltration is now identified as a contributor to declining strength and mobility, independent of muscle size. The potential importance of fatty atrophy in age and diseased muscles has also stimulated the application of various imaging approaches such as magnetic resonance imaging (MRI) to assess lipid content within the muscle.
In a previous study by our group, a standard MRI technique (T1-weighted imaging) revealed an unusual pattern of fat infiltration across three major thigh muscle groups in people with COPD. Such technique provides excellent spatial resolution to detect anatomical structures. However, quantification of fat is limited because each voxel comprising the image can contain different tissues (e.g., water, fat, connective tissue) and therefore possess a signal average of all elements. Proton magnetic resonance spectroscopy (H-MRS) is used in conjunction with MRI to quantify lipid fraction within the muscle.H-MRS produces a chemical spectrum of the tissue where the areas of the spectral peaks correlate with the concentration of chemical present measured in parts per million (Fig. 1A and B). It can also be used to measure biophysical properties of the tissue (Fig. 1C and D), the transverse relaxation time (T2). Changes in T2 values are associated with increased water content in muscle due to inflammation and/or edema, reflecting a pathological process. To our knowledge, no studies have used a combination of MRI and H-MRS to assess muscle quality in COPD.
(Enlarge Image)
Figure 1.
Calf muscles of a person with COPD and a matched healthy individual as assessed by spectroscopy. Proton spectra signals from soleus muscles (TR = 6000 ms, TE = 120 ms) of a 70-yr-old COPD female (A) and a 70-yr-old control subject (B); concentrations of lipid determined relative to water and fraction ratio (lipid/total proton) calculated as a measure of lipid infiltration. Soleus T2 relaxation time of a 70-yr-old COPD female (C) and a 70-yr-old control subject (D) determined from the curve fit of the amplitude of the water peak obtained from five TE. A decline in the water peak is observed with longer TE. T2 was calculated using the following equation: signal intensity = ke(1/T2x) + c, where k = 6 × 108.
The recent focus on the clinical implications of intramuscular fat infiltration in chronic diseases is important because it may further explain the degree of strength deficits and mobility limitations seen in COPD. It could also potentially provide insight into the design of exercise protocols to alleviate muscle dysfunction in these individuals. Therefore, we aimed to quantify lipid and water contents (muscle quality) of lower limb muscles in people with COPD using MRI and H-MRS and compare them with matched control subjects. We also examined the relationship between muscle quality and muscle strength and mobility in the COPD group.
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