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Temporal changes in magnetic resonance imaging in the mdx mouse.

Pratt SJ, Xu S, Mullins RJ, Lovering RM - BMC Res Notes (2013)

Bottom Line: The in vivo cross-sectional T2-weighted image of the healthy (wild type, WT) muscles is homogeneously dark and this homogeneity does not change with time, as there is no disease.We, and others, have shown marked changes in MRI in dystrophic muscle, with multiple, unevenly distributed focal hyperintensities throughout the bulk of the muscles.Temporal MRI scans show an increase in heterogeneity shortly after the critical period, at 9 and 13 weeks of age, with a decrease in heterogeneity thereafter.

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ABSTRACT

Background: Duchenne muscular dystrophy (DMD) is characterized clinically by severe, progressive loss of skeletal muscle. The phenotype is much less severe in the mdx mouse model of DMD than that seen in patients with DMD. However, a "critical period" has been described for the mdx mouse, during which there is a peak in muscle weakness and degeneration/regeneration between the 2nd and 5th weeks of life. A number of studies have employed small animal magnetic resonance imaging (MRI) to examine skeletal muscle in various dystrophic models, but such studies represent a snapshot in time rather than a longitudinal view.

Results: The in vivo cross-sectional T2-weighted image of the healthy (wild type, WT) muscles is homogeneously dark and this homogeneity does not change with time, as there is no disease. We, and others, have shown marked changes in MRI in dystrophic muscle, with multiple, unevenly distributed focal hyperintensities throughout the bulk of the muscles. Here we monitored an mdx mouse using MRI from 5 to 80 weeks of age. Temporal MRI scans show an increase in heterogeneity shortly after the critical period, at 9 and 13 weeks of age, with a decrease in heterogeneity thereafter. The 4.3-fold increase in percent heterogeneity at week 9 and 13 is consistent with the notion of an early critical period described for mdx mice.

Conclusions: Age is a significant variable in quantitative MR studies of the mdx mouse. The mdx mouse is typically studied during the critical period, at a time that most closely mimics the DMD pathology, but the preliminary findings here, albeit based on imaging only one mdx mouse over time, suggest that the changes in MRI can occur shortly after this period, when the muscles are still recovering.

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Temporal changes in MRI heterogeneity.A: Representative images of dystrophic (mdx) mouse hindlimb muscles over time. The mouse was scanned in increments of about 4 weeks, throughout the course of 20 months, starting at 5 weeks of age. Changes in the shape of the legs are a consequence of the custom-designed apparatus used to stabilize them. B: Line graph shows the percent of heterogeneity for each time point. Heterogeneity reaches its peak around 9 and 13 weeks of age, just after the early critical period of the mdx mouse. Interestingly, the drop in heterogeneity of the T2 signal remains relatively stable through 80 weeks of age. Timeline gaps are indicated by breaks in the axis.
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Figure 2: Temporal changes in MRI heterogeneity.A: Representative images of dystrophic (mdx) mouse hindlimb muscles over time. The mouse was scanned in increments of about 4 weeks, throughout the course of 20 months, starting at 5 weeks of age. Changes in the shape of the legs are a consequence of the custom-designed apparatus used to stabilize them. B: Line graph shows the percent of heterogeneity for each time point. Heterogeneity reaches its peak around 9 and 13 weeks of age, just after the early critical period of the mdx mouse. Interestingly, the drop in heterogeneity of the T2 signal remains relatively stable through 80 weeks of age. Timeline gaps are indicated by breaks in the axis.

Mentions: The in vivo cross-sectional T2-weighted image of the healthy (WT) muscles is homogeneously dark at 7 T [16,17] (Figure 1A) and this homogeneity does not change with time, as there is no disease. By contrast, the MRI of mdx muscles shows heterogeneity, with multiple, unevenly distributed focal hyperintensities throughout the bulk of the muscles [11] (Figure 1A, red arrow). The data from the 14 imaging sessions (Figure 2A, from week 5 to week 80) show these unevenly distributed focal hyperintensities throughout the muscles, with a peak in this presentation occurring around 9 and 13 weeks of age (the overall shape of the leg is altered due to the custom-designed apparatus used to stabilize the legs). The mdx mouse is typically studied during the critical period, at a time that most closely mimics the DMD pathology. Interestingly, the heterogeneity in mdx muscles appears to change over time. Percent heterogeneity was quantified (Figure 2B) and shows a peak (10.3%) at 9 weeks of age with a similar peak (8.7%) at week 13. The drop in heterogeneity thereafter remains relatively stable thorough 80 weeks of age. However, there is a stepwise decline in the percent heterogeneity from weeks 5–17 (peak 10.3%), weeks 17–44 (peak 4.7%), and weeks 48–76 (peak 2.8%).


Temporal changes in magnetic resonance imaging in the mdx mouse.

Pratt SJ, Xu S, Mullins RJ, Lovering RM - BMC Res Notes (2013)

Temporal changes in MRI heterogeneity.A: Representative images of dystrophic (mdx) mouse hindlimb muscles over time. The mouse was scanned in increments of about 4 weeks, throughout the course of 20 months, starting at 5 weeks of age. Changes in the shape of the legs are a consequence of the custom-designed apparatus used to stabilize them. B: Line graph shows the percent of heterogeneity for each time point. Heterogeneity reaches its peak around 9 and 13 weeks of age, just after the early critical period of the mdx mouse. Interestingly, the drop in heterogeneity of the T2 signal remains relatively stable through 80 weeks of age. Timeline gaps are indicated by breaks in the axis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3716616&req=5

Figure 2: Temporal changes in MRI heterogeneity.A: Representative images of dystrophic (mdx) mouse hindlimb muscles over time. The mouse was scanned in increments of about 4 weeks, throughout the course of 20 months, starting at 5 weeks of age. Changes in the shape of the legs are a consequence of the custom-designed apparatus used to stabilize them. B: Line graph shows the percent of heterogeneity for each time point. Heterogeneity reaches its peak around 9 and 13 weeks of age, just after the early critical period of the mdx mouse. Interestingly, the drop in heterogeneity of the T2 signal remains relatively stable through 80 weeks of age. Timeline gaps are indicated by breaks in the axis.
Mentions: The in vivo cross-sectional T2-weighted image of the healthy (WT) muscles is homogeneously dark at 7 T [16,17] (Figure 1A) and this homogeneity does not change with time, as there is no disease. By contrast, the MRI of mdx muscles shows heterogeneity, with multiple, unevenly distributed focal hyperintensities throughout the bulk of the muscles [11] (Figure 1A, red arrow). The data from the 14 imaging sessions (Figure 2A, from week 5 to week 80) show these unevenly distributed focal hyperintensities throughout the muscles, with a peak in this presentation occurring around 9 and 13 weeks of age (the overall shape of the leg is altered due to the custom-designed apparatus used to stabilize the legs). The mdx mouse is typically studied during the critical period, at a time that most closely mimics the DMD pathology. Interestingly, the heterogeneity in mdx muscles appears to change over time. Percent heterogeneity was quantified (Figure 2B) and shows a peak (10.3%) at 9 weeks of age with a similar peak (8.7%) at week 13. The drop in heterogeneity thereafter remains relatively stable thorough 80 weeks of age. However, there is a stepwise decline in the percent heterogeneity from weeks 5–17 (peak 10.3%), weeks 17–44 (peak 4.7%), and weeks 48–76 (peak 2.8%).

Bottom Line: The in vivo cross-sectional T2-weighted image of the healthy (wild type, WT) muscles is homogeneously dark and this homogeneity does not change with time, as there is no disease.We, and others, have shown marked changes in MRI in dystrophic muscle, with multiple, unevenly distributed focal hyperintensities throughout the bulk of the muscles.Temporal MRI scans show an increase in heterogeneity shortly after the critical period, at 9 and 13 weeks of age, with a decrease in heterogeneity thereafter.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Duchenne muscular dystrophy (DMD) is characterized clinically by severe, progressive loss of skeletal muscle. The phenotype is much less severe in the mdx mouse model of DMD than that seen in patients with DMD. However, a "critical period" has been described for the mdx mouse, during which there is a peak in muscle weakness and degeneration/regeneration between the 2nd and 5th weeks of life. A number of studies have employed small animal magnetic resonance imaging (MRI) to examine skeletal muscle in various dystrophic models, but such studies represent a snapshot in time rather than a longitudinal view.

Results: The in vivo cross-sectional T2-weighted image of the healthy (wild type, WT) muscles is homogeneously dark and this homogeneity does not change with time, as there is no disease. We, and others, have shown marked changes in MRI in dystrophic muscle, with multiple, unevenly distributed focal hyperintensities throughout the bulk of the muscles. Here we monitored an mdx mouse using MRI from 5 to 80 weeks of age. Temporal MRI scans show an increase in heterogeneity shortly after the critical period, at 9 and 13 weeks of age, with a decrease in heterogeneity thereafter. The 4.3-fold increase in percent heterogeneity at week 9 and 13 is consistent with the notion of an early critical period described for mdx mice.

Conclusions: Age is a significant variable in quantitative MR studies of the mdx mouse. The mdx mouse is typically studied during the critical period, at a time that most closely mimics the DMD pathology, but the preliminary findings here, albeit based on imaging only one mdx mouse over time, suggest that the changes in MRI can occur shortly after this period, when the muscles are still recovering.

Show MeSH
Related in: MedlinePlus