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Published on: June 14, 2018
A Protocol for Simultaneous In Vivo Imaging of Cardiac and Neuroinflammation in Dystrophin-Deficient MDX Mice Using
Joanne M Tang1,2, Andrew McClennan1,2, Linshan Liu2
1Department of Medical Biophysics, Western University, London, ON N6A 3K7, Canada.
Abstract:
Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by dystrophin loss-notably within muscles and the central neurons system. DMD presents as cognitive weakness, progressive skeletal and cardiac muscle degeneration until pre-mature death from cardiac or respiratory failure. Innovative therapies have improved life expectancy; however, this is accompanied by increased late-onset heart failure and emergent cognitive degeneration. Thus, better assessment of dystrophic heart and brain pathophysiology is needed. Chronic inflammation is strongly associated with skeletal and cardiac muscle degeneration; however, neuroinflammation's role is largely unknown in DMD despite being prevalent in other neurodegenerative diseases. Here, we present an inflammatory marker translocator protein (TSPO) positron emission tomography (PET) protocol for in vivo concomitant assessment of immune cell response in hearts and brains of a dystrophin-deficient mouse model [mdx:utrn(+/-)]. Preliminary analysis of whole-body PET imaging using the TSPO radiotracer, [18F]FEPPA in four mdx:utrn(+/-) and six wildtype mice are presented with ex vivo TSPO-immunofluorescence tissue staining. The mdx:utrn(+/-) mice showed significant elevations in heart and brain [18F]FEPPA activity, which correlated with increased ex vivo fluorescence intensity, highlighting the potential of TSPO-PET to simultaneously assess presence of cardiac and neuroinflammation in dystrophic heart and brain, as well as in several organs within a DMD model.
Insights
Duchenne muscular dystrophy (DMD) assessment is improved with a novel positron emission tomography (PET) scan. This imaging technique detects inflammation in the heart and brain of DMD mouse models, aiding in understanding disease progression.
Area of Science:
- Neurology
- Cardiology
- Medical Imaging
Background:
- Duchenne muscular dystrophy (DMD) causes progressive muscle degeneration and cognitive deficits.
- While cardiac and skeletal muscle inflammation are known in DMD, neuroinflammation's role is less understood.
- Current therapies improve lifespan but increase late-onset cardiac and cognitive issues, necessitating better assessment tools.
Purpose of the Study:
- To develop and validate a translocator protein (TSPO) positron emission tomography (PET) protocol for simultaneous in vivo assessment of cardiac and brain inflammation in DMD.
- To evaluate the utility of TSPO-PET for detecting immune cell responses in dystrophic hearts and brains.
Main Methods:
- Utilized a dystrophin-deficient mouse model (mdx:utrn+/-).
- Administered the TSPO radiotracer [18F]FEPPA for whole-body PET imaging.
- Correlated PET findings with ex vivo TSPO-immunofluorescence tissue staining.
Main Results:
- mdx:utrn+/- mice exhibited significantly elevated [18F]FEPPA uptake in both heart and brain compared to wildtype controls.
- PET imaging results correlated with increased ex vivo TSPO fluorescence intensity.
- TSPO-PET successfully identified inflammation in multiple organs, including the heart and brain.
Conclusions:
- TSPO-PET offers a promising non-invasive method for simultaneously assessing cardiac and neuroinflammation in DMD.
- This technique can aid in understanding dystrophic pathophysiology and evaluating therapeutic interventions.
- The study highlights the potential of TSPO-PET for comprehensive disease monitoring in DMD models.
