Photoacoustic imaging in mitochondrial disease

Mitochondrial diseases are a diverse group of inherited neuromuscular disorders leading to progressive disability and early mortality. Mitochondrial myopathy is a common feature of mitochondrial disorders, affecting most patients. Assessment of disease progression and treatment efficacy in mitochondrial disease trials has often relied on muscle biopsies, however, these are increasingly considered unfavourable by patients. Imaging biomarkers of disease could reduce the patient burden, enabling non-invasive longitudinal monitoring of molecular information. Photoacoustic imaging combines the molecular sensitivity of light absorption with the deep tissue imaging capabilities of ultrasound, enabling a safe and fast imaging technique. Tuning the wavelength of light allows for the detection of molecular constituents such as oxy- and deoxy-haemoglobin, lipids, and water. These signatures may reflect underlying pathophysiological alterations and serve as valuable indicators of disease state and progression. We conducted an exploratory study of a photoacoustic imaging dataset in patients with mitochondrial myopathy due to the m.3243A>G mt-tRNALeu mutation and compared to healthy volunteers. We generated photoacoustic measurements at wavelengths in the near infrared, comparing absolute values and ratios derived in the bicep muscle. Confounding factors such as skin colour and sex were considered, and we ensured that these parameters were matched in healthy volunteers and patients. We identified significant differences between patients and controls, revealing changes in ratios between water and total haemoglobin, lipid and total haemoglobin, and lipid and water content. This study highlights the promise of photoacoustic imaging as a novel imaging biomarker in mitochondrial myopathies, paving the way for larger scale studies.