Mapping Slow Speckle Dynamics to Probe Cellular Metabolic Activity In Vivo using Laser Speckle Contrast Imaging

Area of Science:

• Biomedical Optics
• Neuroscience
• Cellular Biophysics

Background:

• Laser speckle contrast imaging (LSCI) traditionally measures blood flow but may capture deeper biological signals.
• Slow speckle dynamics (SSD) have emerged as a potential indicator of intracellular motion, distinct from perfusion.
• Validating the biophysical mechanisms of SSD in vivo is crucial for its application beyond blood flow assessment.

Purpose of the Study:

• To investigate the biophysical origin of slow speckle dynamics (SSD) in vivo within brain tissue.
• To evaluate the sensitivity of SSD to intracellular metabolic activity in the brain.

Main Methods:

• Utilized an epi-illumination LSCI system to measure speckle contrast and decorrelation times.
• Investigated SSD in acute mouse brain slices (blood flow absent) by modulating cellular metabolism with glucose and 2-deoxyglucose.
• Performed in vivo measurements to assess SSD responses to hyperoxia and normoxia post-ischemic stroke.

Main Results:

• SSD signals were observed in brain slices without blood flow, indicating a non-vascular origin.
• Inhibition of glycolysis reduced SSD, while metabolic substrate restoration partially recovered the signal.
• In vivo, SSD increased under hyperoxia post-stroke, correlating with enhanced cellular metabolic activity.

Conclusions:

• SSD is sensitive to energy-dependent cellular processes linked to metabolic activity.
• SSD provides a novel, label-free in vivo optical contrast for assessing cellular metabolic activity and viability.
• This study establishes a mechanistic basis for using SSD as a general optical marker in biological research.