Quantitative hemodynamic imaging: a method to correct the effects of optical properties on laser speckle imaging

Significance: Studying cerebral hemodynamics may provide diagnostic information on neurological conditions. Wide-field imaging techniques, such as laser speckle imaging (LSI) and optical intrinsic signal imaging, are commonly used to study cerebral hemodynamics. However, they often do not account appropriately for the optical properties of the brain that can vary among subjects and even during a single measurement. Here, we describe the combination of LSI and spatial-frequency domain imaging (SFDI) into a wide-field quantitative hemodynamic imaging (QHI) system that can correct the effects of optical properties on LSI measurements to achieve a quantitative measurement of cerebral blood flow (CBF). Aim: We describe the design, fabrication, and testing of QHI. Approach: The QHI hardware combines LSI and SFDI with spatial and temporal synchronization. We characterized system sensitivity, accuracy, and precision with tissue-mimicking phantoms. With SFDI optical property measurements, we describe a method derived from dynamic light scattering to obtain absolute CBF values from LSI and SFDI measurements. We illustrate the potential benefits of absolute CBF measurements in resting-state and dynamic experiments. Results: QHI achieved a 50-Hz raw acquisition frame rate with a 10 x 10 mm field of view and flow sensitivity up to similar to 4 mm/s. The extracted SFDI optical properties agreed well with a commercial system (R2 = 0.98). The system showed high stability with low coefficients of variations over multiple sessions within the same day (<1%) and over multiple days (<4%). When optical properties were considered, the in-vivo hypercapnia gas challenge showed a slight difference in CBF (-1.5% to 0.5% difference). The in-vivo resting-state experiment showed a change in CBF ranking for nine out of 13 animals when the correction method was applied to LSI CBF measurements. Conclusions: We developed a wide-field QHI system to account for the confounding effects of optical properties on CBF LSI measurements using the information obtained from SFDI.