Significance: Quantitative measures of blood flow and metabolism are essential for improved assessment of brain health and response to ischemic injury.
Aim: We demonstrate a multimodal technique for measuring the cerebral metabolic rate of oxygen (CMRO2) in the rodent brain on an absolute scale (μM O2 / min).
Approach: We use laser speckle imaging at 809 nm and spatial frequency domain imaging at 655, 730, and 850 nm to obtain spatiotemporal maps of cerebral blood flow, tissue absorption (μa), and tissue scattering (μs ′ ). Knowledge of these three values enables calculation of a characteristic blood flow speed, which in turn is input to a mathematical model with a “zero-flow” boundary condition to calculate absolute CMRO2. We apply this method to a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation. With this model, the zero-flow condition occurs during entry into CA.
Results: The CMRO2 values calculated with our method are in good agreement with those measured with magnetic resonance and positron emission tomography by other groups.
Conclusions: Our technique provides a quantitative metric of absolute cerebral metabolism that can potentially be used for comparison between animals and longitudinal monitoring of a single animal over multiple days. Though this report focuses on metabolism in a model of ischemia and reperfusion, this technique can potentially be applied to far broader types of acute brain injury and whole-body pathological occurrences.
We describe the development of a perturbation-free technique to measure tissue blood flow and metabolic rate of oxygen (MRO2) using LSI and SFDI. Analytical (diffusion) and computational (Monte Carlo) models are employed to characterize the contributions of diffuse and directed flow to the measured speckle contrast. Measured flow data is combined with the deoxygenated hemoglobin concentration and a path-length factor (both obtained from SFDI) to model tissue oxygen consumption in units of M O2/min. The results of this model were comparable with values of MRO2 measured with other imaging methods (PET, MRI/MRS).
Cardiac arrest (CA) affects over 500,000 people in the United States. Although resuscitation efforts have improved, poor neurological outcome is the leading cause of morbidity in CA survivors, and only 8.3% of out-of-hospital CA survivors have good neurological recovery. Therefore, a detailed understanding of the brain before, during, and after CA and resuscitation is critical. To provide a more complete picture of CBF dynamics associated with CA and resuscitation, we postulate that both temporal and spatial CBF dynamics must be understood. To investigate spatiotemporal dynamics, we used laser speckle imaging (LSI) to image rats that underwent either 5- or 7-min asphyxial CA, followed by cardiopulmonary resuscitation until return of spontaneous circulation (ROSC). During induction of global cerebral ischemia through CA, we observed two time periods during which a decrease in CBF propagates in space in a cranial window over the right hemisphere. The first time-period is during CA and the second after the hyperemic peak, but before CBF plateaus at a hypoperfused state post-ROSC. During CA, the decrease in CBF propagates from the lateral region of the brain to the medial region of the brain. Conversely, post-ROSC, the decrease in CBF propagates from the medial region of the brain to the lateral region of the brain. We postulate that study of spatiotemporal dynamics in a global cerebral ischemia model may lead to important insight into our understanding of cerebral function during and after resuscitation from CA, which may provide clinicians with knowledge that can lead to improvements in neurological outcome.
Quantifying rapidly varying perturbations in cerebral tissue absorption and scattering can potentially help to characterize changes in brain function caused by ischemic trauma. We have developed a platform for rapid intrinsic signal brain optical imaging using macroscopically structured light. The device performs fast, multispectral, spatial frequency domain imaging (SFDI), detecting backscattered light from three-phase binary square-wave projected patterns, which have a much higher refresh rate than sinusoidal patterns used in conventional SFDI. Although not as fast as “single-snapshot” spatial frequency methods that do not require three-phase projection, square-wave patterns allow accurate image demodulation in applications such as small animal imaging where the limited field of view does not allow single-phase demodulation. By using 655, 730, and 850 nm light-emitting diodes, two spatial frequencies (fx=0 and 0.3 mm−1), three spatial phases (120 deg, 240 deg, and 360 deg), and an overall camera acquisition rate of 167 Hz, we map changes in tissue absorption and reduced scattering parameters (μa and μs′) and oxy- and deoxyhemoglobin concentration at ∼14 Hz. We apply this method to a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) to quantify hemodynamics and scattering on temporal scales (Δt) ranging from tens of milliseconds to minutes. We observe rapid concurrent spatiotemporal changes in tissue oxygenation and scattering during CA and following CPR, even when the cerebral electrical signal is absent. We conclude that square-wave SFDI provides an effective technical strategy for assessing cortical optical and physiological properties by balancing competing performance demands for fast signal acquisition, small fields of view, and quantitative information content.
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