Investigation of the cerebral hemodynamic response function in single blood vessels by functional photoacoustic microscopy

Abstract

Abstract. The specificity of the hemodynamic response function (HRF) is determined spatially by the vascular architecture and temporally by the evolution of hemodynamic changes. Here, we used functional photoacoustic microscopy (fPAM) to investigate single cerebral blood vessels of rats after left forepaw stimulation. In this system, we analyzed the spatiotemporal evolution of the HRFs of the total hemoglobin concentration (HbT), cerebral blood volume (CBV), and hemoglobin oxygen saturation (SO 2 ). Changes in specific cerebral vessels corresponding to various electrical stimulation intensities and durations were bilaterally imaged with 36 × 65-μm 2 spatial resolution. Stimulation intensities of 1, 2, 6, and 10 mA were applied for periods of 5 or 15 s. Our results show that the relative functional changes in HbT, CBV, and SO 2 are highly dependent not only on the intensity of the stimulation, but also on its duration. Additionally, the duration of the stimulation has a strong influence on the spatiotemporal characteristics of the HRF as shorter stimuli elicit responses only in the local vasculature (smaller arterioles), whereas longer stimuli lead to greater vascular supply and drainage. This study suggests that the current fPAM system is reliable for studying relative cerebral hemodynamic changes, as well as for offering new insights into the dynamics of functional cerebral hemodynamic changes in small animals.

Rescue of cortical neurovascular functions during the hyperacute phase of ischemia by peripheral sensory stimulation

“…For instance, PA imaging technology is especially suitable for evaluating the progressive changes in the penumbra area of focal ischemia because of its attributes such as the deeper tissue penetration depth and intrinsic blood contrast. Recently, our studies have shown that functional photoacoustic microscopy (fPAM) can be used for the contrast agent-free imaging of functional CBV and hemoglobin oxygen saturation (SO 2 ) changes in the rat cortex following peripheral sensory stimulation (Hu et al, 2009;Liao et al, 2012a;Liao et al, 2012b).…”

Improving neurovascular outcomes with bilateral forepaw stimulation in a rat photothrombotic ischemic stroke model

“…This ECoG-fPAM system allows the simultaneous assessment of two important variables in the pathophysiology of stroke, i.e., changes in regional cerebral perfusion (CBV and SO 2 ) 22 and neuronal integrity (SSEP, coherence, and ADR). 27 In this PTI stroke rat model, a focal infarct was created in the right hemisphere S1FL region by targeting a distal branch of the MCA.…”

“…The vessel pixel was defined as the pixel that possessed a PA signal that was three times greater than the background signal. 21,22,35 Functional images of SO 2 changes ½ΔI Fð560Þ ðtÞ at a given time point t in each block were assessed according to the following equation: …”

“…24 The current fPAM system has been used, with multiwavelength functional analysis, to image specific cortical activation changes in the rat brain with a good penetration depth 25 and to study cerebral autoregulation without the use of contrast agents. 22 This technology has opened up a new avenue to study potential therapeutic interventions (other than thrombolysis) that could further our understanding of the perfusion of the penumbra during the first few hours after stroke onset.…”

“…18 Recently, PA imaging has been reliably used in breast tumor detection, 19 oxygenation monitoring in blood vessels, 18 subcutaneous vasculature imaging, 20 and neurovascular imaging. [21][22][23] Functional photoacoustic microscopy (fPAM) can offer in vivo, label-free measurements of functional changes in total hemoglobin concentration (HbT), cerebral blood volume (CBV), and hemoglobin oxygen saturation (SO 2 ) at a sub-hundred-micrometer resolution. 24 The current fPAM system has been used, with multiwavelength functional analysis, to image specific cortical activation changes in the rat brain with a good penetration depth 25 and to study cerebral autoregulation without the use of contrast agents.…”