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

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 (SO2). Changes in specific cerebral vessels corresponding to various electrical stimulation intensities and durations were bilaterally imaged with 36 × 65-μm2 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 SO2 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. © 2012 Society of Photo-Optical Instrumentation Engineers (SPIE)

Design, simulation and experimental validation of a novel flexible neural probe for deep brain stimulation and multichannel recording

An implantable micromachined neural probe with multichannel electrode arrays for both neural signal recording and electrical stimulation was designed, simulated and experimentally validated for deep brain stimulation (DBS) applications. The developed probe has a rough three-dimensional microstructure on the electrode surface to maximize the electrode-tissue contact area. The flexible, polyimide-based microelectrode arrays were each composed of a long shaft (14.9 mm in length) and 16 electrodes (5 μm thick and with a diameter of 16 μm). The ability of these arrays to record and stimulate specific areas in a rat brain was evaluated. Moreover, we have developed a finite element model (FEM) applied to an electric field to evaluate the volume of tissue activated (VTA) by DBS as a function of the stimulation parameters. The signal-to-noise ratio ranged from 4.4 to 5 over a 50 day recording period, indicating that the laboratory-designed neural probe is reliable and may be used successfully for long-term recordings. The somatosensory evoked potential (SSEP) obtained by thalamic stimulations and in vivo electrode-electrolyte interface impedance measurements was stable for 50 days and demonstrated that the neural probe is feasible for long-term stimulation. A strongly linear (positive correlation) relationship was observed among the simulated VTA, the absolute value of the SSEP during the 200 ms post-stimulus period (ΣSSEP) and c-Fos expression, indicating that the simulated VTA has perfect sensitivity to predict the evoked responses (c-Fos expression). This laboratory-designed neural probe and its FEM simulation represent a simple, functionally effective technique for studying DBS and neural recordings in animal models. © 2012 IOP Publishing Ltd

Transcranial imaging of functional cerebral hemodynamic changes in single blood vessels using in vivo photoacoustic microscopy

Optical imaging of changes in total hemoglobin concentration (HbT), cerebral blood volume (CBV), and hemoglobin oxygen saturation (SO 2) provides a means to investigate brain hemodynamic regulation. However, high-resolution transcranial imaging remains challenging. In this study, we applied a novel functional photoacoustic microscopy technique to probe the responses of single cortical vessels to left forepaw electrical stimulation in mice with intact skulls. Functional changes in HbT, CBV, and SO 2 in the superior sagittal sinus and different-sized arterioles from the anterior cerebral artery system were bilaterally imaged with unambiguous 36 × 65-μm 2 spatial resolution. In addition, an early decrease of SO 2 in single blood vessels during activation (i.e., 'the initial dip') was observed. Our results indicate that the initial dip occurred specifically in small arterioles of activated regions but not in large veins. This technique complements other existing imaging approaches for the investigation of the hemodynamic responses in single cerebral blood vessels. © 2012 ISCBFM All rights reserved