Multiparametric photoacoustic microscopy of the mouse brain with 300-kHz A-line rate

Wang, Tianxiong; Sun, Naidi; Cao, Rui; Ning, Bo; Chen, Ruimin; Zhou, Qifa; Hu, Song

doi:10.1117/1.nph.3.4.045006

Cited by 55 publications

(39 citation statements)

References 19 publications

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“…This limitation prevents it from imaging rapid cerebral hemodynamic responses to neurostimulation and disease onsets (e.g., epileptic seizures). Integrating the head-restraint setting and our recently reported high-speed multi-parametric PAM (Wang et al, 2016) may provide a potential solution. Another limitation lies in the quantification of CMRO 2 .…”

Section: Discussionmentioning

confidence: 99%

Functional and oxygen-metabolic photoacoustic microscopy of the awake mouse brain

et al. 2017

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A long-standing challenge in optical neuroimaging has been the assessment of hemodynamics and oxygen metabolism in the awake rodent brain at the microscopic level. Here, we report first-of-a-kind head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin, and blood flow in awake mice. Combining these hemodynamic measurements allows us to derive two key metabolic parameters—oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2). This enabling technology offers the first opportunity to comprehensively and quantitatively characterize the hemodynamic and oxygen-metabolic responses of the mouse brain to isoflurane, a general anesthetic widely used in preclinical research and clinical practice. Side-by-side comparison of the awake and anesthetized brains reveals that isoflurane induces diameter-dependent arterial dilation, elevated blood flow, and reduced OEF in a dose-dependent manner. As a result of the combined effects, CMRO2 is significantly reduced in the anesthetized brain under both normoxia and hypoxia, which suggests a mechanism for anesthetic neuroprotection. The head-restrained functional and metabolic PAM opens a new avenue for basic and translational research on neurovascular coupling without the strong influence of anesthesia and on the neuroprotective effects of various interventions, including but not limited to volatile anesthetics, against cerebral hypoxia and ischemia.

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Section: Discussionmentioning

confidence: 99%

Functional and oxygen-metabolic photoacoustic microscopy of the awake mouse brain

et al. 2017

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“…OR‐PAM is a hybrid imaging modality that combines optical and ultrasound imaging . It has been reported for various biomedical label‐free imaging applications . A focused nanosecond pulsed laser beam illuminates the sample in OR‐PAM.…”

Section: Introductionmentioning

confidence: 99%

In vivo label‐free functional photoacoustic monitoring of ischemic reperfusion

Dinish

Goh

et al. 2019

Journal of Biophotonics

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Pressure ulcer formation is a common problem among patients confined to bed or restricted to wheelchairs. The ulcer forms when the affected skin and underlying tissues go through repeated cycles of ischemia and reperfusion, leading to inflammation. This theory is evident by intravital imaging studies performed in immune cell–specific, fluorescent reporter mouse skin with induced ischemia‐reperfusion (I‐R) injuries. However, traditional confocal or multiphoton microscopy cannot accurately monitor the progression of vascular reperfusion by contrast agents, which leaks into the interstitium under inflammatory conditions. Here, we develop a dual‐wavelength micro electro mechanical system (MEMS) scanning–based optical resolution photoacoustic microscopy (OR‐PAM) system for continuous label‐free functional imaging of vascular reperfusion in an IR mouse model. This MEMS‐OR‐PAM system provides fast scanning speed for concurrent dual‐wavelength imaging, which enables continuous monitoring of the reperfusion process. During reperfusion, the revascularization of blood vessels and the oxygen saturation (sO2) changes in both arteries and veins are recorded, from which the local oxygen extraction ratios of the ischemic tissue and the unaffected tissue can be quantified. Our MEMS‐OR‐PAM system provides novel perspectives to understand the I‐R injuries. It solves the problem of dynamic label‐free functional monitoring of the vascular reperfusion at high spatial resolution.

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“…4 Recently, laser scanning has been incorporated to steer the optical beam within the acoustic focus for improved imaging speed. 6 A problem of the two-dimensional (2-D) raster scan is that the depth of focus of the optical beam is often insufficient to accommodate the depth variation of the mouse brain surface when the entire cortex is imaged. The out-of-focus issue compromises the image resolution and signal-to-noise ratio (SNR).…”

Section: Introductionmentioning

confidence: 99%

Cortex-wide multiparametric photoacoustic microscopy based on real-time contour scanning

Sun

Cao

et al. 2019

Neurophoton.

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Large-scale, high-resolution imaging of cerebral hemodynamics is essential for brain research. Uniquely capable of comprehensive quantification of cerebral hemodynamics and oxygen metabolism in rodents based on the endogenous hemoglobin contrast, multiparametric photoacoustic microscopy (PAM) is ideally suited for this purpose. However, the out-of-focus issue due to the uneven surface of the rodent brain results in inaccurate PAM measurements and presents a significant challenge to cortex-wide multiparametric recording. We report a large-scale, high-resolution, multiparametric PAM system based on real-time surface contour extraction and scanning, which avoids the prescan and offline calculation of the contour map required by previously reported contour-scanning strategies. The performance of this system has been demonstrated in both phantoms and the live mouse brain through a thinned-skull window. Side-by-side comparison shows that the real-time contour scanning not only improves the quality of structural images by addressing the out-of-focus issue but also ensures accurate measurements of the concentration of hemoglobin (C Hb), oxygen saturation of hemoglobin (sO 2), and cerebral blood flow (CBF) over the entire mouse cortex. Furthermore, quantitative analysis reveals how the out-of-focus issue impairs the measurements of C Hb , sO 2 , and CBF.

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Multiparametric photoacoustic microscopy of the mouse brain with 300-kHz A-line rate

Cited by 55 publications

References 19 publications

Functional and oxygen-metabolic photoacoustic microscopy of the awake mouse brain

Functional and oxygen-metabolic photoacoustic microscopy of the awake mouse brain

In vivo label‐free functional photoacoustic monitoring of ischemic reperfusion

Cortex-wide multiparametric photoacoustic microscopy based on real-time contour scanning

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