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. 2010 Dec 15;194(1):108-15.
doi: 10.1016/j.jneumeth.2010.09.021. Epub 2010 Oct 7.

Label-free in vivo optical imaging of functional microcirculations within meninges and cortex in mice

Yali Jia  1 , Ruikang K Wang
Affiliations

Label-free in vivo optical imaging of functional microcirculations within meninges and cortex in mice

Yali Jia et al. J Neurosci Methods. .

Abstract

Abnormal microcirculation within meninges is common in many neurological diseases. There is a need for an imaging method that is capable of monitoring dynamic meningeal microcirculations, preferably decoupled from cortical blood flow. Optical microangiography (OMAG) is a recently developed label-free imaging method capable of producing 3D images of dynamic blood perfusion within micro-circulatory tissue beds at an imaging depth up to ∼2 mm, with an unprecedented imaging sensitivity to blood flow at ∼4 μm/s. In this paper, we demonstrate the utility of OMAG in imaging the detailed blood flow distributions, at a capillary level resolution, within the meninges and cortex in mice with the cranium left intact. Using a thrombotic mouse model, we show that the OMAG can yield longitudinal measurements of meningeal vascular responses to the insult and can decouple these responses from those in the cortex, giving valuable information regarding the localized hemodynamics along with the dynamic formation of thrombotic event. The results indicate that OMAG can be a useful tool to study therapeutic strategies in preclinical animal models in order to mitigate various pathologies that are mainly related to the meningeal circulations.

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Conflict of interest statement

Conflict of Interest

The authors declare no conflict of interests.

Figures

Fig. 1
Fig. 1
(A) Schematic of the UHS-OMAG system where PC represents the polarization controller. (B) Sketch of the designed probe beam targeting the meninges (drawing not to scale).
Fig. 2
Fig. 2
Typical in vivo UHS-OMAG images of the cerebral microcirculation in mice. Images were taken with the skull left intact. (A) is one typical UHS-OMAG cross-sectional image (B-scan) of microstructures showing morphological features, such as cranium and cortex, and (B) is the corresponding blood flow image where the dural microvessels (e.g., pointed by arrows) are distinguishable from the vessels in cortex. The projection maps of functional blood vessel network within (C) the meninges and (D) the cortex, respectively, obtained from one 3D scan. White bar = 500µm.
Fig. 3
Fig. 3
The functional blood flow networks of the entire brain in mice were imaged by UHS-OMAG in vivo. Because of its depth-resolved imaging capability, OMAG is capable of providing simultaneous imaging of microcirculations within (A) the meninges and (B) the cortex of a mouse. The whole imaging area is ~10×10 mm2. SS, sagittal suture; ACS, anterior coronal suture; PCS, posterior coronal.
Fig. 4
Fig. 4
Representative meningeal microvascular network during thrombus formation induced by FeCl3. (A) is a sketch of the mouse skull; the red box indicates the region imaged (~2.5mm×~1.3mm) by UHS-OMAG and the dotted line indicates the place where the FeCl3 was topically applied. (B) shows serial OMAG images of microvascular occlusion and blood flow changes, indicating development of thrombus for the region shown in (A). Numbers in the bottom left corner of each panel are minutes after application of FeCl3. (C) is a vascular sketch based on the vascular occlusion sequence in (B), where four vessels are indicated in different colors, the numbers indicate their occlusion sequence and the arrows show four regions of interest in which blood flow will be quantified.
Fig. 5
Fig. 5
Representative cortical microvascular network during thrombus formation in the region (~2.5mm×~1.3mm) shown in Fig. 4A. Numbers on the bottom left corner are minutes after application of FeCl3. The dark shadows starting from 5 mins indicate a gradual propagation of the thrombosis in the vicinity of FeCl3 solution, resulting in expansion of the occlusion fronts shown by the dotted outlines.
Fig. 6
Fig. 6
Plots of the velocity profiles across the dural vessels 1 and 2 pointed by arrows in Fig.4C, respectively, along with the second-order polynomial fit and the R-squared value of the fit at the time point as shown [0–15min (vessel 1), 15–30min (vessels 2)]. The time of imaging in minutes is given in the upper right corner of each plot.
Fig. 7
Fig. 7
Quantitative measures of the vessel mean velocity (A), vessel inner diameter (B), and flow rate (C) over the 35-min time course in four individual feeding vessels (see Fig. 4C), following the induction of thrombus. The time evolution of blood volume changes in cortex for the imaged region is shown in (D).
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