Cocaine-induced stroke is among the most serious medical complications associated with its abuse. However the extent to which acute cocaine may induce silent microischemia predisposing the cerebral tissue to neurotoxicity has not been investigated; in part, because of limitations of current neuroimaging tools, i.e., lack of high spatiotemporal resolution and sensitivity to simultaneously measure cerebral blood flow (CBF) in vessels of different calibers (including capillaries) quantitatively and over a large field of view. Here we combine ultrahigh-resolution optical coherence tomography to enable tracker-free 3D microvascular angiography (μOCA) and a new phase-intensity-mapping algorithm to enhance the sensitivity of 3D optical Doppler tomography (μODT) for simultaneous capillary CBF quantization. We apply the technique to study the responses of cerebral microvascular networks to single and repeated cocaine administration in the mouse somatosensory cortex. We show that within 2–3 minutes after cocaine administration CBF markedly decreased (e.g., ~70%) but the magnitude and recovery differed for the various types of vessels; arterioles had the fastest recovery (~5min), capillaries varied drastically (from 4–20min) and venules showed relatively slower recovery (~12min). More importantly, we showed that cocaine interrupted CBF in some arteriolar branches for over 45min and this effect was exacerbated with repeated cocaine administration. These results provide evidence that cocaine doses within the range administered by drug abusers induces cerebral microischemia and that these effects are exacerbated with repeated use. Thus cocaine-induced microischemia is likely to be a contributor to its neurotoxic effects.

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A dual-wavelength laser speckle contrast imaging technique (DW-LSCI) is presented for simultaneous imaging of cerebral blood flow and hemoglobin oxygenation changes at high spatiotemporal resolutions. Experimental validation was performed using a rat transient forebrain ischemia model. The results showed that DW-LSCI was able to track detailed hemodynamic and metabolic changes induced by ischemia, i.e., decreased oxy- and total hemoglobin concentrations and blood flow as well as increased deoxy-hemoglobin concentration in the downstream regions, thus allowing us to distinguish cerebral arterial and venous flows. Simultaneous cerebral blood flow and oxygenation imaging at high spatiotemporal resolutions is crucial to the understanding of neural process and brain functions.

We present an animal study to examine the utility and potential limitations of optical coherence tomography (OCT) for noninvasive evaluation of biomaterial scaffold-assisted wound healing. The transverse and axial resolutions of the OCT system at the wavelength of 1.3 microm were 12 and 10 microm, respectively. A murine full-thickness transcutaneous wound model was employed, in which a phi 10 mm full-thickness wound was created on the back of each male Balb/cJ mouse and a porous collagen scaffold was implanted in the wound bed followed by coverage with a Tegaderm film. Sequential cross-sectional OCT scans were performed at different time points postsurgical intervention to track morphological changes during wound recovery, and the captured OCT images were validated by their corresponding histological specimens. The results indicated that with removal of the high-scattering skin, OCT was capable of imaging to a depth of over 1.5 mm into the wound bed and differentiating various features evolved during wound healing at a high resolution approaching histopathology. OCT was able to not only delineate the epidermis and dermis of normal mouse skin, but also differentiate collagen implant from the underlying subcutaneous tissue; besides, it could track the wound size changes in both lateral and vertical directions. More importantly, OCT was able to detect inflammation, early re-epithelialization, and resorption of the collagen scaffold. These findings suggested the potential of OCT for noninvasive and high-resolution monitoring of assisted wound healing in vivo, longitudinally, and instantaneously.