Characterization of cerebral hemodynamic and oxygenation metabolic changes, as well neuronal function is of great
importance to study of brain functions and the relevant brain disorders such as drug addiction. Compared with other
neuroimaging modalities, optical imaging techniques have the potential for high spatiotemporal resolution and dissection
of the changes in cerebral blood flow (CBF), blood volume (CBV), and hemoglobing oxygenation and intracellular Ca
([Ca2+]i), which serves as markers of vascular function, tissue metabolism and neuronal activity, respectively. Recently,
we developed a multiwavelength imaging system and integrated it into a surgical microscope. Three LEDs of λ1=530nm,
λ2=570nm and λ3=630nm were used for exciting [Ca2+]i fluorescence labeled by Rhod2 (AM) and sensitizing total
hemoglobin (i.e., CBV), and deoxygenated-hemoglobin, whereas one LD of λ1=830nm was used for laser speckle
imaging to form a CBF mapping of the brain. These light sources were time-sharing for illumination on the brain and
synchronized with the exposure of CCD camera for multichannel images of the brain. Our animal studies indicated that
this optical approach enabled simultaneous mapping of cocaine-induced changes in CBF, CBV and oxygenated- and
deoxygenated hemoglobin as well as [Ca2+]i in the cortical brain. Its high spatiotemporal resolution (30μm, 10Hz) and
large field of view (4x5 mm2) are advanced as a neuroimaging tool for brain functional study.
Ca2+ plays a vital role as second messenger in signal transduction and the intracellular Ca2+ ([Ca2+]i) change is an
important indicator of neuronal activity in the brain, including both cortical and subcortical brain regions. Due to the
highly scattering and absorption of brain tissue, it is challenging to optically access the deep brain regions (e.g., striatum
at >3mm under the brain surface) and image [Ca2+]i changes with cellular resolutions. Here, we present two micro-probe
approaches (i.e., microlens, and micro-prism) integrated with a fluorescence microscope modified to permit imaging of
neuronal [Ca2+]i signaling in the striatum using a calcium indicator Rhod2(AM). While a micro-prism probe provides a
larger field of view to image neuronal network from cortex to striatum, a microlens probe enables us to track [Ca2+]i
dynamic change in individual neurons within the brain. Both techniques are validated by imaging neuronal [Ca2+]i
changes in transgenic mice with dopamine receptors (D1R, D2R) expressing EGFP. Our results show that micro-prism
images can map the distribution of D1R- and D2R-expressing neurons in various brain regions and characterize their
different mean [Ca2+]i changes induced by an intervention (e.g., cocaine administration, 8mg/kg., i.p). In addition,
microlens images can characterize the different [Ca2+]i dynamics of D1 and D2 neurons in response to cocaine, including
new mechanisms of these two types of neurons in striatum. These findings highlight the power of the optical
micro-probe imaging for dissecting the complex cellular and molecular insights of cocaine in vivo.
Because of its high spatial resolution and noninvasive imaging capabilities, optical coherence tomography has been used
to characterize the morphological details of various biological tissues including urinary bladder and to diagnose their
alternations (e.g., cancers). In addition to static morphology, the dynamic features of tissue morphology can provide
important information that can be used to diagnose the physiological and functional characteristics of biological tissues.
Here, we present the imaging studies based on optical coherence tomography to characterize motion related physiology
and functions of rat bladder detrusor muscles and compared the results with traditional biomechanical measurements.
Our results suggest that optical coherence tomography is capable of providing quantitative evaluation of contractile
functions of intact bladder (without removing bladder epithelium and connective tissue), which is potentially of more
clinical relevance for future clinical diagnosis - if incorporated with cystoscopic optical coherence tomography.
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