As transient intracellular Ca<sup>2+</sup> changes play an important role in many essential processes including neuronal and astrocytic plasticity, tracking brain activity via Ca<sup>2+</sup> is crucial. Unlike hemodynamics, Ca<sup>2+</sup> change must be measured optically using an ionic fluorescent Ca<sup>2+</sup> indicator. Here, we combine our highly sensitive multimodality optical imaging platform with genetically encoded Ca<sup>2+</sup> indicator (GCaMP6f) expressed in neurons or astrocytes in somatosensory cortex, which enables simultaneous tracking of single-stimulation-evoked neuronal, astrocytic Ca<sup>2+ </sup>transients along with the corresponding hemodynamic responses at high spatiotemporal resolutions. We imaged neuronal and astrocytic Ca<sup>2+</sup> transients from mouse cortex in response to a single electrical pulse (3mA, 0.3ms). Our results show that the neuronal Ca<sup>2+</sup> responses were strong (ΔF/F<sub>N</sub>=6.4±0.29%), fast (latency τ<sub>N</sub>=6±2.7ms) and of short duration (Δt<sub>N</sub>=537±34ms) whereas the astrocyte responses were weak, slow and long-lasting (i.e., ΔF/F<sub>A</sub>=1.7±0.1%, τ<sub>A</sub>=313±65ms, Δt<sub>A</sub> =993±48ms). The synchronized activities among astrocytes were temporally less correlated than those among neurons. These results demonstrate the capability of optical detection of cell-specific Ca<sup>2+</sup> activities from synchronized neuronal, astrocyte ensembles concurrently with the hemodynamic responses within the neuro-glio-vascular network, which can facilitate the study of the roles of astrocytes in the neurovascular coupling process. We also report time-lapse image results to analyze the interactions between stimuli-evoked neurovascular response versus the spontaneous cortical slow oscillations for brain functional studies
Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine’s effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.
Ultra-high resolution optical Doppler coherence tomography (μODT) is a promising tool for brain functional imaging. However, its sensitivity for detecting slow flows in capillary beds may limit its utility in visualizing and quantifying subtle changes in brain microcirculation. To address this limitation, we developed a novel method called contrast-enhanced μODT (c-μODT) in which intralipid is injected into mouse tail vein to enhance μODT detection sensitivity. We demonstrate that after intralipid injection, the flow detection sensitivity of μODT is dramatically enhanced by 230% as quantified by the fill factor (FF) of microvasculature. More importantly, we show that c-μODT preserves the quantitative properties for flow imaging, i.e., showing a comparable change ratio of hypercapnia-induced flow increase in the capillary network before and after injecting intralipid.
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.
Bladder carcinoma in situ (CIS) remains a clinical challenge. We compare the efficacies and potential limitations of
surface imaging modalities, e.g., white light (WL), fluorescence (FC), blue-light imaging (BL) and 3D optical coherence
tomography (3D OCT) for early diagnosis of bladder CIS. SV40T transgenic mice, which develop carcinoma in situ in
about 8 to 20 weeks then high grade papillary tumor in the bladder, were employed as the rodent carcinogenesis model
to closely mimic human bladder CIS. A total of 30 mice (i.e., SV40T mice blinded with its back strain Balb/c mice) were
enrolled in the study, including 20 with CIS and 10 with normal or benign lesions of the bladder mucosa. Our results
show that the low diagnostic sensitivities and specificities of WL, FC and BL for early CIS were significantly enhanced
by quantitative 3D OCT to 95.0% and 90.0%, suggesting the value of image-guided 3D OCT for future clinical
diagnosis of CIS in vivo.