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.
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.
It has been recently demonstrated that the cellular details of bladder epithelium embedded in speckle noise can be uncovered with time-lapse ultrahigh-resolution optical coherence tomography (TL-uOCT) by proper time-lapse frame averaging that takes advantage of cellular micromotion in fresh biological tissue ex vivo. Here, spectral-domain 3-D TL-uOCT is reported to further improve the image fidelity, and new experimental evidence is presented to differentiate normal and cancerous nuclei of rodent bladder epithelia. Results of animal cancer study reveal that despite a slight overestimation (e.g., <10%) of nuclear size (DN) to histological evaluation, TL-uOCT is capable of distinguishing normal (DN7 µm) and cancerous (e.g., high-grade DN13 µm) urothelia, which may potentially be very useful for enhancing the diagnosis of nonpapillary bladder cancer. More animal study is being conducted to examine the utility to differentiate hyperplasia, dysplasia, and carcinoma in situ.
A comparative study between 1.3-µm optical coherence tomography (OCT) and 40-MHz high-frequency ultrasound (HFUS) is presented to enhance imaging of bladder cancers ex vivo. A standard rat bladder cancer model in which transitional cell carcinoma (TCC) was induced by intravesical instillation of AY-27 cells was followed independently with both OCT and HFUS, and the image identifications were compared to histological confirmations. Results indicate that both OCT and HFUS were able to delineate the morphology of rat bladder [e.g., the urothelium (low backscattering/echo) and the underlying lamina propria and muscularis (high backscattering/echo]. OCT differentiated inflammatory lesions (e.g., edema, infiltrates and vasodilatation in lamina propria, hyperplasia) and TCC based on characterization of urothelial thickening and enhanced backscattering or heterogeneity (e.g., papillary features), which HFUS failed due to insufficient image resolution and contrast. On the other hand, HFUS was able to stage large T2 tumors that OCT failed due to limited imaging depth. The results suggest that multimodality cystoscopy combining OCT and HFUS may have the potential to enhance the diagnosis and staging of bladder cancers and to guide tumor resection, in which both high resolution (~10 µm) and enhanced penetration (>3mm) are desirable.
We present the first experimental result of direct delineation of the nuclei of living rat bladder epithelium with ultrahigh-resolution optical coherence tomography (uOCT). We demonstrate that the cellular details embedded in the speckle noise in a uOCT image can be uncovered by time-lapse frame averaging that takes advantage of the micromotion in living biological tissue. The uOCT measurement of the nuclear size (7.9±1.4 µm) closely matches the histological evaluation (7.2±0.8 µm). Unlike optical coherence microscopy (OCM), which requires a sophisticated high-NA microscopic objective, this approach uses a commercial-grade single achromatic lens (f/10 mm, NA/0.25) and provides a cross-sectional image over 0.6 mm of depth without focus tracking, thus holding great promise of endoscopic optical biopsy for diagnosis and grading of flat epithelial cancer such as carcinoma in situ in vivo.
We report the recent technical improvements in our microelectromechanical systems (MEMS)-based spectral-domain endoscopic OCT (SDEOCT) and applications for in vivo bladder imaging diagnosis. With the technical advances in MEMS mirror fabrication and endoscopic light coupling methods, the new SDEOCT system is able to visualize morphological details of the urinary bladder with high image fidelity close to bench-top OCT (e.g., 10 µm/12 µm axial/lateral resolutions, >108 dB dynamic range) at a fourfold to eightfold improved frame rate. An in vivo animal study based on a porcine acute inflammation model following protamine sulfate instillation is performed to further evaluate the utility of SDEOCT system to delineate bladder morphology and inflammatory lesions as well as to detect subsurface blood flow. In addition, a preliminary clinical study is performed to identify the morphological features pertinent to bladder cancer diagnosis, including loss of boundary or image contrast between urothelium and the underlying layers, heterogeneous patterns in the cancerous urothelium, and margin between normal and bladder cancers. The results of a human study (91% sensitivity, 80% specificity) suggest that SDEOCT enables a high-resolution cross-sectional image of human bladder structures to detect transitional cell carcinomas (TCC); however, due to reduced imaging depth of SDEOCT in cancerous lesions, staging of bladder cancers may be limited to T1 to T2a (prior to muscle invasion).
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