Phase II multi-center trial of optical coherence tomography as an adjunct to white light cystoscopy for intravesical real time imaging and staging of bladder cancer.

BACKGROUND: Optical coherence tomography (OCT) is a novel imaging modality that provides microstructural information of different tissue layers using near-infrared light. This prospective, multicenter phase II trial aimed to assess the accuracy of OCT-assisted cystoscopy for bladder tumor staging. METHODS: Patients with primary or recurrent bladder tumors (Ta,T1) identified by outpatient cystoscopy were included. The primary objective was to assess the accuracy and positive predictive value of for determining tumor stage ≥T1 correlated by histopathology. 72 suspicious lesions from 63 patients were eligible to analyze in the study. All suspected lesions were evaluated with conventional cystoscopy, interpreted in real-time using OCT, and then resected. All results were compared to pathology. A total of 363 OCT images of tumor and normal mucosa in 25 patients were obtained to evaluate diagnostic efficacy of the computer-aided texture analysis algorithm. RESULTS: Sensitivity and specificity for predicting invasive tumors (≥ T1, n = 17) were 58.8% and 92.7% for cystoscopy, 64.7% and 100% for OCT-assisted cystoscopy, respectively. Accuracy of cystoscopy and OCT-assisted cystoscopy for predicting invasive tumor was 84.7% and 91.7% (P = 0.063), respectively. Cystoscopy and OCT-assisted cystoscopy correctly predicted T stage in 52/72 and 59/72 cases, respectively (P = 0.016). Cystoscopy missed 2 more invasive tumors than OCT-assisted cystoscopy. Cystoscopy (14.3%, 1/7) and OCT-assisted cystoscopy (28.6%, 2/7) showed relatively low sensitivity in detecting muscle invasion. Computer aided texture analysis demonstrated 75.1% sensitivity, 64.0% specificity, and 74.4% accuracy for differentiating tumor and normal urothelium. CONCLUSION: OCT-assisted cystoscopy is a real time noninvasive and simple procedure that enhanced the accuracy of staging bladder tumors and prediction of any tumor invasion. Though the study did not meet the prespecified primary endpoint, OCT imaging is a promising adjunct to cystoscopy that may supplement intraoperative decision-making during transurethral resection of bladder tumors and additional prospective studies are warranted.

Photocatalytic graphitic carbon nitride-chitosan composites for pathogenic biofilm control under visible light irradiation.

Photocatalysis holds promise for inactivating environmental pathogens. Visible-light-responsive composites of carbon-doped graphitic carbon nitride and chitosan with high reactivity and processability were fabricated, and they can control pathogenic biofilms for environmental, food, biomedical, and building applications. The broad-spectrum biofilm inhibition and eradication of the photocatalytic composites against Staphylococcus epidermidis, Pseudomonas aeruginosa PAO1, and Escherichia coli O157: H7 under visible light irradiation were demonstrated. Extracellular polymeric substances in Escherichia coli O157: H7 biofilms were most resistant to photocatalytic oxidation, which led to reduced performance for biofilm removal. 1O2 produced by the composites was believed to dominate biofilm inactivation. Moreover, the composites exhibited excellent performance for inhibiting biofilm development in urine, highlighting the promise for inactivating environmental biofilms developed from multiple bacterial species. Our study provides fundamental insights into the development of new photocatalytic composites, and elucidates the mechanism of how the photocatalyst reacts with a microbiological system.

Visible-Light-Responsive Photocatalyst of Graphitic Carbon Nitride for Pathogenic Biofilm Control.

Pathogenic biofilms raise significant health and economic concerns, because these bacteria are persistent and can lead to long-term infections in vivo and surface contamination in healthcare and industrial facilities or devices. Compared with conventional antimicrobial strategies, photocatalysis holds promise for biofilm control because of its broad-spectrum effectiveness under ambient conditions, low cost, easy operation, and reduced maintenance. In this study, we investigated the performance and mechanism of Staphylococcus epidermidis biofilm control and eradication on the surface of an innovative photocatalyst, graphitic carbon nitride (g-C3N4), under visible-light irradiation, which overcame the need for ultraviolet light for many current photocatalysts (e.g., titanium dioxide (TiO2)). Optical coherence tomography and confocal laser scanning microscopy (CLSM) suggested that g-C3N4 coupons inhibited biofilm development and eradicated mature biofilms under the irradiation of white light-emitting diodes. Biofilm inactivation was observed occurring from the surface toward the center of the biofilms, suggesting that the diffusion of reactive species into the biofilms played a key role. By taking advantage of scanning electron microscopy, CLSM, and atomic force microscopy for biofilm morphology, composition, and mechanical property characterization, we demonstrated that photocatalysis destroyed the integrated and cohesive structure of biofilms and facilitated biofilm eradication by removing the extracellular polymeric substances. Moreover, reactive oxygen species generated during g-C3N4 photocatalysis were quantified via reactions with radical probes and 1O2 was believed to be responsible for biofilm control and removal. Our work highlights the promise of using g-C3N4 for a broad range of antimicrobial applications, especially for the eradication of persistent biofilms under visible-light irradiation, including photodynamic therapy, environmental remediation, food-industry applications, and self-cleaning surface development.

Development of novel imaging probe for optical/acoustic radiation imaging (OARI).

PURPOSE: Optical/acoustic radiation imaging (OARI) is a novel imaging modality being developed to interrogate the optical and mechanical properties of soft tissues. OARI uses acoustic radiation force to generate displacement in soft tissue. Optical images before and after the application of the force are used to generate displacement maps that provide information about the mechanical properties of the tissue under interrogation. Since the images are optical images, they also represent the optical properties of the tissue as well. In this paper, the authors present the first imaging probe that uses acoustic radiation force in conjunction with optical coherence tomography (OCT) to provide information about the optical and mechanical properties of tissues to assist in the diagnosis and staging of epithelial cancers, and in particular bladder cancer. METHODS: The OARI prototype probe consisted of an OCT probe encased in a plastic sheath, a miniaturized transducer glued to a plastic holder, both of which were encased in a 10 cm stainless steel tube with an inner diameter of 10 mm. The transducer delivered an acoustic intensity of 18 W/cm(2) and the OCT probe had a spatial resolution of approximately 10-20 µm. The tube was filled with deionized water for acoustic coupling and covered by a low density polyethylene cap. The OARI probe was characterized and tested on bladder wall phantoms. The phantoms possessed Young's moduli ranging from 10.2 to 12 kPa, mass density of 1.05 g/cm(3), acoustic attenuation coefficient of 0.66 dB/cm MHz, speed of sound of 1591 m/s, and optical scattering coefficient of 1.80 mm(-1). Finite element model (FEM) theoretical simulations were performed to assess the performance of the OARI probe. RESULTS: The authors obtained displacements of 9.4, 8.7, and 3.4 µm for the 3%, 4%, and 5% bladder wall phantoms, respectively. This shows that the probe is capable of generating optical images, and also has the ability to generate and track displacements in tissue. This will provide information about the optical and mechanical properties of the tissue to assist in epithelial cancer detection. The corresponding theoretical FEM displacement was 5.8, 5.4, and 5.0 µm for the 3%, 4%, and 5% phantoms, respectively. Deviation between OARI displacement and FEM displacement is due to the resolution of the crosscorrelation algorithm used to track the displacement. To the authors' knowledge, this is the first probe that successfully combines OCT with a source of acoustic radiation force. CONCLUSIONS: The OARI probe has the ability to provide information about the mechanical and optical properties of phantoms and soft tissue. This could prove useful in early epithelial cancer detection. Because the probe is 10 mm in diameter, it is currently only useful for skin and oral applications. The probe would have to be reduced in size to make it applicable for cancer detection in other internal sites. Future work will focus on utilizing phase-sensitive optical coherence elastography to obtain the resulting OARI displacements, improving the resolution of the probe, and enable physicians to better evaluate the mechanical properties of soft tissues.

An automatic rat brain extraction method based on a deformable surface model.

The extraction of the brain from the skull in medical images is a necessary first step before image registration or segmentation. While pre-clinical MR imaging studies on small animals, such as rats, are increasing, fully automatic imaging processing techniques specific to small animal studies remain lacking. In this paper, we present an automatic rat brain extraction method, the Rat Brain Deformable model method (RBD), which adapts the popular human brain extraction tool (BET) through the incorporation of information on the brain geometry and MR image characteristics of the rat brain. The robustness of the method was demonstrated on T2-weighted MR images of 64 rats and compared with other brain extraction methods (BET, PCNN, PCNN-3D). The results demonstrate that RBD reliably extracts the rat brain with high accuracy (>92% volume overlap) and is robust against signal inhomogeneity in the images.

Tissue-mimicking bladder wall phantoms for evaluating acoustic radiation force-optical coherence elastography systems.

PURPOSE: Acoustic radiation force-optical coherence elastography (ARF-OCE) systems are novel imaging systems that have the potential to simultaneously quantify and characterize the optical and mechanical properties of in vivo tissues. This article presents the construction of bladder wall phantoms for use in ARF-OCE systems. Mechanical, acoustic, and optical properties are reported and compared to published values for the urinary bladder. METHODS: The phantom consisted of 0.2000 +/- 0.0089 and 6.0000 +/- 0.2830 microm polystyrene microspheres (Polysciences Inc., Warrington, PA, Catalog Nos. 07304 and 07312), 7.5 +/- 1.5 microm copolymer microspheres composed of acrylonitrile and vinylidene chloride, (Expancel, Duluth, GA, Catalog No. 461 DU 20), and bovine serum albumin within a gelatin matrix. Young's modulus was measured by successive compression of the phantom and obtaining the slope of the resulting force-displacement data. Acoustic measurements were performed using the transmission method. The phantoms were submerged in a water bath and placed between transmitting and receiving 13 mm diameter unfocused transducers operating at a frequency of 3.5 MHz. A MATLAB algorithm to extract the optical scattering coefficient from optical coherence tomography (OCT) images of the phantom was used. RESULTS: The phantoms possess a Young's modulus of 17.12 +/- 2.72 kPa, a mass density of 1.05 +/- 0.02 g/cm3, an acoustic attenuation coefficient of 0.66 +/- 0.08 dB/cm/MHz, a speed of sound of 1591 +/- 8.76 m/s, and an optical scattering coefficient of 1.80 +/- 0.23 mm(-1). Ultrasound and OCT images of the bladder wall phantom are presented. CONCLUSIONS: A material that mimics the mechanical, optical, and acoustic properties of healthy bladder wall has been developed. This tissue-mimicking bladder wall phantom was developed as a control tool to investigate the feasibility of using ARF-OCE to detect the mechanical and optical changes that may be indicative of the onset or development of cancer in the urinary bladder. By following the methods used in this article, phantoms matching the optical, acoustic, and mechanical properties of other biological tissues can also be constructed.

Wavelet analysis enables system-independent texture analysis of optical coherence tomography images.

Texture analysis for tissue characterization is a current area of optical coherence tomography (OCT) research. We discuss some of the differences between OCT systems and the effects those differences have on the resulting images and subsequent image analysis. In addition, as an example, two algorithms for the automatic recognition of bladder cancer are compared: one that was developed on a single system with no consideration for system differences, and one that was developed to address the issues associated with system differences. The first algorithm had a sensitivity of 73% and specificity of 69% when tested using leave-one-out cross-validation on data taken from a single system. When tested on images from another system with a different central wavelength, however, the method classified all images as cancerous regardless of the true pathology. By contrast, with the use of wavelet analysis and the removal of system-dependent features, the second algorithm reported sensitivity and specificity values of 87 and 58%, respectively, when trained on images taken with one imaging system and tested on images taken with another.

Computer recognition of cancer in the urinary bladder using optical coherence tomography and texture analysis.

The vast majority of bladder cancers originate within 600 microm of the tissue surface, making optical coherence tomography (OCT) a potentially powerful tool for recognizing cancers that are not easily visible with current techniques. OCT is a new technology, however, and surgeons are not familiar with the resulting images. Technology able to analyze and provide diagnoses based on OCT images would improve the clinical utility of OCT systems. We present an automated algorithm that uses texture analysis to detect bladder cancer from OCT images. Our algorithm was applied to 182 OCT images of bladder tissue, taken from 68 distinct areas and 21 patients, to classify the images as noncancerous, dysplasia, carcinoma in situ (CIS), or papillary lesions, and to determine tumor invasion. The results, when compared with the corresponding pathology, indicate that the algorithm is effective at differentiating cancerous from noncancerous tissue with a sensitivity of 92% and a specificity of 62%. With further research to improve discrimination between cancer types and recognition of false positives, it may be possible to use OCT to guide endoscopic biopsies toward tissue likely to contain cancer and to avoid unnecessary biopsies of normal tissue.

Evaluation of superficial bladder transitional-cell carcinoma by optical coherence tomography.

BACKGROUND AND PURPOSE: Optical coherence tomography (OCT) is a new modality that allows noninvasive examination of the internal structure of biological tissue in vivo with a spatial resolution of 10 to 15 microm. This study evaluated the clinical application of OCT to determine epithelial and subepithelial anatomic structure and invasiveness of bladder epithelial lesions. MATERIALS AND METHODS: The OCT examination was performed with a 980-nm 10 mW superluminescent diode using a 2.7-mm-diameter optical fiber positioned cystoscopically. A total of 261 scans of 1.5 seconds' duration, which generated 200 x 200-pixel images, were performed on 87 areas in 24 patients at high risk of having transitional-cell carcinoma (TCC). Lesions, visually suspect, and normal areas were photographed, scanned, and biopsied. The scans were evaluated independently before comparison with histopathology findings. RESULTS: Of the 87 areas, 29 of 36 visually suspect areas and 35 of 35 normal areas, were correctly diagnosed with OCT. Of the 16 areas with papillary TCC, all 16 were diagnosed correctly as tumor, and 9 of 10 were diagnosed correctly as invasive, including 6 with lamina propria invasion only. Papillary and flat tumors, carcinoma in situ, inflammation, chronic cystitis, and von Brunn's nests were scanned. Overall, OCT had a sensitivity of 100%, overall specificity of 89%, positive predictive value of 75%, and negative predictive value of 100%. The accuracy was 92%. The positive predictive value for invasion was 90%. CONCLUSION: Optical coherence tomography is a simple, portable, promising modality for evaluation of bladder lesions and depth of tumor penetration. Further refinement of this technology may lead to the development of an optical surrogate for biopsy.

A micromachine high frequency ultrasound scanner using photolithographic fabrication.

In this paper we describe two new types of transducer assemblies fabricated from polyimide films with photolithography that use a polyimide micromachine (MEMS) actuator to mechanically scan an ultrasound beam. Forward viewing transducers pivoting on cantilever hinges and side scanning transducers tilting on torsion hinges were fabricated on polyimide substrates with tables 1.125 mm and 2.25 mm wide. PZT transducers fabricated on these tables operating at 20 MHz and 30 MHz yielded insertion losses of 20-26 dB and fractional bandwidths of 34-49%. The transducer assemblies driven by MEMS actuators produced sector scans of 45-60 degrees in air at resonant frequencies of 32 to 90 Hz and sector scans in fluid of 6-8 degrees. Real time images of wire phantoms were obtained using a single channel imaging system based on a personal computer platform with LabVIEW (National Instruments Corp., Austin, TX) software.