High resolution imaging of transitional cell carcinoma with optical coherence tomography: Feasibility for the evaluation of bladder pathology
Abstract and Figures
Significant challenges regarding patient morbidity and mortality remain in the management of transitional cell carcinoma (TCC). Among the most important of these challenges is the inability to identify early neoplastic changes and to assess the degree of tumour invasion into the bladder wall in vivo. Optical coherence tomography (OCT) has been recently developed to provide in situ, high resolution, catheter/endoscope based imaging. This study explored the feasibility of OCT for the evaluation of bladder pathology. Both in vitro and in vivo studies were performed. In vitro imaging of pathological human bladder was performed and compared with normal specimens and histopathology. In vivo imaging of normal rabbit bladder was also performed with our current catheter/endoscope based systems. In the in vitro studies, OCT was able to delineate normal microstructure of the bladder, such as the mucosa, submucosa and muscularis layers. This was in contrast to specimens of invasive carcinoma, where a disruption of the normal bladder wall architecture was seen. The in vivo experiment demonstrated current limitations of the catheter/endoscope based systems and provided valuable information for developing an improved system for bladder imaging. The ability of OCT to delineate microstructure of the bladder wall suggests feasibility for endoscopic based imaging. In particular, there is a potential role envisioned for OCT in the management of TCC, identifying pre-malignant states and the depth of tumour invasion.
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... With the use of OCT in diagnosing non-melanoma skin cancer, the number of invasive skin biopsies can be reduced (Mogensen et al., 2009). Hollow organs like the bronchi, the gastrointestinal tract, and the urinary bladder can by examined with the OCT as it is endoscopic-compatible (Tearney et al., 1997, Jesser et al., 1999, Wang et al., 2001, Tsuboi et al., 2005. ...
... OCT has been used widely in the medical field. Examples include images of the retina, monitoring retinal diseases, diagnosing cardiac and dermatological diseases, and examining hollow organs like gastrointestinal tract and bladder (Tearney et al., 1997, Jesser et al., 1999, Wang et al., 2001, Tsuboi et al., 2005, Low et al., 2006, Marschall et al., 2011. ...
Background: Molar Incisor Hypomineralisation (MIH) can affect one or more first permanent molars (FPM), with or without the permanent incisors, prevalence ranges from 3-40%. Severity varies, and can be associated with hypersensitivity, post-eruptive breakdown (PEB) and aesthetic concerns. Different toothpastes have been suggested to enhance remineralization and reduce sensitivity, including fluoride or Novamin containing toothpastes. Aim: To compare tooth surface loss (TSL) from toothbrushing using different toothpastes in MIH affected and sound FPMs using Optical Coherence Tomography (OCT). Methods: Extracted human FPMs (N=27) Sound or with MIH were collected under ethical approval. Samples were classified using EAPD index 2014, in which type 21 indicates a white/cream opacity and type 22 yellow/brown opacity. Erosion using 1% citric acid was applied, followed by abrasion with an electric toothbrush and (i) saliva, (ii) Sensodyne® complete protection (inc Novamin), & (iii) Sensodyne® children pronamel (inc fluoride) for 100 cycles. A small needle was attached as a reference for calculation of TSL. OCT images were taken every 20 cycles, and the amount of TSL was calculated. Results: TSL was higher in children pronamel group than complete protection and saliva for MIH (type 22) and control samples, with the highest TSL 100µm and a mean of 85µm. The lowest TSL was 7µm in control group brushed with saliva. In MIH sample (type 21), the highest TSL was with Complete protection (85µm). However, the average mean of TSL for type 21 lesions with both complete protection and children pronamel groups was 45µm. Conclusion: Children Pronamel toothpaste resulted in more TSL, whereas complete protection resulted in less TSL in MIH type 22. This suggests Novamin may be beneficial in severely affected MIH teeth, but larger sample sizes are needed before a conclusion can be reached.
... Optical coherence tomography (OCT) is a well-developed biomedical imaging technique [1], which has significant advantages, such as real-time, non-invasive, and high-resolution images [2,3]. Combined with OCT intraluminal imaging's application scenario, there is a better prospect of its clinical application for evaluating intraluminal lesions, which already have mature applications in the cardiovascular system [4][5][6][7], esophagus [8][9][10], gastrointestinal tract [11][12][13][14][15], and reproductive tract system [16][17][18][19][20][21]. ...
Optical coherence tomography (OCT) image processing can provide information about the uterine cavity structure, such as endometrial surface roughness, which is important for the diagnosis of uterine cavity lesions. The accurate segmentation of uterine cavity OCT images is a key step of OCT image processing. We proposed an EA-UNet-based image segmentation model that uses a U-Net network structure with a multi-scale attention mechanism to improve the segmentation accuracy of uterine cavity OCT images. The E(ECA-C) module introduces a convolutional layer combined with the ECA attention mechanism instead of max pool, reduces the loss of feature information, enables the model to focus on features in the region to be segmented, and suppresses irrelevant features to enhance the network’s feature-extraction capability and learning potential. We also introduce the A (Attention Gates) module to improve the model’s segmentation accuracy by using global contextual information. Our experimental results show that the proposed EA-UNet can enhance the model’s feature-extraction ability; furthermore, its MIoU, Sensitivity, and Specificity indexes are 0.9379, 0.9457, and 0.9908, respectively, indicating that the model can effectively improve uterine cavity OCT image segmentation and has better segmentation performance.
... Optical imaging methods include the optical coherence tomography technique (OCT) [93][94][95][96] and the fiber optic confocal microscopy technique (FOCI) [97,98]. ...
Superficial bladder cancer diagnosis-the deliberate choice between fluorescent diagnosis and optical biopsy ABSTRACT Bladder carcinoma in situ (CIS) is a potentially invasive tumor whose early detection is a key step to ensuring the preservation of the bladder, reducing mortality, and improving the quality of patients' life. The early diagnosis of bladder cancer requires a sensitive technique that can detect the lesion to determine its stage and grade. ALA induced-PpIX makes it possible to detect tumors with 90% sensitivity. ALA hexyl ester (hALA) increases the sensitivity to 95%. Macroscopic techniques require a histological biopsy to define the tumor invasiveness. Imaging with Fibered Optic Confocal Fluorescence Microscopy allows the optical sectioning of examined tissues providing images with subcellular resolution after labeling with adequate fluorescent dye chosen based on the sensitivity of the used device. Available fluorescent agents are compatible with used devices; however, their toxicity and mutagenesis studies are unsatisfactory. During imaging, an optical fiber is introduced into the bladder via the urethra and placed in contact with the bladder wall. The distinction between the different types of epithelial cells is based on the cell size, morphology, and signal intensity. Although not fully adopted for clinical application, the FOCM represents a real asset that reduces invasiveness and complements the fluorescence-based endoscopy.
... OCT is mainly used in medicine for structural imaging of the eye structures [1,[2][3][4][5], in dermatology for skin cancer imaging and histological correlations [8], in vascular medicine in angiography, and for visualizing blood vessels [1,4,7,9]. It is also used to detect neoplastic changes such as pulmonary [10], ovarian [11], urinary [12] and gastrointestinal [13,14] pathologies. ...
... OCT is well known for retinal imaging in ophthalmology 5 and studies have shown that OCT has improved diagnostic efficacy in various structures such as the skin, gastrointestinal, respiratory, genitourinary tracts and the oral cavity. [5][6][7][8][9][10][11][12][13] Recently, OCT has been proposed for the early detection of cancer by distinguishing tumorous and nontumorous tissues with its high resolution at large (up to 2 to 3 mm) penetration depths. OCT can be used guided biopsy and can aid in the intraoperative imaging of cancer by providing real-time feedback to surgeons. ...
... OCT has become a standard of care for ophthalmic imaging and diagnostics, 7,8 although further adoption in other tissues has been slow. While widespread use of OCT is limited in some thick tissues due to its ∼1 mm penetration depth, OCT is capable of providing micron-scale tomograms, which have proven valuable in experimental settings for imaging of coronary artery disease, [9][10][11] respiratory lesions, 12,13 breast, 14 urinary, 15 and reproductive 16,17 systems, among other applications. While some limitations persist, improvements in field of view (FOV), 18 automated image analysis, 19 image stabilization, 20 and cost 21 suggest that OCT will emerge as a useful technology across tissue types. ...
Significance:
The current gold standard for monitoring small intestinal transplant (IT) rejection is endoscopic visual assessment and biopsy of suspicious lesions; however, these lesions are only superficially visualized by endoscopy. Invasive biopsies provide a coarse sampling of tissue health without depicting the true presence and extent of any pathology. Optical coherence tomography (OCT) presents a potential alternative approach with significant advantages over traditional white-light endoscopy.
Aim:
The aim of our investigation was to evaluate OCT performance in distinguishing clinically relevant morphological features associated with IT graft failure.
Approach:
OCT was applied to evaluate the small bowel tissues of two rhesus macaques that had undergone IT of the ileum. The traditional assessment from routine histological observation was compared with OCT captured using a handheld surgical probe during the days post-transplant and subsequently was compared with histophaology.
Results:
The reported OCT system was capable of identifying major biological landmarks in healthy intestinal tissue. Following IT, one nonhuman primate (NHP) model suffered a severe graft ischemia, and the second NHP graft failed due to acute cellular rejection. OCT images show visual evidence of correspondence with histological signs of IT rejection.
Conclusions:
Results suggest that OCT imaging has significant potential to reveal morphological changes associated with IT rejection and to improve patient outcomes overall.
... However, the imaging techniques has garnered considerable clinical attention for its ability to resolve the tissue microstructure at 10 times higher resolution than clinically available conventional diagnostic imaging modalities. Beyond cardiovascular medicine [81], applications of OCT include dermatology [82], gastroenterology [83] and oncology [84]. ...
Catheterization of the heart is crucial for many diagnostic and therapeutic procedures in cardiovascular medicine. In this review, we discussed developments of catheter-based optical tools and approaches for cardiovascular medicine. We provided a background in gross and microscopic anatomy of the normal and diseased heart. We overviewed optical properties of cardiac tissues, such as scattering, absorption and fluorescence, and related optical properties to tissues constituents. Furthermore, we introduced optical modalities for tissue characterization, in particular, spectroscopy, confocal, multi-photon and light sheet fluorescence microcopy, and optical coherence tomography. We then surveyed example applications in cardiovascular medicine and contrasted established clinical tools and approaches with catheter-based optical approaches and tools. First, we explored assessment of heart transplant rejection and reviewed alternative catheterized optical approaches. Rejection is commonly assessed using endomyocardial biopsy, i.e. the excision and histological assessment of tissue samples. A further application is atrial fibrosis mapping. Atrial fibrosis is an important predictor for prognosis of atrial fibrillation patients, yet clinical tools for fibrosis mapping in patients are lacking. We surveyed clinical tools for assessing catheter ablation of the heart, which is an indispensable therapy for arrhythmia. Last, we discussed methods and protocols for guiding coronary angioplasty and stent placement. For all applications, we explored the current and potential role of catheterized optical tools. We concluded with a discussion of technical challenges and open questions related to clinical translation of the catheter-based optical approaches. Our review stressed the potential of catheterized optical tools to improve diagnosis and treatment of patients with heart disease.
Optical coherence tomography (OCT) is a technique with which to peer inside a body noninvasively. Tissue structure defined by tissue absorption and scattering coefficients, and the speed of blood flow, is derived from the characteristics of light remitted by the body. Backscattered light detected by partial coherence interferometry (PCI) is used to synthesize the tomographic image coded in false colors. A prerequisite of this technique is a low time‐coherent but high space‐coherent light source, e.g. a superluminescent diode. Alternatively, the imaging technique can be realized using ultrafast wavelength scanning light sources, the so‐called swept sources. For tissue imaging, the light source wavelengths are restricted to the red and near‐infrared (NIR) region from about 600 to 1300 nm, the so‐called therapeutic window, where absorption (μ a ≈ 0.01 mm ⁻¹ ) is sufficiently small. Transverse resolution in OCT is diffraction limited, as in conventional imaging; depth resolution is limited by the coherence length of the light. Both figures are of the order of micrometers. Velocity resolution is of the order of 0.1 mm s ⁻¹ . Several instruments are commercially available. At present, OCT is mainly used in the medical field, particularly in ophthalmology, cardiology, and dermatology. Owing to the high transmissivity of ocular media, the depth penetration is considerable. Corresponding applications in dermatology are somewhat hindered by the strong scattering of epidermic tissue (μ s ≈ 10 ² mm ⁻¹ ). As OCT provides images with a resolution comparable to conventional histology, but in real time, it can be used as a biopsy technique in a wide range of biological systems to detect diseases. These include the tomographic imaging of the internal microstructure of in vitro atherosclerotic plaques, the tomographic real‐time diagnostics for intraoperative monitoring, and in microsurgical intervention. Optical biopsy based on OCT also provides diagnostic information by differentiating the architectural morphology of urological tissue, gastrointestinal tissue, and respiratory tissue.
Nanomedicine is an emerging field that exploits nanotechnology for the development of novel therapeutic and diagnostic modalities. Researches are been focussed in nanoimaging to develop noninvasive, highly sensitive, and reliable tools for diagnosis and visualization in nanomedical field. The application of nanomedicine in healthcare requires in-depth understanding of their structural, physical and morphological properties, internalization inside living system, biodistribution and localization, stability, mode of action and possible toxic health effects. Microscopic techniques including fluorescence-based confocal laser scanning microscopy, super-resolution fluorescence microscopy and multiphoton microscopy; optical-based Raman microscopy, photoacoustic microscopy and optical coherence tomography; photothermal microscopy; electron microscopy (transmission electron microscope and scanning electron microscope); atomic force microscopy; X-ray microscopy and, correlative multimodal imaging are recognized as an indispensable tool in material research and aided in numerous discoveries. Microscopy holds great promise in detecting the fundamental structures of nanoparticles (NPs) that determines their performance and applications. Moreover, the intricate details that allows assessment of chemical composition, surface topology and interfacial properties, molecular, microstructure, and micromechanical properties are also elucidated. With plethora of applications, microscopy-based techniques have been used to characterize novel NPs alongwith their proficient designing and adoption of safe strategies to be exploited in nanomedicine. Consequently, microscopic techniques have been extensively used in the characterization of fabricated NPs, and their biomedical application in diagnostics and therapeutics. The present review provides an overview of the microscopy-based techniques for in vitro and in vivo application in nanomedical investigation alongwith their challenges and advancement to meet the limitations of conventional methods.
A technique called optical coherence tomography (OCT) has been developed
for noninvasive cross-sectional imaging in biological systems. OCT uses
low-coherence interferometry to produce a two-dimensional image of
optical scattering from internal tissue microstructures in a way that is
analogous to ultrasonic pulse-echo imaging. OCT has longitudinal and
lateral spatial resolutions of a few micrometers and can detect
reflected signals as small as ~10-10 of the incident optical
power. Tomographic imaging is demonstrated in vitro in the peripapillary
area of the retina and in the coronary artery, two clinically relevant
examples that are representative of transparent and turbid media,
respectively.
We describe a high-speed optical coherence domain reflectometer. Scan speeds of 40 mm/s are achieved with a dynamic range of >90 dB and a spatial resolution of 17 microm. Two applications are presented: the noninvasive measurement of anterior eye structure in a rabbit in vivo and the charactization of reflections and interelement spacing in a multielement lens.
Optical coherence tomography is a new imaging technique that can perform high-resolution, micrometre-scale, cross-sectional imaging in biological systems. The technology has been developed, and reduced to, preliminary clinical practice in ophthalmology. The challenging problem that OCT may address is the development of 'optical biopsy' techniques. These techniques can provide diagnostic imaging of tissue morphology without the need for excision of specimens. Many investigations remain to identify optimal areas for clinical application, and additional engineering must be done to integrate vertically the technology and to reduce it to clinical practice. Nevertheless, preliminary studies indicate the feasibility of developing this technology for a wide range of clinical and research diagnostic imaging applications. The ability to non-excisionally evaluate tissue morphology using a catheter or an endoscope could have a significant impact on the diagnosis and management of a wide range of diseases.
Optical coherence tomography (OCT) is an recently developed medical diagnostic technology that uses back-reflected infrared light to perform in situ micron scale tomographic imaging. In this work, we investigate the ability of OCT to perform micron scale tomographic imaging of the internal microstructure of in vitro atherosclerotic plaques.
Aorta and relevant nonvascular tissue were obtained at autopsy. Two-dimensional cross-sectional imaging of the exposed surface of the arterial segments was performed in vitro with OCT. A 1300-nm wavelength, superluminescent diode light source was used that allows an axial spatial resolution of 20 microns. The signal-to-noise ratio was 109 dB. Images were displayed in gray scale or false color, Imaging was performed over 1.5 mm into heavily calcified tissue, and a high contrast was noted between lipid- and water-based constituents, making OCT attractive for intracoronary imaging. The 20-microns axial resolution of OCT allowed small structural details such as the width of intimal caps and the presence of fissures to be determined. The extent of lipid collections, which had a low backscattering intensity, also were well documented.
OCT represents a promising new technology for imaging vascular microstructure with a level of resolution not previously achieved with the use of other imaging modalities. It does not required direct contact with the vessel wall and can be performed with a catheter integrated with a relatively inexpensive optical fiber. The high contrast among tissue constituents, high resolution, and ability to penetrate heavily calcified tissue make OCT an attractive new imaging technology for intracoronary diagnostics.
Thermal detectors operate by converting photon energy into heat. However, most thermal detectors are rather inefficient and relatively slow as a result of the time required to change their temperature. Consequently, they are not suitable for most applications in photonics.The operation of photoelectric detectors is based on the photoeffect, in which the absorption of photons by some materials results directly in an electronic transition to a higher energy level and the generation of mobile charge carriers. Under the effect of an electric field these carriers move and produce a measurable electric current.
Even though the majority of patients with bladder malignancies initially present with low stage disease, the clinical epidemiology of these so-called superficial bladder tumours is not well known. In this paper, disease characteristics at initial presentation and during follow-up are described in 1,745 primary cases documented prospectively in the Netherlands. The risk of recurrent disease after primary treatment is very high: in 60% of cases, at least one recurrence is diagnosed within 5 years (95% CI: 58-62%). In patients with a small solitary pTa grade 1 tumour, the 3-year recurrence risk is 37%. In patients with multiple large high grade pT1 tumours, this risk is as high as 77%, despite a significant beneficial effect of adjuvant intravesical chemotherapy. The actuarial risk of disease progression is 10.2% after 3 years (95% CI: 8.6-11.8%). This risk of progression depends on the patient's age at diagnosis, tumour stage, grade, multiplicity and the presence of dysplasia or CIS in random urothelium biopsies. The use of intravesical instillations with chemotherapy or BCG vaccine after TUR does not prevent progressive disease, although this finding is difficult to interpret from a non-randomised study. The 5-year relative survival in patients with superficial TCC of the bladder is 86% (95% CI: 84-88%).
In the search for sensitive and specific tumor markers for bladder carcinoma, expression of various oncogenes and gene products (such as c-erb B-2, p53) and epidermal growth factor receptor merits particular attention. Although the results are not yet conclusive, important predictive markers are about to emerge from ongoing studies in this field. Bacillus Calmette-Guerrin treatment in superficial bladder cancer is probably the most successful immunotherapy in humans. But there is still a large knowledge deficit in the issues of optimal dose schedule and mechanisms of action. Although promising results of neoadjuvant chemotherapy in patients with invasive bladder cancers are reported, we must be cautious about changing our conventional approach until the results of large scale, controlled, randomized studies evaluating the survival are published.
(C) Lippincott-Raven Publishers.
BACKGROUND
Previous Commission on Cancer Data from the National Cancer Data Base (NCDB) have examined time trends in stage of disease, treatment patterns, and survival for selected cancers. The most current (1993) data relating to patients with bladder carcinoma are described here.METHODS
Five calls for data have yielded a total of 3,700,000 cases for the years 1985 through 1993, including 447,679 cases for 1988 and 608,593 cases for 1993, from hospital cancer registries across the U.S. Data were received on 18,053 bladder carcinoma cases in 1988 and 22,606 cases in 1993.RESULTSInteresting trends are 1) younger patients (49 years of age and younger) present with earlier stages of disease than do older patients; 2) women are slightly more likely to be diagnosed with later stages (II, III, and IV) of bladder carcinoma than men; 3) African Americans are less likely to be diagnosed with Stage 0 or Stage I disease than either Hispanic or non-Hispanic whites; and 4) National Cancer Institute designated centers treat more patients with advanced disease than do other types of hospitals.CONCLUSIONS
The NCDB data are important for analyzing what cancer treatments and outcomes are used and occurring in the country. The data suggest that African Americans are diagnosed at later stages of disease progression. The relative survival rates among African Americans are lower than among Hispanics or non-Hispanic whites. Also, the decreasing utility of adjuvant chemotherapy is being recognized. Cancer 1996;78:1505-13.
We assess the value and limitation of transurethral ultrasonography in the diagnostic evaluation of bladder carcinoma.
A total of 115 patients underwent the procedure, either at the same setting as transurethral resection (76) or 2 weeks before radical cystectomy (39). The results were compared with the pathological findings of transurethral and cystectomy specimens.
The correlation between transurethral ultrasonography and pathological staging was 100% in tumors without muscle invasion (stages Ta and T1), 95.7% and 96.8% in muscle invasive tumors (stages T2 and T3a, respectively), and 70% in tumors with extravesical spread.
Transurethral ultrasonography is most valuable in determining the stage of tumor confined to the bladder wall. Also, it is of value in detecting tumors in a diverticulum, and monitoring the distensibility of the bladder wall and transurethral resection of disease. The main limitations are the inabilities to discriminate between stages Ta and T1 tumors, and to detect involvement of the pelvic lymph nodes.
Transitional cell carcinoma of the bladder possesses several features that make it an ideal candidate for screening: metastases rarely occur before tumors invade the muscularis propria; superficial disease is treated very successfully by relatively inexpensive and nonmorbid means; this malignancy is almost never found incidentally at autopsy so that early detection cannot harm a patient; and almost all tumors cause hematuria if one tests frequently enough. When compared with a contemporary age, geography, and gender-matched unscreened population, bladder cancer screening in healthy men age 50 years and older by repeated home hematuria testing using chemical reagent strips significantly decreases bladder cancer morbidity and mortality and is cost-effective. A randomized prospective trial of bladder cancer screening in this population is recommended. Additionally, other potential means of bladder cancer screening and other target populations are discussed in this article.