Recent advances in optical imaging technologies for the detection of bladder cancer
Introduction
Bladder cancer (BC) is a malignancy affecting the urothelium of the bladder [1]. When considering both genders, BC is the 11th most prevalent malignancy in the world [2]. It affects men, three to four times more than women [3]. Its incidence is rapidly increasing, especially in developing countries. In the last decade, there has been approximately a 15% increment in the incidence of BC. Transitional cell carcinoma (TCC) is the most common histological type [4]. An estimated 76,960 new cases and 16,390 deaths from BC have occurred worldwide in 2016 [5].
Approximately 75–85% of newly diagnosed BC belong to the nonmuscle invasive bladder cancer (NMIBC) group (BC invasion degree is shown in Fig. 1), and in most cases, transurethral resection of the bladder tumor (TURBT) with white-light cystoscopy (WLC) is the choice of treatment [3,[5], [6], [7]]. However, 50–70% of cases recur and 10–30% progress to a higher grade and staging [8]. In most cases, the recurrence is owing to incomplete tumor excision during TURBT with WLC [8,9]. Incomplete tumor excision during TURBT increases the rate of early re-TURBT and recurrence at the first follow-up cystoscopy by three times [10]. WLC often fails to detect small papillary and subtle flat carcinoma in situ (CIS) lesions, leading to progression and more invasive lesions [9]. WLC has low sensitivity for the detection of CIS, which is only 50% [8]. Therefore, more efficient methods are needed to detect CIS.
Several technologies have emerged with the goal to improve BC detection and resection [11]. Optical diagnosis involves light-based tissue imaging [12]. It is used as an adjunctive modality for tumor diagnosis rather than replacing WLC [13]. There are three broad categories of imaging technologies related to their field of view, i.e., macroscopic, microscopic, and molecular imaging [11,[13], [14], [15], [16]]. In this paper, we review the latest literature reports of adjunctive optical imaging technologies for the detection of BC.
Section snippets
Photodynamic diagnosis
Photodynamic diagnosis (PDD) is able to detect BC using fluorescent enhancement [[17], [18], [19]]. PDD utilizes photoactive substances that preferentially accumulate approximately 20 times more in neoplastic tissue than in healthy tissue [18]. Intravesical administration of the photoactive substances demonstrates a better safety profile than oral administration [6]. Currently, hexaminolevulinate (HAL) and 5-aminolaevulinic acid (5-ALA) are the most commonly used photoactive substances [1,6,12
Narrow-band imaging
Narrow-band imaging (NBI) is an imaging technique that does not require the use of photoactive substances [14,15]. However, NBI cannot be used to determine the infiltration status and tumor grade [19]. Table 1 shows a comparison between NBI and PDD. NBI is produced by filtering of a white light source into two wavelengths, blue (415 nm) and green bands (540 nm) [13,16,33]. Hemoglobin preferentially absorbs these wavelengths, which makes the submucosal blood vessels and capillaries more visible [
Confocal laser endomicroscopy
Confocal laser endomicroscopy (CLE) couples the systems of confocal microscopy with those of fibreoptics [11,14]. CLE employs a fiber-optic bundle that transmits 488 nm laser light. CLE also uses fluorescein as the contrast agent to provide real-time, microscopic, in vivo histopathologic information [13,15]. Currently, the available flexible CLE probe can pass through standard cystoscopes with a diameter of 0.85–2.6 mm [11,13]. CLE has a high resolution (2–5 μm) with a 240 μm penetration depth [
Optical coherence tomography
Optical coherence tomography (OCT) is a noninvasive real-time microscopic imaging technique [13]. OCT is comparable to B-mode ultrasonography. The difference between these two modalities is that OCT uses near-infrared wavelength light (890–1300 nm) to produce an image [12,14,19]. OCT images are satisfactory for the detection of most BCs with an axial resolution as high as 1 μm, normally approximately 10–20 μm lateral resolution, and up to 2 mm penetration depth [13,19,51]. OCT uses elastic
Raman spectroscopy
Raman spectroscopy (RS) is an endomicroscopic technology that can be used to analyze the tissue’s molecular components and does not require any photoactive substances [13,15,19]. RS utilizes the Raman effect, which analyzes the inelastic photon scattering after its interaction with intramolecular bonds [12,19]. Infrared light (785–845 nm) is employed to stimulate the intrinsic chemical bonds for creating an optical difference [19].
RS can distinguish the healthy bladder wall layers, assess
Molecular imaging
Molecular imaging is a type of imaging that combines optical imaging and intravesical instillation of fluorescent-labeled components (i.e., peptides, antibodies, and other elements) [19]. These molecular contrast agents allow tumor-specific visualization and decrease the false-positive result caused by inflammatory lesions [14]. A recent study used intravesical fluorescently labeled CD47 antibody (anti-CD47) to successfully demonstrate ex vivo endoscopic molecular imaging of BC using CLE and
Other technologies
Other advanced imaging techniques are being developed to improve BC diagnosis and treatment, such as endocystocopy, multiphoton microscopy (MPM), scanning fiber endoscopy (SFE), ultraviolet (UV) autofluorescence, virtual cystoscopy (VC), photoacoustic imaging (PAI), and coherent anti-Stokes Raman scattering (CARS) which will be discussed below.
Endocystoscopy is a novel modality that provides an ultrahigh magnification image (×450–1125). It is a catheter-type device that can be passed through a
Future direction
The combination of imaging modalities harbors the potential to increase diagnostic accuracy. Macroscopic imaging (PDD, NBI) can be utilized to recognize lesions of interest, whereas microscopic imaging (CLE, OCT) could provide the grading or staging information through high-resolution tissue characterization [11]. Schmidbauer et al. found that the combination of PDD and OCT significantly increased per-patient specificity from 62.5% to 87.5% compared with PDD alone [54]. In another study, the
Conclusion
Clinical under staging of invasive BC remains a significant challenge. Technological advances in optical imaging have the potential to improve the detection and treatment of BC. However, all these technological advances are operator-dependent, and their use heavily depends on the experience of the operating doctor. There are only two optical imaging techniques, PDD and NBI, that are already implemented in a clinical setting. Endomicroscopic technologies are still being studied. Further study is
Funding
This study did not receive a grant from any funding agencies.
Declarations of interest
None.
Acknowledgement
None.
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