Advanced optical imaging techniques for bladder cancer detection and diagnosis: a systematic review.

OBJECTIVES: To systematically assess the current available literature concerning advanced optical imaging methods for the detection and diagnosis of bladder cancer (BCa), focusing particularly on the sensitivity and specificity of these techniques. METHODS: First a scoping search was performed to identify all available optical techniques for BCa detection and diagnosis. The optical imaging techniques used for detecting BCa are: the Storz professional image enhancement system (IMAGE1 S), narrow-band imaging (NBI), photoacoustic imaging (PAI), autofluorescence imaging (AFI), photodynamic diagnosis (PDD), and scanning fibre endoscopy (SFE). The staging and grading techniques for BCa are: optical coherence tomography (OCT), confocal laser endomicroscopy (CLE), Raman spectroscopy, endocytoscopy, and non-linear optical microscopy (NLO). Then a systematic literature search was conducted using MEDLINE, EMBASE and Web of Science from inception to 21 November 2023. Articles were screened and selected by two independent reviewers. Inclusion criteria were: reporting on both the sensitivity and specificity of a particular technique and comparison to histopathology, and in the case of a detection technique comparison to white light cystoscopy (WLC). RESULTS: Out of 6707 articles, 189 underwent full-text review, resulting in 52 inclusions. No articles met criteria for IMAGE1 S, PAI, SFE, Raman spectroscopy, and endocytoscopy. All detection techniques showed higher sensitivity than WLC, with NBI leading (87.8-100%). Overall, detection technique specificity was comparable to WLC, with PDD being most specific (23.3-100%). CLE and OCT varied in sensitivity and specificity, with OCT showing higher specificity for BCa diagnosis, notably for carcinoma in situ (97-99%) compared to CLE (62.5-81.3%). NLO demonstrated high sensitivity and specificity (90-97% and 77-100%, respectively) based on limited data from two small ex vivo studies. CONCLUSIONS: Optical techniques with the most potential are PDD for detecting and OCT for staging and grading BCa. Further research is crucial to validate their integration into routine practice and explore the value of other imaging techniques.

Automated Detection and Grading of Non-Muscle-Invasive Urothelial Cell Carcinoma of the Bladder.

Accurate grading of non-muscle-invasive urothelial cell carcinoma is of major importance; however, high interobserver variability exists. A fully automated detection and grading network based on deep learning is proposed to enhance reproducibility. A total of 328 transurethral resection specimens from 232 patients were included, and a consensus reading by three specialized pathologists was used. The slides were digitized, and the urothelium was annotated by expert observers. The U-Net-based segmentation network was trained to automatically detect urothelium. This detection was used as input for the classification network. The classification network aimed to grade the tumors according to the World Health Organization grading system adopted in 2004. The automated grading was compared with the consensus and individual grading. The segmentation network resulted in an accurate detection of urothelium. The automated grading shows moderate agreement (κ = 0.48 ± 0.14 SEM) with the consensus reading. The agreement among pathologists ranges between fair (κ = 0.35 ± 0.13 SEM and κ = 0.38 ± 0.11 SEM) and moderate (κ = 0.52 ± 0.13 SEM). The automated classification correctly graded 76% of the low-grade cancers and 71% of the high-grade cancers according to the consensus reading. These results indicate that deep learning can be used for the fully automated detection and grading of urothelial cell carcinoma.

Needle-based confocal laser endomicroscopy for real-time diagnosing and staging of lung cancer.

Diagnosing lung cancer in the absence of endobronchial abnormalities is challenging. Needle-based confocal laser endomicroscopy (nCLE) enables real-time microscopic imaging of cells. We assessed the feasibility and safety of using nCLE for real-time identification of lung cancer.In patients with suspected or proven lung cancer scheduled for endoscopic ultrasound (EUS), lung tumours and mediastinal lymph nodes were imaged with nCLE before fine-needle aspiration (FNA) was performed. nCLE lung cancer characteristics were identified by comparison with pathology. Multiple blinded raters validated CLE videos of lung tumours and mediastinal nodes twice.EUS-nCLE-FNA was performed in 22 patients with suspected or proven lung cancer in whom 27 lesions (six tumours, 21 mediastinal nodes) were evaluated without complications. Three nCLE lung cancer criteria (dark enlarged pleomorphic cells, dark clumps and directional streaming) were identified. The accuracy of nCLE imaging for detecting malignancy was 90% in tumours and 89% in metastatic lymph nodes. Both inter-observer agreement (mean κ=0.68, 95% CI 0.66-0.70) and intra-observer agreement (mean±sd κ=0.70±0.15) were substantial.Real-time lung cancer detection by endosonography-guided nCLE was feasible and safe. Lung cancer characteristics were accurately recognised.

Confocal Laser Endomicroscopy as a Guidance Tool for Transbronchial Lung Cryobiopsies in Interstitial Lung Disorder.

BACKGROUND: Transbronchial cryobiopsy (TBCB) of the lung parenchyma is a minimally invasive alternative for surgical lung biopsy in interstitial lung disease (ILD) patients. Drawbacks are the nondiagnostic rate and complication risk of pneumothorax and bleeding. Fluoroscopy is the current guidance tool for TBCB, which is limited by 2D imaging and a radiation dose for the patient. Confocal laser endomicroscopy (CLE) is a high-resolution imaging technique that provides immediate feedback during bronchoscopy about the elastin fiber network of peripheral lung areas. Both the visceral pleura and fibrotic lung areas consist of elastin fibers and are therefore potentially detectable with CLE. OBJECTIVES: To investigate whether CLE is capable of (1) distinguishing fibrotic from normal alveolar areas and (2) identifying the pleura. METHODS: In and ex vivo CLE imaging obtained during bronchoscopy was compared with histology of lung biopsies in 14 ILD patients. RESULTS: CLE imaging of the alveolar compartment was feasible in all patients without adverse events. Based on CLE imaging, key characteristics that influence both diagnostic yield (dense fibrotic areas) and complication rate (pleura and subpleural space) were visualized. CONCLUSIONS: CLE seems a promising alternative to fluoroscopy as a guidance tool for TBCB procedures.

Grading upper tract urothelial carcinoma with the attenuation coefficient of in-vivo optical coherence tomography.

INTRODUCTION: With catheter based optical coherence tomography (OCT), high resolution images of the upper urinary tract can be obtained, thereby facilitating the detection of upper tract urothelial carcinomas (UTUC). We hypothesized that the attenuation coefficient of the OCT signal (µOCT ) is related to the histopathologic grade of the tumor. OBJECTIVES: In this study, we aimed to define the µOCT cut-off for discriminating high grade and low grade papillary UTUC. METHODS: For this post-hoc analysis, data from OCT imaging of papillary UTUC was obtained from patients during ureterorenoscopy. OCT images and raw data were simultaneously analyzed with in-house developed software. The µOCT determined in papillary UTUCs and corresponding histopathologic grading from either biopsies or radical resection specimens were compared. RESULTS: Thirty-five papillary UTUC from 35 patients were included. µOCT analysis was feasible in all cases. The median µOCT was 3.3 mm-1 (IQR 2.7-3.7 mm-1 ) for low-grade UTUC and 4.9 mm-1 (IQR 4.3-6.1 mm-1 ) for high-grade UTUC (P = 0.004). ROC analysis yielded a µOCT cut-off value of >4.0 mm-1 (AUC = 0.85, P < 0.001) with a sensitivity of 83% and a specificity of 94% for high-grade papillary UTUC. CONCLUSIONS: This study proposes a µOCT cut-off of 4.0 mm-1 for quantitative grading of UTUC with ureterorenoscopic OCT imaging. The promising diagnostic accuracy calculations justify further studies to validate the proposed cut-off value. Implementation of the software for the µOCT analysis in OCT systems may allow for µOCT assessment at real time during ureterorenoscopy. Lasers Surg. Med. 51:399-406, 2019. © 2019 Wiley Periodicals, Inc.

The First In Vivo Needle-Based Optical Coherence Tomography in Human Prostate: A Safety and Feasibility Study.

OBJECTIVE: To demonstrate the safety and feasibility of clinical in vivo needle-based optical coherence tomography (OCT) imaging of the prostate. MATERIALS AND METHODS: Two patients with prostate cancer underwent each two percutaneous in vivo needle-based OCT measurements before transperineal template mapping biopsy. The OCT probe was introduced via a needle and positioned under ultrasound guidance. To test the safety, adverse events were recorded during and after the procedure. To test the feasibility, OCT and US images were studied during and after the procedure. Corresponding regions for OCT and biopsy were determined. A uropathologist evaluated and annotated the histopathology. Three experts assessed all the corresponding OCT images. The OCT and biopsy conclusions for the corresponding regions were compared. RESULTS: No adverse events during and following the, in total four, in vivo needle-based OCT measurements were reported. The OCT measurements showed images of prostatic tissue with a penetration depth of ~1.5 mm. The histological-proven tissue types, which were also found in the overlapping OCT images, were benign glands, stroma, glandular atrophy, and adenocarcinoma (Gleason pattern 3). CONCLUSIONS: Clinical in vivo needle-based OCT of the prostate is feasible with no adverse events during measurements. OCT images displayed detailed prostatic tissue with a imaging depth up to ~1.5 mm. We could co-register four histological-proven tissue types with OCT images. The feasibility of in vivo OCT in the prostate opens the pathway to the next phase of needle-based OCT studies in the prostate. Lasers Surg. Med. 51:390-398, 2019. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Histopathology: ditch the slides, because digital and 3D are on show.

Due to the growing field of digital pathology, more and more digital histology slides are becoming available. This improves the accessibility, allows teleconsultations from specialized pathologists, improves education, and might give urologist the possibility to review the slides in patient management systems. Moreover, by stacking multiple two-dimensional (2D) digital slides, three-dimensional volumes can be created, allowing improved insight in the growth pattern of a tumor. With the addition of computer-aided diagnosis systems, pathologist can be guided to regions of interest, potentially reducing the workload and interobserver variation. Digital (3D) pathology has the potential to improve dialog between the pathologist and urologist, and, therefore, results in a better treatment selection for urologic patients.

Bronchial Thermoplasty-Induced Acute Airway Effects Assessed with Optical Coherence Tomography in Severe Asthma.

BACKGROUND: Bronchial thermoplasty (BT) is an endoscopic treatment for severe asthma targeting airway smooth muscle (ASM) with radiofrequent energy. Although implemented worldwide, the effect of BT treatment on the airways is unclear. Optical coherence tomography (OCT) is a novel imaging technique, based on near-infrared light, that generates high-resolution cross-sectional airway wall images. OBJECTIVE: To assess the safety and feasibility of OCT in severe asthma patients and determine acute airway effects of BT by OCT and compare these to the untreated right middle lobe (RML). METHODS: Severe asthma patients were treated with BT (TASMA trial). During the third BT procedure, OCT imaging was performed immediately following BT in the airways of the upper lobes, the right lower lobe treated 6 weeks prior, and the untreated RML. RESULTS: 57 airways were imaged in 15 patients. No adverse events occurred. Three distinct OCT patterns were discriminated: low-intensity scattering pattern of (1) bronchial and (2) peribronchial edema and (3) high-intensity scattering pattern of epithelial sloughing. (Peri)bronchial edema was seen in all BT-treated airways, and less pronounced in only 1/3 of the RML airways. These effects extended beyond the ASM layer and more distal than the directly BT-treated areas and were reduced, but not resolved, after 6 weeks. Epithelial sloughing occurred in 11/14 of the BT-treated airways and was absent in untreated RML airways. CONCLUSIONS: Acute BT effects can be safely assessed with OCT and 3 distinct patterns were identified. The acute effects extended beyond the targeted ASM layer and distal of directly BT-treated airway areas, suggesting that BT might also target smaller distal airways.

Periocular CO2 laser resurfacing: severe ocular complications from multiple unintentional laser impacts on the protective metal eye shields.

BACKGROUND AND OBJECTIVES: A 36-year-old woman underwent CO2 laser resurfacing for periocular rhytides using protective stainless steel Cox II ocular shields. Immediately after the treatment, corneal lesions were seen in both eyes. The left eye subsequent developed corneal ulceration and scarring, a deformed iris, cataract, and lower eye lashes showing signs of acute burns. The right cornea had a small inferior mid-peripheral superficial lesion and concomitant lower mid-peripheral burned eye lashes. Our objective was to determine the most likely cause of these ocular complications. STUDY: We estimated temperature-time combinations that could induce corneal injury and cataract. Heat conduction effects from a heated cornea to the lens and from a heated ring of periocular skin to the cornea were computed. The temperature response of a shield following CO2 laser irradiation was determined. RESULTS: We computed that cataract can develop when the corneal temperature reaches, for example, 80 °C for 14 seconds. A periocular ring of heated skin contributes little to the corneal temperature. After 7 pulses of consecutive CO2 laser bursts in 7.5 seconds, the total shield area already reached a homogeneous temperature of 63 °C. CONCLUSION: Despite uncertainties in procedural details and modeling of cataract temperatures, the eye injuries were caused beyond doubt by heating of tear-covered metal eye shields by at least 10 consecutive but unintentional laser impacts. Lasers Surg. Med. 50:980-986, 2018. © 2018 Wiley Periodicals, Inc.

Feasibility of Optical Coherence Tomography (OCT) for Intra-Operative Detection of Blood Flow during Gastric Tube Reconstruction.

In this study; an OCT-based intra-operative imaging method for blood flow detection during esophagectomy with gastric tube reconstruction is investigated. Change in perfusion of the gastric tube tissue can lead to ischemia; with a high morbidity and mortality as a result. Anastomotic leakage (incidence 5⁻20%) is one of the most severe complications after esophagectomy with gastric tube reconstruction. Optical imaging techniques provide for minimal-invasive and real-time visualization tools that can be used in intraoperative settings. By implementing an optical technique for blood flow detection during surgery; perfusion can be imaged and quantified and; if needed; perfusion can be improved by either a surgical intervention or the administration of medication. The feasibility of imaging gastric microcirculation in vivo using optical coherence tomography (OCT) during surgery of patients with esophageal cancer by visualizing blood flow based on the speckle contrast from M-mode OCT images is studied. The percentage of pixels exhibiting a speckle contrast value indicative of flow was quantified to serve as an objective parameter to assess blood flow at 4 locations on the reconstructed gastric tube. Here; it was shown that OCT can be used for direct blood flow imaging during surgery and may therefore aid in improving surgical outcomes for patients.

Percutaneous Needle Based Optical Coherence Tomography for the Differentiation of Renal Masses: a Pilot Cohort.

PURPOSE: We determine the ability of percutaneous needle based optical coherence tomography to differentiate renal masses by using the attenuation coefficient (µOCT, mm(-1)) as a quantitative measure. MATERIALS AND METHODS: Percutaneous needle based optical coherence tomography of the kidney was performed in patients presenting with a solid renal mass. A pathology specimen was acquired in the form of biopsies and/or a resection specimen. Optical coherence tomography results of 40 patients were correlated to pathology results of the resected specimens in order to derive µOCT values corresponding with oncocytoma and renal cell carcinoma, and with the 3 main subgroups of renal cell carcinoma. The sensitivity and specificity of optical coherence tomography in differentiating between oncocytoma and renal cell carcinoma were assessed through ROC analysis. RESULTS: The median µOCT of oncocytoma (3.38 mm(-1)) was significantly lower (p=0.043) than the median µOCT of renal cell carcinoma (4.37 mm(-1)). ROC analysis showed a µOCT cutoff value of greater than 3.8 mm(-1) to yield a sensitivity, specificity, positive predictive value and negative predictive value of 86%, 75%, 97% and 37%, respectively, to differentiate between oncocytoma and renal cell carcinoma. The area under the ROC curve was 0.81. Median µOCT was significantly lower for oncocytoma vs clear cell renal cell carcinoma (3.38 vs 4.36 mm(-1), p=0.049) and for oncocytoma vs papillary renal cell carcinoma (3.38 vs 4.79 mm(-1), p=0.027). CONCLUSIONS: We demonstrated that the µOCT is significantly higher in renal cell carcinoma vs oncocytoma, with ROC analysis showing promising results for their differentiation. This demonstrates the potential of percutaneous needle based optical coherence tomography to help in the differentiation of renal masses, thus warranting ongoing research.

Focal vs extended ablation in localized prostate cancer with irreversible electroporation; a multi-center randomized controlled trial.

BACKGROUND: Current surgical and ablative treatment options for prostate cancer (PCa) may result in a high incidence of (temporary) incontinence, erectile dysfunction and/or bowel damage. These side effects are due to procedure related effects on adjacent structures including blood vessels, bowel, urethra and/or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective and safe in destroying PCa cells and also has the potential advantage of sparing surrounding tissue and vital structures, resulting in less impaired functional outcomes and maintaining men's quality of life. METHODS/DESIGN: In this randomized controlled trial (RCT) on IRE in localized PCa, 200 patients with organ-confined, unilateral (T1c-T2b) low- to intermediate-risk PCa (Gleason sum score 6 and 7) on transperineal template-mapping biopsies (TTMB) will be included. Patients will be randomized into focal or extended ablation of cancer foci with IRE. Oncological efficacy will be determined by multiparametric Magnetic Resonance Imaging, Contrast-Enhanced Ultrasound imaging if available, TTMP and Prostate Specific Antigen (PSA) follow-up. Patients will be evaluated up to 5 years on functional outcomes and quality of life with the use of standardized questionnaires. DISCUSSION: There is critical need of larger, standardized RCTs evaluating long-term oncological and functional outcomes before introducing IRE and other focal therapy modalities as an accepted and safe therapeutic option for PCa. This RCT will provide important short- and long-term data and elucidates the differences between focal or extended ablation of localized, unilateral low- to intermediate-risk PCa with IRE. TRIAL REGISTRATION: Clinicaltrials.gov database registration number NCT01835977. The Dutch Central Committee on Research Involving Human Subjects registration number NL50791.018.14.

Detection of buried Barrett's glands after radiofrequency ablation with volumetric laser endomicroscopy.

BACKGROUND AND AIMS: The prevalence and clinical relevance of buried Barrett's glands (BB) after radiofrequency ablation (RFA) in Barrett's esophagus (BE) are debated. Recent optical coherence tomography studies demonstrated a high prevalence of BBs. Direct histological correlation, however, has been lacking. Volumetric laser endomicroscopy (VLE) is a second-generation optical coherence tomography system capable of scanning a large surface of the esophageal wall layers with low-power microscopy resolution. The aim was to evaluate whether post-RFA subsquamous glandular structures (SGSs), detected with VLE, actually correspond to BBs by pursuing direct histological correlation with VLE images. METHODS: In vivo VLE was performed to detect SGSs in patients with endoscopic regression of BE post-RFA. A second in vivo VLE scan was performed to confirm correct delineation of the SGSs. After endoscopic resection, the specimens were imaged ex vivo with VLE. Extensive histological sectioning of SGS areas was performed, and all histology slides were evaluated by an expert BE pathologist. RESULTS: Seventeen patients underwent successful in vivo VLE (histological diagnosis before endoscopic treatment: early adenocarcinoma in 8 patients and high-grade dysplasia in 9). In 4 of 17 patients, no SGSs were identified during VLE, and a random resection was performed. In the remaining 13 patients (76%), VLE detected SGS areas, which were all confirmed on a second in vivo VLE scan and subsequently resected. Most SGSs identified by VLE corresponded to normal histological structures (eg, dilated glands and blood vessels). However, 1 area containing BBs was found on histology. No specific VLE features to distinguish between BBs and normal SGSs were identified. CONCLUSIONS: VLE is able to detect subsquamous esophageal structures. One area showed BBs beneath endoscopically normal-appearing neosquamous epithelium; however, most post-RFA SGSs identified by VLE correspond to normal histological structures. ( CLINICAL TRIAL REGISTRATION NUMBER: NTR4056.).

Thermal Energy during Irreversible Electroporation and the Influence of Different Ablation Parameters.

PURPOSE: Irreversible electroporation (IRE) uses high-voltage electric fields to achieve cell death. Although the mechanism of IRE is mainly designated as nonthermal, development of secondary Joule heating is inevitable. The study purpose was to gain understanding of temperature development and distribution during IRE. MATERIALS AND METHODS: IRE was performed in a transparent polyacrylamide gel resembling soft tissue. Mechanical effects, changes in temperature gradient, and absolute temperature changes were measured with three different optical techniques (high-speed, color Schlieren, and infrared imaging) to investigate the effect on temperature of variations in voltage, pulse length, active tip length (ATL), interelectrode distance, electrode configuration (parallel, convergent, and divergent), and sequential pulsing (pulse delivery interrupted by breaks). The total delivered energy was calculated. RESULTS: A temperature gradient, starting at the tips of both electrodes and expanding toward each other, developed immediately with pulse delivery. Temperatures increased with increasing voltage (by 2.5°C-40.4°C), pulse length (by 5.3°C-9.8°C), ATL (by 5.9°C-17.6°C), and interelectrode distance (by 7.6°C-21.5°C), in accordance with higher energy delivery. Nonparallel electrode placement resulted in heterogeneous temperature distribution with the peak temperature focused in the area with the shortest interelectrode distance. Sequential pulse delivery significantly reduced the temperature increase compared with continuous pulsing (4.3°C vs 11.7°C). CONCLUSIONS: Voltage, pulse length, interelectrode distance, ATL, and electrode configuration each have a strong effect on temperature development and distribution during IRE. Sequential pulsing reduces the extent and volume of thermal distribution and may prove beneficial with respect to procedural safety.

Irreversible electroporation: just another form of thermal therapy?

BACKGROUND: Irreversible electroporation (IRE) is (virtually) always called non-thermal despite many reports showing that significant Joule heating occurs. Our first aim is to validate with mathematical simulations that IRE as currently practiced has a non-negligible thermal response. Our second aim is to present a method that allows simple temperature estimation to aid IRE treatment planning. METHODS: We derived an approximate analytical solution of the bio-heat equation for multiple 2-needle IRE pulses in an electrically conducting medium, with and without a blood vessel, and incorporated published observations that an electric pulse increases the medium's electric conductance. RESULTS: IRE simulation in prostate-resembling tissue shows thermal lesions with 67-92°C temperatures, which match the positions of the coagulative necrotic lesions seen in an experimental study. Simulation of IRE around a blood vessel when blood flow removes the heated blood between pulses confirms clinical observations that the perivascular tissue is thermally injured without affecting vascular patency. CONCLUSIONS: The demonstration that significant Joule heating surrounds current multiple-pulsed IRE practice may contribute to future in-depth discussions on this thermal issue. This is an important subject because it has long been under-exposed in literature. Its awareness pleads for preventing IRE from calling "non-thermal" in future publications, in order to provide IRE-users with the most accurate information possible. The prospect of thermal treatment planning as outlined in this paper likely aids to the important further successful dissemination of IRE in interventional medicine. Prostate 75:332-335, 2015. © 2014 The Authors. The Prostate Published by Wiley Periodicals, Inc.

The efficacy and safety of irreversible electroporation for the ablation of renal masses: a prospective, human, in-vivo study protocol.

BACKGROUND: Electroporation is a novel treatment technique utilizing electric pulses, traveling between two or more electrodes, to ablate targeted tissue. The first in human studies have proven the safety of IRE for the ablation of renal masses. However the efficacy of IRE through histopathological examination of an ablated renal tumour has not yet been studied. Before progressing to a long-term IRE follow-up study it is vital to have pathological confirmation of the efficacy of the technique. Furthermore, follow-up after IRE ablation requires a validated imaging modality. The primary objectives of this study are the safety and the efficacy of IRE ablation of renal masses. The secondary objectives are the efficacy of MRI and CEUS in the imaging of ablation result. METHODS/DESIGN: 10 patients, age ≥ 18 years, presenting with a solid enhancing mass, who are candidates for radical nephrectomy will undergo IRE ablation 4 weeks prior to radical nephrectomy. MRI and CEUS imaging will be performed at baseline, one week and four weeks post IRE. After radical nephrectomy, pathological examination will be performed to evaluate IRE ablation success. DISCUSSION: The only way to truly assess short-term (4 weeks) ablation success is by histopathology of a resection specimen. In our opinion this trial will provide essential knowledge on the safety and efficacy of IRE of renal masses, guiding future research of this promising ablative technique. TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT02298608 . Dutch Central Committee on Research Involving Human Subjects registration number NL44785.018.13.

The value of optical coherence tomography in determining surgical margins in squamous cell carcinoma of the vulva: a single-center prospective study.

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) is treated with wide local excision. The challenge is to remove as much skin as necessary to prevent recurrence, but meanwhile preserve genital skin to diminish morbidity. Optical coherence tomography (OCT) is a noninvasive imaging tool that produces cross-sectional images. Optical coherence tomography could be helpful in determining appropriate surgical margins during excision of VSCC. OBJECTIVE: This study aimed to assess the value of OCT in determining appropriate surgical margins in patients operated for VSCC. We hypothesize that benign tissue will differ qualitatively (presence of clear epidermal layers) and quantitatively (epidermal layer thickness and attenuation coefficient) from (pre)malignant tissue. MATERIALS AND METHODS: In 18 patients with a pretreatment biopsy of VSCC, before excision, areas within the center (tumor), at the margin (skin next to the center), and in normal vulvar skin outside the area of resection were imaged by OCT. Optical coherence tomography data were assessed on the presence of a clear epidermal layer, thickness of the epidermal layer, and values of µOCT. Results were grouped according to histopathological report in a benign group and a (pre)malignant group. RESULTS: A clear epidermal layer was observed in all OCT images of benign tissue and only in 6 of 23 premalignant lesions (P < 0.001). The epidermal layer thickness as well as the µOCT was significantly smaller for benign vulvar tissue than for (pre)malignant tissue (0.29 vs 1.03 mm, and 2.4 vs 4.1 mm(-1), respectively; P < 0.001). The diagnostic accuracy of OCT, as calculated by receiver operating characteristic curve analysis, showed at defined thresholds a sensitivity of 100% and specificity of 80% when considering layer thickness, and a sensitivity of 100% and specificity of 70% when considering the attenuation coefficient. CONCLUSIONS: We show that qualitative and quantitative OCT imaging can distinguish between benign and (pre)malignant vulvar tissue, enabling appropriate surgical margin detection with noninvasive in vivo OCT imaging.