Image-guided in-Vivo Needle-Based Confocal Laser Endomicroscopy in the Prostate: Safety and Feasibility Study in 2 Patients.

Purpose: To assess the safety and technical feasibility of in-vivo needle-based forward-looking confocal laser endomicroscopy in prostate tissue. Methods: For this feasibility study, 2 patients with a suspicion of prostate cancer underwent transperineal needle-based confocal laser endomicroscopy during ultrasound-guided transperineal template mapping biopsies. After intravenous administration of fluorescein, needle-based confocal laser endomicroscopy imaging was performed with a forward-looking probe (outer diameter 0.9 mm) in 2 trajectories during a manual push-forward and pullback motion. A biopsy was taken in a coregistered parallel adjacent trajectory to the confocal laser endomicroscopy trajectory for histopathologic comparison. Peri- and postprocedural adverse events, confocal laser endomicroscopy device malfunction and procedural failures were recorded. Needle-based confocal laser endomicroscopy image quality assessment, image interpretation, and histology were performed by an experienced confocal laser endomicroscopy rater and uro-pathologist, blinded to any additional information. Results: In both patients, no peri- and post-procedural adverse events were reported following needle-based confocal laser endomicroscopy. No confocal laser endomicroscopy device malfunction nor procedural failures were reported. Within 1.5 min after intravenous administration of fluorescein, needle-based confocal laser endomicroscopy image quality was sufficient for interpretation for at least 14 min, yielding more than 5000 confocal laser endomicroscopy frames per patient. The pullback confocal laser endomicroscopy recordings and most of the push-forward recordings almost only visualized erythrocytes, being classified as non-representative. During the push-forward recordings, prostate tissue was occasionally visualized in single frames, insufficient for histopathologic comparison. Prostate carcinoma was identified by biopsy in one patient (Gleason score 4 + 3 = 7, >50%), while the biopsy from the other patient showed no malignancy. Conclusion: Needle-based confocal laser endomicroscopy imaging of in-vivo prostate tissue with a forward-looking confocal laser endomicroscopy probe is safe without device malfunctions or procedural failures. Needle-based confocal laser endomicroscopy is technically feasible, but the acquired confocal laser endomicroscopy datasets are non-representative. The confocal laser endomicroscopy images' non-representative nature is possibly caused by bleeding artifacts, movement artifacts and a lack of contact time with the tissue of interest. A different confocal laser endomicroscopy probe or procedure might yield representative images of prostatic tissue.

En-face optical coherence tomography for the detection of cancer in prostatectomy specimens: Quantitative analysis in 20 patients.

The increase histopathological evaluation of prostatectomy specimens rises the workload on pathologists. Automated histopathology systems, preferably directly on unstained specimens, would accelerate the pathology workflow. In this study, we investigate the potential of quantitative analysis of optical coherence tomography (OCT) to separate benign from malignant prostate tissue automatically. Twenty fixated prostates were cut, from which 54 slices were scanned by OCT. Quantitative OCT metrics (attenuation coefficient, residue, goodness-of-fit) were compared for different tissue types, annotated on the histology slides. To avoid misclassification, the poor-quality slides, and edges of annotations were excluded. Accurate registration of OCT data with histology was achieved in 31 slices. After removing outliers, 56% of the OCT data was compared with histopathology. The quantitative data could not separate malignant from benign tissue. Logistic regression resulted in malignant detection with a sensitivity of 0.80 and a specificity of 0.34. Quantitative OCT analysis should be improved before clinical use.

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.

One-to-one registration of en-face optical coherence tomography attenuation coefficients with histology of a prostatectomy specimen.

Optical coherence tomography (OCT), enables high-resolution 3D imaging of the morphology of light scattering tissues. From the OCT signal, parameters can be extracted and related to tissue structures. One of the quantitative parameters is the attenuation coefficient; the rate at which the intensity of detected light decays in depth. To couple the quantitative parameters with the histology one-to-one registration is needed. The primary aim of this study is to validate a registration method of quantitative OCT parameters to histological tissue outcome through one-to-one registration of OCT with histology. We matched OCT images of unstained fixated prostate tissue slices with corresponding histology slides, wherein different histologic types were demarcated. Attenuation coefficients were determined by a supervised automated exponential fit (corrected for point spread function and sensitivity roll-off related signal losses) over a depth of 0.32 mm starting from 0.10 mm below the automatically detected tissue edge. Finally, the attenuation coefficients corresponding to the different tissue types of the prostate were compared. From the attenuation coefficients, we produced the squared relative residue and goodness-of-fit metric R2 . This article explains the method to perform supervised automated quantitative analysis of OCT data, and the one-to-one registration of OCT extracted quantitative data with histopathological outcomes.

Needle-based optical coherence tomography for the detection of prostate cancer: a visual and quantitative analysis in 20 patients.

Diagnostic accuracy of needle-based optical coherence tomography (OCT) for prostate cancer detection by visual and quantitative analysis is defined. 106 three-dimensional (3-D)-OCT data sets were acquired in 20 prostates after radical prostatectomy and precisely matched with pathology. OCT images were grouped per histological category. Two reviewers performed blind assessments of the OCT images. Sensitivity and specificity for malignancy detection were calculated. Quantitative analyses by automated optical attenuation coefficient calculation were performed. OCT can reliably differentiate between fat, cystic, and regular atrophy and benign glands. The overall sensitivity and specificity for malignancy detection was 79% and 88% for reviewer 1 and 88% and 81% for reviewer 2. Quantitative analysis for differentiation between stroma and malignancy showed a significant difference (4.6 mm - 1 versus 5.0 mm - 1 Mann-Whitney U-test p < 0.0001). A Kruskal-Wallis test showed a significant difference in median attenuation coefficient between stroma, inflammation, Gleason 3, and Gleason 4 (4.6, 4.1, 5.9, and 5.0 mm - 1, respectively). However, attenuation coefficient varied per patient and a related-samples Wilcoxon signed-rank test showed no significant difference per patient (p = 0.17). This study confirmed the one to one correlation of histopathology and OCT. Precise matching showed that most histological tissues categories in the prostate could be distinguished by their unique pattern in OCT images. In addition, the optical attenuation coefficient can play a role in the differentiation between stroma and malignancy; however, a per patient analysis of the optical attenuation coefficient did not show a significant difference.

Confocal Laser Endomicroscopy and Optical Coherence Tomography for the Diagnosis of Prostate Cancer: A Needle-Based, In Vivo Feasibility Study Protocol (IDEAL Phase 2A).

BACKGROUND: Focal therapy for prostate cancer has been proposed as an alternative treatment to whole-gland therapies in selected men to diminish side effects in localized prostate cancer. As nowadays imaging cannot offer complete prostate cancer disease characterization, multicore systematic biopsies are recommended (transrectal or transperineal). Optical imaging techniques such as confocal laser endomicroscopy and optical coherence tomography allow in vivo, high-resolution imaging. Moreover, they can provide real-time visualization and analysis of tissue and have the potential to offer additive diagnostic information. OBJECTIVE: This study has 2 separate primary objectives. The first is to assess the technical feasibility and safety of in vivo focal imaging with confocal laser endomicroscopy and optical coherence tomography. The second is to identify and define characteristics of prostate cancer and normal prostate tissue in confocal laser endomicroscopy and optical coherence tomography imaging by comparing these images with the corresponding histopathology. METHODS: In this prospective, in vivo feasibility study, needle-based confocal laser endomicroscopy and optical coherence tomography imaging will be performed before transperineal template mapping biopsy or radical prostatectomy. First, confocal laser endomicroscopy and optical coherence tomography will be performed in 4 patients (2 for each imaging modality) undergoing transperineal template mapping biopsy to assess the feasibility and safety of confocal laser endomicroscopy and optical coherence tomography. If proven to be safe and feasible, confocal laser endomicroscopy and optical coherence tomography will be performed in 10 patients (5 for each imaging modality) undergoing radical prostatectomy. Confocal laser endomicroscopy and optical coherence tomography images will be analyzed by independent, blinded observers. Confocal laser endomicroscopy- and optical coherence tomography-based qualitative and quantitative characteristics and histopathology will be compared. The study complies with the IDEAL (Idea, Development, Exploration, Assessment, Long-term study) stage 2a recommendations. RESULTS: At present, the study is enrolling patients and results and outcomes are expected in 2019. CONCLUSIONS: Confocal laser endomicroscopy and optical coherence tomography are promising optical imaging techniques that can visualize and analyze tissue structure, possible tumor grade, and architecture in real time. They can potentially provide real-time, high-resolution microscopic imaging and tissue characteristics of prostate cancer in conjunction with magnetic resonance imaging or transrectal ultrasound fusion-guided biopsy procedures. This study will provide insight into the feasibility and tissue-specific characteristics of confocal laser endomicroscopy and optical coherence tomography for real-time optical analysis of prostate cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT03253458; https://clinicaltrials.gov/ct2/show/NCT03253458 (Archived by WebCite at http://www.webcitation.org/6z9owM66B). REGISTERED REPORT IDENTIFIER: RR1-10.2196/9813.

In vivo, percutaneous, needle based, optical coherence tomography of renal masses.

Optical coherence tomography (OCT) is the optical equivalent of ultrasound imaging, based on the backscattering of near infrared light. OCT provides real time images with a 15 µm axial resolution at an effective tissue penetration of 2-3 mm. Within the OCT images the loss of signal intensity per millimeter of tissue penetration, the attenuation coefficient, is calculated. The attenuation coefficient is a tissue specific property, providing a quantitative parameter for tissue differentiation. Until now, renal mass treatment decisions have been made primarily on the basis of MRI and CT imaging characteristics, age and comorbidity. However these parameters and diagnostic methods lack the finesse to truly detect the malignant potential of a renal mass. A successful core biopsy or fine needle aspiration provides objective tumor differentiation with both sensitivity and specificity in the range of 95-100%. However, a non-diagnostic rate of 10-20% overall, and even up to 30% in SRMs, is to be expected, delaying the diagnostic process due to the frequent necessity for additional biopsy procedures. We aim to develop OCT into an optical biopsy, providing real-time imaging combined with on-the-spot tumor differentiation. This publication provides a detailed step-by-step approach for percutaneous, needle based, OCT of renal masses.