Needle-based confocal laser endomicroscopy for real-time granuloma detection.

BACKGROUND AND OBJECTIVE: Needle-based confocal laser endomicroscopy (nCLE) allows real-time microscopic imaging at the needle tip. nCLE malignancy criteria are used for tool-in-lesion confirmation during bronchoscopic lung nodule analysis. However, to date, nCLE criteria for granulomas are lacking. The aim was to identify and validate nCLE granuloma criteria and assess if blinded raters can distinguish malignant from granulomatous nCLE videos. METHODS: In patients with suspected sarcoidosis, nCLE-imaging of mediastinal lymph nodes was performed during endoscopic ultrasound procedures, followed by needle aspiration. nCLE granuloma criteria were identified by comparison with pathology and final diagnoses. Additionally, nCLE-videos of granulomatous lung nodules part of prospective trials and clinical care were compared to the proposed nCLE granuloma criteria. Blinded raters validated nCLE videos of sarcoid and reactive mediastinal lymph nodes and malignant and granulomatous lung nodules twice. RESULTS: Granuloma criteria were identified (brighter-toned, homogeneous and well-demarcated lesions) based on nCLE-imaging in 14 sarcoidosis patients. Raters evaluated 26 nCLE-videos obtained in lymph nodes (n = 15 sarcoidosis; n = 11 reactive and total of 260 ratings). Granuloma criteria were recognized with 88% accuracy. The inter-observer (κ = 0.63, 95% CI 0.54-0.72) and intra-observer reliability (κ = 0.70 ± 0.06) were substantial. Based on 12 nCLE-videos obtained in lung nodules (n = 4 granulomas, n = 6 malignancy, n = 2 malignancy + granulomas and total of 120 ratings) granuloma and malignancy criteria were recognized with 92% and 75% accuracy. CONCLUSION: nCLE imaging facilitates real-time granuloma visualization. Blinded raters accurately and consistently recognized granulomas on nCLE-imaging and distinguished nCLE granuloma criteria from malignancy. Our data show the potential of nCLE as a real-time bronchoscopic guidance tool for lung nodule analysis.

Bronchoscopic needle-based confocal laser endomicroscopy (nCLE) as a real-time detection tool for peripheral lung cancer.

INTRODUCTION: Diagnosing peripheral lung cancer with the bronchoscope is challenging with near miss of the target lesion as major obstacle. Needle-based confocal laser endomicroscopy (nCLE) enables real-time microscopic tumour visualisation at the needle tip (smart needle). AIM: To investigate feasibility and safety of bronchoscopic nCLE imaging of suspected peripheral lung cancer and to assess whether nCLE imaging allows real-time discrimination between malignancy and airway/lung parenchyma. METHODS: Patients with suspected peripheral lung cancer based on (positron emission tomography-)CT scan underwent radial endobronchial ultrasound (rEBUS) and fluoroscopy-guided flexible bronchoscopy. After rEBUS lesion detection, an 18G needle loaded with the CLE probe was inserted in the selected airway under fluoroscopic guidance. The nCLE videos were obtained at the needle tip, followed by aspirates and biopsies. The nCLE videos were reviewed and compared with the cytopathology of the corresponding puncture and final diagnosis. Five blinded raters validated nCLE videos of lung tumours and airway/lung parenchyma twice. RESULTS: The nCLE imaging was performed in 26 patients. No adverse events occurred. In 24 patients (92%) good to high quality videos were obtained (final diagnosis; lung cancer n=23 and organising pneumonia n=1). The nCLE imaging detected malignancy in 22 out of 23 patients with lung cancer. Blinded raters differentiated nCLE videos of malignancy from airway/lung parenchyma (280 ratings) with a 95% accuracy. The inter-observer agreement was substantial (κ=0.78, 95% CI 0.70 to 0.86) and intra-observer reliability excellent (mean±SD κ=0.81±0.05). CONCLUSION: Bronchoscopic nCLE imaging of peripheral lung lesions is feasible, safe and allows real-time lung cancer detection. Blinded raters accurately distinguished nCLE videos of lung cancer from airway/lung parenchyma, showing the potential of nCLE imaging as real-time guidance tool.

Ablation energies for focal treatment of prostate cancer.

CONTEXT: In recent years, focal therapy has emerged as a treatment option for a selected group of men with localized prostate cancer. Cryotherapy and high-intensity focused ultrasound (HIFU) are the most investigated types of focal treatment with other options currently under evaluation. OBJECTIVE: The objective of the study was to give a comprehensive overview of six available focal treatment options for prostate cancer with their rationale, delivery mechanism, and outcomes. INFORMATION ACQUISITION: The SIU ICUD chapter on available Energies to Treat Prostate Cancer was used as a guide to describe the different technologies. For outcomes, a literature search was conducted using PubMed key words including focal therapy, HIFU, cryotherapy, irreversible electroporation, vascular-targeted photodynamic therapy, laser interstitial therapy, radiofrequency ablation, microwave therapy, and their synonyms in MeSH terms. CONCLUSION: Focal therapy appears to have encouraging outcomes on quality of life and urinary and erectile function. For oncological outcomes, it is challenging to fully interpret the outcomes due to heterogeneity in patient selection and short-term follow-up.

Three-dimensional pointwise comparison of human retinal optical property at 845 and 1060 nm using optical frequency domain imaging.

To compare the optical properties of the human retina, 3-D volumetric images of the same eye are acquired with two nearly identical optical coherence tomography (OCT) systems at center wavelengths of 845 and 1060 nm using optical frequency domain imaging (OFDI). To characterize the contrast of individual tissue layers in the retina at these two wavelengths, the 3-D volumetric data sets are carefully spatially matched. The relative scattering intensities from different layers such as the nerve fiber, photoreceptor, pigment epithelium, and choroid are measured and a quantitative comparison is presented. OCT retinal imaging at 1060 nm is found to have a significantly better depth penetration but a reduced contrast between the retinal nerve fiber, the ganglion cell, and the inner plexiform layers compared to the OCT retinal imaging at 845 nm.

Feasibility of using optical coherence tomography to detect radiation-induced fibrosis and residual cancer extent after neoadjuvant chemo-radiation therapy: an ex vivo study.

Treatment of resectable esophageal cancer includes neoadjuvant chemo-radiation therapy (nCRT) followed by esophagectomy in operable patients. High-risk surgery may have been avoided in patients with a pathological complete response (pCR). We investigated the feasibility of optical coherence tomography (OCT) to detect residual cancer and radiation-induced fibrosis in 10 esophageal cancer patients that underwent nCRT followed by esophagectomy. We compared our OCT findings with histopathology. Overall, OCT was able to differentiate between healthy tissue, fibrotic tissue, and residual cancer with a sensitivity and specificity of 79% and 67%, respectively. Hence, OCT has the potential to add to the assessment of a pCR.

Visibility of fiducial markers used for image-guided radiation therapy on optical coherence tomography for registration with CT: An esophageal phantom study.

PURPOSE: Optical coherence tomography (OCT) is of interest to visualize microscopic esophageal tumor extensions to improve tumor delineation for radiation therapy (RT) planning. Fiducial marker placement is a common method to ensure target localization during planning and treatment. Visualization of these fiducial markers on OCT permits integrating OCT and computed tomography (CT) images used for RT planning via image registration. We studied the visibility of 13 (eight types) commercially available solid and liquid fiducial markers in OCT images at different depths using dedicated esophageal phantoms and evaluated marker placement depth in clinical practice. MATERIALS AND METHODS: We designed and fabricated dedicated esophageal phantoms, in which three layers mimic the anatomical wall structures of a healthy human esophagus. We successfully implanted 13 commercially available fiducial markers that varied in diameter and material property at depths between 0.5 and 3.0 mm. The resulting esophageal phantoms were imaged with OCT, and marker visibility was assessed qualitatively and quantitatively using the contrast-to-background-noise ratio (CNR). The CNR was defined as the difference between the mean intensity of the fiducial markers and the mean intensity of the background divided by the standard deviation of the background intensity. To determine whether, in current clinical practice, the implanted fiducial markers are within the OCT visualization range (up to 3.0 mm depth), we retrospectively measured the distance of 19 fiducial markers to the esophageal lumen on CT scans of 16 esophageal cancer patients. RESULTS: In the esophageal phantoms, all the included fiducial markers were visible on OCT at all investigated depths. Solid fiducial markers were better visible on OCT than liquid fiducial markers with a 1.74-fold higher CNR. Although fiducial marker identification per type and size was slightly easier for superficially implanted fiducial markers, we observed no difference in the ability of OCT to visualize the markers over the investigated depth range. Retrospective distance measurements of 19 fiducial markers on the CT scan of esophageal cancer patients showed that 84% (distance from the closest border of the marker to the lumen) and 53% (distance from the center of the marker to the lumen) of the fiducial markers were located within the OCT visualization range of up to 3.0 mm. CONCLUSIONS: We studied the visibility of eight types of commercially available fiducial markers at different depths on OCT using dedicated esophageal phantoms. All tested fiducial markers were visible at depths ≤3.0 mm and most, but not all, clinically implanted markers were at a depth accessible to OCT. Consequently, the use of fiducial markers as a reference for OCT to CT registration is feasible.

Doppler optical coherence tomography to monitor the effect of photodynamic therapy on tissue morphology and perfusion.

We investigated the feasibility of using optical coherence tomography (OCT) for noninvasive real-time visualization of the vascular effects of photodynamic therapy (PDT) in normal and tumor tissue in mice. Perfusion control measurements were initially performed after administrating vaso-active drugs or clamping of the subcutaneous tumors. Subsequent measurements were made on tumor-bearing mice before and after PDT using the photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC). Tumors were illuminated using either a short drug light interval (D-L, 3 h), when mTHPC is primarily located in the tumor vasculature or a long D-L interval (48 h), when the drug is distributed throughout the whole tumor. OCT enabled visualization of the different layers of tumor, and overlying skin with a maximal penetration of < or =0.5-1 mm. PDT with a short D-L interval resulted in a significant decrease of perfusion in the tumor periphery, to 20% of pre-treatment values at 160 min, whereas perfusion in the skin initially increased by 10% (at 25 min) and subsequently decreased to 60% of pre-treatment values (at 200 min). PDT with a long D-L interval did not induce significant changes in perfusion. The concept of using noninvasive OCT measurements for monitoring early, treatment-related changes in morphology and perfusion may have applications in evaluating effects of anti-angiogenic or antivascular (cancer) therapy.