Publications by authors named "Daniel M de Bruin"

70 Publications

Machine learning for grading and prognosis of esophageal dysplasia using mass spectrometry and histological imaging.

Comput Biol Med 2021 Oct 4;138:104918. Epub 2021 Oct 4.

Department of Precision Medicine, GROW - School for Oncology and Developmental Biology, Maastricht University, 6229 ER Maastricht, The Netherlands; Department of Radiology and Nuclear Medicine, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, 6202 AZ, Maastricht, The Netherlands.

Background: Barrett's esophagus (BE) is a precursor lesion of esophageal adenocarcinoma and may progress from non-dysplastic through low-grade dysplasia (LGD) to high-grade dysplasia (HGD) and cancer. Grading BE is of crucial prognostic value and is currently based on the subjective evaluation of biopsies. This study aims to investigate the potential of machine learning (ML) using spatially resolved molecular data from mass spectrometry imaging (MSI) and histological data from microscopic hematoxylin and eosin (H&E)-stained imaging for computer-aided diagnosis and prognosis of BE.

Methods: Biopsies from 57 patients were considered, divided into non-dysplastic (n = 15), LGD non-progressive (n = 14), LGD progressive (n = 14), and HGD (n = 14). MSI experiments were conducted at 50 × 50 μm spatial resolution per pixel corresponding to a tile size of 96x96 pixels in the co-registered H&E images, making a total of 144,823 tiles for the whole dataset.

Results: ML models were trained to distinguish epithelial tissue from stroma with area-under-the-curve (AUC) values of 0.89 (MSI) and 0.95 (H&E)) and dysplastic grade (AUC of 0.97 (MSI) and 0.85 (H&E)) on a tile level, and low-grade progressors from non-progressors on a patient level (accuracies of 0.72 (MSI) and 0.48 (H&E)).

Conclusions: In summary, while the H&E-based classifier was best at distinguishing tissue types, the MSI-based model was more accurate at distinguishing dysplastic grades and patients at progression risk, which demonstrates the complementarity of both approaches. Data are available via ProteomeXchange with identifier PXD028949.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104918DOI Listing
October 2021

MRI and CT in the follow-up after irreversible electroporation of small renal masses.

Diagn Interv Radiol 2021 Sep;27(5):654-663

Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands.

Purpose: Ablation plays a growing role in the treatment of small renal masses (SRMs) due to its nephron sparing properties and low invasiveness. Irreversible electroporation (IRE) has the potential, although still experimental, to overcome current limitations of thermal ablation. No prospective imaging studies exist of the ablation zone in the follow up after renal IRE in humans. Objectives are to assess computed tomography (CT) and magnetic resonance imaging (MRI) on the ablation zone volume (AZV), enhancement and imaging characteristics after renal IRE.

Methods: Prospective phase 2 study of IRE in nine patients with ten SRMs. MRI imaging was performed pre-IRE, 1 week, 3 months, 6 months and 12 months after IRE. CT was performed pre-IRE, perioperatively (direct after ablation), 3 months, 6 months and 12 months after IRE. AZVs were assessed by two independent observers. Observer variation was analyzed. Evolution of AZVs, and relation between the needle configuration volume (NCV; planned AZV) and CT- and MRI volumes were evaluated.

Results: Eight SRMs were clear cell renal cell carcinomas, one SRM was a papillary renal cell carcinoma and one patient had a non-diagnostic biopsy. On CT, median AZV increased perioperatively until 3 months post-IRE (respectively, 16.8 cm3 and 6.2 cm3) compared to the NCV (4.8 cm3). On MRI, median AZV increased 1-week post-IRE until 3 months post-IRE (respectively, 14.5 cm3 and 4.6 cm3) compared to the NCV (4.8 cm3). At 6 months the AZV starts decreasing (CT 4.8 cm3; MRI 3.0 cm3), continuing at 12 months (CT 4.2 cm3, MRI 1.1 cm3). Strong correlation was demonstrated between the planning and the post-treatment volumes. Inter-observer agreement between observers was excellent (CT 95% CI 0.82-0.95, MRI 95% CI 0.86-0.96). All SRMs appeared non-enhanced immediately after ablation, except for one residual tumour. Subtraction images confirmed non-enhancement on MRI in unclear enhancement cases (3/9). Directly after IRE, gas bubbles, perinephric stranding and edema were observed in all cases.

Conclusion: The AZV increases immediately on CT until 3 months after IRE. On MRI, the AZV increases at 1 week until 3 months post-IRE. At 6 months the AZV starts decreasing until 12 months post-IRE on both CT and MRI. Enhancement was absent post-IRE, except for one residual tumour. Gas bubbles, perinephric stranding and edema are normal findings directly post-IRE.
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http://dx.doi.org/10.5152/dir.2021.19575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480958PMC
September 2021

Toward improved endoscopic surveillance with multidiameter single fiber reflectance spectroscopy in patients with Barrett's esophagus.

J Biophotonics 2021 04 31;14(4):e202000351. Epub 2021 Jan 31.

Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, The Netherlands.

Patients with Barrett's esophagus are at an increased risk to develop esophageal cancer and, therefore, undergo regular endoscopic surveillance. Early detection of neoplasia enables endoscopic treatment, which improves outcomes. However, early Barrett's neoplasia is easily missed during endoscopic surveillance. This study investigates multidiameter single fiber reflectance spectroscopy (MDSFR) to improve Barrett's surveillance. Based on the concept of field cancerization, it may be possible to identify the presence of a neoplastic lesion from measurements elsewhere in the esophagus or even the oral cavity. In this study, MDSFR measurements are performed on non-dysplastic Barrett's mucosa, squamous mucosa, oral mucosa, and the neoplastic lesion (if present). Based on logistic regression analysis on the scattering parameters measured by MDSFR, a classifier is developed that can predict the presence of neoplasia elsewhere in the Barrett's segment from measurements on the non-dysplastic Barrett's mucosa (sensitivity 91%, specificity 71%, AUC = 0.77). Classifiers obtained from logistic regression analysis for the squamous and oral mucosa do not result in an AUC significantly different from 0.5.
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http://dx.doi.org/10.1002/jbio.202000351DOI Listing
April 2021

Deep Learning-based Recurrence Prediction in Patients with Non-muscle-invasive Bladder Cancer.

Eur Urol Focus 2020 Dec 22. Epub 2020 Dec 22.

Department of Biomedical Engineering and Physics, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Biomedical Engineering and Physics, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Background: Non-muscle-invasive bladder cancer (NMIBC) is characterized by frequent recurrence of the disease, which is difficult to predict.

Objective: To combine digital histopathology slides with clinical data to predict 1- and 5-yr recurrence-free survival of NMIBC patients using deep learning.

Design, Setting, And Participants: Data of patients undergoing a transurethral resection of a bladder tumor between 2000 and 2018 at a Dutch academic medical center were selected. Corresponding histological slides were digitized. A three-step approach was used to predict 1- and 5-yr recurrence-free survival. First, a segmentation network was used to detect the urothelium on the digital histopathology slides. Second, a selection network was trained for the selection of patches associated with recurrence. Third, a classification network, combining the information of the selection network with clinical data, was trained to give the probability of 1- and 5-yr recurrence-free survival.

Outcome Measurements And Statistical Analysis: The accuracy of the deep learning-based model was compared with a multivariable logistic regression model using clinical data only.

Results And Limitations: In the 1- and 5-yr follow-up cohorts, 359 and 281 patients were included with recurrence rates of 27% and 63%, respectively. The areas under the curve (AUCs) of the model combining digital histopathology slide data with clinical data were 0.62 and 0.76 for 1- and 5-yr recurrence predictions, respectively, which were higher than those of the model using digital histopathology slide data only (AUCs of 0.56 and 0.72, respectively) and the multivariable logistic regression (AUCs of 0.58 and 0.57, respectively).

Conclusions: In our population, the deep learning-based model combining digital histopathology slides and clinical data enhances the prediction of recurrence (within 5 yr) compared with models using clinical data or image data only.

Patient Summary: By combining histopathology images and patient record data using deep learning, the prediction of recurrence in bladder cancer patients is enhanced.
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http://dx.doi.org/10.1016/j.euf.2020.12.008DOI Listing
December 2020

Quantitative change of perfusion in gastric tube reconstruction by sidestream dark field microscopy (SDF) after esophagectomy, a prospective in-vivo cohort study.

Eur J Surg Oncol 2021 05 13;47(5):1034-1041. Epub 2020 Sep 13.

Amsterdam UMC, University of Amsterdam, Department of Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands.

Background: Anastomotic leakage is one of the most severe complications in patients undergoing esophagectomy with gastric tube reconstruction. Transection of the left gastric and gastro-epiploic artery and vein results in compromised perfusion which is seen as the major contributing factor for anastomotic dehiscence. The main objective of this prospective, observational, in-vivo pilot study is to microscopically evaluate gastric tube perfusion with Sidestream Darkfield Microscopy (SDF).

Methods: Intra-operative microscopic images of gastric-microcirculation were obtained with SDF directly after reconstruction in 22 patients. Quantitative perfusion related parameters were: velocity, Microvascular Flow Index(MFI), Total Vessel Density(TVD), Perfusion Vessel Density(PVD), Proportion of Perfused Vessels(PPV) and De Backer Score(DBS). Dedicated software was used to assess parameters predictive for compromised perfusion.

Results: SDF was feasible to accurately visualize and evaluate microcirculation in all patients. Velocity(μm/sec) was significantly decreased towards the fundus (p = 0.001). MFI, PVD and PVD were decreased distal of the watershed - between the right and left gastro-epiploic artery and vein - and in the fundus, compared to the base of the gastric tube(p = 0.0002). No differences in TVD and DBS were observed; because of vessel-dilation in the fundus-area. This suggests that venous congestion results in comprised inflow of oxygen rich blood and plays a role in the development of ischaemia.

Conclusion: We present quantitative perfusion imaging with SDF of the gastric tube. Velocity, MFI, TVD and PPV are accurate parameters to observe perfusion decrease. Also, venous congestion is visible in the fundus, suggesting an important role in the development of ischaemia. These parameters could allow early risk stratification, and, potentially, can accomplish a reduction in anastomotic leakage.
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http://dx.doi.org/10.1016/j.ejso.2020.09.006DOI Listing
May 2021

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

Am J Pathol 2020 07 10;190(7):1483-1490. Epub 2020 Apr 10.

Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

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.
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http://dx.doi.org/10.1016/j.ajpath.2020.03.013DOI Listing
July 2020

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

J Biophotonics 2020 06 30;13(6):e201960105. Epub 2020 Mar 30.

Department of Biomedical Engineering and Physics, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1002/jbio.201960105DOI Listing
June 2020

Evaluation of acute esophageal radiation-induced damage using magnetic resonance imaging: a feasibility study in mice.

Radiat Oncol 2019 Oct 30;14(1):188. Epub 2019 Oct 30.

Department of Biomedical Engineering and Physics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.

Background: Thoracic and head and neck cancer radiation therapy (RT) can cause damage to nearby healthy organs such as the esophagus, causing acute radiation-induced esophageal damage (ARIED). A non-invasive method to detect and monitor ARIED can facilitate optimizing RT to avoid ARIED while improving local tumor control. Current clinical guidelines are limited to scoring the esophageal damage based on the symptoms of patients. Magnetic resonance imaging (MRI) is a non-invasive imaging modality that may potentially visualize radiation-induced organ damage. We investigated the feasibility of using T2-weighted MRI to detect and monitor ARIED using a two-phased study in mice.

Methods: The first phase aimed to establish the optimal dose level at which ARIED is inducible and to determine the time points where ARIED is detectable. Twenty four mice received a single dose delivery of 20 and 40 Gy at proximal and distal spots of 10.0 mm (in diameter) on the esophagus. Mice underwent MRI and histopathology analysis with esophageal resection at two, three, and 4 weeks post-irradiation, or earlier in case mice had to be euthanized due to humane endpoints. In the second phase, 32 mice received a 40 Gy single dose and were studied at two, three, and 7 days post-irradiation. We detected ARIED as a change in signal intensity of the MRI images. We measured the width of the hyperintense area around the esophagus in all mice that underwent MRI prior to and after irradiation. We conducted a blind qualitative comparison between MRI findings and histopathology as the gold standard.

Results/conclusions: A dose of 40 Gy was needed to induce substantial ARIED. MRI detected ARIED as high signal intensity, visible from 2 days post-irradiation. Quantitative MRI analysis showed that the hyperintense area around the esophagus with severe ARIED was 1.41 mm wider than with no damage and MRI-only mice. The overall sensitivity and specificity were 56 and 43% respectively to detect any form of ARIED. However, in this study MRI correctly detected 100% of severe ARIED cases. Our two-phased preclinical study showed that MRI has the potential to detect ARIED as a change in signal intensity and width of enhancement around the esophagus.
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http://dx.doi.org/10.1186/s13014-019-1396-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822441PMC
October 2019

Toward Automated Bladder Tumor Stratification Using Confocal Laser Endomicroscopy.

J Endourol 2019 11 29;33(11):930-937. Epub 2019 Oct 29.

Department of Biomedical Engineering and Physics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Urothelial carcinoma of the bladder (UCB) is the most common urinary cancer. White-light cystoscopy (WLC) forms the corner stone for the diagnosis of UCB. However, histopathological assessment is required for adjuvant treatment selection. Probe-based confocal laser endomicroscopy (pCLE) enables visualization of the microarchitecture of bladder lesions during WLC, which allows for real-time tissue differentiation and grading of UCB. To improve the diagnostic process of UCB, computer-aided classification of pCLE videos of bladder lesions were evaluated in this study. We implemented preprocessing methods to optimize contrast and to reduce striping artifacts in each individual pCLE frame. Subsequently, a semiautomatic frame selection was performed. The selected frames were used to train a feature extractor based on pretrained ImageNet networks. A recurrent neural network, in specific long short-term memory (LSTM), was used to predict the grade of bladder lesions. Differentiation of lesions was performed at two levels, namely (i) healthy and benign malignant tissue and (ii) low-grade high-grade papillary UCB. A total of 53 patients with 72 lesions were included in this study, resulting in ∼140,000 pCLE frames. The semiautomated frame selection reduced the number of frames to ∼66,500 informative frames. The accuracy for differentiation of (i) healthy and benign malignant urothelium was 79% and (ii) high-grade and low-grade papillary UCB was 82%. A feature extractor in combination with LSTM results in proper stratification of pCLE videos of bladder lesions.
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http://dx.doi.org/10.1089/end.2019.0354DOI Listing
November 2019

Computed Tomography-Mediated Registration of Trapeziometacarpal Articular Cartilage Using Intraarticular Optical Coherence Tomography and Cryomicrotome Imaging: A Cadaver Study.

Cartilage 2019 Jul 11:1947603519860247. Epub 2019 Jul 11.

2 Biomedical Engineering and Physics, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, Netherlands.

Objective: Accurate, high-resolution imaging of articular cartilage thickness is an important clinical challenge in patients with osteoarthritis, especially in small joints. In this study, computed tomography (CT) mediated catheter-based optical coherence tomography (OCT) was utilized to create a digital reconstruction of the articular surface of the trapeziometacarpal (TMC) joint and to assess cartilage thickness in comparison to cryomicrotome data.

Design: Using needle-based introduction of the OCT probe, the articular surface of the TMC joint of 5 cadaver wrists was scanned in different probe positions with matching CT scans to record the intraarticular probe trajectory. Subsequently and based on the acquired CT data, 3-dimensional realignment of the OCT data to the curved intraarticular trajectory was performed for all probe positions. The scanned TMC joints were processed using a cryomicrotome imaging system. Finally, cartilage thickness measurements between OCT and cryomicrotome data were compared.

Results: Successful visualization of TMC articular cartilage was performed using OCT. The CT-mediated registration yielded a digital reconstruction of the articular surface on which thickness measurements could be performed. A near-perfect agreement between OCT and cryomicrotome thickness measurements was found ( = 0.989).

Conclusion: The proposed approach enables 3D reconstruction of the TMC articular surface with subsequent accurate cartilage thickness measurements, encouraging the development of intraarticular cartilage OCT for future (clinical) application.
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http://dx.doi.org/10.1177/1947603519860247DOI Listing
July 2019

Estimation of microvascular perfusion after esophagectomy: a quantitative model of dynamic fluorescence imaging.

Med Biol Eng Comput 2019 Sep 26;57(9):1889-1900. Epub 2019 Jun 26.

Department of Biomedical Engineering & Physics, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

Most common complications of esophagectomy stem from a perfusion deficiency of the gastric conduit at the anastomosis. Fluorescent tracer imaging allows intraoperative visualization of tissue perfusion. Quantitative assessment of fluorescence dynamics has the potential to identify perfusion deficiency. We developed a perfusion model to analyze the relation between fluorescence dynamics and perfusion deficiency. The model divides the gastric conduit into two well-perfused and two anastomosed sites. Hemodynamics and tracer transport were modeled. We analyzed the value of relative time-to-threshold (RTT) as a predictor of the relative remaining flow (RRF). Intensity thresholds for RTT of 20% to 50% of the maximum fluorescence intensity of the well-perfused site were tested. The relation between RTT and RRF at the anastomosed sites was evaluated over large variations of vascular conductance and volume. The ability of RTT to distinguish between sufficient and impaired perfusion was analyzed using c-statistics. We found that RTT was a valuable estimate for low RRF. The threshold of 20% of the maximum fluorescence intensity provided the best prediction of impaired perfusion on the two anastomosed sites (AUC = 0.89 and 0.86). The presented model showed that for low flows, relative time-to-threshold may be used to estimate perfusion deficiency.
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http://dx.doi.org/10.1007/s11517-019-01994-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706368PMC
September 2019

Numerical simulation modeling of the irreversible electroporation treatment zone for focal therapy of prostate cancer, correlation with whole-mount pathology and T2-weighted MRI sequences.

Ther Adv Urol 2019 Jan-Dec;11:1756287219852305. Epub 2019 Jun 7.

Department of Urology, Istanbul Medipol University, Istanbul, Turkey Amsterdam UMC, Amsterdam, the Netherlands.

Background: At present, it is not possible to predict the ablation zone volume following irreversible electroporation (IRE) for prostate cancer (PCa). This study aimed to determine the necessary electrical field threshold to ablate human prostate tissue with IRE.

Methods: In this prospective multicenter trial, patients with localized PCa were treated with IRE 4 weeks before their scheduled radical prostatectomy. In 13 patients, numerical models of the electrical field were generated and compared with the ablation zone volume on whole-mount pathology and T2-weighted magnetic resonance imaging (MRI) sequences. Volume-generating software was used to calculate the ablation zone volumes on histology and MRI. The electric field threshold to ablate prostate tissue was determined for each patient.

Results: A total of 13 patients were included for histological and simulation analysis. The median electrical field threshold was 550 V/cm (interquartile range 383-750 V/cm) for the software-generated histology volumes. The median electrical field threshold was 500 V/cm (interquartile range 386-580 V/cm) when the ablation zone volumes were used from the follow-up MRI.

Conclusions: The electrical field threshold to ablate human prostate tissue was determined using whole-mount pathology and MRI. These thresholds may be used to develop treatment planning or monitoring software for IRE prostate ablation; however, further optimization of simulation methods are required to decrease the variance that was observed between patients.
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http://dx.doi.org/10.1177/1756287219852305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557022PMC
June 2019

Deep learning for automatic Gleason pattern classification for grade group determination of prostate biopsies.

Virchows Arch 2019 Jul 16;475(1):77-83. Epub 2019 May 16.

Department of Biomedical Engineering and Physics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Histopathologic grading of prostate cancer using Gleason patterns (GPs) is subject to a large inter-observer variability, which may result in suboptimal treatment of patients. With the introduction of digitization and whole-slide images of prostate biopsies, computer-aided grading becomes feasible. Computer-aided grading has the potential to improve histopathological grading and treatment selection for prostate cancer. Automated detection of GPs and determination of the grade groups (GG) using a convolutional neural network. In total, 96 prostate biopsies from 38 patients are annotated on pixel-level. Automated detection of GP 3 and GP ≥ 4 in digitized prostate biopsies is performed by re-training the Inception-v3 convolutional neural network (CNN). The outcome of the CNN is subsequently converted into probability maps of GP ≥ 3 and GP ≥ 4, and the GG of the whole biopsy is obtained according to these probability maps. Differentiation between non-atypical and malignant (GP ≥ 3) areas resulted in an accuracy of 92% with a sensitivity and specificity of 90 and 93%, respectively. The differentiation between GP ≥ 4 and GP ≤ 3 was accurate for 90%, with a sensitivity and specificity of 77 and 94%, respectively. Concordance of our automated GG determination method with a genitourinary pathologist was obtained in 65% (κ = 0.70), indicating substantial agreement. A CNN allows for accurate differentiation between non-atypical and malignant areas as defined by GPs, leading to a substantial agreement with the pathologist in defining the GG.
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http://dx.doi.org/10.1007/s00428-019-02577-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611751PMC
July 2019

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

Lasers Surg Med 2019 May 14. Epub 2019 May 14.

Department of Urology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

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. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/lsm.23093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617991PMC
May 2019

Confocal Laser Endomicroscopy as a Guidance Tool for Pleural Biopsies in Malignant Pleural Mesothelioma.

Chest 2019 10 7;156(4):754-763. Epub 2019 May 7.

Department of Respiratory Medicine, Amsterdam University Medical Centers, Amsterdam. Electronic address:

Background: Pleural biopsies in patients with suspected malignant pleural mesothelioma (MPM) are often inconclusive resulting in repeat diagnostic procedures. Confocal laser endomicroscopy (CLE) enables real-time imaging on a cellular level. We investigated pleural CLE imaging as a biopsy guidance technique to distinguish malignant from benign pleural disease.

Methods: Prospective, multicenter study in patients with (suspected) MPM based on PET-CT imaging who were scheduled for pleural biopsies. Patients received 2.5 mL fluorescein intravenously preceding the procedure. In vivo through-the-needle CLE imaging of the pleura and ex vivo CLE imaging of the biopsies were correlated with histology. CLE characteristics for various pleural entities were identified, and their interpretability was tested by CLE video scoring by multiple blinded raters.

Results: CLE imaging was successfully obtained in 19 of 20 diagnostic pleural biopsy procedures (thoracoscopy: n = 4, surgical excision: n = 3, CT scan: n = 3, ultrasound: n = 9, esophageal ultrasound guided: n = 1) in 15 patients. CLE videos (n = 89) and corresponding pleural biopsies (n = 105) were obtained. No study-related adverse events occurred. Tumor deposits of MPM were distinguished from areas with pleural fibrosis based on CLE imaging and recognized by raters (n = 3) (interobserver agreement, 0.56; 95% CI, 0.49-0.64).

Conclusions: CLE imaging was feasible and safe regardless of the biopsy method. Real-time visualization of pleural abnormalities in epithelial and sarcomatoid MPM could be distinguished from pleural fibrosis. Therefore, CLE has potential as a guidance biopsy tool to reduce the current substantial rate of repeat biopsy procedures by identification of areas with malignant cells in vivo (smart needle).

Trial Registry: ClinicalTrials.gov; No.: NCT02689050; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2019.04.090DOI Listing
October 2019

Optical coherence tomography to detect acute esophageal radiation-induced damage in mice: A validation study.

J Biophotonics 2019 09 26;12(9):e201800440. Epub 2019 Jun 26.

Department of Biomedical Engineering and Physics, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Radiation therapy for patients with non-small-cell lung cancer is hampered by acute radiation-induced toxicity in the esophagus. This study aims to validate that optical coherence tomography (OCT), a minimally invasive imaging technique with high resolution (~10 μm), is able to visualize and monitor acute radiation-induced esophageal damage (ARIED) in mice. We compare our findings with histopathology as the gold standard. Irradiated mice receive a single dose of 40 Gy at proximal and distal spots of the esophagus of 10.0 mm in diameter. We scan mice using OCT at two, three, and seven days post-irradiation. In OCT analysis, we define ARIED as a presence of distorted esophageal layering, change in backscattering signal properties, or change in the esophageal wall thickness. The average esophageal wall thickness is 0.53 mm larger on OCT when ARIED is present based on histopathology. The overall sensitivity and specificity of OCT to detect ARIED compared to histopathology are 94% and 47%, respectively. However, the overall sensitivity of OCT to assess ARIED is 100% seven days post-irradiation. We validate the capability of OCT to detect ARIED induced by high doses in mice. Nevertheless, clinical studies are required to assess the potential role of OCT to visualize ARIED in humans.
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http://dx.doi.org/10.1002/jbio.201800440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065648PMC
September 2019

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

Eur Respir J 2019 06 20;53(6). Epub 2019 Jun 20.

Dept of Respiratory Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands

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.
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http://dx.doi.org/10.1183/13993003.01520-2018DOI Listing
June 2019

Three-dimensional histopathological reconstruction of bladder tumours.

Diagn Pathol 2019 Mar 28;14(1):25. Epub 2019 Mar 28.

Department of Biomedical Engineering and Physics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Background: Histopathological analysis is the cornerstone in bladder cancer (BCa) diagnosis. These analysis suffer from a moderate observer agreement in the staging of bladder cancer. Three-dimensional reconstructions have the potential to support the pathologists in visualizing spatial arrangements of structures, which may improve the interpretation of specimen. The aim of this study is to present three-dimensional (3D) reconstructions of histology images.

Methods: En-bloc specimens of transurethral bladder tumour resections were formalin fixed and paraffin embedded. Specimens were cut into sections of 4 μm and stained with Hematoxylin and Eosin (H&E). With a Phillips IntelliSite UltraFast scanner, glass slides were digitized at 20x magnification. The digital images were aligned by performing rigid and affine image alignment. The tumour and the muscularis propria (MP) were manually delineated to create 3D segmentations. In conjunction with a 3D display, the results were visualized with the Vesalius3D interactive visualization application for a 3D workstation.

Results: En-bloc resection was performed in 21 BCa patients. Per case, 26-30 sections were included for the reconstruction into a 3D volume. Five cases were excluded due to export problems, size of the dataset or condition of the tissue block. Qualitative evaluation suggested an accurate registration for 13 out of 16 cases. The segmentations allowed full 3D visualization and evaluation of the spatial relationship of the BCa tumour and the MP.

Conclusion: Digital scanning of en-bloc resected specimens allows a full-fledged 3D reconstruction and analysis and has a potential role to support pathologists in the staging of BCa.
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http://dx.doi.org/10.1186/s13000-019-0803-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440143PMC
March 2019

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

Lasers Surg Med 2019 Mar 28. Epub 2019 Mar 28.

Department of Urology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.

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 (μ ) is related to the histopathologic grade of the tumor.

Objectives: In this study, we aimed to define the μ 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 μ 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. μ analysis was feasible in all cases. The median μ was 3.3 mm (IQR 2.7-3.7 mm ) for low-grade UTUC and 4.9 mm (IQR 4.3-6.1 mm ) for high-grade UTUC (P = 0.004). ROC analysis yielded a μ cut-off value of >4.0 mm (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 μ cut-off of 4.0 mm 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 μ analysis in OCT systems may allow for μ assessment at real time during ureterorenoscopy. Lasers Surg. Med. 9999:1-8, 2019. © 2019 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/lsm.23079DOI Listing
March 2019

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

J Biophotonics 2019 04 28;12(4):e201800274. Epub 2018 Dec 28.

Biomedical Engineering & Physics, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

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 R . 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.
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http://dx.doi.org/10.1002/jbio.201800274DOI Listing
April 2019

Feasibility and safety of irreversible electroporation (IRE) in patients with small renal masses: Results of a prospective study.

Urol Oncol 2019 03 30;37(3):183.e1-183.e8. Epub 2018 Nov 30.

Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands.

Background: Irreversible electroporation (IRE) has the potential to overcome limitations of thermal ablation, enabling small renal mass (SRM) ablation near vital structures.

Purpose: To assess feasibility and safety of percutaneous IRE for the treatment of SRMs.

Materials And Methods: This prospective study is a phase 2 trial (NCT02828709) of IRE for patients with SRMs. Primary endpoints are feasibility and safety. Device- and procedural-adverse events were assessed by Clavien-Dindo and Common Terminology Criteria for Adverse Events version 4.0 grading systems. Technical feasibility was assessed by recording the technical success of the procedures. Technical success was evaluated by performing a CT immediately after ablation where complete tumor coverage and nonenhancement were evaluated. Tumor charcateristics and patient characteristics, procedural and anesthesia details, postprocedural events, and perioperative complications were recorded.

Results: Ten SRMs were included with a mean tumor size of 2.2 cm (range 1.1-3.9 cm) were treated with IRE. Renal mass biopsies revealed 7 clear cell and 1 papillary renal cell carcinoma. Two renal mass biopsies were nondiagnostic. The median follow-up was 6 months (range 3-12 months). Technical success was achieved in 9 out of 10 cases. One patient had a grade 3 Clavien-Dindo complication (1/10, 95% Confidence interval (CI) 0.0179-0.4041). Mean anesthesia time was 3.7 hours (range 3-5 hours), mean procedural time was 2.1 hours (range 1 hour 45 minutes-2 hours 30 minutes) and mean ablation time was 50 minutes (range 20 minutes-1 hour 45 minutes). The creatinine preoperative and postoperative (1 week, 3 months, 6 months, and 12 months) did not significantly differ. In total, 8 out of 10 cases did not experience postoperative pain.

Conclusion: IRE in SRMs is safe and feasible. Renal function is not affected by IRE and postoperative pain is rare. Anesthesia time and procedural time are a potential concern.
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http://dx.doi.org/10.1016/j.urolonc.2018.11.008DOI Listing
March 2019

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

Respiration 2019;97(3):259-263. Epub 2018 Nov 14.

Department of Respiratory Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands,

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.
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http://dx.doi.org/10.1159/000493271DOI Listing
April 2020

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

Respiration 2018;96(6):564-570. Epub 2018 Aug 15.

Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The

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.
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http://dx.doi.org/10.1159/000491676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390463PMC
October 2019

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

Lasers Surg Med 2018 12 8;50(10):980-986. Epub 2018 Jun 8.

Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.

Background And Objectives: A 36-year-old woman underwent CO 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 CO 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 CO 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.
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http://dx.doi.org/10.1002/lsm.22951DOI Listing
December 2018

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

Sensors (Basel) 2018 Apr 25;18(5). Epub 2018 Apr 25.

Department of Biomedical Engineering & Physics, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.3390/s18051331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5982600PMC
April 2018

study in nephroureterectomy specimens defining the role of 3-D upper urinary tract visualization using optical coherence tomography and endoluminal ultrasound.

J Med Imaging (Bellingham) 2018 Jan 12;5(1):017001. Epub 2018 Feb 12.

University of Amsterdam, Academic Medical Center, Department of Biomedical Engineering and Physics, Amsterdam, The Netherlands.

Minimal invasive endoscopic treatment for upper urinary tract urothelial carcinoma (UUT-UC) is advocated in patients with low-risk disease and limited tumor volume. Diagnostic ureterorenoscopy combined with biopsy is the diagnostic standard. This study aims to evaluate two alternative diagnostic techniques for UUT-UC: optical coherence tomography (OCT) and endoluminal ultrasound (ELUS). Following nephroureterectomy, OCT, ELUS, and computed tomography (CT) were performed of the complete nephroureterectomy specimen. Visualization software (AMIRA) was used for reconstruction and coregistration of CT, OCT, and ELUS. Finally, CT was used to obtain exact probe localization. Coregistered OCT and ELUS datasets were compared with histology. Coregistration with three-dimensional CT makes exact data matching possible in this setting to compare histology with OCT and ELUS. In OCT images of normal-appearing renal pelvis and ureter, urothelium, lamina propria, and muscularis were visible. With ELUS, all anatomical layers of the ureter could be distinguished, besides the urothelial layer. ELUS identified suspect lesions, although exact staging and differentiation between noninvasive and invasive lesions were not possible. OCT provides high-resolution imaging of normal ureter and ureter lesions. ELUS, however, is of limited value as it cannot differentiate between noninvasive and invasive tumors.
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http://dx.doi.org/10.1117/1.JMI.5.1.017001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808355PMC
January 2018

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

World J Urol 2018 Apr 2;36(4):549-555. Epub 2018 Feb 2.

Department of Urology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1007/s00345-018-2202-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871638PMC
April 2018

Can we predict necrosis intra-operatively? Real-time optical quantitative perfusion imaging in surgery: study protocol for a prospective, observational, in vivo pilot study.

Pilot Feasibility Stud 2017 25;3:65. Epub 2017 Nov 25.

Academic Medical Center, University of Amsterdam, Dep. of Gastrointestinal Surgery, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

Background: Compromised perfusion as a result of surgical intervention causes a reduction of oxygen and nutrients in tissue and therefore decreased tissue vitality. Quantitative imaging of tissue perfusion during reconstructive surgery, therefore, may reduce the incidence of complications. Non-invasive optical techniques allow real-time tissue imaging, with high resolution and high contrast. The objectives of this study are, first, to assess the feasibility and accuracy of optical coherence tomography (OCT), sidestream darkfield microscopy (SDF), laser speckle contrast imaging (LSCI), and fluorescence imaging (FI) for quantitative perfusion imaging and, second, to identify/search for criteria that enable risk prediction of necrosis during gastric tube and free flap reconstruction.

Methods: This prospective, multicenter, observational in vivo pilot study will assess tissue perfusion using four optical technologies: OCT, SDF, LSCI, and FI in 40 patients: 20 patients who will undergo gastric tube reconstruction after esophagectomy and 20 patients who will undergo free flap surgery. Intra-operative images of gastric perfusion will be obtained directly after reconstruction at four perfusion areas. Feasibility of perfusion imaging will be analyzed per technique. Quantitative parameters directly related to perfusion will be scored per perfusion area, and differences between biologically good versus reduced perfusion will be tested statistically. Patient outcome will be correlated to images and perfusion parameters. Differences in perfusion parameters before and after a bolus of ephedrine will be tested for significance.

Discussion: This study will identify quantitative perfusion-related parameters for an objective assessment of tissue perfusion during surgery. This will likely allow early risk stratification of necrosis development, which will aid in achieving a reduction of complications in gastric tube reconstruction and free flap transplantation.

Trial Registration: Clinicaltrials.gov registration number NCT02902549. Dutch Central Committee on Research Involving Human Subjects registration number NL52377.018.15.
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http://dx.doi.org/10.1186/s40814-017-0204-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702143PMC
November 2017
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