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In 2015 we began a sub-challenge at the EndoVis workshop at MICCAI in Munich using endoscope images of exvivo tissue with automatically generated annotations from robot forward kinematics and instrument CAD models. However, the limited background variation and simple motion rendered the dataset uninformative in learning about which techniques would be suitable for segmentation in real surgery. In 2017, at the same workshop in Quebec we introduced the robotic instrument segmentation dataset with 10 teams participating in the challenge to perform binary, articulating parts and type segmentation of da Vinci instruments. This challenge included realistic instrument motion and more complex porcine tissue as background and was widely addressed with modfications on U-Nets and other popular CNN architectures [1].
In 2018 we added to the complexity by introducing a set of anatomical objects and medical devices to the segmented classes. To avoid over-complicating the challenge, we continued with porcine data which is dramatically simpler than human tissue due to the lack of fatty tissue occluding many organs.
Forschung 2019
(2019)
Objective: Artificial intelligence (AI) may reduce underdiagnosed or overlooked upper GI (UGI) neoplastic and preneoplastic conditions, due to subtle appearance and low disease prevalence. Only disease-specific AI performances have been reported, generating uncertainty on its clinical value.
Design: We searched PubMed, Embase and Scopus until July 2020, for studies on the diagnostic performance of AI in detection and characterisation of UGI lesions. Primary outcomes were pooled diagnostic accuracy, sensitivity and specificity of AI. Secondary outcomes were pooled positive (PPV) and negative (NPV) predictive values. We calculated pooled proportion rates (%), designed summary receiving operating characteristic curves with respective area under the curves (AUCs) and performed metaregression and sensitivity analysis.
Results: Overall, 19 studies on detection of oesophageal squamous cell neoplasia (ESCN) or Barrett's esophagus-related neoplasia (BERN) or gastric adenocarcinoma (GCA) were included with 218, 445, 453 patients and 7976, 2340, 13 562 images, respectively. AI-sensitivity/specificity/PPV/NPV/positive likelihood ratio/negative likelihood ratio for UGI neoplasia detection were 90% (CI 85% to 94%)/89% (CI 85% to 92%)/87% (CI 83% to 91%)/91% (CI 87% to 94%)/8.2 (CI 5.7 to 11.7)/0.111 (CI 0.071 to 0.175), respectively, with an overall AUC of 0.95 (CI 0.93 to 0.97). No difference in AI performance across ESCN, BERN and GCA was found, AUC being 0.94 (CI 0.52 to 0.99), 0.96 (CI 0.95 to 0.98), 0.93 (CI 0.83 to 0.99), respectively. Overall, study quality was low, with high risk of selection bias. No significant publication bias was found.
Conclusion: We found a high overall AI accuracy for the diagnosis of any neoplastic lesion of the UGI tract that was independent of the underlying condition. This may be expected to substantially reduce the miss rate of precancerous lesions and early cancer when implemented in clinical practice.
Signal transmission between different brain regions requires connecting fiber tracts, the structural basis of the human connectome. In contrast to animal brains, where a multitude of tract tracing methods can be used, magnetic resonance (MR)-based diffusion imaging is presently the only promising approach to study fiber tracts between specific human brain regions. However, this procedure has various inherent restrictions caused by its relatively low spatial resolution. Here, we introduce 3D-polarized light imaging (3D-PLI) to map the three-dimensional course of fiber tracts in the human brain with a resolution at a submillimeter scale based on a voxel size of 100 μm isotropic or less. 3D-PLI demonstrates nerve fibers by utilizing their intrinsic birefringence of myelin sheaths surrounding axons. This optical method enables the demonstration of 3D fiber orientations in serial microtome sections of entire human brains. Examples for the feasibility of this novel approach are given here. 3D-PLI enables the study of brain regions of intense fiber crossing in unprecedented detail, and provides an independent evaluation of fiber tracts derived from diffusion imaging data.
Although it has long been presumed that d-amino acids are uncommon in mammalians, substantial amounts of free d-serine have been detected in the mammalian brain. d-Serine has been demonstrated to be an important modulator of glutamatergic neurotransmission and acts as an agonist at the strychnine-insensitive glycine site of N-methyl-d-aspartate receptors. The blood-to-brain transfer of d-serine is thought to be extremely low, and it is assumed that d-serine is generated by isomerization of l-serine in the brain. Stimulated by the observation of a preferred transport of the d-isomer of proline at the blood–brain barrier, we investigated the differential uptake of [3H]-d-serine and [3H]-l-serine in the rat brain 1 h after intravenous injection using quantitative autoradiography. Surprisingly, brain uptake of [3H]-d-serine was significantly higher than that of [3H]-l-serine, indicating a preferred transport of the d-enantiomer of serine at the blood–brain barrier. This finding indicates that exogenous d-serine may have a direct influence on glutamatergic neurotransmission and associated diseases.
Objectives: C-11-methionine (MET) is particularly useful in brain tumor diagnosis but unspecific uptake e.g. in cerebral ischemia has been reported (1). The F-18-labeled amino acid O-(2-[F-18]fluoroethyl)-L-tyrosine (FET) shows a similar clinical potential as MET in brain tumor diagnosis but is applicable on a wider clinical scale. The aim of this study was to evaluate the uptake of FET and H-3-MET in focal cortical ischemia in rats by dual tracer autoradiography.
Methods: Focal cortical ischemia was induced in 12 Fisher CDF rats using the photothrombosis model (PT). One day (n=3) , two days (n=5) and 7 days (n=4) after induction of the lesion FET and H-3-MET were injected intravenously. One hour after tracer injection animals were killed, the brains were removed immediately and frozen in 2-methylbutane at -50°C. Brains were cut in coronal sections (thickness: 20 µm) and exposed first to H-3 insensitive photoimager plates to measure FET distribution. After decay of F-18 the distribution of H-3-MET was determined. The autoradiograms were evaluated by regions of interest (ROIs) placed on areas with increased tracer uptake in the PT and the contralateral brain. Lesion to brain ratios (L/B) were calculated by dividing the mean uptake in the lesion and the brain. Based on previous studies in gliomas a L/B ratio > 1.6 was considered as pathological for FET.
Results: Variable increased uptake of both tracers was observed in the PT and its demarcation zone at all stages after PT. The cut-off level of 1.6 for FET was exceeded in 9/12 animals. One day after PT the L/B ratios were 2.0 ± 0.6 for FET vs. 2.1 ± 1.0 for MET (mean ± SD); two days after lesion 2.2 ± 0.7 for FET vs. 2.7 ± 1.0 for MET and 7 days after lesion 2.4 ± 0.4 for FET vs. 2.4 ± 0.1 for MET. In single cases discrepancies in the uptake pattern of FET and MET were observed.
Conclusions: FET like MET may exhibit significant uptake in infarcted areas or the immediate vincinity which has to be considered in the differential diagnosis of unkown brain lesions. The discrepancies in the uptake pattern of FET and MET in some cases indicates either differences in the transport mechanisms of both amino acids or a different affinity for certain cellular components.
Mass spectrometric imaging (MSI) is a young innovative analytical technique and combines different fields of advanced mass spectrometry and biomedical research with the aim to provide maps of elements and molecules, complexes or fragments. Especially essential metals such as zinc, copper, iron and manganese play a functional role in signaling, metabolism and homeostasis of the cell. Due to the high degree of spatial organization of metals in biological systems their distribution analysis is of key interest in life sciences. We have developed analytical techniques termed BrainMet using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging to measure the distribution of trace metals in biological tissues for biomedical research and feasibility studies—including bioaccumulation and bioavailability studies, ecological risk assessment and toxicity studies in humans and other organisms. The analytical BrainMet techniques provide quantitative images of metal distributions in brain tissue slices which can be combined with other imaging modalities such as photomicrography of native or processed tissue (histochemistry, immunostaining) and autoradiography or with in vivo techniques such as positron emission tomography or magnetic resonance tomography.
Prospective and instrumental developments will be discussed concerning the development of the metalloprotein microscopy using a laser microdissection (LMD) apparatus for specific sample introduction into an inductively coupled plasma mass spectrometer (LMD-ICP-MS) or an application of the near field effect in LA-ICP-MS (NF-LA-ICP-MS). These nano-scale mass spectrometric techniques provide improved spatial resolution down to the single cell level.
Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed and established as an emerging technique in the generation of quantitative images of metal distributions in thin tissue sections of brain samples (such as human, rat and mouse brain), with applications in research related to neurodegenerative disorders. A new analytical protocol is described which includes sample preparation by cryo-cutting of thin tissue sections and matrix-matched laboratory standards, mass spectrometric measurements, data acquisition, and quantitative analysis. Specific examples of the bioimaging of metal distributions in normal rodent brains are provided. Differences to the normal were assessed in a Parkinson’s disease and a stroke brain model. Furthermore, changes during normal aging were studied. Powerful analytical techniques are also required for the determination and characterization of metal-containing proteins within a large pool of proteins, e.g., after denaturing or non-denaturing electrophoretic separation of proteins in one-dimensional and two-dimensional gels. LA-ICP-MS can be employed to detect metalloproteins in protein bands or spots separated after gel electrophoresis. MALDI-MS can then be used to identify specific metal-containing proteins in these bands or spots. The combination of these techniques is described in the second section.
Bioimaging of Metals by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS)
(2010)
The distribution analysis of (essential, beneficial, or toxic) metals (e.g., Cu, Fe, Zn, Pb, and others), metalloids, and non‐metals in biological tissues is of key interest in life science. Over the past few years, the development and application of several imaging mass spectrometric techniques has been rapidly growing in biology and medicine. Especially, in brain research metalloproteins are in the focus of targeted therapy approaches of neurodegenerative diseases such as Alzheimer's and Parkinson's disease, or stroke, or tumor growth. Laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) using double‐focusing sector field (LA‐ICP‐SFMS) or quadrupole‐based mass spectrometers (LA‐ICP‐QMS) has been successfully applied as a powerful imaging (mapping) technique to produce quantitative images of detailed regionally specific element distributions in thin tissue sections of human or rodent brain. Imaging LA‐ICP‐QMS was also applied to investigate metal distributions in plant and animal sections to study, for example, the uptake and transport of nutrient and toxic elements or environmental contamination. The combination of imaging LA‐ICP‐MS of metals with proteomic studies using biomolecular mass spectrometry identifies metal‐containing proteins and also phosphoproteins. Metal‐containing proteins were imaged in a two‐dimensional gel after electrophoretic separation of proteins (SDS or Blue Native PAGE). Recent progress in LA‐ICP‐MS imaging as a stand‐alone technique and in combination with MALDI/ESI‐MS for selected life science applications is summarized.
Purpose
MR-based attenuation correction (AC) will become an integral part of combined PET/MR systems. Here, we propose a toolbox to validate MR-AC of clinical PET/MRI data sets.
Methods
Torso scans of ten patients were acquired on a combined PET/CT and on a 1.5-T MRI system. MR-based attenuation data were derived from the CT following MR–CT image co-registration and subsequent histogram matching. PET images were reconstructed after CT- (PET/CT) and MR-based AC (PET/MRI). Lesion-to-background (L/B) ratios were estimated on PET/CT and PET/MRI.
Results
MR–CT histogram matching leads to a mean voxel intensity difference in the CT- and MR-based attenuation images of 12% (max). Mean differences between PET/MRI and PET/CT were 19% (max). L/B ratios were similar except for the lung where local misregistration and intensity transformation leads to a biased PET/MRI.
Conclusion
Our toolbox can be used to study pitfalls in MR-AC. We found that co-registration accuracy and pixel value transformation determine the accuracy of PET/MRI.
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.
Chest X-Ray (CXR) images as part of a non-invasive diagnosis method are commonly used in today’s medical workflow. In traditional methods, physicians usually use their experience to interpret CXR images, however, there is a large interobserver variance. Computer vision may be used as a standard for assisted diagnosis. In this study, we applied an encoder-decoder neural network architecture for automatic lung region detection. We compared a three-class approach (left lung, right lung, background) and a two-class approach (lung, background). The differentiation of left and right lungs as direct result of a semantic segmentation on basis of neural nets rather than post-processing a lung-background segmentation is done here for the first time. Our evaluation was done on the NIH Chest X-ray dataset, from which 1736 images were extracted and manually annotated. We achieved 94:9% mIoU and 92% mIoU as segmentation quality measures for the two-class-model and the three-class-model, respectively. This result is very promising for the segmentation of lung regions having the simultaneous classification of left and right lung in mind.
Polarized light imaging (PLI) enables the evaluation of fiber orientations in histological sections of human postmortem brains, with ultra-high spatial resolution. PLI is based on the birefringent properties of the myelin sheath of nerve fibers. As a result, the polarization state of light propagating through a rotating polarimeter is changed in such a way that the detected signal at each measurement unit of a charged-coupled device (CCD) camera describes a sinusoidal signal. Vectors of the fiber orientation defined by inclination and direction angles can then directly be derived from the optical signals employing PLI analysis. However, noise, light scatter and filter inhomogeneities interfere with the original sinusoidal PLI signals. We here introduce a novel method using independent component analysis (ICA) to decompose the PLI images into statistically independent component maps. After decomposition, gray and white matter structures can clearly be distinguished from noise and other artifacts. The signal enhancement after artifact rejection is quantitatively evaluated in 134 histological whole brain sections. Thus, the primary sinusoidal signals from polarized light imaging can be effectively restored after noise and artifact rejection utilizing ICA. Our method therefore contributes to the analysis of nerve fiber orientation in the human brain within a micrometer scale.
Computer-assisted analysis of endoscopic images can be helpful to the automatic diagnosis and classification of neoplastic lesions. Barrett's esophagus (BE) is a common type of reflux that is not straight forward to be detected by endoscopic surveillance, thus being way susceptible to erroneous diagnosis, which can cause cancer when not treated properly. In this work, we introduce the Optimum-Path Forest (OPF) classifier to the task of automatic identification of Barrett'sesophagus, with promising results and outperforming the well known Support Vector Machines (SVM) in the aforementioned context. We consider describing endoscopic images by means of feature extractors based on key point information, such as the Speeded up Robust Features (SURF) and Scale-Invariant Feature Transform (SIFT), for further designing a bag-of-visual-wordsthat is used to feed both OPF and SVM classifiers. The best results were obtained by means of the OPF classifier for both feature extractors, with values lying on 0.732 (SURF) - 0.735(SIFT) for sensitivity, 0.782 (SURF) - 0.806 (SIFT) for specificity, and 0.738 (SURF) - 0.732 (SIFT) for the accuracy.
In this work, we propose the use of single channel Color Co-occurrence Matrices for texture description of Barrett’sEsophagus (BE)and adenocarcinoma images. Further classification using supervised learning techniques, such as Optimum-Path Forest (OPF), Support Vector Machines with Radial Basisunction (SVM-RBF) and Bayesian classifier supports the contextof automatic BE and adenocarcinoma diagnosis. We validated three approaches of classification based on patches, patients and images in two datasets (MICCAI 2015 and Augsburg) using the color-and-texture descriptors and the machine learning techniques. Concerning MICCAI 2015 dataset, the best results were obtained using the blue channel for the descriptors and the supervised OPF for classification purposes in the patch-based approach, with sensitivity nearly to 73% for positive adenocarcinoma identification and specificity close to 77% for BE (non-cancerous) patch classification. Regarding the Augsburg dataset, the most accurate results were also obtained using both OPF classifier and blue channel descriptor for the feature extraction, with sensitivity close to 67% and specificity around to76%. Our work highlights new advances in the related research area and provides a promising technique that combines color and texture information, allied to three different approaches of dataset pre-processing aiming to configure robust scenarios for the classification step.
The development of adenocarcinoma in Barrett’s esophagus is difficult to detect by endoscopic surveillance of patients with signs of dysplasia. Computer assisted diagnosis of endoscopic images (CAD) could therefore be most helpful in the demarcation and classification of neoplastic lesions. In this study we tested the feasibility of a CAD method based on Speeded up Robust Feature Detection (SURF). A given database containing 100 images from 39 patients served as benchmark for feature based classification models. Half of the images had previously been diagnosed by five clinical experts as being ”cancerous”, the other half as ”non-cancerous”. Cancerous image regions had been visibly delineated (masked) by the clinicians. SURF features acquired from full images as well as from masked areas were utilized for the supervised training and testing of an SVM classifier. The predictive accuracy of the developed CAD system is illustrated by sensitivity and specificity values. The results based on full image matching where 0.78 (sensitivity) and 0.82 (specificity) were achieved, while the masked region approach generated results of 0.90 and 0.95, respectively.
Even though artificial intelligence and machine learning have demonstrated remarkable performances in medical image computing, their level of accountability and transparency must be provided in such evaluations. The reliability related to machine learning predictions must be explained and interpreted, especially if diagnosis support is addressed. For this task, the black-box nature of deep learning techniques must be lightened up to transfer its promising results into clinical practice. Hence, we aim to investigate the use of explainable artificial intelligence techniques to quantitatively highlight discriminative regions during the classification of earlycancerous tissues in Barrett’s esophagus-diagnosed patients. Four Convolutional Neural Network models (AlexNet, SqueezeNet, ResNet50, and VGG16) were analyzed using five different interpretation techniques (saliency, guided backpropagation, integrated gradients, input × gradients, and DeepLIFT) to compare their agreement with experts’ previous annotations of cancerous tissue. We could show that saliency attributes match best with the manual experts’ delineations. Moreover, there is moderate to high correlation between the sensitivity of a model and the human-and-computer agreement. The results also lightened that the higher the model’s sensitivity, the stronger the correlation of human and computational segmentation agreement. We observed a relevant relation between computational learning and experts’ insights, demonstrating how human knowledge may influence the correct computational learning.
This work presents a systematic review concerning recent studies and technologies of machine learning for Barrett's esophagus (BE) diagnosis and treatment. The use of artificial intelligence is a brand new and promising way to evaluate such disease. We compile some works published at some well-established databases, such as Science Direct, IEEEXplore, PubMed, Plos One, Multidisciplinary Digital Publishing Institute (MDPI), Association for Computing Machinery (ACM), Springer, and Hindawi Publishing Corporation. Each selected work has been analyzed to present its objective, methodology, and results. The BE progression to dysplasia or adenocarcinoma shows a complex pattern to be detected during endoscopic surveillance. Therefore, it is valuable to assist its diagnosis and automatic identification using computer analysis. The evaluation of the BE dysplasia can be performed through manual or automated segmentation through machine learning techniques. Finally, in this survey, we reviewed recent studies focused on the automatic detection of the neoplastic region for classification purposes using machine learning methods.