Lipid availability determines fate of skeletal progenitor cells via SOX9.

The avascular nature of cartilage makes it a unique tissue1-4, but whether and how the absence of nutrient supply regulates chondrogenesis remain unknown. Here we show that obstruction of vascular invasion during bone healing favours chondrogenic over osteogenic differentiation of skeletal progenitor cells. Unexpectedly, this process is driven by a decreased availability of extracellular lipids. When lipids are scarce, skeletal progenitors activate forkhead box O (FOXO) transcription factors, which bind to the Sox9 promoter and increase its expression. Besides initiating chondrogenesis, SOX9 acts as a regulator of cellular metabolism by suppressing oxidation of fatty acids, and thus adapts the cells to an avascular life. Our results define lipid scarcity as an important determinant of chondrogenic commitment, reveal a role for FOXO transcription factors during lipid starvation, and identify SOX9 as a critical metabolic mediator. These data highlight the importance of the nutritional microenvironment in the specification of skeletal cell fate.

Clinical consequences of computer-aided colorectal polyp detection.

BACKGROUND AND AIM: Randomised trials show improved polyp detection with computer-aided detection (CADe), mostly of small lesions. However, operator and selection bias may affect CADe's true benefit. Clinical outcomes of increased detection have not yet been fully elucidated. METHODS: In this multicentre trial, CADe combining convolutional and recurrent neural networks was used for polyp detection. Blinded endoscopists were monitored in real time by a second observer with CADe access. CADe detections prompted reinspection. Adenoma detection rates (ADR) and polyp detection rates were measured prestudy and poststudy. Histological assessments were done by independent histopathologists. The primary outcome compared polyp detection between endoscopists and CADe. RESULTS: In 946 patients (51.9% male, mean age 64), a total of 2141 polyps were identified, including 989 adenomas. CADe was not superior to human polyp detection (sensitivity 94.6% vs 96.0%) but outperformed them when restricted to adenomas. Unblinding led to an additional yield of 86 true positive polyp detections (1.1% ADR increase per patient; 73.8% were <5 mm). CADe also increased non-neoplastic polyp detection by an absolute value of 4.9% of the cases (1.8% increase of entire polyp load). Procedure time increased with 6.6±6.5 min (+42.6%). In 22/946 patients, the additional detection of adenomas changed surveillance intervals (2.3%), mostly by increasing the number of small adenomas beyond the cut-off. CONCLUSION: Even if CADe appears to be slightly more sensitive than human endoscopists, the additional gain in ADR was minimal and follow-up intervals rarely changed. Additional inspection of non-neoplastic lesions was increased, adding to the inspection and/or polypectomy workload.

Lessons for future clinical trials in adults with Becker muscular dystrophy: Disease progression detected by muscle magnetic resonance imaging, clinical and patient-reported outcome measures.

BACKGROUND AND PURPOSE: Because Becker muscular dystrophy (BMD) is a heterogeneous disease and only few studies have evaluated adult patients, it is currently still unclear which outcome measures should be used in future clinical trials. METHODS: Muscle magnetic resonance imaging, patient-reported outcome measures and a wide range of clinical outcome measures, including motor function, muscle strength and timed-function tests, were evaluated in 21 adults with BMD at baseline and at 9 and 18 months of follow-up. RESULTS: Proton density fat fraction increased significantly in 10/17 thigh muscles after 9 months, and in all thigh and lower leg muscles after 18 months. The 32-item Motor Function Measurement (MFM-32) scale (-1.3%, p = 0.017), North Star Ambulatory Assessment (-1.3 points, p = 0.010) and patient-reported activity limitations scale (-0.3 logits, p = 0.018) deteriorated significantly after 9 months. The 6-min walk distance (-28.7 m, p = 0.042), 10-m walking test (-0.1 m/s, p = 0.032), time to climb four stairs test (-0.03 m/s, p = 0.028) and Biodex peak torque measurements of quadriceps (-4.6 N m, p = 0.014) and hamstrings (-5.0 N m, p = 0.019) additionally deteriorated significantly after 18 months. At this timepoint, domain 1 of the MFM-32 was the only clinical outcome measure with a large sensitivity to change (standardized response mean 1.15). DISCUSSION: It is concluded that proton density fat fraction imaging of entire thigh muscles is a sensitive outcome measure to track progressive muscle fat replacement in patients with BMD, already after 9 months of follow-up. Finally, significant changes are reported in a wide range of clinical and patient-reported outcome measures, of which the MFM-32 appeared to be the most sensitive to change in adults with BMD.

Deep learning pipeline for quality filtering of MRSI spectra.

With the rise of novel 3D magnetic resonance spectroscopy imaging (MRSI) acquisition protocols in clinical practice, which are capable of capturing a large number of spectra from a subject's brain, there is a need for an automated preprocessing pipeline that filters out bad-quality spectra and identifies contaminated but salvageable spectra prior to the metabolite quantification step. This work introduces such a pipeline based on an ensemble of deep-learning classifiers. The dataset consists of 36,338 spectra from one healthy subject and five brain tumor patients, acquired with an EPSI variant, which implemented a novel type of spectral editing named SLOtboom-Weng (SLOW) editing on a 7T MR scanner. The spectra were labeled manually by an expert into four classes of spectral quality as follows: (i) noise, (ii) spectra greatly influenced by lipid-related artifacts (deemed not to contain clinical information), (iii) spectra containing metabolic information slightly contaminated by lipid signals, and (iv) good-quality spectra. The AI model consists of three pairs of networks, each comprising a convolutional autoencoder and a multilayer perceptron network. In the classification step, the encoding half of the autoencoder is kept as a dimensionality reduction tool, while the fully connected layers are added to its output. Each of the three pairs of networks is trained on different representations of spectra (real, imaginary, or both), aiming at robust decision-making. The final class is assigned via a majority voting scheme. The F1 scores obtained on the test dataset for the four previously defined classes are 0.96, 0.93, 0.82, and 0.90, respectively. The arguably lower value of 0.82 was reached for the least represented class of spectra mildly influenced by lipids. Not only does the proposed model minimise the required user interaction, but it also greatly reduces the computation time at the metabolite quantification step (by selecting a subset of spectra worth quantifying) and enforces the display of only clinically relevant information.

Optimal 68Ga-PSMA and 18F-PSMA PET window levelling for gross tumour volume delineation in primary prostate cancer.

PURPOSE: This study proposes optimal tracer-specific threshold-based window levels for PSMA PET-based intraprostatic gross tumour volume (GTV) contouring to reduce interobserver delineation variability. METHODS: Nine 68Ga-PSMA-11 and nine 18F-PSMA-1007 PET scans including GTV delineations of four expert teams (GTVmanual) and a majority-voted GTV (GTVmajority) were assessed with respect to a registered histopathological GTV (GTVhisto) as the gold standard reference. The standard uptake values (SUVs) per voxel were converted to a percentage (SUV%) relative to the SUVmax. The statistically optimised SUV% threshold (SOST) was defined as those that maximises accuracy for threshold-based contouring. A leave-one-out cross-validation receiver operating characteristic (ROC) curve analysis was performed to determine the SOST for each tracer. The SOST analysis was performed twice, first using the GTVhisto contour as training structure (GTVSOST-H) and second using the GTVmajority contour as training structure (GTVSOST-MA) to correct for any limited misregistration. The accuracy of both GTVSOST-H and GTVSOST-MA was calculated relative to GTVhisto in the 'leave-one-out' patient of each fold and compared with the accuracy of GTVmanual. RESULTS: ROC curve analysis for 68Ga-PSMA-11 PET revealed a median threshold of 25 SUV% (range, 22-27 SUV%) and 41 SUV% (40-43 SUV%) for GTVSOST-H and GTVSOST-MA, respectively. For 18F-PSMA-1007 PET, a median threshold of 42 SUV% (39-45 SUV%) for GTVSOST-H and 44 SUV% (42-45 SUV%) for GTVSOST-MA was found. A significant pairwise difference was observed when comparing the accuracy of the GTVSOST-H contours with the median accuracy of the GTVmanual contours (median, - 2.5%; IQR, - 26.5-0.2%; p = 0.020), whereas no significant pairwise difference was found for the GTVSOST-MA contours (median, - 0.3%; IQR, - 4.4-0.6%; p = 0.199). CONCLUSIONS: Threshold-based contouring using GTVmajority-trained SOSTs achieves an accuracy comparable with manual contours in delineating GTVhisto. The median SOSTs of 41 SUV% for 68Ga-PSMA-11 PET and 44 SUV% for 18F-PSMA-1007 PET form a base for tracer-specific window levelling. TRIAL REGISTRATION: Clinicaltrials.gov ; NCT03327675; 31-10-2017.

Artificial intelligence and its impact on quality improvement in upper and lower gastrointestinal endoscopy.

Artificial intelligence (AI) and its application in medicine has grown large interest. Within gastrointestinal (GI) endoscopy, the field of colonoscopy and polyp detection is the most investigated, however, upper GI follows the lead. Since endoscopy is performed by humans, it is inherently an imperfect procedure. Computer-aided diagnosis may improve its quality by helping prevent missing lesions and supporting optical diagnosis for those detected. An entire evolution in AI systems has been established in the last decades, resulting in optimization of the diagnostic performance with lower variability and matching or even outperformance of expert endoscopists. This shows a great potential for future quality improvement of endoscopy, given the outstanding diagnostic features of AI. With this narrative review, we highlight the potential benefit of AI to improve overall quality in daily endoscopy and describe the most recent developments for characterization and diagnosis as well as the recent conditions for regulatory approval.

3D Tendon Strain Estimation Using High-frequency Volumetric Ultrasound Images: A Feasibility Study.

Estimation of strain in tendons for tendinopathy assessment is a hot topic within the sports medicine community. It is believed that, if accurately estimated, existing treatment and rehabilitation protocols can be improved and presymptomatic abnormalities can be detected earlier. State-of-the-art studies present inaccurate and highly variable strain estimates, leaving this problem without solution. Out-of-plane motion, present when acquiring two-dimensional (2D) ultrasound (US) images, is a known problem and may be responsible for such errors. This work investigates the benefit of high-frequency, three-dimensional (3D) US imaging to reduce errors in tendon strain estimation. Volumetric US images were acquired in silico, in vitro, and ex vivo using an innovative acquisition approach that combines the acquisition of 2D high-frequency US images with a mechanical guided system. An affine image registration method was used to estimate global strain. 3D strain estimates were then compared with ground-truth values and with 2D strain estimates. The obtained results for in silico data showed a mean absolute error (MAE) of 0.07%, 0.05%, and 0.27% for 3D estimates along axial, lateral direction, and elevation direction and a respective MAE of 0.21% and 0.29% for 2D strain estimates. Although 3D could outperform 2D, this does not occur in in vitro and ex vivo settings, likely due to 3D acquisition artifacts. Comparison against the state-of-the-art methods showed competitive results. The proposed work shows that 3D strain estimates are more accurate than 2D estimates but acquisition of appropriate 3D US images remains a challenge.

Convexity-constrained and nonnegativity-constrained spherical factorization in diffusion-weighted imaging.

Diffusion-weighted imaging (DWI) facilitates probing neural tissue structure non-invasively by measuring its hindrance to water diffusion. Analysis of DWI is typically based on generative signal models for given tissue geometry and microstructural properties. In this work, we generalize multi-tissue spherical deconvolution to a blind source separation problem under convexity and nonnegativity constraints. This spherical factorization approach decomposes multi-shell DWI data, represented in the basis of spherical harmonics, into tissue-specific orientation distribution functions and corresponding response functions, without assuming the latter as known thus fully unsupervised. In healthy human brain data, the resulting components are associated with white matter fibres, grey matter, and cerebrospinal fluid. The factorization results are on par with state-of-the-art supervised methods, as demonstrated also in Monte-Carlo simulations evaluating accuracy and precision of the estimated response functions and orientation distribution functions of each component. In animal data and in the presence of oedema, the proposed factorization is able to recover unseen tissue structure, solely relying on DWI. As such, our method broadens the applicability of spherical deconvolution techniques to exploratory analysis of tissue structure in data where priors are uncertain or hard to define.

Semi-automated brain tumor segmentation on multi-parametric MRI using regularized non-negative matrix factorization.

BACKGROUND: Segmentation of gliomas in multi-parametric (MP-)MR images is challenging due to their heterogeneous nature in terms of size, appearance and location. Manual tumor segmentation is a time-consuming task and clinical practice would benefit from (semi-) automated segmentation of the different tumor compartments. METHODS: We present a semi-automated framework for brain tumor segmentation based on non-negative matrix factorization (NMF) that does not require prior training of the method. L1-regularization is incorporated into the NMF objective function to promote spatial consistency and sparseness of the tissue abundance maps. The pathological sources are initialized through user-defined voxel selection. Knowledge about the spatial location of the selected voxels is combined with tissue adjacency constraints in a post-processing step to enhance segmentation quality. The method is applied to an MP-MRI dataset of 21 high-grade glioma patients, including conventional, perfusion-weighted and diffusion-weighted MRI. To assess the effect of using MP-MRI data and the L1-regularization term, analyses are also run using only conventional MRI and without L1-regularization. Robustness against user input variability is verified by considering the statistical distribution of the segmentation results when repeatedly analyzing each patient's dataset with a different set of random seeding points. RESULTS: Using L1-regularized semi-automated NMF segmentation, mean Dice-scores of 65%, 74 and 80% are found for active tumor, the tumor core and the whole tumor region. Mean Hausdorff distances of 6.1 mm, 7.4 mm and 8.2 mm are found for active tumor, the tumor core and the whole tumor region. Lower Dice-scores and higher Hausdorff distances are found without L1-regularization and when only considering conventional MRI data. CONCLUSIONS: Based on the mean Dice-scores and Hausdorff distances, segmentation results are competitive with state-of-the-art in literature. Robust results were found for most patients, although careful voxel selection is mandatory to avoid sub-optimal segmentation.

Global tractography of multi-shell diffusion-weighted imaging data using a multi-tissue model.

Diffusion-weighted imaging and tractography provide a unique, non-invasive technique to study the macroscopic structure and connectivity of brain white matter in vivo. Global tractography methods aim at reconstructing the full-brain fiber configuration that best explains the measured data, based on a generative signal model. In this work, we incorporate a multi-shell multi-tissue model based on spherical convolution, into a global tractography framework, which allows to deal with partial volume effects. The required tissue response functions can be estimated from and hence calibrated to the data. The resulting track reconstruction is quantitatively related to the apparent fiber density in the data. In addition, the fiber orientation distribution for white matter and the volume fractions of gray matter and cerebrospinal fluid are produced as ancillary results. Validation results on simulated data demonstrate that this data-driven approach improves over state-of-the-art streamline and global tracking methods, particularly in the valid connection rate. Results in human brain data correspond to known white matter anatomy and show improved modeling of partial voluming. This work is an important step toward detecting and quantifying white matter changes and connectivity in healthy subjects and patients.

Hierarchical non-negative matrix factorization to characterize brain tumor heterogeneity using multi-parametric MRI.

Tissue characterization in brain tumors and, in particular, in high-grade gliomas is challenging as a result of the co-existence of several intra-tumoral tissue types within the same region and the high spatial heterogeneity. This study presents a method for the detection of the relevant tumor substructures (i.e. viable tumor, necrosis and edema), which could be of added value for the diagnosis, treatment planning and follow-up of individual patients. Twenty-four patients with glioma [10 low-grade gliomas (LGGs), 14 high-grade gliomas (HGGs)] underwent a multi-parametric MRI (MP-MRI) scheme, including conventional MRI (cMRI), perfusion-weighted imaging (PWI), diffusion kurtosis imaging (DKI) and short-TE (1)H MRSI. MP-MRI parameters were derived: T2, T1 + contrast, fluid-attenuated inversion recovery (FLAIR), relative cerebral blood volume (rCBV), mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK) and the principal metabolites lipids (Lip), lactate (Lac), N-acetyl-aspartate (NAA), total choline (Cho), etc. Hierarchical non-negative matrix factorization (hNMF) was applied to the MP-MRI parameters, providing tissue characterization on a patient-by-patient and voxel-by-voxel basis. Tissue-specific patterns were obtained and the spatial distribution of each tissue type was visualized by means of abundance maps. Dice scores were calculated by comparing tissue segmentation derived from hNMF with the manual segmentation by a radiologist. Correlation coefficients were calculated between each pathologic tissue source and the average feature vector within the corresponding tissue region. For the patients with HGG, mean Dice scores of 78%, 85% and 83% were obtained for viable tumor, the tumor core and the complete tumor region. The mean correlation coefficients were 0.91 for tumor, 0.97 for necrosis and 0.96 for edema. For the patients with LGG, a mean Dice score of 85% and mean correlation coefficient of 0.95 were found for the tumor region. hNMF was also applied to reduced MRI datasets, showing the added value of individual MRI modalities.

Left ventricular four-dimensional rotational angiography with low radiation dose through interphase registration.

AIMS: Ventricular tachycardia ablations could benefit from four-dimensional (4D) (dynamic 3D) visualization of the left ventricle (LV) as roadmap for anatomy-guided procedures. Our aim was to develop an algorithm that combines information of several cardiac phases to improve signal-to-noise ratio in low-dose, noisy rotational angiography [three-dimensional rotational angiography (3DRA)] image datasets, enabling semi-automatic segmentation and generation of 4D rotational angiography (4DRA) LV surface models. METHODS AND RESULTS: We developed a novel slow pacing protocol for low-dose 4DRA imaging and applied interphase registration (IPR) to improve contrast-to-noise ratio (CNR) such that 4D LV segmentation could be achieved using a single iso-intensity value (ISO). The method was applied to construct four-phase dynamic LV models from five porcine experiments. Optimal choice of IPR and ISO parameters and resulting LV model accuracy were assessed by comparison with 'groundtruth' manual LV delineations using surface distance measures [root mean square distance (RMSD), Hausdorff distance (HD), fraction of surface distances ≤3 mm (d3 mm)]. Using IPR with optimized parameters, CNR improved by 88% (P < 0.0001) and increased segmentation accuracy was proven irrespective of ISO. Significant improvement was achieved in RMSD [mean at optimal ISO: -28.3% (95% confidence interval (CI) -21.7 to -35.0, P < 0.0001)], HD [-21.4% (95% CI -18.6 to -24.1, P < 0.0001)], and d3 mm [+7.8% (95% CI +4.6 to +10.9, P < 0.0001)]. An average d3 mm of 95.6 ± 2.8% was reached at optimal ISO. Time to generate a 4D model was ±11.5 min with IPR vs. ±22 min without. CONCLUSION: Interphase registration significantly improves 4DRA image quality and facilitates semi-automatic segmentation, resulting in clinically useful accuracy despite low-dose image acquisition protocols, while shortening 4D model generation time. This opens the prospect of 4D imaging in clinical settings.

Track orientation density imaging (TODI) and track orientation distribution (TOD) based tractography.

Ever since the introduction of the concept of fiber tractography, methods to generate better and more plausible tractograms have become available. Many modern methods can handle complex fiber architecture and take on a probabilistic approach to account for different sources of uncertainty. The resulting tractogram from any such method typically represents a finite random sample from a complex distribution of possible tracks. Generating a higher amount of tracks allows for a more accurate depiction of the underlying distribution. The recently proposed method of track-density imaging (TDI) allows to capture the spatial distribution of a tractogram. In this work, we propose an extension of TDI towards the 5D spatio-angular domain, which we name track orientation density imaging (TODI). The proposed method aims to capture the full track orientation distribution (TOD). Just as the TDI map, the TOD is amenable to spatial super-resolution (or even sub-resolution), but in addition also to angular super-resolution. Through experiments on in vivo human subject data, an in silico numerical phantom and a challenging tractography phantom, we found that the TOD presents an increased amount of regional spatio-angular consistency, as compared to the fiber orientation distribution (FOD) from constrained spherical deconvolution (CSD). Furthermore, we explain how the amplitude of the TOD of a short-tracks distribution (i.e. where the track length is limited) can be interpreted as a measure of track-like local support (TLS). This in turn motivated us to explore the idea of TOD-based fiber tractography. In such a setting, the short-tracks TOD is able to guide a track along directions that are more likely to correspond to continuous structure over a longer distance. This powerful concept is shown to greatly robustify targeted as well as whole-brain tractography. We conclude that the TOD is a versatile tool that can be cast in many different roles and scenarios in the expanding domain of fiber tractography based methods and their applications.

Multimodal imaging of subventricular zone neural stem/progenitor cells in the cuprizone mouse model reveals increased neurogenic potential for the olfactory bulb pathway, but no contribution to remyelination of the corpus callosum.

Multiple sclerosis is a devastating demyelinating disease of the central nervous system (CNS) in which endogenous remyelination, and thus recovery, often fails. Although the cuprizone mouse model allowed elucidation of many molecular factors governing remyelination, currently very little is known about the spatial origin of the oligodendrocyte progenitor cells that initiate remyelination in this model. Therefore, we here investigated in this model whether subventricular zone (SVZ) neural stem/progenitor cells (NSPCs) contribute to remyelination of the splenium following cuprizone-induced demyelination. Experimentally, from the day of in situ NSPC labeling, C57BL/6J mice were fed a 0.2% cuprizone diet during a 4-week period and then left to recover on a normal diet for 8weeks. Two in situ labeling strategies were employed: (i) NSPCs were labeled by intraventricular injection of micron-sized iron oxide particles and then followed up longitudinally by means of magnetic resonance imaging (MRI), and (ii) SVZ NSPCs were transduced with a lentiviral vector encoding the eGFP and Luciferase reporter proteins for longitudinal monitoring by means of in vivo bioluminescence imaging (BLI). In contrast to preceding suggestions, no migration of SVZ NSPC towards the demyelinated splenium was observed using both MRI and BLI, and further validated by histological analysis, thereby demonstrating that SVZ NSPCs are unable to contribute directly to remyelination of the splenium in the cuprizone model. Interestingly, using longitudinal BLI analysis and confirmed by histological analysis, an increased migration of SVZ NSPC-derived neuroblasts towards the olfactory bulb was observed following cuprizone treatment, indicative for a potential link between CNS inflammation and increased neurogenesis.

Test-retest reliability and follow-up of muscle magnetic resonance elastography in adults with and without muscle diseases.

BACKGROUND: We investigated the potential of magnetic resonance elastography (MRE) stiffness measurements in skeletal muscles as an outcome measure, by determining its test-retest reliability, as well as its sensitivity to change in a longitudinal follow-up study. METHODS: We assessed test-retest reliability of muscle MRE in 20 subjects with (n = 5) and without (n = 15) muscle diseases and compared this to Dixon proton density fat fraction (PDFF) and volume measurements. Next, we measured MRE muscle stiffness in 21 adults with Becker muscular dystrophy (BMD) and 21 age-matched healthy controls at baseline, and after 9 and 18 months. We compared two different methods of analysing MRE data in this study: 'Method A' used the stiffness maps generated by the Philips MRE software, and 'Method B' applied a custom-made procedure based on wavelength measurements on the MRE images. RESULTS: Intraclass correlation coefficients (ICC) of muscle stiffness ranged from good (0.83 for left vastus medialis, P < 0.001) to poor (0.19 for right rectus femoris, P = 0.212) for the examined thigh muscles with Method A, but we did not find a significant test-retest reliability with Method B (P > 0.050 for all). The ICC of muscle PDFF and volume measurements was excellent (>0.90; P < 0.001) for all muscles. At baseline, the average stiffness of all thigh muscles was significantly lower in adults with BMD than in controls for both Method A (-0.2 kPa, P = 0.025) and Method B (-0.6 kPa, P < 0.001). Regardless of which method was used, there was no significant difference in the evolution of muscle stiffness in patients and controls over 18 months. CONCLUSIONS: Test-retest reliability of muscle MRE using a simple 2D technique was suboptimal, and did not reliably measure muscle stiffness changes in adults with BMD as compared with controls over 18 months. While the results provide motivation for testing more advanced 3D MRE methods, we conclude that the simple 2D MRE implementation used in this study is not suitable as an outcome measure for characterizing thigh muscle in clinical trials.

Advanced Imaging in Gastrointestinal Endoscopy: A Literature Review of the Current State of the Art.

Background and Aims: Gastrointestinal (GI) endoscopy has known a great evolution in the last decades. Imaging techniques evolved from imaging with only standard white light endoscopes toward high-definition resolution endoscopes and the use of multiple color enhancement techniques, over to automated endoscopic assessment systems based on artificial intelligence. This narrative literature review aimed to provide a detailed overview on the latest evolutions within the field of advanced GI endoscopy, mainly focusing on the screening, diagnosis, and surveillance of common upper and lower GI pathology. Methods: This review comprises only literature about screening, diagnosis, and surveillance strategies using advanced endoscopic imaging techniques published in (inter)national peer-reviewed journals and written in English. Studies with only adult patients included were selected. A search was performed using MESH terms: dye-based chromoendoscopy, virtual chromoendoscopy, video enhancement technique, upper GI tract, lower GI tract, Barrett's esophagus, esophageal squamous cell carcinoma, gastric cancer, colorectal polyps, inflammatory bowel disease, artificial intelligence. This review does not elaborate on the therapeutic application or impact of advanced GI endoscopy. Conclusions: Focusing on current and future applications and evolutions in the field of both upper and lower GI advanced endoscopy, this overview is a practical but detailed projection of the latest developments. Within this review, an active leap toward artificial intelligence and its recent developments in GI endoscopy was made. Additionally, the literature is weighted against the current international guidelines and assessed for its potential positive future impact.

Introdução/objetivos: A endoscopia digestiva conheceu uma grande evolução nas últimas décadas, tendo as técnicas de imagem evoluído de imagens com luz branca para endoscópios de alta definição com possibilidade de uso de várias técnicas de melhoramento de cores e até sistemas automatizados apoiados em inteligência artificial. Esta revisão narrativa da literatura visa fornecer uma visão detalhada das últimas evoluções no campo da endoscopia avançada, focando principalmente no rastreio, diagnóstico e vigilância. Métodos: Pesquisa da literatura sobre estratégias de rastreio, diagnóstico e vigilância utilizando técnicas avançadas de imagem endoscópica publicadas em revistas internacionais revistas por pares e escritas em inglês. Foram selecionados estudos apenas com doentes adultos e foi realizada pesquisa utilizando termos MESH: cromoendoscopia com corante, cromoendoscopia virtual, técnicas de melhoramento de vídeo, tubo digestivo superior, tubo digestivo inferior, esófago de Barrett, carcinoma de células escamosas, cancro gástrico, pólipos colorretais, doença inflamatória intestinal e inteligência artificial. Conclusões: Esta revisão avaliou de uma forma prática os últimos desenvolvimentos no campo da imagem avançada em endoscopia digestiva, avaliando-se também as perspetivas futuras e o potencial impacto da inteligência artificial.

Benefits of automated gross tumor volume segmentation in head and neck cancer using multi-modality information.

PURPOSE: Gross tumor volume (GTV) delineation for head and neck cancer (HNC) radiation therapy planning is time consuming and prone to interobserver variability (IOV). The aim of this study was (1) to develop an automated GTV delineation approach of primary tumor (GTVp) and pathologic lymph nodes (GTVn) based on a 3D convolutional neural network (CNN) exploiting multi-modality imaging input as required in clinical practice, and (2) to validate its accuracy, efficiency and IOV compared to manual delineation in a clinical setting. METHODS: Two datasets were retrospectively collected from 150 clinical cases. CNNs were trained for GTV delineation with consensus delineation as ground truth, with either single (CT) or co-registered multi-modal (CT + PET or CT + MRI) imaging data as input. For validation, GTVs were delineated on 20 new cases by two observers, once manually, once by correcting the delineations generated by the CNN. RESULTS: Both multi-modality CNNs performed better than the single-modality CNN and were selected for clinical validation. Mean Dice Similarity Coefficient (DSC) for (GTVp, GTVn) respectively between automated and manual delineations was (69%, 79%) for CT + PET and (59%,71%) for CT + MRI. Mean DSC between automated and corrected delineations was (81%,89%) for CT + PET and (69%,77%) for CT + MRI. Mean DSC between observers was (76%,86%) for manual delineations and (95%,96%) for corrected delineations, indicating a significant decrease in IOV (p < 10-5), while efficiency increased significantly (48%, p < 10-5). CONCLUSION: Multi-modality automated delineation of GTV of HNC was shown to be more efficient and consistent compared to manual delineation in a clinical setting and beneficial over a single-modality approach.

Automated MRI quantification of volumetric per-muscle fat fractions in the proximal leg of patients with muscular dystrophies.

Muscular dystrophies (MD) are a class of rare genetic diseases resulting in progressive muscle weakness affecting specific muscle groups, depending on the type of disease. Disease progression is characterized by the gradual replacement of muscle tissue by fat, which can be assessed with fat-sensitive magnetic resonance imaging (MRI) and objectively evaluated by quantifying the fat fraction percentage (FF%) per muscle. Volumetric quantification of fat replacement over the full 3D extent of each muscle is more precise and potentially more sensitive than 2D quantification in few selected slices only, but it requires an accurate 3D segmentation of each muscle individually, which is time consuming when this has to be performed manually for a large number of muscles. A reliable, largely automated approach for 3D muscle segmentation is thus needed to facilitate the adoption of fat fraction quantification as a measure of MD disease progression in clinical routine practice, but this is challenging due to the variable appearance of the images and the ambiguity in the discrimination of the contours of adjacent muscles, especially when the normal image contrast is affected and diminished by the fat replacement. To deal with these challenges, we used deep learning to train AI-models to segment the muscles in the proximal leg from knee to hip in Dixon MRI images of healthy subjects as well as patients with MD. We demonstrate state-of-the-art segmentation results of all 18 muscles individually in terms of overlap (Dice score, DSC) with the manual ground truth delineation for images of cases with low fat infiltration (mean overall FF%: 11.3%; mean DSC: 95.3% per image, 84.4-97.3% per muscle) as well as with medium and high fat infiltration (mean overall FF%: 44.3%; mean DSC: 89.0% per image, 70.8-94.5% per muscle). In addition, we demonstrate that the segmentation performance is largely invariant to the field of view of the MRI scan, is generalizable to patients with different types of MD and that the manual delineation effort to create the training set can be drastically reduced without significant loss of segmentation quality by delineating only a subset of the slices.

Factorizer: A scalable interpretable approach to context modeling for medical image segmentation.

Convolutional Neural Networks (CNNs) with U-shaped architectures have dominated medical image segmentation, which is crucial for various clinical purposes. However, the inherent locality of convolution makes CNNs fail to fully exploit global context, essential for better recognition of some structures, e.g., brain lesions. Transformers have recently proven promising performance on vision tasks, including semantic segmentation, mainly due to their capability of modeling long-range dependencies. Nevertheless, the quadratic complexity of attention makes existing Transformer-based models use self-attention layers only after somehow reducing the image resolution, which limits the ability to capture global contexts present at higher resolutions. Therefore, this work introduces a family of models, dubbed Factorizer, which leverages the power of low-rank matrix factorization for constructing an end-to-end segmentation model. Specifically, we propose a linearly scalable approach to context modeling, formulating Nonnegative Matrix Factorization (NMF) as a differentiable layer integrated into a U-shaped architecture. The shifted window technique is also utilized in combination with NMF to effectively aggregate local information. Factorizers compete favorably with CNNs and Transformers in terms of accuracy, scalability, and interpretability, achieving state-of-the-art results on the BraTS dataset for brain tumor segmentation and ISLES'22 dataset for stroke lesion segmentation. Highly meaningful NMF components give an additional interpretability advantage to Factorizers over CNNs and Transformers. Moreover, our ablation studies reveal a distinctive feature of Factorizers that enables a significant speed-up in inference for a trained Factorizer without any extra steps and without sacrificing much accuracy. The code and models are publicly available at https://github.com/pashtari/factorizer.