Prostate volume prediction on MRI: tools, accuracy and variability.

OBJECTIVE: A reliable estimation of prostate volume (PV) is essential to prostate cancer management. The objective of our multi-rater study was to compare intra- and inter-rater variability of PV from manual planimetry and ellipsoid formulas. METHODS: Forty treatment-naive patients who underwent prostate MRI were selected from a local database. PV and corresponding PSA density (PSAd) were estimated on 3D T2-weighted MRI (3 T) by 7 independent radiologists using the traditional ellipsoid formula (TEF), the newer biproximate ellipsoid formula (BPEF), and the manual planimetry method (MPM) used as ground truth. Intra- and inter-rater variability was calculated using the mixed model-based intraclass correlation coefficient (ICC). RESULTS: Mean volumes were 67.00 (± 36.61), 66.07 (± 35.03), and 64.77 (± 38.27) cm3 with the TEF, BPEF, and MPM methods, respectively. Both TEF and BPEF overestimated PV relative to MPM, with the former presenting significant differences (+ 1.91 cm3, IQ = [- 0.33 cm3, 5.07 cm3], p val = 0.03). Both intra- (ICC > 0.90) and inter-rater (ICC > 0.90) reproducibility were excellent. MPM had the highest inter-rater reproducibility (ICC = 0.999). Inter-rater PV variation led to discrepancies in classification according to the clinical criterion of PSAd > 0.15 ng/mL for 2 patients (5%), 7 patients (17.5%), and 9 patients (22.5%) when using MPM, TEF, and BPEF, respectively. CONCLUSION: PV measurements using ellipsoid formulas and MPM are highly reproducible. MPM is a robust method for PV assessment and PSAd calculation, with the lowest variability. TEF showed a high degree of concordance with MPM but a slight overestimation of PV. Precise anatomic landmarks as defined with the BPEF led to a more accurate PV estimation, but also to a higher variability. KEY POINTS: • Manual planimetry used for prostate volume estimation is robust and reproducible, with the lowest variability between readers. • Ellipsoid formulas are accurate and reproducible but with higher variability between readers. • The traditional ellipsoid formula tends to overestimate prostate volume.

How can we combat multicenter variability in MR radiomics? Validation of a correction procedure.

OBJECTIVE: Test a practical realignment approach to compensate the technical variability of MR radiomic features. METHODS: T1 phantom images acquired on 2 scanners, FLAIR and contrast-enhanced T1-weighted (CE-T1w) images of 18 brain tumor patients scanned on both 1.5-T and 3-T scanners, and 36 T2-weighted (T2w) images of prostate cancer patients scanned in one of two centers were investigated. The ComBat procedure was used for harmonizing radiomic features. Differences in statistical distributions in feature values between 1.5- and 3-T images were tested before and after harmonization. The prostate studies were used to determine the impact of harmonization to distinguish between Gleason grades (GGs). RESULTS: In the phantom data, 40 out of 42 radiomic feature values were significantly different between the 2 scanners before harmonization and none after. In white matter regions, the statistical distributions of features were significantly different (p < 0.05) between the 1.5- and 3-T images for 37 out of 42 features in both FLAIR and CE-T1w images. After harmonization, no statistically significant differences were observed. In brain tumors, 41 (FLAIR) or 36 (CE-T1w) out of 42 features were significantly different between the 1.5- and 3-T images without harmonization, against 1 (FLAIR) or none (CE-T1w) with harmonization. In prostate studies, 636 radiomic features were significantly different between GGs after harmonization against 461 before. The ability to distinguish between GGs using radiomic features was increased after harmonization. CONCLUSION: ComBat harmonization efficiently removes inter-center technical inconsistencies in radiomic feature values and increases the sensitivity of studies using data from several scanners. KEY POINTS: • Radiomic feature values obtained using different MR scanners or imaging protocols can be harmonized by combining off-the-shelf image standardization and feature realignment procedures. • Harmonized radiomic features enable one to pool data from different scanners and centers without a substantial loss of statistical power caused by intra- and inter-center variability. • The proposed realignment method is applicable to radiomic features from different MR sequences and tumor types and does not rely on any phantom acquisition.

Monotonic Gaussian Process for spatio-temporal disease progression modeling in brain imaging data.

We introduce a probabilistic generative model for disentangling spatio-temporal disease trajectories from collections of high-dimensional brain images. The model is based on spatio-temporal matrix factorization, where inference on the sources is constrained by anatomically plausible statistical priors. To model realistic trajectories, the temporal sources are defined as monotonic and time-reparameterized Gaussian Processes. To account for the non-stationarity of brain images, we model the spatial sources as sparse codes convolved at multiple scales. The method was tested on synthetic data favourably comparing with standard blind source separation approaches. The application on large-scale imaging data from a clinical study allows to disentangle differential temporal progression patterns mapping brain regions key to neurodegeneration, while revealing a disease-specific time scale associated to the clinical diagnosis.

Predicting PET-derived myelin content from multisequence MRI for individual longitudinal analysis in multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system (CNS). The demyelination process can be repaired by the generation of a new sheath of myelin around the axon, a process termed remyelination. In MS patients, the demyelination-remyelination cycles are highly dynamic. Over the years, magnetic resonance imaging (MRI) has been increasingly used in the diagnosis of MS and it is currently the most useful paraclinical tool to assess this diagnosis. However, conventional MRI pulse sequences are not specific for pathological mechanisms such as demyelination and remyelination. Recently, positron emission tomography (PET) with radiotracer [11C]PIB has become a promising tool to measure in-vivo myelin content changes which is essential to push forward our understanding of mechanisms involved in the pathology of MS, and to monitor individual patients in the context of clinical trials focused on repair therapies. However, PET imaging is invasive due to the injection of a radioactive tracer. Moreover, it is an expensive imaging test and not offered in the majority of medical centers in the world. In this work, by using multisequence MRI, we thus propose a method to predict the parametric map of [11C]PIB PET, from which we derived the myelin content changes in a longitudinal analysis of patients with MS. The method is based on the proposed conditional flexible self-attention GAN (CF-SAGAN) which is specifically adjusted for high-dimensional medical images and able to capture the relationships between the spatially separated lesional regions during the image synthesis process. Jointly applying the sketch-refinement process and the proposed attention regularization that focuses on the MS lesions, our approach is shown to outperform the state-of-the-art methods qualitatively and quantitatively. Specifically, our method demonstrated a superior performance for the prediction of myelin content at voxel-wise level. More important, our method for the prediction of myelin content changes in patients with MS shows similar clinical correlations to the PET-derived gold standard indicating the potential for clinical management of patients with MS.

A model of brain morphological changes related to aging and Alzheimer's disease from cross-sectional assessments.

In this study we propose a deformation-based framework to jointly model the influence of aging and Alzheimer's disease (AD) on the brain morphological evolution. Our approach combines a spatio-temporal description of both processes into a generative model. A reference morphology is deformed along specific trajectories to match subject specific morphologies. It is used to define two imaging progression markers: 1) a morphological age and 2) a disease score. These markers can be computed regionally in any brain region. The approach is evaluated on brain structural magnetic resonance images (MRI) from the ADNI database. The model is first estimated on a control population using longitudinal data, then, for each testing subject, the markers are computed cross-sectionally for each acquisition. The longitudinal evolution of these markers is then studied in relation with the clinical diagnosis of the subjects and used to generate possible morphological evolutions. In the model, the morphological changes associated with normal aging are mainly found around the ventricles, while the Alzheimer's disease specific changes are located in the temporal lobe and the hippocampal area. The statistical analysis of these markers highlights differences between clinical conditions even though the inter-subject variability is quite high. The model is also generative since it can be used to simulate plausible morphological trajectories associated with the disease. Our method quantifies two interpretable scalar imaging biomarkers assessing respectively the effects of aging and disease on brain morphology, at the individual and population level. These markers confirm the presence of an accelerated apparent aging component in Alzheimer's patients but they also highlight specific morphological changes that can help discriminate clinical conditions even in prodromal stages. More generally, the joint modeling of normal and pathological evolutions shows promising results to describe age-related brain diseases over long time scales.

Validation of A Method to Compensate Multicenter Effects Affecting CT Radiomics.

Background Radiomics extracts features from medical images more precisely and more accurately than visual assessment. However, radiomics features are affected by CT scanner parameters such as reconstruction kernel or section thickness, thus obscuring underlying biologically important texture features. Purpose To investigate whether a compensation method could correct for the variations of radiomic feature values caused by using different CT protocols. Materials and Methods Phantom data involving 10 texture patterns and 74 patients in cohorts 1 (19 men; 42 patients; mean age, 60.4 years; September-October 2013) and 2 (16 men; 32 patients; mean age, 62.1 years; January-September 2007) scanned by using different CT protocols were retrospectively included. For any radiomic feature, the compensation approach identified a protocol-specific transformation to express all data in a common space that were devoid of protocol effects. The differences in statistical distributions between protocols were assessed by using Friedman tests before and after compensation. Principal component analyses were performed on the phantom data to evaluate the ability to distinguish between texture patterns after compensation. Results In the phantom data, the statistical distributions of features were different between protocols for all radiomic features and texture patterns (P < .05). After compensation, the protocol effect was no longer detectable (P > .05). Principal component analysis demonstrated that each texture pattern was no longer displayed as different clusters corresponding to different imaging protocols, unlike what was observed before compensation. The correction for scanner effect was confirmed in patient data with 100% (10 of 10 features for cohort 1) and 98% (87 of 89 features for cohort 2) of P values less than .05 before compensation, compared with 30% (three of 10) and 15% (13 of 89) after compensation. Conclusion Image compensation successfully realigned feature distributions computed from different CT imaging protocols and should facilitate multicenter radiomic studies. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Steiger and Sood in this issue.

A biophysical model of brain deformation to simulate and analyze longitudinal MRIs of patients with Alzheimer's disease.

We propose a framework for developing a comprehensive biophysical model that could predict and simulate realistic longitudinal MRIs of patients with Alzheimer's disease (AD). The framework includes three major building blocks: i) atrophy generation, ii) brain deformation, and iii) realistic MRI generation. Within this framework, this paper focuses on a detailed implementation of the brain deformation block with a carefully designed biomechanics-based tissue loss model. For a given baseline brain MRI, the model yields a deformation field imposing the desired atrophy at each voxel of the brain parenchyma while allowing the CSF to expand as required to globally compensate for the locally prescribed volume loss. Our approach is inspired by biomechanical principles and involves a system of equations similar to Stokes equations in fluid mechanics but with the presence of a non-zero mass source term. We use this model to simulate longitudinal MRIs by prescribing complex patterns of atrophy. We present experiments that provide an insight into the role of different biomechanical parameters in the model. The model allows simulating images with exactly the same tissue atrophy but with different underlying deformation fields in the image. We explore the influence of different spatial distributions of atrophy on the image appearance and on the measurements of atrophy reported by various global and local atrophy estimation algorithms. We also present a pipeline that allows evaluating atrophy estimation algorithms by simulating longitudinal MRIs from large number of real subject MRIs with complex subject-specific atrophy patterns. The proposed framework could help understand the implications of different model assumptions, regularization choices, and spatial priors for the detection and measurement of brain atrophy from longitudinal brain MRIs.

Biophysical Modeling Predicts Ventricular Tachycardia Inducibility and Circuit Morphology: A Combined Clinical Validation and Computer Modeling Approach.

INTRODUCTION: Computational modeling of cardiac arrhythmogenesis and arrhythmia maintenance has made a significant contribution to the understanding of the underlying mechanisms of arrhythmia. We hypothesized that a cardiac model using personalized electro-anatomical parameters could define the underlying ventricular tachycardia (VT) substrate and predict reentrant VT circuits. We used a combined modeling and clinical approach in order to validate the concept. METHODS AND RESULTS: Non-contact electroanatomic mapping studies were performed in 7 patients (5 ischemics, 2 non-ischemics). Three ischemic cardiomyopathy patients underwent a clinical VT stimulation study. Anatomical information was obtained from cardiac magnetic resonance imaging (CMR) including high-resolution scar imaging. A simplified biophysical mono-domain action potential model personalized with the patients' anatomical and electrical information was used to perform in silico VT stimulation studies for comparison. The personalized in silico VT stimulations were able to predict VT inducibility as well as the macroscopic characteristics of the VT circuits in patients who had clinical VT stimulation studies. The patients with positive clinical VT stimulation studies had wider distribution of action potential duration restitution curve (APD-RC) slopes and APDs than the patient with a negative VT stimulation study. The exit points of reentrant VT circuits encompassed a higher percentage of the maximum APD-RC slope compared to the scar and non-scar areas, 32%, 4%, and 0.2%, respectively. CONCLUSIONS: VT stimulation studies can be simulated in silico using a personalized biophysical cardiac model. Myocardial spatial heterogeneity of APD restitution properties and conductivity may help predict the location of crucial entry/exit points of reentrant VT circuits.

Impact of the surgical experience on cochleostomy location: a comparative temporal bone study between endaural and posterior tympanotomy approaches for cochlear implantation.

The goal of this study was to evaluate, in the hands of an inexperienced surgeon, the cochleostomy location of an endaural approach (MINV) compared to the conventional posterior tympanotomy (MPT) approach. Since 2010, we use in the ENT department of Nice a new surgical endaural approach to perform cochlear implantation. In the hands of an inexperienced surgeon, the position of the cochleostomy has not yet been studied in detail for this technique. This is a prospective study of 24 human heads. Straight electrode arrays were implanted by an inexperienced surgeon: on one side using MPT and on the other side using MINV. The cochleostomies were all antero-inferior, but they were performed through an endaural approach with the MINV or a posterior tympanotomy approach with the MPT. The positioning of the cochleostomies into the scala tympani was evaluated by microdissection. Cochleostomies performed through the endaural approach were well placed into the scala tympani more frequently than those performed through the posterior tympanotomy approach (87.5 and 16.7 %, respectively, p ≤ 0.001). This study highlights the biggest challenge for an inexperienced surgeon to achieve a reliable cochleostomy through a posterior tympanotomy, which requires years of experience. In case of an uncomfortable view through a posterior tympanotomy, an inexperienced surgeon might be able to successfully perform a cochleostomy through an endaural (combined approach) or an extended round window approach in order to avoid opening the scala vestibuli.

Reference standard for the evaluation of automatic segmentation algorithms: Quantification of inter observer variability of manual delineation of prostate contour on MRI.

PURPOSE: The purpose of this study was to investigate the relationship between inter-reader variability in manual prostate contour segmentation on magnetic resonance imaging (MRI) examinations and determine the optimal number of readers required to establish a reliable reference standard. MATERIALS AND METHODS: Seven radiologists with various experiences independently performed manual segmentation of the prostate contour (whole-gland [WG] and transition zone [TZ]) on 40 prostate MRI examinations obtained in 40 patients. Inter-reader variability in prostate contour delineations was estimated using standard metrics (Dice similarity coefficient [DSC], Hausdorff distance and volume-based metrics). The impact of the number of readers (from two to seven) on segmentation variability was assessed using pairwise metrics (consistency) and metrics with respect to a reference segmentation (conformity), obtained either with majority voting or simultaneous truth and performance level estimation (STAPLE) algorithm. RESULTS: The average segmentation DSC for two readers in pairwise comparison was 0.919 for WG and 0.876 for TZ. Variability decreased with the number of readers: the interquartile ranges of the DSC were 0.076 (WG) / 0.021 (TZ) for configurations with two readers, 0.005 (WG) / 0.012 (TZ) for configurations with three readers, and 0.002 (WG) / 0.0037 (TZ) for configurations with six readers. The interquartile range decreased slightly faster between two and three readers than between three and six readers. When using consensus methods, variability often reached its minimum with three readers (with STAPLE, DSC = 0.96 [range: 0.945-0.971] for WG and DSC = 0.94 [range: 0.912-0.957] for TZ, and interquartile range was minimal for configurations with three readers. CONCLUSION: The number of readers affects the inter-reader variability, in terms of inter-reader consistency and conformity to a reference. Variability is minimal for three readers, or three readers represent a tipping point in the variability evolution, with both pairwise-based metrics or metrics with respect to a reference. Accordingly, three readers may represent an optimal number to determine references for artificial intelligence applications.

WhARIO: whole-slide-image-based survival analysis for patients treated with immunotherapy.

Purpose: Immune checkpoint inhibitors (ICIs) are now one of the standards of care for patients with lung cancer and have greatly improved both progression-free and overall survival, although <20% of the patients respond to the treatment, and some face acute adverse events. Although a few predictive biomarkers have integrated the clinical workflow, they require additional modalities on top of whole-slide images and lack efficiency or robustness. In this work, we propose a biomarker of immunotherapy outcome derived solely from the analysis of histology slides. Approach: We develop a three-step framework, combining contrastive learning and nonparametric clustering to distinguish tissue patterns within the slides, before exploiting the adjacencies of previously defined regions to derive features and train a proportional hazards model for survival analysis. We test our approach on an in-house dataset of 193 patients from 5 medical centers and compare it with the gold standard tumor proportion score (TPS) biomarker. Results: On a fivefold cross-validation (CV) of the entire dataset, the whole-slide image-based survival analysis for patients treated with immunotherapy (WhARIO) features are able to separate a low- and a high-risk group of patients with a hazard ratio (HR) of 2.29 (CI95=1.48 to 3.56), whereas the TPS 1% reference threshold only reaches a HR of 1.81 (CI95=1.21 to 2.69). Combining the two yields a higher HR of 2.60 (CI95=1.72 to 3.94). Additional experiments on the same dataset, where one out of five centers is excluded from the CV and used as a test set, confirm these trends. Conclusions: Our uniquely designed WhARIO features are an efficient predictor of survival for lung cancer patients who received ICI treatment. We achieve similar performance to the current gold standard biomarker, without the need to access other imaging modalities, and show that both can be used together to reach even better results.

Integration of merged delayed-enhanced magnetic resonance imaging and multidetector computed tomography for the guidance of ventricular tachycardia ablation: a pilot study.

BACKGROUND: Delayed enhancement (DE) MRI can assess the fibrotic substrate of scar-related VT. MDCT has the advantage of inframillimetric spatial resolution and better 3D reconstructions. We sought to evaluate the feasibility and usefulness of integrating merged MDCT/MRI data in 3D-mapping systems for structure-function assessment and multimodal guidance of VT mapping and ablation. METHODS: Nine patients, including 3 ischemic cardiomyopathy (ICM), 3 nonischemic cardiomyopathy (NICM), 2 myocarditis, and 1 redo procedure for idiopathic VT, underwent MRI and MDCT before VT ablation. Merged MRI/MDCT data were integrated in 3D-mapping systems and registered to high-density endocardial and epicardial maps. Low-voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were correlated to DE at MRI, and wall-thinning (WT) at MDCT. RESULTS: Endocardium and epicardium were mapped with 391 ± 388 and 1098 ± 734 points per map, respectively. Registration of MDCT allowed visualization of coronary arteries during epicardial mapping/ablation. In the idiopathic patient, integration of MRI data identified previously ablated regions. In ICM patients, both DE at MRI and WT at MDCT matched areas of low voltage (overlap 94 ± 6% and 79 ± 5%, respectively). In NICM patients, wall-thinning areas matched areas of low voltage (overlap 63 ± 21%). In patients with myocarditis, subepicardial DE matched areas of epicardial low voltage (overlap 92 ± 12%). A total number of 266 LAVA sites were found in 7/9 patients. All LAVA sites were associated to structural substrate at imaging (90% inside, 100% within 18 mm). CONCLUSION: The integration of merged MDCT and DEMRI data is feasible and allows combining substrate assessment with high-spatial resolution to better define structure-function relationship in scar-related VT.

MS-CLAM: Mixed supervision for the classification and localization of tumors in Whole Slide Images.

Given the size of digitized Whole Slide Images (WSIs), it is generally laborious and time-consuming for pathologists to exhaustively delineate objects within them, especially with datasets containing hundreds of slides to annotate. Most of the time, only slide-level labels are available, giving rise to the development of weakly-supervised models. However, it is often difficult to obtain from such models accurate object localization, e.g., patches with tumor cells in a tumor detection task, as they are mainly designed for slide-level classification. Using the attention-based deep Multiple Instance Learning (MIL) model as our base weakly-supervised model, we propose to use mixed supervision - i.e., the use of both slide-level and patch-level labels - to improve both the classification and the localization performances of the original model, using only a limited amount of patch-level labeled slides. In addition, we propose an attention loss term to regularize the attention between key instances, and a paired batch method to create balanced batches for the model. First, we show that the changes made to the model already improve its performance and interpretability in the weakly-supervised setting. Furthermore, when using only between 12 and 62% of the total available patch-level annotations, we can reach performance close to fully-supervised models on the tumor classification datasets DigestPath2019 and Camelyon16.

Deep clustering for abdominal organ classification in ultrasound imaging.

Purpose: The purpose of this study is to examine the utilization of unlabeled data for abdominal organ classification in multi-label (non-mutually exclusive classes) ultrasound images, as an alternative to the conventional transfer learning approach. Approach: We present a new method for classifying abdominal organs in ultrasound images. Unlike previous approaches that only relied on labeled data, we consider the use of both labeled and unlabeled data. To explore this approach, we first examine the application of deep clustering for pretraining a classification model. We then compare two training methods, fine-tuning with labeled data through supervised learning and fine-tuning with both labeled and unlabeled data using semisupervised learning. All experiments were conducted on a large dataset of unlabeled images (nu=84967) and a small set of labeled images (ns=2742) comprising progressively 10%, 20%, 50%, and 100% of the images. Results: We show that for supervised fine-tuning, deep clustering is an effective pre-training method, with performance matching that of ImageNet pre-training using five times less labeled data. For semi-supervised learning, deep clustering pre-training also yields higher performance when the amount of labeled data is limited. Best performance is obtained with deep clustering pre-training combined with semi-supervised learning and 2742 labeled example images with an F1-score weighted average of 84.1%. Conclusions: This method can be used as a tool to preprocess large unprocessed databases, thus reducing the need for prior annotations of abdominal ultrasound studies for the training of image classification algorithms, which in turn could improve the clinical use of ultrasound images.

Real-Time Dynamic Data Driven Deformable Registration for Image-Guided Neurosurgery: Computational Aspects.

Current neurosurgical procedures utilize medical images of various modalities to enable the precise location of tumors and critical brain structures to plan accurate brain tumor resection. The difficulty of using preoperative images during the surgery is caused by the intra-operative deformation of the brain tissue (brain shift), which introduces discrepancies concerning the preoperative configuration. Intra-operative imaging allows tracking such deformations but cannot fully substitute for the quality of the pre-operative data. Dynamic Data Driven Deformable Non-Rigid Registration (D4NRR) is a complex and time-consuming image processing operation that allows the dynamic adjustment of the pre-operative image data to account for intra-operative brain shift during the surgery. This paper summarizes the computational aspects of a specific adaptive numerical approximation method and its variations for registering brain MRIs. It outlines its evolution over the last 15 years and identifies new directions for the computational aspects of the technique.

Comparison of physics-based deformable registration methods for image-guided neurosurgery.

This paper compares three finite element-based methods used in a physics-based non-rigid registration approach and reports on the progress made over the last 15 years. Large brain shifts caused by brain tumor removal affect registration accuracy by creating point and element outliers. A combination of approximation- and geometry-based point and element outlier rejection improves the rigid registration error by 2.5 mm and meets the real-time constraints (4 min). In addition, the paper raises several questions and presents two open problems for the robust estimation and improvement of registration error in the presence of outliers due to sparse, noisy, and incomplete data. It concludes with preliminary results on leveraging Quantum Computing, a promising new technology for computationally intensive problems like Feature Detection and Block Matching in addition to finite element solver; all three account for 75% of computing time in deformable registration.

Comparison of the endocranial ontogenies between chimpanzees and bonobos via temporal regression and spatiotemporal registration.

This paper aims at quantifying ontogenetic differences between bonobo (Pan paniscus) and chimpanzee (Pan troglodytes) endocrania, using dental development as a timeline. We utilize a methodology based on smooth and invertible deformations combined with a metric of "currents" that defines a distance between endocranial surfaces and does not rely on correspondence between landmarks. This allows us to perform a temporal surface regression that estimates typical endocranial ontogenetic trajectories separately for bonobos and chimpanzees. We highlight non-linear patterns of endocranial ontogenetic change and significant differences between species at local anatomical levels rather than considering the endocranium as a uniform entity. A spatiotemporal registration permits the quantification of inter-species differences decomposed into a morphological deformation (accounting for size and shape differences independently of age) and a time warp (accounting for changes in the dynamics of development). Our statistical simulations suggest that patterns of endocranial volume (EV) increase may differ significantly between bonobos and chimpanzees, with an earlier phase of a relatively rapid increase (preferentially at some endocranial subdivisions) in the former and a much later phase of relatively rapid increase in the latter. As a consequence, the chimpanzee endocranium appears to reach its adult size later. Moreover, the time warp indicates that juvenile bonobos develop much slower than juvenile chimpanzees, suggesting that inter-specific ontogenetic shifts do not only concern EV increase, but also the rate of shape changes over time. Our method provides, for the first time, a quantitative estimation of inter-specific ontogenetic shifts that appear to differentiate non-linearly.

Automatic zonal segmentation of the prostate from 2D and 3D T2-weighted MRI and evaluation for clinical use.

Purpose: An accurate zonal segmentation of the prostate is required for prostate cancer (PCa) management with MRI. Approach: The aim of this work is to present UFNet, a deep learning-based method for automatic zonal segmentation of the prostate from T2-weighted (T2w) MRI. It takes into account the image anisotropy, includes both spatial and channelwise attention mechanisms and uses loss functions to enforce prostate partition. The method was applied on a private multicentric three-dimensional T2w MRI dataset and on the public two-dimensional T2w MRI dataset ProstateX. To assess the model performance, the structures segmented by the algorithm on the private dataset were compared with those obtained by seven radiologists of various experience levels. Results: On the private dataset, we obtained a Dice score (DSC) of 93.90 ± 2.85 for the whole gland (WG), 91.00 ± 4.34 for the transition zone (TZ), and 79.08 ± 7.08 for the peripheral zone (PZ). Results were significantly better than other compared networks' ( p - value < 0.05 ). On ProstateX, we obtained a DSC of 90.90 ± 2.94 for WG, 86.84 ± 4.33 for TZ, and 78.40 ± 7.31 for PZ. These results are similar to state-of-the art results and, on the private dataset, are coherent with those obtained by radiologists. Zonal locations and sectorial positions of lesions annotated by radiologists were also preserved. Conclusions: Deep learning-based methods can provide an accurate zonal segmentation of the prostate leading to a consistent zonal location and sectorial position of lesions, and therefore can be used as a helping tool for PCa diagnosis.

SimulAD: a dynamical model for personalized simulation and disease staging in Alzheimer's disease.

SimulAD is a computational disease progression model (DPM) originally developed on the ADNI database to simulate the evolution of clinical and imaging markers characteristic of AD, and to quantify the disease severity (DS) of a subject. In this work, we assessed the validity of this estimated DS, as well as the generalization of the DPM., by applying SimulAD on a new cohort from the Geneva Memory Center (GMC). The differences between the estimated DS of healthy, mild cognitive impairment and AD dementia groups were statistically significant (p-values < 0.05; d ≥ 0.8). DS correlated with MMSE (ρ = -0.55), hippocampal atrophy (ρ = -0.62), glucose hypometabolism (ρ = -0.67), amyloid burden (ρ = 0.31) and tau deposition (ρ = 0.62) (p-values < 0.01). Based on the dynamics estimated on the ADNI cohort, we simulated a DPM for the subjects of the GMC cohort. The difference between the temporal evolution of similar biomarkers simulated on the ADNI and GMC cohorts remained below 10%. This study illustrates the robustness and good generalization of SimulAD, highlighting its potential for clinical and pharmaceutical studies.