Extensive T1-weighted MRI preprocessing improves generalizability of deep brain age prediction models.

Brain age is an estimate of chronological age obtained from T1-weighted magnetic resonance images (T1w MRI), representing a straightforward diagnostic biomarker of brain aging and associated diseases. While the current best accuracy of brain age predictions on T1w MRIs of healthy subjects ranges from two to three years, comparing results across studies is challenging due to differences in the datasets, T1w preprocessing pipelines, and evaluation protocols used. This paper investigates the impact of T1w image preprocessing on the performance of four deep learning brain age models from recent literature. Four preprocessing pipelines, which differed in terms of registration transform, grayscale correction, and software implementation, were evaluated. The results showed that the choice of software or preprocessing steps could significantly affect the prediction error, with a maximum increase of 0.75 years in mean absolute error (MAE) for the same model and dataset. While grayscale correction had no significant impact on MAE, using affine rather than rigid registration to brain atlas statistically significantly improved MAE. Models trained on 3D images with isotropic 1mm3 resolution exhibited less sensitivity to the T1w preprocessing variations compared to 2D models or those trained on downsampled 3D images. Our findings indicate that extensive T1w preprocessing improves MAE, especially when predicting on a new dataset. This runs counter to prevailing research literature, which suggests that models trained on minimally preprocessed T1w scans are better suited for age predictions on MRIs from unseen scanners. We demonstrate that, irrespective of the model or T1w preprocessing used during training, applying some form of offset correction is essential to enable the model's performance to generalize effectively on datasets from unseen sites, regardless of whether they have undergone the same or different T1w preprocessing as the training set.

Psychometric evaluation of the 5-item Medication Adherence Report Scale questionnaire in persons with multiple sclerosis.

The 5-item Medication Adherence Report Scale (MARS-5) is a reliable and valid questionnaire for evaluating adherence in patients with asthma, hypertension, and diabetes. Validity has not been determined in multiple sclerosis (MS). We aimed to establish criterion validity and reliability of the MARS-5 in persons with MS (PwMS). Our prospective study included PwMS on dimethyl fumarate (DMF). PwMS self-completed the MARS-5 on the same day before baseline and follow-up brain magnetic resonance imaging (MRI) 3 and 9 months after treatment initiation and were graded as highly and medium adherent upon the 24-cut-off score, established by receiver operator curve analysis. Health outcomes were represented by relapse occurrence from the 1st DMF dispense till follow-up brain MRI and radiological progression (new T2 MRI lesions and quantitative analysis) between baseline and follow-up MRI. Criterion validity was established by association with the Proportion of Days Covered (PDC), new T2 MRI lesions, and Beliefs in Medicines questionnaire (BMQ). The reliability evaluation included internal consistency and the test-retest method. We included 40 PwMS (age 37.6 ± 9.9 years, 75% women), 34 were treatment-naive. No relapses were seen during the follow-up period but quantitative MRI analysis showed new T2 lesions in 6 PwMS. The mean (SD) MARS-5 score was 23.1 (2.5), with 24 PwMS graded as highly adherent. The higher MARS-5 score was associated with higher PDC (b = 0.027, P<0.001, 95% CI: (0.0134-0.0403)) and lower medication concerns (b = -1.25, P<0.001, 95% CI: (-1.93-(-0,579)). Lower adherence was associated with increased number (P = 0.00148) and total volume of new T2 MRI lesions (P = 0.00149). The questionnaire showed acceptable internal consistency (Cronbach α = 0.72) and moderate test-retest reliability (r = 0.62, P < 0.0001, 95% CI: 0.33-0.79). The MARS-5 was found to be valid and reliable for estimating medication adherence and predicting medication concerns in persons with MS.

BASE: Brain Age Standardized Evaluation.

Brain age, most commonly inferred from T1-weighted magnetic resonance images (T1w MRI), is a robust biomarker of brain health and related diseases. Superior accuracy in brain age prediction, often falling within a 2-3 year range, is achieved predominantly through deep neural networks. However, comparing study results is difficult due to differences in datasets, evaluation methodologies and metrics. Addressing this, we introduce Brain Age Standardized Evaluation (BASE), which includes (i) a standardized T1w MRI dataset including multi-site, new unseen site, test-retest and longitudinal data, and an associated (ii) evaluation protocol, including repeated model training and upon based comprehensive set of performance metrics measuring accuracy, robustness, reproducibility and consistency aspects of brain age predictions, and (iii) statistical evaluation framework based on linear mixed-effects models for rigorous performance assessment and cross-comparison. To showcase BASE, we comprehensively evaluate four deep learning based brain age models, appraising their performance in scenarios that utilize multi-site, test-retest, unseen site, and longitudinal T1w brain MRI datasets. Ensuring full reproducibility and application in future studies, we have made all associated data information and code publicly accessible at https://github.com/AralRalud/BASE.git.

A Systematic Review of Deep-Learning Methods for Intracranial Aneurysm Detection in CT Angiography.

Background: Subarachnoid hemorrhage resulting from cerebral aneurysm rupture is a significant cause of morbidity and mortality. Early identification of aneurysms on Computed Tomography Angiography (CTA), a frequently used modality for this purpose, is crucial, and artificial intelligence (AI)-based algorithms can improve the detection rate and minimize the intra- and inter-rater variability. Thus, a systematic review and meta-analysis were conducted to assess the diagnostic accuracy of deep-learning-based AI algorithms in detecting cerebral aneurysms using CTA. Methods: PubMed (MEDLINE), Embase, and the Cochrane Library were searched from January 2015 to July 2023. Eligibility criteria involved studies using fully automated and semi-automatic deep-learning algorithms for detecting cerebral aneurysms on the CTA modality. Eligible studies were assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A diagnostic accuracy meta-analysis was conducted to estimate pooled lesion-level sensitivity, size-dependent lesion-level sensitivity, patient-level specificity, and the number of false positives per image. An enhanced FROC curve was utilized to facilitate comparisons between the studies. Results: Fifteen eligible studies were assessed. The findings indicated that the methods exhibited high pooled sensitivity (0.87, 95% confidence interval: 0.835 to 0.91) in detecting intracranial aneurysms at the lesion level. Patient-level sensitivity was not reported due to the lack of a unified patient-level sensitivity definition. Only five studies involved a control group (healthy subjects), whereas two provided information on detection specificity. Moreover, the analysis of size-dependent sensitivity reported in eight studies revealed that the average sensitivity for small aneurysms (<3 mm) was rather low (0.56). Conclusions: The studies included in the analysis exhibited a high level of accuracy in detecting intracranial aneurysms larger than 3 mm in size. Nonetheless, there is a notable gap that necessitates increased attention and research focus on the detection of smaller aneurysms, the use of a common test dataset, and an evaluation of a consistent set of performance metrics.

Deep geometric learning for intracranial aneurysm detection: towards expert rater performance.

BACKGROUND: Early detection of intracranial aneurysms (IAs) is crucial for patient outcomes. Typically identified on angiographic scans such as CT angiography (CTA) or MR angiography (MRA), the sensitivity of experts in studies on small IAs (diameter <3 mm) was moderate (64-74.1% for CTAs and 70-92.8% for MRAs), and these figures could be lower in a routine clinical setting. Recent research shows that the expert level of sensitivity might be achieved using deep learning approaches. METHODS: A large multisite dataset including 1054 MRA and 2174 CTA scans with expert IA annotations was collected. A novel modality-agnostic two-step IA detection approach was proposed. The first step used nnU-Net for segmenting vascular structures, with model training performed separately for each modality. In the second step, segmentations were converted to vascular surface that was parcellated by sampling point clouds and, using a PointNet++ model, each point was labeled as an aneurysm or vessel class. RESULTS: Quantitative validation of the test data from different sites than the training data showed that the proposed approach achieved pooled sensitivity of 85% and 90% on 157 MRA scans and 1338 CTA scans, respectively, while the sensitivity for small IAs was 72% and 83%, respectively. The corresponding number of false findings per image was low at 1.54 and 1.57, and 0.4 and 0.83 on healthy subject data. CONCLUSIONS: The proposed approach achieved a state-of-the-art balance between the sensitivity and the number of false findings, matched the expert-level sensitivity to small (and other) IAs on external data, and therefore seems fit for computer-assisted detection of IAs in a clinical setting.

Extensive T1-weighted MRI Preprocessing Improves Generalizability of Deep Brain Age Prediction Models.

Brain age is an estimate of chronological age obtained from T1-weighted magnetic resonance images (T1w MRI) and represents a simple diagnostic biomarker of brain ageing and associated diseases. While the current best accuracy of brain age predictions on T1w MRIs of healthy subjects ranges from two to three years, comparing results from different studies is challenging due to differences in the datasets, T1w preprocessing pipelines, and performance metrics used. This paper investigates the impact of T1w image preprocessing on the performance of four deep learning brain age models presented in recent literature. Four preprocessing pipelines were evaluated, differing in terms of registration, grayscale correction, and software implementation. The results showed that the choice of software or preprocessing steps can significantly affect the prediction error, with a maximum increase of 0.7 years in mean absolute error (MAE) for the same model and dataset. While grayscale correction had no significant impact on MAE, the affine registration, compared to the rigid registration of T1w images to brain atlas was shown to statistically significantly improve MAE. Models trained on 3D images with isotropic 1 mm3 resolution exhibited less sensitivity to the T1w preprocessing variations compared to 2D models or those trained on downsampled 3D images. Some proved invariant to the preprocessing pipeline, however only after offset correction. Our findings generally indicate that extensive T1w preprocessing enhances the MAE, especially when applied to a new dataset. This runs counter to prevailing research literature which suggests that models trained on minimally preprocessed T1w scans are better poised for age predictions on MRIs from unseen scanners. Regardless of model or T1w preprocessing used, we show that to enable generalization of model's performance on a new dataset with either the same or different T1w preprocessing than the one applied in model training, some form of offset correction should be applied.

Detection and localization of hyperfunctioning parathyroid glands on [18F]fluorocholine PET/ CT using deep learning - model performance and comparison to human experts.

BACKGROUND: In the setting of primary hyperparathyroidism (PHPT), [18F]fluorocholine PET/CT (FCH-PET) has excellent diagnostic performance, with experienced practitioners achieving 97.7% accuracy in localising hyperfunctioning parathyroid tissue (HPTT). Due to the relative triviality of the task for human readers, we explored the performance of deep learning (DL) methods for HPTT detection and localisation on FCH-PET images in the setting of PHPT. PATIENTS AND METHODS: We used a dataset of 93 subjects with PHPT imaged using FCH-PET, of which 74 subjects had visible HPTT while 19 controls had no visible HPTT on FCH-PET. A conventional Resnet10 as well as a novel mPETResnet10 DL model were trained and tested to detect (present, not present) and localise (upper left, lower left, upper right or lower right) HPTT. Our mPETResnet10 architecture also contained a region-of-interest masking algorithm that we evaluated qualitatively in order to try to explain the model's decision process. RESULTS: The models detected the presence of HPTT with an accuracy of 83% and determined the quadrant of HPTT with an accuracy of 74%. The DL methods performed statistically worse (p < 0.001) in both tasks compared to human readers, who localise HPTT with the accuracy of 97.7%. The produced region-of-interest mask, while not showing a consistent added value in the qualitative evaluation of model's decision process, had correctly identified the foreground PET signal. CONCLUSIONS: Our experiment is the first reported use of DL analysis of FCH-PET in PHPT. We have shown that it is possible to utilize DL methods with FCH-PET to detect and localize HPTT. Given our small dataset of 93 subjects, results are nevertheless promising for further research.

Automated intracranial vessel labeling with learning boosted by vessel connectivity, radii and spatial context.

Cerebrovascular diseases are among the world's top causes of death and their screening and diagnosis rely on angiographic imaging. We focused on automated anatomical labeling of cerebral arteries that enables their cross-sectional quantification and inter-subject comparisons and thereby identification of geometric risk factors correlated to the cerebrovascular diseases. We used 152 cerebral TOF-MRA angiograms from three publicly available datasets and manually created reference labeling using Slicer3D. We extracted centerlines from nnU-net based segmentations using VesselVio and labeled them according to the reference labeling. Vessel centerline coordinates, in combination with additional vessel connectivity, radius and spatial context features were used for training seven distinct PointNet++ models. Model trained solely on the vessel centerline coordinates resulted in ACC of 0.93 and across-labels average TPR was 0.88. Including vessel radius significantly improved ACC to 0.95, and average TPR to 0.91. Finally, focusing spatial context to the Circle of Willis are resulted in best ACC of 0.96 and best average TPR of 0.93. Hence, using vessel radius and spatial context greatly improved vessel labeling, with the attained perfomance opening the avenue for clinical applications of intracranial vessel labeling.

Computer-Assisted Aneurysm Growth Evaluation and Detection (AGED): Comparison with Clinical Aneurysm Follow-Up.

Background and Purpose: Since growing intracranial aneurysms (IA) are more likely to rupture, detecting growth is an important part of unruptured IA follow-up. Recent studies have consistently shown that detecting IA growth can be challenging, especially in smaller aneurysms. In this study, we present an automated computational method to assist detecting aneurysm growth. Materials and Methods: An analysis program, Aneurysm Growth Evaluation & Detection (AGED) based on IA images was developed. To verify the program can satisfactorily detect clinical aneurysm growth, we performed this comparative study using clinical determinations of growth during IA follow-up as a gold standard. Patients with unruptured, saccular IA followed by diagnostic brain CTA to monitor IA progression were reviewed. 48 IA image series from twenty longitudinally-followed ICA IA were analyzed using AGED. A set of IA morphologic features were calculated. Nonparametric statistical tests and ROC analysis were performed to evaluate the performance of each feature for growth detection. Results: The set of automatically calculated morphologic features demonstrated comparable results to standard, manual clinical IA growth evaluation. Specifically, automatically calculated HMAX was superior (AUC = 0.958) at distinguishing growing and stable IA, followed by V, and SA (AUC = 0.927 and 0.917, respectively). Conclusion: Our findings support automatic methods of detecting IA growth from sequential imaging studies as a useful adjunct to standard clinical assessment. AGED-generated growth detection shows promise for characterization and detection of IA growth and time-saving comparing with manual measurements.

Deep Shape Features for Predicting Future Intracranial Aneurysm Growth.

Introduction: Intracranial aneurysms (IAs) are a common vascular pathology and are associated with a risk of rupture, which is often fatal. Aneurysm growth is considered a surrogate of rupture risk; therefore, the study aimed to develop and evaluate prediction models of future artificial intelligence (AI) growth based on baseline aneurysm morphology as a computer-aided treatment decision support. Materials and methods: Follow-up CT angiography (CTA) and magnetic resonance angiography (MRA) angiograms of 39 patients with 44 IAs were classified by an expert as growing and stable (25/19). From the angiograms vascular surface meshes were extracted and the aneurysm shape was characterized by established morphologic features and novel deep shape features. The features corresponding to the baseline aneurysms were used to predict future aneurysm growth using univariate thresholding, multivariate random forest and multi-layer perceptron (MLP) learning, and deep shape learning based on the PointNet++ model. Results: The proposed deep shape feature learning method achieved an accuracy of 0.82 (sensitivity = 0.96, specificity = 0.63), while the multivariate learning and univariate thresholding methods were inferior with an accuracy of up to 0.68 and 0.63, respectively. Conclusion: High-performing classification of future growing IAs renders the proposed deep shape features learning approach as the key enabling tool to manage rupture risk in the "no treatment" paradigm of patient follow-up imaging.

Impact of aerobic exercise on clinical and magnetic resonance imaging biomarkers in persons with multiple sclerosis: An exploratory randomized controlled trial.

BACKGROUND: There is insufficient knowledge about how aerobic exercise impacts the disease process of multiple sclerosis, which is characterized by accumulation of white matter lesions and accelerated brain atrophy. OBJECTIVE: To examine the effect of aerobic exercise on neuroinflammation and neurodegeneration by magnetic resonance imaging and clinical measures of disease activity and progression in persons with multiple sclerosis. PATIENTS AND METHODS: An exploratory 12-week randomized control trial including an intervention group (n = 14, 12 weeks of aerobic exercise twice weekly) and a control group (n = 14, continuation of usual lifestyle). Primary outcomes were magnetic resonance imaging measures (lesion load, brain structure volume change), while secondary outcomes included disability measures, blood cytokine levels, cognitive tests and patient-reported outcomes. RESULTS: The effects of aerobic exercise on whole brain and grey matter atrophy were minor. Surprisingly, the observed effect on volume (atrophy) in selected brain substructures was heterogeneous. Putaminal and posterior cingulate volumes decreased, parahippocampal gyrus volume increased, thalamus and amygdala volume remained the same, and active lesion load and count decreased. However, apart from weak improvements in walking speed and brain-derived neurotrophic factor levels, there was no effect of aerobic exercise on other clinical, cognitive or patient-reported outcomes. CONCLUSION: These results suggest that aerobic exercise in persons with multiple sclerosis has a positive effect on the volume of some of the substructures of the brain, possibly indicating a slowing of the neurodegenerative process in these regions, but a negative impact on the volume of some other substructures, with unclear implications. Further research is needed to determine whether the slight decrease in active lesion volume and count implies an anti-inflammatory effect of aerobic exercise, and the exact significance of the heterogeneous results of volumetric assessments.

Automated Cutting Plane Positioning for Intracranial Aneurysm Quantification.

OBJECTIVE: Aneurysm rupture risk can be assessed by its morphologic and hemodynamics features extracted based on angiographic images. Feature extraction entails aneurysm isolation, typically by manually positioning a cutting plane (MCP). To eliminate intra- and inter-rater variabilities, we propose automatic cutting plane (ACP) positioning based on the analysis of vascular surface mesh. METHODS: Innovative Hough-like and multi-hypothesis-based detection of aneurysm center, parent vessel inlets, and centerlines were proposed. These were used for initialization and iterative ACP positioning by geometry-inspired cost function optimization. For validation and baseline comparison, we tested MCP and manual neck curve-based isolation. Isolated aneurysm morphology was characterized by size, dome height, aspect ratio, and nonsphericity index. RESULTS: Methods were applied to 55 intracranial saccular aneurysms from two sites, involving 3-D digital subtraction angiography, computed tomography angiography, and magnetic resonance angiography modalities. Isolation based on ACP resulted in smaller average inter-curve distances (AICDs), compared to those obtained by MCP. One case had AICD higher than 1.0 mm, while 90% of cases had AICD 0.5 mm. Intra- and inter-rater AICD variability of manual neck curves was higher compared to MCP, validating its robustness for clinical purposes. CONCLUSION: The ACP method achieved high accuracy and reliability of aneurysm isolation, also confirmed by expert visual analysis. So extracted morphologic features were in good agreement with MCP-based ones, therefore, ACP has great potential for aneurysm morphology and hemodynamics quantification in clinical applications. SIGNIFICANCE: The novel method is angiographic modality agnostic; it delivers repeatable isolation important in follow-up aneurysm assessment; its performance is comparable to MCP; and re-evaluation is fast and simple.

Practical Priors for Bayesian Inference of Latent Biomarkers.

Latent biomarkers are quantities that strongly relate to patient's disease diagnosis and prognosis, but are difficult to measure or even not directly observable. The objective of this study was to develop, analyze and validate new priors for Bayesian inference of such biomarkers. Theoretical analysis revealed a relationship between the estimates inferred from the model and the true values of measured quantities, and the impact of the priors. This led to a new prior encoding scheme that incorporates objectively measurable domain knowledge, i.e. by performing two measurements with a reference method, which imply scale of the prior distribution. Second, priors on parameters of systematic error are non-informative, which enables biomarker estimation from a set of different quantities. Analysis showed that the volume of nucleus basalis of Meynert, which is reduced in early stages of Alzheimer's dementia and Parkinson's disease, is inter-related and could be inferred from compartmental brain volume measurements performed on routine clinical MR scans. Another experiment showed that total lesion load, associated to future disability progression in multiple sclerosis patients, could be inferred from lesion volume measurements based on multiple automated MR scan segmentations. Besides, figures of merit derived from the estimates could, without comparing against reference gold standard segmentations, identify the best performing lesion segmentation method. The proposed new priors substantially simplify the application of Bayesian inference for latent biomarkers and thus open an avenue for clinical implementation of new biomarkers, which may ultimately advance the evidence-based medicine.

Reference-free error estimation for multiple measurement methods.

We present a computational framework to select the most accurate and precise method of measurement of a certain quantity, when there is no access to the true value of the measurand. A typical use case is when several image analysis methods are applied to measure the value of a particular quantitative imaging biomarker from the same images. The accuracy of each measurement method is characterized by systematic error (bias), which is modeled as a polynomial in true values of measurand, and the precision as random error modeled with a Gaussian random variable. In contrast to previous works, the random errors are modeled jointly across all methods, thereby enabling the framework to analyze measurement methods based on similar principles, which may have correlated random errors. Furthermore, the posterior distribution of the error model parameters is estimated from samples obtained by Markov chain Monte-Carlo and analyzed to estimate the parameter values and the unknown true values of the measurand. The framework was validated on six synthetic and one clinical dataset containing measurements of total lesion load, a biomarker of neurodegenerative diseases, which was obtained with four automatic methods by analyzing brain magnetic resonance images. The estimates of bias and random error were in a good agreement with the corresponding least squares regression estimates against a reference.

3D-2D registration in endovascular image-guided surgery: evaluation of state-of-the-art methods on cerebral angiograms.

PURPOSE: Image guidance for minimally invasive surgery is based on spatial co-registration and fusion of 3D pre-interventional images and treatment plans with the 2D live intra-interventional images. The spatial co-registration or 3D-2D registration is the key enabling technology; however, the performance of state-of-the-art automated methods is rather unclear as they have not been assessed under the same test conditions. Herein we perform a quantitative and comparative evaluation of ten state-of-the-art methods for 3D-2D registration on a public dataset of clinical angiograms. METHODS: Image database consisted of 3D and 2D angiograms of 25 patients undergoing treatment for cerebral aneurysms or arteriovenous malformations. On each of the datasets, highly accurate "gold-standard" registrations of 3D and 2D images were established based on patient-attached fiducial markers. The database was used to rigorously evaluate ten state-of-the-art 3D-2D registration methods, namely two intensity-, two gradient-, three feature-based and three hybrid methods, both for registration of 3D pre-interventional image to monoplane or biplane 2D images. RESULTS: Intensity-based methods were most accurate in all tests (0.3 mm). One of the hybrid methods was most robust with 98.75% of successful registrations (SR) and capture range of 18 mm for registrations of 3D to biplane 2D angiograms. In general, registration accuracy was similar whether registration of 3D image was performed onto mono- or biplanar 2D images; however, the SR was substantially lower in case of 3D to monoplane 2D registration. Two feature-based and two hybrid methods had clinically feasible execution times in the order of a second. CONCLUSIONS: Performance of methods seems to fall below expectations in terms of robustness in case of registration of 3D to monoplane 2D images, while translation into clinical image guidance systems seems readily feasible for methods that perform registration of the 3D pre-interventional image onto biplanar intra-interventional 2D images.

Locally adaptive magnetic resonance intensity models for unsupervised segmentation of multiple sclerosis lesions.

Multiple sclerosis (MS) is a neurological disease characterized by focal lesions and morphological changes in the brain captured on magnetic resonance (MR) images. However, extraction of the corresponding imaging markers requires accurate segmentation of normal-appearing brain structures (NABS) and the lesions in MR images. On MR images of healthy brains, the NABS can be accurately captured by MR intensity mixture models, which, in combination with regularization techniques, such as in Markov random field (MRF) models, are known to give reliable NABS segmentation. However, on MR images that also contain abnormalities such as MS lesions, obtaining an accurate and reliable estimate of NABS intensity models is a challenge. We propose a method for automated segmentation of normal-appearing and abnormal structures in brain MR images that is based on a locally adaptive NABS model, a robust model parameters estimation method, and an MRF-based segmentation framework. Experiments on multisequence brain MR images of 30 MS patients show that, compared to whole-brain MR intensity model and compared to four popular unsupervised lesion segmentation methods, the proposed method increases the accuracy of MS lesion segmentation.

A Novel Public MR Image Dataset of Multiple Sclerosis Patients With Lesion Segmentations Based on Multi-rater Consensus.

Quantified volume and count of white-matter lesions based on magnetic resonance (MR) images are important biomarkers in several neurodegenerative diseases. For a routine extraction of these biomarkers an accurate and reliable automated lesion segmentation is required. To objectively and reliably determine a standard automated method, however, creation of standard validation datasets is of extremely high importance. Ideally, these datasets should be publicly available in conjunction with standardized evaluation methodology to enable objective validation of novel and existing methods. For validation purposes, we present a novel MR dataset of 30 multiple sclerosis patients and a novel protocol for creating reference white-matter lesion segmentations based on multi-rater consensus. On these datasets three expert raters individually segmented white-matter lesions, using in-house developed semi-automated lesion contouring tools. Later, the raters revised the segmentations in several joint sessions to reach a consensus on segmentation of lesions. To evaluate the variability, and as quality assurance, the protocol was executed twice on the same MR images, with a six months break. The obtained intra-consensus variability was substantially lower compared to the intra- and inter-rater variabilities, showing improved reliability of lesion segmentation by the proposed protocol. Hence, the obtained reference segmentations may represent a more precise target to evaluate, compare against and also train, the automatic segmentations. To encourage further use and research we will publicly disseminate on our website http://lit.fe.uni-lj.si/tools the tools used to create lesion segmentations, the original and preprocessed MR image datasets and the consensus lesion segmentations.

A framework for automatic creation of gold-standard rigid 3D-2D registration datasets.

PURPOSE: Advanced image-guided medical procedures incorporate 2D intra-interventional information into pre-interventional 3D image and plan of the procedure through 3D/2D image registration (32R). To enter clinical use, and even for publication purposes, novel and existing 32R methods have to be rigorously validated. The performance of a 32R method can be estimated by comparing it to an accurate reference or gold standard method (usually based on fiducial markers) on the same set of images (gold standard dataset). Objective validation and comparison of methods are possible only if evaluation methodology is standardized, and the gold standard  dataset is made publicly available. Currently, very few such datasets exist and only one contains images of multiple patients acquired during a procedure. To encourage the creation of gold standard 32R datasets, we propose an automatic framework. METHODS: The framework is based on rigid registration of fiducial markers. The main novelty is spatial grouping of fiducial markers on the carrier device, which enables automatic marker localization and identification across the 3D and 2D images. RESULTS: The proposed framework was demonstrated on clinical angiograms of 20 patients. Rigid 32R computed by the framework was more accurate than that obtained manually, with the respective target registration error below 0.027 mm compared to 0.040 mm. CONCLUSION: The framework is applicable for gold standard setup on any rigid anatomy, provided that the acquired images contain spatially grouped fiducial markers. The gold standard datasets and software will be made publicly available.

Validation of White-Matter Lesion Change Detection Methods on a Novel Publicly Available MRI Image Database.

Changes of white-matter lesions (WMLs) are good predictors of the progression of neurodegenerative diseases like multiple sclerosis (MS). Based on longitudinal magnetic resonance (MR) imaging the changes can be monitored, while the need for their accurate and reliable quantification led to the development of several automated MR image analysis methods. However, an objective comparison of the methods is difficult, because publicly unavailable validation datasets with ground truth and different sets of performance metrics were used. In this study, we acquired longitudinal MR datasets of 20 MS patients, in which brain regions were extracted, spatially aligned and intensity normalized. Two expert raters then delineated and jointly revised the WML changes on subtracted baseline and follow-up MR images to obtain ground truth WML segmentations. The main contribution of this paper is an objective, quantitative and systematic evaluation of two unsupervised and one supervised intensity based change detection method on the publicly available datasets with ground truth segmentations, using common pre- and post-processing steps and common evaluation metrics. Besides, different combinations of the two main steps of the studied change detection methods, i.e. dissimilarity map construction and its segmentation, were tested to identify the best performing combination.

Enhancement of Vascular Structures in 3D and 2D Angiographic Images.

A number of imaging techniques are being used for diagnosis and treatment of vascular pathologies like stenoses, aneurysms, embolisms, malformations and remodelings, which may affect a wide range of anatomical sites. For computer-aided detection and highlighting of potential sites of pathology or to improve visualization and segmentation, angiographic images are often enhanced by Hessian based filters. These filters aim to indicate elongated and/or rounded structures by an enhancement function based on Hessian eigenvalues. However, established enhancement functions generally produce a response, which exhibits deficiencies such as poor and non-uniform response for vessels of different sizes and varying contrast, at bifurcations and aneurysms. This may compromise subsequent analysis of the enhanced images. This paper has three important contributions: i) reviews several established enhancement functions and elaborates their deficiencies, ii) proposes a novel enhancement function, which overcomes the deficiencies of the established functions, and iii) quantitatively evaluates and compares the novel and the established enhancement functions on clinical image datasets of the lung, cerebral and fundus vasculatures.