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.

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.

MCDataset: a public reference dataset of Monte Carlo simulated quantities for multilayered and voxelated tissues computed by massively parallel PyXOpto Python package.

SIGNIFICANCE: Current open-source Monte Carlo (MC) method implementations for light propagation modeling are many times tedious to build and require third-party licensed software that can often discourage prospective researchers in the biomedical optics community from fully utilizing the light propagation tools. Furthermore, the same drawback also limits rigorous cross-validation of physical quantities estimated by various MC codes. AIM: Proposal of an open-source tool for light propagation modeling and an easily accessible dataset to encourage fruitful communications amongst researchers and pave the way to a more consistent comparison between the available implementations of the MC method. APPROACH: The PyXOpto implementation of the MC method for multilayered and voxelated tissues based on the Python programming language and PyOpenCL extension enables massively parallel computation on numerous OpenCL-enabled devices. The proposed implementation is used to compute a large dataset of reflectance, transmittance, energy deposition, and sampling volume for various source, detector, and tissue configurations. RESULTS: The proposed PyXOpto agrees well with the original MC implementation. However, further validation reveals a noticeable bias introduced by the random number generator used in the original MC implementation. CONCLUSIONS: Establishing a common dataset is highly important for the validation of existing and development of MC codes for light propagation in turbid media.

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.

Fast and accurate Monte Carlo simulations of subdiffusive spatially resolved reflectance for a realistic optical fiber probe tip model aided by a deep neural network.

In this work, we introduce a framework for efficient and accurate Monte Carlo (MC) simulations of spatially resolved reflectance (SRR) acquired by optical fiber probes that account for all the details of the probe tip including reflectivity of the stainless steel and the properties of the epoxy fill and optical fibers. While using full details of the probe tip is essential for accurate MC simulations of SRR, the break-down of the radial symmetry in the detection scheme leads to about two orders of magnitude longer simulation times. The introduced framework mitigates this performance degradation, by an efficient reflectance regression model that maps SRR obtained by fast MC simulations based on a simplified probe tip model to SRR simulated using the full details of the probe tip. We show that a small number of SRR samples is sufficient to determine the parameters of the regression model. Finally, we use the regression model to simulate SRR for a stainless steel optical probe with six linearly placed fibers and experimentally validate the framework through the use of inverse models for estimation of absorption and reduced scattering coefficients and subdiffusive scattering phase function quantifiers.

Auto-segmentation of organs at risk for head and neck radiotherapy planning: From atlas-based to deep learning methods.

Radiotherapy (RT) is one of the basic treatment modalities for cancer of the head and neck (H&N), which requires a precise spatial description of the target volumes and organs at risk (OARs) to deliver a highly conformal radiation dose to the tumor cells while sparing the healthy tissues. For this purpose, target volumes and OARs have to be delineated and segmented from medical images. As manual delineation is a tedious and time-consuming task subjected to intra/interobserver variability, computerized auto-segmentation has been developed as an alternative. The field of medical imaging and RT planning has experienced an increased interest in the past decade, with new emerging trends that shifted the field of H&N OAR auto-segmentation from atlas-based to deep learning-based approaches. In this review, we systematically analyzed 78 relevant publications on auto-segmentation of OARs in the H&N region from 2008 to date, and provided critical discussions and recommendations from various perspectives: image modality - both computed tomography and magnetic resonance image modalities are being exploited, but the potential of the latter should be explored more in the future; OAR - the spinal cord, brainstem, and major salivary glands are the most studied OARs, but additional experiments should be conducted for several less studied soft tissue structures; image database - several image databases with the corresponding ground truth are currently available for methodology evaluation, but should be augmented with data from multiple observers and multiple institutions; methodology - current methods have shifted from atlas-based to deep learning auto-segmentation, which is expected to become even more sophisticated; ground truth - delineation guidelines should be followed and participation of multiple experts from multiple institutions is recommended; performance metrics - the Dice coefficient as the standard volumetric overlap metrics should be accompanied with at least one distance metrics, and combined with clinical acceptability scores and risk assessments; segmentation performance - the best performing methods achieve clinically acceptable auto-segmentation for several OARs, however, the dosimetric impact should be also studied to provide clinically relevant endpoints for RT planning.

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.

Variability Analysis of Manual and Computer-Assisted Preoperative Thoracic Pedicle Screw Placement Planning.

STUDY DESIGN: A comparison among preoperative pedicle screw placement plans, obtained from computed tomography (CT) images manually by two spine surgeons and automatically by a computer-assisted method. OBJECTIVE: To analyze and compare the manual and computer-assisted approach to pedicle screw placement planning in terms of the inter- and intraobserver variability. SUMMARY OF BACKGROUND DATA: Several methods for computer-assisted pedicle screw placement planning have been proposed; however, a systematic variability analysis against manual planning has not been performed yet. METHODS: For 256 pedicle screws, preoperative placement plans were determined manually by two experienced spine surgeons, each independently performing two sets of measurements by using a dedicated software for surgery planning. For the same 256 pedicle screws, preoperative placement plans were also obtained automatically by a computer-assisted method that was based on modeling of the vertebral structures in 3D, which were used to determine the pedicle screw size and insertion trajectory by maximizing its fastening strength through the underlying bone mineral density. RESULTS: A total of 1024 manually (2 observers × 2 sets × 256 screws) and 256 automatically (1 computer-assisted method × 256 screws) determined preoperative pedicle screw placement plans were obtained and compared in terms of the inter- and intraobserver variability. A large difference was observed for the pedicle screw sagittal inclination that was, in terms of the mean absolute difference and the corresponding standard deviation, equal to 18.3°â€Š±â€Š7.6° and 12.3°â€Š±â€Š6.5°, respectively for the intraobserver variability of the second observer and for the interobserver variability between the first observer and the computer-assisted method. CONCLUSION: The interobserver variability among the observers and the computer-assisted method is within the intraobserver variability of each observer, which indicates on the potential use of the computer-assisted approach as a useful tool for spine surgery that can be adapted according to the preferences of the surgeon. LEVEL OF EVIDENCE: 3.

Segmentation of parotid glands from registered CT and MR images.

PURPOSE: To develop an automatic multimodal method for segmentation of parotid glands (PGs) from pre-registered computed tomography (CT) and magnetic resonance (MR) images and compare its results to the results of an existing state-of-the-art algorithm that segments PGs from CT images only. METHODS: Magnetic resonance images of head and neck were registered to the accompanying CT images using two different state-of-the-art registration procedures. The reference domains of registered image pairs were divided on the complementary PG regions and backgrounds according to the manual delineation of PGs on CT images, provided by a physician. Patches of intensity values from both image modalities, centered around randomly sampled voxels from the reference domain, served as positive or negative samples in the training of the convolutional neural network (CNN) classifier. The trained CNN accepted a previously unseen (registered) image pair and classified its voxels according to the resemblance of its patches to the patches used for training. The final segmentation was refined using a graph-cut algorithm, followed by the dilate-erode operations. RESULTS: Using the same image dataset, segmentation of PGs was performed using the proposed multimodal algorithm and an existing monomodal algorithm, which segments PGs from CT images only. The mean value of the achieved Dice overlapping coefficient for the proposed algorithm was 78.8%, while the corresponding mean value for the monomodal algorithm was 76.5%. CONCLUSIONS: Automatic PG segmentation on the planning CT image can be augmented with the MR image modality, leading to an improved RT planning of head and neck cancer.

Efficient estimation of subdiffusive optical parameters in real time from spatially resolved reflectance by artificial neural networks.

Subdiffusive reflectance captured at short source-detector separations provides increased sensitivity to the scattering phase function and hence allows superficial probing of the tissue ultrastructure. Consequently, estimation of subdiffusive optical parameters has been the subject of many recent studies focusing on lookup-table-based (LUT) inverse models. Since an adequate description of the subdiffusive reflectance requires additional scattering phase function related optical parameters, the LUT inverse models, which grow exponentially with the number of estimated parameters, become excessively large and computationally inefficient. Herein, we propose, to the best of our knowledge, the first artificial-neural-network-based inverse Monte Carlo model that overcomes the limitations of the LUT inverse models and thus allows efficient real-time estimation of optical parameters from subdiffusive spatially resolved reflectance. The proposed inverse model retains the accuracy, is about four orders of magnitude faster than the LUT inverse models, grows only linearly with the number of estimated optical parameters, and can be easily extended to estimate additional optical parameters.

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.

Virtually increased acceptance angle for efficient estimation of spatially resolved reflectance in the subdiffusive regime: a Monte Carlo study.

Light propagation in biological tissues is frequently modeled by the Monte Carlo (MC) method, which requires processing of many photon packets to obtain adequate quality of the observed backscattered signal. The computation times further increase for detection schemes with small acceptance angles and hence small fraction of the collected backscattered photon packets. In this paper, we investigate the use of a virtually increased acceptance angle for efficient MC simulation of spatially resolved reflectance and estimation of optical properties by an inverse model. We devise a robust criterion for approximation of the maximum virtual acceptance angle and evaluate the proposed methodology for a wide range of tissue-like optical properties and various source configurations.

Lookup table-based sampling of the phase function for Monte Carlo simulations of light propagation in turbid media.

Analytical expressions for sampling the scattering angle from a phase function in Monte Carlo simulations of light propagation are available only for a limited number of phase functions. Consequently, numerical sampling methods based on tabulated values are often required instead. By using Monte Carlo simulated reflectance, we compare two existing and propose an improved numerical sampling method and show that both the number of the tabulated values and the numerical sampling method significantly influence the accuracy of the simulated reflectance. The provided results and guidelines should serve as a good starting point for conducting computationally efficient Monte Carlo simulations with numerical phase function sampling.

Adopting higher-order similarity relations for improved estimation of optical properties from subdiffusive reflectance.

Estimation of optical properties from subdiffusive reflectance acquired at short source-detector separations is challenging due to the sensitivity to the underlying scattering phase function. In recent studies, a second-order similarity parameter γ has been increasingly used alongside the absorption and reduced scattering coefficients to account for some of the phase function variability. By using Monte Carlo simulations, we show that the influence of the scattering phase function on the subdiffusive reflectance for the biologically relevant variations can be captured sufficiently well by considering γ and a third-order similarity parameter δ. Utilizing this knowledge, we construct an inverse model that estimates the absorption and reduced scattering coefficients, γ and δ, from spatially resolved reflectance. Nearly an order of magnitude smaller errors of the estimated optical properties are obtained in comparison to the inverse model that only composes γ.

Segmentation of Pathological Structures by Landmark-Assisted Deformable Models.

Computerized segmentation of pathological structures in medical images is challenging, as, in addition to unclear image boundaries, image artifacts, and traces of surgical activities, the shape of pathological structures may be very different from the shape of normal structures. Even if a sufficient number of pathological training samples are collected, statistical shape modeling cannot always capture shape features of pathological samples as they may be suppressed by shape features of a considerably larger number of healthy samples. At the same time, landmarking can be efficient in analyzing pathological structures but often lacks robustness. In this paper, we combine the advantages of landmark detection and deformable models into a novel supervised multi-energy segmentation framework that can efficiently segment structures with pathological shape. The framework adopts the theory of Laplacian shape editing, that was introduced in the field of computer graphics, so that the limitations of statistical shape modeling are avoided. The performance of the proposed framework was validated by segmenting fractured lumbar vertebrae from 3-D computed tomography images, atrophic corpora callosa from 2-D magnetic resonance (MR) cross-sections and cancerous prostates from 3D MR images, resulting respectively in a Dice coefficient of 84.7 ± 5.0%, 85.3 ± 4.8% and 78.3 ± 5.1%, and boundary distance of 1.14 ± 0.49mm, 1.42 ± 0.45mm and 2.27 ± 0.52mm. The obtained results were shown to be superior in comparison to existing deformable model-based segmentation algorithms.