The value of Augmented Reality in surgery - A usability study on laparoscopic liver surgery.

Augmented Reality (AR) is considered to be a promising technology for the guidance of laparoscopic liver surgery. By overlaying pre-operative 3D information of the liver and internal blood vessels on the laparoscopic view, surgeons can better understand the location of critical structures. In an effort to enable AR, several authors have focused on the development of methods to obtain an accurate alignment between the laparoscopic video image and the pre-operative 3D data of the liver, without assessing the benefit that the resulting overlay can provide during surgery. In this paper, we present a study that aims to assess quantitatively and qualitatively the value of an AR overlay in laparoscopic surgery during a simulated surgical task on a phantom setup. We design a study where participants are asked to physically localise pre-operative tumours in a liver phantom using three image guidance conditions - a baseline condition without any image guidance, a condition where the 3D surfaces of the liver are aligned to the video and displayed on a black background, and a condition where video see-through AR is displayed on the laparoscopic video. Using data collected from a cohort of 24 participants which include 12 surgeons, we observe that compared to the baseline, AR decreases the median localisation error of surgeons on non-peripheral targets from 25.8 mm to 9.2 mm. Using subjective feedback, we also identify that AR introduces usability improvements in the surgical task and increases the perceived confidence of the users. Between the two tested displays, the majority of participants preferred to use the AR overlay instead of navigated view of the 3D surfaces on a separate screen. We conclude that AR has the potential to improve performance and decision making in laparoscopic surgery, and that improvements in overlay alignment accuracy and depth perception should be pursued in the future.

Delineating COVID-19 subgroups using routine clinical data identifies distinct in-hospital outcomes.

The COVID-19 pandemic has been a great challenge to healthcare systems worldwide. It highlighted the need for robust predictive models which can be readily deployed to uncover heterogeneities in disease course, aid decision-making and prioritise treatment. We adapted an unsupervised data-driven model-SuStaIn, to be utilised for short-term infectious disease like COVID-19, based on 11 commonly recorded clinical measures. We used 1344 patients from the National COVID-19 Chest Imaging Database (NCCID), hospitalised for RT-PCR confirmed COVID-19 disease, splitting them equally into a training and an independent validation cohort. We discovered three COVID-19 subtypes (General Haemodynamic, Renal and Immunological) and introduced disease severity stages, both of which were predictive of distinct risks of in-hospital mortality or escalation of treatment, when analysed using Cox Proportional Hazards models. A low-risk Normal-appearing subtype was also discovered. The model and our full pipeline are available online and can be adapted for future outbreaks of COVID-19 or other infectious disease.

Registration of Untracked 2D Laparoscopic Ultrasound to CT Images of the Liver Using Multi-Labelled Content-Based Image Retrieval.

Laparoscopic Ultrasound (LUS) is recommended as a standard-of-care when performing laparoscopic liver resections as it images sub-surface structures such as tumours and major vessels. Given that LUS probes are difficult to handle and some tumours are iso-echoic, registration of LUS images to a pre-operative CT has been proposed as an image-guidance method. This registration problem is particularly challenging due to the small field of view of LUS, and usually depends on both a manual initialisation and tracking to compose a volume, hindering clinical translation. In this paper, we extend a proposed registration approach using Content-Based Image Retrieval (CBIR), removing the requirement for tracking or manual initialisation. Pre-operatively, a set of possible LUS planes is simulated from CT and a descriptor generated for each image. Then, a Bayesian framework is employed to estimate the most likely sequence of CT simulations that matches a series of LUS images. We extend our CBIR formulation to use multiple labelled objects and constrain the registration by separating liver vessels into portal vein and hepatic vein branches. The value of this new labeled approach is demonstrated in retrospective data from 5 patients. Results show that, by including a series of 5 untracked images in time, a single LUS image can be registered with accuracies ranging from 5.7 to 16.4 mm with a success rate of 78%. Initialisation of the LUS to CT registration with the proposed framework could potentially enable the clinical translation of these image fusion techniques.

Evaluation of MRI-derived surrogate signals to model respiratory motion.

An MR-Linac can provide motion information of tumour and organs-at-risk before, during, and after beam delivery. However, MR imaging cannot provide real-time high-quality volumetric images which capture breath-to-breath variability of respiratory motion. Surrogate-driven motion models relate the motion of the internal anatomy to surrogate signals, thus can estimate the 3D internal motion from these signals. Internal surrogate signals based on patient anatomy can be extracted from 2D cine-MR images, which can be acquired on an MR-Linac during treatment, to build and drive motion models. In this paper we investigate different MRI-derived surrogate signals, including signals generated by applying principal component analysis to the image intensities, or control point displacements derived from deformable registration of the 2D cine-MR images. We assessed the suitability of the signals to build models that can estimate the motion of the internal anatomy, including sliding motion and breath-to-breath variability. We quantitatively evaluated the models by estimating the 2D motion in sagittal and coronal slices of 8 lung cancer patients, and comparing them to motion measurements obtained from image registration. For sagittal slices, using the first and second principal components on the control point displacements as surrogate signals resulted in the highest model accuracy, with a mean error over patients around 0.80 mm which was lower than the in-plane resolution. For coronal slices, all investigated signals except the skin signal produced mean errors over patients around 1 mm. These results demonstrate that surrogate signals derived from 2D cine-MR images, including those generated by applying principal component analysis to the image intensities or control point displacements, can accurately model the motion of the internal anatomy within a single sagittal or coronal slice. This implies the signals should also be suitable for modelling the 3D respiratory motion of the internal anatomy.

Thoracic Imaging at Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review.

Exacerbations of chronic obstructive pulmonary disease (COPD) are currently diagnosed based on changes in respiratory symptoms. Characterizing the imaging manifestation of exacerbations could be useful for objective diagnosis of exacerbations in the clinic and clinical trials, as well as provide a mechanism for monitoring exacerbation treatment and recovery. In this systematic review, we employed a comprehensive search across three databases (Medline, EMBASE, Web of Science) to identify studies that performed imaging of the thorax at COPD exacerbation. We included 51 from a total of 5,047 articles which met all our inclusion criteria. We used an adapted version of the Modified Newcastle-Ottawa Quality Assessment Scale for cohort studies to assess the quality of the included studies. Conclusions were weighted towards higher-quality articles. We identified a total of 36 thoracic imaging features studied at exacerbation of COPD. Studies were generally heterogeneous in their measurements and focus. Nevertheless, considering studies which performed consecutive imaging at stable state and exacerbation, which scored highest for quality, we identified salient imaging biomarkers of exacerbations. An exacerbation is characterized by airway wall and airway calibre changes, hyperinflation, pulmonary vasoconstriction and imaging features suggestive of pulmonary arterial hypertension. Most information was gained from CT studies. We present the first ever composite imaging signature of COPD exacerbations. While imaging during an exacerbation is comparatively new and not comprehensively studied, it may uncover important insights into the acute pathophysiologic changes in the cardiorespiratory system during exacerbations of COPD, providing objective confirmation of events and a biomarker of recovery and treatment response.

Disease Progression Modeling in Chronic Obstructive Pulmonary Disease.

Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue→Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway→Tissue" subtype (n = 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r = -0.16 [P < 0.001] in the Tissue→Airway group; r = -0.14 [P = 0.011] in the Airway→Tissue group). SuStaIn placed 30% of smokers with normal lung function at elevated stages, suggesting imaging changes consistent with early COPD. Individuals with early changes were 2.5 times more likely to meet COPD diagnostic criteria at follow-up.Conclusions: We demonstrate two distinct patterns of disease progression in COPD using SuStaIn, likely representing different endotypes. One third of healthy smokers have detectable imaging changes, suggesting a new biomarker of "early COPD."

Reproducibility of an airway tapering measurement in computed tomography with application to bronchiectasis.

We propose a pipeline to acquire a scalar tapering measurement from the carina to the most distal point of an individual airway visible on computed tomography (CT). We show the applicability of using tapering measurements on clinically acquired data by quantifying the reproducibility of the tapering measure. We generate a spline from the centerline of an airway to measure the area and arclength at contiguous intervals. The tapering measurement is the gradient of the linear regression between area in log space and arclength. The reproducibility of the measure was assessed by analyzing different radiation doses, voxel sizes, and reconstruction kernel on single timepoint and longitudinal CT scans and by evaluating the effect of airway bifurcations. Using 74 airways from 10 CT scans, we show a statistical difference, p = 3.4 × 10 - 4 , in tapering between healthy airways ( n = 35 ) and those affected by bronchiectasis ( n = 39 ). The difference between the mean of the two populations is 0.011 mm - 1 , and the difference between the medians of the two populations was 0.006 mm - 1 . The tapering measurement retained a 95% confidence interval of ± 0.005 mm - 1 in a simulated 25 mAs scan and retained a 95% confidence of ± 0.005 mm - 1 on simulated CTs up to 1.5 times the original voxel size. We have established an estimate of the precision of the tapering measurement and estimated the effect on precision of the simulated voxel size and CT scan dose. We recommend that the scanner calibration be undertaken with the phantoms as described, on the specific CT scanner, radiation dose, and reconstruction algorithm that are to be used in any quantitative studies.

VERDICT MRI validation in fresh and fixed prostate specimens using patient-specific moulds for histological and MR alignment.

The VERDICT framework for modelling diffusion MRI data aims to relate parameters from a biophysical model to histological features used for tumour grading in prostate cancer. Validation of the VERDICT model is necessary for clinical use. This study compared VERDICT parameters obtained ex vivo with histology in five specimens from radical prostatectomy. A patient-specific 3D-printed mould was used to investigate the effects of fixation on VERDICT parameters and to aid registration to histology. A rich diffusion data set was acquired in each ex vivo prostate before and after fixation. At both time points, data were best described by a two-compartment model: the model assumes that an anisotropic tensor compartment represents the extracellular space and a restricted sphere compartment models the intracellular space. The effect of fixation on model parameters associated with tissue microstructure was small. The patient-specific mould minimized tissue deformations and co-localized slices, so that rigid registration of MRI to histology images allowed region-based comparison with histology. The VERDICT estimate of the intracellular volume fraction corresponded to histological indicators of cellular fraction, including high values in tumour regions. The average sphere radius from VERDICT, representing the average cell size, was relatively uniform across samples. The primary diffusion direction from the extracellular compartment of the VERDICT model aligned with collagen fibre patterns in the stroma obtained by structure tensor analysis. This confirmed the biophysical relationship between ex vivo VERDICT parameters and tissue microstructure from histology.

VERDICT-AMICO: Ultrafast fitting algorithm for non-invasive prostate microstructure characterization.

VERDICT (vascular, extracellular and restricted diffusion for cytometry in tumours) estimates and maps microstructural features of cancerous tissue non-invasively using diffusion MRI. The main purpose of this study is to address the high computational time of microstructural model fitting for prostate diagnosis, while retaining utility in terms of tumour conspicuity and repeatability. In this work, we adapt the accelerated microstructure imaging via convex optimization (AMICO) framework to linearize the estimation of VERDICT parameters for the prostate gland. We compare the original non-linear fitting of VERDICT with the linear fitting, quantifying accuracy with synthetic data, and computational time and reliability (performance and precision) in eight patients. We also assess the repeatability (scan-rescan) of the parameters. Comparison of the original VERDICT fitting versus VERDICT-AMICO showed that the linearized fitting (1) is more accurate in simulation for a signal-to-noise ratio of 20 dB; (2) reduces the processing time by three orders of magnitude, from 6.55 seconds/voxel to 1.78 milliseconds/voxel; (3) estimates parameters more precisely; (4) produces similar parametric maps and (5) produces similar estimated parameters with a high Pearson correlation between implementations, r2  > 0.7. The VERDICT-AMICO estimates also show high levels of repeatability. Finally, we demonstrate that VERDICT-AMICO can estimate an extra diffusivity parameter without losing tumour conspicuity and retains the fitting advantages. VERDICT-AMICO provides microstructural maps for prostate cancer characterization in seconds.

Spectral Imaging Of Thermal Damage Induced During Microwave Ablation In The Liver.

Induction of thermal damage to tissue through delivery of microwave energy is frequently applied in surgery to destroy diseased tissue such as cancer cells. Minimization of unwanted harm to healthy tissue is still achieved subjectively, and the surgeon has few tools at their disposal to monitor the spread of the induced damage. This work describes the use of optical methods to monitor the time course of changes to the tissue during delivery of microwave energy in the porcine liver. Multispectral imaging and diffuse reflectance spectroscopy are used to monitor temporal changes in optical properties in parallel with thermal imaging. The results demonstrate the ability to monitor the spatial extent of thermal damage on a whole organ, including possible secondary effects due to vascular damage. Future applications of this type of imaging may see the multispectral data used as a feedback mechanism to avoid collateral damage to critical healthy structures and to potentially verify sufficient application of energy to the diseased tissue.

Electromagnetic tracking in image-guided laparoscopic surgery: Comparison with optical tracking and feasibility study of a combined laparoscope and laparoscopic ultrasound system.

PURPOSE: In image-guided laparoscopy, optical tracking is commonly employed, but electromagnetic (EM) systems have been proposed in the literature. In this paper, we provide a thorough comparison of EM and optical tracking systems for use in image-guided laparoscopic surgery and a feasibility study of a combined, EM-tracked laparoscope and laparoscopic ultrasound (LUS) image guidance system. METHODS: We first assess the tracking accuracy of a laparoscope with two optical trackers tracking retroreflective markers mounted on the shaft and an EM tracker with the sensor embedded at the proximal end, using a standard evaluation plate. We then use a stylus to test the precision of position measurement and accuracy of distance measurement of the trackers. Finally, we assess the accuracy of an image guidance system comprised of an EM-tracked laparoscope and an EM-tracked LUS probe. RESULTS: In the experiment using a standard evaluation plate, the two optical trackers show less jitter in position and orientation measurement than the EM tracker. Also, the optical trackers demonstrate better consistency of orientation measurement within the test volume. However, their accuracy of measuring relative positions decreases significantly with longer distances whereas the EM tracker's performance is stable; at 50 mm distance, the RMS errors for the two optical trackers are 0.210 and 0.233 mm, respectively, and it is 0.214 mm for the EM tracker; at 250 mm distance, the RMS errors for the two optical trackers become 1.031 and 1.178 mm, respectively, while it is 0.367 mm for the EM tracker. In the experiment using the stylus, the two optical trackers have RMS errors of 1.278 and 1.555 mm in localizing the stylus tip, and it is 1.117 mm for the EM tracker. Our prototype of a combined, EM-tracked laparoscope and LUS system using representative calibration methods showed a RMS point localization error of 3.0 mm for the laparoscope and 1.3 mm for the LUS probe, the lager error of the former being predominantly due to the triangulation error when using a narrow-baseline stereo laparoscope. CONCLUSIONS: The errors incurred by optical trackers, due to the lever-arm effect and variation in tracking accuracy in the depth direction, would make EM-tracked solutions preferable if the EM sensor is placed at the proximal end of the laparoscope.

Circulating Growth and Sex Hormone Levels and Breast Tissue Composition in Young Nulliparous Women.

BACKGROUND: Endogenous hormones are associated with breast cancer risk, but little is known about their role on breast tissue composition, a strong risk predictor. This study aims to investigate the relationship between growth and sex hormone levels and breast tissue composition in young nulliparous women. METHODS: A cross-sectional study of 415 young (age ∼21.5 years) nulliparous women from an English prebirth cohort underwent a MRI examination of their breasts to estimate percent-water (a proxy for mammographic percent density) and provided a blood sample to measure plasma levels of growth factors (insulin-like growth factor-I, insulin-like growth factor-II, insulin growth factor-binding protein-3, growth hormone) and, if not on hormonal contraception (n = 117) sex hormones (dehydroepiandrosterone, androstenedione, testosterone, estrone, estadiol, sex hormone-binding globulin, prolactin). Testosterone (n = 330) and sex hormone-binding globulin (n = 318) were also measured at age 15.5 years. Regression models were used to estimate the relative difference (RD) in percent-water associated with one SD increment in hormone levels. RESULTS: Estradiol at age 21.5 and sex hormone-binding globulin at age 21.5 were positively associated with body mass index (BMI)-adjusted percent-water [RD (95% confidence interval (CI)): 3% (0%-7%) and 3% (1%-5%), respectively]. There was a positive nonlinear association between androstenedione at age 21.5 and percent-water. Insulin-like growth factor-I and growth hormone at age 21.5 were also positively associated with BMI-adjusted percent-water [RD (95% CI): 2% (0%-4%) and 4% (1%-7%), respectively]. CONCLUSIONS: The findings suggest that endogenous hormones affect breast tissue composition in young nulliparous women. IMPACT: The well-established associations of childhood growth and development with breast cancer risk may be partly mediated by the role of endogenous hormones on breast tissue composition.

Novel CT-Based Objective Imaging Biomarkers of Long-Term Radiation-Induced Lung Damage.

PURPOSE: Recent improvements in lung cancer survival have spurred an interest in understanding and minimizing long-term radiation-induced lung damage (RILD). However, there are still no objective criteria to quantify RILD, leading to variable reporting across centers and trials. We propose a set of objective imaging biomarkers for quantifying common radiologic findings observed 12 months after lung cancer radiation therapy. METHODS AND MATERIALS: Baseline and 12-month computed tomography (CT) scans of 27 patients from a phase 1/2 clinical trial of isotoxic chemoradiation were included in this study. To detect and measure the severity of RILD, 12 quantitative imaging biomarkers were developed. The biomarkers describe basic CT findings, including parenchymal change, volume reduction, and pleural change. The imaging biomarkers were implemented as semiautomated image analysis pipelines and were assessed against visual assessment of the occurrence of each change. RESULTS: Most of the biomarkers were measurable in each patient. The continuous nature of the biomarkers allows objective scoring of severity for each patient. For each imaging biomarker, the cohort was split into 2 groups according to the presence or absence of the biomarker by visual assessment, testing the hypothesis that the imaging biomarkers were different in the 2 groups. All features were statistically significant except for rotation of the main bronchus and diaphragmatic curvature. Most of the biomarkers were not strongly correlated with each other, suggesting that each of the biomarkers is measuring a separate element of RILD pathology. CONCLUSIONS: We developed objective CT-based imaging biomarkers that quantify the severity of radiologic lung damage after radiation therapy. These biomarkers are representative of typical radiologic findings of RILD.

Microstructure Characterization of Bone Metastases from Prostate Cancer with Diffusion MRI: Preliminary Findings.

PURPOSE: To examine the usefulness of rich diffusion protocols with high b-values and varying diffusion time for probing microstructure in bone metastases. Analysis techniques including biophysical and mathematical models were compared with the clinical apparent diffusion coefficient (ADC). METHODS: Four patients were scanned using 13 b-values up to 3,000 s/mm2 and diffusion times ranging 18-52 ms. Data were fitted to mono-exponential ADC, intravoxel incoherent motion (IVIM), Kurtosis and Vascular, extracellular, and restricted diffusion for cytometry in tumors (VERDICT) models. Parameters from the models were compared using correlation plots. RESULTS: ADC and IVIM did not fit the data well, failing to capture the signal at high b-values. The Kurtosis model best explained the data in many voxels, but in voxels exhibiting a more time-dependent signal, the VERDICT model explained the data best. The ADC correlated significantly (p < 0.004) with the intracellular diffusion coefficient (r = 0.48), intracellular volume fraction (r = -0.21), and perfusion fraction (r = 0.46) parameters from VERDICT, suggesting that these factors all contribute to ADC contrast. The mean kurtosis correlated with the intracellular volume fraction parameter (r = 0.26) from VERDICT, consistent with the hypothesis that kurtosis relates to cellularity, but also correlated weakly with the intracellular diffusion coefficient (r = 0.18) and cell radius (r = 0.16) parameters, suggesting that it may be difficult to attribute physical meaning to kurtosis. CONCLUSION: Both Kurtosis and VERDICT explained the diffusion signal better than ADC and IVIM, primarily due to poor fitting at high b-values in the latter two models. The Kurtosis and VERDICT models captured information at high b using parameters (Kurtosis or intracellular volume fraction and radius) that do not have a simple relationship with ADC and that may provide additional microstructural information in bone metastases.

Growth Trajectories, Breast Size, and Breast-Tissue Composition in a British Prebirth Cohort of Young Women.

Mammographic percent density, the proportion of fibroglandular tissue in the breast, is a strong risk factor for breast cancer, but its determinants in young women are unknown. We examined associations of magnetic resonance imaging (MRI) breast-tissue composition at age 21 years with prospectively collected measurements of body size and composition from birth to early adulthood and markers of puberty (all standardized) in a sample of 500 nulliparous women from a prebirth cohort of children born in Avon, United Kingdom, in 1991-1992 and followed up to 2011-2014. Linear models were fitted to estimate relative change in MRI percent water, which is equivalent to mammographic percent density, associated with a 1-standard-deviation increase in the exposure of interest. In mutually adjusted analyses, MRI percent water was positively associated with birth weight (relative change (RC) = 1.03, 95% confidence interval (CI): 1.00, 1.06) and pubertal height growth (RC = 1.07, 95% CI: 1.02, 1.13) but inversely associated with pubertal weight growth (RC = 0.86, 95% CI: 0.84, 0.89) and changes in dual-energy x-ray absorptiometry percent body fat mass (e.g., for change between ages 11 years and 13.5 years, RC = 0.96, 95% CI: 0.93, 0.99). Ages at thelarche and menarche were positively associated with MRI percent water, but these associations did not persist upon adjustment for height and weight growth. These findings support the hypothesis that growth trajectories influence breast-tissue composition in young women, whereas puberty plays no independent role.

Tumour auto-contouring on 2d cine MRI for locally advanced lung cancer: A comparative study.

BACKGROUND AND PURPOSE: Radiotherapy guidance based on magnetic resonance imaging (MRI) is currently becoming a clinical reality. Fast 2d cine MRI sequences are expected to increase the precision of radiation delivery by facilitating tumour delineation during treatment. This study compares four auto-contouring algorithms for the task of delineating the primary tumour in six locally advanced (LA) lung cancer patients. MATERIAL AND METHODS: Twenty-two cine MRI sequences were acquired using either a balanced steady-state free precession or a spoiled gradient echo imaging technique. Contours derived by the auto-contouring algorithms were compared against manual reference contours. A selection of eight image data sets was also used to assess the inter-observer delineation uncertainty. RESULTS: Algorithmically derived contours agreed well with the manual reference contours (median Dice similarity index: ⩾0.91). Multi-template matching and deformable image registration performed significantly better than feature-driven registration and the pulse-coupled neural network (PCNN). Neither MRI sequence nor image orientation was a conclusive predictor for algorithmic performance. Motion significantly degraded the performance of the PCNN. The inter-observer variability was of the same order of magnitude as the algorithmic performance. CONCLUSION: Auto-contouring of tumours on cine MRI is feasible in LA lung cancer patients. Despite large variations in implementation complexity, the different algorithms all have relatively similar performance.

Multiscale biphasic modelling of peritumoural collagen microstructure: The effect of tumour growth on permeability and fluid flow.

We present an in-silico model of avascular poroelastic tumour growth coupled with a multiscale biphasic description of the tumour-host environment. The model is specified to in-vitro data, facilitating biophysically realistic simulations of tumour spheroid growth into a dense collagen hydrogel. We use the model to first confirm that passive mechanical remodelling of collagen fibres at the tumour boundary is driven by solid stress, and not fluid pressure. The model is then used to demonstrate the influence of collagen microstructure on peritumoural permeability and interstitial fluid flow. Our model suggests that at the tumour periphery, remodelling causes the peritumoural stroma to become more permeable in the circumferential than radial direction, and the interstitial fluid velocity is found to be dependent on initial collagen alignment. Finally we show that solid stresses are negatively correlated with peritumoural permeability, and positively correlated with interstitial fluid velocity. These results point to a heterogeneous, microstructure-dependent force environment at the tumour-peritumoural stroma interface.

Breast MRI segmentation for density estimation: Do different methods give the same results and how much do differences matter?

PURPOSE: To compare two methods of automatic breast segmentation with each other and with manual segmentation in a large subject cohort. To discuss the factors involved in selecting the most appropriate algorithm for automatic segmentation and, in particular, to investigate the appropriateness of overlap measures (e.g., Dice and Jaccard coefficients) as the primary determinant in algorithm selection. METHODS: Two methods of breast segmentation were applied to the task of calculating MRI breast density in 200 subjects drawn from the Avon Longitudinal Study of Parents and Children, a large cohort study with an MRI component. A semiautomated, bias-corrected, fuzzy C-means (BC-FCM) method was combined with morphological operations to segment the overall breast volume from in-phase Dixon images. The method makes use of novel, problem-specific insights. The resulting segmentation mask was then applied to the corresponding Dixon water and fat images, which were combined to give Dixon MRI density values. Contemporaneously acquired T1 - and T2 -weighted image datasets were analyzed using a novel and fully automated algorithm involving image filtering, landmark identification, and explicit location of the pectoral muscle boundary. Within the region found, fat-water discrimination was performed using an Expectation Maximization-Markov Random Field technique, yielding a second independent estimate of MRI density. RESULTS: Images are presented for two individual women, demonstrating how the difficulty of the problem is highly subject-specific. Dice and Jaccard coefficients comparing the semiautomated BC-FCM method, operating on Dixon source data, with expert manual segmentation are presented. The corresponding results for the method based on T1 - and T2 -weighted data are slightly lower in the individual cases shown, but scatter plots and interclass correlations for the cohort as a whole show that both methods do an excellent job in segmenting and classifying breast tissue. CONCLUSIONS: Epidemiological results demonstrate that both methods of automated segmentation are suitable for the chosen application and that it is important to consider a range of factors when choosing a segmentation algorithm, rather than focus narrowly on a single metric such as the Dice coefficient.

A hybrid patient-specific biomechanical model based image registration method for the motion estimation of lungs.

This paper presents a new hybrid biomechanical model-based non-rigid image registration method for lung motion estimation. In the proposed method, a patient-specific biomechanical modelling process captures major physically realistic deformations with explicit physical modelling of sliding motion, whilst a subsequent non-rigid image registration process compensates for small residuals. The proposed algorithm was evaluated with 10 4D CT datasets of lung cancer patients. The target registration error (TRE), defined as the Euclidean distance of landmark pairs, was significantly lower with the proposed method (TRE = 1.37 mm) than with biomechanical modelling (TRE = 3.81 mm) and intensity-based image registration without specific considerations for sliding motion (TRE = 4.57 mm). The proposed method achieved a comparable accuracy as several recently developed intensity-based registration algorithms with sliding handling on the same datasets. A detailed comparison on the distributions of TREs with three non-rigid intensity-based algorithms showed that the proposed method performed especially well on estimating the displacement field of lung surface regions (mean TRE = 1.33 mm, maximum TRE = 5.3 mm). The effects of biomechanical model parameters (such as Poisson's ratio, friction and tissue heterogeneity) on displacement estimation were investigated. The potential of the algorithm in optimising biomechanical models of lungs through analysing the pattern of displacement compensation from the image registration process has also been demonstrated.