Radiomic profiles improve prognostication and reveal targets for therapy in cervical cancer.

Cervical cancer (CC) is a major global health problem with 570,000 new cases and 266,000 deaths annually. Prognosis is poor for advanced stage disease, and few effective treatments exist. Preoperative diagnostic imaging is common in high-income countries and MRI measured tumor size routinely guides treatment allocation of cervical cancer patients. Recently, the role of MRI radiomics has been recognized. However, its potential to independently predict survival and treatment response requires further clarification. This retrospective cohort study demonstrates how non-invasive, preoperative, MRI radiomic profiling may improve prognostication and tailoring of treatments and follow-ups for cervical cancer patients. By unsupervised clustering based on 293 radiomic features from 132 patients, we identify three distinct clusters comprising patients with significantly different risk profiles, also when adjusting for FIGO stage and age. By linking their radiomic profiles to genomic alterations, we identify putative treatment targets for the different patient clusters (e.g., immunotherapy, CDK4/6 and YAP-TEAD inhibitors and p53 pathway targeting treatments).

MRI-based radiomic signatures for pretreatment prognostication in cervical cancer.

BACKGROUND: Accurate pretherapeutic prognostication is important for tailoring treatment in cervical cancer (CC). PURPOSE: To investigate whether pretreatment MRI-based radiomic signatures predict disease-specific survival (DSS) in CC. STUDY TYPE: Retrospective. POPULATION: CC patients (n = 133) allocated into training(T) (nT = 89)/validation(V) (nV = 44) cohorts. FIELD STRENGTH/SEQUENCE: T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) at 1.5T or 3.0T. ASSESSMENT: Radiomic features from segmented tumors were extracted from T2WI and DWI (high b-value DWI and apparent diffusion coefficient (ADC) maps). STATISTICAL TESTS: Radiomic signatures for prediction of DSS from T2WI (T2rad ) and T2WI with DWI (T2 + DWIrad ) were constructed by least absolute shrinkage and selection operator (LASSO) Cox regression. Area under time-dependent receiver operating characteristics curves (AUC) were used to evaluate and compare the prognostic performance of the radiomic signatures, MRI-derived maximum tumor size ≤/> 4 cm (MAXsize ), and 2018 International Federation of Gynecology and Obstetrics (FIGO) stage (I-II/III-IV). Survival was analyzed using Cox model estimating hazard ratios (HR) and Kaplan-Meier method with log-rank tests. RESULTS: The radiomic signatures T2rad and T2 + DWIrad yielded AUCT /AUCV of 0.80/0.62 and 0.81/0.75, respectively, for predicting 5-year DSS. Both signatures yielded better or equal prognostic performance to that of MAXsize (AUCT /AUCV : 0.69/0.65) and FIGO (AUCT /AUCV : 0.77/0.64) and were significant predictors of DSS after adjusting for FIGO (HRT /HRV for T2rad : 4.0/2.5 and T2 + DWIrad : 4.8/2.1). Adding T2rad and T2 + DWIrad to FIGO significantly improved DSS prediction compared to FIGO alone in cohort(T) (AUCT 0.86 and 0.88 vs. 0.77), and FIGO with T2 + DWIrad tended to the same in cohort(V) (AUCV 0.75 vs. 0.64, p = 0.07). High radiomic score for T2 + DWIrad was significantly associated with reduced DSS in both cohorts. DATA CONCLUSION: Radiomic signatures from T2WI and T2WI with DWI may provide added value for pretreatment risk assessment and for guiding tailored treatment strategies in CC.

Perfusion estimation using synthetic MRI-based measurements and a porous media flow model.

The measurement of perfusion and filtration of blood in biological tissue give rise to important clinical parameters used in diagnosis, follow-up, and therapy. In this paper, we address techniques for perfusion analysis using processed contrast agent concentration data from dynamic MRI acquisitions. A new methodology for analysis is evaluated and verified using synthetic data generated on a tissue geometry.

Assessing competence needs for doctors in the emergency department duty rosters: an observational study.

BACKGROUND: The purpose of our investigation is to analyze if emergency epidemiology is randomly variable or predictable. If emergency admissions show a predictable pattern, we can use it for multiple planning purposes, especially defining competence needs for duty roster personnel. METHOD: An observational study of consecutive emergency admissions at Haukeland University Hospital in Bergen over six years. We extracted the discharge diagnoses from our electronic patient record and sorted the patients by diagnoses and frequency. Data were loaded into a Jupyter notebook and presented in form of frequency diagrams. The study population, 213,801 patients, comprises all emergency admissions in need of secondary emergency care from the relevant specialities in the catchment area of our hospital in the western health region of Norway. Patients in need of tertiary care from the whole region are also included. RESULTS: Our analysis shows an annually reproducible distribution pattern regarding type and number of patients. The pattern adhere to an exponential curve that is stable from year to year. An exponential distribution pattern also applies when we sort patients according to the capital letters groups in the ICD 10 system. The same applies if patients are sorted adhering to primarily surgical or medical diagnoses. CONCLUSION: Analysis of the emergency epidemiology of all admitted emergency patients in a defined geographical area gives a solid basis for defining competence needs for duty roster work.

Modeling a 3-D multiscale blood-flow and heat-transfer framework for realistic vascular systems.

Modeling of biological domains and simulation of biophysical processes occurring in them can help inform medical procedures. However, when considering complex domains such as large regions of the human body, the complexities of blood vessel branching and variation of blood vessel dimensions present a major modeling challenge. Here, we present a Voxelized Multi-Physics Simulation (VoM-PhyS) framework to simulate coupled heat transfer and fluid flow using a multi-scale voxel mesh on a biological domain obtained. In this framework, flow in larger blood vessels is modeled using the Hagen-Poiseuille equation for a one-dimensional flow coupled with a three-dimensional two-compartment porous media model for capillary circulation in tissue. The Dirac distribution function is used as Sphere of Influence (SoI) parameter to couple the one-dimensional and three-dimensional flow. This blood flow system is coupled with a heat transfer solver to provide a complete thermo-physiological simulation. The framework is demonstrated on a frog tongue and further analysis is conducted to study the effect of convective heat exchange between blood vessels and tissue, and the effect of SoI on simulation results.

Fully Automatic Whole-Volume Tumor Segmentation in Cervical Cancer.

Uterine cervical cancer (CC) is the most common gynecologic malignancy worldwide. Whole-volume radiomic profiling from pelvic MRI may yield prognostic markers for tailoring treatment in CC. However, radiomic profiling relies on manual tumor segmentation which is unfeasible in the clinic. We present a fully automatic method for the 3D segmentation of primary CC lesions using state-of-the-art deep learning (DL) techniques. In 131 CC patients, the primary tumor was manually segmented on T2-weighted MRI by two radiologists (R1, R2). Patients were separated into a train/validation (n = 105) and a test- (n = 26) cohort. The segmentation performance of the DL algorithm compared with R1/R2 was assessed with Dice coefficients (DSCs) and Hausdorff distances (HDs) in the test cohort. The trained DL network retrieved whole-volume tumor segmentations yielding median DSCs of 0.60 and 0.58 for DL compared with R1 (DL-R1) and R2 (DL-R2), respectively, whereas DSC for R1-R2 was 0.78. Agreement for primary tumor volumes was excellent between raters (R1-R2: intraclass correlation coefficient (ICC) = 0.93), but lower for the DL algorithm and the raters (DL-R1: ICC = 0.43; DL-R2: ICC = 0.44). The developed DL algorithm enables the automated estimation of tumor size and primary CC tumor segmentation. However, segmentation agreement between raters is better than that between DL algorithm and raters.

A radiogenomics application for prognostic profiling of endometrial cancer.

Prognostication is critical for accurate diagnosis and tailored treatment in endometrial cancer (EC). We employed radiogenomics to integrate preoperative magnetic resonance imaging (MRI, n = 487 patients) with histologic-, transcriptomic- and molecular biomarkers (n = 550 patients) aiming to identify aggressive tumor features in a study including 866 EC patients. Whole-volume tumor radiomic profiling from manually (radiologists) segmented tumors (n = 138 patients) yielded clusters identifying patients with high-risk histological features and poor survival. Radiomic profiling by a fully automated machine learning (ML)-based tumor segmentation algorithm (n = 336 patients) reproduced the same radiomic prognostic groups. From these radiomic risk-groups, an 11-gene high-risk signature was defined, and its prognostic role was reproduced in orthologous validation cohorts (n = 554 patients) and aligned with The Cancer Genome Atlas (TCGA) molecular class with poor survival (copy-number-high/p53-altered). We conclude that MRI-based integrated radiogenomics profiling provides refined tumor characterization that may aid in prognostication and guide future treatment strategies in EC.

Automated segmentation of endometrial cancer on MR images using deep learning.

Preoperative MR imaging in endometrial cancer patients provides valuable information on local tumor extent, which routinely guides choice of surgical procedure and adjuvant therapy. Furthermore, whole-volume tumor analyses of MR images may provide radiomic tumor signatures potentially relevant for better individualization and optimization of treatment. We apply a convolutional neural network for automatic tumor segmentation in endometrial cancer patients, enabling automated extraction of tumor texture parameters and tumor volume. The network was trained, validated and tested on a cohort of 139 endometrial cancer patients based on preoperative pelvic imaging. The algorithm was able to retrieve tumor volumes comparable to human expert level (likelihood-ratio test, [Formula: see text]). The network was also able to provide a set of segmentation masks with human agreement not different from inter-rater agreement of human experts (Wilcoxon signed rank test, [Formula: see text], [Formula: see text], and [Formula: see text]). An automatic tool for tumor segmentation in endometrial cancer patients enables automated extraction of tumor volume and whole-volume tumor texture features. This approach represents a promising method for automatic radiomic tumor profiling with potential relevance for better prognostication and individualization of therapeutic strategy in endometrial cancer.

Whole-Volume Tumor MRI Radiomics for Prognostic Modeling in Endometrial Cancer.

BACKGROUND: In endometrial cancer (EC), preoperative pelvic MRI is recommended for local staging, while final tumor stage and grade are established by surgery and pathology. MRI-based radiomic tumor profiling may aid in preoperative risk-stratification and support clinical treatment decisions in EC. PURPOSE: To develop MRI-based whole-volume tumor radiomic signatures for prediction of aggressive EC disease. STUDY TYPE: Retrospective. POPULATION: A total of 138 women with histologically confirmed EC, divided into training (nT = 108) and validation cohorts (nV = 30). FIELD STRENGTH/SEQUENCE: Axial oblique T1 -weighted gradient echo volumetric interpolated breath-hold examination (VIBE) at 1.5T (71/138 patients) and DIXON VIBE at 3T (67/138 patients) at 2 minutes postcontrast injection. ASSESSMENT: Primary tumors were manually segmented by two radiologists with 4 and 8 years' of experience. Radiomic tumor features were computed and used for prediction of surgicopathologically-verified deep (≥50%) myometrial invasion (DMI), lymph node metastases (LNM), advanced stage (FIGO III + IV), nonendometrioid (NE) histology, and high-grade endometrioid tumors (E3). Corresponding analyses were also conducted using radiomics extracted from the axial oblique image slice depicting the largest tumor area. STATISTICAL TESTS: Logistic least absolute shrinkage and selection operator (LASSO) was applied for radiomic modeling in the training cohort. The diagnostic performances of the radiomic signatures were evaluated by area under the receiver operating characteristic curve in the training (AUCT ) and validation (AUCV ) cohorts. Progression-free survival was assessed using the Kaplan-Meier and Cox proportional hazard model. RESULTS: The whole-tumor radiomic signatures yielded AUCT /AUCV of 0.84/0.76 for predicting DMI, 0.73/0.72 for LNM, 0.71/0.68 for FIGO III + IV, 0.68/0.74 for NE histology, and 0.79/0.63 for high-grade (E3) tumor. Single-slice radiomics yielded comparable AUCT but significantly lower AUCV for LNM and FIGO III + IV (both P < 0.05). Tumor volume yielded comparable AUCT to the whole-tumor radiomic signatures for prediction of DMI, LNM, FIGO III + IV, and NE, but significantly lower AUCT for E3 tumors (P < 0.05). All of the whole-tumor radiomic signatures significantly predicted poor progression-free survival with hazard ratios of 4.6-9.8 (P < 0.05 for all). DATA CONCLUSION: MRI-based whole-tumor radiomic signatures yield medium-to-high diagnostic performance for predicting aggressive EC disease. The signatures may aid in preoperative risk assessment and hence guide personalized treatment strategies in EC. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

The association of PTSD symptom severity with amygdala nuclei volumes in traumatized youths.

The amygdala is a core component in neurobiological models of stress and stress-related pathologies, including post-traumatic stress disorder (PTSD). While numerous studies have reported increased amygdala activity following traumatic stress exposure and in PTSD, the findings regarding amygdala volume have been mixed. One reason for these mixed findings may be that the amygdala has been considered as a homogenous entity, while it in fact consists of several nuclei with unique cellular and connectivity profiles. Here, we investigated amygdala nuclei volumes of the basolateral and the centrocorticomedial complex in relation to PTSD symptom severity in 47 young survivors from the 2011 Norwegian terror attack 24-36 months post-trauma. PTSD symptoms were assessed 4-5, 14-15 and 24-36 months following the trauma. We found that increased PTSD symptom severity 24-36 months post-trauma was associated with volumetric reductions of all basolateral as well as the central and the medial nuclei. However, only the lateral nucleus was associated with longitudinal symptom development, and mediated the association between 4-5 months and 24-36 months post-trauma symptoms. The results suggest that the amygdala nuclei may be differentially associated with cross-sectional and longitudinal measures of PTSD symptom severity. As such, investigations of amygdala total volume may not provide an adequate index of the association between amygdala and stress-related mental illness.

A new framework for assessing subject-specific whole brain circulation and perfusion using MRI-based measurements and a multi-scale continuous flow model.

A large variety of severe medical conditions involve alterations in microvascular circulation. Hence, measurements or simulation of circulation and perfusion has considerable clinical value and can be used for diagnostics, evaluation of treatment efficacy, and for surgical planning. However, the accuracy of traditional tracer kinetic one-compartment models is limited due to scale dependency. As a remedy, we propose a scale invariant mathematical framework for simulating whole brain perfusion. The suggested framework is based on a segmentation of anatomical geometry down to imaging voxel resolution. Large vessels in the arterial and venous network are identified from time-of-flight (ToF) and quantitative susceptibility mapping (QSM). Macro-scale flow in the large-vessel-network is accurately modelled using the Hagen-Poiseuille equation, whereas capillary flow is treated as two-compartment porous media flow. Macro-scale flow is coupled with micro-scale flow by a spatially distributing support function in the terminal endings. Perfusion is defined as the transition of fluid from the arterial to the venous compartment. We demonstrate a whole brain simulation of tracer propagation on a realistic geometric model of the human brain, where the model comprises distinct areas of grey and white matter, as well as large vessels in the arterial and venous vascular network. Our proposed framework is an accurate and viable alternative to traditional compartment models, with high relevance for simulation of brain perfusion and also for restoration of field parameters in clinical brain perfusion applications.

In Vivo Detection of Chronic Kidney Disease Using Tissue Deformation Fields From Dynamic MR Imaging.

OBJECTIVE: Chronic kidney disease (CKD) is a serious medical condition characterized by gradual loss of kidney function. Early detection and diagnosis is mandatory for adequate therapy and prognostic improvement. Hence, in the current pilot study we explore the use of image registration methods for detecting renal morphologic changes in patients with CKD. METHODS: Ten healthy volunteers and nine patients with presumed CKD underwent dynamic T1 weighted imaging without contrast agent. From real and simulated dynamic time series, kidney deformation fields were estimated using a poroelastic deformation model. From the deformation fields several quantitative parameters reflecting pressure gradients, and volumetric and shear deformations were computed. Eight of the patients also underwent a kidney biopsy as a gold standard. RESULTS: We found that the absolute deformation, normalized volume changes, as well as pressure gradients correlated significantly with arteriosclerosis from biopsy assessments. Furthermore, our results indicate that current image registration methodologies are lacking sensitivity to recover mild changes in tissue stiffness. CONCLUSION: Image registration applied to dynamic time series correlated with structural renal changes and should be further explored as a tool for invasive measurements of arteriosclerosis. SIGNIFICANCE: Under the assumption that the proposed framework can be further developed in terms of sensitivity and specificity, it can provide clinicians with a non-invasive tool of high spatial coverage available for characterization of arteriosclerosis and potentially other pathological changes observed in chronic kidney disease.

Estimating the discretization dependent accuracy of perfusion in coupled capillary flow measurements.

One-compartment models are widely used to quantify hemodynamic parameters such as perfusion, blood volume and mean transit time. These parameters are routinely used for clinical diagnosis and monitoring of disease development and are thus of high relevance. However, it is known that common estimation techniques are discretization dependent and values can be erroneous. In this paper we present a new model that enables systematic quantification of discretization errors. Specifically, we introduce a continuous flow model for tracer propagation within the capillary tissue, used to evaluate state-of-the-art one-compartment models. We demonstrate that one-compartment models are capable of recovering perfusion accurately when applied to only one compartment, i.e. the whole region of interest. However, substantial overestimation of perfusion occurs when applied to fractions of a compartment. We further provide values of the estimated overestimation for various discretization levels, and also show that overestimation can be observed in real-life applications. Common practice of using compartment models for fractions of tissue violates model assumptions and careful interpretation is needed when using the computed values for diagnosis and treatment planning.

Workflow sensitivity of post-processing methods in renal DCE-MRI.

OBJECTIVE: Estimation of renal filtration using dynamic contrast-enhanced imaging (DCE-MRI) requires a series of analysis steps. The possible number of distinct post-processing chains is large and grows rapidly with increasing number of processing steps or options. In this study we introduce a framework for systematic evaluation of the post-processing chains. The framework is later used to highlight the workflow processing chain sensitivity towards accuracy in estimation of glomerular filtration rate (GFR). METHODS: Twenty healthy volunteers underwent DCE-MRI examinations as well as iohexol clearance for reference GFR measurements. In total, 692 different combinations of post-processing steps were explored for analysis, including options for kidney segmentation, B1 inhomogeneity correction, placement of arterial input function, gadolinium concentration estimation as well as handling of motion-corrupted volumes and breathing motion. The evaluation of various processing chains is presented using a classification tree framework and random forest ensemble learning. RESULTS: Among the processing steps subject to testing, methods for calculating the gadolinium concentration as well as B1 inhomogeneity correction had the largest impact on accuracy of GFR estimations. Different segmentation methods did not play an important role in the post-processing of the MR data except from one processing chain where the automated segmentation outperformed the manual segmentation. CONCLUSION: The proposed classification trees were efficiently used as a statistical tool for visualization and communication of results to distinguish between important and less influential processing steps in renal DCE-MRI. We also identified several crucial factors in the processing chain.

Semi-automatic 3D morphological reconstruction of neurons with densely branching morphology: Application to retinal AII amacrine cells imaged with multi-photon excitation microscopy.

BACKGROUND: Accurate reconstruction of the morphology of single neurons is important for morphometric studies and for developing compartmental models. However, manual morphological reconstruction can be extremely time-consuming and error-prone and algorithms for automatic reconstruction can be challenged when applied to neurons with a high density of extensively branching processes. NEW METHOD: We present a procedure for semi-automatic reconstruction specifically adapted for densely branching neurons such as the AII amacrine cell found in mammalian retinas. We used whole-cell recording to fill AII amacrine cells in rat retinal slices with fluorescent dyes and acquired digital image stacks with multi-photon excitation microscopy. Our reconstruction algorithm combines elements of existing procedures, with segmentation based on adaptive thresholding and reconstruction based on a minimal spanning tree. We improved this workflow with an algorithm that reconnects neuron segments that are disconnected after adaptive thresholding, using paths extracted from the image stacks with the Fast Marching method. RESULTS: By reducing the likelihood that disconnected segments were incorrectly connected to neighboring segments, our procedure generated excellent morphological reconstructions of AII amacrine cells. COMPARISON WITH EXISTING METHODS: Reconstructing an AII amacrine cell required about 2h computing time, compared to 2-4days for manual reconstruction. To evaluate the performance of our method relative to manual reconstruction, we performed detailed analysis using a measure of tree structure similarity (DIADEM score), the degree of projection area overlap (Dice coefficient), and branch statistics. CONCLUSIONS: We expect our procedure to be generally useful for morphological reconstruction of neurons filled with fluorescent dyes.

Dynamic contrast-enhanced MRI measurement of renal function in healthy participants.

Background High repeatability, accuracy, and precision for renal function measurements need to be achieved to establish renal dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a clinically useful diagnostic tool. Purpose To investigate the repeatability, accuracy, and precision of DCE-MRI measured renal perfusion and glomerular filtration rate (GFR) using iohexol-GFR as the reference method. Material and Methods Twenty healthy non-smoking volunteers underwent repeated DCE-MRI and an iohexol-GFR within a period of 10 days. Single-kidney (SK) MRI measurements of perfusion (blood flow, Fb) and filtration (GFR) were derived from parenchymal intensity time curves fitted to a two-compartment filtration model. The repeatability of the SK-MRI measurements was assessed using coefficient of variation (CV). Using iohexol-GFR as reference method, the accuracy of total MR-GFR was determined by mean difference (MD) and precision by limits of agreement (LoA). Results SK-Fb (MR1, 345 ± 84; MR2, 371 ± 103 mL/100 mL/min) and SK-GFR (MR1, 52 ± 14; MR2, 54 ± 10 mL/min/1.73 m2) measurements achieved a repeatability (CV) in the range of 15-22%. With reference to iohexol-GFR, MR-GFR was determined with a low mean difference but high LoA (MR1, MD 1.5 mL/min/1.73 m2, LoA [-42, 45]; MR2, MD 6.1 mL/min/1.73 m2, LoA [-26, 38]). Eighty percent and 90% of MR-GFR measurements were determined within ± 30% of the iohexol-GFR for MR1 and MR2, respectively. Conclusion Good repeatability of SK-MRI measurements and good agreement between MR-GFR and iohexol-GFR provide a high clinical potential of DCE-MRI for renal function assessment. A moderate precision in MR-derived estimates indicates that the method cannot yet be used in clinical routine.

Quantification of Single-Kidney Function and Volume in Living Kidney Donors Using Dynamic Contrast-Enhanced MRI.

OBJECTIVE: The objective of our study was to investigate whether dynamic contrast-enhanced MRI (DCE-MRI) can detect differences and potential adaption in single-kidney parenchymal volume, blood flow, glomerular filtration rate (GFR), and filtration fraction in the remaining kidney of healthy donors compared with nondonors. Further, we evaluated the agreement in donor GFRs measured using DCE-MRI versus serum clearance of iohexol. SUBJECTS AND METHODS: Twenty living kidney donors and 20 healthy control subjects underwent DCE-MRI and iohexol GFR. Renal parenchymal volume was assessed from maximum-signal-intensity maps. Single-kidney MRI measurements of blood flow and GFR were derived from parenchymal signal intensity-time curves fitted to a two-compartment filtration model. The Student t test, Pearson correlation coefficient, mean differences, and limits of agreement were applied to analyze MRI measurements between groups and agreement with iohexol GFR. RESULTS: MRI findings showed significantly higher blood flow (difference in mean values of donors vs control subjects, 54%; p = 0.001), GFR (78%, p < 0.0001), and renal parenchymal volume (65%, p < 0.0001) in the single kidney of donors compared with the single kidney of healthy control subjects. In the donors, a proportional increase in blood flow and GFR resulted in a comparable filtration fraction, as was observed in the control subjects. Significant correlations were found between MRI-derived GFR and parenchymal volume (p < 0.0016) as well as with iohexol GFR (p < 0.0001). The mean difference between MRI-derived GFR and iohexol GFR was 14.0 mL/min, and the limits of agreement between MRI-derived GFR and iohexol GFR were -24.1 and 52.1 mL/min. CONCLUSION: DCE-MRI-derived values for single-kidney function and volume in kidney donors were significantly higher than those in control subjects and suggest a future potential benefit of DCE-MRI for diagnostic and prognostic structural and functional assessments in living kidney donors.

Physical Models for Simulation and Reconstruction of Human Tissue Deformation Fields in Dynamic MRI.

OBJECTIVE: Medical image registration can be formulated as a tissue deformation problem, where parameter estimation methods are used to obtain the inverse deformation. However, there is limited knowledge about the ability to recover an unknown deformation. The main objective of this study is to estimate the quality of a restored deformation field obtained from image registration of dynamic MR sequences. METHODS: We investigate the behavior of forward deformation models of various complexities. Further, we study the accuracy of restored inverse deformations generated by image registration. RESULTS: We found that the choice of 1) heterogeneous tissue parameters and 2) a poroelastic (instead of elastic) model had significant impact on the forward deformation. In the image registration problem, both 1) and 2) were found not to be significant. Here, the presence of image features were dominating the performance. We also found that existing algorithms will align images with high precision while at the same time obtain a deformation field with a relative error of 40%. CONCLUSION: Image registration can only moderately well restore the true deformation field. Still, estimation of volume changes instead of deformation fields can be fairly accurate and may represent a proxy for variations in tissue characteristics. Volume changes remain essentially unchanged under choice of discretization and the prevalence of pronounced image features. SIGNIFICANCE: We suggest that image registration of high-contrast MR images has potential to be used as a tool to produce imaging biomarkers sensitive to pathology affecting tissue stiffness.

PDE Based Algorithms for Smooth Watersheds.

Watershed segmentation is useful for a number of image segmentation problems with a wide range of practical applications. Traditionally, the tracking of the immersion front is done by applying a fast sorting algorithm. In this work, we explore a continuous approach based on a geometric description of the immersion front which gives rise to a partial differential equation. The main advantage of using a partial differential equation to track the immersion front is that the method becomes versatile and may easily be stabilized by introducing regularization terms. Coupling the geometric approach with a proper "merging strategy" creates a robust algorithm which minimizes over- and under-segmentation even without predefined markers. Since reliable markers defined prior to segmentation can be difficult to construct automatically for various reasons, being able to treat marker-free situations is a major advantage of the proposed method over earlier watershed formulations. The motivation for the methods developed in this paper is taken from high-throughput screening of cells. A fully automated segmentation of single cells enables the extraction of cell properties from large data sets, which can provide substantial insight into a biological model system. Applying smoothing to the boundaries can improve the accuracy in many image analysis tasks requiring a precise delineation of the plasma membrane of the cell. The proposed segmentation method is applied to real images containing fluorescently labeled cells, and the experimental results show that our implementation is robust and reliable for a variety of challenging segmentation tasks.