| 1. |
- West, Janne
(författare)
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Quantitative Magnetic Resonance Imaging of the Brain : Applications for Tissue Segmentation and Multiple Sclerosis
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Magnetic resonance imaging (MRI) is a sensitive technique for assessing white matter (WM) lesions in multiple sclerosis (MS), but there is a low correlation between MRI findings and clinical disability. Because of this, other pathological changes are of interest, including changes in normal appearing white matter (NAWM) and diffusely abnormal white matter (DAWM). Even so, the mechanisms leading to permanent disability in MS remain unclear.In contrast to conventional MRI, quantitative MRI (qMRI) is aimed at the direct measurement of the physical tissue properties, such as the relaxation times, T1 and T2, as well as the proton density (PD). QMRI is promising for characterising and quantifying changes in MS and for brain tissue segmentation.The present work describes a novel method of qMRI for the human brain (QMAP), and a segmentation method based on this. The developed methods were validated in control subjects and MR phantoms. Furthermore, an application in diseased human brain was demonstrated in MS patients. In all, 50 healthy controls and 35 MS patients were scanned with qMRI in a total of 225 acquisitions.One major finding of this work was that qMRI was able to detect and quantify changes in the MS disease that were not visible using conventional MRI. In particular, it was found that DAWM appears to constitute an intermediate between focal white matter (WM) lesions and NAWM. These changes may be caused by pathological processes that are not entirely attributable to Wallerian degeneration.This study showed that the QMAP method had high accuracy and relatively high precision, within a clinically acceptable time. This work also demonstrated that qMRI could be used for brain tissue segmentation and volume estimation of the whole brain, using pre-defined tissue characteristics. The results showed that brain tissue segmentation had high repeatability, which was somewhat lower when different geometries were acquired or different field strengths used. In particular, small differences were found between 1.5 T and 3.0 T in deep brain structures, the cerebellum and the brain stem.This work leads the way for early clinical applications of qMRI, and the challenge for the years to come is to understand the connection between qMRI properties of the brain and underlying biology.
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| 2. |
- Dahlström, Nils, 1969-
(författare)
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Quantitative Evaluation of Contrast Agent Dynamics in Liver MRI
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The studies presented here evaluate the biliary, parenchymal and vascular enhancement effects of two T1-shortening liver-specific contrast agents, Gd-BOPTA and Gd-EOB-DTPA, in Magnetic Resonance Imaging (MRI) of healthy subjects and of patients.Ten healthy volunteers were examined with both contrast agents in a 1.5 T MRI system using three-dimensional gradient echo sequences for dynamic imaging until five hours after injection. The enhancement of the common hepatic duct in contrast to the liver parenchyma was analyzed in the first study. This was followed by a study of the image contrasts of the hepatic artery, portal vein and middle hepatic vein versus the liver parenchyma.While Gd-EOB-DTPA gave an earlier and more prolonged enhancement and image contrast of the bile duct, Gd-BOPTA achieved higher maximal enhancement and higher image contrast for all vessels studied during the arterial and portal venous phases. There was no significant difference in the maximal enhancement obtained in the liver parenchyma.In a third study, another 10 healthy volunteers were examined with the same protocol in another 1.5 T MRI system. Using signal normalization and a more quantitative, pharmacokinetic analysis, the hepatocyte-specific uptake of Gd-EOB-DTPA and Gd-BOPTA was calculated. A significant between-subjects correlation of the uptake estimates was found and the ratio of these uptake rates was of the same magnitude as has been reported in pre-clinical studies. The procedure also enabled quantitative analysis of vascular enhancement properties of these agents. Gd-BOPTA was found to give higher vessel-to-liver contrast than Gd-EOB-DTPA when recommended doses were given.In the final study, retrospectively gathered datasets from patients with hepatobiliary disease were analyzed using the quantitative estimation of hepatic uptake of Gd-EOB-DTPA described in the third study. The uptake rate estimate provided significant predictive ability in separating normal from disturbed hepatobiliary function, which is promising for future evaluations of regional and global liver disease.In conclusion, the differing dynamic enhancement profiles of the liver-specific contrast agents presented here can be beneficial in one context and challenging in another. Diseases of the liver and biliary system may affect the vasculature, parenchyma or biliary excretion, or a combination of these. The clinical context in terms of the relative importance of vascular, hepatic parenchymal and biliary processes should therefore determine the contrast agent for each patient and examination. A quantitative approach to analysis of contrast-enhanced liver MRI examinations is feasible and may prove valuable for their interpretation.
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| 3. |
- Hedlund, Anna, 1973-
(författare)
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MRI Contrast Enhancement and Cell Labeling using Gd2O3 Nanoparticles
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is an increasing interest for nanomaterials in bio-medical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3 ) have been investigated as a novel contrast agent for magnetic resonance imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as such multimodal contrast agent. Relaxivity measurements show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and an increase in signal intensity in T1-mapped images. The cellular uptake of Gd2O3 nanoparticles were increased with the use of transfection agent protamine sulfate. This work shows that Gd2O3 nanoparticles possess good relaxation properties that are retained in different biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in forinstance cell labeling experiments.
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| 4. |
- Tisell, Anders
(författare)
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The Non-Invasive Brain Biopsy : Implementation and Application of Quantitative Magnetic Resonance Spectroscopy on Healthy and Diseased Human Brain
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: In this thesis, one of the major objectives was to implement a method for (absolute) quantitative magnetic resonance spectroscopy (qMRS) of the human brain, intended for clinical use. The implemented method was based on standard spatially selective MRS sequences. The tissue water was used as an internal reference, which was calibrated using whole brain quantitative magnetic resonance imaging (qMRI). The second objective was to apply the method in clinical neuroimaging investigation, of different disease processes in the human brain.Materials and Methods: In total, 158 subjects were included and 507 MRS measurements (330 in white matter and 177 in the thalamus) were acquired.In a cross-sectional study of multiple sclerosis (MS), 35 ‘clinically definite MS’ (CDMS) patients were included, of which 15 were atypical CDMS patients with a very low number of white matter lesions (two or fewer), and 20 were typical CDMS patients with white matter lesions (three or more) were included. The metabolite concentrations in normal appearing white matter (NAWM) and the thalamus were assessed using the qMRS method developed in this thesis, and the brain parenchymal fraction (BPF) was calculated from the qMRI data. A cohort of 27 CDMS patients were then treated with Natalizumab and examined both at baseline, and after one year of treatment. Both qMRS and CSF samples for the purpose of assessing intrathecal inflammation were obtained. In addition, the frontal deep white matter (FDWM) and the thalamus were investigated in 20 idiopathic normal pressure hydrocephalus (iNPH) patients using qMRS. Finally, the left thalamus of 14 Kleine-Levin Syndrome (KLS) patients were examined using both qMRS and functional MRI (fMRI) of neurological activation of the left thalamus during a working memory test. Moreover, 63 healthy subjects were included as controls for this work.Results: A quantitative MRS method based on water referencing was successfully developed, implemented, and evaluated at 1.5 T. Both healthy subjects and MS patients showed a positive correlation between the concentrations of total Creatine (tCr) and myo Inositol (mIns) and age, and also a negative correlation with BPF were observed. Glutamate and Glutamine (Glx) levels were elevated for all MS patient groups compared to healthy controls. In contrast, lower concentrations of total N-acetyl aspartate and N-acetyl aspartate glutamate (tNA) and higher mIns concentrations in NAWM were only observed in MS patients that had developed white matter lesions. Moreover, the change in concentrations of tCr and total Choline (tCho) in MS patients during Natalizumab-treatment were positively correlated with markers of intrathecal inflammation. The iNPH patients had lower tNA and N-acetyl aspartate (NAA) concentrations in the thalamus compared to the controls. In addition, the NAA concentrations in the left thalamus were inversely correlated to the fMRI activation in the left thalamus during the working memory test in KLS patients.Discussion: The calculated calibration factors were in good agreement with the results found in the literature, indicating that the calibration factors were accurate.The observed elevated Glx concentration in MS could be due to increased concentrations of glutamate (Glu), which is neurotoxic at high concentrations, thus the elevated Glx could be linked to the clinically observed neurodegeneration in MS both in patients that have developed lesions and in atypical patients that do not develop any (or extremely few) lesions.Both tCr and mIns can be used as glia markers, thus the correlations of tCr and mIns concentrations with both age and BPF indicates that the local glia cell density, or tissue fraction, increases with age and atrophy. Moreover, the higher mIns concentrations in the NAWM of MS patients with a substantial white matter lesion load indicate that the glia tissue amount in NAWM is increased in MS patients that develop lesions. NAA is neuronal-specific, thus the lower tNA concentrations indicate that the neurone concentration is lower in the NAWM of MS patients that develop MS lesions. The lack of correlation between tNA with age and BPF in combination with the presence of correlation between tCr and mIns with both age and BPF, might be explained using a model for neurodegeneration. In which, there is a higher neurone loss compared to the glia loss. However, the lost tissue is compensated by compression of the tissue, which keeps the density of neurones more or less constant and the density of glia increased.The low concentration levels of the neuronal marker NAA in the thalamus of the iNPH patients indicates that the basal ganglia-thalamic-subcortical frontal circuits are damage or at least strongly modulated in the thalamus.The correlation between strong activation in left thalamus during a working memory test with the neuronal marker NAA indicate that the KLS patients that have low neuronal concentration also needed to utilise the working memory circuitry more heavily in order to perform the task as healthy subjects.Conclusion: It is possible to use qMRI for accurate and robust determination of qMRS in clinical practice, even at 1.5 T field strength. The tGlx concentration may be an important marker for pathology in the nonlesional white matter of MS-patients. The increased glia and loss of neurones in the NAWM are associated with the formation of white matter lesions.
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| 5. |
- Stenman, Carina
(författare)
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New workflow method for ultrasound examinations
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Growing demand for ultrasound examinations and higher quality requirements motivate searching for routines combining the diagnostic accuracy of radiologist-performed examinations with the economical advantages of sonographerperformed examinations. One possible approach is to use strictly standardized examination protocols and documentation made by cine-loops that will give the radiologist access to all relevant information after the examination. Ultrasound examinations are usually regarded as observer dependent, but using documentation with cine-loops acquired in a standardized way attempts to reduce this problem.Aims: The aim of study I was to compare a recently introduced routine, combining acquisition by a radiographer, documentation as standardized cine-loops, and review by a radiologist (“standardized method”), with the formerly used routine where the diagnosis is made bed-side by the radiologist (“traditional method”). The aim of study II was to evaluate the intra-observer and inter-observer agreement of the standardized method in ultrasound liver examinations.Material and Methods: In study I there was 64 policlinic patients examining the kidneys ( n = 27) or the gallbladder ( n =37) by both the standardized and the traditional method. The radiologists’ findings of hydronephrosis, tumors, cysts, echogenicity changes, and cortical thickness (in the kidneys), and wall thickness, concrements, and polyps (in the gallbladder) were compared between the methods with respect to agreement as well as systematic differences. In study II 98 out-patients were examined by a radiographer using the standardized method. Three radiologists with 10 – 20 years of experience of ultrasound reviewed the cine-loops retrospectively and independently filled out a predetermined protocol. After 4 weeks, the review was repeated, blinded to the initial reading.Results: Study I showed for the gallbladder examination a median agreement of 97% (86 – 100%; kappa =0.64 – 1.00) and for the kidney examination an agreement of 90% (78 – 100%; kappa = 0.69 – 1.00). There were no significant systematic differences between the two methods. In study II, the intra-observer agreement was highest for concrements in the gallbladder (kappa = 0.91 to 0.96) and lowest when assessing the need for further examination (kappa = 0.38 to 0.64). For increased liver echogenicity, kappa varied between 0.51 and 0.85, and for skip areas between 0.73 and 0.90. The interobserver agreement was also highest for concrements in the gallbladder (kappa = 0.84 to 1.00) and lowest for need for further examination (kappa = -0.12 to 0.46). For most other findings, substantial intra-observer agreement (kappa ≥ 0.61) was found.Conclusion: The satisfactory agreement in study I indicates that the new workflow with ultrasound examinations performed by a radiographer and analyzed off-line by a radiologist is promising. Study II shows a fairly good inter-observer agreement for ultrasound examinations acquired with a standardized technique by an experienced radiographer and reviewed by experienced radiologists. In general, intra-observer agreement was higher than inter-observer agreement.
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| 6. |
- Wang, Chunliang, 1980-, et al.
(författare)
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Automatic multi-organ segmentation in non-enhanced CT datasets using hierarchical shape priors
- 2014
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Ingår i: 2014 22ND INTERNATIONAL CONFERENCE ON PATTERN RECOGNITION (ICPR). - : IEEE Computer Society. - 9781479952083 - 9781479952090 ; , s. 3327-3332
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Konferensbidrag (refereegranskat)abstract
- An automatic multi-organ segmentation method using hierarchical-shape-prior guided level sets is proposed. The hierarchical shape priors are organized according to the anatomical hierarchy of the human body, so that major structures with less population variety are at the top and smaller structures with higher irregularities are linked at a lower level. The segmentation is performed in a top-down fashion, where major structures are first segmented with higher confidence, and their location information is then passed down to the lower level to initialize the segmentation, while boundary information from higher-level structures also provides extra cues to guide the segmentation of the lower-level structures. The proposed method was combined with a novel coherent propagating level set method, which is capable to detect local convergence and skip calculation in those parts, therefore significantly reducing computation time. Preliminary experiment results on a small number of clinical datasets are encouraging; the proposed method yielded a Dice coefficient above 90% for most major organs within a reasonable processing time without any user intervention.
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| 7. |
- Wang, Chunliang, 1980-, et al.
(författare)
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Automatic multi–organ segmentation using fast model based level set method and hierarchical shape priors
- 2014
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Ingår i: Proceedings of the VISCERAL Organ Segmentation and Landmark Detection Challenge, co-located with IEEE International Symposium on Biomedical Imaging (ISBI 2014), Beijing, China, May 1, 2014. - : CEUR-WS. ; , s. 25-31
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Konferensbidrag (refereegranskat)abstract
- An automatic multi-organ segmentation pipeline is presented. The segmentation starts with stripping the body of skin and subcutaneous fat using threshold-based level-set methods. After registering the image to be processed against a standard subject picked from the training datasets, a series of model-based level set segmentation operations is carried out guided by hierarchical shape priors. The hierarchical shape priors are organized according to the anatomical hierarchy of the human body, starting with ventral cavity, and then divided into thoracic cavity and abdominopelvic cavity. The third level contains the individual organs such as liver, spleen and kidneys. The segmentation is performed in a top-down fashion, where major structures are segmented first, and their location information is then passed down to the lower level to initialize the segmentation, while boundary information from higher-level structures also constrains the segmentation of the lower-level structures. In our preliminary experiments, the proposed method yielded a Dice coeffcient around 90% for most major thoracic and abdominal organs in both contrastenhanced CT and non-enhanced datasets, while the average running time for segmenting ten organs was about 10 minutes.
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| 8. |
- Wang, Chunliang, 1980-, et al.
(författare)
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Can segmented 3D images be used for stenosis evaluation in coronary CT angiography?
- 2012
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Ingår i: Acta Radiologica. - : Sage Publications. - 0284-1851 .- 1600-0455. ; 53:8, s. 845-851
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Tidskriftsartikel (refereegranskat)abstract
- Background: Thanks to the development of computed tomography (CT) scanners and computer software, accurate coronary artery segmentation can be achieved with minimum user interaction. However, the question remains whether we can use these segmented images for reliable diagnosis. Purpose: To retrospectively evaluate the diagnostic accuracy of coronary CT angiography (CCTA) using segmented 3D data for the detection of significant stenosis. Material and Methods: CCTA data-sets from 30 patients were acquired with a 64-slice CT scanner and segmented using the region growing (RG) method and the "virtual contrast injection" (VC) method. Three types of images of each patient were reviewed by different reviewers for the presence of stenosis with diameter reduction of 50% or more. The evaluation was performed on four main arteries of each patient (120 arteries in total). For the original series, the reviewer was allowed to use all the 2D and 3D visualization tools available (conventional method). For the segmented results from RG and VC, only maximum intensity projection was used. Evaluation results were compared with catheter angiography (CA) for each artery in a blinded fashion. Results: Overall, 34 arteries with significant stenosis were identified by CA. The percentage of evaluable arteries, accuracy and negative predictive value for detecting stenosis were, respectively, 86%, 74%, and 93% for the conventional method, 83%, 71%, and 92% for VC, and 64%, 56%, and 93% for RG. Accuracy was significantly lower for the RG method than for the other two methods (P < 0.01), whereas there was no significant difference in accuracy between the VC method and the conventional method (P = 0.22). Conclusion: The diagnostic accuracy for the RG-segmented 3D data is lower than those with access to 2D images, whereas the VC method shows diagnostic accuracy similar to the conventional method.
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| 9. |
- Wang, Chunliang, 1980-
(författare)
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Computer-Assisted Coronary CT Angiography Analysis : From Software Development to Clinical Application
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Advances in coronary Computed Tomography Angiography (CTA) have resulted in a boost in the use of this new technique in recent years, creating a challenge for radiologists due to the increasing number of exams and the large amount of data for each patient. The main goal of this study was to develop a computer tool to facilitate coronary CTA analysis by combining knowledge of medicine and image processing, and to evaluate the performance in clinical settings.Firstly, a competing fuzzy connectedness tree algorithm was developed to segment the coronary arteries and extract centerlines for each branch. The new algorithm, which is an extension of the “virtual contrast injection” (VC) method, preserves the low-density soft tissue around the artery, and thus reduces the possibility of introducing false positive stenoses during segmentation. Visually reasonable results were obtained in clinical cases.Secondly, this algorithm was implemented in open source software in which multiple visualization techniques were integrated into an intuitive user interface to facilitate user interaction and provide good overviews of the processing results. An automatic seeding method was introduced into the interactive segmentation workflow to eliminate the requirement of user initialization during post-processing. In 42 clinical cases, all main arteries and more than 85% of visible branches were identified, and testing the centerline extraction in a reference database gave results in good agreement with the gold standard.Thirdly, the diagnostic accuracy of coronary CTA using the segmented 3D data from the VC method was evaluated on 30 clinical coronary CTA datasets and compared with the conventional reading method and a different 3D reading method, region growing (RG), from a commercial software. As a reference method, catheter angiography was used. The percentage of evaluable arteries, accuracy and negative predictive value (NPV) for detecting stenosis were, respectively, 86%, 74% and 93% for the conventional method, 83%, 71% and 92% for VC, and 64%, 56% and 93% for RG. Accuracy was significantly lower for the RG method than for the other two methods (p<0.01), whereas there was no significant difference in accuracy between the VC method and the conventional method (p = 0.22).Furthermore, we developed a fast, level set-based algorithm for vessel segmentation, which is 10-20 times faster than the conventional methods without losing segmentation accuracy. It enables quantitative stenosis analysis at interactive speed.In conclusion, the presented software provides fast and automatic coronary artery segmentation and visualization. The NPV of using only segmented 3D data is as good as using conventional 2D viewing techniques, which suggests a potential of using them as an initial step, with access to 2D reviewing techniques for suspected lesions and cases with heavy calcification. Combining the 3D visualization of segmentation data with the clinical workflow could shorten reading time.
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| 10. |
- Wang, Chunliang, 1980-, et al.
(författare)
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Fast level-set based image segmentation using coherent propagation
- 2014
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Ingår i: Medical physics (Lancaster). - : John Wiley and Sons Ltd. - 0094-2405. ; 41:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The level-set method is known to require long computation time for 3D image segmentation, which limits its usage in clinical workflow. The goal of this study was to develop a fast level-set algorithm based on the coherent propagation method and explore its character using clinical datasets. Methods: The coherent propagation algorithm allows level set functions to converge faster by forcing the contour to move monotonically according to a predicted developing trend. Repeated temporary backwards propagation, caused by noise or numerical errors, is then avoided. It also makes it possible to detect local convergence, so that the parts of the boundary that have reached their final position can be excluded in subsequent iterations, thus reducing computation time. To compensate for the overshoot error, forward and backward coherent propagation is repeated periodically. This can result in fluctuations of great magnitude in parts of the contour. In this paper, a new gradual convergence scheme using a damping factor is proposed to address this problem. The new algorithm is also generalized to non-narrow band cases. Finally, the coherent propagation approach is combined with a new distance-regularized level set, which eliminates the needs of reinitialization of the distance. Results: Compared with the sparse field method implemented in the widely available ITKSnap software, the proposed algorithm is about 10 times faster when used for brain segmentation and about 100 times faster for aorta segmentation. Using a multiresolution approach, the new method achieved 50 times speed-up in liver segmentation. The Dice coefficient between the proposed method and the sparse field method is above 99% in most cases. Conclusions: A generalized coherent propagation algorithm for level set evolution yielded substantial improvement in processing time with both synthetic datasets and medical images.
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