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Novel multistage three-dimensional medical image segmentation: methodology and validation.

In this paper, we propose a novel multistage method for three-dimensional (3-D) segmentation of medical images and a new radial distance-based segmentation validation approach. For the 3-D segmentation method, we first employ a morphological recursive erosion operation to reduce the connectivity between the region of interest and its surrounding neighborhood; then we design a hybrid segmentation method to achieve an initial result. The hybrid approach integrates an improved fast marching method and a morphological reconstruction algorithm. Finally, a morphological recursive dilation is employed to recover any lost structure from the first stage of the multistage method. This approach is tested on 12 CT and 3 MRI images of the brain, heart, and kidney, to demonstrate the effectiveness and accuracy of this technique across a variety of imaging modalities and organ systems. In order to validate the multistage segmentation method, a novel radial distance-based validation method is proposed that uses a global accuracy (GA) measure. The GA is calculated based on local radial distance errors (LRDE), where LRDE are calculated on the radii emitted from points along the skeleton of the object rather than the centroid, in order to accommodate more complicated organ structures. The experimental results demonstrate that the proposed multistage segmentation method is fast and accurate, with comparable performance to existing segmentation methods, but with a significantly higher execution speed.

Algorithms↗

Localization and segmentation of aortic endografts using marker detection.

A method for localization and segmentation of bifurcated aortic endografts in computed tomographic angiography (CTA) images is presented. The graft position is determined by detecting radiopaque markers sewn on the outside of the graft. The user indicates the first and the last marker, whereupon the remaining markers are automatically detected. This is achieved by first detecting marker-like structures through second-order scaled derivative analysis, which is combined with prior knowledge of graft shape and marker configuration. The identified marker centers approximate the graft sides and, derived from these, the central axis. The graft boundary is determined by maximizing the local gradient in the radial direction along a deformable contour passing through both sides. Three segmentation methods were tested. The first performs graft contour detection in the initial CT-slices, the second in slices that were reformatted to be orthogonal to the approximated graft axis, and the third uses the segmentation from the second method to find a more reliable approximation of the axis and subsequently performs contour detection. The methods have been applied to ten CTA images and the results were compared to manual marker indication by one observer and region growing aided segmentation by three observers. Out of a total of 266 markers, 262 were detected. Adequate approximations of the graft sides were obtained in all cases. The best segmentation results were obtained using a second iteration orthogonal to the axis determined from the first segmentation, yielding an average relative volume of overlap with the expert segmentations of 92%, while the interexpert reproducibility is 95%. The averaged difference in volume measured by the automated method and by the experts equals the difference among the experts: 3.5%.

Anatomy, Cross-Sectional↗

Colonic polyp segmentation in CT colonography-based on fuzzy clustering and deformable models.

An automatic method to segment colonic polyps in computed tomography (CT) colonography is presented in this paper. The method is based on a combination of knowledge-guided intensity adjustment, fuzzy c-mean clustering, and deformable models. The computer segmentations were compared with manual segmentations to validate the accuracy of our method. An average 76.3% volume overlap percentage among 105 polyp detections was reported in the validation, which was very good considering the small polyp size. Several experiments were performed to investigate the intraoperator and interoperator repeatability of manual colonic polyp segmentation. The investigation demonstrated that the computer-human repeatability was as good as the interoperator repeatability. The polyp segmentation was also applied in computer-aided detection (CAD) to reduce the number of false positive (FP) detections and provide volumetric features for polyp classification. Our segmentation method was able to eliminate 30% of FP detections. The volumetric features computed from the segmentation can further reduce FP detections by 50% at 80% sensitivity.

Algorithms↗

Segmentation of thrombus in abdominal aortic aneurysms from CTA with nonparametric statistical grey level appearance modeling.

This paper presents a new method for deformable model-based segmentation of lumen and thrombus in abdominal aortic aneurysms from computed tomography (CT) angiography (CTA) scans. First the lumen is segmented based on two positions indicated by the user, and subsequently the resulting surface is used to initialize the automated thrombus segmentation method. For the lumen, the image-derived deformation term is based on a simple grey level model (two thresholds). For the more complex problem of thrombus segmentation, a grey level modeling approach with a nonparametric pattern classification technique is used, namely k-nearest neighbors. The intensity profile sampled along the surface normal is used as classification feature. Manual segmentations are used for training the classifier: samples are collected inside, outside, and at the given boundary positions. The deformation is steered by the most likely class corresponding to the intensity profile at each vertex on the surface. A parameter optimization study is conducted, followed by experiments to assess the overall segmentation quality and the robustness of results against variation in user input. Results obtained in a study of 17 patients show that the agreement with respect to manual segmentations is comparable to previous values reported in the literature, with considerable less user interaction.

Algorithms↗

Intrathoracic airway trees: segmentation and airway morphology analysis from low-dose CT scans.

The segmentation of the human airway tree from volumetric computed tomography (CT) images builds an important step for many clinical applications and for physiological studies. Previously proposed algorithms suffer from one or several problems: leaking into the surrounding lung parenchyma, the need for the user to manually adjust parameters, excessive runtime. Low-dose CT scans are increasingly utilized in lung screening studies, but segmenting them with traditional airway segmentation algorithms often yields less than satisfying results. In this paper, a new airway segmentation method based on fuzzy connectivity is presented. Small adaptive regions of interest are used that follow the airway branches as they are segmented. This has several advantages. It makes it possible to detect leaks early and avoid them, the segmentation algorithm can automatically adapt to changing image parameters, and the computing time is kept within moderate values. The new method is robust in the sense that it works on various types of scans (low-dose and regular dose, normal subjects and diseased subjects) without the need for the user to manually adjust any parameters. Comparison with a commonly used region-grow segmentation algorithm shows that the newly proposed method retrieves a significantly higher count of airway branches. A method that conducts accurate cross-sectional airway measurements on airways is presented as an additional processing step. Measurements are conducted in the original gray-level volume. Validation on a phantom shows that subvoxel accuracy is achieved for all airway sizes and airway orientations.

Algorithms↗

Maximum-likelihood techniques for joint segmentation-classification of multispectral chromosome images.

Traditional chromosome imaging has been limited to grayscale images, but recently a 5-fluorophore combinatorial labeling technique (M-FISH) was developed wherein each class of chromosomes binds with a different combination of fluorophores. This results in a multispectral image, where each class of chromosomes has distinct spectral components. In this paper, we develop new methods for automatic chromosome identification by exploiting the multispectral information in M-FISH chromosome images and by jointly performing chromosome segmentation and classification. We (1) develop a maximum-likelihood hypothesis test that uses multispectral information, together with conventional criteria, to select the best segmentation possibility; (2) use this likelihood function to combine chromosome segmentation and classification into a robust chromosome identification system; and (3) show that the proposed likelihood function can also be used as a reliable indicator of errors in segmentation, errors in classification, and chromosome anomalies, which can be indicators of radiation damage, cancer, and a wide variety of inherited diseases. We show that the proposed multispectral joint segmentation-classification method outperforms past grayscale segmentation methods when decomposing touching chromosomes. We also show that it outperforms past M-FISH classification techniques that do not use segmentation information.

Algorithms↗

Joint multiregion segmentation and parametric estimation of image motion by basis function representation and level set evolution.

The purpose of this study is to investigate a variational method for joint segmentation and parametric estimation of image motion by basis function representation of motion and level set evolution. The functional contains three terms. One term is of classic regularization to bias the solution toward a segmentation with smooth boundaries. A second term biases the solution toward a segmentation with boundaries which coincide with motion discontinuities, following a description of motion discontinuities by a function of the image spatio-temporal variations. The third term refers to region information and measures conformity of the parametric representation of the motion of each region of segmentation to the image spatio-temporal variations. The components of motion in each region of segmentation are represented as functions in a space generated by a set of basis functions. The coefficients of the motion components considered combinations of the basis functions are the parameters of representation. The necessary conditions for a minimum of the functional, which are derived taking into consideration the dependence of the motion parameters on segmentation, lead to an algorithm which condenses to concurrent curve evolution, implemented via level sets, and estimation of the parameters by least squares within each region of segmentation. The algorithm and its implementation are verified on synthetic and real images using a basis of cosine transforms.

Artificial Intelligence↗

Combining intensity, edge and shape information for 2D and 3D segmentation of cell nuclei in tissue sections.

We present a region-based segmentation method in which seeds representing both object and background pixels are created by combining morphological filtering of both the original image and the gradient magnitude of the image. The seeds are then used as starting points for watershed segmentation of the gradient magnitude image. The fully automatic seeding is done in a generous fashion, so that at least one seed will be set in each foreground object. If more than one seed is placed in a single object, the watershed segmentation will lead to an initial over-segmentation, i.e. a boundary is created where there is no strong edge. Thus, the result of the initial segmentation is further refined by merging based on the gradient magnitude along the boundary separating neighbouring objects. This step also makes it easy to remove objects with poor contrast. As a final step, clusters of nuclei are separated, based on the shape of the cluster. The number of input parameters to the full segmentation procedure is only five. These parameters can be set manually using a test image and thereafter be used on a large number of images created under similar imaging conditions. This automated system was verified by comparison with manual counts from the same image fields. About 90% correct segmentation was achieved for two- as well as three-dimensional images.

Automation↗

Preferential rearrangements of the V gamma I subgroup of the gamma-chain of the T-cell antigen receptor to J gamma 2C gamma 2 gene segments in peripheral blood lymphocyte transcripts from normal donors.

To investigate whether there are preferential VJC gene rearrangements of the gamma-chain of the human T-cell antigen receptor (TCR), we amplified and sequenced gamma-chain TCR transcripts from peripheral blood lymphocytes from adult normal donors. cDNA was synthesized from total RNA and amplified by the polymerase chain reaction (PCR) using 5' primers specific for either the V gamma I or the V gamma II subgroups of the gamma-chain of the TCR. The amplified cDNAs were then cloned and sequenced. The majority (approximately 83%) of the cDNAs employing V-I subgroup gene segments rearranged to J gamma 2 (J gamma 2.1 or J gamma 2.3) C gamma 2 gene segments. This was in contrast to the predominant rearrangement of the V gamma II subgroup (V gamma 9) to J gamma 1.2C gamma 1. The remaining 13% of the cDNAs employing V gamma I subgroup gene segments rearranged to J gamma 1.1C gamma 1 or J gamma 1.3C gamma 1. There was significant N diversity as well as imprecise joining at the VJ junction. gamma delta TCR utilizing the C gamma 1 gene segment are disulfide-linked, whereas those utilizing the C gamma 2 gene segment are non-disulfide-linked. These results demonstrate that peripheral blood gamma-chain transcripts exhibit preferential rearrangements of V gamma I subgroup gene segments to J gamma 2(2.1,2.3)C gamma 2 gene segments. By contrast, V gamma II subgroup (V gamma 9) transcripts exhibit rearrangements to J gamma 1.2C gamma 1.

Amino Acid Sequence↗

Synthesis of phospho-urodilatin by combination of global phosphorylation with the segment coupling approach.

The chemical synthesis of biologically active phosphorylated urodilatin (CDD/ANP-95-126) was achieved by using a strategy of coupling protected peptide segments in solution. Three protected peptide segments corresponding to urodilatin (1-14) with side chain-unprotected Ser10, (15-24) and (25-32) were prepared manually using Fmoc chemistry on an aminopropyl polystyrene resin with the super acid-labile HMPB linker. For the coupling of segments, the carboxy group of the C-terminal segment (25-32) was converted into the tert-butyl ester by treatment with TBTA. The protected peptide segments were coupled in the presence of EDC/HOOBt or TBTU/HOBt to yield fully protected urodilatin with a free hydroxy function at Ser10. Introduction of the phosphate was performed with Et2NP(OtBu)2 and tetrazole followed by oxidation of the phosphite. Alternatively, a prephosphorylated protected segment (1-14) was used in the segment condensation. Our investigations indicate that both pathways, phosphorylation of protected urodilatin in solution and use of a prephosphorylated building block, are suitable methods to obtain a large phosphopeptide of high purity without formation of H-phosphonates or other by-products.

Amino Acid Sequence↗

Segmental angioarchitecture of the testicular lobule in man.

There is a close correlation between the angioarchitecture of the human testis and its inner subdivision into testicular lobules. Serial sections from paraffin and epon-embedded testicular tissue were used to examine the angioarchitecture of the human testis, and computer-aided 3-D-reconstruction was used to demonstrate the correlation between blood vessels and tissue organization. The recurrent arteries arise from the centripetal arteries, and run in the central axis of the testicular lobule. At regular intervals of on average, 300 microns the segmental arteries arise from the recurrent artery, which supplies segments of the testicular parenchyma perpendicular to the long axis of the testicular lobules. Within such a segment, the segmental artery supplies the microvasculature, which is partly surrounded by Leydig cells and partly stands in close contact with the wall of the seminiferous tubules. The venous drainage occurs through the intralobular veins, which run to the periphery of the lobule (towards the septum). These veins lead into the septum and there they join the collecting veins. A lobule can have several segments depending on its size. The base of such a tissue segment is directed towards the septum whereas the top is directed towards the centre of the lobule. Sections of several seminiferous tubules can be found in such a segment. The flow of blood from the arterial to the venous side of the testicular circulation occurs radially from the centre of the lobule to the septum.

Arteries↗

Clinicopathological characteristics of the focal and segmental form of idiopathic membranous nephropathy: comparison with the typical form of this disease.

Although idiopathic membranous nephropathy (IMN) is thought to represent a diffuse glomerulopathy, it was found that three of 31 children histologically diagnosed as IMN showed focal and segmental deposition of immunoglobulin G (IgG) and C3 on the glomerular capillary walls. The present study attempted to comparatively investigate clinical and pathological features of the diffuse group and the focal segmental group in 31 IMN children. Immunofluorescence study revealed that 28 of 31 IMN exhibited diffuse granular deposition of IgG along glomerular capillary walls. In contrast, focal and segmental deposition of IgG and C3 was noted in three children with IMN. In addition, focal and segmental electron-dense deposits were identified in these cases. In two children of the focal segmental group, immunofluorescent patterns of IgG deposition were unchanged even at the second biopsy. The focal segmental form of IMN tended to occur in younger children than diffuse IMN. However, other clinical parameters such as the range of proteinuria, hematuria, serum albumin and prognosis did not show any significant differences between both groups. Electrophoretic profiles of urinary proteins on sodium dodecylsulfate-polyacrylamide gel electrophoresis were not different between both groups. It is proposed that the focal segmental form of IMN may have a distinctive glomerulopathy from the typical form of IMN.

Child, Preschool↗

The anatomical basis for segment III cholangiojejunostomy with analysis of 13 cases.

BACKGROUND: The majority of patients who require palliation for jaundice and pruritus resulting from malignant hilar obstruction are treated by stenting. Stenting is usually achieved from below after performing an endoscopic retrograde cholangiopancreatography. In some cases the rendezvous technique is employed, negotiating the passage through a malignant stricture from above and stenting from below. A minority of cases, such as those who had a previous polyagastrectomy and those in whom attempts at stenting have failed, are considered to be suitable for a Segment III cholangiojejunostomy. We have investigated the anatomical basis for Segment III duct bypass and have critically analysed the results in 13 patients. Ten patients were treated by Segment III duct bypass alone, and three patients had a Segment III duct bypass combined with stenting of the right liver. METHODS: The anatomy of the biliary tree was investigated by dissection of 54 normal livers removed at autopsy. Clinical details of the 13 patients who had Section III cholangiojejunostomy were obtained from hospital records and by contacting treating practitioners. RESULTS: In 64.8% of the anatomical dissections, the findings were favourable for a Section III cholangiojejunostomy. In these specimens the Segment III duct bypass would have drained Segments II, III and IV. In 35.2% of the specimens the anatomical disposition was potentially unfavourable, mainly due to the Segment II or IV ducts joining close to the confluence and therefore liable to obstruction by the tumour. In nine of the 54 specimens the true left hepatic duct was less than 6 mm in length, making it unsuitable for a bypass procedure to drain the left hemi liver. Of the 10 patients who were subjected to a palliative Section III cholangiojejunostomy only, there was one postoperative death. Of the nine patients who survived, six obtained excellent palliation of jaundice and pruritus. CONCLUSIONS: In carefully selected cases, Section III cholangiojejunostomy achieves excellent palliation in patients with unresectable hilar malignancies that have been unable to be stented pre-operatively or who have unresectable tumours at the time of laparotomy.

Bile Duct Neoplasms↗

Anterior ST segment depression in inferior myocardial infarction: effect on complications and long-term survival.

The effect of anterior ST segment depression in inferior myocardial infarction on early complications and long-term prognosis was studied. A modification of the Minnesota Code was used for grading the extent of ST segment depression in leads V2 to V4 on the first hospital electrocardiogram. In 267 patients with acute inferior myocardial infarction, 107 had isoelectric anterior ST segments, 84 had minor (less than or equal to 0.5 mm) depression, and 76 had major (greater than 0.5 mm) depression. Patients with anterior ST segment depression had higher serum enzyme levels, higher Norris coronary prognostic indices, and more frequent cardiac failure during the acute stages, but similar 28 day case fatality rate (11.1%) compared with patients without anterior ST segment depression (12.6%). In the subsequent four years total cardiac death rates were not significantly different and the pattern of survival was not influenced, but there was a higher fatal re-infarction rate in patients with major anterior ST segment depression. Thus, anterior ST segment depression in inferior myocardial infarction was associated with more severe infarction in the early phase but was not a reliable marker of high risk after recovery. Selection of patients for further investigation should not be based on this observation alone.

Actuarial Analysis↗

Diagnosis of pulmonary embolus using ventilation/perfusion lung scintigraphy: more than 0.5 segment of ventilation/perfusion mismatch is sufficient.

BACKGROUND: To determine the optimal diagnostic cut-off point using a simplified criterion for the detection of pulmonary embolus (PE) and to evaluate the criterion's utility and reporter reproducibility. METHODS: Lung scintigraphy was carried out in 924 patients for the diagnosis of PE. This group consisted of 316 men and 608 women with median age of 63 years (range 18-94 years). Ventilation imaging was carried out with Tc-99m Technegas followed by perfusion imaging using 190 MBq Tc-99m macroaggregated albumin. Studies were classified using a 6-category probability criterion of incremental ventilation/perfusion (V/Q) mismatch: A, normal; B, low (minor matched V/Q defects or segmental matched V/Q defects without opacity on chest X-ray); C, low-moderate (a partial segment of V/Q mismatch); D, moderate (1 segment of mismatch); E, moderate-high (1-2 segments of V/Q mismatch) and F, high probability (=2 segments of V/Q mismatch). Clinical end-points at 3 and 6 months were death by PE or PE treated with anticoagulation therapy. Three-reporter reproducibility was determined by kappa statistic on a subgroup of patients (53/924). RESULTS: A total of 122 patients (13%) had a confirmed diagnosis of PE at 3 months and no additional cases were registered at 6 months. The lung scintigraphy probability classification showed: normal 152 (16%), low 620 (67%), low-moderate 20 (2%), moderate 28 (3%), moderate-high 24 (3%) and high 80 (9%). The respective sensitivities and specificities, where the diagnostic cut-offs were established at F, high; E, moderate-high; D, moderate and C, low-moderate probability, were F, 64 and 100%; E, 82 and 99%; D, 95 and 98% and C, 98 and 96%. The respective false-negative cases for F, E, D and C cut-offs were 44, 22, 7 and 3. Using the revised Prospective Investigation of Pulmonary Embolism Diagnosis reporting classification reporter agreement showed kappa values of 0.31-0.48. Using a simplified 2-category (>0.5 segment of V/Q mismatch positive, all others negative) criterion resulted in a higher reporting agreement (kappa 0.74-0.83). There were only 3% of indeterminate cases if this was defined by the D category and a maximum of 8% if categories C, D and E were included. CONCLUSIONS: Using a simplified diagnostic criterion where all studies showing >0.5 segments of V/Q mismatch are regarded as positive and all others as negative, lung scintigraphy, incorporating Tc-99m Technegas ventilation imaging or its equivalent, can achieve a very high diagnostic accuracy for the detection of PE. Using this technique, less than 5% of scans are indeterminate. A simplified, unambiguous approach to reporting is recommended.

Adolescent↗

Infarct transmurality and adjacent segmental function as determinants of wall thickening in revascularized chronic ischemic heart disease.

BACKGROUND: There are many factors which influence regional left ventricular wall thickening (WT) in ischemic heart disease (IHD). We used magnetic resonance imaging (MRI) to explore, in patients with chronic ischemic heart disease (CIHD), how regional WT is affected by both infarct transmurality (IT) and the function of adjacent segments. We also compared these findings with a group of healthy volunteers (controls). METHODS: Twenty patients (20 men, mean age 63, range 45-80 years) were imaged with cine MRI for function and delayed enhancement MRI for infarction 6 months after revascularization. Twenty age and sex matched controls underwent cine MRI. Short-axis images were analysed using a 12-segment per slice model in four midventricular slices per subject. RESULTS: WT and IT were inversely related (r(2) = 0.11, P<0.001). WT of non-infarcted segments in patients was lower than corresponding segments in controls (5.1 versus 4.6 mm, P<0.001). WT in patients decreased with an increasing number of dysfunctional adjacent segments (P<0.001) and increasing IT (P<0.001). WT was more strongly influenced by the number of dysfunctional adjacent segments (t = -22.93, P<0.001) than by IT (t = -4.50, P<0.001). CONCLUSIONS: The number of dysfunctional adjacent segments is a greater determinant than infarct transmurality on regional wall thickening.

Aged↗

Effects of spatial segmentation in the continuous model of excitation propagation in cardiac muscle.

INTRODUCTION: Spatial segmentation is essential for the numerical simulation of excitation propagation in cardiac muscle. METHODS AND RESULTS: This study evaluated the effects of spatial segmentation on action potential and on the velocity of propagation in a continuous one-dimensional model of cardiac muscle [intracellular and extracellular resistivities along (L) and transverse (T) to the muscle fibers: 402 omega(cm) (R(e), L), 3,620 omega(cm) (R(e), T), 48 omega(cm) (R(e), L), and 126 omega(cm) (R(e), T), J of Physiol 255:335-346, 1976) and either Luo-Rudy (L-R, Circ Res 68:1501-1526, 1991) or Beeler-Reuter (B-R, J Physiol 268:177-210, 1977) ionic currents. Related cable equations for active membrane are derived. Spatial segmentations of < 31.2 microm (L, L-R), < 11.5 microm (T, L-R), < 44.7 microm (L, B-R), and < 16.5 microm (T, B-R) were required for < 1% errors in the characteristic parameters of action potential. Similarly, spatial segmentations of < 54.5 microm (L, L-R), < 20.1 microm (T, L-R), < 84.3 microm (L, B-R), and < 31.2 microm (T, B-R) were required for < 1 % errors in the velocity of conduction. CONCLUSION: In general, spatial segmentations of < 26.9% and < 50.8% of the space constant of a fully activated membrane gave < 1.0% errors in the characteristic parameters of action potential and in the velocity of propagation, respectively, for both membranes. The action potential duration was relatively insensitive to the spatial segmentation. Our analysis suggests that lambda(full is a better criterion for the selection of spatial segmentation in numerical simulation than the space constant of the resting membrane.

Action Potentials↗

Utility and limitations of linear models for echocardiographic estimation of left ventricular ejection fraction by segmental wall-motion scoring. A geometric analysis.

Although the geometric relation between left ventricular (LV) volume and its internal dimensions is nonlinear, recent clinical study has shown that LV ejection fraction (EF) predicted by a linear combination of segmental contraction scores correlates well with the EF by radionuclide angiography. To determine whether the linear coefficients found by empirical study are consistent with basic geometric principles, we compared the LV EF obtained by exact geometric calculation to the EF predicted using a simple linear combination of segmental contraction scores over a wide range of segmental function, from marked dyskinesis to marked hyperkinesis. We found that an optimal linear equation for global EF on geometric grounds is: Global EF = 4 + 0.28xC1 + 0.24xC2 + 0.12xC3, where C1, C2, and C3 are the mean segmental contraction scores at the base, mid-left ventricle, and the apex, respectively. The EF predicted by this formula differs by less than 6 percentage points from the EF predicted by exact geometry when segmental contraction ranges from normal to akinetic, and the coefficients are in close accord with those found empirically by regression of linearly-derived EFs against the radionuclide EFs in 50 patients. However, when segmental contraction is significantly hyperkinetic or dyskinetic, agreement with the exact geometric formula is poor. We conclude that: (1) a linear combination of segmental contraction scores can provide reasonable estimates of LV EF over a broad range of contraction; (2) previous, empirically determined linear coefficients are consistent with geometric principles; and (3) exact, nonlinear formulas may be required for ventricles with significant degrees of hyperkinesis or dyskinesis.

Echocardiography↗