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Three-dimensional ultrasound imaging and its use in quantifying organ and pathology volumes.

Although ultrasonography is an important cost-effective imaging modality, technical improvements are needed before its full potential is realized for accurate and reproducible monitoring of disease progression or regression. Two-dimensional viewing of three-dimensional anatomy, using conventional ultrasonography, limits our ability to quantify and visualize pathology and is partly responsible for the reported variability in diagnosis and monitoring of disease progression. Efforts of investigators have focused on overcoming these deficiencies by developing 3D ultrasound imaging techniques that are capable of acquiring B-mode images using existing conventional ultrasound systems, reconstructing the information into 3D images, and then allowing interactive viewing of the 3D images on inexpensive desktop computers. In addition, the availability of 3D ultrasound images has allowed the development of manual and semi-automated techniques to quantify normal and abnormal anatomical volumes. In this paper we review our semi-automated 3D segmentation approaches for segmenting the surface of the carotid arteries and plaques, and segmenting the prostate. These techniques demonstrate that efficient segmentation techniques can be used with 3D ultrasound images to quantify anatomical organ volumes and morphology.

Carotid Arteries↗

Automatic morphology-based brain segmentation (MBRASE) from MRI-T1 data.

A method called morphology-based brain segmentation (MBRASE) has been developed for fully automatic segmentation of the brain from T1-weighted MR image data. The starting point is a supervised segmentation technique, which has proven highly effective and accurate for quantitation and visualization purposes. The proposed method automates the required user interaction, i.e., defining a seed point and a threshold range, and is based on the simple operations thresholding, erosion, and geodesic dilation. The thresholds are detected in a region growing process and are defined by connections of the brain to other tissues. The method is first evaluated on three computer simulated datasets by comparing the automated segmentations with the original distributions. The second evaluation is done on a total of 30 patient datasets, by comparing the automated segmentations with supervised segmentations carried out by a neuroanatomy expert. The comparison between two binary segmentations is performed both quantitatively and qualitatively. The automated segmentations are found to be accurate and robust. Consequently, the proposed method can be used as a default segmentation for quantitation and visualization of the human brain from T1-weighted MR images in routine clinical procedures.

Adolescent↗

3D visualization, analysis, and treatment of the prostate using trans-urethral ultrasound.

In the year 2000, it is estimated that over 20,000 men underwent transperineal interstitial permanent prostate brachytherapy (TIPPB) for treatment of prostate cancer. Trans-urethral ultrasound (TUUS) is a new interactive, real-time 3D imaging method that may be effective in therapy-guidance during and after TIPPB. TUUS provides higher resolution than trans-rectal ultrasound (TRUS). TUUS can be used to accurately localize radioactive seeds and therefore contribute to more accurate determination of radiation dose distribution throughout the tissue after the completion of the procedure, similar to information currently provided by expensive and offline CT scans. A TUUS catheter can be used to acquire 2D section images or 3D volume images for detailed analyses of the prostate and associated tissue. Initial development of TUUS imaging was carried out on an ultrasound-equivalent prostate phantom with cylindrical dummy radiation sources. This was followed by preliminary studies in animals and then in patients. Both CT and TRUS data were acquired in these studies for comparative purposes. Segmentation of the prostate capsule and radioactive seeds was carried out using several semi-automated 3D algorithms and image processing techniques. Presentation of the data to the clinician is provided by a variety of complementary 2D and 3D display methods. In comparison with the CT data, TUUS data provided both greater spatial resolution and better soft tissue differentiation. In comparison to the TRUS data, TUUS data provided greater resolution and better seed localization. Combining these advantages suggests the possibility of TUUS becoming the exclusive imaging method in prostate cancer brachytherapy.

Humans↗

An automated image cytometry system for monitoring DNA ploidy and other cell features of radiotherapy and chemotherapy patients.

DNA content and distribution in cell nuclei were studied in samples of fine-needle aspiration (FNA) from 27 locally advanced breast and head and neck cancers in two going randomized trials that compared accelerated fractionation to standard fractionation radiation in locally advanced breast cancer and head and neck cancer. Two image cytometry methods were compared: a new, fully automated DNA image cytometry system (AIC) and a conventional image cytometry (CIC) system with manual selection, focusing, and segmentation of cells. The results of both techniques were compared on the basis of DNA histogram parameters including DNA index (DI), mean DNA values (MDV), and Auer's DNA histogram patterns. An excellent correlation was achieved between the two imaging techniques in terms of DI (r=0.985, p<0.001) and MDV (r=0.951, p<0.001) as well as between Auer's histogram patterns, where both methods agreed completely. It was concluded in these analyses that the two image cytometry methods were equivalent. However, the AIC offered an advantage by scanning samples in a fully automated way, which represented significant time saving for cytopathologists working with the system, as well as a larger number of cells used in the automated analysis. With the automated image cytometer, 500 relevant cells were collected and analyzed in about 10 minutes, where with the interactive (manual) method, it took typically an hour to collect and analyze only about 250 cells. Seventeen samples were sufficient for flow analysis. Image cytometry and flow cytometry showed good agreement in DI determination; however, three cases reported as diploid by flow cytometry were found to be aneuploid by image cytometry techniques.

Antineoplastic Combined Chemotherapy Protocols↗

Evaluation of automated threshold selection methods for accurately sizing microscopic fluorescent cells by image analysis.

The accurate measurement of bacterial and protistan cell biomass is necessary for understanding their population and trophic dynamics in nature. Direct measurement of fluorescently stained cells is often the method of choice. The tedium of making such measurements visually on the large numbers of cells required has prompted the use of automatic image analysis for this purpose. Accurate measurements by image analysis require an accurate, reliable method of segmenting the image, that is, distinguishing the brightly fluorescing cells from a dark background. This is commonly done by visually choosing a threshold intensity value which most closely coincides with the outline of the cells as perceived by the operator. Ideally, an automated method based on the cell image characteristics should be used. Since the optical nature of edges in images of light-emitting, microscopic fluorescent objects is different from that of images generated by transmitted or reflected light, it seemed that automatic segmentation of such images may require special considerations. We tested nine automated threshold selection methods using standard fluorescent microspheres ranging in size and fluorescence intensity and fluorochrome-stained samples of cells from cultures of cyanobacteria, flagellates, and ciliates. The methods included several variations based on the maximum intensity gradient of the sphere profile (first derivative), the minimum in the second derivative of the sphere profile, the minimum of the image histogram, and the midpoint intensity. Our results indicated that thresholds determined visually and by first-derivative methods tended to overestimate the threshold, causing an underestimation of microsphere size. The method based on the minimum of the second derivative of the profile yielded the most accurate area estimates for spheres of different sizes and brightnesses and for four of the five cell types tested. A simple model of the optical properties of fluorescing objects and the video acquisition system is described which explains how the second derivative best approximates the position of the edge.

Cyanobacteria↗

Automated localization of implanted seeds in 3D TRUS images used for prostate brachytherapy.

An algorithm has been developed in this paper to localize implanted radioactive seeds in 3D ultrasound images for a dynamic intraoperative brachytherapy procedure. Segmentation of the seeds is difficult, due to their small size in relatively low quality of transrectal ultrasound (TRUS) images. In this paper, intraoperative seed segmentation in 3D TRUS images is achieved by performing a subtraction of the image before the needle has been inserted, and the image after the seeds have been implanted. The seeds are searched in a "local" space determined by the needle position and orientation information, which are obtained from a needle segmentation algorithm. To test this approach, 3D TRUS images of the agar and chicken tissue phantoms were obtained. Within these phantoms, dummy seeds were implanted. The seed locations determined by the seed segmentation algorithm were compared with those obtained from a volumetric cone-beam flat-panel micro-CT scanner and human observers. Evaluation of the algorithm showed that the rms error in determining the seed locations using the seed segmentation algorithm was 0.98 mm in agar phantoms and 1.02 mm in chicken phantoms.

Algorithms↗

Automated measurement of kidney lysosomes by light microscopy. Influence of cyclosporine treatment.

After staining for acid phosphatase, video images were acquired from 1-micron sections of the kidneys of rats treated with cyclosporine. Automated segmentation of the lysosomes was followed by measurements of their area, number and optical density; tubular area was delineated manually. In addition to small lysosomes, representing more than 80% of the total number, all kidneys contained a second population of larger organelles. Cyclosporine treatment with 50 mg/kg/day for one week and with 25 mg/kg/day for three weeks, but not with 25 mg/kg/day for one week, induced a significant increase of lysosomal area, especially in the larger organelles (+200%). In a few animals, this was accompanied by a reduction in the number of lysosomes, suggesting a fusion of the organelles. Other parameters were not consistently modified by treatment. Cyclosporine treatment also elicited the appearance of fat droplets; however, lysosomes were not enlarged in tubular cells containing fat droplets.

Animals↗

Interactive algorithms for the segmentation and quantitation of 3-D MRI brain scans.

Interactive algorithms are an attractive approach to the accurate segmentation of 3D brain scans as they potentially improve the reliability of fully automated segmentation while avoiding the labour intensiveness and inaccuracies of manual segmentation. We present a 3D image analysis package (MIDAS) with a novel architecture enabling highly interactive segmentation algorithms to be implemented as add on modules. Interactive methods based on intensity thresholding, region growing and the constrained application of morphological operators are also presented. The methods involve the application of constraints and freedoms on the algorithms coupled with real time visualisation of the effect. This methodology has been applied to the segmentation, visualisation and measurement of the whole brain and a small irregular neuroanatomical structure, the hippocampus. We demonstrate reproducible and anatomically accurate segmentations of these structures. The efficacy of one method in measuring volume loss (atrophy) of the hippocampus in Alzheimer's disease is shown and is compared to conventional methods.

Algorithms↗

Comparative evaluation of multiresolution optimization strategies for multimodality image registration by maximization of mutual information.

Maximization of mutual information of voxel intensities has been demonstrated to be a very powerful criterion for three-dimensional medical image registration, allowing robust and accurate fully automated affine registration of multimodal images in a variety of applications, without the need for segmentation or other preprocessing of the images. In this paper, we investigate the performance of various optimization methods and multiresolution strategies for maximization of mutual information, aiming at increasing registration speed when matching large high-resolution images. We show that mutual information is a continuous function of the affine registration parameters when appropriate interpolation is used and we derive analytic expressions of its derivatives that allow numerically exact evaluation of its gradient. Various multiresolution gradient- and non-gradient-based optimization strategies, such as Powell, simplex, steepest-descent, conjugate-gradient, quasi-Newton and Levenberg-Marquardt methods, are evaluated for registration of computed tomography (CT) and magnetic resonance images of the brain. Speed-ups of a factor of 3 on average compared to Powell's method at full resolution are achieved with similar precision and without a loss of robustness with the simplex, conjugate-gradient and Levenberg-Marquardt method using a two-level multiresolution scheme. Large data sets such as 256(2) x 128 MR and 512(2) x 48 CT images can be registered with subvoxel precision in <5 min CPU time on current workstations.

Algorithms↗

Experience-dependent changes in basal dendritic branching of layer 2/3 pyramidal neurons during a critical period for developmental plasticity in rat barrel cortex.

In rat barrel cortex, development of layer 2/3 receptive fields can be disrupted by sensory deprivation, with a critical period ending around postnatal day (PND) 14. To determine if experience-dependent plasticity of dendritic morphology could contribute to the reorganization of synaptic inputs, we analyzed dendritic structure in acute brain slices using two-photon laser scanning microscopy (2PLSM) and automated segmentation and analysis software. Layer 2/3 pyramidal cells from control and deprived rats were imaged from PND 9 to PND 20, spanning the critical period. Detailed analyses were performed on basal arbors, which receive the majority of synaptic input from layer 4. Some parameters (number of primary dendrites, volume subtended, aspect ratios) were stable, suggesting that development of several important properties of basal arbors has ceased by age PND 9. However, the spatial organization of secondary branching changed with age and experience. In older neurons there was a larger fraction of branch points farther from the soma. Deprivation from age PND 9 delayed these changes in secondary branching. This effect of deprivation was rapid (detectable at PND 10) and present at all ages observed. Deprivation initiated at PND 15 had no effect on basal branching measured at PND 20. Thus the spatial organization of secondary dendritic branching is experience-dependent and shares a critical period with receptive field plasticity.

Adaptation, Physiological↗

Analysis of soft tissue tumors by an attributed minimum spanning tree.

Histologic slides of 22 soft tissue tumors (9 malignant fibrous histiocytoma, 8 fibrosarcoma, 2 rhabdomyosarcoma, 2 osteosarcoma, 1 Askin tumor) were Feulgen stained. Using an automated image analyzing system (Cambridge 570) at low magnification (25x), the tumor cell nuclei were segmented. The geometrical center of the nuclei was considered the vertex. A basic graph was constructed according to the neighborhood condition of O'Callaghan. Neighboring tumor cell nuclei were visualized by connecting edges. Several features of tumor cell nuclei were measured, including area, surface, major and minor axis of best fitting ellipsis and extinction (DNA content). Nuclear features are attributed to the vertices. The differences, or "distances," between features of connected vertices are attributed to the corresponding edges, which are dependent on the attributes. Thus, different minimum spanning trees (MST) result. Each MST can be decomposed into clusters using a suitable decomposition function on the edges, which rejects an edge if its attributes differ from the mean of the attributed values of surrounding edges more than a neighbor dependent bound (lower limit). Taking into account the length and other attributes of edges (e.g., differences in orientation of the major axis), clusters of different nuclear orientation can be detected. A cluster tree can be constructed by defining the geometric center of a cluster as a new vertex, and by computing the neighborhood of the cluster vertices. The result is an attributed MST containing characteristic structural properties of the image (in cases of sarcomatous tumors, local orientation of tumor cell nuclei and local DNA abnormalities).

Cell Nucleus↗

Automated identification of diabetic retinal exudates in digital colour images.

AIM: To identify retinal exudates automatically from colour retinal images. METHODS: The colour retinal images were segmented using fuzzy C-means clustering following some key preprocessing steps. To classify the segmented regions into exudates and non-exudates, an artificial neural network classifier was investigated. RESULTS: The proposed system can achieve a diagnostic accuracy with 95.0% sensitivity and 88.9% specificity for the identification of images containing any evidence of retinopathy, where the trade off between sensitivity and specificity was appropriately balanced for this particular problem. Furthermore, it demonstrates 93.0% sensitivity and 94.1% specificity in terms of exudate based classification. CONCLUSIONS: This study indicates that automated evaluation of digital retinal images could be used to screen for exudative diabetic retinopathy.

Color↗

Automated segmentation of the left ventricle in cardiac MRI.

We present a fully automated deformable model technique for myocardium segmentation in 3D MRI. Loss of signal due to blood flow, partial volume effects and significant variation of surface grey value appearance make this a difficult problem. We integrate various sources of prior knowledge learned from annotated image data into a deformable model. Inter-individual shape variation is represented by a statistical point distribution model, and the spatial relationship of the epi- and endocardium is modeled by adapting two coupled triangular surface meshes. To robustly accommodate variation of grey value appearance around the myocardiac surface, a prior parametric spatially varying feature model is established by classification of grey value surface profiles. Quantitative validation of 121 3D MRI datasets in end-diastolic (end-systolic) phase demonstrates accuracy and robustness, with 2.45 mm (2.84 mm) mean deviation from manual segmentation.

Algorithms↗

Time to onset of regional relaxation: feasibility, variability and utility of a novel index of regional myocardial function by strain rate imaging.

OBJECTIVES: Time to onset of regional relaxation (T(R)) has been proposed as a novel index of regional myocardial function. This study sought to prospectively establish the feasibility and variability of T(R) in healthy volunteers (CONTROL) and to examine its utility in patients with inducible ischemia (PATIENT). BACKGROUND: Strain rate imaging (SRI) depicts myocardial deformation and enables quantitation of regional myocardial function with high temporal and spatial resolution. Thus, regional mechanical events can be accurately timed with SRI. The time point of regional transition from contraction to relaxation is altered in pathologic states. METHODS: Resting mean segmental T(R) was determined in 60 subjects: 20 in the CONTROL group and 40 in the PATIENT group. T(R) was also measured at peak dobutamine stress in the PATIENT group. An automated image analysis program determined the time point of transition from regional contraction to relaxation activity, and calculated T(R), defined as the time, in milliseconds, from the electrocardiogram R-wave to this transition point. RESULTS: Automated T(R) measurements were feasible in more than 90% of the segments in CONTROL and PATIENT groups. Mean T(R) was 353 +/- 24 ms and was shorter in the mid segments compared to apical and basal segments. Intra- and interobserver variability were low (6% and 9%, respectively). In the PATIENT group, the percent decrease in T(R) during dobutamine stress was significantly higher in normal compared to ischemic segments (30% vs. 19%, respectively, p = 0.01). A percent change >20% in T(R) identified patients with an ischemic response during dobutamine infusion (sensitivity 92%, specificity 75%). CONCLUSIONS: T(R), a novel quantitative index of regional myocardial function, can be determined with low variability and satisfactory feasibility in routine clinical settings. Percent change in T(R) identifies ischemic segments during dobutamine stress echocardiography (DSE) and may allow quantitative assessment of DSE.

Adult↗

Automated brain segmentation from single slice, multislice, or whole-volume MR scans using prior knowledge.

PURPOSE: An automated procedure has been developed to isolate the brain in single/multislice or whole-volume MR images obtained from various sequences. METHOD: T1-weighted, T2-weighted, and inversion recovery images were acquired. The brain segmentation procedure employed (A) a knowledge base that held generic information about the brain in the three orthogonal views and (B) a texture definition and intensity characteristics of features within the head. The brain was segmented by selectively blurring scans using components of B; contour following with region growing was initiated until the isolated feature satisfied the measurements in A. RESULTS: The brain was segmented automatically from 210 subjects (whole volume) and 52 subjects (multi/single slice). Detailed analysis of seven segmented brains showed that < 0.8% of the contour pixels were erroneously identified. Whole-volume head scans consisting of 140 x 256 x 256 pixels were segmented in < 30 min. CONCLUSION: A robust, fast, and efficient procedure has been developed to segment the brain from MR images.

Adult↗

Automated nasopharyngeal carcinoma detection with dynamic gadolinium-enhanced MR imaging.

OBJECTIVES: The purpose of this research is to develop an automatic medical diagnosis for segmenting nasopharyngeal carcinoma (NPC) with dynamic gadolinium-enhanced MR imaging. METHODS: This system is a multistage process, involving motion correction, head mask generation, dynamic MR data quantitative evaluation, rough segmentation, and rough segmentation refinement. Two approaches, a relative signal increase method and a slope method, are proposed for the quantitative evaluation of dynamic MR data. RESULTS: The NPC detection results obtained using the proposed methods had a rating of 85% in match percent compared with these lesions identified by an experienced radiologist. The match percent for the two proposed methods did not have significant differences. However, the computation cost for the slope method was about twelve times faster than the relative signal increase method. CONCLUSIONS: The proposed methods can identify the NPC regions quickly and effectively. This system can enhance the performance of clinical diagnosis.

Analysis of Variance↗

Autofluorescence characteristics of early, atrophic, and high-risk fellow eyes in age-related macular degeneration.

PURPOSE: To assess the relationships of drusen, pigment, and focally increased autofluorescence (FIAF) and the reticular pattern of hypoautofluorescence, to distinguish the combined photographic and AF characteristics of early, atrophic, and high-risk fellow eyes in AMD. METHODS: In a retrospective interinstitutional clinical study, AF and color photograph pairs of 221 eyes were examined: 166 eyes of 83 patients with bilateral large, soft drusen, with and without geographic atrophy (GA), and 55 fellow eyes of 55 patients with unilateral choroidal neovascularization (CNV). Forty-two eyes (one eye from each of 42 patients with early or atrophic AMD) were divided into four groups: 14 with drusen only, 9 with drusen and pigment abnormalities, 11 fellow eyes of patients with unilateral GA, and 8 eyes of patients with bilateral GA (acronyms for the groups: D-D, D-Pig, D-GA and GA-GA, respectively). The 55 fellow eyes of patients with CNV were divided into three groups: 19 eyes with no FIAF (CNV-0), 16 with FIAF without reticular AF (CNV-1), and 20 eyes with reticular AF and/or pseudodrusen (CNV-R). Image pairs of eyes with FIAF were registered, and drusen, pigment, and FIAF were segmented using automated background leveling and thresholding. All 221 eyes were surveyed for reticular AF and reticular pseudodrusen. The main outcome measures were (1) the fraction and relative probability of FIAF colocalizing with drusen and pigment and (2) the presence or absence of reticular AF and reticular pseudodrusen. RESULTS: The mean fractions of FIAF that colocalized with large drusen were: D-D group, 0.46 +/- 0.21; D-Pig group, 0.42 +/- 0.29; D-GA group, 0.13 +/- 0.09; and GA-GA group, 0.11 +/- 0.12. Comparisons between groups showed significant differences when comparing either the D-D group or the D-Pig group with either the D-GA group or the GA-GA group (P between 0.0001 and 0.015), whereas other comparisons were nonsignificant (Mann-Whitney rank sum test). The mean probabilities of FIAF colocalizing with large drusen relative to chance (1.0) were: D-D group, 4.7 +/- 2.5; D-Pig group, 4.3 +/- 2.3; D-GA group, 1.4 +/- 0.8; and GA-GA group, 1.8 +/- 1.3, with similar significant differences as for the colocalization fractions. The mean probability of FIAF colocalizing with small to intermediate drusen in the D-D group was 1.5 +/- 1.3, which was not significantly different from chance. In the D-Pig group, the median probability of FIAF colocalizing with pigment abnormalities was 10.0 (range, 1.1-51.0). The AF patterns in 15 of 19 eyes in the CNV-0 group were normal; the remainder had nonreticular hypoautofluorescence only. In the CNV-1 group, the relations of FIAF with drusen and pigment were similar to those in the early AMD groups. CNV-R comprised 20 of 55 eyes in the CNV group, but reticular autofluorescence and/or pseudodrusen were found in only 14 of 166 eyes of the early and atrophic groups. Of the 34 total eyes with reticular AF or pseudodrusen, 28 had both, 4 had reticular AF only, and 2 had reticular pseudodrusen only. CONCLUSIONS: There are clear relationships between AF patterns and clinical AMD status. In early AMD, FIAF's colocalization with large, soft drusen and hyperpigmentation is several times greater than chance, suggesting linked disease processes. In advanced atrophic AMD, FIAF is found mostly adjacent to drusen and GA, suggesting that dispersal of drusen-associated lipofuscin is a marker of atrophic disease progression. In the neovascular case, a large group of fellow eyes have no FIAF abnormalities, suggesting that lipofuscin is not a major determinant of CNV. However, reticular hypoautofluorescence, consistent with widespread inflammatory damage to the RPE, appears to be a highly sensitive imaging marker for the disease that determines reticular pseudodrusen and is strongly associated with CNV.

Atrophy↗

Automatic vessel segmentation and quantification of the rat aortic ring assay of angiogenesis.

BACKGROUND: Pharmacologic control of angiogenesis is a promising new approach to the treatment of a variety of pathologic conditions including cancer. The recently developed in vitro rat aortic ring model provides a simple, reproducible assay for discovering angiogenic agonists and antagonists. However, quantification of results in this assay is time consuming, tedious, and subjective, because it involves visual inspection of images and manually counting the newly formed microvessels extending from the cultured aortic ring. This report describes an automated image analysis-based procedure for quantification of this assay that overcomes these difficulties. EXPERIMENTAL DESIGN: The designed image processing algorithm segments the vessels from gray scale images. A high-pass filter is used, and the results are separated into nonvascular and vessel compartments based on object size and shape. Quantification relies on identification of vessels intersecting a closed transect set a fixed distance from the aortic ring. The number and the total area of these vessels are determined. The entire operation has been automated and packaged in an application called Vessels. RESULTS: The correlation between computer-determined vessel area/vessel number and visual microvessel count is high (r2 = 0.91 and r2 = 0.86, respectively). CONCLUSION: Vessels offers high-speed, fully automatic batch processing including production of a hard copy for documentation. The application runs on the Apple family of computers. On a Quadra 800, the application can process approximately 30 images/hour, which is approximately 2.5 times faster than manual quantification of this assay.

Animals↗