Heung Kook Choi

Brightness preserving weight clustering histogram equalization

Histogram equalization (GHE) is a simple and widely accepted method for contrast enhancement. Although there are extensions of GHE that can preserve the brightness of the original image better than the original method, these extensions sometimes fail to enhance the visualization of the original image. Therefore, we propose a new method called Brightness Preserving Weight Clustering Histogram Equalization (BPWCHE) that can simultaneously preserve the brightness of the original image and enhance visualization of the original image. BPWCHE assigns each non-zero bin of the original images histogram to a separate cluster, and computes each clusters weight. Then, to reduce the number of clusters, we use three criteria (cluster weight, weight ratio and widths of two neighboring clusters) to merge pairs of neighboring clusters. The clusters acquire the same partitions as the result image histogram. Finally, transformation functions for each clusters sub-histogram are calculated based on the traditional GHE method in the new acquired partitions of the result image histogram, and the sub-histograms gray levels are mapped to the result image by the corresponding transformation functions. We showed experimentally that BPWCHE can preserve image brightness and enhance visualization of images more effectively than GHE and other brightness preserving methods.

Weight Clustering Histogram Equalization for Medical Image Enhancement

Contrast enhancement is important and useful for medical images. One of the widely accepted contrast enhancement method is histogram equalization (GHE). Although GHE achieves comparatively better performance on almost all types of image, GHE sometimes produces excessive visual deterioration. Some extensions of GHE are developed, however these extensions sometimes either fail to enhance the visualization or over enhance contrast of the original image. By over-enhancing contrast, some important information may be lost. Therefore we propose a new method called Weight Clustering Histogram Equalization (WCHE). WCHE assigns each non-zero bin of the original images histogram to a separate cluster, and computes each clusters weight. The cluster numbers are reduced by three suggesting criteria. Then, the clusters acquire the same partitions as the result image histogram. Finally, transformation functions for each clusters sub-histogram are calculated based on the traditional GHE method in the new acquired partitions of the result image histogram, and the sub-histograms gray levels are mapped to the result image by the corresponding transformation functions. We showed experimentally that WCHE bas been validated with some numerical results.

Multinucleation of koilocytes is in fact multilobation and is related to aberration of the G2 checkpoint.

Aims: To clarify the fine structure of koilocytes and correlate this with genetic aberration of the G2 checkpoint Methods: Three dimensional reconstruction from confocal fluorescent images, together with functional assays for key molecules of the G2 checkpoint—cdc2 and cyclin B1—was performed in human uterine cervical samples. After confirming 22 human papillomavirus (HPV) types using a DNA chip from 30 cervical swabs, previously confirmed as 15 cervical low grade and 15 high grade intraepithelial lesions, the activity of molecules involved in the G2 checkpoint was evaluated using western blotting for cyclin B1, cdc2, and phospho-cdc2 (Y15 and T161), a nuclear extraction fractional assay, and a reverse transcription polymerase chain reaction assay. In addition, three dimensional confocal image restoration was performed on confirmed cervical intraepithelial neoplasia tissue samples. Results: T161 phospho-cdc2 and cyclin B1 expression was higher in HPV infected cervical lesions than in normal samples. Immunofluorescence, revealed that cyclin B1 was present predominantly in the nuclei of HPV infected cells, confirming the results of the nuclear fractional assay. On restoration of three dimensional confocal images, the multinucleation of koilocytes was revealed to be multilobation of a single nucleus, rather than true multinucleation. This multilobation appeared to be associated with chromosomal instability and aberration of the G2 checkpoint. Conclusions: The multiple nuclei of koilocytes are in fact multilobation of a single nucleus, and this phenomenon is associated with upregulation of gene products related to the G2 checkpoint.

Grading and Interpretation of White Matter Hyperintensities Using Statistical Maps

Background and Purpose— We aimed to generate rigorous graphical and statistical reference data based on volumetric measurements for assessing the relative severity of white matter hyperintensities (WMHs) in patients with stroke. Methods— We prospectively mapped WMHs from 2699 patients with first-ever ischemic stroke (mean age=66.8±13.0 years) enrolled consecutively from 11 nationwide stroke centers, from patient (fluid-attenuated-inversion-recovery) MRIs onto a standard brain template set. Using multivariable analyses, we assessed the impact of major (age/hypertension) and minor risk factors on WMH variability. Results— We have produced a large reference data library showing the location and quantity of WMHs as topographical frequency-volume maps. This easy-to-use graphical reference data set allows the quantitative estimation of the severity of WMH as a percentile rank score. For all patients (median age=69 years), multivariable analysis showed that age, hypertension, atrial fibrillation, and left ventricular hypertrophy were independently associated with increasing WMH (0–9.4%, median=0.6%, of the measured brain volume). For younger (⩽69) hypertensives (n=819), age and left ventricular hypertrophy were positively associated with WMH. For older (≥70) hypertensives (n=944), age and cholesterol had positive relationships with WMH, whereas diabetes mellitus, hyperlipidemia, and atrial fibrillation had negative relationships with WMH. For younger nonhypertensives (n=578), age and diabetes mellitus were positively related to WMH. For older nonhypertensives (n=328), only age was positively associated with WMH. Conclusions— We have generated a novel graphical WMH grading (Kim statistical WMH scoring) system, correlated to risk factors and adjusted for age/hypertension. Further studies are required to confirm whether the combined data set allows grading of WMH burden in individual patients and a tailored patient-specific interpretation in ischemic stroke-related clinical practice.

Stroke outcomes are worse with larger leukoaraiosis volumes

Leukoaraiosis or white matter hyperintensities are frequently observed on magnetic resonance imaging of stroke patients. We investigated how white matter hyperintensity volumes affect stroke outcomes, generally and by subtype. In total, 5035 acute ischaemic stroke patients were enrolled. Strokes were classified as large artery atherosclerosis, small vessel occlusion, or cardioembolism. White matter hyperintensity volumes were stratified into quintiles. Mean age (± standard deviation) was 66.3 ± 12.8, 59.6% male. Median (interquartile range) modified Rankin Scale score was 2 (1–3) at discharge and 1 (0–3) at 3 months; 16.5% experienced early neurological deterioration, and 3.3% recurrent stroke. The Cochran-Mantel-Haenszel test with adjustment for age, stroke severity, sex, and thrombolysis status showed that the distributions of 3-month modified Rankin Scale scores differed across white matter hyperintensity quintiles (P < 0.001). Multiple ordinal logistic regression analysis showed that higher white matter hyperintensity quintiles were independently associated with worse 3-month modified Rankin Scale scores; adjusted odds ratios (95% confidence interval) for the second to fifth quintiles versus the first quintile were 1.29 (1.10–1.52), 1.40 (1.18–1.66), 1.69 (1.42–2.02) and 2.03 (1.69–2.43), respectively. For large artery atherosclerosis (39.0%), outcomes varied by white matter hyperintensity volume (P = 0.01, Cochran-Mantel-Haenszel test), and the upper three white matter hyperintensity quintiles (versus the first quintile) had worse 3-month modified Rankin Scale scores; adjusted odds ratios were 1.45 (1.10–1.90), 1.86 (1.41–2.47), and 1.89 (1.41–2.54), respectively. Patients with large artery atherosclerosis were vulnerable to early neurological deterioration (19.4%), and the top two white matter hyperintensity quintiles were more vulnerable still: 23.5% and 22.3%. Moreover, higher white matter hyperintensities were associated with poor modified Rankin Scale improvement: adjusted odds ratios for the upper two quintiles versus the first quintile were 0.66 (0.47–0.94) and 0.62 (0.43–0.89), respectively. For small vessel occlusion (17.8%), outcomes tended to vary by white matter hyperintensitiy volume (P = 0.10, Cochran-Mantel-Haenszel test), and the highest quintile was associated with worse 3-month modified Rankin Scale scores: adjusted odds ratio for the fifth quintile versus first quintile, 1.98 (1.23–3.18). In this subtype, worse white matter hyperintensities were associated with worse National Institute of Health Stroke Scale scores at presentation. For cardioembolism (20.6%), outcomes did not vary significantly by white matter hyperintensity volume (P = 0.19, Cochran-Mantel-Haenszel test); however, the adjusted odds ratio for the highest versus lowest quintiles was 1.62 (1.09–2.40). Regardless of stroke subtype, white matter hyperintensities were not associated with stroke recurrence within 3 months of follow-up. In conclusion, white matter hyperintensity volume independently correlates with stroke outcomes in acute ischaemic stroke. There are some suggestions that stroke outcomes may be affected by leukoaraiosis differentially depending on stroke subtypes, to be confirmed in future investigations.

3D Texture Analysis in Renal Cell Carcinoma Tissue Image Grading

One of the most significant processes in cancer cell and tissue image analysis is the efficient extraction of features for grading purposes. This research applied two types of three-dimensional texture analysis methods to the extraction of feature values from renal cell carcinoma tissue images, and then evaluated the validity of the methods statistically through grade classification. First, we used a confocal laser scanning microscope to obtain image slices of four grades of renal cell carcinoma, which were then reconstructed into 3D volumes. Next, we extracted quantitative values using a 3D gray level cooccurrence matrix (GLCM) and a 3D wavelet based on two types of basis functions. To evaluate their validity, we predefined 6 different statistical classifiers and applied these to the extracted feature sets. In the grade classification results, 3D Haar wavelet texture features combined with principal component analysis showed the best discrimination results. Classification using 3D wavelet texture features was significantly better than 3D GLCM, suggesting that the former has potential for use in a computer-based grading system.

A New Image-Based Stroke Registry Containing Quantitative Magnetic Resonance Imaging Data

Background: Conventional stroke registries contain alphanumeric text-based data on the clinical status of stroke patients, but this format captures imaging data in a very limited form. There is a need for a new type of stroke registry to capture both text- and image-based data. Methods and Results: We designed a next-generation stroke registry containing quantitative magnetic resonance imaging (MRI) data, ‘DUIH_SRegI’, developed a supporting software package, ‘Image_QNA’, and performed experiments to assess the feasibility and utility of the system. Image_QNA enabled the mapping of stroke-related lesions on MR onto a standard brain template and the storage of this extracted imaging data in a visual database. Interuser and intrauser variability of the lesion mapping procedure was low. We compared the results from the semi automatic lesion registration using Image_QNA with automatic lesion registration using SPM5 (Statistical Parametric Mapping version 5), a well-regarded standard neuroscience software package, in terms of lesion location, size and shape, and found Image_QNA to be superior. We assessed the clinical usefulness of an image-based registry by studying 47 consecutive patients with first-ever lacunar infarcts in the corona radiata. We used the enriched dataset comprised of both image-based and alphanumeric databases to show that diffusion MR lesions overlapped in a more posterolateral brain location for patients with high NIH Stroke Scale scores (≧4) than for patients with low scores (≤3). In April 2009, we launched the first prospective image-based acute (≤1 week) stroke registry at our institution. The registered data include high signal intensity ischemic lesions on diffusion, T2-weighted, or fluid attenuation inversion recovery MRIs, and low signal intensity hemorrhagic lesions on gradient-echo MRIs. An interim analysis at 6 months showed that the time requirement for the lesion registration (183 consecutive patients, 3,226 MR slices with visible stroke-related lesions) was acceptable at about 1 h of labor per patient by a trained assistant with physician oversight. Conclusions: We have developed a novel image-based stroke registry, with database functions that allow the formulation and testing of intuitive, image-based hypotheses in a manner not easily achievable with conventional alphanumeric stroke registries.

Computerized Renal Cell Carcinoma Nuclear Grading Using 3D Textural Features

An extraction of important features in cancer cell image analysis is a key process in grading renal cell carcinoma. In this study, we applied three-dimensional (3D) texture feature extraction methods to cancer cell nuclei images and evaluated the validity of them for computerized cell nuclei grading. Individual images of 1,800 cell nuclei were extracted from 8 classes of renal cell carcinomas (RCCs) tissues using confocal laser scanning microscopy (CLSM). First, we extracted the chromatin texture quantitatively by calculating 3D gray-level co-occurrence matrices (3D GLCM) and 3D run length matrices (3D GLRLM). To demonstrate the suitability of 3D texture features for grading, we had performed a principal component analysis to reduce feature dimensionality, then, we also performed discriminant analysis as statistical classifier. Finally this result was compared with the result of classification using several optimized features that extracted from stepwise features selection. Additionally AUC (area under curve) analysis was performed for the grade 2 and 3 cell images. Three dimensional texture features have potential for use as fundamental elements in developing a new nuclear grading system with accurate diagnosis and predicting prognosis.

Quantitative analysis of chemotherapeutic effects in tumors using in vivo staining and correlative histology.

Aims: To microscopically analyze the chemotherapeutic response of tumors using in vivo staining based on an annexinV-Cy5.5 probe and independently asses their apoptotic count using quantitative histological analysis. Methods: Lewis Lung Carcinomas cells, that are sensitive (CS-LLC) and resistant (CR-LLC) to chemotherapy were implanted in nude mice and grown to tumours. Mice were treated with cyclophosphamide and injected with a Cy5.5-annexinV fluorescent probe. In vivo imaging was performed using Fluorescence Molecular Tomography. Subsequently tumours were excised and prepared for histology. The histological tumour sections were stained for apoptosis using a terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. A minimum of ten tissue sections were analyzed per tumour for apoptosis quantification by TUNEL staining and corresponding Cy5.5 distribution. Results: We detected higher levels of apoptosis and corresponding higher levels of Cy5.5 fluorescence in the CS-LLC vs. the CR-LLC tumours. The cell count rate on CS-LLC sections over CR-LLC was found to be ∼2u2009:1 where the corresponding area observed on Cy5.5 distribution measurements revealed a ∼1.7u2009:1 ratio of CS-LLC over CR-LLC. These observations are consistent with the higher apoptotic index expected from the CS-LLC cell line. Conclusions: Quantitative analysis of histological slices revealed higher fluorescence and higher apoptotic count in the CS-LLC tumour images compared to the CR-LLC tumour images. These observations demonstrate that the annexinV-Cy5.5 probe sensed the chemotherapeutic effect of cyclophospamide and further confirmed in vivo FMT measurements.

Regional contractility measurement of the left ventricle using gated myocardial SPECT

Maximal elastance (E/sub max/: maximal ratio of pressure over volume) of left ventricular myocardium obtained from time-varying elastance curves represents myocardial contractility, which is independent of preload and afterload. A non-invasive method of quantifying myocardial global contractility using a single systolic PV loop was developed by Senzaki et al. and extended by Lee et al. by measuring time-volume curve using gated myocardial SPECT. Since these previous methods provide only the overall contractile function of left ventricle, we developed a method to quantify the regional contractility of myocardium. For total 55-72 regions, regional volume curve was estimated. Regional volume curves were obtained by extracting endocardial surface of left ventricle from each gated frame.