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Computer-aided differential diagnosis system for Alzheimer’s disease based on machine learning with functional and morphological image features in magnetic resonance imaging  [PDF]
Yasuo Yamashita, Hidetaka Arimura, Takashi Yoshiura, Chiaki Tokunaga, Ohara Tomoyuki, Koji Kobayashi, Yasuhiko Nakamura, Nobuyoshi Ohya, Hiroshi Honda, Fukai Toyofuku
Journal of Biomedical Science and Engineering (JBiSE) , 2013, DOI: 10.4236/jbise.2013.611137

Alzheimer’s disease (AD) is a dementing disorder and one of the major public health problems in countries with greater longevity. The cerebral cortical thickness and cerebral blood flow (CBF), which are considered as morphological and functional image features, respectively, could be decreased in specific cerebral regions of patients with dementia of Alzheimer type. Therefore, the aim of this study was to develop a computer-aided classification system for AD patients based on machine learning with the morphological and functional image features derived from a magnetic resonance (MR) imaging system. The cortical thicknesses in ten cerebral regions were derived as morphological features by using gradient vector trajectories in fuzzy membership images. Functional CBF maps were measured with an arterial spin labeling technique, and ten regional CBF values were obtained by registration between the CBF map and Talairach atlas using an affine transformation and a free form deformation. We applied two systems based on an arterial neural network (ANN) and a support vector machine (SVM), which were trained with 4 morphological and 6 functional image features, to 15 AD patients and 15 clinically normal (CN) subjects for classification of AD. The area under the receiver operating characteristic curve (AUC) values for the two systems based on the ANN and SVM with both image features were 0.901 and 0.915, respectively. The AUC values for the ANN-and SVM-based systems with the morphological features were 0.710 and 0.660, respectively, and those with the functional features were 0.878 and 0.903, respectively. Our preliminary results suggest that the proposed method may have potential for assisting radiologists in the differential diagnosis of AD patients by using morphological and functional image features.

Automated measurement of three-dimensional cerebral cortical thickness in Alzheimer’s patients using localized gradient vector trajectory in fuzzy membership maps  [PDF]
Chiaki Tokunaga, Hidetaka Arimura, Takashi Yoshiura, Tomoyuki Ohara, Yasuo Yamashita, Kouji Kobayashi, Taiki Magome, Yasuhiko Nakamura, Hiroshi Honda, Hideki Hirata, Masafumi Ohki, Fukai Toyofuku
Journal of Biomedical Science and Engineering (JBiSE) , 2013, DOI: 10.4236/jbise.2013.63A042

Our purpose in this study was to develop an automated method for measuring three-dimensional (3D) cerebral cortical thicknesses in patients with Alzheimer’s disease (AD) using magnetic resonance (MR) images. Our proposed method consists of mainly three steps. First, a brain parenchymal region was segmented based on brain model matching. Second, a 3D fuzzy membership map for a cerebral cortical region was created by applying a fuzzy c-means (FCM) clustering algorithm to T1-weighted MR images. Third, cerebral cortical thickness was three- dimensionally measured on each cortical surface voxel by using a localized gradient vector trajectory in a fuzzy membership map. Spherical models with 3 mm artificial cortical regions, which were produced using three noise levels of 2%, 5%, and 10%, were employed to evaluate the proposed method. We also applied the proposed method to T1-weighted images obtained from 20 cases, i.e., 10 clinically diagnosed AD cases and 10 clinically normal (CN) subjects. The thicknesses of the 3 mm artificial cortical regions for spherical models with noise levels of 2%, 5%, and 10% were measured by the proposed method as 2.953 ± 0.342, 2.953 ± 0.342 and 2.952 ± 0.343 mm, respectively. Thus the mean thicknesses for the entire cerebral lobar region were 3.1 ± 0.4 mm for AD patients and 3.3 ± 0.4 mm for CN subjects, respectively (p < 0.05). The proposed method could be feasible for measuring the 3D cerebral cortical thickness on individual cortical surface voxels as an atrophy feature in AD.

Serum biomarker tests are useful in delineating between patients with gastric atrophy and normal, healthy stomach
Katsunori Iijima, Yasuhiko Abe, Ryosuke Kikuchi, Tomoyuki Koike, Shuichi Ohara, Pentti Sipponen, Tooru Shimosegawa
World Journal of Gastroenterology , 2009,
Abstract: AIM: To study the value of serum biomarker tests to differentiate between patients with healthy or diseased stomach mucosa: i.e. those with Helicobacter pylori (H pylori) gastritis or atrophic gastritis, who have a high risk of gastric cancer or peptic ulcer diseases.METHODS: Among 162 Japanese outpatients, pepsinogen I (Pg I) and II (Pg II) were measured using a conventional Japanese technique, and the European GastroPanel examination (Pg I and Pg II, gastrin-17 and H pylori antibodies). Gastroscopy with gastric biopsies was performed to classify the patients into those with healthy stomach mucosa, H pylori non-atrophic gastritis or atrophic gastritis.RESULTS: Pg I and Pg II assays with the GastroPanel and the Japanese method showed a highly significant correlation. For methodological reasons, however, serum Pg I, but not Pg II, was twice as high with the GastroPanel test as with the Japanese test. The biomarker assays revealed that 5% of subjects had advanced atrophic corpus gastritis which was also verified by endoscopic biopsies. GastroPanel examination revealed an additional seven patients who had either advanced atrophic gastritis limited to the antrum or antrum-predominant H pylori gastritis. When compared to the endoscopic biopsy findings, the GastroPanel examination classified the patients into groups with “healthy” or “diseased” stomach mucosa with 94% accuracy, 95% sensitivity and 93% specificity.CONCLUSION: Serum biomarker tests can be used to differentiate between subjects with healthy and diseased gastric mucosa with high accuracy.
Brain activity following esophageal acid infusion using positron emission tomography
Shigeyuki Kobayashi, Yasuhiko Abe, Manabu Tashiro, Tomoyuki Koike, Katsunori Iijima, Akira Imatani, Shuichi Ohara, Satoshi Watanabe, Shin Fukudo, Tooru Shimosegawa
World Journal of Gastroenterology , 2010,
Abstract: AIM: To investigate symptoms and brain activity following esophageal acid infusion.METHODS: Fifteen healthy volunteers were recruited for the study. Hydrochloric acid (pH 1 and 2) and distilled water (pH 7) were randomly and repeatedly infused into the esophagus. The brain activity was evaluated by positron emission tomography. The severity of heartburn elicited by the infusion was rated on an auditory analog scale of 0-10.RESULTS: The severity of heartburn following each infusion showed a step-wise increase with increasing acidity of the perfusate. The heartburn scores were significantly higher in the second pH 1 infusion compared with the first infusion. Acid and distilled water infusion induced activation of various brain areas such as the anterior insula, temporal gyrus, and anterior/posterior cingulate cortex. At pH 1 or 2, in particular, activation was observed in some emotion-related brain areas such as the more anterior part of the anterior cingulate cortex, parahippocampal gyrus, or the temporal pole. Strong activation of the orbitofrontal cortex was found by subtraction analysis of the two second pH 1 infusions, with a significant increase of heartburn symptoms.CONCLUSION: Emotion-related brain areas were activated by esophageal acid stimulation. The orbitofrontal area might be involved in symptom processing, with esophageal sensitization induced by repeated acid stimulation.
Identification of the layered morphology of the esophageal wall by optical coherence tomography
Satoshi Yokosawa, Tomoyuki Koike, Yasushi Kitagawa, Waku Hatta, Kaname Uno, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa
World Journal of Gastroenterology , 2009,
Abstract: AIM: To assess each layer of the optical coherence tomography (OCT) image of the esophageal wall with reference to the histological structure.METHODS: Resected specimens of fresh pig esophagus was used as a model for the esophageal wall. We injected cyanoacrylate adhesive into the specimens to create a marker, and scanned them using a miniature OCT probe. The localization of these markers was assessed in the OCT images. Then we compared the OCT-imaged morphology with the corresponding histological section, guided by the cyanoacrylate adhesive markers. We prepared a second set of experiments using nylon sutures as markers.RESULTS: The OCT image of the esophageal specimen has a clear five-layered morphology. First, it consisted of a relatively less reflective layer; second, a more reflective layer; third, a less reflective layer; fourth, a more reflective layer; and fifth, a less reflective layer. Comparing the OCT images with marked histological sections showed that the first layer corresponded to stratified squamous epithelium; the second to lamina propria; the third to muscularis mucosa; fourth, submucosa; and fifth, muscularis propria with deeper structures of the esophageal wall.CONCLUSION: We demonstrated that the OCT image of the normal esophageal wall showed a five-layered morphology, which corresponds to histological esophageal wall components.
Incidence of reflux esophagitis and Helicobacter pylori infection in diabetic patients
Ken Ariizumi, Tomoyuki Koike, Shuichi Ohara, Yoshifumi Inomata, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Yoshitomo Oka, Tooru Shimosegawa
World Journal of Gastroenterology , 2008,
Abstract: AIM: To investigate the incidence of reflux esophagitis (RE) and H pylori infection in the diabetic patient.METHODS: The incidence of RE and H pylori infection were investigated in 85 patients with diabetes mellitus and the results were compared with controls.RESULTS: The incidence of RE in diabetic patients was 17.6%. Although this tended to be higher in diabetic patients, there were no statistically significant differences between diabetic patients and controls. The incidence of H pylori infection in diabetic patients was 53.7% but no statistically significant difference was seen between diabetic patients and controls in the incidence of H pylori infection.CONCLUSION: No significant differences could be seen between diabetic patients and controls in the incidence of RE and H pylori infection.
On the Convergence of Observed Partial Likelihood under Incomplete Data with Two Class Possibilities  [PDF]
Tomoyuki Sugimoto
Open Journal of Statistics (OJS) , 2014, DOI: 10.4236/ojs.2014.42012

In this paper, we discuss the theoretical validity of the observed partial likelihood (OPL) constructed in a Coxtype model under incomplete data with two class possibilities, such as missing binary covariates, a cure-mixture model or doubly censored data. A main result is establishing the asymptotic convergence of the OPL. To reach this result, as it is difficult to apply some standard tools in the survival analysis, we develop tools for weak convergence based on partial-sum processes. The result of the asymptotic convergence shown here indicates that a suitable order of the number of Monte Carlo trials is less than the square of the sample size. In addition, using numerical examples, we investigate how the asymptotic properties discussed here behave in a finite sample.

Stronger inhibition of gastric acid secretion by lafutidine, a novel H receptor antagonist, than by the proton pump inhibitor lansoprazole
Hatsushi Yamagishi, Tomoyuki Koike, Shuichi Ohara, Toru Horii, Ryousuke Kikuchi, Shigeyuki Kobayashi, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Kaori Suzuki, Takanori Hishinuma, Junichi Goto, Tooru Shimosegawa
World Journal of Gastroenterology , 2008,
Abstract: AIM: To compare the antisecretory activity and plasma drug concentrations of a single oral dose of 10 mg lafutidine, a novel H2 receptor antagonist, with those of the proton pump inhibitor lansoprazole (LPZ) 30 mg.METHODS: Ten volunteers without H pylori infection participated in this crossover study comparing lafutidine 10 mg with LPZ 30 mg. Intragastric pH was monitored for 6 h in all participants, and blood samples were collected from four randomly selected individuals after single-dose administration of each drug.RESULTS: The median intragastric pH was significantly higher in individuals who received lafutidine 10 mg than in those who received LPZ 30 mg 2, 3, 4, 5, and 6 h after administration. Maximal plasma drug concentration was reached more promptly with lafutidine 10 mg than with LPZ 30 mg.CONCLUSION: In H pylori-negative individuals, gastric acid secretion is more markedly inhibited by lafutidine than by LPZ.
Prevalence of gastroesophageal reflux symptoms in a large unselected general population in Japan
Hatsushi Yamagishi, Tomoyuki Koike, Shuichi Ohara, Shigeyuki Kobayashi, Ken Ariizumi, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Yoshifumi Inomata, Katsuaki Kato, Daisuke Shibuya, Shigemitsu Aida, Tooru Shimosegawa
World Journal of Gastroenterology , 2008,
Abstract: AIM: To examine the prevalence of gastroesophageal reflux disease (GERD) symptoms in a large unselected general population in Japan.METHODS: In Japan, mature adults are offered regular check-ups for the prevention of gastric cancer. A notice was sent by mail to all inhabitants aged > 40 years. A total of 160 983 Japanese (60 774 male, 100 209 female; mean age 61.9 years) who underwent a stomach check up were enrolled in this study. In addition, from these 160 983 subjects, we randomly selected a total of 82 894 (34 275 male, 48 619 female; mean age 62.4 years) to evaluate the prevalence of abdominal pain. The respective subjects were prospectively asked to complete questionnaires concerning the symptoms of heartburn, dysphagia, and abdominal pain for a 1 mo period.RESULTS: The respective prevalences of the symptoms in males and females were: heartburn, 15.8% vs 20.7%; dysphagia, 5.4% vs 7.8%; and abdominal pain, 6.6% vs 9.6%. Among these symptoms, heartburn was significantly high compared with the other symptoms, and the prevalence of heartburn was significantly more frequent in females than in males in the 60-89-year age group. Dysphagia was also significantly more frequent in female patients.CONCLUSION: The prevalence of typical GERD symptoms (heartburn) was high, at about 20% of the Japan population, and the frequency was especially high in females in the 60-89 year age group.
Early effects of Lansoprazole orally disintegrating tablets on intragastric pH in CYP2C19 extensive metabolizers
Hatsushi Yamagishi, Tomoyuki Koike, Shuichi Ohara, Toru Horii, Ryousuke Kikuchi, Shigeyuki Kobayashi, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Kaori Suzuki, Takanori Hishinuma, Junichi Goto, Tooru Shimosegawa
World Journal of Gastroenterology , 2008,
Abstract: AIM: To compare rabeprazole (RPZ; 10 mg) with Lansoprazole orally disintegrating tablets (LPZ; 30 mg OD) in terms of antisecretory activity and blood drug concentration after a single dose.METHODS: Eight H pylori-negative cytochrome P450 (CYP) 2C19 extensive metabolizers were assigned to receive a single oral dose of RPZ 10 mg or LPZ 30 mg OD. Twelve hour intragastric pH monitoring was performed on the day of treatment. Blood samples were also collected after the administration of each drug.RESULTS: LPZ 30 mg OD induced a significantly earlier rise in blood drug concentration than RPZ 10 mg; consequently, LPZ 30 mg OD induced a significantly earlier rise in median pH in the third and fourth hours of the study.CONCLUSION: In H pylori-negative CYP2C19 extensive metabolizers, LPZ 30 mg OD induced a significantly faster inhibition of gastric acid secretion than RPZ 10 mg.
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