Does cerebrospinal fluid pulsation affect diffusion-weighted imaging thermometry? A study in healthy volunteers.

Diffusion-weighted imaging (DWI)-based thermometry offers potential as a noninvasive method for measuring temperatures deep inside the human brain. However, DWI might be influenced by the pulsatile flow of cerebrospinal fluid (CSF). This study aimed to investigate the influence of such pulsations on DWI thermometry in healthy individuals. A total of 104 participants (50 men, 54 women; mean [± standard deviation] age, 44.2 ± 14.3 years; range 21-69 years) were investigated. DWI-based brain temperature (TDWI ) was acquired at three speeds (maximum and minimum speeds of ascending flow and random timing at the cerebral aqueduct) of CSF pulsation using a 3-T magnetic resonance imaging scanner. Magnetic resonance spectroscopy (MRS)-based temperature (TMRS ) at the thalamus was also obtained as a reference standard for brain temperature. The three different CSF pulsatile flows were monitored by heart rate during the scan. The difference between reference temperature and brain temperature (ΔT = TDWI - TMRS ) along with the three CSF speeds were statistically compared using Student's matched pair t-test. No significant difference in ΔT was evident among CSF speeds (p > 0.05). No significant linear correlation between ΔT and CSF flow speed at the cerebral aqueduct was observed. Using DWI thermometry with clinical acquisition settings, which utilizes mean values within thresholds, no effect of CSF pulsation speed was observed in the estimation of ΔT.

[Usefulness of the Principle of Selective Excitation Technique Non-electrocardiogramgated 3D-TOF Method in Lower-extremity MRA Using a Whole-body Coil].

PURPOSE: Generally, non-contrast, lower-extremity, magnetic resonance angiography (MRA) uses electrocardiography; thus, examination is difficult in patients who exhibit arrhythmia. However, the use of electrocardiography can be avoided by using the selective excitation technique in non-electrocardiogram-gated three-dimensional time-of-flight (TOF) (pNon-Gate) MRA. Therefore, patients who exhibit arrhythmia can be examined with pNon-Gate MRA. The purpose of this study was to assess the usefulness of pNon-Gate MRA by using a whole-body coil. METHODS: Images acquired using pNon-Gate MRA were compared with images acquired using electrocardiogram-gated two-dimensional TOF (Gate) MRA. Comparisons comprised visual evaluation, as well as comparisons of contrast-to-noise ratio and imaging time. RESULTS: In visual evaluation of the pelvic region, Gate MRA showed better results than pNon-Gate MRA. In terms of contrast-to-noise ratio, there were no significant differences in either region. Imaging time showed no significant differences between the two methods. However, it exceeded 30 minutes frequently for Gate MRA, but rarely for pNon-Gate MRA. CONCLUSIONS: pNon-Gate MRA is useful in patients with frequent arrhythmia and in those with difficulty in maintaining long-term postures. By using a whole-body coil, pNon-Gate MRA enables easier patient positioning and setting. Therefore, pNon-Gate MRA can be used in routine examinations.

Transition of deformation modes from bending to auxetic compression in origami-based metamaterials for head protection from impact.

For the protection of the human head by energy absorption structures, a soft mechanical response upon contact with the head is required to mitigate the effect of impact, while a hard mechanical response for highly efficient energy absorption is required to stop the movement of the head. This study realized the opposite mechanical properties during head protection by transitioning the deformation mode from bending to auxetic compression. First, non-linear finite element (FE) models were constructed to numerically reproduce the bending behavior. The calculated force responses agreed well with forces in bending tests. Using the FE models, the EA structures with proper transition of deformation modes were designed and installed in the seat headrests of real vehicles. Head protection was evaluated by dynamic loading in sled testing, in which the force on the head of the crash test dummy was measured. The head injury criterion improved from 274 to 155, indicating the superior performance of the tested structures compared to that achieved by energy absorption structures based on steel plates. Moreover, the deformation of auxetic structures prevented neck bending by holding the head. These findings present new possibilities for effectively protecting the human body by mitigating impact, facilitating energy absorption, and ensuring head stability.

[Fundus photoplanimetry of the optic nerve head in the Sakurae Study].

PURPOSE: To explore the fundus photoplanimetric distribution of the optic nerve head in a population-based health survey conducted in Sakurae area, in Shimane, Japan(the Sakurae Study). METHODS: After the exclusion of poor quality images from the 1660 right eye-fundus photos obtained from the Sakurae Study in 1991, 1583 photos were digitized, and then were planimetrically analyzed using a newly developed computer software, CDSketch. The parameters calculated included vertical and horizontal cup-to-disc (C/D) ratios, superior and inferior rim-to-disc (R/D) ratios, disc and cup vertical-to-horizontal (V/H) ratios, and disc-macular distance-to-disc diameter (DM/DD) ratio. RESULTS: For the vertical and horizontal C/D, superior and inferior R/D, disc and cup V/H, and DM/DD ratios, mean values were calculated to be 0.58, 0.59, 0.20, 0.18, 1.11, 1.09, 2.60, respectively, and median values were calculated to be 0.58, 0.59, 0.19, 0.18, 1.11, 1.09, 2.57, respectively; no parameter showed any remarkably skewed distribution. The vertical C/D ratio was positively correlated with the cup V/H ratio, but was not correlated with the disc V/ H ratio. The vertical and horizontal C/D, and the disc and cup V/H ratios were negatively correlated with the DM/DD ratio. CONCLUSIONS: The distributions of the various optic nerve head parameters and their correlations in the Sakurae Study are reported. Both mean and median values of the vertical C/D ratio were approximately 0.6 in this study population. These values were larger than the previously reported C/D ratios obtained by direct ophthalmoscopic observations and/or by subjective methods.

Effects of different fat-suppression methods on T1 values in dynamic contrast-enhanced magnetic resonance imaging: a phantom study.

Dynamic contrast-enhanced MRI may yield variable longitudinal-relaxation time (T1) values depending on the precision of the fat-suppression (FS) technique. This study aimed to investigate the influences of FS methods on T1 value measurements on phantoms containing test tubes filled with mixtures of five volumes of fat, six amounts of contrast agent, and water. Volumetric interpolated images were obtained using several FS methods and flip angles. T1 maps were created based on the variable flip angle approach. The T1 values of water obtained by point-resolved single-voxel spectroscopy (SVS) were used as reference values. Notably, FS methods were shown to have substantial effects on the measurement of T1 values. Among the tested FS methods, the Dixon (water) method produced T1 values most similar to SVS, which can be considered as a reference value for clinical practice.

Quantitative depth analysis of optic nerve head using stereo retinal fundus image pair.

Depth analysis of the optic nerve head (ONH) in the retinal fundus is important for the early detection of glaucoma. In this study, we investigate an automatic reconstruction method for the quantitative depth measurement of the ONH from a stereo retinal fundus image pair. We propose a technique to obtain the depth value from the stereo retinal fundus image pair, which mainly consists of five steps: 1. cutout of the ONH region from the stereo retinal fundus image pair, 2. registration of the stereo image pair, 3. disparity measurement, 4. noise reduction, and 5. quantitative depth calculation. Depth measurements of 12 normal eyes are performed using the stereo fundus camera and the Heidelberg Retina Tomograph (HRT), which is a confocal laser-scanning microscope. The depth values of the ONH obtained from the stereo retinal fundus image pair were in good accordance with the value obtained using HRT (r=0.80+/-0.15). These results indicate that our proposed method could be a useful and easy-to-handle tool for assessing the cup depth of the ONH in routine diagnosis as well as in glaucoma screening.

Computer-aided diagnosis: the emerging of three CAD systems induced by Japanese health care needs.

The aim of this paper is to describe three emerging computer-aided diagnosis (CAD) systems induced by Japanese health care needs. CAD has been developing fast in the last two decades. The idea of using a computer to help in medical image diagnosis is not new. Some pioneer studies are dated back to the 1960s. In 1998, the first U.S. FDA (Food and Drug Administration) approved commercial CAD system, a film-digitized mammography system, was launched by R2 Technologies, Inc. The success was quickly repeated by a number of companies. The approval of Medicare CAD reimbursement in the U.S. in 2001 further boosted the industry. Today, CAD has its significance in the economy of the medical industry. FDA approved CAD products in the field of breast imaging (mammography, ultrasonography and breast MRI) and chest imaging (radiography and CT) can be seen. In Japan, as part of the "Knowledge Cluster Initiative" of the government, three computer-aided diagnosis (CAD) projects are hosted at the Gifu University since 2004. These projects are regarding the development of CAD systems for the early detection of (1) cerebrovascular diseases using brain MRI and MRA images by detecting lacunar infarcts, unruptured aneurysms, and arterial occlusions; (2) ocular diseases such as glaucoma, diabetic retinopathy, and hypertensive retinopathy using retinal fundus images; and (3) breast cancers using ultrasound 3-D volumetric whole breast data by detecting the breast masses. The projects are entering their final development stage. Preliminary results are presented in this paper. Clinical examinations will be started soon, and commercialized CAD systems for the above subjects will appear by the completion of this project.

Can we shorten the q-space imaging to make it clinically feasible?

PURPOSE: Q-space imaging (QSI) is a novel magnetic resonance imaging (MRI) technique that enables assessment of micro-structural changes of white matter. The acquisition time, however, is comparatively long to use for routine clinical assessment. Therefore, the present study investigated the clinically feasible b value combinations to measure the water molecular displacement probability density function (PDF) in healthy subjects. METHODS: The subjects consisted of five healthy volunteers (1 female and 4 male; 40.8 ± 13.2 years). All MRIs were examined at 1.5 T. The QSI was acquired using a single-shot echo-planar imaging and Δ/δ = 142/17 ms. The magnitude of the gradients was incremented in nine steps to reach a maximal b = 10,000 s/mm2. The total acquisition time of this original QSI was 17.4 min. The feasibility of ten alternative b value combinations with the zero-filling or curve fitting technique was assessed. The mean diffusivities (MDs), kurtosis, and zero displacement probability (ZDP) were obtained, and these results were compared in manually segmented regions of interest. RESULTS: There were alternative b value combinations with a 7.5-min acquisition time and with almost the same PDF. CONCLUSION: A few alternative b value combinations with the curve fitting technique were found to be able to shorten the QSI acquisition for its clinical feasibility of MD and ZDP.

Lower prevalence of circulating natural killer T cells in patients with angina: a potential novel marker for coronary artery disease.

OBJECTIVE: Atherosclerosis is an inflammatory disease. Natural killer T cells are a unique lymphocyte subset that can recognize lipid antigens presented by CD1d and secrete copious amounts of pro-atherogenic cytokines such as interferon-gamma. We have previously shown that natural killer T cells accelerate atherosclerosis in mice and macrophages incubated with oxidized low-density lipoproteins induce natural killer T cells to produce interferon-gamma. Thus, whether the prevalence of natural killer T cells in peripheral blood is altered in patients with angina pectoris and its correlation with coronary risk factors was determined. METHOD: Cell profiling was performed using flow cytometry in patients with stable angina, unstable angina (Braunwald IIIB), and healthy controls. Natural killer T cells in peripheral blood were identified by the expression of natural killer T specific invariant T cell receptor alpha-chain (Valpha24) and T cell receptor beta-chain (Vbeta11). RESULTS: Prevalence of natural killer T (Valpha24-Vbeta11 double positive) cells was significantly decreased in patients with unstable angina and stable angina compared with that in controls. No significant differences were observed in the prevalence between unstable and stable angina. Reduction of natural killer T cells was independently associated with the presence of angina. CONCLUSIONS: Lower prevalence of circulating natural killer T cells is related to the presence of coronary artery disease. As T cell receptor down-regulation or apoptosis after natural killer T cell activation and subsequent interferon-gamma release may contribute to atherogenesis, natural killer T cells can become a novel therapeutic target for the prevention and treatment of atherosclerotic vascular diseases.

Intraobserver and interobserver agreement of computer software-assisted optic nerve head photoplanimetry.

PURPOSE: To report the reproducibility profile of optic nerve head parameters obtained by computer software-assisted fundus photoplanimetry. METHODS: Fundus photographs obtained during a population-based health survey (Sakurae Study) were planimetrically analyzed using newly developed computer software, CDSketch. The parameters assessed included vertical and horizontal cup-to-disc (C/D) ratios, superior and inferior rim-to-disc (R/D) ratios, disc and cup vertical-to-horizontal (V/H) ratios, and disc-macular distance-to-disc diameter (DM/DD) ratio. For intraobserver and interobserver agreement assessments, we calculated the coefficients of variation (CVs) and intraclass correlation coefficients (ICCs) of the mean of three measurements obtained by one observer and a one-time measurement by three observers, respectively. RESULTS: The intraobserver CVs were between 2.4 % (DM/DD ratio) and 11.0 % (inferior R/D ratio), and the ICCs were between 0.868 (cup V/H ratio) and 0.976 (DM/DD ratio); all intraobserver ICCs had almost perfect agreement (>0.81). The interobserver CVs were between 2.6 % (disc V/H ratio) and 18.0 % (inferior R/D ratio), and the ICCs were between 0.762 (cup V/H ratio) and 0.930 (DM/DD ratio); the interobserver ICCs were categorized as substantial (0.61-0.80) for the inferior R/D and cup V/H ratios and as almost perfect for the other five parameters. CONCLUSIONS: The consistent profiles of the planimetric parameters suggest the suitability of software-assisted photoplanimetry for assessing optic disc characteristics in glaucoma clinical study and practice.

Stereoscopic analysis of optic nerve head parameters in primary open angle glaucoma: the glaucoma stereo analysis study.

PURPOSE: The Glaucoma Stereo Analysis Study (GSAS), a cross sectional multicenter collaborative study, used a stereo fundus camera to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients and investigated the relationships between these parameters and patient characteristics. SUBJECTS AND METHODS: The study included 187 eyes of 187 subjects with primary open angle glaucoma or normal tension glaucoma (male: female  = 100: 87, age  = 61±9 years). Stereo pairs of ONH photographs were made with a stereo fundus camera (nonmyd WX). ONH morphological parameters were calculated with prototype analysis software. In addition to 35 standard parameters, we defined three novel parameters: disc tilt angle, rim decentering, and the absolute value of rim decentering. The correlation between each parameter and patient characteristics was analyzed with Spearman's rank correlation coefficient. RESULTS: Patient characteristics included refractive error of -3.38±3.75 diopters, intraocular pressure (IOP) of 13.6±2.6 mmHg, and visual field mean deviation (MD) of -4.71±3.26 dB. Representative ONH parameters included a horizontal disc width of 1.66±0.28 mm, vertical disc width of 1.86±0.23 mm, disc area of 2.42±0.63 mm2, cup area of 1.45±0.57 mm2, and cup volume of 0.31±0.22 mm3. Correlation analysis revealed significant negative associations between vertical cup-to-disc ratio (0.82±0.08) and MD (r = -0.40, P<0.01) and between disc tilt angle (10.5±12.5 degrees) and refractive error (r = -0.36, P<0.01). Seventy-five percent of the eyes had a positive value for rim decentering (0.30±0.42), indicating that rim thinning manifested more often as an inferior lesion than a superior lesion. CONCLUSION: We used stereoscopic analysis to establish a database of ONH parameters, which may facilitate future studies of glaucomatous changes in ONH morphology.

Automated determination of cup-to-disc ratio for classification of glaucomatous and normal eyes on stereo retinal fundus images.

Early diagnosis of glaucoma, which is the second leading cause of blindness in the world, can halt or slow the progression of the disease. We propose an automated method for analyzing the optic disc and measuring the cup-to-disc ratio (CDR) on stereo retinal fundus images to improve ophthalmologists' diagnostic efficiency and potentially reduce the variation on the CDR measurement. The method was developed using 80 retinal fundus image pairs, including 25 glaucomatous, and 55 nonglaucomatous eyes, obtained at our institution. A disc region was segmented using the active contour method with the brightness and edge information. The segmentation of a cup region was performed using a depth map of the optic disc, which was reconstructed on the basis of the stereo disparity. The CDRs were measured and compared with those determined using the manual segmentation results by an expert ophthalmologist. The method was applied to a new database which consisted of 98 stereo image pairs including 60 and 30 pairs with and without signs of glaucoma, respectively. Using the CDRs, an area under the receiver operating characteristic curve of 0.90 was obtained for classification of the glaucomatous and nonglaucomatous eyes. The result indicates potential usefulness of the automated determination of CDRs for the diagnosis of glaucoma.

Automated segmentation of optic disc region on retinal fundus photographs: Comparison of contour modeling and pixel classification methods.

The automatic determination of the optic disc area in retinal fundus images can be useful for calculation of the cup-to-disc (CD) ratio in the glaucoma screening. We compared three different methods that employed active contour model (ACM), fuzzy c-mean (FCM) clustering, and artificial neural network (ANN) for the segmentation of the optic disc regions. The results of these methods were evaluated using new databases that included the images captured by different camera systems. The average measures of overlap between the disc regions determined by an ophthalmologist and by using the ACM (0.88 and 0.87 for two test datasets) and ANN (0.88 and 0.89) methods were slightly higher than that by using FCM (0.86 and 0.86) method. These results on the unknown datasets were comparable with those of the resubstitution test; this indicates the generalizability of these methods. The differences in the vertical diameters, which are often used for CD ratio calculation, determined by the proposed methods and based on the ophthalmologist's outlines were even smaller than those in the case of the measure of overlap. The proposed methods can be useful for automatic determination of CD ratios.

Improvement of automated detection method of hemorrhages in fundus images.

This paper describes an improved method for detecting hemorrhages in fundus images. The detection of hemorrhages is one of the important factors in the early diagnosis of diabetic retinopathy. So, we had suggested several methods for detecting abnormalities in fundus images, but our methods had some problems. We propose a new method for preprocessing and false positive elimination in the present study. The brightness of the fundus image was changed by the nonlinear curve with brightness values of the hue saturation value (HSV) space. In order to emphasize brown regions, gamma correction was performed on each red, green, and blue-bit image. Subsequently, the histograms of each red, blue, and blue-bit image were extended. After that, the hemorrhage candidates were detected using density analysis. Finally, false positives were removed by using rule-based method and 3 Mahalanobis distance classifiers with a 45-feature analysis. To evaluate the new method for the detection of hemorrhages, we examined 125 fundus images, including 35 images with hemorrhages and 90 normal images. The sensitivity and specificity for the detection of abnormal cases were 80% and 80%, respectively.

Radial-searching contour extraction method based on a modified active contour model for mammographic masses.

In this study, we developed an automatic extraction scheme for the precise recognition of the contours of masses on digital mammograms in order to improve a computer-aided diagnosis (CAD) system. We propose a radial-searching contour extraction method based on a modified active contour model (ACM). In this technique, after determining the central point of a mass by searching for the direction of the density gradient, we arranged an initial contour at the central point, and the movement of a control point was limited to directions radiating from the central point. Moreover, it became possible to increase the extraction accuracy by sorting out the pixel used for processing and using two images-an edge-intensity image and a degree-of-separation image defined based on the pixel-value histogram-for calculation of the image forces used for constraints on deformation of the ACM. We investigated the accuracy of the automated extraction method by using 53 masses with several "difficult contours" on 53 digitized mammograms. The extraction results were compared quantitatively with the "correct segmentation" represented by an experienced physician's sketches. The numbers of cases in which the extracted region corresponded to the correct region with overlap ratios of more than 81 and 61% were 30 and 45, respectively. The initial results obtained with this technique show that it will be useful for the segmentation of masses in CAD schemes.

Three-dimensional reconstruction of optic nerve head from stereo fundus images and its quantitative estimation.

It is important for diagnosis of glaucoma to grasp 3-D structure of an optic nerve head (ONH). The quantitative 3-D reconstruction of the ONH is required for the diagnosis. We propose a technique to obtain the depth value from stereo image pair of a retinal fundus for the 3-D reconstruction of the ONH. Our technique mainly consists of four steps: (1) cutout of the ONH region from the fundus images, (2) registration of the stereo pair, (3) disparity detection, and (4) depth calculation. For quantitative estimation of the depth value measured by using this method, the depth value was compared with the measurement results determined from the Heidelberg Retina Tomograph (HRT), which is a confocal laser-scanning microscope. As a result, the depth value of the ONH obtained using the stereo retinal image pair was in accordance with that obtained using the HRT (r=0.91). These results indicate that the stereo fundus images could be useful for assessing the depth value of the ONH for the diagnosis of glaucoma.

Automated detection algorithm for arteriolar narrowing on fundus images.

We have developed a computer-aided diagnosis system (CAD) to detect abnormalities in fundus images. In Japan, ophthalmologists usually detect hypertensive changes by identifying arteriolar narrowing and focal arteriolar narrowing. The purpose of this study is to develop an automated method for detecting arteriolar narrowing and focal arteriolar narrowing on fundus images. The blood vessel candidates were detected by the density analysis method. In blood vessel tracking, a local detection function was used to determine the centerline of the blood vessel. A direction comparison function using three vectors was designed to optimally estimate the next possible location of a blood vessel. After the connectivity of vessel segments was adjusted based on the recognized intersections, the true tree-like structure of the blood vessels was established. The blood vessels were recognized as arteries or veins by hue of HSV color space and their diameters. The arteriolar narrowing was detected by the ratio of diameters (artery vs. vein; A/V ratio). Focal arteriolar narrowing was detected by measuring the diameter of an artery. By applying this method to 100 fundus images, the detection sensitivity for arteriolar narrowing was found to be 76% when the specificity was 91%. Furthermore, by applying this method to 70 other different fundus images, the detection sensitivity for the focal arteriolar narrowing was 75% with 2.9 false positives per image. The number of some false positives is planned to be reduced during the next stage of development. Such an automated detection of abnormal vessels could help ophthalmologists in diagnosing ocular diseases.

[Follow-up studies of Hokkaido residents with Kawasaki disease].

OBJECTIVES: Sixteen national surveys of Kawasaki disease in Japan from 1970 to 2000 have identified a total of 169,117 patients with Kawasaki disease. Based on that figure, 8,460 residents of Hokkaido probably have a history of Kawasaki disease. It is also estimated that almost 270 Hokkaido residents would have Kawasaki disease-related coronary artery disease. We underwent follow-up studies of Hokkaido residents > or = 15 years with Kawasaki disease. METHODS: We mailed a questionnaire to the departments of internal medicine, cardiology or cardiovascular surgery inquiring about the health status of patients with Kawasaki disease at 451 hospitals with 20 or more beds in Hokkaido. RESULTS: We obtained replies from 185 hospitals (41.0%). Only 11 hospitals(5.9%) reported experience of patients with Kawasaki disease(with or without coronary artery disease) at hospital follow-up. Detailed patient histories for 60 patients from 7 hospitals were obtained: Twenty patients had Kawasaki disease complicated with coronary artery disease, whereas 40 patients had a history of Kawasaki disease and no present coronary artery disease. Thirty-seven patients without coronary artery disease were followed up at one hospital. The 60 patients were aged from 15 to 36 years. Thirty-nine patients(65%) were in the 15 to 20 year age bracket. Coronary aneurysms were recognized in 25 patients(24 males and 1 female) with Kawasaki disease(41.7%) at the onset of the disease. Twenty patients had an aneurysm(s) in the left main trunk and/or the left anterior descending artery, and 13 patients in the right coronary artery. There was a history of myocardial infarction in four patients (6.7%) and nine patients(15.0%) still suffered from angina pectoris. Aortocoronary bypass surgery was performed in one patient, whereas two patients required percutaneous coronary intervention. CONCLUSIONS: Our study suggests that the majority of Hokkaido residents with Kawasaki disease(with or without coronary artery disease) are not being followed up at area hospitals. The characteristics of patients who were followed up included age < or = 20 years, male sex and the presence of severe coronary artery disease other than circumflex involvement.