An equation to estimate the renal cortex volume in chronic kidney disease patients.

BACKGROUND: The renal cortex volume is associated with the kidney function and chronic kidney disease (CKD) risk factors, and it may also be a prognostic factor. We aimed to create an equation to estimate the renal cortex volume of CKD patients in day-to-day clinical practice. METHODS: The subjects included 116 ethnic Japanese CKD patients who were ≥ 18 years of age. The renal size (length, width and thickness) was measured by ultrasound. The body height, weight, year of age, sex, birth weight, gestational age, diabetes status, hypertension status, family history of CKD and dialysis and estimated glomerular filtration rate (eGFR) were collected as expected dependent variables. We made models for the equation regarding the renal cortex volume measured by non-contrast magnetic resonance imaging as a true renal cortex volume. Stepwise multiple linear regression analyses were performed with the log-transformation of dependent and independent variables. The accuracy of the models was compared using the leave one out cross-validation method. RESULTS: The estimated volume of the renal cortex (cm3) = 0.012 × renal length (cm)0.92 × width (cm)0.53 × body weight (kg)0.40 × body height (cm)0.67 × eGFR (ml/min/1.73 m2)0.22 × 1.12 if diabetes. The adjusted R 2 value and the accuracy within 30 and 50% were 0.73, 0.94 and 0.99, respectively. CONCLUSIONS: This study provided a new method for estimating the renal cortex volume in day-to-day clinical practice.

Determinants of renal shape in chronic kidney disease patients.

BACKGROUND: The determinants of renal shape are not well established. The purpose of this study was to investigate the relationship between the renal shape, as measured by ultrasound, and the clinical characteristics in chronic kidney disease (CKD) patients. METHODS: The study included 121 CKD patients who had undergone kidney biopsy. The renal shape was defined by: (1) the renal shape index: renal length/(renal width + renal thickness) and (2) the renal width/length. IgA nephritis patients (excluding patients with diabetes), comprised the largest subgroup (n = 49) and were analyzed separately. RESULTS: The correlation analyses and two-sample Student's t test results showed that age, eGFR, BMI, cortex volume fraction measured by MRI (cortex volume/renal volume), percentage of global sclerosis, weight, sex, hypertension and diabetes were significantly correlated with the renal shape in both kidneys. In a stepwise multiple linear regression analysis, old age and high BMI were independently associated with plump kidney. As for the left renal shape index, low cortex volume fraction was also independently associated with plump kidney. In the IgA nephritis patient subgroup, the cortex volume fraction was the most significant factor contributing to the left renal shape index (r = 0.50, p < 0.01) and the width/length (r = -0.47, p < 0.01). CONCLUSION: Age and BMI were stronger determinants of renal shape than renal function in CKD patients. The left renal cortex volume fraction was also an independent determinant and a more important factor in IgA nephritis patients.

Effects of chewing on cognitive processing speed.

In recent years, chewing has been discussed as producing effects of maintaining and sustaining cognitive performance. We have reported that chewing may improve or recover the process of working memory; however, the mechanisms underlying these phenomena are still to be elucidated. We investigated the effect of chewing on aspects of attention and cognitive processing speed, testing the hypothesis that this effect induces higher cognitive performance. Seventeen healthy adults (20-34 years old) were studied during attention task with blood oxygenation level-dependent functional (fMRI) at 3.0 T MRI. The attentional network test (ANT) within a single task fMRI containing two cue conditions (no cue and center cue) and two target conditions (congruent and incongruent) was conducted to examine the efficiency of alerting and executive control. Participants were instructed to press a button with the right or left thumb according to the direction of a centrally presented arrow. Each participant underwent two back-to-back ANT sessions with or without chewing gum, odorless and tasteless to remove any effect other than chewing. Behavioral results showed that mean reaction time was significantly decreased during chewing condition, regardless of speed-accuracy trade-off, although there were no significant changes in behavioral effects (both alerting and conflict effects). On the other hand, fMRI analysis revealed higher activations in the anterior cingulate cortex and left frontal gyrus for the executive network and motor-related regions for both attentional networks during chewing condition. These results suggested that chewing induced an increase in the arousal level and alertness in addition to an effect on motor control and, as a consequence, these effects could lead to improvements in cognitive performance.

Predicting the outcome of chronic kidney disease by the estimated nephron number: the rationale and design of PRONEP, a prospective, multicenter, observational cohort study.

BACKGROUND: The nephron number is thought to be associated with the outcome of chronic kidney disease (CKD). If the nephron number can be estimated in the clinical setting, it could become a strong tool to predict renal outcome. This study was designed to estimate the nephron number in CKD patients and to establish a method to predict the outcome by using the estimated nephron number. METHODS/DESIGN: The hypothesis of this study is that the estimated nephron number can predict the outcome of a CKD patient. This will be a multicenter, prospective (minimum 3 and maximum 5 years follow-up) study. The subjects will comprise CKD patients aged over 14 years who have undergone a kidney biopsy. From January 2011 to March 2013, we will recruit 600 CKD patients from 10 hospitals belonging to the National Hospital Organization of Japan. The primary parameter for assessment is the composite of total mortality, renal death, cerebro-cardiovascular events, and a 50% reduction in the eGFR. The secondary parameter is the rate of eGFR decline per year. The nephron number will be estimated by the glomerular density in biopsy specimens and the renal cortex volume. This study includes one sub-cohort study to establish the equation to calculate the renal cortex volume. Enrollment will be performed at the time of the kidney biopsy, and the data will consist of a medical interview, ultrasound for measurement of the kidney size, blood or urine test, and the pathological findings of the kidney biopsy. Patients will continue to have medical consultations and receive examinations and/or treatment as usual. The data from the patients will be collected once a year after the kidney biopsy until March 2016. All data using this study are easily obtained in routine clinical practice. DISCUSSION: This study includes the first trials to estimate the renal cortex volume and nephron number in the general clinical setting. Furthermore, this is the first prospective study to examine whether the nephron number predicts the outcome of CKD patients. The results from this study should provide powerful new tools for nephrologists in routine clinical practice. TRIAL REGISTRATION: UMIN-Clinical Trial Registration, UMIN000004784.

Specific metabolites in the medial prefrontal cortex are associated with the neurocognitive deficits in schizophrenia: a preliminary study.

We measured brain metabolites in the medial prefrontal cortex of 19 schizophrenic patients and 18 healthy controls by 3 T proton magnetic resonance spectroscopy ((1)H MRS), and examined the relationship between prefrontal cortex-related neurocognitive functions and brain metabolites in the medial prefrontal cortex. The patients with schizophrenia exhibited deficits on the verbal fluency, Wisconsin card sorting test (WCST), trail making test, Stroop test and digit span distraction test (DSDT), but not on the Iowa gambling test. The patients showed statistical significant changes in the ratio of glutamine/glutamate, the ratio of N-acetyl-l-aspartate (NAA)/glycerophosphorylcholine plus phosphorylcholine (GPC+PC) and the levels of taurine in the medial prefrontal cortex compared with normal controls. Furthermore, we found significant correlations of the ratio of glutamine/glutamate with WCST and DSDT scores, the ratio of NAA/(GPC+PC) with verbal fluency and WCST scores, and the levels of taurine with scores on the Stroop test and Trail making test A among the participants. The ratios of NAA/(GPC+PC) and (GPC+PC)/(Cr+PCr) had significant relationships with the duration of untreated psychosis of the schizophrenic patients. The glutamine/glutamate ratio and levels of taurine were significantly related to the duration of illness of the patients. These data suggest that specific metabolites of the medial prefrontal cortex are associated with the neurocognitive deficits in schizophrenia.

A case of adult-onset type II citrullinemia with comorbid epilepsy even after liver transplantation.

The current study using single case voxel-based morphometry (VBM) of magnetic resonance imaging (MRI) and ¹H-MR-spectroscopy (¹H-MRS) explores the neural background of unexplained seizure attacks and electroencephalography (EEG) abnormalities persisting even after liver transplantation in a patient with adult-onset type II citrullinemia (CTLN2). Although the MRI had shown no gross abnormality, the VBM revealed significantly smaller-than-normal regional volume in the left hippocampus of the patient as compared with 111 age-matched controls. ¹H-MRS further indicated reduction of all metabolite concentrations in the left hippocampus compared with those in the right homolog region, with the single exception of elevated glutamate concentration. These results are similar to those of patients with mesial temporal lobe epilepsy (TLE), although CTLN2-complicated mesial TLE has rarely been reported. In contrast to TLE, periictal asterixis and interictal slow activities on EEG support another possibility that the patient might have slight metabolic encephalopathy even after the liver transplantation.

A multi-compartmental SE-BOLD interpretation for stimulus-related signal changes in diffusion-weighted functional MRI.

A new interpretation is proposed for stimulus-induced signal changes in diffusion-weighted functional MRI. T(2)-weighted spin-echo echo-planar images were acquired at different diffusion-weightings while visual stimulation was presented to human volunteers. The amplitudes of the positive stimulus-correlated response and post-stimulus undershoot (PSU) in the functional time-courses were found to follow different trends as a function of b-value. Data were analysed using a three-compartment signal model, with one compartment being purely vascular and the other two dominated by fast- and slow-diffusing molecules in the brain tissue. The diffusion coefficients of the tissue were assumed to be constant throughout the experiments. It is shown that the stimulus-induced signal changes can be decomposed into independent contributions originating from each of the three compartments. After decomposition, the fast-diffusion phase displays a substantial PSU, while the slow-diffusion phase demonstrates a highly reproducible and stimulus-correlated time-course with minimal undershoot. The decomposed responses are interpreted in terms of the spin-echo blood oxygenation level dependent (SE-BOLD) effect, and it is proposed that the signal produced by fast- and slow-diffusing molecules reflect a sensitivity to susceptibility changes in arteriole/venule- and capillary-sized vessels, respectively. This interpretation suggests that diffusion-weighted SE-BOLD imaging may provide subtle information about the haemodynamic and neuronal responses.

Effects of chewing in working memory processing.

It has been generally suggested that chewing produces an enhancing effect on cognitive performance-related aspects of memory by the test battery. Furthermore, recent studies have shown that chewing is associated with activation of various brain regions, including the prefrontal cortex. However, little is known about the relation between cognitive performances affected by chewing and the neuronal activity in specified regions in the brain. We therefore examined the effects of chewing on neuronal activities in the brain during a working memory task using fMRI. The subjects chewed gum, without odor and taste components, between continuously performed two- or three-back (n-back) working memory tasks. Chewing increased the BOLD signals in the middle frontal gyrus (Brodmann's areas 9 and 46) in the dorsolateral prefrontal cortex during the n-back tasks. Furthermore, there were more prominent activations in the right premotor cortex, precuneus, thalamus, hippocampus and inferior parietal lobe during the n-back tasks after the chewing trial. These results suggest that chewing may accelerate or recover the process of working memory besides inducing improvement in the arousal level by the chewing motion.

Evaluating glycogen signal contamination in muscle by (13)C MRS of the liver.

To evaluate the contamination of glycogen signal synthesized in skeletal muscle by that in the liver, long-term monitoring of over 7 h of in vivo [1-(13)C] glycogen synthesis/degradation at the right abdomen and left shoulder was achieved using a 3.0-T clinical MR system. (13)C MR spectra without localization were obtained from five healthy volunteers before and after oral administration of 85 g of d-glucose, including 10 g of 99% [1-(13)C] glucose. In all volunteers, the relative signal intensities at the abdomen to those at shoulder were about two- to fivefold, and those of time-course changes at the abdomen and shoulder were dissimilar. It is considered that the quantity of muscle-synthesized glycogen signal at the abdomen is less than that at the shoulder because of the lesser muscle volume at the abdomen, and it may be less affected for evaluating glycogen synthesis/degradation in the liver even without localization pulses.

Modification of nitroxyl contrast agents with multiple spins and their proton T(1) relaxivity.

The purpose of this study is to test the performance of multispin nitroxyl contrast agents in improving the sensitivity of MR detection for nitroxyl contrast agents. The relation between T(1) relaxivity and the number of paramagnetic centers in a molecule was investigated. Compound 1 is a single molecule of methoxycarbonyl-PROXYL (MC-PROXYL). Two and three MC-PROXYL molecules were chemically coupled to obtain Compounds 2 and 3, which have two and three nitroxyl spins in the molecule, respectively. A good linear relation, the slope of which increased depending on the number of nitroxyl spins in the molecule, was obtained between T(1)-weighted (fast low-angle shot) MR image contrast enhancement at 7 T and the concentration of nitroxyl contrast agents. T(1)-weighted MR image contrast enhancement and T(1) relaxivity levels of nitroxyl contrast agents were increased depending on the number of nitroxyl spins in the molecule. Multicoupling nitroxyl molecules can enhance the T(1)-weighted contrast effect while maintaining the quantitative behavior of the molecule for up to three spins.

A new approach for diagnosis of hepatolithiasis: magnetic resonance cholangiopancreatography: potential usefulness of dehydrocholic acid (DHCA) administration in the evaluation of hepatolithiasis.

BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous dehydrocholic acid (DHCA) was useful to enhance the delineation of hepatolithiasis. METHODOLOGY: Our study population comprised 9 patients. Magnetic resonance cholangiopancreatography (MRCP) was acquired before and after the administration of DHCA. Two different MRCP snap-shot techniques were applied: thick-slab two-dimensional (2D) (coronal) single shot turbo spin echo T2-weighted sequences and multisection thin-slab, 2D (coronal) single shot turbo spin echo T2-weighted sequences with three-dimensional (3D) maximum intensity projection (MIP) post processing. RESULTS: DHCA provided a better visualization of hepatolithiasis in 8 of 9 cases (88.9%). CONCLUSIONS: It was suggested that administration of DHCA could enhance the delineation of the hepatolithiasis on MRCP images.

Magnetic resonance cholangiopancreatography: potential usefulness of dehydrocholic acid (DHCA) administration in the evaluation of anastomotic site.

BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous dehydrocholic acid (DHCA) was useful to enhance the delineation of anastomotic site. METHODOLOGY: DHCA is a cholagogue which produces an immediate effect by acting directly on liver cells. Its choleretic effect is strong, appearing 1 to 3 minutes after intravenous injection, reaching the maximum level in 20 to 30 minutes. Our study population comprised 9 patients. Magnetic resonance cholangiopancreatography (MRCP) was acquired before and after the administration of DHCA. Two different MRCP snap-shot techniques were applied: thick-slab two-dimensional (2D) (coronal) single-shot turbo spin echo T2-weighted sequences and multisection thin-slab, 2D (coronal) single shot turbo spin echo T2-weighted sequences with three-dimensional (3D) maximum intensity projection (MIP) post processing. RESULTS: DHCA provided a better visualization of the anastomotic site in 7 patients (77.8%). The two patients without improvement in visualization of anastomotic site included 1 patient with liver cirrhosis secondary to portoenterostomy for congenital biliary dilatation and 1 patient, who was not eligible for the evaluation because of motion artifact caused by the difficulty of breath holding motion artifact. CONCLUSIONS: It was suggested that administration of DHCA could enhance the delineation of the anastomotic site on MRCP images.

Magnetic resonance cholangiopancreatography: potential usefulness of dehydrocholic acid (DHCA) administration in the evaluation of biliary disease.

BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous dehydrocholic acid (DHCA) was useful to enhance the delineation of the biliary tree. METHODOLOGY: Our study population comprised 14 patients. Magnetic resonance cholangiopancreatography was acquired before and after the administration of DHCA. Two different MRCP snap shot techniques were applied: thick-slab two-dimensional (2D) (coronal) single shot turbo spin echo T2-weighted sequences and multisection thin-slab, 2D (coronal) single shot turbo spin echo T2-weighted sequences with three-dimensional (3D) maximum intensity projection (MIP) post processing. Volume rendering was prepared based on the source images, and the pixel size was visually adjusted to the biliary area of MRCP to measure the biliary tree volume. RESULTS: DHCA increased the bile duct volume in 13 of the 14 patients. It provided a better visualization of the biliary tree in 11 patients. The three patients without improvement in visualization included 1 patient with liver cirrhosis secondary to portoenterostomy for congenital biliary dilatation and 2 patients with cholecystectomy who had the bile ducts filled with bile by the time of the administration. CONCLUSIONS: It was suggested that administration of DHCA could enhance the delineation of the biliary tree on MRCP images.

Reduction of a high-field dielectric artifact with homemade gel.

We developed an original dielectric-equivalent gel (Japanese Patent Application ID: P2004-236876A, February 6, 2003) pad that could improve inhomogeneous images caused primarily by B(1) homogeneity on a high-tesla magnetic resonance (MR) system. Made easily from various ingredients, our gel could reduce interference from radiofrequency waves at an object's surface and show changes in B(1) inhomogeneity. We herein assess the gel's effect using a plastic-bottle phantom on a 3T MR system.

Laterality and aging of thalamic subregions measured by diffusion tensor imaging.

Thalamic nuclei are comprised of fibers connecting associated cortical regions, and abnormalities of the thalamus are correlated with abnormalities in cognition and behavior. Some previous studies showed the laterality of the whole thalamus and the regional differences among thalamic nuclei. This led us to assess regional characteristics in five major subregions of both sides of the thalamus using diffusion-tensor imaging. Statistically significant lateralities and regional differences were found among the thalamic subregions. Age has a significant correlation with diffusion-tensor imaging metrics where their projection areas are thought to be vulnerable to normal aging. Our results confirmed that the thalamic subregions behave independently, and their respective microstructures warrant further investigations.

Comparisons of EPR imaging and T1-weighted MRI for efficient imaging of nitroxyl contrast agents.

The resolution and signal to noise ratio of EPR imaging and T(1)-weighted MRI were compared using an identical phantom. Several solutions of nitroxyl contrast agents with different EPR spectral shapes were tested. The feasibility of T(1)-weighted MRI to detect nitroxyl contrast agents was described. T(1)-weighted MRI can detect nitroxyl contrast agents with a complicated EPR spectrum easier and quicker; however, T(1)-weighted MRI has less quantitative ability especially for lipophilic nitroxyl contrast agents, because T(1)-relaxivity, i.e. accessibility to water, is affected by the hydrophilic/hydrophobic micro-environment of a nitroxyl contrast agent. The less quantitative ability of T(1)-weighted MRI may not be a disadvantage of redox imaging, which obtains reduction rate of a nitroxyl contrast. Therefore, T(1)-weighted MRI has a great advantage to check the pharmacokinetics of newly modified and/or designed nitroxyl contrast agents.

Development of a patch antenna array RF coil for ultra-high field MRI.

In radiofrequency (RF) coil design for ultra-high-field magnetic resonance (MR) imaging, short RF wavelengths present various challenges to creating a big volume coil. When imaging a human body using an ultra-high magnetic field MR imaging system (magnetic flux density of 7 Tesla or more), short wavelength may induce artifacts from dielectric effect and other factors. To overcome these problems, we developed a patch antenna array coil (PAAC), which is a coil configured as a combination of patch antennas. We prototyped this type of coil for 7T proton MR imaging, imaged a monkey brain, and confirmed the coil's utility as an RF coil for ultra-high-field MR imaging.

Optimizing T2-weighted magnetic resonance sequences for surface coil microimaging of the eye with regard to lid, eyeball and head moving artifacts.

PURPOSE: To acquire high-resolution magnetic resonance (MR) images, we developed a new blinking artifact reduced pulse (BARP) sequence with a surface coil specialized for microscopic imaging (47 mm in diameter). MATERIALS AND METHODS: To reduce eye movement, we ascertained that the subjects' eyes were kept open and fixated to the target in the 1.5-T MR gantry. To reduce motion artifacts from blinking, we inserted rest periods for blinking (1.5 s within every 5 s) during MR scanning (T2-weighted fast spin echo; repetition time, 5 s; echo time, 100 ms; echo train, 11; matrix, 256 x 128; field of view, 5 cm; 1-mm thickness x 30 slices). Three scans (100 s x 3) were performed for each normal subject, and they were added together after automatic adjustment for location to reduce quality loss caused by head motion. RESULTS: T2-weighted MR images were acquired with a high resolution and a high signal-to-noise ratio. Motion artifacts were reduced with BARP, as compared with those with random blinking. Intraocular structures such as the iris and ciliary muscles were clearly visualized. Because the whole eye can be covered with a 1-mm thickness by this method, three-dimensional maps can easily be generated from the obtained images. CONCLUSION: The application of BARP with a surface coil of the human eye might become a useful and widely adopted procedure for MR microimaging.

Time course evaluation of reparative cartilage with MR imaging after autologous chondrocyte implantation.

The aim of this study was to evaluate the qualitative change in reparative cartilage after autologous chondrocyte implantation (ACI). Ten knees of 10 patients were studied. The signal intensities of reparative and normal cartilage were evaluated by fat-suppressed three-dimensional spoiled-gradient recalled (FS 3D-SPGR) MR imaging. The signal intensity (SI) index (signal intensity of reparative cartilage divided by that of normal cartilage) was defined and the change in SI index was investigated. Histological and biochemical evaluation was done at the second look arthroscopy. The SI index was at its lowest level immediately after ACI and increased with time to 9 months thereafter. After 9-12 months, the SI index settled to almost level and was maintained at that value for at least 2-3 years postoperatively. The average of the SI indexes after 12 months to the last examination was 74.2 +/- 4.6 (range 64.2-82.8), which means signal intensity of reparative cartilage was maintained at a value lower than that of normal cartilage. The total ICRS score was 11.6 +/- 2.3 points (mean +/- SD). The GAG concentration was 107.9 +/- 17.0 microg/mg (mean +/- SD) in normal cartilage and 65.9 +/- 9.4 microg/mg in reparative cartilage. The quality of reparative cartilage as hyaline cartilage was inferior to that of normal cartilage. In the present study, the time course change in the SI index indicates that the major maturation process of implanted chondrocytes neared completion in 9-12 months. Minor changes, such as matrix remodeling with reorganization of the collagen fibers in reparative cartilage, may continue, but an almost identical condition seemed to be maintained during the first 2-3 years of follow-up. SI index does not always reflect all properties of reparative cartilage but may be a useful parameter for noninvasive evaluation.

Development of high-radiation-sensitive polymer gel for magnetic resonance imaging in three-dimensional dosimetry.

We developed a high radiation sensitive polymer gel by modifying the amounts of the gel components and the temperature for the gel preparation. We evaluated its relaxation time linearity against dose and compared the measured dose distribution with the calculated one. For the relaxation time-dose linearity, irradiations were carried out with a linear accelerator using 6 MV photons and doses ranging from 0-5.0 Gy. The relationship between dose and R(2) value (reciprocal of T(2) relaxation time) was measured and it had good linearity over a wide range (0.3-5 Gy). The measured dose distributions were in good agreement with calculated ones. Since the present gel has higher sensitivity and it is synthesized more easily at lower cost than conventional polymer gels, we expect to see improved three-dimensional (3D) dosimetry using it.