Minoru Onozuka

Staging Hepatic Fibrosis: Comparison of Gadoxetate Disodium- enhanced and Diffusion-weighted MR Imaging: Preliminary Observations

PURPOSE To evaluate the utility of hepatocyte-phase gadoxetate disodium-enhanced magnetic resonance (MR) imaging in staging hepatic fibrosis and to compare it with diffusion-weighted imaging. MATERIALS AND METHODS This retrospective study had institutional review board approval, and the requirement for informed consent was waived. Gadoxetate disodium-enhanced and diffusion-weighted MR images obtained in 114 consecutive patients (70 men, 44 women; age range, 37-91 years) were evaluated. Liver-to-muscle signal intensity (SI) ratio on hepatocyte-phase images (SI(post)), contrast enhancement index calculated as SI(post) /SI(pre), where SI(pre) is liver-to-muscle SI ratio on nonenhanced images, and apparent diffusion coefficient (ADC) of the liver were measured. Necroinflammatory activity grades and hepatic fibrosis stages were histopathologically determined in 99 patients. Multiple regressions of SI(post), contrast enhancement index, ADC, serum albumin concentration, serum total bilirubin level, prothrombin time, and Child-Pugh score were examined to determine correlation with hepatic necroinflammatory activity grades and fibrosis stages. RESULTS Among the MR, hematologic, and clinical parameters, contrast enhancement index was most strongly correlated with fibrosis stage (r = -0.79, P < .001). Multiple regression analysis showed that the contrast enhancement index, ADC, and prothrombin time were significantly correlated (r(2) = 0.66, P < .05) with fibrosis stage and that the contrast enhancement index and serum total bilirubin level were weakly correlated (r(2) = 0.24, P < .05) with the necroinflammatory activity grade. CONCLUSION Gadoxetate disodium-enhanced MR imaging is more reliable for staging hepatic fibrosis than are diffusion-weighted MR imaging, hematologic, and clinical parameters.

Occlusion and brain function: mastication as a prevention of cognitive dysfunction

Research in animals and humans has shown that mastication maintains cognitive function in the hippocampus, a brain area important for learning and memory. Reduced mastication, an epidemiological risk factor for the development of dementia in humans, attenuates spatial memory and causes hippocampal neurons to deteriorate morphologically and functionally, especially in aged animals. Active mastication rescues the stress-attenuated hippocampal memory process in animals and attenuates the perception of stress in humans by suppressing endocrinological and autonomic stress responses. Active mastication further improves the performance of sustained cognitive tasks by increasing the activation of the hippocampus and the prefrontal cortex, the brain regions that are essential for cognitive processing. Abnormal mastication caused by experimental occlusal disharmony in animals produces chronic stress, which in turn suppresses spatial learning ability. The negative correlation between mastication and corticosteroids has raised the hypothesis that the suppression of the hypothalamic-pituitary-adrenal (HPA) axis by masticatory stimulation contributes, in part, to preserving cognitive functions associated with mastication. In the present review, we examine research pertaining to the mastication-induced amelioration of deficits in cognitive function, its possible relationship with the HPA axis, and the neuronal mechanisms that may be involved in this process in the hippocampus.

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 (Brodmanns 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.

Preoperative T Staging of Urinary Bladder Cancer: Does Diffusion-Weighted MRI Have Supplementary Value?

OBJECTIVE The objective of our study was to evaluate whether diffusion-weighted MRI has supplementary value in the preoperative T staging of urinary bladder cancer. MATERIALS AND METHODS Nineteen consecutive patients (18 men and one woman; age range, 55-83 years; mean, 71 years) known to have or suspected of having urinary bladder cancer underwent MRI at our institution. Urinary bladder cancer was pathologically proven in 18 patients. The pathologic stages were T1 in 14 patients, T2 in two, T3 in one, and T4 in one. Three separate MR image sets were retrospectively reviewed by two independent radiologists: unenhanced T1-weighted images (TR/TE, 607/10) and T2-weighted images (TR(eff)/TE(eff), 4,415/100); unenhanced T1-weighted, T2-weighted, and gadolinium-enhanced images (TR/TE, 10/4.2); and unenhanced T1-weighted, T2-weighted, and diffusion-weighted images (TR(eff)/TE(eff), 2,191/69; b factor, 1,000 s/mm(2)). The radiologists, who were blinded to the pathology findings, assigned T stages and confidence levels for tumors of stage T2 or greater. We used pathologic stages documented in the official pathologic reports as the standard of reference. Observer performance was tested using Spearmans rank correlation, the McNemar test, and receiver operating characteristic (ROC) curve analysis. RESULTS The correlation between the radiologic and pathologic stages was greater with the diffusion sequence (rho = 0.66) than with the unenhanced (0.62) or gadolinium-enhanced (0.62) sequence (p = 0.34). The sensitivity, specificity, accuracy, and area under the ROC curve for tumors of stage T2 or greater were 80%, 79%, 79%, and 0.71 for the unenhanced sequence; 80%, 79%, 79%, and 0.77 for the gadolinium sequence; and 40%, 93%, 79%, and 0.56 for the diffusion-weighted sequence, respectively (p > 0.05). CONCLUSION Our results suggest that diffusion-weighted MRI might have high specificity for the detection of invasive urinary bladder tumors. Patients with suspected urinary bladder carcinomas may well be evaluated by MRI including diffusion-weighted imaging for better preoperative T staging.

Occlusal disharmony induces spatial memory impairment and hippocampal neuron degeneration via stress in SAMP8 mice

We examined the effect of occlusal disharmony in senescence-accelerated (SAMP8) mice on plasma corticosterone levels, hippocampal neuron number, and spatial performance in the water maze. The bite-raised condition was associated with an accelerated age-related decline in spatial memory, increased plasma corticosterone levels, and a decreased number of neurons in the hippocampal CA3 region. The findings suggest that the bite-raised condition in aged SAMP8 mice induces hippocampal neuron loss, thereby leading to senile memory deficits.

MDCT of the Liver and Hypervascular Hepatocellular Carcinomas: Optimizing Scan Delays for Bolus-Tracking Techniques of Hepatic Arterial and Portal Venous Phases

OBJECTIVE The purpose of our study was to determine the optimal scan delays required for hepatic arterial and portal venous phase imaging and for the detection of hypervascular hepatocellular carcinomas (HCCs) in contrast-enhanced MDCT of the liver using a bolus-tracking program. SUBJECTS AND METHODS CT images (2.5-mm collimation, 5-mm thickness with no intersectional gap) detected an increase in the CT value of 50 H in the lower thoracic aorta. The images were obtained after an IV bolus injection of 2 mL/kg of nonionic iodine contrast material (300 mg I/mL) at 4 mL/s in 171 patients, who were prospectively randomized into three groups with scans commencing at 5, 20, and 45 seconds; 10, 25, and 50 seconds; and 15, 30, and 55 seconds for the first (acquisition time: 4.3 seconds), second (4.3 seconds), and third (9.1 seconds) phases, respectively, after a bolus-tracking program. CT values of the aorta, spleen, proximal portal veins, liver parenchyma, and hepatic veins were measured. Increases in CT values from unenhanced to contrast-enhanced CT were assessed using a contrast enhancement index (CEI). Spleen-to-liver and HCC-to-liver contrasts were also assessed. A qualitative degree of contrast enhancement in each organ was prospectively assessed by two independent radiologists. RESULTS At 10-15 seconds, the CEI of the aorta reached 300-336 H and that of the spleen reached 97-108 H without significant enhancement of liver parenchyma (15-25 H). The CEI of the proximal portal veins moderately increased (75-104 H) at 10-15 seconds, but no significant enhancement of hepatic veins was observed (24-51 H). The CEI of liver parenchyma peaked (59-63 H) at 45-55 seconds, when the CEIs of the aorta (117-125 H) and spleen (73-82 H) decreased. Spleen-to-liver contrast (81-84 H) was highest at 10-20 seconds and HCC-to-liver contrast (39-44 H) was highest at 10-15 seconds. The qualitative results correlated well with quantitative results. CONCLUSION The optimal scan delays for hepatic arterial and portal venous phases after the bolus-tracking program detected threshold enhancement by 50 H in the lower thoracic aorta for the detection of hypervascular HCCs were 10-15 and 45-55 seconds, respectively.

Behavior of intracellular cyclic nucleotide and calcium in pentylenetetrazole-induced bursting activity in snail neurons

To elucidate the intracellular mechanism of the bursting activity which is characteristic of seizure discharge, the behavior of the intracellular cyclic nucleotide and the intracellular calcium during pentylenetetrazole (PTZ)-induced bursting activity in snail neurons was investigated. Cyclic AMP was increased about 3-fold by the incubation of ganglia with PTZ. The effect of PTZ on phosphodiesterase activity measured using either cyclic AMP or cyclic GMP as substrate showed a slight increase in cyclic AMP phosphodiesterase activity. The release of calcium from the lysosome fraction was increased by the incubation of ganglia with dibutyryl cyclic AMP. Protein kinase activity was stimulated by the incubation of ganglia with PTZ. Adenylate cyclase activity was stimulated by the incubation of ganglia with PTZ. These findings suggest that PTZ-induced bursting activity in snail neurons is initiated by an intracellular increase of cyclic AMP, which promotes calcium release from lysosomes and induces protein kinase activation.

MDCT of the Pancreas: Optimizing Scanning Delay with a Bolus-Tracking Technique for Pancreatic, Peripancreatic Vascular, and Hepatic Contrast Enhancement

OBJECTIVE The purpose of this study was to determine the optimal MDCT scanning delay for peripancreatic arterial, pancreatic parenchymal, peripancreatic venous, and hepatic parenchymal contrast enhancement with a bolus-tracking technique. SUBJECTS AND METHODS Three-phase 8-MDCT of the pancreas was performed on 170 patients after administration of 2 mL/kg of 300 mg I/mL contrast medium injected at 4 mL/s to a total dose of 150 mL. Patients were prospectively randomized into three groups with different scanning delays for the three phases (arterial, pancreatic, and venous) after bolus tracking was triggered at 50 H of aortic contrast enhancement: group 1 (5, 20, 45 seconds); group 2 (10, 25, 50 seconds); and group 3 (15, 30, 55 seconds). Mean attenuation values of the abdominal aorta, superior mesenteric artery, pancreatic parenchyma, splenic vein, superior mesenteric vein, portal vein, and hepatic parenchyma were measured. Increases in attenuation values after contrast administration were assessed as change in attenuation value. Qualitative analysis also was performed. RESULTS Mean contrast enhancement in the aorta (change in attenuation, 321-327 H) and the superior mesenteric artery (change in attenuation, 304-307 H) approached peak enhancement 5-10 seconds after bolus tracking was triggered. Pancreatic parenchyma became most intensely enhanced (change in attenuation, 84-85 H) 15-20 seconds after triggering, and then the enhancement gradually decreased. Enhancement of the splenic vein and portal vein peaked 25 seconds and that of the superior mesenteric vein peaked 30 seconds after triggering. Liver parenchyma reached 52 H 30 seconds after triggering and reached a plateau (change in attenuation, 58-61 H) at a further scanning delay of 45-55 seconds. Qualitative results were in good agreement with quantitative results. CONCLUSION For the injection protocol used in this study, optimal scanning delay after triggering of bolus tracking at 50 H of aortic contrast enhancement was 5-10 seconds for the peripancreatic arterial phase, 15-20 seconds for the pancreatic parenchymal phase, and 45-55 seconds for the hepatic parenchymal phase.

Pentylenetetrazole-induced bursting activity and cellular protein phosphorylation in snail neurons

To elucidate the intracellular mechanism of seizure discharge, phosphorylation of cellular protein during pentylenetetrazole (PTZ)-induced bursting activity in snail neurons was investigated. PTZ markedly enhanced the phosphorylation of proteins of 34,000 and 50,000 molecular weight. Similar effects were observed by application of a calcium ionophore, A23187. Calmodulin antagonist, N-(6-aminohexyl)-5-chloronaphthalenesulfonamide hydrochloride (W-7), inhibited the PTZ-induced increased phosphorylation of these two proteins. Dibutyryl cyclic AMP and iosobutylmethylxanthine (IBMX) showed no significant effect on the phosphorylation pattern. Bath application of the calcium ionophore produced bursting activity followed by long-lasting hyperpolarization. Bath application of W-7 completely inhibited the PTZ-induced bursting activity. These results suggest that the phosphorylation of proteins of 34,000 and 50,000 in molecular weight is related to the generation of bursting activity by PTZ.

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.