Biomedical subjects

N Sadato

Publications and source records attributed to N Sadato.

At least 73 records · Page 4Linked to original sources

PubMed1998

Cerebral processes related to visuomotor imagery and generation of simple finger movements studied with positron emission tomography.

Positron emission tomography was used to compare the functional anatomy of visual imagination and generation of movement. Subjects were asked to generate visual images of their finger movement in response to a preparatory signal. Four conditions were tested: in two, no actual movement was required; in the other two, a second signal prompted the subjects to execute the imagined movement. Which movement to imagine was either specified by the preparatory stimulus or freely selected by the subjects. Compared with a rest condition, tasks involving only imagination activated several cortical regions (inferoparietal cortex, presupplementary motor area, anterior cingulate cortex, premotor cortex, dorsolateral prefrontal cortex) contralateral to the imagined movement. Tasks involving both imagination and movement additionally increased activity in the ipsilateral cerebellum, thalamus, contralateral anteroparietal, and motor cortex and decreased activity in the inferior frontal cortex. These results support the hypothesis that distinct functional systems are involved in visuomotor imagination and generation of simple finger movements: associative parietofrontal areas are primarily related to visuomotor imagination, with inferior frontal cortex likely engaged in active motor suppression, and primary motor structures contribute mainly to movement execution.

Adult↗

PubMed1998

Influence of ANOVA design and anatomical standardization on statistical mapping for PET activation.

We have created images of z value, error, and variation components for a PET activation study using various ANOVA designs and anatomical standardization methods. Data were acquired in four PET centers. In each center, CBF was measured on six normal male subjects under resting and covert verb generation, three times for each. The images were anatomically standardized with LINEAR transformation, SPM (Ver. 95), HBA (Karolinska/Tohoku), or MICHIGAN (Minoshima). ANOVA was performed pixel by pixel to compute t (and z) for the task main effect (Verb vs Rest) in four different designs: (i) two way (subject and task) (2W), (ii) two-way with interaction (2WI), (iii) subject considered a random factor (2WI-MX), and (iv) three-way (subject, task, and replication) (3W). A large area extending from the Broca to the left premotor cortex was activated. The localization of the highest peak depended both on the anatomical standardization and on the ANOVA design, the variation ranging 3-4 cm. Smoothing reduced the variation while erasing possible subfoci. The z images of 2W, 2WI, and 3W looked alike, whereas 2WI-MX presented lower peak z values. SPM tended to present higher z values than the other methods. The error was high in the gray and low in the white matter. The root mean square for the subject effect was high on the border of gray matter especially in LINEAR and HBA, revealing intersubject mismatch in the gray matter distribution. The root mean square for the subject-by-task interaction effect revealed individual variation in activation.

Adult↗

PubMed1998

Comparative study of event-related potentials and positron emission tomography activation during a paired-associate memory paradigm.

Event-related potentials (ERP) and regional cerebral blood flow (rCBF) activation using 15O-labeled water associated with retrieval and retention of episodic memory were studied during a visual paired-association task with delayed response in eight healthy subjects. In both studies, the subjects memorized four pairs of figures during the learning period. They were presented with each cue (S1) and asked to judge whether the following figure (S2) formed one of the memorized pairs. In an attempt to identify brain activity related to memory function, a choice reaction task with delay was used as a behavioral control. The ERP study showed a posterior positive component in the difference waveform, which was obtained by subtracting responses in the choice reaction task from those in the paired association task, between 300 and 850 ms after S1 presentation. It was maximal at the parietal midline electrode and distributed predominantly over the left posterior quadrant of the scalp. The rCBF activation study showed a greater increase in rCBF in the right dorsolateral prefrontal cortex (Brodmann's area 46), left inferior frontal cortex (Brodmann's area 44/45), left thalamus, and bilateral cerebellar hemisphere during the paired association task as compared to the choice reaction task, which suggests a possible involvement of cerebello-thalamo-cortical circuit in the memory processing. Additionally, it is suggested that the scalp distribution of the ERP component may not necessarily represent regional cortical activation below the electrodes where such a component is observed and could indirectly represent activation in remote areas such as subcortical regions. It seems that ERP and rCBF activation may provide information about different aspects of higher brain function.

Adolescent↗

PubMed1998

Non-invasive estimation of the net influx constant using the standardized uptake value for quantification of FDG uptake of tumours.

To reduce the variability of the standardized uptake value (SUV) which is widely used to evaluate 2-[18F]fluoro-2-deoxy-d-glucose (FDG) uptake by neoplasms, net influx constant (Ki) was derived from SUV. The relationship Ki=SUV.kp.V0, where kp is the plasma clearance rate and V0 is the initial distribution volume of FDG, was utilized. A total of 71 plasma input functions were measured up to 60 min after intravenous injection of FDG in 55 patients and were analysed to obtain kp and V0. SUV and V0 were calculated based on either body weight or body surface area. To validate the Ki estimation, another group of eight patients with squamous cell carcinoma of the head and neck was included. Parametric images of the net influx constant were obtained by Patlak graphical analysis of dynamic positron emission tomography (PET) data and measured plasma input function. V0 based on body weight was 0.1627+/-0.0329 (ml/g) and showed a weak negative correlation with body weight (y=0.23356-0.00138x, r=0.591). V0 based on body surface area was 5540+/-871 (ml/m2) and had no significant correlation with body weight. kp at 50 min post injection was 0. 03272+/-0.00243 (1/min), and had no correlation with the plasma glucose concentration. A highly significant positive correlation was noted between true Ki and estimated Ki based on both body weight (y=0.0033+1.0371x, r2=0.897), and body surface area (y=0.0033+1. 0351x, r2=0.926). Ki, a better indicator of FDG uptake by tumour than SUV, is derivable non-invasively. Quantification of FDG uptake by Ki will aid standardization of diagnostic criteria of FDG PET oncology.

Carcinoma, Squamous Cell↗

PubMed1998

Multiple single sections Turbo FLASH MR arterial portography in the detection of hepatic neoplasms.

OBJECTIVE: To determine the sensitivity of multiple single sections Turbo FLASH MR arterial portography (MRAP) in the detection of hepatic neoplasms. METHODS AND PATIENTS: Twelve patients with hepatic mass underwent MRAP prior to hepatic resection. Findings of MRAP were compared with surgical specimen and intra-operative ultrasonography (US). RESULTS: A total of 19 separate malignant neoplastic nodules were identified in the resected specimens or intra-operative ultrasonography. The sensitivity was 89.5% (17/19) for MRAP. MRAP depicted all neoplasms more than 1.0 cm in diameter. Two lesions not depicted on MRAP had a diameter of 5 and 9 mm, respectively. One lesion identified by MRAP was confirmed to false positive lesion by intra-operative US. CONCLUSION: Multiple single sections Turbo FLASH MRAP may be a valuable adjunct for pre-operative detection of malignant hepatic neoplasms.

Carcinoma, Hepatocellular↗

PubMed1998

Task-related coherence and task-related spectral power changes during sequential finger movements.

In order to investigate the activity of cortical regions in the control of complex movements, we studied task-related coherence (TRCoh) and task-related spectral power (TRPow) changes in 8 right-handed subjects during the execution of 4 different finger movement sequences of increasing complexity. All sequences were performed with the right hand and were paced by a metronome at 2 Hz. EEG power spectra and coherence values were computed within alpha (8-12 Hz) and beta (13-20 Hz) frequency bands for 29 scalp EEG positions during the execution of the sequences and were compared with values obtained during a rest (control) condition. Movement sequences were associated with TRPow decreases in the alpha and beta frequency bands over bilateral sensorimotor and parietal areas, with a preponderance over the contralateral hemisphere. Increases of TRCoh occurred over bilateral frontocentral regions. TRCoh decreases were present over the temporal and occipital areas. The spatial extent and the magnitude of TRPow decreases and TRCoh increases in both frequency bands were greater for sequential movements of higher complexity than for simpler ones. These results are consistent with previous findings of bilateral activation of sensorimotor areas during sequential finger movements. Moreover, the present results indicate an active intercommunication between bilateral and mesial central and prefrontal regions which becomes more intense with more complex sequential movements.

Adult↗

PubMed1998

The importance of glucose transport activity as the rate-limiting step of 2-deoxyglucose uptake in tumor cells in vitro.

Glucose transporter (GLUT) expression and hexokinase activity are thought to be related to high [18F]-fluorodeoxyglucose (FDG) uptake in tumor cells, but their relative importance is still unknown. To determine which is the predominant factor in FDG uptake in tumor cells, cultured tumor cell lines and a normal cell line were studied in vitro with respect to 2-deoxyglucose (DG) uptake, hexokinase activity, and the initial uptake rate of 3-O-methylglucose (3-O-MG) transport, which is generally accepted as indicating the amount of GLUT expressed on the plasma membrane. In 16 types of tumor cells and one fibroblast cell line, DG uptake was assessed for 60 min, the initial uptake rate of 3-O-MG transport was measured for 1 min, and total hexokinase activity, including that in the mitochondrial fraction, was determined. Across all 16 tumor cell lines, there was a significant correlation between DG uptake and 3-O-MG transport (p = 0.0012, F test), but not between DG uptake and hexokinase activity. Hexokinase activity of the tumor cells was comparable to that of the human fibroblast cells in the exponential growth phase. Most tumor cells showed higher DG uptake and 3-O-MG transport than the human fibroblast cells. The results suggest that DG uptake of cultured tumor cells is governed by GLUT expression, which may be a distinct characteristic of the neoplastic process.

3-O-Methylglucose↗

PubMed1998

Regional cerebral blood flow changes in human brain related to ipsilateral and contralateral complex hand movements--a PET study.

The purpose of this study was to investigate the cortical motor areas activated in relation to unilateral complex hand movements of either hand, and the motor area related to motor skill learning. Regional cerebral blood flow (rCBF) was measured in eight right-handed healthy male volunteers using positron emission tomography during a two-ball-rotation task using the right hand, the same task using the left hand and two control tasks. In the two-ball-rotation tasks, subjects were required to rotate the same two iron balls either with the right or left hand. In the control task, they were required to hold two balls in each hand without movement. The primary motor area, premotor area and cerebellum were activated bilaterally with each unilateral hand movement. In contrast, the supplementary motor area proper was activated only by contralateral hand movements. In addition, we found a positive correlation between the rCBF to the premotor area and the degree of improvement in skill during motor task training. The results indicate that complex hand movements are organized bilaterally in the primary motor areas, premotor areas and cerebellum, that functional asymmetry in the motor cortices is not evident during complex finger movements, and that the premotor area may play an important role in motor skill learning.

Adult↗

PubMed1998

Neural networks for Braille reading by the blind.

To explore the neural networks used for Braille reading, we measured regional cerebral blood flow with PET during tactile tasks performed both by Braille readers blinded early in life and by sighted subjects. Eight proficient Braille readers were studied during Braille reading with both right and left index fingers. Eight-character, non-contracted Braille-letter strings were used, and subjects were asked to discriminate between words and non-words. To compare the behaviour of the brain of the blind and the sighted directly, non-Braille tactile tasks were performed by six different blind subjects and 10 sighted control subjects using the right index finger. The tasks included a non-discrimination task and three discrimination tasks (angle, width and character). Irrespective of reading finger (right or left), Braille reading by the blind activated the inferior parietal lobule, primary visual cortex, superior occipital gyri, fusiform gyri, ventral premotor area, superior parietal lobule, cerebellum and primary sensorimotor area bilaterally, also the right dorsal premotor cortex, right middle occipital gyrus and right prefrontal area. During non-Braille discrimination tasks, in blind subjects, the ventral occipital regions, including the primary visual cortex and fusiform gyri bilaterally were activated while the secondary somatosensory area was deactivated. The reverse pattern was found in sighted subjects where the secondary somatosensory area was activated while the ventral occipital regions were suppressed. These findings suggest that the tactile processing pathways usually linked in the secondary somatosensory area are rerouted in blind subjects to the ventral occipital cortical regions originally reserved for visual shape discrimination.

Adult↗

PubMed1998

Glucose transporter protein-independent tumor cell accumulation of fluorine-18-AFDG, a lipophilic fluorine-18-FDG analog.

UNLABELLED: Fluorine-18-fluorodeoxyglucose (FDG) is used clinically for tumor diagnosis, but its mechanism of accumulation in tumor cells is complicated because two factors, glucose transporter protein (GLUT) and hexokinase, govern [18F]FDG uptake directly. We selected a lipophilic [18F]FDG analog, 1,3,4,6-tetra-acetyl-2-[18F]-2-deoxy-D-glucose ([18F]AFDG), to regulate the effects of hexokinase and evaluated its characteristics in an in vitro cell culture system. METHODS: Fluorine-18-AFDG was synthesized by the method used to produce [18F]FDG, as an intermediate of [18F]FDG. Fluorine-18-AFDG uptake study was performed with LS180 tumor cells, and its metabolites were also investigated by thin-layer chromatography. To evaluate the relationship between [18F]AFDG and GLUT, we also examined [18F]AFDG uptake in the presence of cytochalasin B or with increased medium glucose concentration. The effects of lowered temperature (4 degrees C) on [18F]AFDG uptake were also investigated. RESULTS: Fluorine-18-AFDG (lipophilicity: octanol/water = 3.5) uptake was 3.3-fold higher than that of [18F]FDG. Metabolic analysis showed that [18F]AFDG was extremely stable in the incubation medium but was quickly hydrolyzed and metabolized to 2-fluoro-[18F]-2-deoxy-D-glucose-6-phosphate ([18F]FDG-6P) in tumor cells. Fluorine-18-FDG-6P accounted for approximately 45% of the total radioactivity after a 60-min incubation of [18F]AFDG. Incubation with 50 microM cytochalasin B did not affect [18F]AFDG uptake. In medium with double the control glucose level, [18F]FDG uptake was decreased by about 50%, but [18F]AFDG uptake was not affected. Fluorine-18-AFDG uptake and [18F]FDG-6P production did not show saturation and increased linearly with addition of a 10-fold higher concentration of [18F]AFDG. Lowered incubation temperature caused decreased [18F]AFDG uptake due to reduced [18F]FDG-6P production. CONCLUSION: Fluorine-18-AFDG rapidly penetrated the cell membrane as a result of its high lipophilicity and was metabolized to [18F]FDG-6P within cells. Fluorine-18-AFDG was thus characterized as "GLUT-independent [18F]FDG."

Cytochalasin B↗

PubMed1998

Fluorine-18-fluorodeoxyglucose PET versus thallium-201 scintigraphy evaluation of thyroid tumors.

UNLABELLED: To determine whether PET could help differentiate malignant from benign thyroid tumors, 18F-fluorodeoxyglucose (FDG) accumulation and 201Tl scintigraphy were examined relative to histological diagnosis. METHODS: Nodular thyroid lesions in 11 patients were evaluated before surgical resection. Static PET scanning with 370 MBq FDG was done for 20 min (from 40 to 60 min postinjection) in all patients, and standardized uptake values (SUVs) in these lesions were calculated. In addition, eight patients were evaluated with dynamic PET scan up to 60 min postinjection, and the lesions were further evaluated using graphical analysis. Thallium-201 delayed images were visually evaluated in 10 patients. RESULTS: Four of 11 nodules were well-differentiated papillary carcinoma, another five were benign follicular adenomas, one was a multinodular goiter and another a case of chronic thyroiditis that was proved not to contain a nodule. Time-activity curves of FDG uptake showed different patterns in malignant and benign tumors. In the malignant tumors, FDG uptake increased with time after the tracer injection. By contrast, FDG uptake in benign tumors gradually decreased. With use of a cutoff value of 5.0 mg/ml for SUV and 10 microl x min(-1) x ml(-1) for Kc (K complex value determined using the linear fitting of the time-activity curve of FDG accumulation), all of the four malignant nodules and the six benign nodules were separated correctly. Chronic thyroiditis had high SUV in the malignant range. Of the four patients with thyroid carcinoma, the delayed 201Tl images revealed a slightly higher or equal uptake to background activity. In a patient with chronic thyroiditis, the delayed 201Tl images revealed diffuse accumulation higher than background activity. CONCLUSION: FDG-PET is superior to 201Tl in differentiating malignant from benign tumors. Both SUVs and Kc values were useful indexes for this discrimination. Although careful evaluation is needed for chronic inflammatory lesions, this technique appears to be useful in evaluating thyroid nodules.

Adenoma↗

PubMed1998

Coregistration of FDG PET and MRI of the head and neck using normal distribution of FDG.

UNLABELLED: For better localization of head and neck structures by PET with 2-(18)F-2-deoxy-D-glucose (FDG), direct incorporation of anatomical information from MRI by the coregistration of FDG PET and MRI without external markers is proposed. METHODS: Seventeen patients with neoplasms and 16 normal subjects who had both FDG PET and MRI were studied. First, the three-dimensional normal distribution of FDG was evaluated, and then the structures of the head and neck regions with normal distribution patterns of FDG were used as internal markers for the coregistration of PET and MRI. The effectiveness of the coregistration was evaluated using focal neoplasms that were identified by both PET and MRI as fiducial internal markers. RESULTS: The normal structures selected as internal landmarks for coregistration were the tonsils, salivary glands, mucosal layers of the oral cavity and pharynx, spinal cord, inferior portion of the frontal lobe, cerebellum and nasal turbinates. These structures were more easily observed in sagittal or coronal sections than in transaxial sections. All primary neoplasms were delineated by PET, whereas 4 were missed by MRI. Thirteen primary tumors and 7 cervical lymph node metastases coregistered well, with a center-of-mass distance of <2 mm, whereas 10 lymph node metastases were slightly misregistered, with a center-of-mass distance of 7.8+/-6.5 mm (mean+/-s.d.), probably due to differences in neck positions. CONCLUSION: Normal distribution of FDG uptake in the head and neck regions delineated by multidirectional sections is important for effective coregistration of FDG PET with MRI.

Aged↗

PubMed1997

Role of the supplementary motor area and the right premotor cortex in the coordination of bimanual finger movements.

To obtain a better understanding of the cortical representation of bimanual coordination, we measured regional cerebral blood flow (rCBF) with 15O-labeled water and positron emission tomography (PET). To detect areas with changes of rCBF during bimanual finger movements of different characteristics, we studied 12 right-handed normal volunteers. A complete session consisted of three rest scans and six scans with acoustically paced (1 Hz) bimanual, mirror, or parallel sequential finger movements. Activation of the right dorsal premotor area (PMd) extending to the posterior supplementary motor area (SMA) was significantly stronger during the parallel movements than during the mirror sequential movements (p < 0.05, at cluster level with correction for multiple comparisons). To determine whether these cortical areas truly represented bimanual coordination, a different group of nine normal volunteers was studied with a different task. Subjects performed acoustically paced (2 Hz) abduction-adduction movements of the index finger, making right only, left only, and bimanual mirror and parallel movements. Activation of the posterior SMA and right PMd was significantly greater during the parallel movements than during the bimanual mirror movements or the unimanual movements of either hand (p < 0.01, with anatomical constraint). Thus, the posterior SMA and right PMd appear to be related to the bimanual coordination of finger movements.

Adult↗

PubMed1997

A rapid brain metabolic change in infants detected by fMRI.

To determine developmental changes of activity-related metabolism in human visual cortex, we performed functional magnetic resonance imaging (fMRI) from the neonatal period. A rapid metabolic changing pattern accompanying normal human brain maturation was revealed by fMRI with photic stimulation. Infants older than 8 weeks of age showed a stimulus-related signal decrease in the visual cortex, whereas younger neonates showed a signal increase. This inversion of response in infants suggests a change in oxygen consumption during neuronal activation, which is related to rapid synapse formation and accompanying increased metabolism. fMRI can detect dynamic metabolic changes during the brain maturation, and provides a new clue in the detection of abnormal brain development or CNS plasticity.

Aging↗

PubMed1997

Functional relevance of cross-modal plasticity in blind humans.

Functional imaging studies of people who were blind from an early age have revealed that their primary visual cortex can be activated by Braille reading and other tactile discrimination tasks. Other studies have also shown that visual cortical areas can be activated by somatosensory input in blind subjects but not those with sight. The significance of this cross-modal plasticity is unclear, however, as it is not known whether the visual cortex can process somatosensory information in a functionally relevant way. To address this issue, we used transcranial magnetic stimulation to disrupt the function of different cortical areas in people who were blind from an early age as they identified Braille or embossed Roman letters. Transient stimulation of the occipital (visual) cortex induced errors in both tasks and distorted the tactile perceptions of blind subjects. In contrast, occipital stimulation had no effect on tactile performance in normal-sighted subjects, whereas similar stimulation is known to disrupt their visual performance. We conclude that blindness from an early age can cause the visual cortex to be recruited to a role in somatosensory processing. We propose that this cross-modal plasticity may account in part for the superior tactile perceptual abilities of blind subjects.

Adult↗

PubMed1997

Mapping of cortical areas involved in color vision in non-human primates.

Positron emission tomography (PET) was used to measure changes in the regional cerebral blood flow (rCBF) of rhesus monkeys performing visual discrimination tasks. In comparison with both position and brightness discrimination tasks, the color discrimination task activated the posterior inferior temporal cortex and a ventromedial occipital region, which is located along the anterior one-third of the calcarine sulcus. In contrast, the position task activated the middle temporal area and intraparietal cortex as compared with the color task. These results confirm the segregation of visual pathways and delineate the visual areas involved in color vision. This approach might bridge the gap between invasive studies in animals and functional imaging studies in humans.

Animals↗

PubMed1997

Clinical value of triple-energy window scatter correction in simultaneous dual-isotope single-photon emission tomography with 123I-BMIPP and 201Tl.

To improve the image quality in simultaneous dual-isotope single-photon emission tomography (SPET) with iodine-123 labelled 15-(p-iodophenyl)-3-methylpentadecanoic acid (BMIPP) and thallium-201, we applied the triple-energy window method (TEW) for correction of the cross-talk and scatter artifact. Seventy-one patients with coronary artery disease were included. 201Tl cross-talk into the 123I acquisition window (group 1, n = 30) and 123I cross-talk into the 201Tl window (group 2, n = 41) were studied. In group 1, 123I images were first obtained (single-isotope images), followed by 201Tl injection and SPET acquisition using dual-isotope windows (dual-isotope images). In group 2, the order was reversed. The dual-isotope SPET images with and without TEW were compared with the single-isotope images. Qualitative evaluation was performed by scoring the segmental defect pattern. Detectability of the mismatched fatty acid metabolism on dual-isotope SPET was evaluated by receiver operating characteristic (ROC) curve analysis. Segmental defect pattern agreement between dual and corrected single images was significantly improved by TEW correction (P<0.01). The agreement was particularly improved in segments with absence of uptake. There was no significant difference between TEW-corrected dual-isotope SPET and corresponding single-isotope SPET with regard to either % defect count or background activity. Mismatched fatty acid metabolism depicted by dual-isotope SPET predicted abnormal wall motion more accurately with TEW than without TEW. With TEW, a practical method for scatter and cross-talk correction in clinical settings, simultaneous dual 123I-BMIPP/201Tl SPET is feasible for the assessment of myocardial perfusion/metabolism mismatch.

Case-Control Studies↗

PubMed1997

Effects of antitumor agents on 3H-2-deoxyglucose uptake in tumor cells and their relationship with the main targets of the antitumor agents.

To investigate the effects of antitumor drugs on 3H-2-deoxyglucose (DG) uptake in tumor cells, we performed DG uptake studies of the short-term treatment of four kinds of antitumor drugs in a cell culture system. The antitumor drugs adriamycin (ADM) and cisplatin (cDDP), which affect on DNA synthesis, did not greatly affect DG uptake, but DG uptake was lowered by antitumor drugs, actinomycin D (AcD) and cycloheximide (CHX), which target the gene expression system. To investigate the mechanism of DG uptake changes, we also tested the effects of some glucose metabolic inhibitors on DG uptake. An inhibitor of glycolytic flow (iodoacetate) lowered DG uptake whereas mitochondrial inhibition increased DG uptake. These results on the inhibition of glucose metabolism indicated that there were two types of factors affecting DG uptake directly; one affects glycolysis and the other affects oxidative phosphorylation. The two antitumor drugs with effects on gene expression were thought to act by the former. The effects of the drug treatments for tumors on DG uptake could be divided into three groups; glycolysis inhibition, mitochondrial inhibition and no relation to glucose metabolism. With the further observations of FDG uptake changes based on this prediction, the biochemical relationship between treatment effects and FDG uptake changes will be clarified.

2,4-Dinitrophenol↗