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ABSTRACT: To elucidate the dynamic effects of deep brain stimulation (DBS) in the subthalamic nucleus (STN) during activity on the dopaminergic system, 12 PD patients who had STN-DBS operations at least 1 month prior, underwent two positron emission tomography scans during right-foot movement in DBS-off and DBS-on conditions. To quantify motor performance changes, the motion speed and mobility angle of the foot at the ankle were measured twice. Estimations of the binding potential of [(11)C]raclopride (BP(ND)) were based on the Logan plot method. Significant motor recovery was found in the DBS-on condition. The STN-DBS during exercise significantly reduced the [(11)C]raclopride BP(ND) in the caudate and the nucleus accumbens (NA), but not in the dorsal or ventral putamen. The magnitude of dopamine release in the NA correlated negatively with the magnitude of motor load, indicating that STN-DBS facilitated motor behavior more smoothly and at less expense to dopamine neurons in the region. The lack of dopamine release in the putamen and the significant dopamine release in the ventromedial striatum by STN-DBS during exercise indicated dopaminergic activation occurring in the motivational circuit during action, suggesting a compensatory functional activation of the motor loop from the nonmotor to the motor loop system.Journal of Cerebral Blood Flow & Metabolism advance online publication, 5 December 2012; doi:10.1038/jcbfm.2012.183.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 12/2012; · 5.46 Impact Factor
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ABSTRACT: Although D2/3 agonists have been used as a first-line medication for idiopathic restless legs syndrome (iRLS), findings on D2/3 receptors have been inconsistent. Here, we aimed to clarify the contribution of D2/3 receptor function to the clinical symptoms of iRLS by comparing the binding potential (BP(ND)) of [(11)C]raclopride with clinical improvements after D2/3 stimulation by pramipexole. Eight drug-naïve, iRLS patients and eight age-matched healthy subjects were scanned with positron emission tomography (PET). After PET scans, all patients received pramipexole (0.125 mg) orally for 2 weeks. Patients were evaluated every day with several standardized clinical tests. The BP(ND) values were compared using regions of interest and voxel-based methods. Results showed that the mean magnitude of [(11)C]raclopride BP(ND) in the mesolimbic dopamine region (nucleus accumbens (NA) and caudate) was significantly lower in the iRLS group. No significant differences between groups were observed in the putamen. The NA [(11)C]raclopride BP(ND) levels correlated negatively with clinical severity scores and positively with the degree of posttreatment improvement in iRLS. The present results suggest that alterations in mesolimbic D2/3 receptor function reflect the pathophysiology of iRLS, and the baseline availability of D2/3 receptors may predict the clinical outcome after D2/3 agonist treatment.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 01/2012; 32(4):654-62. · 5.46 Impact Factor
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Shigeyuki Yamamoto,
Yasuomi Ouchi,
Daisaku Nakatsuka,
Tsuyoshi Tahara,
Kei Mizuno,
Seiki Tajima,
Hirotaka Onoe, Etsuji Yoshikawa,
Hideo Tsukada,
Masao Iwase,
Kouzi Yamaguti,
Hirohiko Kuratsune,
Yasuyoshi Watanabe
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ABSTRACT: Numerous associations between brain-reactive antibodies and neurological or psychiatric symptoms have been proposed. Serum autoantibody against the muscarinic cholinergic receptor (mAChR) was increased in some patients with chronic fatigue syndrome (CFS) or psychiatric disease. We examined whether serum autoantibody against mAChR affected the central cholinergic system by measuring brain mAChR binding and acetylcholinesterase activity using positron emission tomography (PET) in CFS patients with positive [CFS(+)] and negative [CFS(-)] autoantibodies.
Five CFS(+) and six CFS(-) patients, as well as 11 normal control subjects underwent a series of PET measurements with N-[(11)C]methyl-3-piperidyl benzilate [(11)C](+)3-MPB for the mAChR binding and N-[(11)C]methyl-4-piperidyl acetate [(11)C]MP4A for acetylcholinesterase activity. Cognitive function of all subjects was assessed by neuropsychological tests. Although the brain [(11)C](+)3-MPB binding in CFS(-) patients did not differ from normal controls, CFS(+) patients showed significantly lower [(11)C](+)3-MPB binding than CFS(-) patients and normal controls. In contrast, the [(11)C]MP4A index showed no significant differences among these three groups. Neuropsychological measures were similar among groups.
The present results demonstrate that serum autoantibody against the mAChR can affect the brain mAChR without altering acetylcholinesterase activity and cognitive functions in CFS patients.
PLoS ONE 01/2012; 7(12):e51515. · 4.09 Impact Factor
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Mitsuru Kikuchi,
Tetsu Hirosawa,
Masamichi Yokokura,
Shunsuke Yagi,
Norio Mori, Etsuji Yoshikawa,
Yujiro Yoshihara,
Genichi Sugihara,
Kiyokazu Takebayashi,
Yasuhide Iwata,
Katsuaki Suzuki,
Kazuhiko Nakamura,
Takatoshi Ueki,
Yoshio Minabe,
Yasuomi Ouchi
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ABSTRACT: Brain β-amyloid (Aβ) deposition during normal aging is highlighted as an initial pathogenetic event in the development of Alzheimer's disease. Many recent brain imaging studies have focused on areas deactivated during cognitive tasks [the default mode network (DMN), i.e., medial frontal gyrus/anterior cingulate cortex and precuneus/posterior cingulate cortex], where the strength of functional coordination was more or less affected by cerebral Aβ deposits. In the present positron emission tomography study, to investigate whether regional glucose metabolic alterations and Aβ deposits seen in nondemented elderly human subjects (n = 22) are of pathophysiological importance in changes of brain hemodynamic coordination in DMN during normal aging, we measured cerebral glucose metabolism with [(18)F]FDG, Aβ deposits with [(11)C]PIB, and regional cerebral blood flow during control and working memory tasks by H(2)(15)O on the same day. Data were analyzed using both region of interest and statistical parametric mapping. Our results indicated that the amount of Aβ deposits was negatively correlated with hemodynamic similarity between medial frontal and medial posterior regions, and the lower similarity was associated with poorer working memory performance. In contrast, brain glucose metabolism was not related to this medial hemodynamic similarity. These findings suggest that traceable Aβ deposition, but not glucose hypometabolism, in the brain plays an important role in occurrence of neuronal discoordination in DMN along with poor working memory in healthy elderly people.
Journal of Neuroscience 08/2011; 31(31):11193-9. · 7.11 Impact Factor
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Masamichi Yokokura,
Norio Mori,
Shunsuke Yagi, Etsuji Yoshikawa,
Mitsuru Kikuchi,
Yujiro Yoshihara,
Tomoyasu Wakuda,
Genichi Sugihara,
Kiyokazu Takebayashi,
Shiro Suda,
Yasuhide Iwata,
Takatoshi Ueki,
Kenji J Tsuchiya,
Katsuaki Suzuki,
Kazuhiko Nakamura,
Yasuomi Ouchi
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ABSTRACT: Amyloid β protein (Aβ) is known as a pathological substance in Alzheimer's disease (AD) and is assumed to coexist with a degree of activated microglia in the brain. However, it remains unclear whether these two events occur in parallel with characteristic hypometabolism in AD in vivo. The purpose of the present study was to clarify the in vivo relationship between Aβ accumulation and neuroinflammation in those specific brain regions in early AD.
Eleven nootropic drug-naïve AD patients underwent a series of positron emission tomography (PET) measurements with [(11)C](R)PK11195, [(11)C]PIB and [(18)F]FDG and a battery of cognitive tests within the same day. The binding potentials (BPs) of [(11)C](R)PK11195 were directly compared with those of [(11)C]PIB in the brain regions with reduced glucose metabolism.
BPs of [(11)C](R)PK11195 and [(11)C]PIB were significantly higher in the parietotemporal regions of AD patients than in ten healthy controls. In AD patients, there was a negative correlation between dementia score and [(11)C](R)PK11195 BPs, but not [(11)C]PIB, in the limbic, precuneus and prefrontal regions. Direct comparisons showed a significant negative correlation between [(11)C](R)PK11195 and [(11)C]PIB BPs in the posterior cingulate cortex (PCC) (p < 0.05, corrected) that manifested the most severe reduction in [(18)F]FDG uptake.
A lack of coupling between microglial activation and amyloid deposits may indicate that Aβ accumulation shown by [(11)C]PIB is not always the primary cause of microglial activation, but rather the negative correlation present in the PCC suggests that microglia can show higher activation during the production of Aβ in early AD.
European Journal of Nuclear Medicine 02/2011; 38(2):343-51. · 4.53 Impact Factor
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ABSTRACT: We devised a new computer-aided diagnosis method to segregate dementia using one estimated index (Total Z score) derived from the Brodmann area (BA) sensitivity map on the stereotaxic brain atlas. The purpose of this study is to investigate its accuracy to differentiate patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) from normal adults (NL).
We studied 101 adults (NL: 40, AD: 37, MCI: 24) who underwent (18)FDG positron emission tomography (PET) measurement. We divided NL and AD groups into two categories: a training group with (Category A) and a test group without (Category B) clinical information. In Category A, we estimated sensitivity by comparing the standard uptake value per BA (SUVR) between NL and AD groups. Then, we calculated a summated index (Total Z score) by utilizing the sensitivity-distribution maps and each BA z-score to segregate AD patterns. To confirm the validity of this method, we examined the accuracy in Category B. Finally, we applied this method to MCI patients.
In Category A, we found that the sensitivity and specificity of differentiation between NL and AD were all 100%. In Category B, those were 100% and 95%, respectively. Furthermore, we found this method attained 88% to differentiate AD-converters from non-converters in MCI group.
The present automated computer-aided evaluation method based on a single estimated index provided good accuracy for differential diagnosis of AD and MCI. This good differentiation power suggests its usefulness not only for dementia diagnosis but also in a longitudinal study.
PLoS ONE 01/2011; 6(9):e25033. · 4.09 Impact Factor
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ABSTRACT: It is still unclear why some early Parkinson disease (PD) patients with unilateral parkinsonism develop bilateral parkinsonism soon after the diagnosis is made as Hoehn and Yahr (HY) stage 1 and others remain stable for a long time. Here, we examined in vivo changes in the brain dopaminergic system using PET with a dopamine transporter radiotracer, (11)C-2-B-carbomethoxy-3B-(4-fluorophenyl) tropane ((11)C-CFT), to elucidate the pathophysiologic characteristics of the dopamine system in early converters.
Twelve drug-naïve PD patients with HY stage 1 disease and 8 age-matched healthy subjects participated in this study. Clinical evaluation of their parkinsonism was performed monthly until their HY stage 1 (unilateral parkinsonism) disease had become stage 2 (bilateral parkinsonism) disease according to the Unified Parkinson Disease Rating Scale. The endpoint of the follow-up study was the time of the conversion. Region-of-interest analysis was used to examine (11)C-CFT binding in the mesocortical (nucleus accumbens, caudate, orbitofrontal cortex) and nigrostriatal (putamen) dopamine projection regions. Multiregression analyses between these PET data and clinical parameters were performed within the PD group.
Between-group comparisons showed that, irrespective of the duration of conversion, all PD patients clinically diagnosed at HY stage 1 had a significant reduction in (11)C-CFT binding in the bilateral striatum (affected, -46%; unaffected, -35%). Regression analysis showed that the level of (11)C-CFT binding in the nucleus accumbens and orbitofrontal cortex on the unaffected side was significantly positively correlated with the conversion interval. This positive correlation indicates that the more severe a dysfunction presents in the mesocortical dopamine system on the seemingly intact side, the more rapidly the parkinsonism proceeds to the intact side (bilateral parkinsonism).
The finding of bilateral reduction in the striatal (11)C-CFT binding even in HY stage 1 PD patients confirms that molecular changes in the dopamine system precede clinical phenotype, suggesting an advantage of PET for detecting an early abnormality of the disease. The spread of parkinsonism to the unaffected side soon after the diagnosis of HY stage 1 PD may be related to the degree of mesocortical dopamine dysfunction.
Journal of Nuclear Medicine 08/2010; 51(8):1250-7. · 6.38 Impact Factor
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Seiki Tajima,
Shigeyuki Yamamoto,
Masaaki Tanaka,
Yosky Kataoka,
Masao Iwase, Etsuji Yoshikawa,
Hiroyuki Okada,
Hirotaka Onoe,
Hideo Tsukada,
Hirohiko Kuratsune,
Yasuomi Ouchi,
Yasuyoshi Watanabe
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ABSTRACT: Fatigue is an indispensable bioalarm to avoid exhaustive state caused by overwork or stresses. It is necessary to elucidate the neural mechanism of fatigue sensation for managing fatigue properly. We performed H(2) ( 15)O positron emission tomography scans to indicate neural activations while subjects were performing 35-min fatigue-inducing task trials twice. During the positron emission tomography experiment, subjects performed advanced trail-making tests, touching the target circles in sequence located on the display of a touch-panel screen. In order to identify the brain regions associated with fatigue sensation, correlation analysis was performed using statistical parametric mapping method. The brain region exhibiting a positive correlation in activity with subjective sensation of fatigue, measured immediately after each positron emission tomography scan, was located in medial orbitofrontal cortex (Brodmann's area 10/11). Hence, the medial orbitofrontal cortex is a brain region associated with mental fatigue sensation. Our findings provide a new perspective on the neural basis of fatigue.
Neurology research international. 01/2010; 2010:671421.
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Kazuhiko Nakamura,
Yoshimoto Sekine,
Yasuomi Ouchi,
Masatsugu Tsujii, Etsuji Yoshikawa,
Masami Futatsubashi,
Kenji J Tsuchiya,
Genichi Sugihara,
Yasuhide Iwata,
Katsuaki Suzuki,
Hideo Matsuzaki,
Shiro Suda,
Toshiro Sugiyama,
Nori Takei,
Norio Mori
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ABSTRACT: Autism is a neurodevelopmental disorder that is characterized by repetitive and/or obsessive interests and behavior and by deficits in sociability and communication. Although its neurobiological underpinnings are postulated to lie in abnormalities of the serotoninergic and dopaminergic systems, the details remain unknown.
To determine the occurrence of changes in the binding of serotonin and dopamine transporters, which are highly selective markers for their respective neuronal systems.
Using positron emission tomography, we measured the binding of brain serotonin and dopamine transporters in each individual with the radioligands carbon 11 ((11)C)-labeled trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]isoquinoline ([(11)C](+)McN-5652) and 2beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane ([(11)C]WIN-35,428), respectively. Statistical parametric mapping was used for between-subject analysis and within-subject correlation analysis with respect to clinical variables.
Participants recruited from the community.
Twenty men (age range, 18-26 years; mean [SD] IQ, 99.3 [18.1]) with autism and 20 age- and IQ-matched control subjects.
Serotonin transporter binding was significantly lower throughout the brain in autistic individuals compared with controls (P < .05, corrected). Specifically, the reduction in the anterior and posterior cingulate cortices was associated with the impairment of social cognition in the autistic subjects (P < .05, corrected). A significant correlation was also found between repetitive and/or obsessive behavior and interests and the reduction of serotonin transporter binding in the thalamus (P < .05, corrected). In contrast, the dopamine transporter binding was significantly higher in the orbitofrontal cortex of the autistic group (P < .05, corrected in voxelwise analysis). In the orbitofrontal cortex, the dopamine transporter binding was significantly inversely correlated with serotonin transporter binding (r = -0.61; P = .004).
The brains of autistic individuals have abnormalities in both serotonin transporter and dopamine transporter binding. The present findings indicate that the gross abnormalities in these neurotransmitter systems may underpin the neurophysiologic mechanism of autism. Our sample was not characteristic or representative of a typical sample of adults with autism in the community.
Archives of general psychiatry 01/2010; 67(1):59-68. · 12.26 Impact Factor
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ABSTRACT: Whether preclinical depression is one of the pathophysiologic features of Alzheimer disease (AD) has been under debate. In vivo molecular imaging helps clarify this kind of issue. Here, we examined in vivo changes in the brain serotoninergic system and glucose metabolism by scanning early- to moderate-stage AD patients with and without depression using PET with a radiotracer for the serotonin transporter, (11)C-3-amino-4-(2-dimethylaminomethylphenylsulfanyl) benzonitrile (DASB), and a metabolic marker, (18)F-FDG.
Fifteen AD patients (8 nondepressed and 7 depressed) and 10 healthy subjects participated. All participants underwent 3-dimensional MRI and quantitative (11)C-DASB PET measurements, followed by (18)F-FDG PET scans in the AD group. Region-of-interest analysis was used to examine changes in (11)C-DASB binding potential estimated quantitatively by the Logan plot method in the serotonergic projection region. In addition, statistical parametric mapping was used to examine whether glucose metabolism in any brain region correlated with levels of (11)C-DASB binding in the dense serotonergic projection region (striatum) in AD.
Psychologic evaluation showed that general cognitive function (Mini-Mental State Examination) was similar between the 2 AD subgroups. Striatal (11)C-DASB binding was significantly lower in AD patients, irrespective of depression, than in healthy controls (P < 0.05, corrected), and (11)C-DASB binding in other dense projection areas decreased significantly in the depressive group, compared with the control group. The (11)C-DASB binding potential levels in the subcortical serotonergic projection region correlated negatively with depression score (Spearman correlation, P < 0.01) but not with dementia score. Statistical parametric mapping correlation analysis showed that glucose metabolism in the right dorsolateral prefrontal cortex was positively associated with the level of striatal (11)C-DASB binding in AD.
The significant reduction in (11)C-DASB binding in nondepressed AD patients suggests that presynaptic serotonergic function is altered before the development of psychiatric problems such as depression in AD. The depressive AD group showed greater and broader reductions in binding, suggesting that a greater loss of serotonergic function relates to more severe psychiatric symptoms in the disease. This serotonergic dysfunction may affect the activity of the right dorsolateral prefrontal cortex, a higher center of cognition and emotion in AD.
Journal of Nuclear Medicine 09/2009; 50(8):1260-6. · 6.38 Impact Factor
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ABSTRACT: This study was designed to compare tumor (18)F-FDG uptake between a single 20-s acquisition of deep-inspiration breath-hold PET/CT and free-breathing PET/CT for lung cancer.
Before the clinical study, a phantom study was performed to determine the optimum breath-hold time for the PET scan. We studied 47 patients with lung cancer who underwent free-breathing PET/CT with the standard clinical protocol, followed by deep-inspiration breath-hold PET/CT of the thorax. In breath-hold PET/CT, the patients were asked to hold their breath in deep inspiration for 10 s during the CT scan and for 20 s during the PET scan. Maximum tumor (18)F-FDG standardized uptake value (SUVmax) was measured in free-breathing PET and breath-hold PET, and the percentage difference between these 2 values was calculated.
Breath-hold PET showed a significant increase in SUVmax, as compared with free-breathing PET (8.26 +/- 4.59 vs. 11.25 +/- 7.24, P < 0.0001). The mean difference in SUVmax was 39.5% +/- 43.4%, and the range was 2.9%-248.3%. The difference in SUVmax was significant when compared between tumors in the upper lung (n = 22) and tumors in the lower lung (n = 25) (24.4% +/- 17.7% vs. 52.9% +/- 54.3%, P = 0.0077). The mean tumor size of the group with a high SUVmax difference (n = 13) was significantly smaller than that of the group with a low SUVmax difference (n = 34) (2.45 +/- 0.87 cm vs. 3.21 +/- 1.22 cm, P = 0.043), using a cutoff of 39.5%.
The single 20-s acquisition of breath-hold PET/CT enabled more precise measurement of SUVmax, especially in the lower lung field and for small tumors, which may be affected by respiratory motion. This technique is feasible in the clinical setting and requires only a minor increase in examination time.
Journal of Nuclear Medicine 09/2009; 50(10):1579-84. · 6.38 Impact Factor
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Yoshimoto Sekine,
Yasuomi Ouchi,
Genichi Sugihara,
Nori Takei, Etsuji Yoshikawa,
Kazuhiko Nakamura,
Yasuhide Iwata,
Kenji J Tsuchiya,
Shiro Suda,
Katsuaki Suzuki,
Masayoshi Kawai,
Kiyokazu Takebayashi,
Shigeyuki Yamamoto,
Hideo Matsuzaki,
Takatoshi Ueki,
Norio Mori,
Mark S Gold,
Jean L Cadet
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ABSTRACT: Methamphetamine is a popular addictive drug whose use is associated with multiple neuropsychiatric adverse events and toxic to the dopaminergic and serotonergic systems of the brain. Methamphetamine-induced neuropathology is associated with increased expression of microglial cells that are thought to participate in either pro-toxic or protective mechanisms in the brain. Although reactive microgliosis has been observed in animal models of methamphetamine neurotoxicity, no study has reported on the status of microglial activation in human methamphetamine abusers. The present study reports on 12 abstinent methamphetamine abusers and 12 age-, gender-, and education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [(11)C](R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([(11)C](R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials of [(11)C](R)-PK11195 in brain regions with dopaminergic and/or serotonergic innervation. The mean levels of [(11)C](R)-PK11195 binding were higher in methamphetamine abusers than those in control subjects in all brain regions (>250% higher; p < 0.01 for all). In addition, the binding levels in the midbrain, striatum, thalamus, and orbitofrontal and insular cortices (p < 0.05) correlated inversely with the duration of methamphetamine abstinence. These results suggest that chronic self-administration of methamphetamine can cause reactive microgliosis in the brains of human methamphetamine abusers, a level of activation that appears to subside over longer periods of abstinence.
Journal of Neuroscience 06/2008; 28(22):5756-61. · 7.11 Impact Factor
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ABSTRACT: Gait disturbance in idiopathic normal pressure hydrocephalus (iNPH) is reminiscent of parkinsonism. Our recent PET study showed reduction in postsynaptic D(2) receptor binding concomitant with a normality of presynaptic dopamine transporter binding. Here, we investigated the plasticity of D(2) receptor in treating iNPH patients with ventriculoperitoneal (VP) shunting using PET with (11)C-raclopride and discuss the contribution of D(2) receptor to the pathophysiology of iNPH.
Eight iNPH patients participated in this study. After evaluation of their neuropsychologic abilities, all patients underwent 3-dimensional MRI and quantitative PET measurements twice before and 1 mo after VP shunting. MRI-based morphometric analyses were performed to examine postoperative variations of the ventricles. Estimation of binding potential (BP) for (11)C-raclopride was based on Logan plot analysis. Region-of-interest analysis was used to examine changes in (11)C-raclopride BP in the striatum. A 2-tailed paired t test was used for evaluating changes in PET and MRI parameters between conditions, and correlation analysis was used to investigate clinicopathophysiologic relevance (clinical vs. in vivo findings).
Clinical evaluation revealed significant recovery in a 5-m back-and-forth navigation test and an affect test and a mild increase in Mini-Mental State Examination scores after VP shunting. Significant postoperative increases in (11)C-raclopride BP were found in the nucleus accumbens and dorsal putamen, and the increases were significantly associated with emotional (Spearman rank r = 0.66, P < 0.05) and navigational improvement (r = 0.72, P < 0.05), respectively. The (11)C-raclopride BP increase in the striaum as a whole correlated significantly with improvement in general cognitive ability. There was a mild ventricular shrinkage after surgery, albeit there was no correlation of its size with clinical and PET parameters.
Striatal upregulation of D(2) receptor after VP shunting is associated with amelioration of hypokinetic gait disturbance and anhedonic mentation in iNPH patients, indicating that the effect of VP shunting may reside in noninhibition of functionally suppressed D(2) receptor in the striatum. D(2) receptor responsiveness may indicate a mechanism for iNPH pathophysiology.
Journal of Nuclear Medicine 12/2007; 48(12):1981-6. · 6.38 Impact Factor
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ABSTRACT: Differentiation of impaired gait seen in idiopathic normal pressure hydrocephalus (iNPH) from parkinsonian gait is sometimes a great challenge and important for future medication in the clinical setting. To investigate dopaminergic contribution to its pathophysiology, two aspects of the trans-synaptic dopamine functions in the striatal region in eight iNPH patients naïve to dopaminergic drugs were examined using positron emission tomography with a presynaptic marker [11C]CFT ([11C]2-beta-carbomethoxy-3beta-(4-fluorophenyl) tropane) that binds to dopamine transporter and a postsynaptic marker [11C]raclopride that binds to D2 receptor. Quantitative values of binding potentials (BPs) for [11C]CFT and [11C]raclopride were compared between patients and eight age-matched healthy subjects. The BPs and magnetic resonance imaging-based morphometric measures in iNPH were used for correlation analyses between the magnitude of binding of these in vivo markers and clinical severity of the patients. Analysis of variance showed significant reduction in [11C]raclopride binding in the putamen and nucleus accumbens (P<0.05, corrected for multiple comparison) and unchanged striatal [11C]CFT binding in iNPH. The dorsal putamen [11C]raclopride binding correlated negatively with gait severity (r=0.720, P<0.05), and the nucleus accumbens [11C]raclopride binding correlated positively with emotional recognition score (r=0.727, P<0.05) in the disease group. No significant relationship was observed between BPs and morphometric measures. The current result of the postsynaptic D2 receptor reduction along with preserved presynaptic activity in the nigrostriatal dopaminergic system reflects a pathophysiology of iNPH. Postsynaptic D2 receptor hypoactivity in the dorsal putamen may predict the severity of gait impairment in iNPH.
Journal of Cerebral Blood Flow & Metabolism 04/2007; 27(4):803-10. · 5.01 Impact Factor
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ABSTRACT: To investigate changes in regional cerebral blood flow (rCBF) under the prone condition with and without light massage on the back, we measured rCBF quantitatively in healthy human subjects using positron emission tomography with H(2)15O. Biochemical tests showed that the light massage (palm-pressure) reduced levels of stress-related serum cortisol and salivary stress protein chromogranin-A measured after the PET examination. Absolute rCBF significantly increased in the parietal cortex (precuneus) under the prone condition compared with the supine condition, and this rCBF increase was in parallel with comfortable sensation and slowing heart rate during the massage. Correlation analysis in statistical parametric mapping showed that the amygdalar and basal forebrain rCBF correlated with parasympathetic function (heart rate reduction), indicating involvement of the forebrain-amygdala system in mediating activities in the autonomic nervous system in the presence of comfortable sensation. To conclude, prone posture itself can stimulate the precuneus region to raise awareness, and the light massage on the back may help accommodate the brain to comfortable stimulation.
Neuroscience Letters 11/2006; 407(2):131-5. · 2.11 Impact Factor
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Yoshimoto Sekine,
Yasuomi Ouchi,
Nori Takei, Etsuji Yoshikawa,
Hiroyuki Okada,
Yoshio Minabe,
Kazuhiko Nakamura,
Katsuaki Suzuki,
Yasuhide Iwata,
Kenji J Tsuchiya,
Genichi Sugihara,
Norio Mori
Journal of Clinical Psychopharmacology 11/2006; 26(5):531-3. · 4.10 Impact Factor
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ABSTRACT: With the recent increase in FDG-PET examinations, concern has mounted regarding radiation exposure to hospital staff and the general public from patients injected with FDG. Because our PET institution is located 15 km from the hospital that provides these examinations, a driver has been designated to transport patients injected with FDG. This study was designed to measure the radiation dose to the driver from these patients (n=28) and to compare it with the estimated dose. A pocket dosimeter was used to measure radiation exposure to the driver. When the distances between the driver and patient were 1.1 m and 1.9 m, mean measured doses were 7.31 microSv and 2.26 microSv, respectively, while mean estimated doses were 8.61 microSv and 2.82 microSv, respectively, per trip. It was presumed that maximum radiation exposure per year was between 3.02 mSv (1.1 m) and 0.92 mSv (1.9 m). According to our data, the measured dose was 20% lower than the estimated dose. This discrepancy may be due to the difference between the volume source (measured dose) and point source (estimated dose).
Nippon Hoshasen Gijutsu Gakkai zasshi 09/2006; 62(8):1105-10.
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ABSTRACT: For surgical planning of uterine corpus cancer, prior knowledge of the depth of myometrial invasion is important. Curative tumour resection is possible in superficial invasion (stages IA and IB), while post-surgical chemotherapy or radiation therapy is required in deep invasion (stage IC). We evaluated the value of positron emission tomography with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG PET) for estimating the myometrial invasion in uterine corpus cancer.
We studied 22 patients with clinical stage I uterine corpus cancer, who underwent FDG PET prior to surgery. Standardized uptake value (SUV; tracer activity per injected dose normalized to body weight) was calculated on the PET image. PET findings were compared with magnetic resonance imaging (MRI) and the surgical staging.
The surgical stage was IA in five, IB in 11 and IC in six patients. SUVs in deep invasion (15.69+/-4.73, 8.83-21.84) were significantly higher than those in superficial invasion (9.09+/-3.29, 2.68-15.41) (P<0.005). Using 12.0 as a cut-off value of SUV for the differentiation of these two groups, PET results were correct in 19 patients but were incorrect in three patients. Although both PET and MRI provided correct staging in 14 patients, only MRI overestimated the myometrial invasion in four patients with stage IB and showed inconclusive findings in one patient with stage IC. Four of these five patients were post-menopausal.
The cut-off value of SUV (=12.0) may be a useful index for the differentiation of superficial invasion and deep invasion. FDG PET may be feasible for predicting the myometrial infiltration of uterine corpus cancer, especially when uterine atrophy makes it difficult at MRI in post-menopausal patients.
Nuclear Medicine Communications 07/2006; 27(6):481-7. · 1.40 Impact Factor
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Etsuko Ohmae,
Yasuomi Ouchi,
Motoki Oda,
Toshihiko Suzuki,
Shuji Nobesawa,
Toshihiko Kanno, Etsuji Yoshikawa,
Masami Futatsubashi,
Yukio Ueda,
Hiroyuki Okada,
Yutaka Yamashita
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ABSTRACT: We compared pharmacologically-perturbed hemodynamic parameters (cerebral blood volume; CBV, and flow; CBF) by acetazolamide administration in six healthy human subjects studied with positron emission tomography (PET) and near-infrared (NIR) time-resolved spectroscopy (TRS) simultaneously to investigate whether NIR-TRS could measure in vivo hemodynamics in the brain tissue quantitatively. Simultaneously with the PET measurements, TRS measurements were performed at the forehead with four different optode spacing from 2 cm to 5 cm. Total hemoglobin and oxygen saturation (SO2) measured by TRS significantly increased after administration of acetazolamide at any optode spacing in all subjects. In PET study, CBV and CBF were estimated in the following three volumes of interest (VOIs) determined on magnetic resonance images, VOI1: scalp and skull, VOI2: gray matter region, VOI3: gray and white matter regions. Acetazolamide treatment elevated CBF and CBV significantly in VOI2 and VOI3 but VOI1. TRS-derived CBV was more strongly correlated with PET-derived counterpart in VOI2 and VOI3 when the optode spacing was above 4 cm, although optical signal from cerebral tissue could be caught with any optode spacing. As to increase of the CBV, 4 cm of optode spacing correlated best with VOI2. To support the result of TRS-PET experiment, we also estimated the contribution ratios of intracerebral tissue to observed absorption change based on diffusion theory. The contribution ratios at 4 cm were estimated as follows: 761 nm: 50%, 791 nm: 72%, 836 nm: 70%. These results demonstrated that NIR-TRS with 4 cm of optode spacing could measure cerebral hemodynamic responses optimally and quantitatively.
NeuroImage 03/2006; 29(3):697-705. · 5.89 Impact Factor
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Yoshimoto Sekine,
Yasuomi Ouchi,
Nori Takei, Etsuji Yoshikawa,
Kazuhiko Nakamura,
Masami Futatsubashi,
Hiroyuki Okada,
Yoshio Minabe,
Katsuaki Suzuki,
Yasuhide Iwata,
Kenji J Tsuchiya,
Hideo Tsukada,
Masaomi Iyo,
Norio Mori
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ABSTRACT: In animals, methamphetamine is known to have a neurotoxic effect on serotonin neurons, which have been implicated in the regulation of mood, anxiety, and aggression. It remains unknown whether methamphetamine damages serotonin neurons in humans.
To investigate the status of brain serotonin neurons and their possible relationship with clinical characteristics in currently abstinent methamphetamine abusers.
Case-control analysis.
A hospital research center.
Twelve currently abstinent former methamphetamine abusers (5 women and 7 men) and 12 age-, sex-, and education-matched control subjects recruited from the community.
The brain regional density of the serotonin transporter, a structural component of serotonin neurons, was estimated using positron emission tomography and trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]isoquinoline ([(11)C](+)McN-5652). Estimates were derived from region-of-interest and statistical parametric mapping methods, followed by within-case analysis using the measures of clinical variables.
The duration of methamphetamine use, the magnitude of aggression and depressive symptoms, and changes in serotonin transporter density represented by the [(11)C](+)McN-5652 distribution volume.
Methamphetamine abusers showed increased levels of aggression compared with controls. Region-of-interest and statistical parametric mapping analyses revealed that the serotonin transporter density in global brain regions (eg, the midbrain, thalamus, caudate, putamen, cerebral cortex, and cerebellum) was significantly lower in methamphetamine abusers than in control subjects, and this reduction was significantly inversely correlated with the duration of methamphetamine use. Furthermore, statistical parametric mapping analyses indicated that the density in the orbitofrontal, temporal, and anterior cingulate areas was closely associated with the magnitude of aggression in methamphetamine abusers.
Protracted abuse of methamphetamine may reduce the density of the serotonin transporter in the brain, leading to elevated aggression, even in currently abstinent abusers.
Archives of General Psychiatry 02/2006; 63(1):90-100. · 12.02 Impact Factor
