The Experts below are selected from a list of 390648 Experts worldwide ranked by ideXlab platform
Jeffrey H. Meyer - One of the best experts on this subject based on the ideXlab platform.
-
seasonal variation in human brain serotonin transporter Binding
Archives of General Psychiatry, 2008Co-Authors: N Praschakrieder, Sylvain Houle, Alan A Wilson, M Willeit, Jeffrey H. MeyerAbstract:Context It is a common experience in temperate zones that individuals feel happier and more energetic on bright and sunny days and many experience a decline in mood and energy during the dark winter season. Brain serotonin is involved in the regulation of physiologic functions, such as mating, feeding, energy balance, and sleep. Although these behaviors and serotonin-related conditions show a clear seasonal pattern in humans, the molecular background of seasonal changes in serotonin function is entirely unknown. The serotonin transporter is a key element in regulating intensity and spread of the serotonin signal. Objectives To detect seasonal variations in serotonin transporter Binding in the living human brain and to detect correlations between serotonin transporter Binding and duration of daily sunshine. Design Regional serotonin transporter Binding Potential values, an index of serotonin transporter density, were assessed from December 1, 1999, to December 9, 2003, in a consecutive sample of healthy volunteers. Binding Potential values were related to meteorologic data. Setting Tertiary care psychiatric hospital. Participants Volunteer sample of 88 drug-naive healthy individuals. Intervention Carbon 11–labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile positron emission tomography. Main Outcome Measure Regional serotonin transporter Binding Potential values. Results Serotonin transporter Binding Potential values were significantly higher in all investigated brain regions in individuals investigated in the fall and winter compared with those investigated in the spring and summer ( P = .01 to .001). Moreover, Binding Potential values showed negative correlations with average duration of daily sunshine in all brain regions (ρ = −0.21 to −0.39; P = .05 to Conclusions Serotonin transporter Binding Potential values vary throughout the year with the seasons. Since higher serotonin transporter density is associated with lower synaptic serotonin levels, regulation of serotonin transporter density by season is a previously undescribed physiologic mechanism that has the Potential to explain seasonal changes in normal and pathologic behaviors.
-
elevated putamen d 2 receptor Binding Potential in major depression with motor retardation an 11 c raclopride positron emission tomography study
American Journal of Psychiatry, 2006Co-Authors: Jeffrey H. Meyer, Alan A Wilson, Heather E Mcneely, Sandra Sagrati, Anahita Boovariwala, Krystle Martin, Paul N L G Verhoeff, Sylvain HouleAbstract:Objective: Several antidepressants raise striatal dopamine, but the role of striatal dopamine during major depressive episodes is unclear. Striatal [ 11 C]raclopride Binding Potential measured with positron emission tomography is an index of D 2 type receptors and is sensitive to extracellular dopamine levels (higher D 2 Binding Potential occurs when dopamine is lower). It was hypothesized that putamen D 2 Binding Potential would be higher during major depressive episodes featuring motor retardation. Method: Drug-free, nonsmoking subjects experiencing a major depressive episode (N=21) underwent [ 11 C]raclopride PET imaging as did 21 healthy age-matched comparison subjects. Motor retardation was measured with the finger tapping test. Results: The depressed subjects exhibiting motor retardation had significantly higher D 2 Binding Potential in both the left and right putamen than did healthy subjects, and putamen D 2 Binding Potential correlated significantly with motor speed in the depressed subjects. Con...
-
brain serotonin transporter Binding Potential measured with carbon 11 labeled dasb positron emission tomography effects of major depressive episodes and severity of dysfunctional attitudes
Archives of General Psychiatry, 2004Co-Authors: Jeffrey H. Meyer, Sylvain Houle, Sandra Sagrati, Anna Carella, Doug Hussey, Nathalie Ginovart, Verdell S Goulding, James L Kennedy, Alan A WilsonAbstract:Background Although brain serotonin transporter (5-HTT) density has been investigated in subjects with a history of major depressive episodes (MDE), there has never been an investigation of brain 5-HTT during a current MDE. Brain 5-HTT Binding Potential (BP) may have an important role during MDE due to major depressive disorder, because the 5-HTT regulates extracellular 5-HT. The BP is an index of receptor density. Carbon 11–labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB) positron emission tomography (PET) is the first brain imaging technique that can measure the 5-HTT BP in cortical and subcortical brain regions in vivo. The purposes of this study were to investigate 5-HTT BP during MDE and to determine the relationship between 5-HTT BP and negativistic dysfunctional attitudes during MDE. Dysfunctional attitudes are negatively biased assumptions and beliefs regarding oneself, the world, and the future. Our recent publication of increased serotonin 2 BP in MDE with severely negativistic dysfunctional attitudes suggests that this subgroup of MDE subjects has very low levels of extracellular serotonin. Methods Regional 5-HTT BP was measured in 20 nonsmoking medication-free (≥3 months) depressed subjects and 20 age-matched nonsmoking, medication-free, healthy subjects using [ 11 C]DASB PET. Dysfunctional attitudes were measured using the Dysfunctional Attitudes Scale. Results No difference in regional 5-HTT BP was found between MDE and healthy subjects; however, the subgroup of MDE subjects with highly negativistic dysfunctional attitudes had significantly higher 5-HTT BP compared with healthy subjects in brain regions mainly sampling serotonergic nerve terminals (prefrontal cortex, anterior cingulate, thalamus, bilateral caudate, and bilateral putamen; average, 21% greater; F 1,26 , 5.6-12.2 [ P values, .03-.002]). In the MDE subjects, increased 5-HTT BP was strongly associated with more negativistic dysfunctional attitudes in brain regions primarily sampling serotonergic nerve terminals (prefrontal cortex, anterior cingulate, thalamus, caudate, and putamen; r = 0.64-0.74 [ P values, .003 to Conclusions Serotonin transporters play an important role during depression. The magnitude of regional 5-HTT BP can provide a vulnerability to low levels of extracellular serotonin and symptoms of extremely negativistic dysfunctional attitudes.
-
serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses an 11c dasb positron emission tomography study
American Journal of Psychiatry, 2004Co-Authors: Jeffrey H. Meyer, Alan A Wilson, Sandra Sagrati, Anna Carella, Doug Hussey, Nathalie Ginovart, William Z Potter, Edgar P Spencer, Andy Cheok, Sylvain HouleAbstract:OBJECTIVE: Minimum therapeutic doses of paroxetine and citalopram produce 80% occupancy for the serotonin (5-HT) transporter (5-HTT). The authors used [11C]DASB positron emission tomography to measure occupancies of three other selective serotonin reuptake inhibitors (SSRIs) at minimum therapeutic doses. The relationship between dose and occupancy was also investigated. METHOD: Striatal 5-HTT Binding Potential was measured in 77 subjects before and after 4 weeks of medication administration. Binding Potential is proportional to the density of receptors not blocked by medication. Subjects received citalopram, fluoxetine, sertraline, paroxetine, or extended-release venlafaxine. Healthy subjects received subtherapeutic doses; subjects with mood and anxiety disorders received therapeutic doses. Percent reduction in 5-HTT Binding Potential for each medication and dose was calculated. To obtain test-retest data, Binding Potential was measured before and after 4 weeks in six additional healthy subjects. RESULTS:...
-
occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression a 11 c dasb pet imaging study
American Journal of Psychiatry, 2001Co-Authors: Jeffrey H. Meyer, Alan A Wilson, Doug Hussey, Nathalie Ginovart, Verdell S Goulding, Karen Hood, Sylvain HouleAbstract:OBJECTIVE: Selective serotonin reuptake inhibitors are commonly used to treat major depression; however, the percentage of serotonin (5-HT) transporter (5-HTT) sites occupied during clinical dosing is unknown. This study measured the proportion of 5-HTT sites blocked during paroxetine and citalopram treatment of depression and assessed the relationship between serum paroxetine levels and the proportion of 5-HTT sites blocked. METHOD: Twelve medication-free depressed patients completed a 6-week trial of either paroxetine (N=8) or citalopram (N=4). Striatal 5-HTT Binding Potential was measured with [11C]DASB and positron emission tomography, before and after 4 weeks of treatment. The Binding Potential is proportional to receptor density. Striatal 5-HTT Binding Potential was measured twice in six healthy subjects and once in 11 healthy subjects. RESULTS: A significant decrease in striatal 5-HTT Binding Potential was found after either treatment, compared to changes found over a 4-week period in healthy subje...
Sylvain Houle - One of the best experts on this subject based on the ideXlab platform.
-
seasonal variation in human brain serotonin transporter Binding
Archives of General Psychiatry, 2008Co-Authors: N Praschakrieder, Sylvain Houle, Alan A Wilson, M Willeit, Jeffrey H. MeyerAbstract:Context It is a common experience in temperate zones that individuals feel happier and more energetic on bright and sunny days and many experience a decline in mood and energy during the dark winter season. Brain serotonin is involved in the regulation of physiologic functions, such as mating, feeding, energy balance, and sleep. Although these behaviors and serotonin-related conditions show a clear seasonal pattern in humans, the molecular background of seasonal changes in serotonin function is entirely unknown. The serotonin transporter is a key element in regulating intensity and spread of the serotonin signal. Objectives To detect seasonal variations in serotonin transporter Binding in the living human brain and to detect correlations between serotonin transporter Binding and duration of daily sunshine. Design Regional serotonin transporter Binding Potential values, an index of serotonin transporter density, were assessed from December 1, 1999, to December 9, 2003, in a consecutive sample of healthy volunteers. Binding Potential values were related to meteorologic data. Setting Tertiary care psychiatric hospital. Participants Volunteer sample of 88 drug-naive healthy individuals. Intervention Carbon 11–labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile positron emission tomography. Main Outcome Measure Regional serotonin transporter Binding Potential values. Results Serotonin transporter Binding Potential values were significantly higher in all investigated brain regions in individuals investigated in the fall and winter compared with those investigated in the spring and summer ( P = .01 to .001). Moreover, Binding Potential values showed negative correlations with average duration of daily sunshine in all brain regions (ρ = −0.21 to −0.39; P = .05 to Conclusions Serotonin transporter Binding Potential values vary throughout the year with the seasons. Since higher serotonin transporter density is associated with lower synaptic serotonin levels, regulation of serotonin transporter density by season is a previously undescribed physiologic mechanism that has the Potential to explain seasonal changes in normal and pathologic behaviors.
-
elevated putamen d 2 receptor Binding Potential in major depression with motor retardation an 11 c raclopride positron emission tomography study
American Journal of Psychiatry, 2006Co-Authors: Jeffrey H. Meyer, Alan A Wilson, Heather E Mcneely, Sandra Sagrati, Anahita Boovariwala, Krystle Martin, Paul N L G Verhoeff, Sylvain HouleAbstract:Objective: Several antidepressants raise striatal dopamine, but the role of striatal dopamine during major depressive episodes is unclear. Striatal [ 11 C]raclopride Binding Potential measured with positron emission tomography is an index of D 2 type receptors and is sensitive to extracellular dopamine levels (higher D 2 Binding Potential occurs when dopamine is lower). It was hypothesized that putamen D 2 Binding Potential would be higher during major depressive episodes featuring motor retardation. Method: Drug-free, nonsmoking subjects experiencing a major depressive episode (N=21) underwent [ 11 C]raclopride PET imaging as did 21 healthy age-matched comparison subjects. Motor retardation was measured with the finger tapping test. Results: The depressed subjects exhibiting motor retardation had significantly higher D 2 Binding Potential in both the left and right putamen than did healthy subjects, and putamen D 2 Binding Potential correlated significantly with motor speed in the depressed subjects. Con...
-
brain serotonin transporter Binding Potential measured with carbon 11 labeled dasb positron emission tomography effects of major depressive episodes and severity of dysfunctional attitudes
Archives of General Psychiatry, 2004Co-Authors: Jeffrey H. Meyer, Sylvain Houle, Sandra Sagrati, Anna Carella, Doug Hussey, Nathalie Ginovart, Verdell S Goulding, James L Kennedy, Alan A WilsonAbstract:Background Although brain serotonin transporter (5-HTT) density has been investigated in subjects with a history of major depressive episodes (MDE), there has never been an investigation of brain 5-HTT during a current MDE. Brain 5-HTT Binding Potential (BP) may have an important role during MDE due to major depressive disorder, because the 5-HTT regulates extracellular 5-HT. The BP is an index of receptor density. Carbon 11–labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB) positron emission tomography (PET) is the first brain imaging technique that can measure the 5-HTT BP in cortical and subcortical brain regions in vivo. The purposes of this study were to investigate 5-HTT BP during MDE and to determine the relationship between 5-HTT BP and negativistic dysfunctional attitudes during MDE. Dysfunctional attitudes are negatively biased assumptions and beliefs regarding oneself, the world, and the future. Our recent publication of increased serotonin 2 BP in MDE with severely negativistic dysfunctional attitudes suggests that this subgroup of MDE subjects has very low levels of extracellular serotonin. Methods Regional 5-HTT BP was measured in 20 nonsmoking medication-free (≥3 months) depressed subjects and 20 age-matched nonsmoking, medication-free, healthy subjects using [ 11 C]DASB PET. Dysfunctional attitudes were measured using the Dysfunctional Attitudes Scale. Results No difference in regional 5-HTT BP was found between MDE and healthy subjects; however, the subgroup of MDE subjects with highly negativistic dysfunctional attitudes had significantly higher 5-HTT BP compared with healthy subjects in brain regions mainly sampling serotonergic nerve terminals (prefrontal cortex, anterior cingulate, thalamus, bilateral caudate, and bilateral putamen; average, 21% greater; F 1,26 , 5.6-12.2 [ P values, .03-.002]). In the MDE subjects, increased 5-HTT BP was strongly associated with more negativistic dysfunctional attitudes in brain regions primarily sampling serotonergic nerve terminals (prefrontal cortex, anterior cingulate, thalamus, caudate, and putamen; r = 0.64-0.74 [ P values, .003 to Conclusions Serotonin transporters play an important role during depression. The magnitude of regional 5-HTT BP can provide a vulnerability to low levels of extracellular serotonin and symptoms of extremely negativistic dysfunctional attitudes.
-
serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses an 11c dasb positron emission tomography study
American Journal of Psychiatry, 2004Co-Authors: Jeffrey H. Meyer, Alan A Wilson, Sandra Sagrati, Anna Carella, Doug Hussey, Nathalie Ginovart, William Z Potter, Edgar P Spencer, Andy Cheok, Sylvain HouleAbstract:OBJECTIVE: Minimum therapeutic doses of paroxetine and citalopram produce 80% occupancy for the serotonin (5-HT) transporter (5-HTT). The authors used [11C]DASB positron emission tomography to measure occupancies of three other selective serotonin reuptake inhibitors (SSRIs) at minimum therapeutic doses. The relationship between dose and occupancy was also investigated. METHOD: Striatal 5-HTT Binding Potential was measured in 77 subjects before and after 4 weeks of medication administration. Binding Potential is proportional to the density of receptors not blocked by medication. Subjects received citalopram, fluoxetine, sertraline, paroxetine, or extended-release venlafaxine. Healthy subjects received subtherapeutic doses; subjects with mood and anxiety disorders received therapeutic doses. Percent reduction in 5-HTT Binding Potential for each medication and dose was calculated. To obtain test-retest data, Binding Potential was measured before and after 4 weeks in six additional healthy subjects. RESULTS:...
-
occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression a 11 c dasb pet imaging study
American Journal of Psychiatry, 2001Co-Authors: Jeffrey H. Meyer, Alan A Wilson, Doug Hussey, Nathalie Ginovart, Verdell S Goulding, Karen Hood, Sylvain HouleAbstract:OBJECTIVE: Selective serotonin reuptake inhibitors are commonly used to treat major depression; however, the percentage of serotonin (5-HT) transporter (5-HTT) sites occupied during clinical dosing is unknown. This study measured the proportion of 5-HTT sites blocked during paroxetine and citalopram treatment of depression and assessed the relationship between serum paroxetine levels and the proportion of 5-HTT sites blocked. METHOD: Twelve medication-free depressed patients completed a 6-week trial of either paroxetine (N=8) or citalopram (N=4). Striatal 5-HTT Binding Potential was measured with [11C]DASB and positron emission tomography, before and after 4 weeks of treatment. The Binding Potential is proportional to receptor density. Striatal 5-HTT Binding Potential was measured twice in six healthy subjects and once in 11 healthy subjects. RESULTS: A significant decrease in striatal 5-HTT Binding Potential was found after either treatment, compared to changes found over a 4-week period in healthy subje...
John J Mann - One of the best experts on this subject based on the ideXlab platform.
-
estimation of the Binding Potential bpnd without a reference region or blood samples for brain pet studies
NeuroImage, 2017Co-Authors: Martin Schain, John J Mann, Francesca Zanderigo, Todd R OgdenAbstract:Abstract Binding Potential ( BP ND ) is a commonly used PET outcome measure because it can be estimated without blood sampling if a brain reference region (RR) devoid of the target of interest exists. For many radioligands, however, no RR exists, and the total distribution volume ( V T ), whose estimation requires arterial blood sampling, is normally considered as the outcome measure. Here, we present a method that allows calculation of BP ND without requiring either blood samples or a RR. The method extends our previous algorithm for estimating non-displaceable distribution volumes ( V ND ) without using a RR. Here we show that if a template input function, with arbitrary amplitude but a shape similar to the actual arterial input function, is used in the algorithm, estimation of V T and V ND are both proportionally biased, and thus this bias cancels out in the estimation of BP ND . The method is evaluated using simulated data, human data acquired with the serotonin 1A receptor radioligand [ 11 C]WAY-100635, and blocking data acquired in baboons using the serotonin 1A receptor radioligand [ 11 C]CUMI-101. We evaluated two versions of template input functions: an arbitrarily downscaled version of the actual arterial input function, and an unscaled population-based input function. In addition, we evaluated how shape modifications of the template input function impact the estimates of BP ND . With the downscaled input function, BP ND values close to the gold standard were obtained. When the unscaled population-based based input function was used, greater variability was observed but no discernable bias was introduced. When the input function shape was modified, a systematic but small bias in BP ND was introduced. We conclude that, provided the shape of the arterial input function is adequately described, determination of its amplitude is not necessary for estimation of BP ND .
-
higher 5 ht1a receptor Binding Potential during a major depressive episode predicts poor treatment response preliminary data from a naturalistic study
Neuropsychopharmacology, 2006Co-Authors: Ramin V Parsey, Maria A Oquendo, Yungyu Huang, Todd R Ogden, Doreen M Olvet, John J MannAbstract:Serotonin 1A (5-HT1A) Binding Potential (BP) as assessed by positron emission tomography (PET) is higher in major depressive disorder (MDD) in association with the higher expressing GG genotype of the 5-HT1A C-1019G polymorphism. We hypothesize that higher 5HT1A BP and the GG genotype predict remission failure on antidepressant treatment. We determined 5-HT1A BP by PET and 5-HT1A C-1019G genotype in 43 controls and 22 medication-free MDD subjects. MDD was treated naturalistically and remission was defined as 450% reduction and a score of p10 on the 24 item Hamilton Scale 1 year after initiation of treatment after scanning. Despite equivalent treatment, nonremitters have higher pretreatment cortical BP and the GG genotype is over-represented compared with remitters. Higher 5-HT1A BP, perhaps due to greater gene expression, may predict antidepressant medication nonremission. The findings should be tested in a controlled prospective treatment study. Neuropsychopharmacology (2006) 31, 1745–1749. doi:10.1038/sj.npp.1300992; published online 4 January 2006
-
effects of sex age and aggressive traits in man on brain serotonin 5 ht1a receptor Binding Potential measured by pet using c 11 way 100635
Brain Research, 2002Co-Authors: Ramin V Parsey, Maria A Oquendo, Norman R Simpson, Todd R Ogden, Ronald L Van Heertum, Victoria Arango, John J MannAbstract:Serotonin (5-HT) 1A receptors have been implicated in a variety of conditions including, depression, suicidal behavior, and aggression. Post-mortem brain studies and in vivo imaging studies report a variety of age and sex effects on brain 5-HT1A Binding. Behavioral data from 5-HT1A specific pharmacological challenges suggest a role for 5-HT1A receptors in aggression. The goal of the present study was to determine age, sex, and severity of life-time aggression effects on 5-HT1A Binding Potential (BP) in vivo using positron emission tomography (PET) and the high affinity 5-HT1A antagonist, [carbonyl-C-11]WAY-100635 in 12 healthy females (ages 41.0±15.7 years) and 13 healthy males (ages 39.6±15.5 years). Regions of interest included the dorsal raphe, anterior cingulate cortex, cingulate body, hippocampus, amygdala, medial prefrontal cortex (PFC), and orbital PFC. No significant correlation between age and BP was detected in any brain region. MANOVA of the first three principle components demonstrated a significantly higher BP in females compared with males (P=0.0127). Post-hoc tests confirmed sex differences (P<0.05) in the following regions: dorsal raphe, amygdala, anterior cingulate, cingulate body, medial PFC, and orbital PFC. The cerebellar volume of distribution was also significantly higher in females. There is a significant negative correlation between Binding in several regions and lifetime aggression. We have replicated our post-mortem finding of higher 5-HT1A Binding in females compared to males. We did not detect an age dependent decrease in Binding in males or females. Lower 5-HT1A Binding in more aggressive individuals is consistent with pharmacological challenge studies. Future studies should determine whether the Binding is a state or trait effect.
Kuniaki Ogasawara - One of the best experts on this subject based on the ideXlab platform.
-
crossed cerebellar tracer uptake on acute stage 123i iomazenil spect imaging predicts 3 month functional outcome in patients with nonfatal hypertensive putaminal or thalamic hemorrhage
Clinical Nuclear Medicine, 2018Co-Authors: Daigo Kojima, Nobukazu Komoribayashi, Shinichi Omama, Kohki Oikawa, Yoshitaka Kubo, Masakazu Kobayashi, Shunrou Fujiwara, Kazunori Terasaki, Kuniaki OgasawaraAbstract:PurposeWhereas SPECT images obtained 180 minutes after administration of 123I-iomazenil (IMZ) (late images) are proportional to the distribution of central benzodiazepine receptor–Binding Potential, SPECT images obtained within 30 minutes after 123I-IMZ administration (early images) correlate with r
-
chronological changes in brain blood flow and central benzodiazepine receptor Binding Potential in a patient with symptomatic epilepsy after surgery for aneurysmal subarachnoid hemorrhage 123i iomazenil single photon emission computed tomography stud
Case Reports in Neurology, 2017Co-Authors: Toshiyuki Murakami, Hidehiko Endo, Hiroshi Kashimura, Hiroki Kuroda, Kuniaki OgasawaraAbstract:Early 123I-iomazenil single-photon emission computed tomography (SPECT) images are correlated with blood flow in the brain, and late images are correlated with cortical benzodiazepine receptor Binding Potential. Reduced metabolism in the contralateral cerebral hemisphere is indicated by crossed cerebellar hypoperfusion (CCH). We present the case of a 63-year-old man who developed symptomatic epilepsy 13 days after surgery for an aneurysmal subarachnoid hemorrhage. Early images on 123I-iomazenil SPECT 2 days after seizure onset revealed CCH and hyperperfusion in the affected cerebral hemisphere where benzodiazepine receptor Binding Potential was reduced in late images on 123I-iomazenil SPECT. These abnormal findings resolved on repeated 123I-iomazenil SPECT 1 month after seizure onset. The case we present here is consistent with the idea that the central benzodiazepine receptor system in the human brain undergoes changes that are related to seizures due to epilepsy.
-
accuracy of central benzodiazepine receptor Binding Potential cerebral blood flow spect imaging for detecting misery perfusion in patients with unilateral major cerebral artery occlusive diseases comparison with cerebrovascular reactivity to acetazolamide and cerebral blood flow spect imaging
Clinical Nuclear Medicine, 2012Co-Authors: Hiroki Kuroda, Taro Suzuki, Kohei Chida, Kuniaki Ogasawara, Masakazu Kobayashi, Shunrou Fujiwara, Kenji Yoshida, Kenta Aso, K Terasaki, Yoshitaka KuboAbstract:Purpose The aim of the present study was to determine whether central benzodiazepine receptor Binding Potential (BRBP)/cerebral blood flow (CBF) or a combination of CBF and cerebrovascular reactivity (CVR) to acetazolamide on single-photon emission computed tomography (SPECT) more accurately detects misery perfusion, indicating elevation of absolute value of oxygen extraction fraction (OEF) on positron emission tomography (PET), in patients with unilateral major cerebral artery occlusive diseases. Methods In 84 patients, OEF, CBF, CVR to acetazolamide, and BRBP were assessed using ¹⁵O-PET and N-isopropyl-p-[¹²³I]-iodoamphetamine and [¹²³I]-iomazenil SPECT, respectively. A region of interest was automatically placed in the middle cerebral artery territory using a 3-dimensional stereotactic region of interest template. Results Sensitivity, specificity, and positive and negative predictive values for the affected side-to-contralateral side asymmetry on SPECT-BRBP/CBF to detect the abnormally elevated PET-OEF in the affected hemisphere were 100%, 86.4%, 66.7%, and 100%, respectively. Area under the receiver operating characteristic curve in detecting the abnormally elevated PET-OEF in the affected hemisphere did not differ between analysis of the combination of SPECT-CBF and SPECT-CVR in the affected hemisphere (0.89; 95% confidence interval, 0.80-0.94) and that of the affected side-to-contralateral side asymmetry on SPECT-BRBP/CBF (0.93; 95% confidence interval, 0.86-0.97). The combination of the 3 detected abnormally elevated PET-OEF with 97.0% specificity and 90.0% positive predictive value. Conclusions The accuracy of central BRBP/CBF asymmetry on SPECT is equivalent to that of the combination of CBF and CVR to acetazolamide on SPECT for detecting misery perfusion in patients with unilateral major cerebral artery occlusive disease.
-
combination of preoperative cerebral blood flow and 123i iomazenil spect imaging predicts postoperative cognitive improvement in patients undergoing uncomplicated endarterectomy for unilateral carotid stenosis
Clinical Nuclear Medicine, 2012Co-Authors: Takeshi Yamashita, Taro Suzuki, Yoshitaka Kubo, Kohei Chida, Kuniaki Ogasawara, Hiroki Kuroda, Masakazu Kobayashi, Kenji Yoshida, Akira OgawaAbstract:Purpose:The purpose of the present study was to determine whether preoperative cerebral blood flow (CBF) or cortical central benzodiazepine receptor Binding Potential as measured by brain perfusion or 123I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) imaging, respectively, can
-
preoperative central benzodiazepine receptor Binding Potential and cerebral blood flow images on spect predict development of new cerebral ischemic events and cerebral hyperperfusion after carotid endarterectomy
The Journal of Nuclear Medicine, 2011Co-Authors: Yuiko Sato, Taro Suzuki, Kohei Chida, Kuniaki Ogasawara, Hiroki Kuroda, Masakazu Kobayashi, Shunrou Fujiwara, Kenji Yoshida, Kenta Aso, Kazunori TerasakiAbstract:Risk factors for cerebrovascular complications developing during or after carotid endarterectomy (CEA) include preoperative impairments in cerebral hemodynamics, as detected by the demonstration of decreased cerebrovascular reactivity (CVR) to acetazolamide on brain perfusion SPECT. Central benzodiazepine receptor Binding Potential (CBRBP) and cerebral blood flow (CBF) images on SPECT provide high sensitivity and high specificity for detecting misery perfusion in patients with chronic unilateral major cerebral artery occlusive disease. The aim of the present study was to determine whether preoperative CBRBP/CBF images on SPECT could identify patients at risk for new cerebral ischemic events, including neurologic deficits and cerebral ischemic lesions on diffusion-weighted MRI, or cerebral hyperperfusion after CEA and to compare the predictive accuracy of CBRBP/CBF with that of CVR to acetazolamide on SPECT. Methods: CBF, CVR, and CBRBP were assessed using N-isopropyl-p-123I-iodoamphetamine (123I-IMP) and 123I-iomazenil SPECT before CEA in 112 patients with unilateral internal carotid artery stenosis (≥70%). CBF measurement using 123I-IMP SPECT was also performed immediately and 3 d after CEA. A region of interest was automatically placed in the middle cerebral artery territory in both cerebral hemispheres using a 3-dimensional stereotactic region-of-interest template. Diffusion-weighted MRI was performed within 3 d before and 24 h after surgery. Results: A preoperative increase in the affected side–to–contralateral side asymmetry on CBRBP/CBF value was the only significant independent predictor of postoperative new cerebral ischemic events (95% confidence intervals [CI], 1.145–1.608; P = 0.0004) or post-CEA hyperperfusion (95% CI, 1.244–2.252; P = 0.0007). There was no difference in the ability to predict post-CEA hyperperfusion when comparing the area under the receiver-operating-characteristic curve of the affected side–to–contralateral side asymmetry on CBRBP/CBF and that of the CVR in the affected hemisphere. However, the former value (0.924; 95% CI, 0.854–0.972) was significantly greater than the latter value (0.782; 95% CI, 0.697–0.852) for the prediction of new postoperative cerebral ischemic events (P
Hiroto Kuwabara - One of the best experts on this subject based on the ideXlab platform.
-
Metabotropic glutamate receptor 5 tracer [18F]-FPEB displays increased Binding Potential in postcentral gyrus and cerebellum of male individuals with autism: a pilot PET study.
Cerebellum & ataxias, 2018Co-Authors: S. Hossein Fatemi, Dean F. Wong, James R. Brasic, Hiroto Kuwabara, Anil Mathur, Timothy D. Folsom, Suma Jacob, George M. Realmuto, José V. Pardo, Susanne S. LeeAbstract:Autism is a neurodevelopmental disorder that is first manifested during early childhood. Postmortem experiments have identified significantly elevated expression of metabotropic glutamate receptor 5 (mGluR5) in cerebellar vermis and prefrontal cortex of individuals with autism. In the current study we employed the mGluR5 tracer [18F]-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([18F]-FPEB) to quantify mGluR5 Binding in vivo in adults with autism vs. healthy controls using positron emission tomography (PET). We identified significantly higher [18F]-FPEB Binding Potential in the postcentral gyrus and cerebellum of individuals with autism. There was a significant negative correlation between age and [18F]-FPEB Binding Potential in the cerebellum but not in the postcentral gyrus. In the precuneus, [18F]-FPEB Binding Potential correlated positively with the lethargy subscale score for the Aberrant Behavioral Checklist (ABC). In cerebellum, there were significant negative correlations between [18F]-FPEB Binding Potential and ABC total score, ABC hyperactivity subscale score, and the ABC inappropriate speech subscale score. These novel findings demonstrate for the first time that mGluR5 Binding is altered in critical brain areas of subjects with autism, suggesting abnormal glutamate signaling in these regions. Finally, the correlations between altered [18F]-FPEB Binding Potential in the cerebellum and precuneus suggest that some autistic symptoms may be influenced by abnormal glutamate signaling.
-
metabotropic glutamate receptor 5 tracer 18f fpeb displays increased Binding Potential in postcentral gyrus and cerebellum of male individuals with autism a pilot pet study
Cerebellum & Ataxias, 2018Co-Authors: Hossein S Fatemi, Dean F. Wong, James R. Brasic, Hiroto Kuwabara, Anil Mathur, Timothy D. Folsom, Suma Jacob, George M. Realmuto, José V. PardoAbstract:Autism is a neurodevelopmental disorder that is first manifested during early childhood. Postmortem experiments have identified significantly elevated expression of metabotropic glutamate receptor 5 (mGluR5) in cerebellar vermis and prefrontal cortex of individuals with autism. In the current study we employed the mGluR5 tracer [18F]-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([18F]-FPEB) to quantify mGluR5 Binding in vivo in adults with autism vs. healthy controls using positron emission tomography (PET). We identified significantly higher [18F]-FPEB Binding Potential in the postcentral gyrus and cerebellum of individuals with autism. There was a significant negative correlation between age and [18F]-FPEB Binding Potential in the cerebellum but not in the postcentral gyrus. In the precuneus, [18F]-FPEB Binding Potential correlated positively with the lethargy subscale score for the Aberrant Behavioral Checklist (ABC). In cerebellum, there were significant negative correlations between [18F]-FPEB Binding Potential and ABC total score, ABC hyperactivity subscale score, and the ABC inappropriate speech subscale score. These novel findings demonstrate for the first time that mGluR5 Binding is altered in critical brain areas of subjects with autism, suggesting abnormal glutamate signaling in these regions. Finally, the correlations between altered [18F]-FPEB Binding Potential in the cerebellum and precuneus suggest that some autistic symptoms may be influenced by abnormal glutamate signaling.
-
18f fpeb a pet radiopharmaceutical for quantifying metabotropic glutamate 5 receptors a first in human study of radiochemical safety biokinetics and radiation dosimetry
The Journal of Nuclear Medicine, 2013Co-Authors: Dean F Wong, James R. Brasic, Hiroto Kuwabara, Robert F Dannals, Rikki N Waterhouse, Jongho Kim, Wichana Chamroonrat, Michael Stabins, Daniel P Holt, Terence G HamillAbstract:Identification of safe and valid PET radioligands for metabotropic glutamate receptor, type 5 (mGluR5), is essential to measure changes in brain mGluR5 in neuropsychiatric disorders, to confirm central mGluR5 occupancy of drug candidates, and to guide dose selection for obtaining an optimum therapeutic window. Here we present the results of a first-inhuman study assessing the safety and effectiveness of a novel PET radiopharmaceutical, 18 F-3-fluoro-5-[(pyridin-3-yl)ethynyl] benzonitrile (18F-FPEB), for quantifying regional brain concentrations of mGluR5. Methods: Quantification of whole-body biokinetics was conducted in 6 healthy adults (3 men and 3 women). The radiation safety profile was estimated with OLINDA/EXM software. Subsequently, pairs of dynamic brain scans were obtained for 11 healthy men to identify optimal methods for derivation of regional distribution volume and Binding Potential and to determine the repeatability of measurement. Results: The whole-body effective radiation dose was approximately 17 mSv/MBq (62 mrem/mCi), with the gallbladder receiving the highest dose of 190 mSv/MBq. In brain studies, time–activity curves showed high accumulation in the insula/caudate nucleus, moderate uptake in the thalamus, and the lowest concentration in the cerebellum/pons. The plasma reference graphical analysis method appeared optimal for 18F-FPEB; it showed acceptable test–retest variability of nondisplaceable Binding Potential (,10%) and identified the highest nondisplaceable Binding Potential values (from ; 0.5 in the globus pallidus to ;3.5 in the insula) for target regions. Safety assessments revealed no clinically meaningful changes in vital signs, electrocardiogram, or laboratory values. Conclusion: 18 F-FPEB is safe and well tolerated, and its regional cerebral distribution is consistent with previous reports in the literature for metabotropic glutamate receptors. The repeatability of
-
influence of oprm1 asn40asp variant a118g on 11c carfentanil Binding Potential preliminary findings in human subjects
The International Journal of Neuropsychopharmacology, 2013Co-Authors: Elise M Weerts, Hiroto Kuwabara, Mary E Mccaul, Xiaoju Yang, Xiaoqiang Xu, Robert F Dannals, James J Frost, Dean F Wong, Gary S WandAbstract:The Asn40Asp variant (A118G) of the µ opioid receptor ( OPRM1 ) gene is thought to contribute to the development and treatment of alcohol dependence. Employing positron emission tomography (PET), we first examined whether the single nucleotide polymorphism (SNP) modifies Binding Potential (BPND) of the µ-selective ligand [11C]carfentanil in healthy control (Con) and 5-d abstinent alcohol-dependent (AD) subjects (unblocked basal scan). Second, we examined whether the allelic variants were associated with differences in OPRM1 occupancy by naltrexone (50 mg) in AD subjects. Con and AD carriers of the G allele (AG) had lower global BPND at the basal scan than subjects homozygous for the A allele (AA). In AD subjects, naltrexone occupancy was slightly higher in AG subjects (98.9%) compared to AA subjects (93.1%), but this was not significant. We are the first to demonstrate using PET in healthy normal and AD subjects that the A118G SNP alters OPRM1 availability.