秋田県脳血管研究センター

印刷発表　放射線医学研究部

放射線医学研究部　DEPARTMENT OF RADIOLOGY AND NUCLEAR MEDICINE

01a・411・01
Evaluation of Novel PET Ligands (+)N-[11C]Methyl-3-piperidyl Benzilate ([11C](+)3-MPB) and Its Stereoisomer [11C](-)3-MPB for Muscarinic Cholinergic Receptors in the Conscious Monkey Brain: A PET Study in Comparison with [11C]4-MPB

Tsukada H， Takahashi K， Miura S， Nishiyama S， Kakiuchi T， Ohba H， Sato K， Hatazawa J， Okudera T
SYNAPSE　39：182縲鰀192，2001

The novel muscarinic cholinergic ligands, (+)N-[11C]methyl-3-piperidyl benzilate ([11C](+)3-MPB) and its stereoisomer [11C](-)3-MPB were evaluated in comparison with [11C]4-MPB in the brains of conscious monkeys (Macaca mulatta) using high-resolution positron emission tomography (PET). The regional distribution patterns of [11C](+)3-MPB and [11C]4-MPB at 60-91 min post-injection were almost identical; highest in the striatum and occipital cortex, intermediate in the temporal and frontal cortices, cingulate gyrus, hippocampus, and thalamus, lower in the pons, and lowest in the cerebellum. The uptake of [11C](+)3-MPB in all regions was higher, and the dynamic range of regional uptake differences of [11C](+)3-MPB was better than those of [11C]4-MPB. The levels of [11C](-)3-MPB were much lower in all regions of the brain than [11C](+)3-MPB and [11C]4-MPB. Administration of scopolamine, a muscarinic cholinergic antagonist, at a dose of 50 µg/kg reduced the radio-activity of [11C](+)3-MPB and [11C]4-MPB in all regions except the cerebellum. Time-activity curves of [11C](+)3-MPB peaked in all regions, while those of [11C]4-MPB showed gradual increases with time in all regions except the thalamus, pons and cerebellum. Two graphical analyses (Logan plot and Patlak plot) with plasma radioactivity as an input function into the brain were applied to evaluate receptor binding in vivo. [11C](+)3-MPB showed linear regression curves on Logan plot analysis and nonlinear curves on Patlak plot in all regions, suggesting that [11C](+)3-MPB bound reversibly to the muscarinic receptors. The in vivo binding parameters as well as uptake at 60-91 min postinjection of [11C](+)3-MPB were consistent with muscarinic receptor density in the brain as reported in vitro. 

01a・411・02
Evaluation of PET Ligands (+)N-[11C]Ethyl-3-piperidyl Benzilate and (+)N-[11C]Propyl-3-piperidyl Benzilate for Muscarinic Cholinergic Receptors: A PET Study with Microdialysis in Comparison with (+)N-[11C]Methyl-3-piperidyl Benzilate in the Conscious Monkey Brain

Nishiyama S， Tsukada H， Sato K， Kakiuchi T， Ohba H， Harada N， Takahashi K
SYNAPSE　40：159縲鰀169，2001

We developed PET ligands (+)N-[11C]ethyl-3-piperidyl benzilate ([11C](+)3-EPB) and (+)N-[11C]propyl-3-piperidyl benzilate ([11C](+)3-PPB) for cerebral muscarinic cholinergic receptors. The distribution and kinetics of the novel ligands were evaluated for comparison with the previously reported ligand (+)N-[11C]methyl-3-piperidyl benzilate ([11C](+)3-MPB) in the monkey brain (Macaca mulatta) in the conscious state using high-resolution positron emission tomography (PET). At 60-91 min post injection, regional distribution patterns of these three ligands were almost identical, and were consistent with the muscarinic receptor density in the brain as previously reported in vitro. However, the time-activity curves of [11C](+)3-EPB and [11C](+)3-PPB showed earlier peak times of radioactivity and faster clearance rate than [11C](+)3-MPB in cortical regions rich in the receptors. Kinetic analysis using the three-compartment model with time-activity curves of radioactivity in metabolite-corrected arterial plasma as input functions revealed that labeling with longer [11C]alkyl chain length induced lower binding potential (BP = k3/k4), consistent with the rank order of affinity of these ligands obtained by an in vitro assay using rat brain slices and [3H]QNB. The cholinesterase inhibitor Aricept administered at doses of 50 and 250 µg/kg increased acetylcholine level in extracellular fluid of the frontal cortex, and the binding of [11C](+)3-PPB with the lowest affinity to the receptors was displaced by the endogenous acetylcholine induced by cholinesterase inhibition, while [11C](+)3-MPB with the highest affinity was not significantly affected. Taken together, these observations indicated that the increase in [11C]alkyl chain length could alter the kinetic properties of conventional receptor ligands for PET by reducing the affinity to receptors, which might make it possible to assess the interaction between endogenous neurotransmitters and ligand-receptor binding in vivo as measured by PET.

01a・411・03
Age Differences in Muscarinic Cholinergic Receptors Assayed with (+)N-[11C]Methyl-3-piperidyl Benzilate in the Brains of Conscious Monkeys

Tsukada H， Kakiuchi T， Nishiyama S， Ohba H， Sato K， Harada N， Takahashi K
SYNAPSE　41：248縲鰀257，2001 　 　

Age-related changes in muscarinic cholinergic receptors were evaluated with the novel ligand (+)N-[11C]methyl-3-piperidyl benzilate ((+)3-MPB) in the living brains of young (5.9±1.8 years old) and aged (19.0±3.3 years old) monkeys (Macaca mulatta) in the conscious state using high-resolution positron emission tomography (PET). For quantitative analysis of receptor binding in vivo, metabolite-corrected arterial plasma radioactivity curves were obtained as an input function into the brain, and kinetic analyses using the three-compartment model and graphical Logan plot analysis were applied. Kinetic analyses of [11C](+)3-MPB indicated a regionally specific decrease in the receptor binding in vivo determined as binding potential (BP) = k3/k4 in aged animals compared with young animals. Thus, the frontal and temporal cortices as well as the striatum showed age-related reduction of muscarinic cholinergic receptors in vivo, reflecting the reduced receptor density (Bmax) determined by Scatchard plot analysis in vivo. In the hippocampus, although BP of [11C](+)3-MPB indicated no significant age-related changes, it showed an inverse correlation with individual cortisol levels in plasma. When the graphical Logan plot analysis was applied, all regions assayed showed significant age-related decrease of [11C](+)3-MPB binding. These results demonstrated the usefulness of kinetic three compartment model analysis of [11C](+)3-MPB with metabolite-corrected arterial plasma input as an indicator for the aging process of the cortical muscarinic cholinergic receptors in vivo as measured by PET.

01a・423・01
Error Analysis for Quantification of [11C]FLB 457 Binding to Extrastriatal D2 Dopamine Receptors in the Human Brain

Ito H， Sudo Y， Suhara T， Okubo Y， Halldin C， Farde L
NeuroImage　13：531縲鰀539，2001 　

To estimate receptor binding of ligand by positron emission tomography (PET) without an arterial input function, several quantitative approaches based on the use of a reference region have been proposed. We compared three approaches for quantifying extrastriatal D2 dopamine receptors using [11C]FLB 457. The PET measurements were performed on seven healthy men. Binding potential (BP) of [11C]FLB 457 was calculated by the reference tissue model method, transient equilibrium method, and late time method. The reference tissue model describes the time-activity curve in a brain region in terms of that in the reference region, assuming that the level of nondisplaceable radioligand binding in both regions are same. The transient equilibrium theoretically occurs when the derivative for specific binding is zero. With the late time method, BP is calculated by integrating a late part of the time-activity curve. BP values obtained by all methods were in good agreement with those obtained by the kinetic approach, and the highest coefficient of correlation was observed in the reference tissue model method. In the simulation study, the error of BP calculated by the reference tissue model method was smallest. Moreover, the effect of the difference in the influx rate constant K1 between the brain and reference regions on BP was nearly avoided as theoretically predicted. We concluded that the reference tissue model method is most suitable for calculating BP of extrastriatal D2 dopamine receptors with [11C]FLB 457.

01a・423・02
Arterial Fraction of Cerebral Blood Volume in Humans Measured by Positron Emission Tomography

Ito H， Kanno I， Iida H， Hatazawa J， Shimosegawa E， Tamura H， Okudera
T Ann Nucl Med　15：111縲鰀116，2001 　

In quantitative functional neuroimaging with positron emission tomography (PET) and magnetic resonance imaging (MRI), cerebral blood volume (CBV) and its three components, arterial, capillary and venous blood volumes are important factors. The arterial fraction for systemic circulation of the whole body has been reported to be 20-30%, but there is no report of this fraction in the brain. In the present study, we estimated the arterial fraction of CBV with PET in the living human brain. C15O and dynamic H215O PET studies were performed in each of seven healthy subjects to determine the CBV and arterial blood volume (Va), respectively. A two-compartment model (influx: K1, efflux: k2) that takes Va into account was applied to describe the regional time-activity curve of dynamic H215O PET. K1, k2 and Va were calculated by a non-linear least squares fitting procedure. The Va and CBV values were 0.011±0.004 ml/ml and 0.031±0.003 ml/ml (mean±SD), respectively, for cerebral cortices. The arterial fraction of CBV was 37%. Considering the limited first-pass extraction fraction of H215O, the true arterial fraction of CBV is estimated to be about 30%. The estimated arterial fraction of CBV was quite similar to that of the systemic circulation, whereas it was greater than that (16%) widely used for the measurement of the cerebral metabolic rate for oxygen (CMRO2) with PET. The venous plus capillary fraction of CBV was 63-70% which is an important factor for the measurement of CMRO2 with MRI.

01a・423・03
Changes in Human Regional Cerebral Blood Flow and Cerebral Blood Volume During Visual Stimulation Measured by Positron Emission Tomography

Ito H， Takahashi K， Hatazawa J， Kim S-G， Kanno I
J Cereb Blood Flow Metab　21：608縲鰀612，2001 　

The hemodynamic mechanism of increase in CBF during neural activation is not elucidated in humans. In the present study, changes in both regional CBF and cerebral blood volume (CBV) during visual stimulation in humans were investigated. CBF and CBV were measured by positron emission tomography using H215O and 11CO, respectively, at rest and during 2-Hz and 8-Hz photic flicker stimulation in each of 10 subjects. Changes in CBF in the primary visual cortex were 16±16% and 68±20% for the visual stimulation of 2 Hz and 8 Hz, respectively. The changes in CBV were 10±13% and 21±5% for 2-Hz and 8-Hz stimulation, respectively. Significant differences between changes in CBF and CBV were observed for visual stimulation of 8 Hz. The relation between CBF and CBV values during rest and visual stimulation was CBV=0.88CBF0.30. This indicates that when the increase in CBF during neural activation is great, that increase is caused primarily by the increase in vascular blood velocity rather than by the increase in CBV. This observation is consistent with reported findings obtained during hypercapnia.

01a・423・04 Reproducibility of [11C] FLB 457 Binding in Extrastriatal Regions

Sudo Y， Suhara T， Inoue M， Ito H， Suzuki K， Saijo T， Halldin C， Farde L
Nucl Med Commun　22：1215縲鰀1221，2001

01a・450・01
穿通枝領域のみに梗塞をきたした右中大脳動脈塞栓症と考えられる1例

A case of cerebral emobolism presented a lacunar infarction in the right internal capsule
岡根　久美子， 畑澤　順， 下瀬川　恵久， 伊藤　浩， 田村　元， 奥寺　利男， 黒川　富貴子， 佐藤　美佳
臨床放射線　46：447縲鰀450，2001

01a・450・02
＜脳卒中への初期対応　その急性期医療の最前線＞脳卒中に用いられる画像診断とその限界

Values and limitations of diagnostic imaging in stroke
畑澤　順
Modern Physician　21：942縲鰀946，2001

01a・450・03
＜特集：抗血小板薬と抗凝固薬をどう使い分けるか　血栓症と塞栓症予防への対応＞ 画像診断からみた血栓症と塞栓症

Diagnostic Imaging; Thrombotic Infarction vs Embolic Infarction
岡根　久美子， 奥寺　利男
臨床成人病　 31：883縲鰀888，2001

01a・450・04
＜特集：脳血管障害の臨床　最近のトピックス＞ 脳梗塞超急性期の画像診断

Clinical neuroimaging for acute cerebral infarction
伊藤　浩， 畑澤　順， 奥寺　利男
神経研究の進歩　 45：410縲鰀416，2001

01a・450・05
High-Intensity Facial Nerve Lesions on T2-Weighted Images in Chronic Persistent Facial Nerve Palsy

Kinoshita T， Ishii K， Okitsu T， Ogawa T， Okudera T
Neuroradiology　43：388縲鰀392，2001

01a・450・06
無症候性脳梗塞の画像診断と脳実質内血管構築

Neuroimaging of asymptomatic cerebral infarction: Correlation with cerebral intraparenchymal vasculature
奥寺　利男， 上村　和夫， 吉田　泰二
老年期痴呆研究会誌　12：81縲鰀91，2001

01a・450・07
＜特集：脳卒中　診断から治療までの最前線　画像診断・超音波診断＞ MRI-PerfusionおよびDiffusion MRIを中心に

MRI-perfusion and diffusion weighted imaging
奥寺　利男， 田村　元， 豊嶋　英仁， 畑澤　順
カレントテラピー　19：33縲鰀37，2001

01a・450・08
＜生涯教育シリーズ56　脳血管障害の臨床＞ 繹ｽ．脳血管障害の検査法：脳血管造影

Angiography
奥寺　利男
日本医師会雑誌　125（特別号）：S103縲鰀108，2001

01a・450・09
＜脳ドック　脳ドックで用いる検査＞ 脳ドックのMRI

MRI in brain doc
奥寺　利男， 田村　元， 豊嶋　英仁， 畑澤　順
Modern Physician　21：1357縲鰀1362，2001

01a・450・10
Facial Nerve Palsy: Evaluation by Contrastenhanced MR Imaging

Kinoshita T， Ishii K， Okitsu T， Okudera T， Ogawa T
Clin Radiol　56：926縲鰀932，2001

01a・450・11
＜無症候性脳血管障害＞ 39．MRI診断の進歩ーラクナ梗塞のMRI（血管周囲腔との鑑別を中心に）

MR imaging of lacunar infarction
奥寺　利男
医学のあゆみ　別冊（脳血管障害ー臨床と研究の最前線） 177縲鰀181，2001

01a・451・01
Chordoma with Postoperative Subcutaneous Implantation and Meningeal Dissemination: MRI

Kinoshita T， Okudera T， Shimosegawa E， Yoshida Y， Yasui N， Ogawa T， Hatazawa J
Neuroradiology　43：763縲鰀766，2001

01a・456・01
２．大脳白質

Cerebral white matter
高橋　昭喜， 田村　元
高橋昭喜編「脳MRI繹ｰ正常解剖」，秀潤社，東京，p. 32縲鰀48，2001

01a・456・02
内大脳静脈およびガレン静脈の解剖　放射線学的アプローチ　

Anatomy of internal cerebral vein and vein of Galen 　 Radiologic approach
奥寺　利男， 佐々木　真理， 鈴木　秀憲， 畑澤　順， 伊藤　寿介， Huang YP
顕微鏡下手術のための脳神経外科解剖　（協）　脳室系の立体解剖（第15回微小脳神経外科解剖セミナー講演集）　69縲鰀80，2001

01a・459・01
素潜りによる潜水障害

Decompression illness caused by breath-hold dives
合志　清隆， 玉木　英樹， 奥寺　利男， 加藤　貴彦， Wong RM， 眞野　喜洋
日本高気圧環境医学会雑誌　36：45縲鰀52，2001

01a・459・02
職業性素潜りダイバー（あま）の中枢神経障害

Central nervous system involvement in Japanese professional breath-hold (AMA) divers
合志　清隆， Wong RM， 奥寺　利男
日本職業・災害医学会会誌　 49：543縲鰀549，2001

01a・460・01
＜シンポジウム繹ｼ-6．脳血管障害診療の進歩＞ 脳血管障害における画像診断の進歩

Recent progress in diagnostic imaging of cerebrovascular diseases
畑澤　順
臨床神経学　40：1254縲鰀1256，2000

01a・460・02
＜特集＞ 脳血管障害の画像診断：最新の進歩

Nuclear medicine in cerebrovascular disease
畑澤　順
臨床画像　16：542縲鰀548，2000

01a・460・03
＜特集：超急性期脳虚血診断とIVR＞ SPECT画像の超急性期脳虚血診断における有用性

Brain SPECT in acute ischemic stroke
畑澤　順
全国循環器撮影研究会誌　13：76縲鰀79，2001

01a・460・04
＜脳血管疾患セミナー＞脳 血管疾患診断　 CT，MRI，SPECTを使いこなす

Diagnosis of cerebrovascular disease: Using CT, MRI, and SPECT efficiently
田村　元， 奥寺　利男
Medical Practice　18：573縲鰀578，2001

01a・460・05
＜特別講演2＞ くも膜下出血に伴う脳循環代謝障害

Cerebral blood flow and oxygen metabolism in patients with subarachnoid hemorrhage due to rupture of intracranial aneurysms
畑澤　順
脳血管攣縮　16（第16回　スパズム・シンポジウム講演集）：10縲鰀18，2001

01a・460・06
＜解説　測定法　第22回＞ 脳循環測定におけるMRIの進歩

Progress in MRI or measurement of brain perfusion
畑澤　順， 下瀬川　恵久， 豊嶋　英仁， 田村　元， 奥寺　利男
脳と循環　 6：169縲鰀172，2001

01a・460・07
PETによる慢性期脳主幹動脈閉塞性病変の脳循環代謝

Cerebral blood flow and metabolism in patients with ceerebral artery occlusion
鈴木　明， 木内　博之， 笹嶋　寿郎， 溝井　和夫， 畑澤　順
第23回　東北脳血管障害懇話会学術集会記録集　71縲鰀77，2001

01a・460・08
第2章　脳疾患　2．脳血管障害

Cerebrovascular disease
畑澤　順
クリニカルPET編集委員会編「臨床医のためのクリニカルPET」，先端医療技術研究所，東京， p.122縲鰀127，2001

01a・460・09
第2章　脳疾患　3．脳血管性痴呆

Vascular dementia
畑澤　順
クリニカルPET編集委員会編「臨床医のためのクリニカルPET」，先端医療技術研究所，東京， p.128縲鰀130，2001

01a・460・10
第2章　脳疾患　8B．脳疾患診断のピットフォール

Pitfall in diagnosis of neurological disease
畑澤　順
クリニカルPET編集委員会編「臨床医のためのクリニカルPET」，先端医療技術研究所，東京， p.166縲鰀167，2001

01a・469・01
[11C] Methionine Positron Emission Tomography for the Evaluation of Pancreatic Exocrine Function in Chronic Pancreatitis

Takasu A， Shimosegawa T， Shimosegawa E，Hatazawa J， Nagasaki Y， Kimura K， Fujita M， Toyota T
Pancreas　22：203縲鰀209，2001

Positron emission tomography (PET) can be used for the quantitative analysis of amino acid metabolism. The aim of this study was to investigate whether pancreatic exocrine function can be evaluated by [11C] methionine PET in chronic pancreatitis (CP) patients. Dynamic PET scan of the pancreas and liver was performed in eight healthy subjects and seven patients with CP after intravenous (i.v.) injection of [11C] methionine. Simultaneously, duodenal juice was collected with the background of continuous i.v. administration of secretin (125 ng/kg/h). The radioactivity ratio of the pancreas to that of the liver (PLR) was calculated by regions of interest (ROI) analysis. Amylase output and bicarbonate concentration were measured in the duodenal aspirates. The PLR of CP patients was significantly lower than that of healthy subjects at all time points after methionine injection. The PLRs at 4.5 minutes (PLR 4.5) after methionine injection were positively correlated with the amylase output, mean bicarbonate concentration, and volume of duodenal aspirates (R=0.74, 0.69, 0.46). It is concluded that [11C] methionine PET would be a noninvasive method for the evaluation of exocrine pancreatic function, which may represent total amino acids uptake of viable acinar cells in the pancreas.

01a・470・01
Activation CBF Varied by Perturbation of PaCO2 and PaO2 Level: PET Study

Kanno I， Shimosegawa E， Fujita H， Hatazawa J
Ischemic Blood Flow in the Brain (Eds: Fukuuchi Y, Tomita M, Koto A)，Springer-Verlag，Tokyo，p.221縲鰀225，2001 

01a・470・02
Frequency Dependence of Local Cerebral Blood Flow Induced by Somatosensory Hind Paw Stimulation in Rat Under Normo- and Hypercapnia

Bakalova R， Matsuura T， Kanno I
Jpn J Physiol　51：201縲鰀208，2001

We measured the field potential and the changes in the local cerebral blood flow (LCBF) response during somatosensory activation (evoked LCBF) in a-chloralose-anesthetized rats by laser-Doppler flowmetry under normocapnia (PaCO2=34.3±3.8 mmHg) and hypercapnia (PaCO2=70.1±9.8 mmHg). Somatosensory activation was induced by electrical stimulation (0.2, 1 and 5 Hz with 1.5 mA for 5 s) of the hind paw. The neuronal activity of the somatosensory area of the hind paw was linear to the stimulus frequency, and there was no significant difference in the neuronal activity between hypercapnia and normocapnia. The baseline level of LCBF under hypercapnia was about 72.2 % higher than that under normocapnia (p<0.01). The absolute response magnitude under hypercapnia was greater than that under normocapnia (p<0.05). The evoked LCBF under both conditions showed a frequency-dependent increase in the 0.2-5 Hz range, and the difference in the absolute response magnitude at the same stimulus frequency between normocapnia and hypercapnia became large with increasing stimulus frequency (p<0.05). On the other hand, after normalization to each baseline level, there was no significant difference in the response magnitude of the normalized evoked LCBF between normocapnia and hypercapnia, indicating that the normalized evoked LCBF reflects neuronal activity even when the baseline LCBF was changed by the PaCO2 level. The peak-time and termination-time of LCBF response curves with respect to the graded neuronal activity at 1 and 5 Hz stimulation increased significantly under hypercapnia compared with those under normocapnia (p<0.05), although the rise-time of 0.5 s was nearly constant. In conclusion, the results suggest a synergistic effect of the combined application of graded neuronal stimuli and hypercapnia on the LCBF response.

01a・473・01
＜特集：これだけは知っておきたい周産期の画像診断＞ 胎児中枢神経の正常発達と異常のMRI 　正常な脳発達のMRI

MRI in normal development
木下　良正， 奥寺　利男， 津留　英智， 横田　晃
臨床画像　17：1388縲鰀1395，2001

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