Jun Hatazawa

YNICL Journal 2018 Journal Article

Inflammatory projections after focal brain injury trigger neuronal network disruption: An 18F-DPA714 PET study in mice

• Sanae Hosomi
• Tadashi Watabe
• Yuki Mori
• Yoshihisa Koyama
• Soichiro Adachi
• Namiko Hoshi
• Mitsuo Ohnishi
• Hiroshi Ogura

Due to the heterogeneous pathology of traumatic brain injury (TBI), the exact mechanism of how initial brain damage leads to chronic inflammation and its effects on the whole brain remain unclear. Here, we report on long-term neuroinflammation, remote from the initial injury site, even after subsiding of the original inflammatory response, in a focal TBI mouse model. The use of translocator protein-positron emission tomography in conjunction with specialised magnetic resonance imaging modalities enabled us to visualize "previously undetected areas" of spreading inflammation after focal cortical injury. These clinically available modalities further revealed the pathophysiology of thalamic neuronal degeneration occurring as resident microglia sense damage to corticothalamic neuronal tracts and become activated. The resulting microglial activation plays a major role in prolonged inflammatory processes, which are deleterious to the thalamic network. In light of the association of this mechanism with neuronal tracts, we propose it can be termed "brain injury related inflammatory projection". Our findings on multiple spatial and temporal scales provide insight into the chronic inflammation present in neurodegenerative diseases after TBI.

YNIMG Journal 2016 Journal Article

Language-related cerebral oscillatory changes are influenced equally by genetic and environmental factors

• Toshihiko Araki
• Masayuki Hirata
• Takufumi Yanagisawa
• Hisato Sugata
• Mai Onishi
• Yoshiyuki Watanabe
• Soshiro Ogata
• Kazuo Hayakawa

Twin studies have suggested that there are genetic influences on inter-individual variation in terms of verbal abilities, and candidate genes have been identified by genome-wide association studies. However, the brain activities under genetic influence during linguistic processing remain unclear. In this study, we investigated neuromagnetic activities during a language task in a group of 28 monozygotic (MZ) and 12 dizygotic (DZ) adult twin pairs. We examined the spatio-temporal distribution of the event-related desynchronizations (ERDs) in the low gamma band (25–50Hz) using beamformer analyses and time–frequency analyses. Heritability was evaluated by comparing the respective MZ and DZ correlations. The genetic and environmental contributions were then estimated by structural equation modeling (SEM). We found that the peaks of the low gamma ERDs were localized to the left frontal area. The power of low gamma ERDs in this area exhibited higher similarity between MZ twins than that between DZ twins. SEM estimated the genetic contribution as approximately 50%. In addition, these powers were negatively correlated with the behavioral verbal scores. These results improve our understanding of how genetic and environmental factors influence cerebral activities during linguistic processes.

YNIMG Journal 2012 Journal Article

Quantification of metabotropic glutamate subtype 5 receptors in the brain by an equilibrium method using 18F-SP203

• Yasuyuki Kimura
• Fabrice G. Siméon
• Sami S. Zoghbi
• Yi Zhang
• Jun Hatazawa
• Victor W. Pike
• Robert B. Innis
• Masahiro Fujita

A new PET ligand, 3-fluoro-5-(2-(2-18F-(fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile (18F-SP203) can quantify metabotropic glutamate subtype 5 receptors (mGluR5) in human brain by a bolus injection and kinetic modeling. As an alternative approach to a bolus injection, binding can simply be measured as a ratio of tissue to metabolite-corrected plasma at a single time point under equilibrium conditions achieved by administering the radioligand with a bolus injection followed by a constant infusion. The purpose of this study was to validate the equilibrium method as an alternative to the standard kinetic method for measuring 18F-SP203 binding in the brain. Nine healthy subjects were injected with 18F-SP203 using a bolus plus constant infusion for 300min. A single ratio of bolus-to-constant infusion (the activity of bolus equaled to that of infusion over 219min) was applied to all subjects to achieve equilibrium in approximately 120min. As a measure of ligand binding, we compared total distribution volume (V T) calculated by the equilibrium and kinetic methods in each scan. The equilibrium method calculated V T by the ratio of radioactivity in the brain to the concentration of 18F-SP203 in arterial plasma at 120min, and the kinetic method calculated V T by a two-tissue compartment model using brain and plasma dynamic data from 0 to 120min. V T obtained via the equilibrium method was highly correlated with V T obtained via kinetic modeling. Inter-subject variability of V T obtained via the equilibrium method was slightly smaller than V T obtained via the kinetic method. V T obtained via the equilibrium method was ~10% higher than V T obtained via the kinetic method, indicating a small difference between the measurements. Taken together, the results of this study show that using the equilibrium method is an acceptable alternative to the standard kinetic method when using 18F-SP203 to measure mGluR5. Although small differences in the measurements obtained via the equilibrium and kinetic methods exist, both methods consistently measured mGluR5 as indicated by the highly correlated V T values; the equilibrium method was slightly more precise, as indirectly measured by the smaller coefficient of variability across subjects. In addition, when using 18F-SP203, the equilibrium method is more efficient because it requires much less data.

YNIMG Journal 2010 Journal Article

11C-methionine uptake correlates with tumor cell density rather than with microvessel density in glioma: A stereotactic image-histology comparison

• Yoshiko Okita
• Manabu Kinoshita
• Tetsu Goto
• Naoki Kagawa
• Haruhiko Kishima
• Eku Shimosegawa
• Jun Hatazawa
• Naoya Hashimoto

11C-methionine positron emission tomography (11C-methionine PET) provides accurate detection of brain tumors. Several reports have analyzed the correlation between uptake of 11C-methionine and Ki-67 index or microvessel density non-stereotactically and suggested that 11C-methionine uptake reflects both proliferation potential and angiogenic capability in gliomas. As gliomas possess heterogeneous histological architecture, non-stereotactic comparison of the histology and 11C-methionine PET image may not be accurate. In the present study, the correlation between 11C-methionine uptake and cell or microvessel density was analyzed using histological specimens obtained by stereotactic biopsy, and an exact local comparison of 11C-methionine PET image and histological specimens was conducted. The tumor/normal tissue (T/N) ratio of 11C-methionine positron emission tomography was found to correlate better with cell density (R =0. 747, p =0. 000042) and Ki-67 index (R =0. 675, p =0. 00041) than with microvessel density (R =0. 467, p =0. 025) in a histological comparison using a stereotactic image. Furthermore, multiple linear regression analysis revealed that cell density was the key determinant for predicting 11C-methionine level while microvessel density was not. These results suggest that cell density contributes more to 11C-methionine uptake than microvessel density in glioma tissues and that the previously reported correlation of 11C-methionine uptake and microvessel density in glioma patients requires reevaluation.

YNIMG Journal 2010 Journal Article

Evaluation of cerebral astrocyte specific energy metabolism in normal human volunteers by [C-11]acetate and PET

• Hiroshi Watabe
• Toshiko Ishikawa
• Yuka Matsuo
• Yasukazu Kanai
• Masao Imaizumi
• Hiroki Katoh
• Eku Shimosegawa
• Jun Hatazawa

YNIMG Journal 2010 Journal Article

Modulation of neuronal activity after spinal cord stimulation for neuropathic pain; H215O PET study

• Haruhiko Kishima
• Youichi Saitoh
• Satoru Oshino
• Koichi Hosomi
• Mohamed Ali
• Tomoyuki Maruo
• Masayuki Hirata
• Tetsu Goto

Spinal cord stimulation (SCS) is an effective therapy for chronic neuropathic pain. However, the detailed mechanisms underlying its effects are not well understood. Positron emission tomography (PET) with H2 15O was applied to clarify these mechanisms. Nine patients with intractable neuropathic pain in the lower limbs were included in the study. All patients underwent SCS therapy for intractable pain, which was due to failed back surgery syndrome in three patients, complex regional pain syndrome in two, cerebral hemorrhage in two, spinal infarction in one, and spinal cord injury in one. Regional cerebral blood flow (rCBF) was measured by H2 15O PET before and after SCS. The images were analyzed with statistical parametric mapping software (SPM2). SCS reduced pain; visual analog scale values for pain decreased from 76. 1±25. 2 before SCS to 40. 6±4. 5 after SCS (mean±SE). Significant rCBF increases were identified after SCS in the thalamus contralateral to the painful limb and in the bilateral parietal association area. The anterior cingulate cortex (ACC) and prefrontal areas were also activated after SCS. These results suggest that SCS modulates supraspinal neuronal activities. The contralateral thalamus and parietal association area would regulate the pain threshold. The ACC and prefrontal areas would control the emotional aspects of intractable pain, resulting in the reduction of neuropathic pain after SCS.

YNIMG Journal 2009 Journal Article

Use of fractional anisotropy for determination of the cut-off value in 11C-methionine positron emission tomography for glioma

• Manabu Kinoshita
• Naoya Hashimoto
• Tetsu Goto
• Takufumi Yanagisawa
• Yoshiko Okita
• Naoki Kagawa
• Haruhiko Kishima
• Hisashi Tanaka

Multimodal imaging is one of the necessary steps in the treatment of malignant brain tumors, and use of magnetic resonance imaging (MRI) and positron emission tomography (PET) are the current gold standard technique for the morphological and biological assessment of malignant brain tumors. In addition, fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) and 11C-methionine PET are useful to determine the tumor border at the tumor and white matter interface. Although there is no question of their value, a universally accepted cut-off value to discriminate normal and abnormal tissue has not been established. In this study we attempted to calculate and determine the cut-off values in FA and 11C-methionine PET that will allow delineation of the tumor border at the tumor and white matter interface by combining these two modalities. We were able to determine individual cut-off values for 11 patients, and then found an average cut-off value in the T/N ratio of 11C-methionine PET of 1. 27 and in FA of 0. 26, values similar to those previously confirmed by histological study. Moreover, reconstructing images delineating the tumor border was possible combining these two imaging modalities. We propose that the combined analysis of DTI and 11C-methionine PET has the potential to improve tumor border imaging in glioma patients, providing important information for establishing neurosurgical strategies.

YNIMG Journal 2007 Journal Article

Differential brain processing of audiovisual sexual stimuli in men: Comparative positron emission tomography study of the initiation and maintenance of penile erection during sexual arousal

• Yasushi Miyagawa
• Akira Tsujimura
• Kazutoshi Fujita
• Yasuhiro Matsuoka
• Tohru Takahashi
• Tetsuya Takao
• Shingo Takada
• Kiyomi Matsumiya

The human male psychosexual cycle consists of four phases: excitation, plateau, orgasm, and resolution. Identification of the specific neural substrates of each phase may provide information regarding the brain’s pathophysiology of sexual dysfunction. We previously analyzed regional cerebral blood flow (rCBF) with H2 15O-positron emission tomography (PET) during the excitation phase (initiation of penile erection) induced by audiovisual sexual stimuli (AVSS) and identified activation of the cerebellar vermis, the bilateral extrastriate cortex, and right orbitofrontal cortex, suggesting a role of cognition/emotion in the excitement phase. In the present study, we analyzed rCBF of the same six healthy volunteers during the plateau phase (maintenance of penile erection) induced by AVSS and compared the results with those of the excitation phase. Penile rigidity was monitored in real time with RigiScan Plus® during PET scanning. Images were analyzed by statistical parametric mapping (SPM) software, and rCBF in the amygdala, hypothalamus, anterior cingulate, and insula was measured. During the plateau phase, primary subcortical activation was noted in the right ventral putamen, indicating motivational factors in the sexual response via the limbic reward circuit. A significant increase in rCBF in the left hypothalamus was also observed during the plateau phase. The right anterior cingulate and left insula were specifically activated during the excitation phase but not during the plateau phase. These results indicate a significant role of the ventral putamen and the hypothalamus in the plateau phase and confirm that paralimbic and limbic components of the human brain differentially coordinate the sexual response in a psychosexual phase-dependent manner.

YNIMG Journal 2002 Journal Article

Regional Changes in Human Cerebral Blood Flow during Dipyridamole Stress: Neural Activation in the Thalamus and Prefrontal Cortex

• Hiroshi Ito
• Ikuo Yokoyama
• Yoshikazu Tamura
• Toshibumi Kinoshita
• Jun Hatazawa
• Ryuta Kawashima
• Hidehiro Iida

Intravenous dipyridamole increases the concentration of circulating adenosine and produces coronary vasodilation. However, it decreases global cerebral blood flow (CBF) due to hyperventilation side effect of adenosine. In the present study, changes in regional CBF during dipyridamole stress were identified in detail. In 11 healthy men (51–71 years of age), CBF was measured by positron emission tomography with oxygen-15-labeled water at rest (baseline) and during dipyridamole stress. All images were normalized to global CBF and transformed to standard brain anatomy. A t map between baseline and dipyridamole stress conditions was then created on a pixel-by-pixel basis. CBF was globally decreased during dipyridamole stress. However, a significant relative increase in CBF was observed bilaterally in the thalamus and prefrontal cortex, indicating neural activation in these regions. Adenosine plays an important role in the production of anginal pain by stimulation of A1 adenosine receptors. Neural activation in the thalamus and prefrontal cortex during angina pectoris has been reported. Although no subject felt chest pain during dipyridamole stress, neural activation in the thalamus and prefrontal cortex indicates that stimulation of A1 adenosine receptors during dipyridamole stress may produce input from the heart to the thalamus through the vagal fiber.