気分状態に依存しない双極性障害と大うつ病性障害における脳梁の白質微細構造の差異

OBJECTIVE: It is difficult to distinguish between bipolar disorder and major depressive disorder (MDD) in patients lacking a clear history of mania. There is an urgent need for an objective biomarker for differential diagnosis. Using diffusion tensor imaging, this study investigated the differences in the brain white matter microstructure between patients with bipolar disorder and MDD. METHODS: Participants included 16 patients with bipolar disorder and 23 patients with MDD having depressed or euthymic states based on DSM-IV-TR criteria and 23 healthy volunteers. Whole-brain voxel-based morphometric analysis was used to detect any significant differences in fractional anisotropy between patients with bipolar disorder and MDD. The study was conducted between August 2011 and July 2015. RESULTS: We found a significant decrease in fractional anisotropy values in the anterior part of the corpus callosum in patients with bipolar disorder compared with MDD (P < .001), which did not depend on the patients' affective state. This decrease was associated with increased radial diffusivity values (P < .05), which was also found in patients with bipolar disorder when compared with healthy volunteers (P < .05). We predicted bipolar disorder and MDD in all patients using the fractional anisotropy values, with a correct classification rate of 76.9%. CONCLUSIONS: The present study revealed that patients with bipolar disorder have microstructural abnormalities in the corpus callosum during depressed or euthymic states, which may deteriorate the exchange of emotional information between the cerebral hemispheres, resulting in emotional dysregulation. Our results indicate the possible use of diffusion tensor imaging as a differential diagnostic tool.博士（医学）・甲第662号・平成29年3月15日© Copyright 2017 Physicians Postgraduate Press, Inc.発行元の規定により、本文の登録不可。本文は以下のURLを参照 "http://dx.doi.org/10.4088/JCP.15m09851" （※全文閲覧は学内限定

Evaluation of [F-18]F-DPA PET for Detecting Microglial Activation in the Spinal Cord of a Rat Model of Neuropathic Pain

Purpose Recent studies have linked activated spinal glia to neuropathic pain. Here, using a positron emission tomography (PET) scanner with high spatial resolution and sensitivity, we evaluated the feasibility and sensitivity of N,N-diethyl-2-(2-(4-([18F]fluoro)phenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin3-yl)acetamide -([F-18]F-DPA) imaging for detecting spinal cord microglial activation after partial sciatic nerve ligation (PSNL) in rats.Procedures Neuropathic pain was induced in rats (n = 20) by PSNL, and pain sensation tests were conducted before surgery and 3 and 7 days post- injury. On day 7, in vivo PET imaging and ex vivo autoradiography were performed using -[F-18]F-DPA or -[C-11]PK11195. Ex vivo biodistribution and PET imaging of the removed spinal cord were carried out with -[F-18]F-DPA. Sham-operated and PK11195pretreated animals were also examined.Results Mechanical allodynia was confirmed in the PSNL rats from day 3 through day 7. Ex vivo autoradiography showed a higher lesion-to-background uptake with -[F-18]F-DPA compared with -[C-11]PK11195. Ex vivo PET imaging of the removed spinal cord showed -[F-18]F-DPA accumulation in the inflammation site, which was immunohistochemically confirmed to coincide with microglia activation. Pretreatment with PK11195 eliminated the uptake. The SUV values of in vivo -[F-18]F-DPA and -[C-11]PK11195 PET were not significantly increased in the lesion compared with the reference region, and were fivefold higher than the values obtained from the ex vivo data. Ex vivo biodistribution revealed a twofold higher -[F-18] F-DPA uptake in the vertebral body compared to that seen in the bone from the skull.Conclusions[F-18]F-DPA aided visualization of the spinal cord inflammation site in PSNL rats on ex vivo autoradiography and was superior to -[C-11]PK11195. In vivo -[F-18]F-DPA PET did not allow for visualization of tracer accumulation even using a high-spatial-resolution PET scanner. The main reason for this result was due to insufficient SUVs in the spinal cord region as compared with the background noise, in addition to a spillover from the vertebral body.</p

System evaluation of automated production and inhalation of O-15-labeled gaseous radiopharmaceuticals for the rapid O-15-oxygen PET examinations

Background(15)O-oxygen inhalation PET is unique in its ability to provide fundamental information regarding cerebral hemodynamics and energy metabolism in man. However, the use of O-15-oxygen has been limited in a clinical environment largely attributed to logistical complexity, in relation to a long study period, and the need to produce and inhale three sets of radiopharmaceuticals. Despite the recent works that enabled shortening of the PET examination period, radiopharmaceutical production has still been a limiting factor. This study was aimed to evaluate a recently developed radiosynthesis/inhalation system that automatically supplies a series of O-15-labeled gaseous radiopharmaceuticals of (CO)-O-15, O-15(2), and (CO2)-O-15 at short intervals.MethodsThe system consists of a radiosynthesizer which produces (CO)-O-15, O-15(2), and (CO2)-O-15; an inhalation controller; and an inhalation/scavenging unit. All three parts are controlled by a common sequencer, enabling automated production and inhalation at intervals less than 4.5min. The gas inhalation/scavenging unit controls to sequentially supply of qualified radiopharmaceuticals at given radioactivity for given periods at given intervals. The unit also scavenges effectively the non-inhaled radioactive gases. Performance and reproducibility are evaluated.ResultsUsing an O-15-dedicated cyclotron with deuteron of 3.5MeV at 40A, (CO)-O-15, O-15(2), and (CO2)-O-15 were sequentially produced at a constant rate of 1400, 2400, and 2000MBq/min, respectively. Each of radiopharmaceuticals were stably inhaled at </p

A Noninvasive Method for Quantifying Cerebral Metabolic Rate of Oxygen by Hybrid PET/MRI: Validation in a Porcine Model

The gold standard for imaging the cerebral metabolic rate of oxygen (CMRO2) is positron emission tomography (PET); however, it is an invasive and complex procedure that also requires correction for recirculating 15O-H2O and the blood-borne activity. We propose a noninvasive reference-based hybrid PET/magnetic resonance imaging (MRI) method that uses functional MRI techniques to calibrate 15O-O2-PET data. Here, PET/MR imaging of oxidative metabolism (PMROx) was validated in an animal model by comparison to PET-alone measurements. Additionally, we investigated if the MRI-perfusion technique arterial spin labelling (ASL) could be used to further simplify PMROx by replacing 15O-H2O-PET, and if the PMROx was sensitive to anesthetics-induced changes in metabolism. Methods: 15O-H2O and 15O-O2 PET data were acquired in a hybrid PET/MR scanner (3 T Siemens Biograph mMR), together with simultaneous functional MRI (OxFlow and ASL), from juvenile pigs (n = 9). Animals were anesthetized with 3% isoflurane and 6 mL/kg/h propofol for the validation experiments and arterial sampling was performed for PET-alone measurements. PMROx estimates were obtained using whole-brain (WB) CMRO2 from OxFlow and local cerebral blood flow (CBF) from either noninvasive 15O-H2O-PET or ASL (PMROxASL). Changes in metabolism were investigated by increasing the propofol infusion to 20 mL/kg/h. Results: Good agreement and correlation were observed between regional CMRO2 measurements from PMROx and PET-alone. No significant differences were found between OxFlow and PET-only measurements of WB oxygen extraction fraction (0.30 ± 0.09 and 0.31 ± 0.09) and CBF (54.1 ± 16.7 and 56.6 ± 21.0 mL/100 g/min), or between PMROx and PET-only CMRO2 estimates (1.89 ± 0.16 and 1.81 ± 0.10 mLO2/100 g/min). Moreover, PMROx and PMROxASL were sensitive to propofol-induced reduction in CMRO2 Conclusion: This study provides initial validation of a noninvasive PET/MRI technique that circumvents many of the complexities of PET CMRO2 imaging. PMROx does not require arterial sampling and has the potential to reduce PET imaging to 15O-O2 only; however, future validation involving human participants are required

Dysregulation of RNF213 promotes cerebral hypoperfusion

RNF213 is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role of RNF213 in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils on Rnf213 knockout (KO) and vascular endothelial cell-specific Rnf213 mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice. Temporal CBF changes were measured by arterial spin-labelling magnetic resonance imaging. In the cortical area, no significant difference in CBF was found before surgery between the genotypes. Three of eight (37.5%) KO mice died after surgery but all wild-type and EC-Tg mice survived hypoperfusion. KO mice had a significantly more severe reduction in CBF on day 7 than wild-type mice (KO, 29.7% of baseline level; wild-type, 49.3%; p = 0.038), while CBF restoration on day 28 was significantly impaired in both KO (50.0%) and EC-Tg (56.1%) mice compared with wild-type mice (69.5%; p = 0.031 and 0.037, respectively). Changes in the subcortical area also showed the same tendency as the cortical area. Additionally, histological analysis demonstrated that angiogenesis was impaired in both EC-Tg and KO mice. These results are indicative of the essential role of RNF213 in the maintenance of CBF

Accuracy of Non-invasive Arterial Input Functions and Error in Quantitative Images in the Cerebellar Reference Method

PURPOSE: We developed and validated the accuracy of a method to calculate the arterial input function (AIF) from PET images only, without the need for the arterial blood sampling, in the absolute quantitation of functional parametric values in 15O- gas PET examinations.METHODS: We extended the method reported by Iguchi et al. (2013) to derive the arterial input function, thus absolute quantitative functional parametric images of cerebral perfusion and oxygen metabolism by a reference tissue approach. We compared shapes of the AIF and reproducibility of the absolute functional values. Existing test data that were carried out with the continuous arterial blood sampling were used for this study.RESULTS: The estimated AIF shapes agreed well with those estimated from the continuous arterial blood sampling. The error range of the absolute quantitative values was approximately ±20%, with a fairly well reproducibility in the relative values being less than 3%.CONCLUSION: The AIFs by this method were reproducible. Although the absolute quantitative values varied depending on the assumed functional values in the reference region in individual cases, the relative images showed fairly good agreement with the results from the standard technique that employed the arterial blood sampling. The present technique may provide significant contribution to clinical examination.</p

Hybrid MR-PET Imaging: Systems, Methods and Applications

Using molecules radiolabelled with positron emitters, positron emission tomography (PET) imaging provides information relating to a multitude of physiological and metabolic functions. Whereas primary PET images give a qualitative insight into these functions, when PET images are combined with data of the time course of the PET radiopharmaceutical in the blood, in an appropriate biological model, the extraction of quantified parameters of the observed function becomes possible. This chapter gives an introduction into kinetic modelling used with PET and the related mathematical procedures. Additionally, some basic and often used applications are described and are followed by an overview of the application of kinetic modelling in the case of MR-PET.</p