研究者詳細 - 菅　博人

Blood-Brain Barrier Function Associates with Brain Iron Dynamics along Developmental Trajectory: A Combined Quantitative Magnetic Resonance Imaging Study during Childhood

Anisotropy of the R1/T2* value dependent on white matter fiber orientation with respect to the B0 field.

Kawaguchi S, Kan H, Uchida Y, Kasai H, Hiwatashi A, Ueki Y

Magnetic resonance imaging 2024年2月

Longitudinal Changes in Iron and Myelination Within Ischemic Lesions Associate With Neurological Outcomes: A Pilot Study.

Uchida Y, Kan H, Kano Y, Onda K, Sakurai K, Takada K, Ueki Y, Matsukawa N, Hillis AE, Oishi K

Stroke 2024年1月

Brain Abnormalities in Becker Muscular Dystrophy: Evaluation by Voxel-Based DTI and Morphometric Analysis.

Maki H, Mori-Yoshimura M, Matsuda H, Hashimoto Y, Ota M, Kimura Y, Shigemoto Y, Ishihara N, Kan H, Chiba E, Arizono E, Yoshida S, Takahashi Y, Sato N

AJNR. American journal of neuroradiology 2023年11月

Uchida, Y; Kan, H; Furukawa, G; Onda, K; Sakurai, K; Takada, K; Matsukawa, N; Oishi, K

ANNALS OF NEUROLOGY 94 巻頁： S209 - S210 2023年9月

Relationship between brain iron dynamics and blood-brain barrier function during childhood: a quantitative magnetic resonance imaging study.

Uchida Y, Kan H, Furukawa G, Onda K, Sakurai K, Takada K, Matsukawa N, Oishi K

Fluids and barriers of the CNS 20 巻 ( 1 ) 頁： 60 2023年8月

Three-compartment spectral diffusion analysis for breast cancer magnetic resonance imaging.

Ogawa M, Kan H, Urano M, Kawai T, Nakajima H, Murai K, Miyaji H, Toyama T, Hiwatashi A

Magnetic resonance imaging 2023年5月

Voxel-Based and Surface-Based Morphometry Analysis in Patients with Pathologically Confirmed Argyrophilic Grain Disease and Alzheimer's Disease.

Sakurai K, Kaneda D, Morimoto S, Uchida Y, Inui S, Kimura Y, Kan H, Kato T, Ito K, Hashizume Y

Journal of Alzheimer's disease : JAD 2023年3月

Contributions of blood-brain barrier imaging to neurovascular unit pathophysiology of Alzheimer's disease and related dementias.

Uchida Y, Kan H, Sakurai K, Oishi K, Matsukawa N

Frontiers in aging neuroscience 15 巻頁： 1111448 2023年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers in Aging Neuroscience

The blood–brain barrier (BBB) plays important roles in the maintenance of brain homeostasis. Its main role includes three kinds of functions: (1) to protect the central nervous system from blood-borne toxins and pathogens; (2) to regulate the exchange of substances between the brain parenchyma and capillaries; and (3) to clear metabolic waste and other neurotoxic compounds from the central nervous system into meningeal lymphatics and systemic circulation. Physiologically, the BBB belongs to the glymphatic system and the intramural periarterial drainage pathway, both of which are involved in clearing interstitial solutes such as β-amyloid proteins. Thus, the BBB is believed to contribute to preventing the onset and progression for Alzheimer’s disease. Measurements of BBB function are essential toward a better understanding of Alzheimer’s pathophysiology to establish novel imaging biomarkers and open new avenues of interventions for Alzheimer’s disease and related dementias. The visualization techniques for capillary, cerebrospinal, and interstitial fluid dynamics around the neurovascular unit in living human brains have been enthusiastically developed. The purpose of this review is to summarize recent BBB imaging developments using advanced magnetic resonance imaging technologies in relation to Alzheimer’s disease and related dementias. First, we give an overview of the relationship between Alzheimer’s pathophysiology and BBB dysfunction. Second, we provide a brief description about the principles of non-contrast agent-based and contrast agent-based BBB imaging methodologies. Third, we summarize previous studies that have reported the findings of each BBB imaging method in individuals with the Alzheimer’s disease continuum. Fourth, we introduce a wide range of Alzheimer’s pathophysiology in relation to BBB imaging technologies to advance our understanding of the fluid dynamics around the BBB in both clinical and preclinical settings. Finally, we discuss the challenges of BBB imaging techniques and suggest future directions toward clinically useful imaging biomarkers for Alzheimer’s disease and related dementias.

DOI： 10.3389/fnagi.2023.1111448

Assessing white matter microstructural changes in idiopathic normal pressure hydrocephalus using voxel-based R2* relaxometry analysis.

Kano Y, Uchida Y, Kan H, Sakurai K, Kobayashi S, Seko K, Mizutani K, Usami T, Takada K, Matsukawa N

Frontiers in neurology 14 巻頁： 1251230 2023年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers in Neurology

Background: R2* relaxometry and quantitative susceptibility mapping can be combined to distinguish between microstructural changes and iron deposition in white matter. Here, we aimed to explore microstructural changes in the white matter associated with clinical presentations such as cognitive impairment in patients with idiopathic normal-pressure hydrocephalus (iNPH) using R2* relaxometry analysis in combination with quantitative susceptibility mapping. Methods: We evaluated 16 patients clinically diagnosed with possible or probable iNPH and 18 matched healthy controls (HC) who were chosen based on similarity in age and sex. R2* and quantitative susceptibility mapping were compared using voxel-wise and atlas-based one-way analysis of covariance (ANCOVA). Finally, partial correlation analyses were performed to assess the relationship between R2* and clinical presentations. Results: R2* was lower in some white matter regions, including the bilateral superior longitudinal fascicle and sagittal stratum, in the iNPH group compared to the HC group. The voxel-based quantitative susceptibility mapping results did not differ between the groups. The atlas-based group comparisons yielded negative mean susceptibility values in almost all brain regions, indicating no clear paramagnetic iron deposition in the white matter of any subject. R2* and cognitive performance scores between the left superior longitudinal fasciculus (SLF) and right sagittal stratum (SS) were positively correlated. In addition to that, R2* and gait disturbance scores between left SS were negatively correlated. Conclusion: Our analysis highlights the microstructural changes without iron deposition in the SLF and SS, and their association with cognitive impairment and gait disturbance in patients with iNPH.

DOI： 10.3389/fneur.2023.1251230

Noncontrast time-resolved pulmonary magnetic resonance angiography with consecutive beam saturation pulse and variable flip angles using three-dimensional fast spin echo: A preliminary study. 国際誌

Kan H, Mizuno K, Takizawa M, Shimohira M, Kawai T, Aoki T, Tsubokura S, Kasai H

Magnetic resonance imaging 94 巻頁： 80 - 88 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Magnetic Resonance Imaging

To develop and validate a novel noncontrast time-resolved magnetic resonance angiography (NC TR-MRA) using consecutive beam pulses with variable flip angles for visualizing hemodynamics in the pulmonary artery, we performed phantom and volunteer studies and applied the novel NC TR-MRA to a 51-year-old woman with pulmonary arteriovenous malformation (PAVM).The novel NC TR-MRA sequence utilized consecutive multiple-beam saturation pulses with variable flip angles considering venous blood T1 relaxation to alter the visualized blood signal length. The flowing blood signal length is suppressed according to the number of beam saturation pulses. NC TR-MRA in each flow phase was assessed by subtracting the images with and without beam saturation pulses. In the flow phantom study, three flow velocities were used to simulate physiological pulmonary arterial blood flow. Signal profiles along the flow direction were evaluated in each flow phase. In the volunteer study, five healthy volunteers were recruited, and NC TR-MRA was applied to evaluate relationships between the flow-saturated time and signal enhancement rates. Four regions of interest (ROIs) were determined on the proximal and distal portions of the right basal artery. A patient with PAVM was included to validate whether a PAVM lesion could be visualized using NC TR-MRA. The visualized flow signal lengths extended proportionally with the number of beam saturation pulses in the steady-flow phantom at all velocities. In the volunteer study, NC TR-MRA images showed signal enhancement from the proximal to distal portions of the right basal artery with increase in the flow-saturated time. Signal enhancement rates in all ROIs were significantly positively correlated with the flow-saturated time (p < 0.001 in all ROIs). Further, the lesion and its hemodynamics could be explicitly visualized in the patient with PAVM. Hence, NC TR-MRA using beam saturation pulse can visualize the hemodynamics of the pulmonary artery and may be useful for diagnosing and following patients with PAVM.

DOI： 10.1016/j.mri.2022.09.001

Memantine for the patients with mild cognitive impairment in Parkinson’s disease: a pharmacological fMRI study

Kawashima S., Shimizu Y., Horiba M., Ueki Y., Akanabe R., Kan H., Kasai H., Kunitomo H., Tanaka S., Toyota T., Kawashima S., Mizuno M., Okita K., Matsukawa N.

BMC Neurology 22 巻 ( 1 ) 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BMC Neurology

Background: Mild cognitive impairment in Parkinson’s disease (PD-MCI) is associated with an increased risk of cognitive decline. PD-MCI is characterized by impairments in executive function and visuospatial recognition. The visuospatial n-back test is useful for assessing both domains. The 0-back test reflects visuospatial recognition, while the 1-back and 2-back tests reflect working memory. Cholinesterase inhibitors are effective in the treatment of PD-MCI and dementia in PD (PDD). Although some studies have reported the efficacy of memantine for PDD, the therapeutic efficacy of memantine in patients with PD-MCI remains uncertain. Methods: This study aimed to investigate the effects of memantine on brain function in patients with PD-MCI, using a randomized double-blinded crossover protocol and functional MRI (fMRI). Ten patients who completed 16 weeks of follow-up were included. They were randomly assigned to either the memantine or placebo. Patients in the memantine group received 5 mg/day of memantine in the first week. The memantine dose was increased by 5 mg/day per week, until a final dose of 20 mg/day. Patients in the placebo group received the placebo following the same regimen as memantine. After the intervention, they underwent a 4 weeks washout period. Following the crossover protocol, a second intervention was conducted after the washout period. In each intervention, fMRI and neuropsychological tests were performed at the maximum dose period. Comparing the memantine and placebo groups, we investigated difference in the brain regions using the visuospatial n-back test. Results: There were no significant regions enhanced by memantine comparing with placebo at any load of n-back tests. In contrast, exploring regions reduced by memantine, we found significant reduction of activations within right lingual gyrus and left superior frontal gyrus in comparison between 2-back and 0-back test. A number of correct answers of the 2-back test and time to complete Trail Making Test-A were worse during memantine intervention. Conclusions: Memantine did not improve visuospatial working memory of the patients with PD-MCI. Treatment for PD should be planned carefully considering the impact on cognitive function. Further study is needed to establish new therapeutic strategy. Trial registration: UMIN000046104. Retrospectively registered. First registration date: 28 Sept 2017.

DOI： 10.1186/s12883-022-02699-x

APOE ɛ4 dose associates with increased brain iron and β-amyloid via blood-brain barrier dysfunction. 国際誌

Uchida Y, Kan H, Sakurai K, Horimoto Y, Hayashi E, Iida A, Okamura N, Oishi K, Matsukawa N

Journal of neurology, neurosurgery, and psychiatry 93 巻 ( 7 ) 頁： 772 - 778 2022年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Neurology, Neurosurgery and Psychiatry

Objective To examine the effect of apolipoprotein E (APOE) ϵ4 dose on blood-brain barrier (BBB) clearance function, evaluated using an advanced MRI technique and analyse its correlation with brain iron and β-amyloid accumulation in the early stages of the Alzheimer's continuum. Methods In this single-centre observational prospective cohort study, 24 APOE ϵ4 non-carriers, 22 heterozygotes and 20 homozygotes in the early stages of the Alzheimer's continuum were scanned with diffusion-prepared arterial spin labelling, which estimates the water exchange rate across the BBB (k w). Participants also underwent quantitative susceptibility mapping, [11 C]Pittsburgh compound B-positron emission tomography and neuropsychological testing. Using an atlas-based approach, we compared the regional k w of the whole brain among the groups and analysed its correlation with the neuroradiological and neuropsychological findings. Results The BBB k w values in the neocortices differed significantly among the groups (APOE ϵ4 non-carriers>heterozygotes>homozygotes). These values correlated with brain iron levels (frontal lobe: r=-0.476, 95% CI=-0.644 to-0.264, p=0.011; medial temporal lobe: r=-0.455, 95% CI=-0.628 to-0.239, p=0.017), β-amyloid loads (frontal lobe: r=-0.504, 95% CI=-0.731 to-0.176, p=0.015; medial temporal lobe: r=-0.452, 95% CI=-0.699 to-0.110, p=0.036) and neuropsychological scores, after adjusting for age, sex and APOE ϵ4 dose. Interpretation Our results suggest that an increased APOE ϵ4 dose is associated with decreased effective brain-waste clearance, such as iron and β-amyloid, through the BBB.

DOI： 10.1136/jnnp-2021-328519

Delineation of prostatic calcification using quantitative susceptibility mapping: Spatial accuracy for magnetic resonance-only radiotherapy planning. 国際誌

Kan H, Tsuchiya T, Yamada M, Kunitomo H, Kasai H, Shibamoto Y

Journal of applied clinical medical physics 23 巻 ( 2 ) 頁： e13469 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Applied Clinical Medical Physics

To investigate the spatial accuracy of delineating prostatic calcifications by quantitative susceptibility mapping (QSM) in comparison with computed tomography (CT), we conducted phantom and human studies. Five differently-sized spherical hydroxyapatites mimicking prostatic calcification (pseudo-calcification) were arranged in the order of their sizes at the center of a plastic container filled with gelatin. This calcification phantom underwent magnetic resonance (MR) imaging, including the multiple spoiled gradient-echo sequences (SPGR) for the QSM and CT as a reference. The volume of each pseudo-calcification and center-to-center distance between the pseudo-calcifications delineated by QSM and CT were measured. In the human study, eight patients with prostate cancer who underwent radiation therapy and had some prostatic calcifications were included. The patients underwent CT and SPGR and modified DIXON sequence for MR-only simulation. The hybrid QSM processing combined with the complex signals in the SPGR and water and fat fraction maps estimated from the modified DIXON sequence were used to reconstruct the pelvic susceptibility map in humans. The threshold of CT numbers was set at 130 HU, while the QSM images were manually segmented in the calcification phantom and human studies. In the phantom study, there was an excellent agreement in the pseudo-calcification volumes between QSM and CT (y = 1.02x – 7.38, R2 = 0.99). The signal profiles had similar trends in CT and QSM. The center-to-center distances between the pseudo-calcifications in the phantom were also identical in QSM and CT. The calcification volumes were almost identical between the QSM and CT in the human study (y = 0.95x – 9.32, R2 = 1.00). QSM can offer geometric and volumetric accuracies to delineate prostatic calcifications, similar to CT. The prostatic calcification delineated by QSM may facilitate image-guided radiotherapy in the MR-only simulation workflow.

DOI： 10.1002/acm2.13469