論文 - 藤原　広和

Non-lesional white matter changes depicted by q-space diffusional MRI correlate with clinical disabilities in multiple sclerosis

Motegi H., Kufukihara K., Kitagawa S., Sekiguchi K., Hata J., Fujiwara H., Jinzaki M., Okano H., Nakamura M., Iguchi Y., Nakahara J.

Journal of the Neurological Sciences （Journal of the Neurological Sciences）  456 2024年01月

ISSN  0022510X

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Background: We previously developed an optimized q-space diffusional MRI technique (normalized leptokurtic diffusion [NLD] map) to delineate the demyelinated lesions of multiple sclerosis (MS) patients. Herein, we evaluated the utility of NLD maps to discern the white matter abnormalities in normal-appearing white matter (NAWM) and the abnormalities' possible associations with physical and cognitive disabilities in MS. Methods: We conducted a retrospective observational study of MS patients treated at our hospital (Jan. 2012 to Dec. 2022). Clinical and MRI data were collected; Processing Speed Test (PST) data were obtained when possible. For a quantitative analysis of the NLD maps, we calculated the NLD index as GVROI/GVREF, where GV is a mean grayscale value in the regions of interest (ROIs) and the reference area (REF; cerebrospinal fluid). Results: One hundred-one individuals with MS were included. The lower corpus callosum and non-lesional WM NLD index were associated with worse Expanded Disability Status Scale (EDSS) and PST scores. The NLD indexes in the corpus callosum (p < 0.0001) and non-lesional white matter (p < 0.0001) were significantly reduced in progressive MS compared to relapsing-remitting MS. We categorized MS severity as moderate/severe (EDSS score ≥ 4 points) and mild (EDSS score < 4 points). The NLD indexes in the corpus callosum (p < 0.0001) and non-lesional white matter (p < 0.0001) were significantly lower in the moderate/severe MS group compared to the mild MS group. Conclusion: The NLD map revealed abnormalities in the non-lesional white matter, providing valuable insights for evaluating manifestations in MS patients.

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“Missing-piece” sign with dural arteriovenous fistula at craniocervical junction: A case report

Tezuka T., Nukariya T., Katsumata M., Miyauchi T., Tokuyasu D., Azami S., Izawa Y., Nagoshi N., Fujiwara H., Mizutani K., Akiyama T., Toda M., Nakahara J., Nishimoto Y.

Journal of Stroke and Cerebrovascular Diseases （Journal of Stroke and Cerebrovascular Diseases）  32 （ 7 ）  2023年07月

ISSN  10523057

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Objectives: Spinal dural arteriovenous fistula (sDAVF) is a rare and often underdiagnosed spinal disease. Early diagnosis is required because the deficits are reversible and delays in treatment cause permanent morbidity. Although the abnormal vascular flow void is a critical radiographic feature of sDAVF, they are not always present. A characteristic enhancement pattern of sDAVF has been recently reported as the “missing-piece” sign which can lead to the early and correct diagnosis. Methods: We presented imaging findings, treatment decisions, and the outcome of a rare case of sDAVF, in which the “missing-piece” sign appeared atypical. Results: A 60-year-old woman developed numbness and weakness in her extremities. Spinal MRI revealed longitudinal hyperintensity in the T2-weighted image, extending from the thoracic level to medulla oblongata. At first, myelopathy with inflammation or tumor was suspected because of the lack of flow voids and vascular abnormalities in CT-angiography and MR-DSA. However, we administered intravenous methylprednisolone and her symptom got worse with the appearance of the “missing-piece” sign. Then, we successfully diagnosed sDAVF by angiography. The “missing-piece” sign was considered to derive from inconsistency of the intrinsic venous system of spinal cord, with the abrupt segments without enhancement. The same etiology was considered in our case. Conclusions: Detecting the “missing-piece” sign can lead to the correct diagnosis of sDAVF, even if the sign appeared atypical.

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Cranial defect and pneumocephalus are associated with significant postneurosurgical positional brain shift: evaluation using upright computed tomography

Yoshida K., Toda M., Yamada Y., Yamada M., Yokoyama Y., Tsutsumi K., Fujiwara H., Kosugi K., Jinzaki M.

Scientific Reports （Scientific Reports）  12 （ 1 ）  2022年12月

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Only few studies have assessed brain shift caused by positional change. This study aimed to identify factors correlated with a large postneurosurgical positional brain shift (PBS). Sixty-seven patients who underwent neurosurgical procedures had upright computed tomography (CT) scan using settings similar to those of conventional supine CT. The presence of a clinically significant PBS, defined as a brain shift of ≥ 5 mm caused by positional change, was evaluated. The clinical and radiological findings were investigated to identify factors associated with a larger PBS. As a result, twenty-one patients had a clinically significant PBS. The univariate analysis showed that supratentorial lesion location, intra-axial lesion type, craniectomy procedure, and residual intracranial air were the predictors of PBS. Based on the multivariate analysis, craniectomy procedure (p < 0.001) and residual intracranial air volume (p = 0.004) were the predictors of PBS. In a sub-analysis of post-craniectomy patients, PBS was larger in patients with supratentorial craniectomy site and parenchymal brain injury. A large craniectomy area and long interval from craniectomy were correlated with the extent of PBS. In conclusion, patients who undergo craniectomy and those with residual intracranial air can present with a large PBS. In post-craniectomy patients, the predisposing factors of a large PBS are supratentorial craniectomy, presence of parenchymal injury, large skull defect area, and long interval from craniectomy. These findings can contribute to safe mobilization among postneurosurgical patients and the risk assessment of sinking skin flap syndrome.

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Changes in cross-sectional areas of posterior extensor muscles in thoracic spine: a 10-year longitudinal MRI study

Umezawa H., Daimon K., Fujiwara H., Nishiwaki Y., Michikawa T., Okada E., Nojiri K., Watanabe M., Katoh H., Shimizu K., Ishihama H., Fujita N., Tsuji T., Nakamura M., Matsumoto M., Watanabe K.

Scientific Reports （Scientific Reports）  12 （ 1 ）  2022年12月

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Age-related changes in the posterior extensor muscles of the cervical and lumbar spine have been reported in some studies; however, longitudinal changes in the thoracic spine of healthy subjects are rarely reported. Therefore, this study aimed to evaluate changes in the cross-sectional areas (CSAs) of posterior extensor muscles in the thoracic spine over 10 years and identify related factors. The subjects of this study were 85 volunteers (mean age: 44.7 ± 11.5) and the average follow-up period was about 10 years. The CSAs of the transversospinalis muscles, erector spinae muscles, and total CSAs of the extensor muscles from T1/2 to T11/12 were measured on magnetic resonance imaging. The extent of muscle fat infiltration was assessed by the signal intensity (luminance) of the extensor muscles’ total cross-section compared to a section of pure muscle. We applied a Poisson regression model, which is included in the generalized linear model, and first examined the univariate (crude) association between each relevant factor (age, sex, body mass index, lifestyle, back pain, neck pain, neck stiffness, and intervertebral disc degeneration) and CSA changes. Then, we constructed a multivariate model, which included age, sex, and related factors in the univariate analysis. The mean CSAs of the transversospinalis muscles, erector spinae muscles, and total CSAs of the extensor muscles significantly increased over 10 years. Exercise habit was associated with increased CSAs of the erector spinae muscles and the total area of the extensor muscles. The cross-section mean luminance significantly increased from baseline, indicating a significant increase of fat infiltration in the posterior extensor muscles. Progression of disc degeneration was inversely associated with increased fat infiltration in the total extensor muscles.

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Synthetic magnetic resonance imaging for primary prostate cancer evaluation: Diagnostic potential of a non-contrast-enhanced bi-parametric approach enhanced with relaxometry measurements

Arita Y., Akita H., Fujiwara H., Hashimoto M., Shigeta K., Kwee T.C., Yoshida S., Kosaka T., Okuda S., Oya M., Jinzaki M.

European Journal of Radiology Open （European Journal of Radiology Open）  9 2022年01月

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Purpose: Bi-parametric magnetic resonance imaging (bpMRI) with diffusion-weighted images has wide utility in diagnosing clinically significant prostate cancer (csPCa). However, bpMRI yields more false-negatives for PI-RADS category 3 lesions than multiparametric (mp)MRI with dynamic-contrast-enhanced (DCE)-MRI. We investigated the utility of synthetic MRI with relaxometry maps for bpMRI-based diagnosis of csPCa. Methods: One hundred and five treatment-naïve patients who underwent mpMRI and synthetic MRI before prostate biopsy for suspected PCa between August 2019 and December 2020 were prospectively included. Three experts and three basic prostate radiologists evaluated the diagnostic performance of conventional bpMRI and synthetic bpMRI for csPCa. PI-RADS version 2.1 category 3 lesions were identified by consensus, and relaxometry measurements (T1-value, T2-value, and proton density [PD]) were performed. The diagnostic performance of relaxometry measurements for PI-RADS category 3 lesions in peripheral zone was compared with that of DCE-MRI. Histopathological evaluation results were used as the reference standard. Statistical analysis was performed using the areas under the receiver operating characteristic curve (AUC) and McNemar test. Results: In 102 patients without significant MRI artefacts, the diagnostic performance of conventional bpMRI was not significantly different from that of synthetic bpMRI for all readers (p = 0.11–0.79). The AUCs of the combination of T1-value, T2-value, and PD (T1 + T2 + PD) for csPCa in peripheral zone for PI-RADS category 3 lesions were 0.85 for expert and 0.86 for basic radiologists, with no significant difference between T1 + T2 + PD and DCE-MRI for both expert and basic radiologists (p = 0.29–0.45). Conclusion: Synthetic MRI with relaxometry maps shows promise for contrast media-free evaluation of csPCa.

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Effect of gravity on brain structure as indicated on upright computed tomography

Yokoyama Y., Yamada Y., Kosugi K., Yamada M., Narita K., Nakahara T., Fujiwara H., Toda M., Jinzaki M.

Scientific Reports （Scientific Reports）  11 （ 1 ）  2021年12月

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We aimed to use upright computed tomography (CT) to depict posture-related changes in the brain tissue under normal gravity. Thirty-two asymptomatic volunteers underwent upright CT in the sitting position and conventional CT in the supine position on the same day. We compared the shift of the pineal body, cerebellar tonsil, the length of pituitary stalk, optic nerve sheath area and perimeter (ONSA and ONSP, respectively), and lateral ventricular volume between the supine and sitting positions. We also compared shape changes of the cerebrospinal fluid (CSF) spaces at different sites between both positions. In the sitting position, the pineal body shifted 0.68 ± 0.27 mm in the ventral direction and 0.76 ± 0.24 mm in the caudal direction, the length of pituitary stalk decreased by 1.23 ± 0.71 mm, the cerebellar tonsil descended by 2.10 ± 0.86 mm, the right ONSA decreased by 15.21 ± 6.54%, the left ONSA decreased by 15.30 ± 7.37%, the right ONSP decreased by 8.52 ± 3.91%, the left ONSP decreased by 8.20 ± 4.38%, and the lateral ventricular volume decreased by 5.07 ± 3.24% (all P < 0.001). We also observed changes in the shape of CSF spaces with changes in posture. We concluded that the intracranial structure of healthy subjects and volume of ventricles changed according to posture on Earth.

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Orthostatic Enlargement of a Supracerebellar Arachnoid Cyst With Cerebellar Descent Visualized by Upright Computed Tomography

Yoshida K., Toda M., Yamada Y., Yamada M., Yokoyama Y., Fujiwara H., Kosugi K., Sasaki H., Jinzaki M.

World Neurosurgery （World Neurosurgery）  145   256 - 259 2021年01月

ISSN  18788750

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Background: Posterior fossa arachnoid cysts are often asymptomatic, but can rarely cause postural headache, the mechanism of which remains unknown. Case Description: We present a 40-year-old woman with an asymptomatic supracerebellar arachnoid cyst. Upright computed tomography (CT) showed enlargement of the arachnoid cyst and caudal descent of the cerebellum compared with supine CT with narrowing of the craniocervical junction cerebrospinal fluid space. Conclusions: This finding aids in understanding the association of posterior fossa arachnoid cysts with orthostatic headache. Clinicians should be aware of possible posture-related changes in intracranial structures.

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A case of neuromyelitis optica spectrum disorder in which headache preceded visual field disturbances by 2 months

Isago E., Ishizuchi K., Takizawa T., Fujiwara H., Izawa Y., Nakahara J.

Clinical Neurology （Clinical Neurology）  61 （ 11 ） 722 - 726 2021年

ISSN  0009918X

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A quinquagenarian woman visited our hospital due to experiencing headache around the right upper eyelid for the previous 2 months. T2-weighted MRI of the head showed multiple high-signal-intensity lesions in the corpus callosum and bilateral corona radiata. She was thought to have an autoimmune disease and was treated with steroid pulse therapy, but the light reflex of the right eye diminished and the patient developed inferior horizontal hemianopsia. T2-weighted orbital MRI showed an enlarged right optic nerve, a high-intensity signal in the superior half of the optic nerve, and an enhancing effect. She also tested positive for anti-aquaporin 4 antibodies, so she was diagnosed with neuromyelitis optica spectrum disorder (NMOSD). This case shows that headache can be an initial symptom of NMOSD and that clinicians should consider NMOSD when attempting to diagnose patients presenting with headaches.

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The Long-Term Impact of Whiplash Injuries on Patient Symptoms and the Associated Degenerative Changes Detected Using MRI A Prospective 20-Year follow-up Study Comparing Patients with Whiplash-Associated Disorders with Asymptomatic Subjects

Watanabe, Kota MD, PhDa; Daimon, Kenshi MD, PhDa; Fujiwara, Hirokazu MD, PhDb; Nishiwaki, Yuji MD, PhDc; Okada, Eijiro MD, PhDa; Nojiri, Kenya MD, PhDd; Watanabe, Masahiko MD, PhDi; Katoh, Hiroyuki MD, PhDi; Shimizu, Kentaro MD, PhDe; Ishihama, Hiroko MDe; Fujita, Nobuyuki MD, PhDg; Ichihara, Daisuke MD, PhDf; Tsuji, Takashi MD, PhDh; Nakamura, Masaya MD, PhDa; Matsumoto, Morio MD, PhD

Spine （Spine）  46 （ 11 ） 710 - 716 2020年12月

ISSN  03622436

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Study Design.A longitudinal, 20-year comparative study of patients with whiplash-associated disorders (WAD).Objective.The aim of this study was to clarify the long-term impact of WAD on patient symptoms and on magnetic resonance imaging (MRI) findings of the cervical spine, in comparison with asymptomatic volunteers.Summary of Background Data.The long-term impact of WAD has not been fully elucidated.Methods.Between 1993 and 1996, we conducted a cross-sectional comparative study of 508 acute WAD patients and 497 asymptomatic volunteers, all of whom underwent MRI on cervical spine and physical examinations. For this 20-year follow-up comparative study, 75 WAD patients and 181 control subjects aged <60years were recruited from the original cohort. The MRI findings, including discs' signal intensities, posterior disc protrusions, anterior dural compressions, spinal cord disc space narrowing, and foraminal stenoses, were evaluated using two to four numerical grades. The results of the WAD patients and control subjects were compared.Results.In this follow-up, the prevalence of shoulder stiffness (72.0% vs. 45.9%), headache (24.0% vs. 12.2%), and arm pain (13.3% vs. 3.9%) were significantly greater in WAD patients than in control subjects. The multiregression analysis revealed that a history of WAD was associated with shoulder stiffness (odds ratio [OR]: 3.36), headache (OR: 2.39), and arm pain (OR: 3.82). Although MRI findings in WAD patients were more degenerated than in control subjects in the initial study, all MRI findings were similar at the 20-year follow-up. There were no significant correlations between clinical cervical symptoms and progression in each MR finding in either group.Conclusion.After 20years, whiplash injuries significantly impacted the residual symptoms of shoulder stiffness, headache, and arm pain when compared with initially asymptomatic volunteers. The progression of degenerative changes in the cervical intervertebral discs after 20years revealed no association with existing whiplash injuries, neither did the residual cervical-related symptoms.Level of Evidence: 3.

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Posture-induced changes in the vessels of the head and neck: evaluation using conventional supine CT and upright CT

Kosugi K., Yamada Y., Yamada M., Yokoyama Y., Fujiwara H., Yoshida K., Yoshida K., Toda M., Jinzaki M.

Scientific Reports （Scientific Reports）  10 （ 1 ）  2020年12月

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Since the venous system is affected by gravity, upright computed tomography (CT) in addition to conventional supine CT has great potential for evaluating postural changes in the venous system. We evaluated the morphological differences in the head and neck vessels by performing a contrast CT study in both the supine and the sitting positions. In this study, the 20 included participants (10 men and 10 women) were healthy adults aged 30 to 55 years. The cross-sectional area of the cervical vessels, craniocervical junction veins, and intracranial vessels were obtained quantitatively. Venous sinuses and venous plexuses that were difficult to measure were evaluated qualitatively. The average change in areas from a supine to an upright posture was − 77.87 ± 15.99% (P < 0.0001) in the right internal jugular vein (IJV), − 69.42 ± 23.15% (P < 0.0001) in the left IJV, − 61.52 ± 12.81% (P < 0.0001) in the right external jugular vein (EJV), and − 58.91 ± 17.37% (P < 0.0001) in the left EJV. In contrast, the change in the anterior condylar vein (ACV) from a supine to an upright posture was approximately + 144% (P < 0.005) on the right side and + 110% (P < 0.05) on the left side. In addition, according to the qualitative analysis, the posterior venous structures including the anterior condylar confluence (ACC) of the craniocervical junction became more prominent in an upright posture. Despite these changes, the intracranial vessels showed almost no change between postures. From a supine to an upright position, the IJVs and EJVs above the heart collapsed, and venous channels including the ACCs and ACVs opened, switching the main cerebral venous drainage from the IJVs to the vertebral venous system. Upright head CT angiography can be useful for investigating physiological and pathophysiological hemodynamics of the venous system accompanying postural changes.

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123-IMP single-photon emission computed tomography imaging in visual snow syndrome: A case series

Shibata M., Tsutsumi K., Iwabuchi Y., Kameyama M., Takizawa T., Nakahara T., Fujiwara H., Jinzaki M., Nakahara J., Dodick D.W.

Cephalalgia （Cephalalgia）  40 （ 14 ） 1671 - 1675 2020年12月

ISSN  03331024

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Background: Visual snow syndrome (VSS) is a neurological condition characterized by persistent flickering dots in the visual fields, palinopsia, enhanced entoptic phenomenon, photophobia, and nyctalopia. Neuroimaging evidence supports the role of the visual association cortex in visual snow syndrome. Case series: We provided clinical care to three patients with visual snow syndrome, in whom [ I]-IMP single-photon emission computed tomography (SPECT) imaging was performed. Case 1 was a 21-year-old male with a past history of migraine with aura who exhibited visual snow and entoptic phenomenon. In this patient, [ I]-IMP SPECT imaging revealed right occipital and temporal hypoperfusion with a distribution matching the ventral visual stream. [ I]-IMP SPECT imaging detected only mild bilateral frontal hypoperfusion in Case 2 and no overt abnormalities in Case 3. Conclusion: Although visual snow syndrome seems to be a heterogenous condition, our observations indicate that abnormal visual processing within the ventral visual stream may play a role in the pathogenesis of this condition. 123 123 123

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Sinking skin flap syndrome visualized by upright computed tomography

Yoshida K., Toda M., Yamada Y., Yamada M., Yokoyama Y., Fujiwara H., Kosugi K., Fukumura M., Koike K., Takahashi S., Yoshida K., Jinzaki M.

Acta Neurochirurgica （Acta Neurochirurgica）  162 （ 8 ） 1825 - 1828 2020年08月

ISSN  00016268

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Sinking skin flap syndrome is a craniectomy complication characterized by new neurological dysfunction that typically worsens in the upright position and improves after cranioplasty. We present a 33-year-old man who experienced hemiparesis in the upright position after craniectomy. Upright computed tomography (CT) before cranioplasty showed a remarkable shift of the brain compared to supine CT. After cranioplasty, both symptoms and brain shift on CT resolved. Upright CT enables detection and objective evaluation of paradoxical herniation and midline shift that is not obvious on supine imaging modalities. Clinicians need to be aware of positional brain shift in postcraniectomy patients.

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Analysis of the superficial middle cerebral vein in sphenoid ridge meningioma using contrast-enhanced dynamic computed tomography angiography

Murase M., Mizutani K., Kawata K., Fujiwara H., Jinzaki M., Toda M., Yoshida K.

Clinical Neurology and Neurosurgery （Clinical Neurology and Neurosurgery）  191 2020年04月

ISSN  03038467

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Objective: The superficial middle cerebral vein (SMCV) is of clinical importance because of its contribution to the venous drainage of the superficial part of the cerebrum. Sphenoid ridge meningioma (SRM) grows adjacent to the SMCV and its drainage routes, and is thought to occasionally influence the hemodynamics of the SMCV, although this has seldom been suggested in the literature. We investigated the effect of SRM on the SMCV via blood flow analysis using multi-detector computed tomography. Patients and Methods: Overall, 22 patients with SRM who preoperatively underwent contrast-enhanced dynamic computed tomography at our institution were included in this study. We serially measured the Hounsfield units at each point of the SMCV and its adjacent veins on the side on which the tumor was located. We then obtained a time-density curve for each point via gamma distribution fitting. We determined the time-to-peak at each point by calculating the derivative of the time-density curve function and deduced the direction of blood passing through each vein by comparing the time-to-peak values between several points. Results: In total, 26 SMCVs were measured in 19 out of 22 cases. Of the 26 SMCVs, 16 were patent in the medial portion and contributed to normal venous drainage: 4 of them emptied into the cavernous sinus (CS), and 12 of them into the para-cavernous sinus (ParaCS). Out of the 10 that had their medial portions occluded because of the effects of the tumor, 6 SMCVs mainly drained into the vein of Labbé and/or the vein of Trolard retrogradely. However, in 2 of these, the small medial portions of the SMCVs near the occluded portion were maintained anterogradely by the collateral venous structures. In 4 SMCVs, the blood flow through the collateral veins remained anterograde; this was considered to contribute to normal venous drainage. Conclusion: The SRM is likely to cause occlusion or stenosis in the SMCV and influence its hemodynamics. In cases in which the connection between the SMCV and the CS or the ParaCS has been lost, the SMCV may still be involved in normal venous drainage via the collateral veins in some of those cases. Thus, the contribution of these veins to normal venous drainage in the brain should be analyzed preoperatively in careful detail.

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Silent MRA: arterial spin labeling magnetic resonant angiography with ultra-short time echo assessing cerebral arteriovenous malformation

Nobuhiko Arai 1, Takenori Akiyama 2, Hirokazu Fujiwara 3, Kazunari Koike 2, Satoshi Takahashi 2, Takashi Horiguchi 2, Masahiro Jinzaki 3, Kazunari Yoshida 2

Neuroradiology （Neuroradiology）  62 （ 4 ） 455 - 461 2020年01月

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Residual lumbar curvature that developed during adolescence accelerates intervertebral disc degeneration in adulthood

Suzuki S., Fujiwara H., Nori S., Tsuji O., Nagoshi N., Okada E., Fujita N., Yagi M., Nohara A., Kawakami N., Michikawa T., Nakamura M., Matsumoto M., Watanabe K.

Spine Deformity （Spine Deformity）  9 （ 3 ） 711 - 720 2020年

ISSN  2212134X

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Purpose: To elucidate the influence of spinal deformity in adolescent idiopathic scoliosis (AIS) on lumbar intervertebral disc (IVD) degeneration in adulthood using magnetic resonance imaging (MRI). Methods: A total of 102 patients (8 men, 94 women; mean age, 31.4 years) who had developed idiopathic scoliosis at the age of 10–18 years and underwent preoperative lumbar spine MRI at the age of ≥ 20 were included in the study. Twenty volunteers (3 men, 17 women; mean age, 33.6 years) without scoliosis were assessed as controls. We divided the adult scoliosis patients into two groups: Group A consisted of patients with lumbar modifier A, and Group BC consisted of those with modifiers B and C. IVD degeneration from L1/2 to L5/S1 was assessed by MRI. The Scoliosis Research Society-22 (SRS-22) patient questionnaire was used in the patients’ clinical assessment. Results: There were 40 patients in the Group A and 62 in the Group BC. Compared to the control groups, significant IVD degeneration was observed at L2/3 and L3/4 in Group A, and at all levels except for L5/S1 in Group BC. The proportion of degenerated IVDs patients (Grades 1c and 2) was significantly higher in Group BC than those in Group A at L3/L4 and L4/L5. Furthermore, the severity of IVD degeneration was significantly greater in the group BC than in the group A at all levels, except for L5/S1, especially in patients aged > 30 years. The mean scores of all subdomains in the SRS-22 questionnaire were comparable between the two groups. Conclusion: Our study showed that the residual lumbar curvature from AIS may have accelerated IVD degeneration in adulthood, especially in patients aged > 30 years. Level of evidence: III.

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A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2

Tamura R., Fujioka M., Morimoto Y., Ohara K., Kosugi K., Oishi Y., Sato M., Ueda R., Fujiwara H., Noji S., Oishi N., Ogawa K., Kawakami Y., Ohira T., Yoshida K., Toda M.

Nature Communications （Nature Communications）  10 （ 1 ）  2019年12月

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The anti-VEGF antibody bevacizumab has shown efficacy for the treatment of neurofibromatosis type 2 (NF2). Theoretically, vascular endothelial growth factor receptors (VEGFRs)-specific cytotoxic T lymphocytes (CTLs) can kill both tumor vessel cells and tumor cells expressing VEGFRs. Here we show an exploratory clinical study of VEGFRs peptide vaccine in seven patients with progressive NF2-derived schwannomas. Hearing improves in 2/5 assessable patients (40%) as determined by international guidelines, with increases in word recognition scores. Tumor volume reductions of ≥20% are observed in two patients, including one in which bevacizumab had not been effective. There are no severe adverse events related to the vaccine. Both VEGFR1-specific and VEGFR2-specific CTLs are induced in six patients. Surgery is performed after vaccination in two patients, and significant reductions in the expression of VEGFRs in schwannomas are observed. Therefore, this clinical immunotherapy study demonstrates the safety and preliminary efficacy of VEGFRs peptide vaccination in patients with NF2.

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Ten-year Longitudinal Follow-up MRI Study of Age-related Changes in Thoracic Intervertebral Discs in Asymptomatic Subjects

Okada E., Daimon K., Fujiwara H., Nishiwaki Y., Nojiri K., Watanabe M., Katoh H., Ishihama H., Fujita N., Tsuji T., Nakamura M., Matsumoto M., Watanabe K.

Spine （Spine）  44 （ 22 ） E1317 - E1324 2019年11月

ISSN  03622436

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STUDY DESIGN: Prospective longitudinal study. OBJECTIVE: The aim of this study was to evaluate long-term degenerative changes in intervertebral discs in the thoracic spine in healthy asymptomatic subjects. SUMMARY OF BACKGROUND DATA: Longitudinal magnetic resonance imaging (MRI) studies of intervertebral disc degeneration have been reported for the cervical and lumbar but not the thoracic spine. METHODS: In this longitudinal study (average follow-up 10.0 ± 0.6 years), we assessed degenerative changes in the thoracic spine of 103 volunteers (58 men) of 223 healthy volunteers in the initial MRI study of the thoracic spine (follow-up rate 46.2%). The mean age at the initial study was 45.0 ± 11.5 years (24-77 years). Initial and follow-up thoracic-spine MRIs were graded for the following 4 factors of degenerative changes: decrease in signal intensity of intervertebral disc (DSI), posterior disc protrusion (PDP), anterior compression of dura and spinal cord (AC), and disc-space narrowing (DSN) from T1-2 to T12-L1. We assessed associations between changes in MRI grade and demographical factors such as age, sex, body mass index, smoking habits, sports activities, and disc degeneration in the cervical spine. RESULTS: MRIs revealed that 63.1% of the subjects had degenerative changes in the thoracic intervertebral discs that had progressed at least one grade during the follow-up period. DSI progressed in 44.7% of subjects, PDP in 21.4%, and AC in 18.4% during the 10-year period. No DSN progression was seen. DSI was frequently observed in the upper thoracic spine (T1-2 to T4-5). Disc degeneration was relatively scarce in the lower thoracic spine (T9-10 to T12-L1). PDP was frequently observed in the middle thoracic spine (T5-6 toT8-9). We found significant associations between DSI and cervical-spine degeneration (P = .004) and between AC and smoking (P = .04). CONCLUSION: Progressive thoracic disc degeneration, observed in 63.1% of subjects; was significantly associated with smoking and with cervical-spine degeneration.2.

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A Novel Flow Dynamics Study of the Intracranial Veins Using Whole Brain Four-Dimensional Computed Tomography Angiography

Mizutani K., Arai N., Toda M., Akiyama T., Fujiwara H., Jinzaki M., Yoshida K.

World Neurosurgery （World Neurosurgery）  131   e176 - e185 2019年11月

ISSN  18788750

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© 2019 Elsevier Inc. Background: The flow dynamics of the intracranial venous channels are fundamentally important for understanding intracranial physiology and pathophysiology. However, the method clinically applicable to the evaluation of the flow dynamics of the intracranial venous system has not been well described in the reported data. We have developed a new method to evaluate intracranial venous flow direction and velocity using 4-dimensional (4D) computed tomography angiography (CTA). The aim of the present study was to verify the accuracy and validity of 4D-CTA in a clinical setting. Methods: We retrospectively analyzed 97 veins from 26 patients (16 cases of arteriovenous shunt disease, 9 intracranial tumor cases, and 1 cerebral aneurysm case) who had undergone both 4D-CTA and conventional digital subtraction angiography (DSA). Using 4D-CTA, we analyzed the time-density curve with gamma distribution extrapolation and obtained the direction of the flow and flow velocity of each vein. The direction of the flow in 4D-CTA was also collated with that obtained using conventional DSA to verify the experimental method. Results: The direction of the flow determined by 4D-CTA was consistent with that of conventional DSA in 94.8% of cases. The average venous flow velocity was 64.3 mm/second and 81.8 mm/second, respectively, in the antegrade and retrograde channels affected by arteriovenous shunts. Conclusions: The present flow analysis using 4D-CTA enabled us to evaluate the direction and velocity of intracranial venous flow. Other than some limitations, the presented method is reliable and its potential for application in clinical settings is promising.

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Review of synthetic MRI in pediatric brains: Basic principle of MR quantification, its features, clinical applications, and limitations

Andica C., Hagiwara A., Hori M., Kamagata K., Koshino S., Maekawa T., Suzuki M., Fujiwara H., Ikeno M., Shimizu T., Suzuki H., Sugano H., Arai H., Aoki S.

Journal of Neuroradiology （Journal of Neuroradiology）  46 （ 4 ） 268 - 275 2019年07月

ISSN  01509861

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© 2019 Elsevier Masson SAS Quantitative magnetic resonance imaging (MRI)with multislice, multi-echo, and multi-delay acquisition enables simultaneous quantification of R1 and R2 relaxation rates, proton density, and the B1 field in a single acquisition, and requires only about 6 minutes for full-head coverage. Using dedicated SyMRI software, radiologists can generate any contrast-weighted image by manipulating the acquisition parameters, including repetition time, echo time, and inversion time. Moreover, automatic brain tissue segmentation, volumetry, and myelin measurement can also be performed. Using the SyMRI approach, a shorter scan time, an objective examination, and personalized MR imaging parameters can be obtained in daily clinical pediatric imaging. Here we summarize and review the use of SyMRI in imaging of the pediatric brain, including the basic principles of MR quantification along with its features, clinical applications, and limitations.

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Modic changes in the cervical spine: Prospective 20-year follow-up study in asymptomatic subjects

Tsuji T., Fujiwara H., Nishiwaki Y., Daimon K., Okada E., Nojiri K., Watanabe M., Katoh H., Shimizu K., Ishihama H., Fujita N., Nakamura M., Matsumoto M., Watanabe K.

Journal of Orthopaedic Science （Journal of Orthopaedic Science）  24 （ 4 ） 612 - 617 2019年07月

ISSN  09492658

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© 2019 The Japanese Orthopaedic Association Background: Few studies have characterized the development of Modic changes in the cervical spine over time. We evaluated Modic changes of the cervical spine that developed over a 20-year period in a healthy cohort, and sought to clarify the relationship between Modic changes and the development of clinical symptoms. Methods: For this multicenter prospective cohort study, we recruited 193 subjects from an original cohort of asymptomatic volunteers who underwent MRI of the cervical spine between 1993 and 1996. Each cervical level from C2/3 to C7/T1 (total n = 1158 intervertebral levels) was assessed on current MRIs as normal or showing type 1, 2, or 3 Modic change, and we asked about symptoms related to the cervical spine. Relationships between the presence of Modic changes and patient characteristics, pre-existing disc degenerations or clinical symptoms were evaluated by logistic regression analysis. Results: After 20-year follow-up, Modic changes affected 31 subjects (16.1%) at 47 intervertebral disc levels. Of these 47 intervertebral disc levels, type 2, found at 30 levels (63.8%), was the most frequent, followed by type 1 at 15 levels (31.9%) and type 3 at two levels (4.3%). The most frequent changes were observed at the C5/6 segment with type 2 Modic changes. The presence of Modic changes correlated with pre-existing posterior disc protrusion (odds ratio 3.31, 95% confidence interval 1.21–9.05) and neck pain (odds ratio 2.71, 95% confidence interval 1.08–6.80). Conclusions: In the cervical spine over a 20-year period, type 2 Modic changes were most frequent at the C5/6 segment. The Modic changes were associated with pre-existing disc degeneration and neck pain but not with age, BMI, smoking, shoulder stiffness, arm pain or numbness.

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