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Simple Summary: To test the hypothesis that quantitative magnetic resonance relaxometry reflects glioma tumor load within tissue and that it can be an imaging surrogate for visualizing non-contrast-enhancing tumors, we investigated the correlation between T1- and T2-weighted relaxation times, apparent diffusion coefficient (ADC) on magnetic resonance imaging, and 11C-methionine (MET) on positron emission tomography (PET). Moreover, we compared T1- and T2-relaxation times and ADC with tumor cell density (TCD) findings obtained via stereotactic image-guided tissue sampling. A T1-relaxation time of >1850 ms but <3200 ms or a T2-relaxation time of >115 ms but <225 ms under 3 T indicated high MET uptake. The stereotactic tissue sampling findings confirmed that the T1-relaxation time of 1850–3200 ms significantly indicated higher TCD while the T2-relaxation time and ADC did not significantly correlate with the stereotactic tissue sampling findings. However, synthetically synthesized tumor load images from the T1- and T2-relaxation maps were able to visualize MET uptake presented on PET. One of the most crucial yet challenging issues for glioma patient care is visualizing non-contrast-enhancing tumor regions. In this study, to test the hypothesis that quantitative magnetic resonance relaxometry reflects glioma tumor load within tissue and that it can be an imaging surrogate for visualizing non-contrast-enhancing tumors, we investigated the correlation between T1- and T2-weighted relaxation times, apparent diffusion coefficient (ADC) on magnetic resonance imaging, and 11C-methionine (MET) on positron emission tomography (PET). Moreover, we compared the T1- and T2-relaxation times and ADC with tumor cell density (TCD) findings obtained via stereotactic image-guided tissue sampling. Regions that presented a T1-relaxation time of >1850 ms but <3200 ms or a T2-relaxation time of >115 ms but <225 ms under 3 T indicated a high MET uptake. In addition, the stereotactic tissue sampling findings confirmed that the T1-relaxation time of 1850–3200 ms significantly indicated a higher TCD (p = 0.04). However, ADC was unable to show a significant correlation with MET uptake or with TCD. Finally, synthetically synthesized tumor load images from the T1- and T2-relaxation maps were able to visualize MET uptake presented on PET. [ABSTRACT FROM AUTHOR]

There is a lack of data regarding the safety and effectiveness of implanting the Pipeline Embolization Device with Shield technology (PED-Shield) compared with the previous generation of Pipeline (PED-Flex). This retrospective single-center study aimed to compare treatment outcomes between the PED-Shield and PED-Flex for treating unruptured internal carotid artery aneurysms. The PED-Flex was used in 62 procedures (67 aneurysms, 59 patients) and the PED-Shield in 53 procedures (59 aneurysms, 58 patients). The mean aneurysm diameter was significantly lower in the PED-Shield group than in the PED-Flex group (11.9 ± 7.0 mm vs. 15.2 ± 6.9 mm, p < 0.001). At the 12-month follow-up, the complete angiographic occlusion rate was 72.1% and 72.3% in the PED-Flex and PED-Shield groups, respectively (p = 0.9808). Limited to aneurysms larger than 10 mm, 70.6% and 68.0%, respectively (p = 0.8175). The incidence of more than three high signal intensity areas on diffusion-weighted imaging after treatment was significantly lower in the PED-Shield group than in the PED-Flex group (27.7% vs. 67.7%; p < 0.001). Limited to aneurysms larger than 10 mm, 41.1% and 69.6%, respectively (p < 0.0117). Symptomatic ischemic complications occurred within 30 days of four PED-Flex procedures (6.5%) and one PED-Shield procedure (2.0%) (p = 0.2315). Limited to aneurysms larger than 10 mm, 1.8% and 3.2%, respectively (p = 0.6677). The incidence of mRS score worsening at 6 months was 3.2% and 1.9% in the PED-Flex and PED-Shield groups, respectively (p = 0.6534). The PED-Shield can achieve outcomes equivalent to or better than the PED-Flex. Further large-scale studies are warranted to confirm our findings.

Background: The ONO-4059-02 phase 1/2 study showed favorable efficacy and acceptable safety profile of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, for relapsed/refractory primary central nervous system lymphoma (PCNSL). Here, we report the long-term efficacy and safety after a 3-year follow-up., Methods: Eligible patients were aged ≥ 20 years with histologically diagnosed PCNSL and KPS of ≥ 70. Patients received oral tirabrutinib once daily at 320 or 480 mg, or 480 mg under fasted conditions., Results: Between October 19, 2017, and June 13, 2019, 44 patients were enrolled: 33 and 9 had relapsed and refractory, respectively. The 320, 480, and 480 mg fasted groups included 20, 7, and 17 patients, respectively. The median follow-up was 37.1 months. The overall response rate was 63.6% (95% CI: 47.8-77.6) with complete response (CR), unconfirmed CR, and partial response in 9, 7, and 12 patients, respectively. The median duration of response (DOR) was 9.2 months, with a DOR rate of 19.8%; the median progression-free survival (PFS) and median overall survival (OS) were 2.9 months and not reached, respectively, with PFS and OS rates of 13.9% and 56.7%, respectively. Adverse events occurred in 38 patients (86.4%): grade ≥ 3 in 23 (52.3%) including 1 patient with grade 5 events. KPS and quality of life (QoL) scores were well maintained among patients receiving long-term treatment., Conclusions: The results demonstrated the long-term clinical benefit of tirabrutinib, with deep and durable response in a subset of patients and acceptable safety profile, while KPS and QoL scores were maintained., Competing Interests: All authors received support for developing the manuscript, which includes funding, medical writing, and article processing charge. HY reports honoraria from Ono, Chugai, Fujifilm, and Novocure global. YN reports grants from Chugai, Sumitomo Pharma, Eisai, Otsuka, SBI, AbbVie, Daiichi Sankyo, Stella Pharma, and Meiji Seika; honoraria from Chugai, Sumitomo Pharma, Eisai, Otsuka, SBI, AbbVie, Daiichi Sankyo, Stella Pharma, and Meiji Seika. MN reports grants from Chugai, MSD, Nippon Kayaku, Bristol Myers Squibb, Pfizer, Takeda, Shionogi, Kyowa Kirin, Teijin Pharma, Asahi Kasei Medical, HOYA Technosurgical, AbbVie, Eisai, Daiichi Sankyo, Otsuka, Astellas, Tsumura, Sanofi, Mitsubishi Tanabe Pharma, Sanei, CSF Behring, and Ono; consulting fees from Ono, Nippon Shinyaku, and Novocure; honoraria from Chugai, MSD, Nippon Kayaku, UCB Japan, Sumitomo Pharma, Ono, Ohara, AbbVie, Eisai, Daiichi Sankyo, Novocure, Bristol Myers Squibb, and Kyowa Kirin; support for attending meetings and/or travel from Ono, Eisai, Denka, Kyowa Kirin, and Nippon Kayaku; Participation on a Data Safety Monitoring Board or Advisory Board in Novocure; and medical writing support from Ono and Chugai. KM reports grants from Chugai, Eisai, Gunze Medical, Otsuka, Nihon Medi-Physics, Gunze, Stryker Japan, Kyowa Kirin, MSD, Teijin Pharma, AbbVie, Daiichi Sankyo, Novocure, HOYA Technosurgical, Ohara, and CSL Behring; and honoraria from Ono and Chugai. YA reports grants from Philips, Otsuka, Chugai, Nihon Medi-Physics, Daiichi Sankyo, Stryker, Eisai, Japan Blood Products Organization, Ono, Taiho, Sumitomo Pharma, Astellas, Incyte Biosciences, and Servier; and honoraria for lectures from Nippon Kayaku, Novocure, UCB Japan, Ono, Brainlab, Merck, Chugai, Eisai, Daiichi Sankyo, Carl Zeiss, and Nihon Medi-Physics. KA reports honoraria and support for attending meetings and/or travel from Ono. NF reports grants from Ono, Bayer, Chugai, Celgene, and Genmab and Incyte; honoraria from AstraZeneca, Bristol Myers Squibb, Chugai, CSL Behring, Sumitomo Pharma, Eisai, Janssen, Kyowa Kirin, Nippon Shinyaku, Novartis, Ono, Otsuka, Sanofi, SymBio, Takeda, and Zenyaku; and participation on a data safety monitoring board in Huya Japan and an advisory board in AstraZeneca, AbbVie, Eli Lilly, Genmab, and Novartis. KS reports honoraria from Daiichi Sankyo, Eisai, Meiji Seika Pharma, Bristol Myers Squibb, Novartis, Ono, and Nobel Pharma. AA is employed in Ono and holds stocks of Ono. RN reports grants from MSD, Eisai, AbbVie, and Chugai; and consulting fee from Novocure; honoraria from AbbVie, Chugai, Daiichi Sankyo, Eisai, Novocure, and Ono., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Objective: An intraosseous arteriovenous fistula (AVF) is a rare fistula with an intracranial shunted pouch. A case of an intraosseous AVF at the squamous part of the occipital bone with spontaneous occlusion of diploic venous drainage is described., Case Presentation: The patient, a Japanese woman in her 80s, presented with headaches at the back of the head and a history of multiple unruptured cerebral aneurysms but no recent head trauma. MRA showed abnormal signals in the occipital diploic region, and DSA showed an intraosseous AVF with a shunted pouch in the squamous part of the occipital bone near the inion. This was not seen on MRA 6 months earlier. One month later, follow-up examinations showed spontaneous occlusion of the diploic venous drainage, leading to a change in retrograde drainage into the superior sagittal sinus. Transvenous coil embolization was performed, and the shunted pouch was completely occluded. Postoperatively, the patient's symptoms resolved, and subsequent follow-ups showed no recurrence of the AVF., Conclusion: This case suggested that the vascular architecture of intraosseous AVFs might change over a short period. Transvenous embolization was effective in obliterating the intraosseous shunted pouch., (©2024 The Japanese Society for Neuroendovascular Therapy.)

Objective: Treatment of anterior choroidal artery (AChA) aneurysms is frequently associated with ischemic complications. This study aimed to report the outcomes of treatment of unruptured AChA aneurysms in our hospital., Methods: Between January 2015 and March 2022, 40 patients were treated for an unruptured AChA aneurysm in our hospital. Age, sex, aneurysm size, AChA branching type, treatment, occlusion rate, complications, modified Rankin Scale (mRS) score before surgery and after 90 days, and recurrence were investigated. The branching type was classified as internal carotid artery (ICA), neck, or dome type based on the location of the AChA origin., Results: The mean age was 61.1 ± 1.9 years; 15 patients were men and 25 were women. The mean aneurysm diameter was 4.4 ± 0.3 mm. The branching type was ICA in four patients, neck in 35, and dome in one. Treatment was surgical clipping in 22 patients and endovascular coil embolization in 18 (14 with stent assistance). Motor-evoked potential (MEP) monitoring was used in all patients of the clipping group and 9 cases of the coiling group. Treatment complications occurred in eight patients (20%). mRS score worsened by more than one point 90 days after treatment in four patients (10%); however, the proportion of patients who experienced this did not significantly differ between the clipping and coiling groups. Although the odds of a thrombotic complication were higher with coiling than clipping, the difference was not significant (odds ratio: 10.2; P = 0.08). The rate of complete occlusion was lower in the coiling group (72.2% vs. 95.3%), but the difference was not significant. The median follow-up was 696 days (range: 99-2053). No aneurysm recurrence or rupture occurred., Conclusion: AChA branching type is important for treatment decision-making in patients with AChA aneurysms. Rates of complications and occlusion do not significantly differ between clipping and coiling of AChA aneurysms. MEP monitoring may be useful in preventing thrombotic complications during coil embolization., (©2024 The Japanese Society for Neuroendovascular Therapy.)

Objective: The authors sought to compare methods of measurement for venous phase delay (VPD) or mean stump pressure (MSTP) to rank their potential to predict ischemic tolerance during balloon test occlusion in the internal carotid artery, exploring a more correlative and convenient way to measure cerebral blood flow (CBF) that could be utilized even in the acute phase or in institutions not adequately equipped to measure CBF during the test., Methods: X-ray angiography perfusion analysis using diagnostic digital subtraction angiography (DSA) equipment enables 1-step examination (without any room-to-room transfer of patients) to measure CBF, VPD, and MSTP completely simultaneously, which has not been accomplished by any previous perfusion studies., Results: This analysis was applied to 17 patients and resulted in successful estimation of all 3 parameters in each case. The average VPD of several cortical veins had a strong correlation with relative CBF (rCBF) between bilateral hemispheres with a correlation coefficient of 0.89443, a correlation as strong as that (0.90357) of the "approximate VPD," which is interpreted based on the trend line of the scatterplot of the time to peak contrast opacification in cortical veins and their spatial positioning from the median sagittal plane. MSTP and classic visual determination of VPD have weaker correlation coefficients with rCBF (0.56119 and 0.70048, respectively). Overall, subjective visual determination in combination with the calculation of the trend line to estimate VPD provided a considerably strong correlation with rCBF (R = 0.86660) without any dedicated software or hardware., Conclusions: VPD has a stronger correlation with rCBF than MSTP. rCBF could be successfully predicted on common DSA equipment, even by visual determination without expensive software, if the trend line is adopted for processing to estimate VPD.

Background: X-ray angiography perfusion (XAP) is a perfusion imaging technique based on conventional DSA., Objective: In this study, we aimed to validate parameters derived from XAP by comparing them with 15 O-gas/water positron emission tomography (PET), using data from patients with chronic ischemic cerebrovascular disease., Methods: 18 consecutive patients were included. XAP was performed with intra-arterial infusion of contrast media, and a time-density curve was constructed for each cerebral hemisphere. From the curves, the relative values of mean transit time (rMTT) and wash-in rate (rWiR) were obtained by dividing the values of the right hemisphere by those of the left hemisphere. These were then compared with the relative values of cerebral blood flow (rCBF) and rMTT calculated from the PET data., Results: XAP rWiR correlated strongly with PET rCBF (r=0.86, P<0.0001). rMTT measurements from the two modalities were also strongly correlated (r=0.85, P<0.0001). Bland-Altman analysis revealed a bias of 0.14±0.18 (95% limits of agreement -0.22 to 0.51) for PET rCBF versus XAP rWiR, and 0.016±0.093 (95% limits of agreement -0.17 to 0.20) for rMTT between the two modalities., Conclusions: The relative values obtained from XAP were validated across a population of patients with chronic ischemic cerebrovascular disease., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Two cases of ruptured blood blister-like internal carotid artery aneurysms for which low flow bypass was sufficient to attain successful treatment of trapping are reported. In the acute stage of rupture, it is troublesome to perform accurate examinations of tolerance to ischemia like balloon occlusion test(BOT)for estimating the required amount of bypass flow. In our cases, X-ray angiography perfusion(XAP)analysis was introduced, which could be performed in a couple dozen seconds without room-to-room transfer of patients, following the ordinary examination of diagnostic digital subtraction angiography. The perfusion index(PI)ratio measured in this analysis is equivalent to the laterality of cerebral blood flow between the right and left hemispheres. The PI ratio of 0.85 approximately corresponds to the mean stump pressure(MSTP)of 40mmHg, on the basis of the correlation diagram between the PI ratio and MSTP(approximate straight line:PI ratio%=0.6×MSTP+60). Even though the PI ratio of the cases was superior to this threshold of tolerance for parent artery occlusion, complementary low flow bypass was added in the acute case for the overwhelming succeeding vasospasm and for securing the flow to peripheral perforators, which resulted in a successful treatment without any ischemic events.

Cryptococcosis is a fungal infection, which mainly invades the lungs and central nervous system. In Japan, most cases of cryptococcosis are caused by Cryptococcus neoformans(C. neoformans). Until now, only three cases which the infectious agent was Cryptococcus neoformans var. gattii(C. gattii)have been reported. As compared with cryptococcosis caused by C. neoformans, which is often observed in immunocompromised hosts, cryptococcosis caused by C. gattii occurs predominantly in immunocompetent hosts and is resistant to antifungal drugs. Here, we report a case of refractory cerebral cryptococcoma that was successfully treated by surgical resection of the lesions. A 33-year-old man with no medical history complained of headache, hearing disturbance, and irritability. Pulmonary CT showed a nodular lesion in the left lung. Cerebrospinal fluid examination with Indian ink indicated cryptococcal meningitis, and PCR confirmed infection with C. gattii. C. gattii is usually seen in the tropics and subtropics. Since this patient imported trees and soils from abroad to feed stag beetles, parasite or fungal infection was, as such, suspected. Although he received 2 years of intravenous and intraventricular antifungal treatment, brain cryptococcomas were formed and gradually increased. Because of the refractory clinical course, the patient underwent surgical resection of the cerebral lesions. With continuation of antifungal drugs for 6 months after the surgeries, Cryptococcus could not be cultured from cerebrospinal fluid, and no lesions were seen on MR images. If cerebral cryptococcosis responds poorly to antifungal agents, surgical treatment of the cerebral lesion should be considered.

A 50-year-old man presented with altered mental status during hospitalization for pneumonia. MRI showed multifocal ring-enhanced lesions, which consisted of multiple cerebral abscesses. We started empirical antibiotic therapy, but the following morning, his condition rapidly deteriorated and a CT scan revealed acute hydrocephalus, which required ventricular drainage. Gram staining of cerebro-spinal fluid from the ventricular drainage showed gram-positive cocci in chains, but culture results were negative. 16S ribosomal RNA sequencing with broad-range PCR of the cerebro-spinal fluid identified Streptococcus intermedius. On the basis of this identification, the antibiotic regimen was changed to ampicillin monotherapy. After 1 year of antibiotic therapy, all the abscesses had disappeared and the patient was discharged without any sequelae. Bacterial 16S rRNA gene analysis with broad-range PCR is a very useful method for facilitating the etiological diagnosis and selection of appropriate treatment for culture-negative infections.