Role of Computational Fluid Dynamics for Predicting Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: Study Protocol for a Multicenter Prospective Study.

BACKGROUND: Delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). Recently, we reported the possibility that computational fluid dynamics (CFD) could predict DCI in terms of the cross-sectional area and flow velocity of the ipsilateral extracranial internal carotid and distal parent arteries in a single-center retrospective study. METHODS: This is a multicenter, prospective, cohort study. Patients with aneurysmal SAH will undergo CFD analyses using preoperative three-dimensional computed tomography angiography, and we will investigate hemodynamic features of cerebral arteries in an acute stage of SAH. Primary outcome measures will be CFD features in patients with subsequent occurrence of DCI. Secondary outcome measures will be CFD features in patients with subsequent occurrence of cerebral vasospasm and cerebral infarction and the relationships with eventual modified Rankin scale score at 3 months. CONCLUSIONS: The present protocol for a multicenter prospective study is expected to provide a novel diagnostic method to predict DCI before aneurysmal obliteration in an acute stage of SAH.

Prophylactic intra-arterial administration of fasudil hydrochloride for vasospasm following subarachnoid haemorrhage.

PURPOSE: We evaluated patients treated with prophylactic intra-arterial administration of fasudil hydrochloride (IAF) after subarachnoid haemorrhage (SAH). MATERIALS AND METHODS: Between August 1998 and December 2012, 92 patients with aneurysmal SAH were treated with IAF for angiographic vasospasm without ischemic symptoms after their follow-up angiography. Patients comprised 50 women and 42 men, aged 24-83 (mean 56.6) years. IAF consisted of 15 mg of fasudil hydrochloride dissolved in 20 ml physiological saline and injected through a catheter during approximately 15 min, after diagnostic angiography. The clinical outcome was evaluated using the Glasgow Outcome Scale (GOS) at discharge and ischemic lesions resulting from vasospasm were assessed on computed tomography (CT) scan at discharge. RESULTS: Forty-eight patients underwent surgical clipping and 44 patients underwent endovascular coiling. Angiographic improvement was observed in all patients (100 %). At discharge, 76 (83.0 %) of 92 patients showed good recovery on GOS. Nine patients developed progression of delayed ischemic neurological deficits (DIND) and three of these patients had ischemic lesions on CT scans. No patient had any significant changes in vital signs or any other adverse effects resulting from IAF. CONCLUSION: IAF therapy was safe and effective for patients with vasospasm following SAH. Prophylactic IAF therapy may prevent symptomatic vasospasm.

A Perspective on the 6th International Conference on Sports Concussion.

The International Conference on Sports Concussion, held every four years since 2001, has been instrumental in forming the international consensus on sports-related concussions. However, due to the unprecedented global pandemic of COVID-19, not only the Tokyo Olympics 2020, but also the initially scheduled sixth conference was postponed multiple times. Finally, the 6th International Conference on Sports Concussion took place in Amsterdam at the end of October 2022. In July 2023, the Amsterdam Declaration, reflecting the outcomes of this sixth conference, was released. This paper provides an overview of the conference, in which significant updates were revealed and introduced, including revisions to the definition of sports-related concussions, as well as the latest version of the Sports Concussion Assessment Tool (SCAT), known as SCAT6, the Office Assessment Tool (SCOAT), and the updated staged return-to-play protocol.

Delayed Pseudoprogression in Glioblastoma Patients Treated With Tumor-Treating Fields.

Tumor-treating fields (TTFields) is an established treatment modality for glioblastoma. False progression to chemoradiation is a known problem in patients with glioblastoma multiforme (GBM), with most cases occurring within three months of radiation therapy. In this report, we present two cases of delayed pseudoprogression caused by TTFields. Two patients with GBM who received TTFields showed signs of radiographic progression six months after the completion of radiation therapy. Patient 1 was a 37-year-old female with a glioblastoma in the right temporal lobe. Patient 2 was a 70-year-old male with glioblastoma in the left temporal lobe. Both patients received radiation therapy, followed by temozolomide (TMZ) maintenance therapy and TTFields. Patient 1 underwent a second resection; however, the pathology revealed only a treatment effect, and the final diagnosis was a pseudoprogression. In Case 2, the disease resolved with steroid therapy alone. In both patients, the lesions appeared later than during the typical pseudoprogression period. A recent study reported that TTFields increase the permeability of the plasma cell membrane, which may result in further leakage of gadolinium into the extracellular lumen. Further studies are needed to better characterize delayed pseudoprogression and improve treatment outcomes.

Comparative Study of Postmortem MRI and Pathological Findings in Malignant Brain Tumors.

This study compared magnetic resonance imaging (MRI) findings of postmortem brain specimens with neuropathological findings to evaluate the value of postmortem MRI. Postmortem MRI was performed on five formalin-fixed whole brains with malignant tumors. Postmortem T2-weighted images detected all neuropathological abnormalities as high-signal regions but also showed histological tumor invasion in areas without edema. Tumor lesions with high necrosis and edema showed high signal intensity on T2-weighted images; in three cases, lesion enlargement was detected on the final prenatal imaging and postmortem MRI. Disease progression immediately before death may have contributed to this difference. In conclusion, the correlation between MRI and neuropathological findings facilitates understanding of the mechanisms responsible for MRI abnormalities. Increased free water due to edema, necrosis, and brain tissue injury can explain the increased signal intensity observed on T2-weighted images. Postmortem MRI may contribute to effective pathology by identifying subtle abnormalities prior to brain dissection.

Evaluation of Treatment Strategies for Male Prolactin-Secreting Pituitary Neuroendocrine Tumors.

Prolactin-secreting pituitary neuroendocrine tumors (PitNETs) are more common in women. Male patients may also have few symptoms and have macroadenomas extending outside the sella turcica. This study aimed to report the results of cabergoline treatment in male patients with prolactin-secreting PitNET. The study included nine male patients aged 26-65 years (median, 46 years) diagnosed with prolactin-secreting PitNETs. The age at onset, prolactin values, tumor size, symptoms, and treatment were assessed. The mean prolactin value at the initial presentation was 2734.6 ng/mL, and the mean maximum tumor diameter was 40.4 mm. Visual field disturbance was the most common symptom (44.4%), followed by headaches (33.3%), asymptomatic symptoms (11.1%), and galactorrhea (11.1%). Eight patients responded to cabergoline treatment with normalization of prolactin levels and tumor shrinkage. One patient did not respond to the cabergoline treatment and required surgical intervention. There were no cases of cerebrospinal fluid leakage. Cabergoline was found to be an effective treatment for male prolactin-secreting PitNETs.

Predictive Value of Acute Neurological Progression Using Bayesian CT Perfusion for Acute Ischemic Stroke with Large or Median Vessel Occlusion.

Objective: Since the efficacy of mechanical thrombectomy (MT) for acute cerebral infarction due to large vessel occlusion has been proven, the time available for treatment has gradually increased. Currently, under certain conditions, treatment is indicated up to 24 h from onset. Based on neurological signs and imaging diagnosis, Stroke Treatment Guideline 2021 recommends initiation of MT within 6-24 h from onset. Herein, we retrospectively investigated the relationship between cerebral perfusion imaging evaluation and prognosis in patients with acute cerebral infarction due to large or median vessel occlusion. Methods: Fifty-one patients diagnosed with acute cerebral infarction due to large or median vessel occlusions in anterior circulation between November 2019 and December 2021 were divided into medical care and reconstructive therapy (including tissue plasminogen activator [t-PA] therapy and MT) groups. The primary outcome was changes in the National Institutes of Health Stroke Scale (NIHSS) at admission and 1 week after onset. Patients in the medical care group were divided into those whose NIHSS did not worsen and those whose NIHSS worsened. Those in the reconstructive therapy group were divided into those whose NIHSS improved and those whose NIHSS did not improve. We evaluated the relationship between improvement factors in acute neurological symptoms and penumbral and core volumes from computed tomography perfusion performed at admission. Results: Of 45 eligible patients, 10 received medical care without t-PA or MT and 35 underwent reconstructive therapy, including t-PA and MT. Among the 10 patients in the medical care group, 3 had worsening symptoms and 7 did not. The mean and median (interquartile range [IQR]) penumbra volumes were significantly higher in patients with worsening symptoms than in those without. The receiver operating characteristic (ROC) curve showed a threshold value of 28.6 mL with an area under the curve (AUC) of 0.952. Among the 35 patients in the reconstructive therapy group, symptoms improved for 29 but did not improve for 6. The mean and median (IQR) core volumes were significantly higher in patients whose symptoms did not improve than in those whose symptoms improved. The ROC curve showed a threshold value of 25 mL and an AUC of 0.632. Conclusion: Evaluation of penumbra volumes could detect cases with worsening symptoms in cases where medical care was performed, and evaluation of core volumes may detect cases with non-improved symptoms in cases that received reconstructive therapy.

Transport of actin-decorated liposomes along myosin molecules in vitro.

We examined whether actin filaments bound to positively charged liposomes could interact with myosin molecules and induce liposome motility. When liposomes were constructed from the mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and cationic N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium (DOTAP), actin filaments bound to the liposomes. The actin-bound liposomes exhibited movement on myosin molecules in the presence of adenosine-5'-triphosphate (ATP). The displacement was almost linearly increased with time and the behavior differed from that of Brownian motion. Furthermore, the presence of 30% DOTAP in liposomes was most effective for transport. These data show that the actomyosin system was successfully integrated into the liposomes and possesses the ability to actively transport useful agents enclosed within the liposomes.

Support and guide performance comparison of balloon guide catheters.

Background: Several types of balloon guide catheters (BGCs) are used in mechanical thrombus retrieval. However, direct comparisons of their supporting and guiding performance have not been reported. We compared the supporting and guiding performance of the Branchor, Flowgate, and Optimo BGCs using a type 3 aorta artificial vascular model. Methods: An inner catheter was pushed into the artificial vascular model using a linear actuator for the supporting performance evaluation. A previously placed BGC in the internal carotid artery was then intentionally caused to slip. Supporting performance was evaluated by measuring the distance the BGC slipped and generated maximum resistance during Inner catheter insertion. For the guiding performance experiment, a linear actuator was used to guide the BGC into the internal carotid artery of the artificial vessel model. The guiding performance was evaluated by measuring the distance reached by the BGC, maximum resistance generated during insertion of the guiding catheter, and distance the inner catheter slipped. Each experiment was replicated 5 times. Results: No statistically significant differences were observed in the results of the five supporting performance experiments. However, the results of the first and second experiments suggested that the Optimo offers better supporting performance. In the guiding performance experiment, significant differences were observed, suggesting that the Branchor and Flowgate have superior guiding performance in comparison with the Optimo. Conclusion: The Optimo offered superior supporting performance, while the Branchor and Flowgate showed better guiding performance than the Optimo.

Experimental Safety Evaluation of Inflated Assisting Balloons for Endovascular Surgery.

Objective: The balloon-assisted technique is one of the methods used for cerebral aneurysm embolization. There are several applications of assisting balloons such as remodeling the neck of cerebral aneurysms, protecting blood vessel branches, and stabilizing the microcatheter. In this study, we measured the pressure inside inflated assisting balloons to assess safety or procedure. Methods: A T-junction silicone model was used. The pressure inside the balloon inflated to the set herniation levels in the T-junction model was measured using a fiber pressure sensor. We compared the pressure and difference between each assisting balloon. Results: The pressure required for inflating the balloon to the set herniation level in the T-junction model varied depending on the type of assisting balloon. The results suggest that differences in pressure among inflated balloons are likely attributable to differences in the materials used in the lumens of the balloons. Conclusion: The pressure inside various inflated assisting balloons was measured for comparison and differences were found. This experiment contributes to the safety of the balloon-assisted technique.

Dynamics of global gene expression changes during brain metastasis formation.

As methods of cancer diagnosis and treatment improve, interest in metastatic brain tumors continues to increase. In the present study, we attempted to characterize genetically the dynamic changes occurring during brain metastasis formation by DNA microarray, and attempted to compare these findings with histological observations. Lewis lung carcinoma cells were injected into C57BL/6Ncrj mice carotid arteries. The mice were sacrificed at days 1-9 after injection. We performed histological observation and genome-wide expression profiling using a DNA microarray. In histological observation, tumor cells were observed in capillary vessels at day 1 after injection. At day 3, the tumor cells had begun to proliferate. At day 6, the metastatic foci showed "perivascular proliferations". Next, we performed a pairwise comparison of gene expression microarray data from day 1 to day 9 after injection. The first major change occurred between Phase Two and Phase Three. When hierarchical clustering was performed between different samples using the 867 genes, they could be classified into identical clusters for days 1 and 2, identical clusters for day 3 to day 5, and identical clusters for day 6 to day 9. For time course analysis, we extracted 623 genes by the pairwise comparison. By using the quality threshold (QT) nonhierarchical clustering method, we identified 37 expression patterns. These patterns can be separated into eight clusters by using the k-means method. The microarray results reported here strongly suggest that a large number of genes exhibit a spike pattern, which is tantamount to phase-specific expression.

Measurement of cerebral vascular reserves with I-123 IMP SPECT without an arterial input function using the microsphere model and radiopharmaceutical dose calibration.

OBJECTIVES: Cerebral vascular reserve (CVR) is an important indicator for the management of and therapy for cerebral arterial occlusive disease (CAOD). Vasodilatory function is measured using the standard IMP-ARG method. The IMP autoradiography (IMP-ARG) method employed here uses a standardized input function, which was derived from 12 patients between 31 and 71 years of age. Because the population of elderly patients continues to increase in Japan, additional therapies are required to assess CVR in elderly patients with chronic cardiopulmonary disease or a history of smoking, in particular. Despite its popularity, alternatives to the IMP-ARG method are necessary. Here, we proposed the microsphere (MS) method without an input function. METHOD: Using this method and the IMP-ARG method, we measured the CVRs of 18 CAOD patients. RESULTS: The CVRs derived with these two methods were significantly and linearly correlated (r = 0.89, p < 0.01). CVRs categorized by severity were also found to correspond between the two methods (κ = 0.87). CONCLUSIONS: Thus, the method proposed here may serve as a supplemental to and be compatible with the IMP-ARG method for the assessment of CVR. Furthermore, the two methods, when used in conjunction, may result in less error than either would alone.

The Oncogene Addiction Switch from NOTCH to PI3K Requires Simultaneous Targeting of NOTCH and PI3K Pathway Inhibition in Glioblastoma.

The NOTCH pathway regulates neural stem cells and glioma initiating cells (GICs). However, blocking NOTCH activity with γ-secretase inhibitors (GSIs) fails to alter the growth of GICs, as GSIs seem to be active in only a fraction of GICs lines with constitutive NOTCH activity. Here we report loss of PTEN function as a critical event leading to resistance to NOTCH inhibition, which causes the transfer of oncogene addiction from the NOTCH pathway to the PI3K pathway. Drug cytotoxicity testing of eight GICs showed a differential growth response to GSI, and the GICs were thus stratified into two groups: sensitive and resistant. In the sensitive group, GICs with loss of PTEN function appeared less sensitive to GSI treatment. Here we show that NOTCH regulates PTEN expression and the activity of the PI3K pathway in GICs, as treatment with GSI attenuated the NOTCH pathway and increased PTEN expression. NOTCH regulates PTEN expression via Hes-1, as knockdown of Notch or Hes1 increased expression of PTEN. This novel observation suggests that both pathways must be simultaneously inhibited in order to improve therapeutic efficacy in human glioblastomas (GBMs).

Genetic and Lineage Classification of Glioma-Initiating Cells Identifies a Clinically Relevant Glioblastoma Model.

The Cancer Genome Atlas (TCGA) project described a robust gene expression-based molecular classification of glioblastoma (GBM), but the functional and biological significance of the subclasses has not been determined. The present comprehensive analysis of 25 glioma-initiating cell (GIC) lines classifies GIC lines into four subtypes (classical, mesenchymal, proneural, and neural) that are closely related to the TCGA GBM subclasses and display distinct lineage characteristics and differentiation behavior that recapitulate neural development. More importantly, the GIC subtypes exhibit distinct biological phenotypes in relation to self-renewal capacity, proliferation, invasiveness, and angiogenic potential in vitro and in vivo. In addition, the GIC subtypes exhibit divergent patterns of signaling pathway activation and deactivation of the Wnt, Notch, and TGF-ß pathways. These results will improve drug discovery targeting certain genetic mutation in glioblastoma and improve the development of precision medicine.

Comparison of metastatic brain tumour models using three different methods: the morphological role of the pia mater.

As methods of cancer diagnosis and treatment progress, interest in metastatic brain tumours continues to increase. There are many studies using various methods of animal model and we considered that each model reflects different pathological processes because of the unique composition of the brain. We prepared metastatic brain tumour models using three different methods. In this study, we attempted to elucidate the roles of the pia mater in brain metastasis. The metastatic foci showed an angiocentric pattern, forming collars of neoplastic cells, and were designated 'perivascular proliferations'. Furthermore, we observed neoplastic cells that infiltrated the brain parenchyma, the border of which had become indistinct. These were labelled 'invasive proliferations'. The internal carotid artery injection model reflects haematogenous metastasis. In this model, both perivascular and invasive proliferations were observed. The intrathecal injection model reflects leptomeningeal carcinomatosis. In this model, metastasis to the meninges was observed. In the stereotactic injection model, the tumour proliferation at the injection site and the infiltration into the brain parenchyma were observed. The pia-glial membrane serves as a scaffold when neoplastic cells spread to the perivascular space forming angiocentric pattern. The pia-glial membrane is found between the brain parenchyma and blood vessels. Blood vessels penetrate the brain through tunnels known as perivascular spaces that are covered by pia mater. Three different methods which we prepared reflect three different pathological processes. Our findings suggest that the pia mater is a critical factor in brain metastasis.

Corrigendum to "Relationship between the Direction of Ophthalmic Artery Blood Flow and Ocular Microcirculation before and after Carotid Artery Stenting".

[This corrects the article DOI: 10.1155/2016/2530914.].

Intra-arterial administration of fasudil hydrochloride for vasospasm following subarachnoid hemorrhage - analysis of time-density curve with digital subtraction angiography.

The cerebral circulatory dynamics were evaluated before and after intra-arterial administration of fasudil hydrochloride in 20 patients with angiographic vasospasm after subarachnoid hemorrhage (SAH). The region of interest time-density curves obtained before and after intra-arterial administration of fasudil hydrochloride were compared in the proximal portion of the middle cerebral artery in the early arterial phase, the distal portion of the middle cerebral artery in the late arterial phase, and the transverse sinus in the venous phase. In the early arterial phase, the time to peak and the time to half-peak were significantly reduced. In the late arterial phase and venous phase, the time to peak was significantly reduced. These results suggest that intra-arterial administration of fasudil hydrochloride induced dilation of the proximal arteries, and improved cerebral microcirculation. The present study suggests that intra-arterial administration of fasudil hydrochloride is effective as a treatment for vasospasm following SAH.

[A case of encapsulated intracerebral hematoma mimicking metastatic brain tumor].

We report a case of encapsulated intracranial hematoma (EIH) mimicking metastatic brain tumor. A 77-year-old male with a medical history of prostate cancer was admitted to our hospital presenting with progressive left hemiparesis. Previous head CT scan and MRI findings during 3 weeks before admission revealed a subcortical acute to subacute hematoma under the right precentral gyrus with growing perifocal brainedema. The Head DSA showed tumor-stain with vascular compression corresponding to the hemorrhagic mass, and Tl-201 SPECT study revealed high L/N ratio (3.0) and high L/E ratio (0.8). The preoperative diagnosis was metastatic brain tumor originating from prostate cancer, and total removal of the mass was undergone with the postoperative diagnosis of EIH. Neither tumoral component nor vascular malformation was found even by detailed pathological study. EIH is a rare variant of intracranial hemorrhage and most of cases in past reports are preoperatively misdiagnosed as malignant brain tumor. In our case, even Tl-201 SPECT and DSA, which are reported as key studies for distinguishing EIH from other brain tumors, demonstrated brain tumor-like findings. It is necessary to consider the possibility of EIH when we encounter hemorrhagic mass in the brain parenchyma even with brain tumor-like radiographical images.