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Background/Objectives : Bilateral steno-occlusive disease of the internal carotid artery (ICA) carries an increased stroke risk with associated high morbidity and mortality. Management of these patients is often complex. In this study, we evaluate the value of non-invasive optimal vessel analysis quantitative magnetic resonance angiography (NOVA-qMRA) for studying flow and collateral patterns in patients with bilateral carotid steno-occlusive disease. Methods : Patients with bilateral ICA-stenosis ≥ 50% who received NOVA-qMRA were included in this study. The volume flow rates (VFRs) of the A2-segment of the anterior cerebral artery (A2-ACA), M1-segment of the middle cerebral artery (M1-MCA), and P2-segment of the posterior cerebral artery (P2-PCA) were analyzed. Demographic, clinical, and treatment data were collected. Results : Twenty-two patients (mean age ± SD: 68 ± 10 years) were included. Nineteen patients (86%) were symptomatic. Thirteen patients (59%) were revascularized; among them, M1-VFR was significantly lower ( p -value = 0.01) on the side selected for revascularization (88 mL/min ± 53) compared to the contralateral one (130 mL/min ± 56). P2-VFR was significantly higher ( p -value = 0.04) in the treated subgroup (108 mL/min ± 41) than in the non-treated one (83 mL/min ± 34). Conclusions : The present study supports the use of NOVA-qMRA to study flow and collateral patterns in patients with bilateral steno-occlusive carotid disease, especially M1- and P2-VFR. This information may be helpful for decision-making and to tailor revascularization treatment.

Background: Management of unruptured intracranial aneurysms (UIAs) is complex, balancing the risk of rupture and risk of treatment. Therefore, prediction scores have been developed to support clinicians in the management of UIAs. We analyzed the discrepancies between interdisciplinary cerebrovascular board decision-making factors and the results of the prediction scores in our cohort of patients who received microsurgical treatment of UIAs., Methods: Clinical, radiological, and demographical data of 221 patients presenting with 276 microsurgically treated aneurysms were collected, from January 2013 to June 2020. UIATS, PHASES, and ELAPSS were calculated for each treated aneurysm, resulting in subgroups favoring treatment or conservative management for each score. Cerebrovascular board decision-factors were collected and analyzed., Results: UIATS, PHASES, and ELAPSS recommended conservative management in 87 (31.5%) respectively in 110 (39.9%) and in 81 (29.3%) aneurysms. The cerebrovascular board decision-factors leading to treatment in these aneurysms (recommended to manage conservatively in the three scores) were: high life expectancy/young age (50.0%), angioanatomical factors (25.0%), multiplicity of aneurysms (16.7%). Analysis of cerebrovascular board decision-making factors in the "conservative management" subgroup of the UIATS showed that angioanatomical factors (P=0.001) led more frequently to surgery. PHASES and ELAPSS subgroups "conservative management" were more frequently treated due to clinical risk factors (P=0.002)., Conclusions: Our analysis showed more aneurysms were treated based on "real-world" decision-making than recommended by the scores. This is because these scores are models trying to reproduce reality, which is yet not fully understood. Aneurysms, which were recommended to manage conservatively, were treated mainly because of angioanatomy, high life expectancy, clinical risk factors, and patient's treatment wish. The UIATS is suboptimal regarding assessment of angioanatomy, the PHASES regarding clinical risk factors, complexity, and high life expectancy, and the ELAPSS regarding clinical risk factors and multiplicity of aneurysms. These findings support the need to optimize prediction models of UIAs.

Background and Purposes: Non-invasive optimal vessel analysis quantitative magnetic resonance angiography (NOVA-QMRA) has emerged as a valuable tool to characterize cerebral hemodynamics in intracranial atherosclerotic disease (ICAD). Our aim was to explore the eventual correlation between volume flow rate (VFR) measured via NOVA-QMRA and signal intensity ratio (SIR) of time-of-flight (TOF) MRA in M1- and P2-segments bilaterally in patients with unilateral internal carotid artery (ICA) occlusion., Materials and Methods: Patients with acute, subacute or chronic unilaterall ICA occlusion receiving NOVA-QMRA between June 2019 and June 2021 were retrospectively included. In bilateral M1- and P2-segments VFR was assessed by means of NOVA-QMRA and a region of interest (ROI) was selected to measure TOF SIR. A correlation between TOF SIR and VFR was tested by means of Pearson correlation coefficient. Mean difference of TOF SIR and VFR between ipsilateral (to occluded ICA) and contralateral M1- and P2-segments was analyzed using a two-sided Welch's t test., Results: Fifty-five patients with unilateral ICA occlusion were included (acute: 28; subacute: 8; chronic: 19). Both ipsilateral (r = 0.536, p < 0.001) and contralateral (r = 0.757, p < 0.001) TOF SIR correlated significantly with NOVA VFR. This observation proved especially true for patients with chronic ICA occlusion. Both VFR (165.18 vs 110.60, p < 0.001) and TOF SIR (4.96 vs 2.70, p < 0.001) were higher in contralateral than ipsilateral M1-segments; whereas, the contrary was observed for P2-segments (VFR 72.35 vs 102.12, p < 0.001, TOF SIR 2.87 vs 3.39, p = 0.016)., Conclusion: The study results showed that TOF SIR significantly correlated with phase-contrast derived flow volume in patients with symptomatic ICA occlusion. This correlation remains the same regardless of the stage of the ischemic stroke (acute vs subacute vs chronic). Furthermore, significantly high VFR and TOF SIR in ipsilateral P2-segments may provide evidence of leptomeningeal collateralization in acute patients. Standardly performed TOF SIR Sequences might be of help for a qualitative evaluation of the flow in M1- and P2-segments in patients with unilateral ICA occlusions. NOVA QMRA allows precise quantitative measurements of the flow in cerebral vessels., Competing Interests: Declarations. Conflict of interest: No conflicts of interest nor financial funding to disclose. Ethical approval: The study was approved by the local Ethics Committee and performed in accordance with the Declaration of Helsinki. Human or animal rights: Research on human participants. Informed consent: Patients provided informed consent for the use of personal data for scientific purposes at the time of admission., (© 2024. The Author(s).)

Background and Purpose: Identifying and assessing hemodynamic and flow status in patients with symptomatic internal carotid artery (ICA) occlusion is crucial for evaluating recurrent stroke risk. The aim of this study was to analyze the correlation between two quantitative imaging modalities: (1) blood oxygenation level-dependent (BOLD) cerebrovascular reactivity (CVR) and (2) quantitative magnetic resonance angiography (qMRA) with non-invasive optimal vessel analysis (NOVA), measuring volume flow rate (VFR). Comparing these modalities is relevant for assessing collateral circulation and hemodynamic impairment., Materials and Methods: In this retrospective analysis of prospectively collected data, 37 symptomatic patients with unilateral ICA occlusion, who underwent both, NOVA-qMRA and BOLD-CVR investigation, were included. The correlation analysis between NOVAqMRA-derived second segment of the posterior cerebral artery (PCA-P2) VFR and BOLD-CVR (hemispheric and MCA territory CVR) was done by using a linear mixed-effects model., Results: A moderate correlation was found between P2-VFR and BOLD-CVR values for the ipsilateral MCA territory (|r|=0.44, R 2 =0.2, p<0.001) and the ipsilateral hemisphere (|r| =0.39, R 2 =0.15, p<0.001), indicating that 20% of the variance in P2-VFR can be explained by the BOLD-CVR of the MCA territory and 15% by the BOLD-CVR of the affected hemisphere., Conclusions: This correlation suggests that impaired BOLD-CVR is partly linked to an increased PCA-P2 volume flow rate, potentially indicating the activation of leptomeningeal collaterals in severe hemodynamic conditions. Both imaging techniques could aid clinicians in in creating personalized treatment strategies for patients with symptomatic ICA occlusion., Abbreviations: ACA = anterior cerebral artery; BOLD = blood oxygenation-level dependent; CVR = cerebrovascular reactivity; M1 = first segment of the middle cerebral artery; MCA =middle cerebral artery; NOVA = non-invasive optimal vessel analysis; P2 = second segment of the posterior cerebral artery; PCA = posterior cerebral artery; PCOM= posterior communicating artery; VFR = volume flow rate., Competing Interests: The authors declare no conflicts of interest related to the content of this article., (© 2024 by American Journal of Neuroradiology.)

Introduction: A significant number of patients who present with mild symptoms following large-vessel occlusion acute ischemic stroke (LVO-AIS) are currently considered ineligible for EVT. However, they frequently experience neurological deterioration during hospitalization. This study aimed to investigate the association between neurological deterioration and hemodynamic impairment by assessing steal phenomenon derived from blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) in this specific patient cohort., Patients and Methods: From the database of our single-center BOLD-CVR observational cohort study (June 2015-October 2023) we retrospectively identified acute ischemic stroke patients with admission NIHSS < 6, a newly detected large vessel occlusion of the anterior circulation and ineligible for EVT. Neurological deterioration during hospitalization as well as outcome at hospital discharge were rated with NIHSS score. We analyzed the association between these two outcomes and BOLD-CVR-derived steal phenomenon volume through regression analysis. Additionally, we investigated the discriminatory accuracy of steal phenomenon volume for predicting neurological deterioration., Results: Forty patients were included in the final analysis. Neurological deterioration occurred in 35% of patients. In the regression analysis, a strong association between steal phenomenon volume and neurological deterioration (OR 4.80, 95% CI 1.32-31.04, p  = 0.04) as well as poorer NIHSS score at hospital discharge (OR 3.73, 95% CI 1.52-10.78, p  = 0.007) was found. The discriminatory accuracy of steal phenomenon for neurological deterioration prediction had an AUC of 0.791 (95% CI 0.653-0.930)., Discussion: Based on our results we may distinguish two groups of patients with minor stroke currently ineligible for EVT, however, showing hemodynamic impairment and exhibiting neurological deterioration during hospitalization: (1) patients exhibiting steal phenomenon on BOLD-CVR imaging as well as hemodynamic impairment on resting perfusion imaging; (2) patients exhibiting steal phenomenon on BOLD-CVR imaging, however, no relevant hemodynamic impairment on resting perfusion imaging., Conclusion: The presence of BOLD-CVR derived steal phenomenon may aid to further study hemodynamic impairment in patients with minor LVO-AIS not eligible for EVT., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Intravoxel incoherent motion (IVIM) imaging, a contrast agent-free magnetic resonance imaging technique, enables the evaluation of microvascular perfusion abnormalities in acute stroke. Prior research reported reduced IVIM values within the infarct core in acute stroke. However, findings concerning IVIM characteristics in the penumbra have been mixed and the relationship between IVIM and clinical outcomes remains unknown. We employed a longitudinal multimodal imaging approach for ischemic stroke patients (n analyzed=24; pre-/post-treatment and 90-day post-stroke assessments) including IVIM, diffusion-weighted, and contrast-enhanced perfusion-weighted imaging. We evaluated IVIM in relevant stroke areas after endovascular treatment. Reduced post-treatment IVIM perfusion fraction in infarct core and recanalized penumbra was associated with poorer functional recovery at 90-days post-stroke (NIH Stroke Scale [NIHSS]; r=-0.64 and r=-0.69). Including IVIM perfusion fraction increased the explained variance of NIHSS from 42% up to 83% compared to well-known prognostic factors core volume and patient age. Additionally, IVIM perfusion fraction was reduced in the core and recanalized penumbra compared to contralateral healthy tissue, suggesting impaired microvascular reperfusion after endovascular treatment. In conclusion, IVIM characteristics of the infarct core and recanalized penumbra are strong prognostic factors for long-term outcome in stroke patients and IVIM shows promise for characterizing microvascular perfusion in relevant stroke areas., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background and Purpose: We report on an intensive two-day training program on microanastomoses performed on perfused human placenta models. A specific scoring system was elaborated to evaluate the participants' microsurgical skills and report the participants' results., Materials and Methods: Trainees who attended the Zurich Microsurgery Courses in 2023 were included in the study. Before performing the microanastomoses, each participant received a visual didactic training. Training was made on perfused human placenta models. To perform the microvascular anastomoses, vessels of different diameters were chosen, and 9-0 and 10-0 microsutures were used. The course was structured in two days. On day one, participants practiced microvascular dissection, microsuturing and end-to-end anastomoses, while the second day was dedicated to end-to-side and to repeat the most useful microanastomosis depending on the specialty. A score system for the evaluation of a successful microanastomosis was developed and applied to assess the participants' anastomoses. User satisfaction was measured by means of a survey-based questionnaire., Results: Fifty-two participants from different institutions, specializations and levels of experience were included. A significant improvement in the overall microsurgical skills of the included cohort was documented (p < 0.005). The initial average score per anastomosis of 3.56 points (SD 0.71) increased to an average of 3.8 points (SD 0.87) at the end of the course. The steepest learning curve was observed in the placement of knots (Δ 0.48 points, p = 0.003) and microvascular dissection (Δ 0.44 points, p = 0.002). Most participants rated the fidelity and importance of the placental microsuturing course as extremely high., Conclusion: The two-day training program is efficient to teach microvascular dissection and microanastomosis techniques. A significant improvement of participants' microsurgical skills was reported. The human placenta model proved to be a high-fidelity simulator with great user satisfaction., Competing Interests: Declarations Ethical approval The use of each placenta at the Zurich Microsurgery Course required presence of a written consent for imaging and biologic data use signed by the mother. The trainees at the Zurich Microsurgery Courses participated voluntarily to the study and no consent was signed. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The literature lacks a combined analysis of neurosurgical microvascular anastomosis training models. We performed a systematic literature search to provide an overview of the existing models and proposed a classification system based on the level of simulation and reproducibility of the microvascular anastomosis., Methods: The systematic literature search followed the PRISMA guidelines. We consulted MEDLINE, Web of Knowledge, and EMBASE independently for papers about bypass training models. Every training model was analyzed according to six tasks supposed to esteem their fidelity to the real operative setting by using a scoring system from zero to two. Finally, authors classified the models into five classes, from A to E, by summing the individual scores., Results: This study included 109 papers for analysis. Training models were grouped into synthetic tubes, ex vivo models (animal vessels, fresh human cadavers, human placentas) and in vivo simulators (live animals-rats, rabbits, pigs). By applying the proposed classification system, live animals and placentas obtained the highest scores, falling into class A (excellent simulators). Human cadavers and animal vessels (ex vivo) were categorized in class B (good simulators), followed by synthetic tubes (class C, reasonable simulators)., Conclusions: The proposed classification system helps the neurosurgeon to analyze the available training models for microvascular anastomosis critically, and to choose the most appropriate one according to the skills they need to improve.

Background: Basal cisternostomy (BC) is a surgical technique to reduce intracranial hypertension following moderate to severe traumatic brain injury (TBI). As the efficacy and safety of BC in patients with TBI has not been well-studied, we aim to summarize the published evidence on the effect of BC as an adjunct to decompressive hemicraniectomy (DHC) on clinical outcome following moderate to severe TBI., Methods: A systematic literature review was carried out in PubMed/MEDLINE and EMBASE to identify studies evaluating BC as an adjunct to decompressive hemicraniectomy (DHC) in moderate to severe TBI. Random effects meta-analysis was performed to calculate summary effect estimates., Results: Eight studies reporting on 1345 patients were included in the qualitative analysis, of which five (1206 patients) were considered for meta-analysis. Overall, study quality was low and clinical heterogeneity was high. Adjuvant BC (BC + DHC) compared to standalone DHC was associated with a reduction in the length of stay in the ICU (Mean difference [MD]: -3.25 days, 95% CI: -5.41 to -1.09 days, p = 0.003), significantly lower mean brain outward herniation (MD: -0.68 cm, 95% CI: -0.90 to -0.46 cm, p < 0.001), reduced odds of requiring osmotherapy (OR: 0.09, 95% CI: 0.02 to 0.41, p = 0.002) as well as decreased odds of mortality at discharge (OR 0.68, 95% CI: 0.4 to 0.96, p = 0.03). Adjuvant BC compared to DHC did not result in higher odds of a favourable neurological outcome (OR = 2.50, 95% CI: 0.95-6.55, p = 0.06) and did not affect mortality at final follow-up (OR: 0.80, 95% CI: 0.17 to 3.74, p = 0.77)., Conclusion: There is insufficient data to demonstrate a potential beneficial effect of adjuvant BC. Despite some evidence for reduced mortality and length of stay, there is no effect on neurological outcome. However, these results need to be interpreted with caution as they carry a high risk of bias due to overall scarcity of published clinical data, technical variations, methodological differences, limited cohort sizes, and a considerable heterogeneity in study design and reported outcomes., (© 2024. The Author(s).)

Objective: A superficial temporal artery-middle cerebral artery (STA-MCA) bypass is classically considered a low-flow bypass. It is known that the flow in the flow augmentation STA-MCA bypass is influenced by flow demand of the revascularized territory and can reach significantly higher values. The authors report their intraoperative flow measurement data in a consecutive series of 100 STA-MCA bypasses performed at their institution. Moreover, in a subanalysis, they show the postoperative bypass flow measured with quantitative MR angiography (qMRA) noninvasive optimal vessel analysis (NOVA)., Methods: Between January 2013 and October 2023, 100 patients with acute, subacute, or chronic large-vessel occlusion (LVO) or moyamoya disease underwent a flow augmentation STA-MCA bypass revascularization at the authors' department with intraoperative bypass flow measurement. Patients with atherosclerotic LVO who underwent bypass surgery within a 6-week period following the onset of ischemic stroke symptoms were categorized into the acute bypass group, encompassing both acute and subacute LVO cases. Conversely, those who underwent bypass surgery > 6 weeks after the last occurrence of ischemic stroke were classified as the chronic group. Since May 2019, a consecutive subgroup of 37 patients received a postoperative (before discharge) bypass flow measurement with the qMRA-NOVA imaging tool., Results: The mean ± SD intraoperative bypass flow in this consecutive series of 100 STA-MCA bypasses was 53.5 ± 28.8 ml/min (range 14-145 ml/min). In the subanalysis, there was no difference in the intraoperative flow capacity between the acute and chronic groups and between the moyamoya and acute groups. Patients in the moyamoya group showed a significantly higher flow rate in the STA-MCA bypass compared with the chronic group (63.0 ± 30.2 ml/min vs 48.4 ± 26.5 ml/min, p = 0.03). In a consecutive subanalysis of 37 STA-MCA bypass cases, postoperative flow measurements were also performed using qMRA-NOVA, showing a significant increase in the flow of STA-MCA bypasses after surgery compared with intraoperative flow measurements (mean intraoperative bypass flow rate vs qMRA-NOVA postoperative bypass flow rate: 73.4 ± 29.9 ml/min vs 111.3 ± 51.4 ml/min, p = 0.005)., Conclusions: Using intraoperative and postoperative quantitative flow measurements of the STA, the data confirm that the flow in the flow augmentation STA-MCA bypass is influenced by the flow demand of the revascularized territory and can reach high values if needed. Moreover, the significant flow increase in the postoperative flow measurement using qMRA-NOVA demonstrates that the bypass can increase its flow over time.

Revascularization surgery for the symptomatic hemisphere with hemodynamic impairment is effective for Moyamoya vasculopathy patients. However, careful patient selection is crucial and ideally supported by advanced quantitative hemodynamic imaging. Recently, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) and quantitative magnetic resonance angiography with non-invasive optimal vessel analysis (qMRA-NOVA) have gained prominence in assessing these patients. This study aims to present the results of BOLD-CVR and qMRA-NOVA imaging along with the changes in cerebral hemodynamics and flow status following flow augmentation with superficial temporal artery-middle cerebral artery (STA-MCA) bypass in our Moyamoya vasculopathy patient cohort. Symptomatic patients with Moyamoya vasculopathy treated at the Clinical Neuroscience Center of the University Hospital Zurich who underwent hemodynamic and flow imaging (BOLD-CVR and qMRA-NOVA) before and after bypass were included in the analysis. Reduced hemispheric volume flow rates, as well as impaired BOLD-CVR, were measured in all 12 patients with Moyamoya vasculopathy before STA-MCA bypass surgery. Following the surgical procedure, post-operative BOLD-CVR demonstrated a non-significant increase in BOLD-CVR values within the revascularized, symptomatic middle cerebral artery territory and cerebral hemisphere. The results of the statistical tests should be viewed as indicative due to the small sample size. Additionally, post-operative qMRA-NOVA revealed a significant improvement in the hemispheric volume flow rate of the affected hemisphere due to the additional bypass flow rate. Our findings affirm the presence of hemodynamic and flow impairments in the symptomatic hemisphere of the Moyamoya vasculopathy patients. Bypass surgery proves effective in improving both BOLD-CVR impairment and the hemispheric volume flow rate in our patient cohort.

Background: Transient hypoxia-induced deoxyhemoglobin (dOHb) has recently been shown to represent a comparable contrast to gadolinium-based contrast agents for generating resting perfusion measures in healthy subjects. Here, we investigate the feasibility of translating this non-invasive approach to patients with brain tumors. Methods: A computer-controlled gas blender was used to induce transient precise isocapnic lung hypoxia and thereby transient arterial dOHb during echo-planar-imaging acquisition in a cohort of patients with different types of brain tumors (n = 9). We calculated relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit time (MTT) using a standard model-based analysis. The transient hypoxia induced-dOHb MRI perfusion maps were compared to available clinical DSC-MRI. Results: Transient hypoxia induced-dOHb based maps of resting perfusion displayed perfusion patterns consistent with underlying tumor histology and showed high spatial coherence to gadolinium-based DSC MR perfusion maps. Conclusion: Non-invasive transient hypoxia induced-dOHb was well-tolerated in patients with different types of brain tumors, and the generated rCBV, rCBF and MTT maps appear in good agreement with perfusion maps generated with gadolinium-based DSC MR perfusion., Competing Interests: JF and DM contributed to the development of the automated end-tidal targeting device, RespirAct™ (Thornhill Research Inc., TRI) used in this study and have equity in the company. ES, OS, and JD are part time employees of TRI. TRI did not commission, provide support for the study, or review the manuscript. MW has received research grants from Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Bayer, Curevac, Medac, Novartis, Novocure, Orbus, Philogen, Roche and Sandoz. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stumpo, Sayin, Bellomo, Sobczyk, van Niftrik, Sebök, Weller, Regli, Kulcsár, Pangalu, Bink, Duffin, Mikulis, Fisher and Fierstra.)

Background: Impaired cerebrovascular reactivity (CVR) has been correlated with recurrent ischemic stroke. However, for clinical purposes, most CVR techniques are rather complex, time-consuming, and lack validation for quantitative measurements. The recent adaptation of a standardized hypercapnic stimulus in combination with a blood-oxygenation-level-dependent (BOLD) magnetic resonance imaging signal as a surrogate for cerebral blood flow offers a potential universally comparable CVR assessment. We investigated the association between impaired BOLD-CVR and risk for recurrent ischemic events., Methods: We conducted a retrospective analysis of patients with symptomatic cerebrovascular large vessel disease who had undergone a prospective hypercapnic-challenged BOLD-CVR protocol at a single tertiary stroke referral center between June 2014 and April 2020. These patients were followed up for recurrent acute ischemic events for up to 3 years. BOLD-CVR (%BOLD signal change per mm Hg CO 2 ) was calculated on a voxel-by-voxel basis. Impaired BOLD-CVR of the affected (ipsilateral to the vascular pathology) hemisphere was defined as an average BOLD-CVR, falling 2 SD below the mean BOLD-CVR of the right hemisphere in a healthy age-matched reference cohort (n=20). Using a multivariate Cox proportional hazards model, the association between impaired BOLD-CVR and ischemic stroke recurrence was assessed and Kaplan-Meier survival curves to visualize the acute ischemic stroke event rate., Results: Of 130 eligible patients, 28 experienced recurrent strokes (median, 85 days, interquartile range, 5-166 days). Risk factors associated with an increased recurrent stroke rate included impaired BOLD-CVR, a history of atrial fibrillation, and heart insufficiency. After adjusting for sex, age group, and atrial fibrillation, impaired BOLD-CVR exhibited a hazard ratio of 10.73 (95% CI, 4.14-27.81; P <0.001) for recurrent ischemic stroke., Conclusions: Among patients with symptomatic cerebrovascular large vessel disease, those exhibiting impaired BOLD-CVR in the affected hemisphere had a 10.7-fold higher risk of recurrent ischemic stroke events compared with individuals with nonimpaired BOLD-CVR., Competing Interests: Disclosures The device used in this study was developed by Thornhill Medical, Inc (TMI) a for-profit spin-off from the University Health Network, University of Toronto, to enable cerebrovascular reactivity studies. It is not a commercial product and is made available to academic centers for certified research under ethics board approval. Drs Fisher and Mikulis are appointees at the University of Toronto and employees of, and own shares in, TMI. Dr Katant is a consultant for AstraZeneca and Brahms GmbH, and receives funding from Bayer Healthcare, both of which are not related to the current article. Currently, Dr Katant has a dual appointment at the University Hospital of Zürich and the University Hospital Basel. Dr Wegener receives funding through the following institutes: Baugarten Stiftung, the Betty and David Koetser Foundation, Hartmann Müller-Stiftung für Medizinische Forschung, and the Swiss National Science Foundation and is the co-applicant of the UZH CRPP Stroke of the University Hospital of Zürich. Dr Luft is a consultant for Amgen, Boehringer Ingelheim, and Moleac Ltd. Dr Kulcsár is a consultant for Johnson and Johnson International, Medtronic, and Stryker. The other authors report no conflicts.

Background: A major clinical challenge is the adequate identification of patients with acute (<1 week) and subacute (1-6 weeks) ischemic stroke due to internal carotid artery (ICA) occlusion who could benefit from a surgical revascularization after a failure of endovascular and/or medical treatment. Recently, two novel quantitative imaging modalities have been introduced: (I) quantitative magnetic resonance angiography (qMRA) with non-invasive optimal vessel analysis (NOVA) for quantification of blood flow in major cerebral arteries (in mL/min), and (II) blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to assess cerebrovascular reactivity (CVR). The aim of this study is to present our cohort of patients who underwent surgical revascularization in the acute and subacute phase of ischemic stroke as well as to demonstrate the importance of hemodynamic and flow assessment for the decision-making regarding surgical revascularization in patients with acute and subacute stroke and ICA-occlusion., Methods: Symptomatic patients with acute and subacute ischemic stroke because of persistent ICA-occlusion despite optimal medical/endovascular recanalization therapy who were treated at the Neuroscience Clinical Center of the University Hospital Zurich underwent both BOLD-CVR and qMRA-NOVA to study the hemodynamic and collateral vessel status. Patients selected for surgical revascularization according to our previously published flowchart were included in this prospective cohort study. Repeated NOVA and BOLD-CVR investigations were done after bypass surgery as follow up as well as clinical follow up. Continuous BOLD-CVR and qMRA-NOVA variables were compared using paired Student t -test., Results: Between May 2019 and September 2022, superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery was performed in 12 patients with acute and subacute stroke because of ICA-occlusion despite of optimal endovascular and/or medical treatment prior to the surgery. Impaired BOLD-CVR in the occluded vascular territory [MCA territory: ipsilateral vs. contralateral: -0.03±0.07 vs. 0.11±0.07 %BOLD/mmHgCO 2 , P<0.001] as well as reduced hemispheric flow with qMRA-NOVA (ipsilateral vs. contralateral: 228.00±54.62 vs. 384.50±70.99 mL/min, P=0.01) were measured indicating insufficient collateralization. Post-operative qMRA-NOVA showed improved hemispheric flow (via bypass) (pre-bypass vs. post-bypass: 236.60±76.45 vs. 334.20±131.33 mL/min, P=0.02) and the 3-month-follow-up with BOLD-CVR showed improved cerebral hemodynamics (MCA territory: pre-bypass vs. post-bypass: -0.01±0.05 vs. 0.06±0.03 %BOLD/mmHgCO 2 , P=0.02) in all patients studied., Conclusions: Quantitative assessment with BOLD-CVR and qMRA-NOVA allows us to evaluate the pre- and post-operative cerebral hemodynamics and collateral vessel status in patients with acute/subacute stroke due to ICA occlusion who may benefit from surgical revascularization after failure of endovascular/medical treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-876/coif). A.R.L. reports consulting fees from Boehringer Ingelheim and Speaker honoraria from Moleac Snc. G.E. reports honoraria for lectures and presentations for Aesculap B Braun and Baxter, and also reports president of the board of the Brain Disease Foundation. The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background and Objectives: Mixed reality (MxR) benefits neurosurgery by improving anatomic visualization, surgical planning and training. We aim to validate the usability of a dedicated certified system for this purpose., Methods: All cases prepared with MxR in our center in 2022 were prospectively collected. Holographic rendering was achieved using an incorporated fully automatic algorithm in the MxR application, combined with contrast-based semiautomatic rendering and/or manual segmentation where necessary. Hologram segmentation times were documented. Visualization during surgical preparation (defined as the interval between finalized anesthesiological induction and sterile draping) was performed using MxR glasses and direct streaming to a side screen. Surgical preparation times were compared with a matched historical cohort of 2021. Modifications of the surgical approach after 3-dimensional (3D) visualization were noted. Usability was assessed by evaluating 7 neurosurgeons with more than 3 months of experience with the system using a Usefulness, Satisfaction and Ease of use (USE) questionnaire., Results: One hundred-seven neurosurgical cases prepared with a 3D hologram were collected. Surgical indications were oncologic (63/107, 59%), cerebrovascular (27/107, 25%), and carotid endarterectomy (17/107, 16%). Mean hologram segmentation time was 39.4 ± 20.4 minutes. Average surgical preparation time was 48.0 ± 17.3 minutes for MxR cases vs 52 ± 17 minutes in the matched 2021 cohort without MxR (mean difference 4, 95% CI 1.7527-9.7527). Based on the 3D hologram, the surgical approach was modified in 3 cases. Good usability was found by 57% of the users., Conclusion: The perioperative use of 3D holograms improved direct anatomic visualization while not significantly increasing intraoperative surgical preparation time. Usability of the system was adequate. Further technological development is necessary to improve the automatic algorithms and reduce the preparation time by circumventing manual and semiautomatic segmentation. Future studies should focus on quantifying the potential benefits in teaching, training, and the impact on surgical and functional outcomes., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Congress of Neurological Surgeons.)

Background: Staging of hemodynamic failure (HF) in symptomatic patients with cerebrovascular steno-occlusive disease is required to assess the risk of ischemic stroke. Since the gold standard positron emission tomography-based perfusion reserve is unsuitable as a routine clinical imaging tool, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) with CO 2 is a promising surrogate imaging approach. We investigated the accuracy of standardized BOLD-CVR to classify the extent of HF., Methods and Results: Patients with symptomatic unilateral cerebrovascular steno-occlusive disease, who underwent both an acetazolamide challenge ( 15 O-)H 2 O-positron emission tomography and BOLD-CVR examination, were included. HF staging of vascular territories was assessed using qualitative inspection of the positron emission tomography perfusion reserve images. The optimum BOLD-CVR cutoff points between HF stages 0-1-2 were determined by comparing the quantitative BOLD-CVR data to the qualitative ( 15 O-)H 2 O-positron emission tomography classification using the 3-dimensional accuracy index to the randomly assigned training and test data sets with the following determination of a single cutoff for clinical application. In the 2-case scenario, classifying data points as HF 0 or 1-2 and HF 0-1 or 2, BOLD-CVR showed an accuracy of >0.7 for all vascular territories for HF 1 and HF 2 cutoff points. In particular, the middle cerebral artery territory had an accuracy of 0.79 for HF 1 and 0.83 for HF 2, whereas the anterior cerebral artery had an accuracy of 0.78 for HF 1 and 0.82 for HF 2., Conclusions: Standardized and clinically accessible BOLD-CVR examinations harbor sufficient data to provide specific cerebrovascular reactivity cutoff points for HF staging across individual vascular territories in symptomatic patients with unilateral cerebrovascular steno-occlusive disease.

Background: Perfused placentas provide an excellent and accessible model for microvascular dissection, microsuturing and microanastomosis training - particularly in the early microsurgical learning curve. This way, a significant amount of live animals can be spared., Method: We present the Zurich Microsurgery Lab protocol, detailing steps for obtaining, selecting, cleaning, flushing, cannulating, and preserving human placentas - as well as microsurgical training examples - in a tried-and-true, safe, cost-effective, and high-yield fashion., Conclusion: Our technique enables highly realistic microsurgical training (microdissection, microvascular repair, microanastomosis) based on readily available materials. Proper handling, preparation, and preservation of the perfused placenta models is key., (© 2023. The Author(s).)

Introduction: Brain areas exhibiting negative blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) responses to carbon dioxide (CO 2 ) are thought to suffer from a completely exhausted autoregulatory cerebrovascular reserve capacity and exhibit vascular steal phenomenon. If this assumption is correct, the presence of vascular steal phenomenon should subsequently result in an equal negative fMRI signal response during a motor-task based BOLD-fMRI study (increase in metabolism without an increase in cerebral blood flow due to exhausted reserve capacity) in otherwise functional brain tissue. To investigate this premise, the aim of this study was to further investigate motor-task based BOLD-fMRI signal responses in brain areas exhibiting negative BOLD-CVR., Material and Methods: Seventy-one datasets of patients with cerebrovascular steno-occlusive disease without motor defects, who underwent a CO 2 -calibrated motor task-based BOLD-fMRI study with a fingertapping paradigm and a subsequent BOLD-CVR study with a precisely controlled CO 2 -challenge during the same MRI examination, were included. We compared BOLD-fMRI signal responses in the bilateral pre- and postcentral gyri - i.e. Region of Interest (ROI) with the corresponding BOLD-CVR in this ROI. The ROI was determined using a second level group analysis of the BOLD-fMRI task study of 42 healthy individuals undergoing the same study protocol., Results: An overall decrease in BOLD-CVR was associated with a decrease in BOLD-fMRI signal response within the ROI. For patients exhibiting negative BOLD-CVR, we found both positive and negative motor-task based BOLD-fMRI signal responses., Conclusion: We show that the presence of negative BOLD-CVR responses to CO 2 is associated with heterogeneous motor task-based BOLD-fMRI signal responses, where some patients show -more presumed- negative BOLD-fMRI signal responses, while other patient showed positive BOLD-fMRI signal responses. This finding may indicate that the autoregulatory vasodilatory reserve capacity does not always need to be completely exhausted for vascular steal phenomenon to occur., Competing Interests: Declaration of Competing Interest Dr. Fisher and Dr. Mikulis report that they contributed to the development of an automated end-tidal targeting device, RespirAct™ which is designed, assembled, and made available as a research tool by Thornhill Medical Inc. Thornhill Medical Inc. is a for profit spin-off company from the University Health Network/University of Toronto. Drs. Fisher and Mikulis have equity in Thornhill Medical Inc. The other authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In acute ischemic stroke due to large-vessel occlusion (LVO), the clinical outcome after endovascular thrombectomy (EVT) is influenced by the extent of autoregulatory hemodynamic impairment, which can be derived from blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR). BOLD-CVR imaging identifies brain areas influenced by hemodynamic steal. We sought to investigate the presence of steal phenomenon and its relationship to DWI lesions and clinical deficit in the acute phase of ischemic stroke following successful vessel recanalization.From the prospective longitudinal IMPreST (Interplay of Microcirculation and Plasticity after ischemic Stroke) cohort study, patients with acute ischemic unilateral LVO stroke of the anterior circulation with successful endovascular thrombectomy (EVT; mTICI scale ≥ 2b) and subsequent BOLD-CVR examination were included for this analysis. We analyzed the spatial correlation between brain areas exhibiting BOLD-CVR-associated steal phenomenon and DWI infarct lesion as well as the relationship between steal phenomenon and NIHSS score at hospital discharge.Included patients (n = 21) exhibited steal phenomenon to different extents, whereas there was only a partial spatial overlap with the DWI lesion (median 19%; IQR, 8-59). The volume of steal phenomenon outside the DWI lesion showed a positive correlation with overall DWI lesion volume and was a significant predictor for the NIHSS score at hospital discharge.Patients with acute ischemic unilateral LVO stroke exhibited hemodynamic steal identified by BOLD-CVR after successful EVT. Steal volume was associated with DWI infarct lesion size and with poor clinical outcome at hospital discharge. BOLD-CVR may further aid in better understanding persisting hemodynamic impairment following reperfusion therapy., (© 2023. The Author(s).)

Objective: The reason for a rebleed after an initial hemorrhage in patients with aneurysmal subarachnoid hemorrhage (aSAH) is considered multifactorial. Antiplatelet use is one of the factors that has been related to early rebleed and worse outcome after aSAH. Thrombocyte transfusion overcomes the inhibitory effects of antiplatelet agents by increasing the number of functional thrombocytes, but its impact on the rebleed rate and clinical outcome remains unknown. The aim of this study was to assess the effect of thrombocyte transfusion on rebleeding and clinical outcome in patients with aSAH and prehemorrhage antiplatelet use, considering confounding factors., Methods: Data were prospectively collected at a single tertiary reference center for aSAH in Zurich, Switzerland. Patients with aSAH and prehemorrhage antiplatelet use were divided into "thrombocyte transfusion" and "nontransfusion" groups based on whether they did or did not receive any thrombocyte transfusion in the acute stage of aSAH after hospital admission and before the exclusion of the bleeding source. Using multivariate logistic regression analysis, the impact of thrombocyte transfusion on the rebleed rate and on clinical outcome (defined as Glasgow Outcome Scale score 1-3) was calculated., Results: One hundred fifty-seven patients were included, 87 (55.4%) of whom received thrombocyte transfusion. Eighteen (11.5%) of 157 patients had a rebleed during the hospital stay. The rebleed risk was 6.9% in the thrombocyte transfusion group and 17.1% in the nontransfusion group. After adjusting for confounders, thrombocyte transfusion showed evidence for a reduction in the rebleed rate (adjusted OR [aOR] 0.29, 95% CI 0.10-0.87). Fifty-seven patients (36.3%) achieved a poor outcome at 6 months' follow-up. Among those 57 patients, 31 (54.4%) underwent at least one thrombocyte transfusion. Thrombocyte transfusion was not associated with poor clinical outcome at 6 months' follow-up (aOR 0.91, 95% CI 0.39-2.15)., Conclusions: Thrombocyte transfusion in patients with aSAH and prehemorrhage antiplatelet use is independently associated with a reduction in rebleeds but shows no impact on clinical outcome at 6 months' follow-up. Larger and randomized studies are needed to investigate the impact of thrombocyte transfusion on rebleed and outcome.

Recurrent stroke is a dreaded complication of symptomatic internal carotid artery occlusion (ICAO). Transcranial Duplex (TCD)-derived increased flow velocity in the ipsilateral posterior cerebral artery (PCA)-P2 segment indicates activated leptomeningeal collateral recruitment and hemodynamic impairment. Leptomeningeal collaterals are pial vascular connections between the anterior and posterior vascular territories. These secondary collateral routes are activated when primary collaterals via the Circle of Willis are insufficient. Our goal was to test the TCD parameter PCA-P2 flow for prediction of ipsilateral ischemia recurrence. We retrospectively analyzed clinical and ultrasound parameters in patients with ICAO. Together with clinical variables, we tested systolic PCA-P2 flow velocity as predictor of a recurrent ischemic event using logistic regression models. Of 111 patients, 13 showed a recurrent ischemic event within the same vascular territory. Increased flow in the ipsilateral PCA-P2 on transcranial ultrasound (median and interquartile range [IQR]: 60 cm/s [IQR 26] vs. 86 cm/s [IQR 41], p  = <0.001), as well as previous transient ischemic attack (TIA) and low NIHSS were associated with ischemia recurrence. Combined into one model, accuracy of these parameters to predict recurrent ischemia was 89.2%. Our data suggest that in patients with symptomatic ICAO, flow increases in the ipsilateral PCA-P2 suggest intensified compensatory efforts when other collaterals are insufficient. Together with the clinical variables, this non-invasive and easily assessable duplex parameter detects ICAO patients at particular risk of recurrent ischemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jud, Klövekorn, van Niftrik, Herzog, Sebök, Schweizer, Luft, Fierstra and Wegener.)

Background: Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD) is a recently proposed imaging-based scoring system that incorporates the severity of disease and its impact on parenchymal hemodynamics in order to better support clinical management and evaluate response to intervention. In particular, PIRAMD may have merit in identifying symptomatic patients that may benefit most from revascularization. Our aim was to validate the PIRAMD scoring system., Methods: Patients with ischemic Moyamoya disease, who underwent catheter angiographic [modified Suzuki Score (mSS) and collateralization status], morphological MRI and a parenchymal hemodynamic evaluation with blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) at two transatlantic centers, were retrospectively included. The primary outcome was the presence of neurological symptoms. The diagnostic capacity of each PIRAMD feature alone was evaluated, as well as combined and the inter-institutional differences of each parameter were evaluated., Results: Seventy-two hemispheres of 38 patients were considered for analysis, of which 39 (54%) were classified as symptomatic. The presence of a prior infarct had the highest odds ratio [odds ratio (OR) =24; 95% CI: 6.7-87.2] for having neurological symptoms, followed by impaired CVR (OR =17; 95% CI: 5-62). No inter-institutional differences in the odds ratios or area under the curve (AUC) were found for any study parameter. The PIRAMD score had an AUC of 0.88 (95% CI: 0.80-0.96) with a similar AUC for the PIRAMD grading score., Conclusions: Our multicentric validation of the recently published PIRAMD scoring system was highly effective in rating the severity of ischemic Moyamoya disease with excellent inter-institutional agreement. Future studies should investigate the prognostic value of this novel imaging-based score in symptomatic patients with Moyamoya disease., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-1062/coif). JAF and DJM report that they contributed to the development of an automated end-tidal targeting device, RespirActTM which is designed, assembled, and made available as a research tool by Thornhill Medical Inc. (TMI). TMI is a for profit spin-off company from the University Health Network/University of Toronto. JAF and DJM have equity in TMI. The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objective: Acute hydrocephalus is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH). Among patients needing CSF diversion, some cannot be weaned. Little is known about the comparative neurological, neuropsychological, and health-related quality-of-life (HRQOL) outcomes in patients with successful and unsuccessful CSF weaning. The authors aimed to assess outcomes of patients by comparing those with successful and unsuccessful CSF weaning; the latter was defined as occurring in patients with permanent CSF diversion at 3 months post-aSAH., Methods: The authors included prospectively recruited alert (i.e., Glasgow Coma Scale score 13-15) patients with aSAH in this retrospective study from six Swiss neurovascular centers. Patients underwent serial neurological (National Institutes of Health Stroke Scale), neuropsychological (Montreal Cognitive Assessment), disability (modified Rankin Scale), and HRQOL (EuroQol-5D) examinations at < 72 hours, 14-28 days, and 3 months post-aSAH., Results: Of 126 included patients, 54 (42.9%) developed acute hydrocephalus needing CSF diversion, of whom 37 (68.5%) could be successfully weaned and 17 (31.5%) required permanent CSF diversion. Patients with unsuccessful weaning were older (64.5 vs 50.8 years, p = 0.003) and had a higher rate of intraventricular hemorrhage (52.9% vs 24.3%, p = 0.04). Patients who succeed in restoration of physiological CSF dynamics improve on average by 2 points on the Montreal Cognitive Assessment between 48-72 hours and 14-28 days, whereas those in whom weaning fails worsen by 4 points (adjusted coefficient 6.80, 95% CI 1.57-12.04, p = 0.01). They show better neuropsychological recovery between 48-72 hours and 3 months, compared to patients in whom weaning fails (adjusted coefficient 7.60, 95% CI 3.09-12.11, p = 0.02). Patients who receive permanent CSF diversion (ventriculoperitoneal shunt) show significant neuropsychological improvement thereafter, catching up the delay in neuropsychological improvement between 14-28 days and 3 months post-aSAH. Neurological, disability, and HRQOL outcomes at 3 months were similar., Conclusions: These results show a temporary but clinically meaningful cognitive benefit in the first weeks after aSAH in successfully weaned patients. The resolution of this difference over time may be due to the positive effects of permanent CSF diversion and underlines its importance. Patients who do not show progressive neuropsychological improvement after weaning should be considered for repeat CT imaging to rule out chronic (untreated) hydrocephalus.

Objective: Epileptic seizures in patients with brain arteriovenous malformations (bAVMs) may be caused by hemodynamic alterations due to the complex angioarchitecture of bAVMs. In particular, an arterial steal phenomenon and venous outflow disruption may play an etiological role in seizure development but remain challenging to demonstrate quantitatively. Blood oxygenation level-dependent (BOLD) cerebrovascular reactivity (CVR) imaging is an emerging technique that can measure both arterial steal phenomenon (as a paradoxical BOLD signal decrease during a vasodilatory stimulus) and impaired perinidal BOLD-CVR (which has been found in the presence of venous congestion on conventional angiography in bAVM patients with epilepsy). By applying this innovative BOLD-CVR technique, the aim is to better study CVR patterns and their correlation with morphological features on conventional angiography in patients with bAVM with and without epilepsy., Methods: Twenty-two patients with unruptured and previously untreated bAVMs (8 with and 14 without epilepsy) were included in this case-control study. Quantitative CVR measurements were derived from BOLD functional MRI volumes using a novel standardized and precise hypercapnic stimulus (i.e., % BOLD/mm Hg CO2). In addition, 22 matched healthy controls underwent an identical BOLD-CVR study. Evaluation of venous congestion was performed on conventional angiography for all patients with bAVM., Results: Patients with bAVM-associated epilepsy showed impaired whole-brain BOLD-CVR compared to those in the nonepilepsy group, even after correction for AVM volume and AVM grade (epilepsy vs nonepilepsy group: 0.17 ± 0.07 vs 0.25 ± 0.07, p = 0.04). A BOLD-CVR-derived arterial steal phenomenon was observed in 2 patients with epilepsy (25%). Venous congestion was noted in 3 patients with epilepsy (38%) and in 1 patient without epilepsy (7%; p = 0.08)., Conclusions: These data suggest that whole-brain CVR impairment, and more pronounced hemodynamic alterations (i.e., arterial steal phenomenon and venous outflow restriction), may be more present in patients with bAVM-associated epilepsy. The association of impaired BOLD-CVR and bAVM-associated epilepsy will need further investigation in a larger patient cohort.

Background: Literature is inconclusive regarding the association between antiplatelet agents use and outcome after aneurysmal subarachnoid hemorrhage., Aims: To investigate the association between clinical outcome and prehemorrhage use in aneurysmal subarachnoid hemorrhage patients as well as the impact of thrombocyte transfusion on rebleed and clinical outcome., Methods: Data were collected from prospective databases of two European tertiary reference centers for aneurysmal subarachnoid hemorrhage patients. Patients were divided into "antiplatelet-user" and "non-user" according to the use of acetylsalicylic acid prior to the hemorrhage. Primary outcome was poor clinical outcome at six months (Glasgow Outcome Scale score 1-3). Secondary outcomes were in-hospital mortality and impact of thrombocyte transfusion., Results: Of the 1033 patients, 161 (15.6%) were antiplatelet users. The antiplatelet users were older with higher incidence of cardiovascular risk factors. Antiplatelet use was associated with poor outcome and in-hospital mortality. After correction for age, sex, World Federation of Neurosurgical Societies score, infarction and heart disorder, pre-hemorrhage acetylsalicylic acid use was only associated with poor clinical outcome at six months (adjusted OR 1.80, 95% CI 1.08-3.02). Thrombocyte transfusion was not associated with a reduction in rebleed or poor clinical outcome., Conclusion: In this multicenter study, the prehemorrhage acetylsalicylic acid use in aneurysmal subarachnoid hemorrhage patients was independently associated with poor clinical outcome at six months. Thrombocyte transfusion was not associated with the rebleed rate or poor clinical outcome at six months.

Objective: While prior retrospective studies have suggested that delayed cerebral ischemia (DCI) is a predictor of neuropsychological deficits after aneurysmal subarachnoid hemorrhage (aSAH), all studies to date have shown a high risk of bias. This study was designed to determine the impact of DCI on the longitudinal neuropsychological outcome after aSAH, and importantly, it includes a baseline examination after aSAH but before DCI onset to reduce the risk of bias., Methods: In a prospective, multicenter study (8 Swiss centers), 112 consecutive alert patients underwent serial neuropsychological assessments (Montreal Cognitive Assessment [MoCA]) before and after the DCI period (first assessment, < 72 hours after aSAH; second, 14 days after aSAH; third, 3 months after aSAH). The authors compared standardized MoCA scores and determined the likelihood for a clinically meaningful decline of ≥ 2 points from baseline in patients with DCI versus those without., Results: The authors screened 519 patients, enrolled 128, and obtained complete data in 112 (87.5%; mean [± SD] age 53.9 ± 13.9 years; 66.1% female; 73% World Federation of Neurosurgical Societies [WFNS] grade I, 17% WFNS grade II, 10% WFNS grades III-V), of whom 30 (26.8%) developed DCI. MoCA z-scores were worse in the DCI group at baseline (-2.6 vs -1.4, p = 0.013) and 14 days (-3.4 vs -0.9, p < 0.001), and 3 months (-0.8 vs 0.0, p = 0.037) after aSAH. Patients with DCI were more likely to experience a decline of ≥ 2 points in MoCA score at 14 days after aSAH (adjusted OR [aOR] 3.02, 95% CI 1.07-8.54; p = 0.037), but the likelihood was similar to that in patients without DCI at 3 months after aSAH (aOR 1.58, 95% CI 0.28-8.89; p = 0.606)., Conclusions: Aneurysmal SAH patients experiencing DCI have worse neuropsychological function before and until 3 months after the DCI period. DCI itself is responsible for a temporary and clinically meaningful decline in neuropsychological function, but its effect on the MoCA score could not be measured at the time of the 3-month follow-up in patients with low-grade aSAH with little or no impairment of consciousness. Whether these findings can be extrapolated to patients with high-grade aSAH remains unclear. Clinical trial registration no.: NCT03032471 (ClinicalTrials.gov).

Diffuse gliomas are the most common primary malignant intracranial neoplasms. Aside from the challenges pertaining to their treatment-glioblastomas, in particular, have a dismal prognosis and are currently incurable-their pre-operative assessment using standard neuroimaging has several drawbacks, including broad differentials diagnosis, imprecise characterization of tumor subtype and definition of its infiltration in the surrounding brain parenchyma for accurate resection planning. As the pathophysiological alterations of tumor tissue are tightly linked to an aberrant vascularization, advanced hemodynamic imaging, in addition to other innovative approaches, has attracted considerable interest as a means to improve diffuse glioma characterization. In the present part A of our two-review series, the fundamental concepts, techniques and parameters of hemodynamic imaging are discussed in conjunction with their potential role in the differential diagnosis and grading of diffuse gliomas. In particular, recent evidence on dynamic susceptibility contrast, dynamic contrast-enhanced and arterial spin labeling magnetic resonance imaging are reviewed together with perfusion-computed tomography. While these techniques have provided encouraging results in terms of their sensitivity and specificity, the limitations deriving from a lack of standardized acquisition and processing have prevented their widespread clinical adoption, with current efforts aimed at overcoming the existing barriers.

Gliomas, and glioblastoma in particular, exhibit an extensive intra- and inter-tumoral molecular heterogeneity which represents complex biological features correlating to the efficacy of treatment response and survival. From a neuroimaging point of view, these specific molecular and histopathological features may be used to yield imaging biomarkers as surrogates for distinct tumor genotypes and phenotypes. The development of comprehensive glioma imaging markers has potential for improved glioma characterization that would assist in the clinical work-up of preoperative treatment planning and treatment effect monitoring. In particular, the differentiation of tumor recurrence or true progression from pseudoprogression, pseudoresponse, and radiation-induced necrosis can still not reliably be made through standard neuroimaging only. Given the abundant vascular and hemodynamic alterations present in diffuse glioma, advanced hemodynamic imaging approaches constitute an attractive area of clinical imaging development. In this context, the inclusion of objective measurable glioma imaging features may have the potential to enhance the individualized care of diffuse glioma patients, better informing of standard-of-care treatment efficacy and of novel therapies, such as the immunotherapies that are currently increasingly investigated. In Part B of this two-review series, we assess the available evidence pertaining to hemodynamic imaging for molecular feature prediction, in particular focusing on isocitrate dehydrogenase (IDH) mutation status, MGMT promoter methylation, 1p19q codeletion, and EGFR alterations. The results for the differentiation of tumor progression/recurrence from treatment effects have also been the focus of active research and are presented together with the prognostic correlations identified by advanced hemodynamic imaging studies. Finally, the state-of-the-art concepts and advancements of hemodynamic imaging modalities are reviewed together with the advantages derived from the implementation of radiomics and machine learning analyses pipelines.