Flow capacity of a superficial temporal artery as a donor in a consecutive series of 100 patients with superficial temporal artery-middle cerebral artery bypass.

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.

Evaluation of flow diverters for cerebral aneurysm therapy: recommendations for imaging analyses in clinical studies, endorsed by ESMINT, ESNR, OCIN, SILAN, SNIS, and WFITN.

BACKGROUND: Multiple studies and meta-analyses have described the technical and clinical outcomes in large cohorts of aneurysm patients treated with flow diverters (FDs). Variations in evaluation methodology complicate making comparisons among studies, hinder understanding of the device behavior, and pose an obstacle in the assessment of further advances in FD therapy. METHODS: A multidisciplinary panel of neurointerventionalists, imaging experts, and neuroradiologists convened with the goal of establishing consensus recommendations for the standardization of image analyses in FD studies. RESULTS: A standardized methodology is proposed for evaluating and reporting radiological outcomes of FD treatment of intracranial aneurysms. The recommendations include general imaging considerations for clinical studies and evaluations of longitudinal changes, such as neointimal lining and stenosis. They cover standards for classification of aneurysm location, morphology, measurements, as well as the assessment of aneurysm occlusion, wall apposition, and neck coverage. These reporting standards further define four specific braid deformation patterns: foreshortening, fish-mouthing, braid bump deformation, and braid collapse, collectively termed 'F2B2'. CONCLUSIONS: When widely applied, standardization of methods of measuring and reporting outcomes will help to harmonize the assessment of treatment outcomes in clinical studies, help facilitate communication of results among specialists, and help enable research and development to focus on specific aspects of FD techniques and technology.

Endovascular Embolization as a Stand-Alone Treatment of Head and Neck Paragangliomas with Long-Term Tumor Control.

BACKGROUND AND PURPOSE: The impact of therapeutic embolization as a stand-alone treatment of head and neck paragangliomas considered surgically high-risk remains insufficiently understood. The aim of this study was to investigate the procedural risks and long-term volumetric development in head and neck paragangliomas with high surgical risk following therapeutic endovascular embolization as a stand-alone treatment. MATERIALS AND METHODS: A retrospective database review of patients who underwent endovascular embolization as primary treatment for head and neck paragangliomas lacking appropriate curative treatment options at our institution (from January 2000 to February 2023) was conducted. Tumor volumetric analyses were performed before embolization and during follow-up. To assess the changes in tumor volume over time, the measurements were performed after embolization, first at 6 months and then on a yearly basis up to 6 years (mean follow-up time was 33.7 ± 24.4 months). Subgroup analyses were conducted for vagal and jugular/jugulotympanic paragangliomas. RESULTS: A total of 32 head and neck paragangliomas in 28 patients (mean age, 56.1 years ± 16.5 [standard deviation]; 18 female) with therapeutic embolization as stand-alone treatment were evaluated, of which 11 were vagal paragangliomas, 15 jugular/jugulotympanic paragangliomas, and 6 carotid body tumors. After a mean follow-up duration of 33.7 ± 24.4 months, tumor control was achieved in 75%, with significant median tumor volume reduction at 6 months (P = .02, n = 21). Vagal paragangliomas responded the most to embolization with a significantly decreased median volume from 22.32 cm3 to 19.09 cm3 (P = .008, n = 8). Transient complications occurred in 3.4%. CONCLUSIONS: Therapeutic embolization as a stand-alone treatment offers a low-risk control of tumor growth in surgically high-risk lesions, with a significant reduction in tumor volume after treatment. Among the different subtypes, vagal paragangliomas exhibited the strongest and longest regression of the tumor volume.

Transient deoxyhemoglobin formation as a contrast for perfusion MRI studies in patients with brain tumors: a feasibility study.

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.

Flow-augmentation STA-MCA bypass for acute and subacute ischemic stroke due to internal carotid artery occlusion and the role of advanced neuroimaging with hemodynamic and flow-measurement in the decision-making: preliminary data.

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/mmHgCO2, 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/mmHgCO2, 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.

Cytotoxic lesions of the corpus callosum: a systematic review.

OBJECTIVES: Cytotoxic lesions of the corpus callosum (CLOCC) are a common magnetic resonance imaging (MRI) finding associated with various systemic diseases including COVID-19. Although an increasing number of such cases is reported in the literature, there is a lack of systematic evidence summarizing the etiology and neuroimaging findings of these lesions. Thus, the aim of this systematic review was to synthesize the applied nomenclature, neuroimaging and clinical features, and differential diagnoses as well as associated disease entities of CLOCC. MATERIALS AND METHODS: A comprehensive literature search in three biomedical databases identified 441 references, out of which 324 were eligible for a narrative summary including a total of 1353 patients. RESULTS: Our PRISMA-conform systematic review identifies a broad panel of disease entities which are associated with CLOCC, among them toxic/drug-treatment-associated, infectious (viral, bacterial), vascular, metabolic, traumatic, and neoplastic entities in both adult and pediatric individuals. On MRI, CLOCC show typical high T2 signal, low T1 signal, restricted diffusion, and lack of contrast enhancement. The majority of the lesions were reversible within the follow-up period (median follow-up 3 weeks). Interestingly, even though CLOCC were mostly associated with symptoms of the underlying disease, in exceptional cases, CLOCC were associated with callosal neurological symptoms. Of note, employed nomenclature for CLOCC was highly inconsistent. CONCLUSIONS: Our study provides high-level evidence for clinical and imaging features of CLOCC as well as associated disease entities. CLINICAL RELEVANCE STATEMENT: Our study provides high-level evidence on MRI features of CLOCC as well as a comprehensive list of disease entities potentially associated with CLOCC. Together, this will facilitate rigorous diagnostic workup of suspected CLOCC cases. KEY POINTS: • Cytotoxic lesions of the corpus callosum (CLOCC) are a frequent MRI feature associated with various systemic diseases. • Cytotoxic lesions of the corpus callosum show a highly homogenous MRI presentation and temporal dynamics. • This comprehensive overview will benefit (neuro)radiologists during diagnostic workup.

The Brainbox-a tool to facilitate correlation of brain magnetic resonance imaging features to histopathology.

Magnetic resonance imaging (MRI) has limitations in identifying underlying tissue pathology, which is relevant for neurological diseases such as multiple sclerosis, stroke or brain tumours. However, there are no standardized methods for correlating MRI features with histopathology. Thus, here we aimed to develop and validate a tool that can facilitate the correlation of brain MRI features to corresponding histopathology. For this, we designed the Brainbox, a waterproof and MRI-compatible 3D printed container with an integrated 3D coordinate system. We used the Brainbox to acquire post-mortem ex vivo MRI of eight human brains, fresh and formalin-fixed, and correlated focal imaging features to histopathology using the built-in 3D coordinate system. With its built-in 3D coordinate system, the Brainbox allowed correlation of MRI features to corresponding tissue substrates. The Brainbox was used to correlate different MR image features of interest to the respective tissue substrate, including normal anatomical structures such as the hippocampus or perivascular spaces, as well as a lacunar stroke. Brain volume decreased upon fixation by 7% (P = 0.01). The Brainbox enabled degassing of specimens before scanning, reducing susceptibility artefacts and minimizing bulk motion during scanning. In conclusion, our proof-of-principle experiments demonstrate the usability of the Brainbox, which can contribute to improving the specificity of MRI and the standardization of the correlation between post-mortem ex vivo human brain MRI and histopathology. Brainboxes are available upon request from our institution.

Comparison of clinically available dynamic susceptibility contrast post processing software to differentiate progression from pseudoprogression in post-treatment high grade glioma.

INTRODUCTION: The purpose of this retrospective study was to compare two, widely available software packages for calculation of Dynamic Susceptibility Contrast (DSC) perfusion MRI normalized relative Cerebral Blood Volume (rCBV) values to differentiate tumor progression from pseudoprogression in treated high-grade glioma patients. MATERIAL AND METHODS: rCBV maps processed by Siemens Syngo.via (Siemens Healthineers) and Olea Sphere (Olea Medical) software packages were co-registered to contrast-enhanced T1 (T1-CE). Regions of interest based on T1-CE were transferred to the rCBV maps. rCBV was calculated using mean values and normalized using contralateral normal- appearing white matter. The Wilcoxon test was performed to assess for significant differences, and software-specific optimal rCBV cutoff values were determined using the Youden index. Interrater reliability was evaluated for two raters using the intraclass correlation coefficient. RESULTS: 41 patients (18 females; median age = 59 years; range 21-77 years) with 49 new or size-increasing post-treatment contrast-enhancing lesions were included (tumor progression = 40 lesions; pseudoprogression = 9 lesions). Optimal rCBV cutoffs of 1.31 (Syngo.via) and 2.40 (Olea) were significantly different, with an AUC of 0.74 and 0.78, respectively. Interrater reliability was 0.85. DISCUSSION: We demonstrate that different clinically available MRI DSC-perfusion software packages generate significantly different rCBV cutoff values for the differentiation of tumor progression from pseudoprogression in standard-of-care treated high grade gliomas. Physicians may want to determine the unique value of their perfusion software packages on an institutional level in order to maximize diagnostic accuracy when faced with this clinical challenge. Furthermore, combined with implementation of current DSC-perfusion recommendations, multi-center comparability will be improved.

Resolving the Smoking Paradox: No Evidence for Smoking-Induced Preconditioning in Large Vessel Occlusion Stroke.

INTRODUCTION: Smoking is an established risk factor for stroke. However, several studies have reported a better outcome after stroke for patients who smoke. According to this "smoking paradox" hypothesis, smoking might promote less severe strokes, higher collateral scores, and smaller infarct cores. METHODS: In this retrospective study, we screened data of 2,980 acute ischemic stroke patients with MCA-M1 occlusion treated with mechanical thrombectomy. Patients were categorized according to smoking status (current, former, or never). We assessed univariate associations between clinical characteristics and smoking status. Subsequently, we used adjusted regression analysis to evaluate associations of smoking with stroke severity on admission (National Institutes of Health Stroke Scale [NIHSS]; primary endpoint), infarct core volume, and collateral status (secondary endpoints). RESULTS: Out of 320 patients, 19.7% (n = 63) were current smokers and 18.8% (n = 60) were former smokers. Admission NIHSS, reperfusion success, and modified Rankin Scale (mRS) after 3-6 months were similar in all groups. Current smokers were younger, more often male and less likely to have atrial fibrillation compared to former and never smokers. In regression analyses, smoking status was neither associated with admission NIHSS (estimate 0.54, 95% confidence interval [CI]: -1.27-2.35, p = 0.557) nor with collateral status (estimate 0.79, 95% CI: 0.44-1.44, p = 0.447) or infarct core volume (estimate -0.69, 95% CI: -15.15-13.77, p = 0.925 for current vs. never smokers). CONCLUSION: We could not confirm the smoking paradox. Our results support the fact that smoking causes stroke at a younger age, highlighting the role of smoking as a modifiable vascular risk factor.

A dual-center validation of the PIRAMD scoring system for assessing the severity of ischemic Moyamoya disease.

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.

World federation of interventional and therapeutic neuroradiology (WFITN) federation assembly neurointerventional surgery safety checklist.

Over the last 10 years, there has been a rise in neurointerventional case complexity, device variety and physician distractions. Even among experienced physicians, this trend challenges our memory and concentration, making it more difficult to remember safety principles and their implications. Checklists are regarded by some as a redundant exercise that wastes time, or as an attack on physician autonomy. However, given the increasing case and disease complexity along with the number of distractions, it is even more important now to have a compelling reminder of safety principles that preserve habits that are susceptible to being overlooked because they seem mundane. Most hospitals have mandated a pre-procedure neurointerventional time-out checklist, but often it ends up being done in a cursory fashion for the primary purpose of 'checking off boxes'. There may be value in iterating the checklist to further emphasize safety and communication. The Federation Assembly of the World Federation of Interventional and Therapeutic Neuroradiology (WFITN) decided to construct a checklist for neurointerventional cases based on a review of the literature and insights from an expert panel.

Interaction between intravenous thrombolysis and clinical outcome between slow and fast progressors undergoing mechanical thrombectomy: a post-hoc analysis of the SWIFT-DIRECT trial.

BACKGROUND: In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors. METHODS: The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0-2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay. RESULTS: We included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65-81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13-20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses. CONCLUSION: In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors.

Prognostic assessment in patients operated for brain metastasis from systemic tumors.

BACKGROUND: Established models for prognostic assessment in patients with brain metastasis do not stratify for prior surgery. Here we tested the prognostic accuracy of the Graded Prognostic Assessment (GPA) score model in patients operated for BM and explored further prognostic factors. METHODS: We included 285 patients operated for brain metastasis at the University Hospital Zurich in the analysis. Information on patient characteristics, imaging, staging, peri- and postoperative complications and survival were extracted from the files and integrated into a multivariate Cox hazard model. RESULTS: The GPA score showed an association with outcome. We further identified residual tumor after surgery (p = 0.007, hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.1-2.3) steroid use (p = 0.021, HR 1.7, 95% CI 1.1-2.6) and number of extracranial metastasis sites (p = 0.009, HR 1.4, 95% CI 1.1-1.6) at the time of surgery as independent prognostic factors. A trend was observed for postoperative infection of the subarachnoid space (p = 0.102, HR 3.5, 95% CI 0.8-15.7). CONCLUSIONS: We confirm the prognostic capacity of the GPA score in a cohort of operated patients with brain metastasis. However, extent of resection and steroid use provide additional aid for the prognostic assessment in these patients.

Single-antiplatelet regimen in ruptured cerebral blood blister and dissecting aneurysms treated with flow-diverter stent reconstruction.

BACKGROUND: Flow diversion treatment of ruptured cerebral aneurysms remains challenging due to the need for double-antiplatelet therapy. We report our experience with flow-diverter stent (FDS) reconstruction with single-antiplatelet therapy of ruptured cerebral blood blister and dissecting aneurysms. METHODS: In this case series we performed a retrospective analysis of all patients with ruptured cerebral aneurysms who were treated with a phosphoryl-bonded FDS between 2019 and 2022 in a single center. Periprocedurally, all patients received weight-adapted eptifibatide IV and heparin IV. After 6-24 hours, eptifibatide was switched to oral prasugrel as monotherapy. We analyzed the rate of bleeding complications, thromboembolic events, occlusion rate and clinical outcome. RESULTS: Nine patients with subarachnoid hemorrhage were treated, eight within 24 hours of symptom onset. Seven patients were treated with one FDS and two patients received two FDS in a telescopic fashion. Two aneurysms were additionally coil embolized. Fatal re-rupture occurred in one case; eight patients survived and had no adverse events associated with the FDS. Six patients showed complete occlusion of the aneurysm after 3 months (n=2) and 1 year (n=4), respectively. Two patients showed subtotal occlusion of the aneurysm at the last follow-up after 3 months and 6 months, respectively. Favorable clinical outcome was achieved in five patients. CONCLUSIONS: Peri-interventional single-antiplatelet therapy with eptifibatide followed by prasugrel was sufficient to prevent thromboembolic events and reduce re-bleeding using an anti-thrombogenic FDS. FDS with single-antiplatelet therapy might be a viable option for ruptured blood blister and dissecting cerebral aneurysms.

Hemodynamic Imaging in Cerebral Diffuse Glioma-Part A: Concept, Differential Diagnosis and Tumor Grading.

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.

Hemodynamic Imaging in Cerebral Diffuse Glioma-Part B: Molecular Correlates, Treatment Effect Monitoring, Prognosis, and Future Directions.

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.

Flow augmentation STA-MCA bypass evaluation for patients with acute stroke and unilateral large vessel occlusion: a proposal for an urgent bypass flowchart.

OBJECTIVE: Endovascular recanalization trials have shown a positive impact on the preservation of ischemic penumbra in patients with acute large vessel occlusion (LVO). The concept of penumbra salvation can be extended to surgical revascularization with bypass in highly selected patients. For selecting these patients, the authors propose a flowchart based on multimodal MRI. METHODS: All patients with acute stroke and persisting internal carotid artery (ICA) or M1 occlusion after intravenous lysis or mechanical thrombectomy undergo advanced neuroimaging in a time window of 72 hours after stroke onset including perfusion MRI, blood oxygenation level-dependent functional MRI to evaluate cerebrovascular reactivity (BOLD-CVR), and noninvasive optimal vessel analysis (NOVA) quantitative MRA to assess collateral circulation. RESULTS: Symptomatic patients exhibiting persistent hemodynamic impairment and insufficient collateral circulation could benefit from bypass surgery. According to the flowchart, a bypass is considered for patients 1) with low or moderate neurological impairment (National Institutes of Health Stroke Scale score 1-15, modified Rankin Scale score ≤ 3), 2) without large or malignant stroke, 3) without intracranial hemorrhage, 4) with MR perfusion/diffusion mismatch > 120%, 5) with paradoxical BOLD-CVR in the occluded vascular territory, and 6) with insufficient collateral circulation. CONCLUSIONS: The proposed flowchart is based on the patient's clinical condition and multimodal MR neuroimaging and aims to select patients with acute stroke due to LVO and persistent inadequate collateral flow, who could benefit from urgent bypass.

Feasibility of glioblastoma tissue response mapping with physiologic BOLD imaging using precise oxygen and carbon dioxide challenge.

OBJECTIVES: Innovative physiologic MRI development focuses on depiction of heterogenous vascular and metabolic features in glioblastoma. For this feasibility study, we employed blood oxygenation level-dependent (BOLD) MRI with standardized and precise carbon dioxide (CO2) and oxygen (O2) modulation to investigate specific tumor tissue response patterns in patients with newly diagnosed glioblastoma. MATERIALS AND METHODS: Seven newly diagnosed untreated patients with suspected glioblastoma were prospectively included to undergo a BOLD study with combined CO2 and O2 standardized protocol. %BOLD signal change/mmHg during hypercapnic, hypoxic, and hyperoxic stimulus was calculated in the whole brain, tumor lesion and segmented volumes of interest (VOI) [contrast-enhancing (CE) - tumor, necrosis and edema] to analyze their tissue response patterns. RESULTS: Quantification of BOLD signal change after gas challenges can be used to identify specific responses to standardized stimuli in glioblastoma patients. Integration of this approach with automatic VOI segmentation grants improved characterization of tumor subzones and edema. Magnitude of BOLD signal change during the 3 stimuli can be visualized at voxel precision through color-coded maps overlayed onto whole brain and identified VOIs. CONCLUSIONS: Our preliminary investigation shows good feasibility of BOLD with standardized and precise CO2 and O2 modulation as an emerging physiologic imaging technique to detail specific glioblastoma characteristics. The unique tissue response patterns generated can be further investigated to better detail glioblastoma lesions and gauge treatment response.