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Background and purposeIn 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 and collateral recruitment, 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.MethodsFrom 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.ResultsIncluded patients (n=21) exhibited steal phenomenon to different extents, whereas there was only a partial spatial overlap with the DWI lesion (median 18.51%; IQR, 8.44-59.09). 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.ConclusionsPatients 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.

For patients with symptomatic unilateral internal carotid artery (ICA) occlusion, impaired cerebrovascular reactivity (CVR) indicates increased stroke risk. Here, the role of collateral activation remains a matter of debate, whereas angio-anatomical collateral abundancy does not necessarily imply sufficient compensatory flow provided. We aimed to further elucidate the role of collateral activation in the presence of impaired CVR. From a prospective database, 62 patients with symptomatic unilateral ICA occlusion underwent blood oxygenation-level dependent (BOLD) fMRI CVR imaging and a transcranial Doppler (TCD) investigation for primary and secondary collateral activation. Descriptive statistic and multivariate analysis were used to evaluate the relationship between BOLD-CVR values and collateral activation. Patients with activated secondary collaterals exhibited more impaired BOLD-CVR values of the ipsilateral hemisphere (p = 0.02). Specifically, activation of leptomeningeal collaterals showed severely impaired ipsilateral hemisphere BOLD-CVR values when compared to activation of ophthalmic collaterals (0.05 ± 0.09 vs. 0.12 ± 0.04, p = 0.005). Moreover, the prediction analysis showed leptomeningeal collateral activation as a strong independent predictor for ipsilateral hemispheric BOLD-CVR. In our study, ipsilateral leptomeningeal collateral activation is the sole collateral pathway associated with severely impaired BOLD-CVR in patients with symptomatic unilateral ICA occlusion.

BACKGROUND In patients with steno-occlusive disease, recent findings suggest that hemodynamic alterations may also be associated with crossed cerebellar diaschisis (CCD) rather than a functional disruption alone. PURPOSE To use a quantitative multiparametric hemodynamic MRI to gain a better understanding of hemodynamic changes related to CCD in patients with unilateral anterior circulation stroke. STUDY TYPE Prospective cohort study. POPULATION Twenty-four patients (25 datasets) with symptomatic unilateral anterior circulation stroke. FIELD STRENGTH/SEQUENCE 3T/two sequences: single-shot (echo-planar imaging) EPI sequence and T2* gradient echo perfusion-weighted imaging study. ASSESSMENT The presence of CCD was inferred from the cerebellar asymmetry index (CAI) of the blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) exam, which was calculated from the mean BOLD-CVR and standard deviation of the CAI of the healthy control group. For all perfusion-weighted (PW)-MRI parameters, the cerebellar and middle cerebral artery (MCA) territory asymmetry indices were calculated. STATISTICAL TESTS Independent Student's t-test to compare the variables from the CCD positive(+) and CCD negative(-) groups and analysis of covariance (ANCOVA) to statistically control the effect of covariates (infarct volume and time since ischemia onset). RESULTS CCD was present in 33% of patients. In the MCA territory of the affected hemisphere, BOLD-CVR was significantly more impaired in the CCD(+) group as compared to the CCD(-) group (mean BOLD-CVR ± SD [%BOLD signal/ΔmmHgCO2 ]: -0.03 ± 0.12 vs. 0.11 ± 0.13, P

Crossed cerebellar diaschisis (CCD) can be associated with impaired cerebrovascular reactivity (CVR) and poor clinical outcome, but whether this holds true for patients with diffuse glioma is unknown. With blood oxygenation level–dependent (BOLD)-CVR imaging, we determined the presence of CCD in patients with diffuse glioma and investigated its relationship with cerebrovascular reactivity and clinical outcome. For eighteen enrolled subjects (nineteen datasets) with diffuse glioma, CCD was deferred from BOLD-CVR using a predetermined cerebellar asymmetry index (CAI) cutoff value of 6.0%. A FET-PET study was done as a verification of the CCD diagnosis. BOLD-CVR values as well as clinical performance scores (i.e., Karnofsky performance score (KPS), disability rating scale (DRS), and modified Rankin scale (mRS)) by BOLD-CVR scan at 3-month clinical follow-up were assessed and compared for the CCD-positive and CCD-negative group. CCD was present in 26.3% of subjects and strongly associated with impaired BOLD-CVR of the affected (i.e., the hemisphere harboring the glioma) and unaffected supratentorial hemisphere (CCD(+) vs. CCD(−): 0.08 ± 0.11 vs. 0.18 ± 0.04; p = 0.007 and 0.08 ± 0.12 vs. 0.19 ± 0.04; p = 0.007, respectively). This finding was independent of tumor volume (p = 0.48). Furthermore, poorer initial (by scan) clinical performance scores at follow-up were found for the CCD(+) group. The presence of crossed cerebellar diaschisis in patients with diffuse glioma is associated with impaired supratentorial cerebrovascular reactivity and worse clinical outcome. Electronic supplementary material The online version of this article (10.1007/s12311-020-01174-y) contains supplementary material, which is available to authorized users.

Crossed cerebellar diaschisis (CCD) in internal carotid artery (ICA) stroke refers to attenuated blood flow and energy metabolism in the contralateral cerebellar hemisphere. CCD is associated with an interruption of cerebro-cerebellar tracts, but the precise mechanism is unknown. We hypothesized that in patients with ICA occlusions, CCD might indicate severe hemodynamic impairment in addition to tissue damage. Duplex sonography and clinical data from stroke patients with unilateral ICAO who underwent blood oxygen-level-dependent MRI cerebrovascular reserve (BOLD-CVR) assessment were analysed. The presence of CCD (either CCD+ or CCD−) was inferred from BOLD-CVR. We considered regions with negative BOLD-CVR signal as areas suffering from hemodynamic steal. Twenty-five patients were included (11 CCD+ and 14 CCD−). Stroke deficits on admission and at 3 months were more severe in the CCD+ group. While infarct volumes were similar, CCD+ patients had markedly larger BOLD steal volumes than CCD− patients (median [IQR] 122.2 [111] vs. 11.6 [50.6] ml; p

Background Accuracy of intraoperative cerebrovascular neuronavigation is difficult to maintain because of the ongoing need for brain shift correction. By including 3-dimensional rotational intraoperative digital subtraction angiography (3D-iDSA), the intraoperative cerebrovascular neuronavigation can be updated and upgraded throughout the microneurosurgical procedure. The aim of this technical note is to demonstrate the feasibility and advantage of updating and upgrading the accuracy of targeted cerebrovascular neuronavigation with an intraoperative 3D-DSA dataset. Methods A preoperative diagnostic selective 3D-DSA was registered with the neuronavigation software, followed by the automated segmentation of the vascular object of interest (an aneurysm in this case). After acquiring additional 3D-iDSA volumes, these steps were repeated, thereby updating the cerebrovascular roadmap and neuronavigation accuracy (i.e., brain shift correction). Results This technique was applied successfully in a patient who underwent elective microneurosurgical clipping of a right-sided middle cerebral artery (MCA) bifurcation aneurysm in a hybrid neurosurgical operating setting. After clipping of the MCA aneurysm, a selective 3D iDSA was performed that was then used to update the projection and accuracy of the initial 3D neurovascular object of interest (i.e., the aneurysm). In this revised rotational view, the projection refined the target segments of the clipped MCA aneurysm, the accuracy of clipping, and brain shift correction. Conclusions 3D-iDSA vascular segmentations can update und upgrade the intraoperative neurovascular roadmap by thereby enhancing accuracy of cerebrovascular neuronavigation, as well as correcting brain shift. This technique is feasible within the hybrid operation room. Evaluation in larger series is required to support these findings.

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 (COSeven newly diagnosed untreated patients with suspected glioblastoma were prospectively included to undergo a BOLD study with combined COQuantification 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.Our preliminary investigation shows good feasibility of BOLD with standardized and precise CO

Machine learning (ML) and artificial intelligence (AI) applications in the field of neuroimaging have been on the rise in recent years, and their clinical adoption is increasing worldwide. Deep learning (DL) is a field of ML that can be defined as a set of algorithms enabling a computer to be fed with raw data and progressively discover-through multiple layers of representation-more complex and abstract patterns in large data sets. The combination of ML and radiomics, namely the extraction of features from medical images, has proven valuable, too: Radiomic information can be used for enhanced image characterization and prognosis or outcome prediction. This chapter summarizes the basic concepts underlying ML application for neuroimaging and discusses technical aspects of the most promising algorithms, with a specific focus on Convolutional Neural Networks (CNNs) and Generative Adversarial Networks (GANs), in order to provide the readership with the fundamental theoretical tools to better understand ML in neuroimaging. Applications are highlighted from a practical standpoint in the last section of the chapter, including: image reconstruction and restoration, image synthesis and super-resolution, registration, segmentation, classification, and outcome prediction.

PurposeCell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) may be one of the main drivers of secondary brain injury after aneurysmal subarachnoid hemorrhage. Haptoglobin scavenging of CSF-Hb has been shown to mitigate cerebrovascular disruption. Using digital subtraction angiography (DSA) and blood oxygenation-level dependent cerebrovascular reactivity imaging (BOLD-CVR) the aim was to assess the acute toxic effect of CSF-Hb on cerebral blood flow and autoregulation, as well as to test the protective effects of haptoglobin.MethodsDSA imaging was performed in eight anesthetized and ventilated sheep (mean weight: 80.4 kg) at baseline, 15, 30, 45 and 60 minutes after infusion of hemoglobin (Hb) or co-infusion with haptoglobin (Hb:Haptoglobin) into the left lateral ventricle. Additionally, 10 ventilated sheep (mean weight: 79.8 kg) underwent BOLD-CVR imaging to assess the cerebrovascular reserve capacity.ResultsDSA imaging did not show a difference in mean transit time or cerebral blood flow. Wholebrain BOLD-CVR compared to baseline decreased more in the Hb group after 15 minutes (Hb vs Hb:Haptoglobin: −0.03 ±0.01 vs −0.01 ±0.02) and remained diminished compared to Hb:Haptoglobin group after 30 minutes (Hb vs Hb:Haptoglobin: −0.03 ±0.01 vs 0.0 ±0.01), 45 minutes (Hb vs Hb:Haptoglobin: −0.03 ±0.01 vs 0.01 ±0.02) and 60 minutes (Hb vs Hb:Haptoglobin: −0.03 ±0.02 vs 0.01 ±0.01).ConclusionIt is demonstrated that CSF-Hb toxicity leads to rapid cerebrovascular reactivity impairment, which is blunted by haptoglobin co-infusion. BOLD-CVR may therefore be further evaluated as a monitoring strategy for CSF-Hb toxicity after aSAH.

Machine learning (ML) and artificial intelligence (AI) applications in the field of neuroimaging have been on the rise in recent years, and their clinical adoption is increasing worldwide. Deep learning (DL) is a field of ML that can be defined as a set of algorithms enabling a computer to be fed with raw data and progressively discover-through multiple layers of representation-more complex and abstract patterns in large data sets. The combination of ML and radiomics, namely the extraction of features from medical images, has proven valuable, too: Radiomic information can be used for enhanced image characterization and prognosis or outcome prediction. This chapter summarizes the basic concepts underlying ML application for neuroimaging and discusses technical aspects of the most promising algorithms, with a specific focus on Convolutional Neural Networks (CNNs) and Generative Adversarial Networks (GANs), in order to provide the readership with the fundamental theoretical tools to better understand ML in neuroimaging. Applications are highlighted from a practical standpoint in the last section of the chapter, including: image reconstruction and restoration, image synthesis and super-resolution, registration, segmentation, classification, and outcome prediction.

Remote dysconnectivity following cerebellar ischaemic stroke may have a negative impact on supratentorial brain tissue. Since the cerebellum is connected to the individual cerebral lobes via contralateral tracts, cerebellar lesion topography might determine the distribution of contralateral supratentorial brain tissue changes. We investigated (i) the occurrence of delayed cerebral atrophy after cerebellar ischaemic stroke and its relationship to infarct volume; (ii) whether cerebellar stroke topography determines supratentorial atrophy location; and (iii) how cortical atrophy after cerebellar stroke impacts clinical outcome. We performed longitudinal volumetric MRI analysis of patients with isolated cerebellar stroke from the Swiss Stroke Registry database. Stroke location and volume were determined at baseline MRI. Delayed cerebral atrophy was measured as supratentorial cortical volumetric change at follow-up, in contralateral target as compared to ipsilateral reference-areas. In patients with bilateral stroke, both hemispheres were analysed separately. We obtained maps of how cerebellar lesion topography, determines the probability of delayed atrophy per distinct cerebral lobe. Clinical performance was measured with the National Institutes of Health Stroke Scale and modified Rankin Scale. In 29 patients (age 58 ± 18; 9 females; median follow-up: 6.2 months), with 36 datasets (7 patients with bilateral cerebellar stroke), delayed cerebral atrophy occurred in 28 (78%) datasets. A multivariable generalized linear model for a Poisson distribution showed that infarct volume (milliliter) in bilateral stroke patients was positively associated with the number of atrophic target areas (Rate ratio = 1.08; P = 0.01). Lobe-specific cerebral atrophy related to distinct topographical cerebellar stroke patterns. By ordinal logistic regression (shift analysis), more atrophic areas predicted higher 3-month mRS scores in patients with low baseline scores (baseline score 3–5: Odds ratio = 1.34; P = 0.02; baseline score 0–2: OR = 0.71; P = 0.19). Our results indicate that (i) isolated cerebellar ischaemic stroke commonly results in delayed cerebral atrophy and stroke volume determines the severity of cerebral atrophy in patients with bilateral stroke; (ii) cerebellar stroke topography affects the location of delayed cerebral atrophy; and (iii) delayed cerebral atrophy negatively impacts clinical outcome., Van Niftrik et al. show that cerebellar stroke commonly results in delayed cerebral atrophy and that stroke volume determines the severity of atrophy in patients with bilateral stroke. Furthermore, they observed that cerebellar stroke topography affects the location of cerebral atrophy and that delayed cerebral atrophy negatively impacts clinical outcome., Graphical Abstract Graphical Abstract

OBJECTIVE In symptomatic patients with cerebrovascular steno-occlusive disease, impaired blood oxygenation level–dependent cerebrovascular reactivity (BOLD-CVR) and increased flow velocity of the P2 segment of the posterior cerebral artery (PCA-P2) on transcranial Doppler (TCD) ultrasonography have been introduced as emerging clinical imaging parameters to identify patients at high risk for recurrent ischemic events. Since hemodynamic physiology differs between the acute and chronic stages of ischemic stroke, the authors sought to investigate whether those parameters have merit for both the acute and chronic stages of ischemic stroke. METHODS From a prospective database, patients who underwent BOLD-CVR and TCD examinations in the acute stroke stage (< 10 days) were matched to patients in the chronic stroke stage (> 3 months). A linear regression analysis for both groups was performed between ipsilateral PCA-P2 systolic flow velocity and BOLD-CVR of the ipsilateral (affected) hemisphere, the ipsilateral middle cerebral artery (MCA) territory, and the ipsilateral steal volume (i.e., paradoxical BOLD-CVR response). The resulting slopes and intercepts were statistically compared to evaluate differences between groups. RESULTS Forty matched patient pairs were included. Regression analysis showed no significant difference for either the intercept (p = 0.84) or the slope (p = 0.85) between PCA-P2 flow velocity and BOLD-CVR as measured for the ipsilateral (affected) hemisphere. Similarly, no significant difference was seen between PCA-P2 flow velocity and BOLD-CVR of the ipsilateral MCA territory (intercept, p = 0.72; slope, p = 0.36) or between PCA-P2 flow velocity and steal volume (intercept, p = 0.59; slope, p = 0.34). CONCLUSIONS The study results indicated that the relationship between ipsilateral PCA-P2 systolic flow velocity and BOLD-CVR remains the same during the acute and chronic stages of ischemic stroke. This provides further support that these novel hemodynamic imaging parameters may have merit to assess the risk for recurrent ischemic events for a wide ischemic stroke population. PCA-P2 systolic flow velocity, in particular, may be a highly practical screening tool, independent of ischemic stroke stage.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is one of the most common neurosurgical complications, occurring in 4% to 32% of surgical cases, with a higher incidence in complicated skull base surgery, intradural spine surgery, and the surgery of the posterior fossa. Our group developed a Dural Sealant Patch (DSP) for watertight dural closure after cranial surgery. OBJECTIVE: To clinically study for the first time the safety and performance of the DSP as a means of reducing CSF leakage in patients undergoing elective cranial intradural surgery with a dural closure procedure. METHODS: We will conduct an open-label, single-arm, multicenter study with a 360 d (12 mo) follow-up. A total of 40 patients will be enrolled at 3 sites. The primary endpoint is a combination of occurrences of one of the following events: postoperative percutaneous CSF leakage, intraoperative leakage at 20 cm H2O, or postoperative wound infection. The secondary endpoints are pseudomeningocele and thickness of dura + DSP. EXPECTED OUTCOMES: Not more than 3 patients will meet the primary endpoint suggesting safety and efficacy. DISCUSSION: As a next step, a randomized controlled trial against the best current practice will follow to evaluate if DSP reduces CSF leakage while its safety is noninferior. © Congress of Neurological Surgeons 2019.

Introduction Reliable preoperative identification of patients at high risk for early postoperative complications occurring within 24 h (EPC) of intracranial tumor surgery can improve patient safety and postoperative management. Statistical analysis using machine learning algorithms may generate models that predict EPC better than conventional statistical methods. Objective To train such a model and to assess its predictive ability. Methods This cohort study included patients from an ongoing prospective patient registry at a single tertiary care center with an intracranial tumor that underwent elective neurosurgery between June 2015 and May 2017. EPC were categorized based on the Clavien-Dindo classification score. Conventional statistical methods and different machine learning algorithms were used to predict EPC using preoperatively available patient, clinical, and surgery-related variables. The performance of each model was derived from examining classification performance metrics on an out-of-sample test dataset. Results EPC occurred in 174 (26%) of 668 patients included in the analysis. Gradient boosting machine learning algorithms provided the model best predicting the probability of an EPC. The model scored an accuracy of 0.70 (confidence interval [CI] 0.59-0.79) with an area under the curve (AUC) of 0.73 and a sensitivity and specificity of 0.80 (CI 0.58-0.91) and 0.67 (CI 0.53-0.77) on the test set. The conventional statistical model showed inferior predictive power (test set: accuracy: 0.59 (CI 0.47-0.71); AUC: 0.64; sensitivity: 0.76 (CI 0.64-0.85); specificity: 0.53 (CI 0.41-0.64)). Conclusion Using gradient boosting machine learning algorithms, it was possible to create a prediction model superior to conventional statistical methods. While conventional statistical methods favor patients' characteristics, we found the pathology and surgery-related (histology, anatomical localization, surgical access) variables to be better predictors of EPC.

Background Comprehensive hemodynamic impairment mapping using blood oxygenation‐level dependent (BOLD) cerebrovascular reactivity (CVR) can be used to identify hemodynamically relevant symptomatic unilateral carotid artery disease. Methods and Results This prospective cohort study was conducted between February 2015 and July 2020 at the Clinical Neuroscience Center of the University Hospital Zurich, Zurich, Switzerland. One hundred two patients with newly diagnosed symptomatic unilateral internal carotid artery (ICA) occlusion or with 70% to 99% ICA stenosis were included. An age‐matched healthy cohort of 12 subjects underwent an identical BOLD functional magnetic resonance imaging examination. Using BOLD functional magnetic resonance imaging with a standardized CO 2 stimulus, CVR impairment was evaluated. Moreover, embolic versus hemodynamic ischemic patterns were evaluated on diffusion‐weighted imaging. Sixty‐seven patients had unilateral ICA occlusion and 35 patients unilateral 70% to 99% ICA stenosis. Patients with ICA occlusion exhibited lower whole‐brain and ipsilateral hemisphere mean BOLD‐CVR values as compared with healthy subjects (0.12±0.08 versus 0.19±0.04, P =0.004 and 0.09±0.09 versus 0.18±0.04, P P =0.01 and 0.09±0.09 versus 0.15±0.05, P =0.01); however, only 40 (58%) patients of the cohort showed significant BOLD‐CVR impairment. Conversely, there was no difference in mean BOLD‐CVR values between healthy patients and patients with ICA stenosis, although 5 (14%) patients with ICA stenosis showed a significant BOLD‐CVR impairment. No significant BOLD‐CVR difference was discernible between patients with hemodynamic ischemic infarcts versus those with embolic infarct distribution (0.11±0.08 versus 0.13±0.06, P =0.12). Conclusions Comprehensive BOLD‐CVR mapping allows for identification of hemodynamically relevant symptomatic unilateral carotid artery stenosis or occlusion.

Background Diffuse gliomas exhibit diffuse infiltrative growth, often beyond the magnetic resonance imaging (MRI)-detectable tumor lesion. Within this lesion, hypermetabolism and impaired cerebrovascular reactivity (CVR) are found, but its exact distribution pattern into the peritumoral environment is unknown. Our aim was to better characterize the extent of diffuse glioma tissue infiltration, beyond the visible lesion (ie, beyond the T1-contrast-enhancing lesion and/or T2/FLAIR-defined tumor border), with metabolic positron emission tomography (PET), and functional MRI CVR (blood oxygenation-level-dependent CVR [BOLD-CVR]) mapping. Methods From a prospective glioma database, 18 subjects (19 datasets) with diffuse glioma (n = 2 with anaplastic astrocytoma, n = 10 with anaplastic oligodendroglioma, and n = 7 with glioblastoma) underwent a BOLD-CVR and metabolic PET study between February 2016 and September 2019, 7 of them at primary diagnosis and 12 at tumor recurrence. In addition, 19 matched healthy controls underwent an identical BOLD-CVR study. The tumor lesion was defined using high-resolution anatomical MRI. Volumes of interest starting from the tumor lesion outward up to 30 mm were created for a detailed peritumoral PET and BOLD-CVR tissue analysis. Student’s t test was used for statistical analysis. Results Patients with diffuse glioma exhibit impaired BOLD-CVR 12 mm beyond the tumor lesion (P = .02) with normalization of BOLD-CVR values after 24 mm. Metabolic PET shows a difference between the affected and contralateral hemisphere of 6 mm (P = .05) with PET values normalization after 12 mm. Conclusion We demonstrate hypermetabolism and impaired CVR beyond the standard MRI-defined tumor border, suggesting active tumor infiltration in the peritumoral environment.

Blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) has gained attention in recent years as an effective way to investigate CVR, a measure of the hemodynamic state of the brain, with high spatial and temporal resolution. An association between impaired CVR and diverse pathologies has been observed, especially in ischemic cerebrovascular diseases and brain gliomas. The ability to obtain this information intraoperatively is novel and has not been widely tested. We report our first experience with this intraoperative technique in vascular and oncologic neurosurgical patients, discuss the results of its feasibility, and the possible developments of the intraoperative employment of BOLD-CVR.

Increased Transcranial Doppler flow velocity in the ipsilateral P2-segment of the posterior cerebral artery (PCA-P2: cm/second) is associated with recurrent cerebrovascular events in patients with unilateral internal carotid artery occlusion. However, its predictive value and correlation with hemodynamic impairment in an overall stroke patient cohort remains to be determined.Transcranial doppler PCA-P2 flow velocity was measured in 88 patients with symptomatic unilateral steno-occlusive disease who also underwent blood oxygenation-level dependent cerebrovascular reactivity imaging (blood oxygenation-level dependent [BOLD]-cerebrovascular reactivity [CVR]). A multivariate linear regression was used to evaluate the independent correlation between the ipsilateral PCA-P2 flow velocity measurements and hemispheric BOLD-CVR. Follow-up BOLD-CVR imaging data, available in 25 patients, were used to evaluate the temporal evolution of the BOLD-CVR and PCA-P2 flow velocity association using a mixed-effect model. Furthermore, a transcranial doppler cutoff for hemodynamic failure stage 2 was determined.The ipsilateral systolic PCA-P2 flow velocity strongly correlated with hemispheric BOLD-CVR (R=0.79; RIn patients with symptomatic unilateral steno-occlusive disease, increased ipsilateral transcranial doppler PCA-P2 systolic flow velocity independently correlates with BOLD-CVR based hemodynamic failure. A cutoff value of 85 cm/second appears to indicate hemodynamic failure stage 2, but this finding needs to be validated in an independent patient cohort.

Background: Current imaging-based discrimination between radiation necrosis versus recurrent glioblastoma contrast-enhancing lesions remains imprecise but is paramount for prognostic and therapeutic evaluation. We examined whether patients with radiation necrosis exhibit distinct patterns of blood oxygenation-level dependent fMRI cerebrovascular reactivity (BOLD-CVR) as the first step to better distinguishing patients with radiation necrosis from recurrent glioblastoma compared with patients with newly diagnosed glioblastoma before surgery and radiotherapy. Methods: Eight consecutive patients with primary and secondary brain tumors and a multidisciplinary clinical and radiological diagnosis of radiation necrosis, and fourteen patients with a first diagnosis of glioblastoma underwent BOLD-CVR mapping. For all these patients, the contrast-enhancing lesion was derived from high-resolution T1-weighted MRI and rendered the volume-of-interest (VOI). From this primary VOI, additional 3 mm concentric expanding VOIs up to 30 mm were created for a detailed perilesional BOLD-CVR tissue analysis between the two groups. Receiver operating characteristic curves assessed the discriminative properties of BOLD-CVR for both groups. Results: Mean intralesional BOLD-CVR values were markedly lower in radiation necrosis than in glioblastoma contrast-enhancing lesions (0.001 ± 0.06 vs. 0.057 ± 0.05, p = 0.04). Perilesionally, a characteristic BOLD-CVR pattern was observed for radiation necrosis and glioblastoma patients, with an improvement of BOLD-CVR values in the radiation necrosis group and persisting lower perilesional BOLD-CVR values in glioblastoma patients. The ROC analysis discriminated against both groups when these two parameters were analyzed together (area under the curve: 0.85, 95% CI: 0.65–1.00). Conclusions: In this preliminary analysis, distinctive intralesional and perilesional BOLD-cerebrovascular reactivity patterns are found for radiation necrosis.

ObjectiveSpecific anatomical patterns are seen in various diseases affecting the brain. Clinical studies on the topography of pathologies are often limited by the absence of a normalization of the prevalence of pathologies to the relative volume of the affected anatomical structures. A comprehensive reference on the relative volumes of clinically relevant anatomical structures serving for such a normalization, is currently lacking.MethodsThe analyses are based on anatomical high-resolution three-dimensional T1-weighted magnetic resonance imaging data of 30 healthy Caucasian volunteers, including 14 females (mean age 37.79 years, SD 13.04) and 16 males (mean age 38.31 years, SD 16.91). Semi-automated anatomical segmentation was used, guided by a neuroanatomical parcellation algorithm differentiating 96 structures. Relative volumes were derived by normalizing parenchymal structures to the total individual encephalic volume and ventricular segments to the total individual ventricular volume.ResultsThe present investigation provides the absolute and relative volumes of 96 anatomical parcellation units of the human encephalon. A larger absolute volume in males than in females is found for almost all parcellation units. While parenchymal structures display a trend towards decreasing volumes with increasing age, a significant inverse effect is seen with the ventricular system. The variances in volumes as well as the effects of gender and age are given for each structure before and after normalization.ConclusionThe provided atlas constitutes an anatomically detailed and comprehensive analysis of the absolute and relative volumes of the human encephalic structures using a clinically oriented parcellation algorithm. It is intended to serve as a reference for volume-standardization in clinical studies on the topographic prevalence of pathologies.

Blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) has gained attention in recent years as an effective way to investigate CVR, a measure of the hemodynamic state of the brain, with high spatial and temporal resolution. An association between impaired CVR and diverse pathologies has been observed, especially in ischemic cerebrovascular diseases and brain gliomas. The ability to obtain this information intraoperatively is novel and has not been widely tested. We report our first experience with this intraoperative technique in vascular and oncologic neurosurgical patients, discuss the results of its feasibility, and the possible developments of the intraoperative employment of BOLD-CVR.

INTRODUCTION Results of two randomized trials did not show benefit of revascularization with extracranial-intracranial (EC-IC) flow augmentation bypass in patients with symptomatic occlusion of internal carotid artery (ICA). However, patients with acute stroke were not included in these studies. Herein, we systematically analyze and discuss the literature about flow augmentation bypass for treatment of acute ischemic stroke. EVIDENCE ACQUISITION This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. MEDLINE, Web of Science and EMBASE were independently searched by two reviewers for published series to identify literature relating to EC-IC bypass in the surgical management of acute ischemic stroke up to June 2020. Studies were categorized according to their level of evidence. EVIDENCE SYNTHESIS Nineteen studies met the inclusion criteria for the systematic literature review, including 16 level IV studies (ten case series and six6 case reports) and three level III studies (retrospective cohort case-control studies). Occurrence of fatal or non-fatal ischemic or hemorrhagic postoperative stroke, as well as clinical functional outcome at follow-up were considered as primary and secondary endpoints, respectively. CONCLUSIONS The literature about flow augmentation bypass for treatment of acute ischemic stroke is scarce and heterogenous, with only 19 studies. The results of the present systematic review encourage further study to explore and validate the use of EC-IC bypass in the treatment of anterior circulation acute ischemic stroke in highly selected patients (symptomatic and with persistent penumbra despite best medical/endovascular treatment).

When evaluating brain arteriovenous malformations (bAVMs) for microsurgical resection, the natural history of bAVM rupture must be balanced against the perioperative risks. It is therefore adamant to have a reliable surgical grading system, balancing these important factors. This study systematically reviews the literature in order to identify and assess the quality of grading systems with regard to microsurgical bAVM treatment. A systematic literature review was performed to provide an overview of all available bAVM grading systems relevant for microsurgical treatment evaluation and to assess the most comprehensive grading system specifically for each subgroup of bAVM (i.e., unruptured, ruptured, and posterior fossa). Screening of 865 papers revealed thirteen grading systems for bAVM microsurgical risk stratification. Among them, two systems were specifically developed for ruptured bAVM and one specifically for posterior fossa bAVM. With one system being fundamentally different for supratentorial bAVM, the remaining nine systems used the same parameters: “size,” “eloquence,” “venous drainage,” “arterial feeders,” “age,” “nidus compactness,” and “hemorrhagic presentation”. This study provides a comprehensive overview of all available bAVM grading systems relevant for surgical risk stratification. Furthermore, in the absence of a universal system appropriate to score all bAVMs, a workflow for selection of the best applicable scoring system in accordance with bAVM subgroups is presented.

The presence of peritumorally impaired blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) has been unequivocally demonstrated in patients with diffuse glioma, and may have value to better identify tumor infiltration zone. Since BOLD-CVR does not measure hemodynamic changes directly, we performed additional MR perfusion studies to better characterize the peritumoral hemodynamic environment.Seventeen patients with WHO grade III and IV diffuse glioma underwent high resolution advanced hemodynamic MR imaging including BOLD-CVR and MR perfusion. The obtained multiparametric hemodynamic factors (i.e., regional cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT), time-to-peak (TTP) and BOLD-CVR, were analyzed within 10 concentric expanding 3 mm volumes of interest (VOIs) up to 30 mm from the tumor tissue mask.BOLD-CVR impairment was found within the tumor tissue mask and the peritumoral VOIs up to 21 mm as compared to the contralateral flipped CVR analysis (p0.05). In the affected hemisphere, we observed positive spatial correlations including all VOIs between BOLD-CVR and rCBV values (r=0.27; p0.001), rCBF (r=0.42; p0.001) and a negative correlation between BOLD-CVR and TTP (r=-0.47; p0.001).Peritumorally impaired BOLD-CVR is associated with concomitant hemodynamic alterations with severity correlating to tumor volume. The distribution of these multiparametric hemodynamic MRI patterns may be considered for future studies characterizing the hemodynamic peritumoral environment, thereby better identifying the extent of tumor infiltration.

Background Case fatality and poor outcome rates are different between brain arteriovenous malformation associated intracerebral hemorrhage (bAVM-ICH) and spontaneous intracerebral hemorrhage (SICH). These outcome rates, however, have never been compared in patients who need neurosurgical evacuation of the intracerebral hemorrhage (ICH). Objective To compare the short- and long-term functional outcome between surgically treated patients with bAVM-ICH and SICH. Methods We collected data from surgically treated ICH patients at the department of neurosurgery, University hospital Zurich, from January 2015 to July 2018. We performed logistic regression analysis to compare the functional outcome between groups, adjusting for demographics, admission characteristics and stroke risk factors. Results A total of 26 bAVM-ICH and 115 SICH patients were included in the final analysis. Patients with bAVM-ICH were younger and less likely to have hypertension without significant differences in ICH volume, hematoma location, intraventricular hemorrhage and other stroke risk factors. A significantly better functional outcome rate was seen in bAVM-ICH patients at short- and long-term follow-up. These differences remained significant after adjusting for confounders. Conclusions Patients with a bAVM who need surgical evacuation of an ICH have a more favorable outcome than surgically treated patients with spontaneous ICH, even after correction for confounding factors, such as younger age and less premorbid hypertension.