Efficacy Assessment of Cerebral Perfusion Augmentation Through Functional Connectivity in an Acute Canine Stroke Model.

BACKGROUND AND PURPOSE: Ischemic stroke disrupts functional connectivity within the brain's resting-state networks (RSNs), impacting recovery. This study evaluates the effects of NEH (Norepinephrine and Hydralazine), a cerebral perfusion augmentation therapy, on RSN integrity in a hyper-acute canine stroke model. MATERIALS AND METHODS: Fifteen adult purpose-bred mongrel canines, divided into treatment and control (natural history) groups, underwent endovascular induction of acute middle cerebral artery occlusion (MCAO). Post-occlusion, the treatment group received intra-arterial Norepinephrine (0.1-1.52 µg/kg/min, adjusted for 25-45 mmHg above baseline mean arterial pressure) and Hydralazine (20mg). Resting-state fMRI data were acquired with a 3.0 T scanner using a BOLD-sensitive EPI sequence (TR/TE=1400 ms/20ms, 2.5 mm slices, 300 temporal positions). Preprocessing included motion correction, spatial smoothing (2.5 mm FWHM), and high-pass filtering (0.01 Hz cutoff). Functional connectivity within RSNs were analyzed through group-level independent component analysis (ICA) and weighted whole-brain ROI-to-ROI connectome, pre-and post-MCAO. RESULTS: NEH therapy significantly maintained connectivity post-MCAO in the Higher-order Visual and Parietal RSNs, as evidenced by thresholded statistical mapping (TFCE p-corr > 0.95). However, this preservation was network-dependent, with no significant changes in the Primary Visual and Sensorimotor networks. CONCLUSIONS: NEH demonstrates potential as a proof-of-concept therapy for maintaining RSN functional connectivity following ischemic stroke, emphasizing the therapeutic promise of perfusion augmentation. These insights reinforce the role of functional connectivity as a measurable endpoint for stroke intervention efficacy, suggesting clinical translatability for patients with insufficient collateral circulation. ABBREVIATIONS: NEH＝ Norepinephrine and Hydralazine; RSN＝ Resting-State Network; ICA = Independent Component Analysis; rsfMRI = resting-state Functional Magnetic Resonance Imaging; MCAO = Middle Cerebral Artery Occlusion; TFCE = Threshold-Free Cluster Enhancement.

Quantitative perfusion and water transport time model from multi b-value diffusion magnetic resonance imaging validated against neutron capture microspheres.

Purpose: Quantification of perfusion in ml/100 g/min, rather than comparing relative values side-to-side, is critical at the clinical and research levels for large longitudinal and multi-center trials. Intravoxel incoherent motion (IVIM) is a non-contrast magnetic resonance imaging diffusion-based scan that uses a multitude of b-values to measure various speeds of molecular perfusion and diffusion, sidestepping inaccuracy of arterial input functions or bolus kinetics. Questions remain as to the original of the signal and whether IVIM returns quantitative and accurate perfusion in a pathology setting. This study tests a novel method of IVIM perfusion quantification compared with neutron capture microspheres. Approach: We derive an expression for the quantification of capillary blood flow in ml/100 g/min by solving the three-dimensional Gaussian probability distribution and defining water transport time (WTT) as when 50% of the original water remains in the tissue of interest. Calculations were verified in a six-subject pre-clinical canine model of normocapnia, CO2 induced hypercapnia, and middle cerebral artery occlusion (ischemic stroke) and compared with quantitative microsphere perfusion. Results: Linear regression analysis of IVIM and microsphere perfusion showed agreement (slope = 0.55, intercept = 52.5, R2=0.64) with a Bland-Altman mean difference of -11.8 [-78,54] ml/100 g/min. Linear regression between dynamic susceptibility contrast mean transit time and IVIM WTT asymmetry in infarcted tissue was excellent (slope=0.59, intercept = 0.3, R2=0.93). Strong linear agreement was found between IVIM and reference standard infarct volume (slope = 1.01, R2=0.79). The simulation of cerebrospinal fluid (CSF) suppression via inversion recovery returned a blood signal reduced by 82% from combined T1 and T2 effects. Conclusions: The accuracy and sensitivity of IVIM provides evidence that observed signal changes reflect cytotoxic edema and tissue perfusion and can be quantified with WTT. Partial volume contamination of CSF may be better removed during post-processing rather than with inversion recovery.

Augmentation of perfusion with simultaneous vasodilator and inotropic agents in experimental acute middle cerebral artery occlusion: a pilot study.

BACKGROUND: This study tests the hypothesis that simultaneous cerebral blood pressure elevation and potent vasodilation augments perfusion to ischemic tissue in acute ischemic stroke and it varies by degree of pial collateral recruitment. METHODS: Fifteen mongrel canines were included. Subjects underwent permanent middle cerebral artery occlusion; pial collateral recruitment was scored before treatment. Seven treatment subjects received a continuous infusion of norepinephrine (0.1-1.52 µg/kg/min; titrated 25-45 mmHg above baseline mean arterial pressure while keeping systolic blood pressure below 180 mmHg) and hydralazine (20 mg) starting 30 min post-occlusion. Perfusion (cerebral blood flow-CBF) was evaluated with quantitative dynamic susceptibility contrast MRI 2.5 hours post-occlusion to produce images in mL/100 g/min, and relative CBF measured as ratios. Mean region of interest (ROI) values were reported, and compared and subject to regression analysis to elucidate trends. RESULTS: Differences in quantitative CBF (qCBF) between treatment and control group varied by degree of pial collateral recruitment, based on Wilcoxon rank sum scores and regression model fit. For poorly collateralized subjects, ipsilateral anatomic, core infarct, and penumbra regions showed treatment with higher qCBF, raised above the ischemic threshold, compared with the control, while well collateralized subjects showed a paradoxical decrease maintained above the ischemic threshold for neuronal death. qCBF on the contralateral side increased regardless of collateralization. CONCLUSION: Results suggest that perfusion can be augmented in ischemic stroke with norepinephrine and hydralazine. Perfusion augmentation depends on degree of collateralization and territory in question, with some evidence of vascular steal.

Effect of early Sanguinate (PEGylated carboxyhemoglobin bovine) infusion on cerebral blood flow to the ischemic core in experimental middle cerebral artery occlusion.

BACKGROUND: Sanguinate, a bovine PEGylated carboxyhemoglobin-based oxygen carrier with vasodilatory, oncotic and anti-inflammatory properties designed to release oxygen in hypoxic tissue, was tested to determine if it improves infarct volume, collateral recruitment and blood flow to the ischemic core in hyperacute middle cerebral artery occlusion (MCAO). METHODS: Under an IACUC approved protocol, 14 mongrel dogs underwent endovascular permanent MCAO. Seven received Sanguinate (8 mL/kg) intravenously over 10 min starting 30 min following MCAO and seven received a similar volume of normal saline. Relative cerebral blood flow (rCBF) was assessed using neutron-activated microspheres prior to MCAO, 30 min following MCAO and 30 min following intervention. Pial collateral recruitment was scored and measured by arterial arrival time (AAT) immediately prior to post-MCAO microsphere injection. Diffusion-weighted 3T MRI was used to assess infarct volume approximately 2 hours after MCAO. RESULTS: Mean infarct volumes for control and Sanguinate-treated subjects were 4739 mm3 and 2585 mm3 (p=0.0443; r2=0.687), respectively. Following intervention, rCBF values were 0.340 for controls and 0.715 in the Sanguinate group (r2=0.536; p=0.0064). Pial collateral scores improved only in Sanguinate-treated subjects and AAT decreased by a mean of 0.314 s in treated subjects and increased by a mean of 0.438 s in controls (p<0.0276). CONCLUSION: Preliminary results indicate that topload bolus administration of Sanguinate in hyperacute ischemic stroke significantly improves infarct volume, pial collateral recruitment and CBF in experimental MCAO immediately following its administration.

A Roadmap for Developing Plasma Diagnostic and Prognostic Biomarkers of Cerebral Cavernous Angioma With Symptomatic Hemorrhage (CASH).

BACKGROUND: Cerebral cavernous angioma (CA) is a capillary microangiopathy predisposing more than a million Americans to premature risk of brain hemorrhage. CA with recent symptomatic hemorrhage (SH), most likely to re-bleed with serious clinical sequelae, is the primary focus of therapeutic development. Signaling aberrations in CA include proliferative dysangiogenesis, blood-brain barrier hyperpermeability, inflammatory/immune processes, and anticoagulant vascular domain. Plasma levels of molecules reflecting these mechanisms and measures of vascular permeability and iron deposition on magnetic resonance imaging are biomarkers that have been correlated with CA hemorrhage. OBJECTIVE: To optimize these biomarkers to accurately diagnose cavernous angioma with symptomatic hemorrhage (CASH), prognosticate the risk of future SH, and monitor cases after a bleed and in response to therapy. METHODS: Additional candidate biomarkers, emerging from ongoing mechanistic and differential transcriptome studies, would further enhance the sensitivity and specificity of diagnosis and prediction of CASH. Integrative combinations of levels of plasma proteins and characteristic micro-ribonucleic acids may further strengthen biomarker associations. We will deploy advanced statistical and machine learning approaches for the integration of novel candidate biomarkers, rejecting noncorrelated candidates, and determining the best clustering and weighing of combined biomarker contributions. EXPECTED OUTCOMES: With the expertise of leading CA researchers, this project anticipates the development of future blood tests for the diagnosis and prediction of CASH to clinically advance towards precision medicine. DISCUSSION: The project tests a novel integrational approach of biomarker development in a mechanistically defined cerebrovascular disease with a relevant context of use, with an approach applicable to other neurological diseases with similar pathobiologic features.

Influence of simultaneous pressor and vasodilatory agents on the evolution of infarct growth in experimental acute middle cerebral artery occlusion.

BACKGROUND: This study sought to test the hypothesis that simultaneous central blood pressure elevation and potent vasodilation can mitigate pial collateral-dependent infarct growth in acute ischemic stroke. METHODS: Twenty mongrel canines (20-30 kg) underwent permanent middle cerebral artery occlusion (MCAO). Eight subjects received continuous infusion of norepinephrine (0.1-1.5200 µg/kg/min; titrated to a median of 34 mmHg above baseline mean arterial pressure) and hydralazine (20 mg) starting 30 min following MCAO. Pial collateral recruitment was scored prior to treatment and used to predict infarct volume based on a previously reported parameterization. Serial diffusion magnetic resonance imaging (MRI) acquisitions tracked infarct volumes over a 4-hour time frame. Infarct volumes and infarct volume growth between treatment and control groups were compared with each other and to predicted values. Fluid-attenuated inversion recovery (FLAIR) MRI, susceptibility weighted imaging (SWI), and necropsy findings were included in the evaluation. RESULTS: Differences between treatment and control group varied by pial collateral recruitment based on indicator-variable regression effects analysis with interaction confirmed by regression model fit. Benefit in treatment group was only in subjects with poor collaterals which had 35.7% less infarct volume growth (P=0.0008; ANOVA) relative to controls. Measured infarct growth was significantly lower than predicted by the model (linear regression partial F-test, slope P<0.001, intercept=0.003). There was no evidence for cerebral hemorrhage or posterior reversible encephalopathy syndrome. CONCLUSION: Our results indicate that a combination of norepinephrine and hydralazine administered in the acute phase of ischemic stroke mitigates infarct evolution in subjects with poor but not good collateral recruitment.

QSM in canine model of acute cerebral ischemia: A pilot study.

PURPOSE: In the present study, we investigated the potential of QSM to assess the physiological state of cortical tissue in the middle cerebral artery occlusion canine model of a cerebral ischemia. METHODS: Experiments were performed in 8 anesthetized canines. Gradient echo, perfusion, and DWI data of brains at normal and ischemic states were acquired. In the postprocessed susceptibility and quantitative cerebral blood flow maps, changes in values within the middle cerebral artery-fed cortical territories were quantified both on the ischemic and normal contralateral hemisphere side. RESULTS: QSM values in critically ischemic tissue were significantly different from contralateral values-namely, susceptibility increase was observed in the cases in which cerebral perfusion was maintained above the threshold of neuronal death. Furthermore, the data indicates presence of a significant correlation between the changes in susceptibility values, cerebral perfusion, and the infarct volume and pial collateral scores. Additionally, our data suggests that difference in cortical susceptibility is prospectively indicative of the infarct growth rate. CONCLUSION: In an experimental permanent middle cerebral artery occlusion model, QSM was shown to correlate with the functional parameters characterizing viability of ischemic tissue, thus warranting further research on its ability to provide complementary information during acute stroke MRI examinations in humans.

Common transcriptome, plasma molecules, and imaging signatures in the aging brain and a Mendelian neurovascular disease, cerebral cavernous malformation.

Brain senescence is associated with impaired endothelial barrier function, angiogenic and inflammatory activity, and propensity to brain hemorrhage. The same pathological changes occur in cerebral cavernous malformations (CCM), a genetic neurovascular anomaly. We hypothesized common transcriptomic and plasma cytokine signatures in the aging brain and CCM. We identified 320 genes [fold change ≥1.5; p < 0.05; false discovery rate (FDR) corrected] commonly dysregulated in the aging brain and CCM. Ontology and pathway analyses of the common differentially expressed genes were related to inflammation and extracellular matrix organization. Plasma levels of C-reactive protein and angiopoietin-2 were significantly greater in older compared to younger healthy non-CCM subjects and were also greater in CCM (Sporadic and Familial) subjects regardless of age (all: p < 0.05; FDR corrected). Plasma levels of vascular endothelial growth factor were significantly greater in older compared to younger subjects, in both healthy non-CCM and Sporadic-CCM groups (all: padj < 0.05). Plasma levels of vascular endothelial growth factor were also significantly greater in Familial-CCM cases with germ line mutations regardless of age (all: padj < 0.05) compared to both healthy non-CCM and Sporadic-CCM subjects. Brain white matter vascular permeability assessed by MRI followed the same pattern as vascular endothelial growth factor across all groups. In addition, quantitative susceptibility mapping of brain white matter, a measure of iron deposition, was increased in older compared to younger healthy non-CCM subjects. Genetic aberrations, plasma molecules, and imaging biomarkers in a well characterized Mendelian neurovascular disease may also be applicable in the aging brain. Graphical abstract.

Mechanical Thrombectomy for Patients with In-Hospital Ischemic Stroke: A Case-Control Study.

BACKGROUND AND AIM: Patients with in-hospital acute ischemic stroke (AIS) have, in general, worse outcomes compared to those presenting from the community, partly attributed to the numerous contraindications to intravenous thrombolysis. We aimed to identify and analyze a group of patients with in-hospital AIS who remain suitable candidates for acute endovascular therapies. METHODS: A retrospective 6-year data analysis was conducted in patients evaluated through the in-hospital stroke alert protocol in a single tertiary care university hospital to identify those with in-hospital AIS due to acute intracranial large vessel occlusion (ILVO). Feasibility and safety of mechanical thrombectomy for in-hospital AIS was assessed in a case-control study comparing inpatients to those presenting from the community. RESULTS: From 1460 in-hospital stroke alert activations, 11% had a final diagnosis of AIS (n = 167). One hundred and two patients with in-hospital AIS had emergent intracranial vessel imaging and were included in our cohort. Acute ILVO was identified in 27 patients within this cohort. Patients were younger in the ILVO group and had more severe neurologic deficit on presentation. Compared to a matched (1:2) control group of patients presenting from the community, inpatients who underwent mechanical thrombectomy achieved equivalent technical success, safety, and clinical outcomes. CONCLUSIONS: The incidence of acute ILVO in patients with in-hospital AIS who underwent emergent vessel imaging is similar to the reported incidence of ILVO in patients presenting with community-onset AIS. Among patients with in-hospital AIS secondary to ILVO, mechanical thrombectomy is a feasible and safe therapy associated with favorable outcomes.

Predictors for the extent of pial collateral recruitment in acute ischemic stroke.

BACKGROUND: Pial arterioles can provide a variable degree of collateral flow to ischemic vascular territories during acute ischemic stroke. This study sought to identify predictive factors of the degree of pial collateral recruitment in acute ischemic stroke. METHODS: Clinical information and arteriograms from 62 consecutive patients with stroke due to either middle cerebral artery (MCA) M1 segment or internal carotid artery (ICA) terminus occlusion within 6 h following symptom onset were retrospectively reviewed. Pial collaterals were defined based on the extent of reconstitution of the MCA territory. Patients with slow antegrade flow distal to the occlusion site were excluded and no anesthetics were used prior or during angiography. Results were analyzed using multivariate nominal logistic regression. RESULTS: Better pial collateral recruitment was associated with proximal MCA versus ICA terminus occlusion (p = 0.005; odds ratio (OR) = 9.3; 95% confidence interval (CI), 2.16-53.3), lower presenting National Institutes of Health Stroke Scale Score (NIHSSS) (p = 0.023; OR = 6.51; 95% CI, 1.49-41.7), and lower diastolic blood pressure (p = 0.0411; OR = 5.05; 95% CI, 1.20-29.2). Age, gender, symptom duration, diabetes, laterality, systolic blood pressure, glucose level, hematocrit, platelet level, and white blood cell count at presentation were not found to have a statistically significant association with pial collateral recruitment. CONCLUSIONS: Extent of pial collateral recruitment is strongly associated with the occlusion site (MCA M1 segment versus ICA terminus) and less strongly associated with presenting NIHSSS and diastolic blood pressure.

High-Resolution MRI Microscopy Coil Assessment of Parotid Masses.

The goal of this study was to determine whether high-resolution magnetic resonance imaging (MRI) microscopy coil imaging can improve the depiction parotid masses. A total of 14 parotid masses, including 7 salivary neoplasms, 2 abnormal lymph nodes, and 5 benign cystic lesions were imaged with T2-weighted and fat-suppressed postcontrast T1-weighted sequences using a 47-mm diameter microscopy coil in addition to conventional MRI sequences acquired with a conventional head and neck neurovascular coil. Compared to conventional parotid MRI sequences, microscopy coil images provided better definition of the margins of neoplasms, provide more detailed definition of lymph node morphology, and better depict certain cyst contents in the superficial portions of the parotid gland. The microscopy coil images provided significantly better definition of lesions and surrounding tissues within the superficial parotid gland with resptect to the deep parotid gland structures due to loss of signal. Furthermore, the fat-suppressed postcontrast T1-weighted microscopy coil images were significantly better than the corresponding T2-weighted images for delineating the superficial parotid gland. Ultimately, the microscopy coil sequences added over 10 minutes to the examination time.

Absolute quantitative MR perfusion and comparison against stable-isotope microspheres.

PURPOSE: This work sought to compare a quantitative T1 bookend dynamic susceptibility contrast MRI based perfusion protocol for absolute cerebral blood flow (qCBF) against CBF measured by the stable-isotope neutron capture microsphere method, a recognized reference standard for measuring tissue blood flow, at normocapnia, hypercapnia, and in acute stroke. METHODS: CBF was measured in anesthetized female canines by MRI and microspheres over 2 consecutive days for each case. On day 1, 5 canines were measured before and during a physiological challenge induced by carbogen inhalation; on day 2, 4 canines were measured following permanent occlusion of the middle cerebral artery. CBF and cerebrovascular reactivity measured by MRI and microsphere deposition were compared. RESULTS: MRI correlated strongly with microspheres at the hemispheric level for CBF during normo- and hypercapnic states (r2 = 0.96), for individual cerebrovascular reactivity (r2 = 0.84), and for postocclusion CBF (r2 = 0.82). Correction for the delay and dispersion of the contrast bolus resulted in a significant improvement in the correlation between MRI and microsphere deposition in the ischemic state (r2 = 0.96). In all comparisons, moderate correlations were found at the regional level. CONCLUSION: In an experimental canine model with and without permanent occlusion of the middle cerebral artery, MRI-based qCBF yielded moderate to strong correlations for absolute quantitative CBF and cerebrovascular reactivity measurements during normocapnia and hypercapnia. Correction for delay and dispersion greatly improved the quantitation during occlusion of the middle cerebral artery, underscoring the importance for this correction under focal ischemic condition.

Educational Impact of Trainee-Facilitated Head and Neck Radiology-Pathology Correlation Conferences.

The goal of this study was to evaluate the benefits of resident and fellow-facilitated radiology-pathology head and neck conferences. A total of seven resident-facilitated and six fellow-facilitated head and neck radiology-pathology cases were presented as part of the radiology department conference series. The radiology residents were surveyed regarding the perceived quality and effectiveness of the fellow-facilitated sessions. The number of publications yielded from all the cases presented was tracked. Overall, the residents assessed the quality of the fellow-facilitated conferences with an average score of 3.9 out of 5 and the overall helpfulness with an average of 3.5 out of 5. The overall average level of resident understanding among the residents for the topics presented to them by the fellows at baseline was 2.5 out of 5 and 3.4 out of 5 after the presentations, which was a significant increase (p-value < 0.01). There were three peer-reviewed publications generated from the resident presentations and four peer-reviewed publications generated from the fellow presentations, which represents a 54% publication rate collectively. Therefore, trainee-facilitated head and neck radiology-pathology conferences at our institution provide added learning and scholarly activity opportunities.

Atorvastatin Treatment of Cavernous Angiomas with Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial.

BACKGROUND: More than a million Americans harbor a cerebral cavernous angioma (CA), and those who suffer a prior symptomatic hemorrhage have an exceptionally high rebleeding risk. Preclinical studies show that atorvastatin blunts CA lesion development and hemorrhage through inhibiting RhoA kinase (ROCK), suggesting it may confer a therapeutic benefit. OBJECTIVE: To evaluate whether atorvastatin produces a difference compared to placebo in lesional iron deposition as assessed by quantitative susceptibility mapping (QSM) on magnetic resonance imaging in CAs that have demonstrated a symptomatic hemorrhage in the prior year. Secondary aims shall assess effects on vascular permeability, ROCK activity in peripheral leukocytes, signal effects on clinical outcomes, adverse events, and prespecified subgroups. METHODS: The phase I/IIa placebo-controlled, double-blinded, single-site clinical trial aims to enroll 80 subjects randomized 1-1 to atorvastatin (starting dose 80 mg PO daily) or placebo. Dosing shall continue for 24-mo or until reaching a safety endpoint. EXPECTED OUTCOMES: The trial is powered to detect an absolute difference of 20% in the mean percent change in lesional QSM per year (2-tailed, power 0.9, alpha 0.05). A decrease in QSM change would be a signal of potential benefit, and an increase would signal a safety concern with the drug. DISCUSSION: With firm mechanistic rationale, rigorous preclinical discoveries, and biomarker validations, the trial shall explore a proof of concept effect of a widely used repurposed drug in stabilizing CAs after a symptomatic hemorrhage. This will be the first clinical trial of a drug aimed at altering rebleeding in CA.

A printed information leaflet about MRI and radiologists improves neuroradiology patient health literacy.

PURPOSE: To determine the health literacy benefit of a printed informational leaflet for patients scheduled to undergo brain magnetic resonance imaging (MRI) scans. METHODS AND MATERIALS: A two-page leaflet that provided an overview of MRI and the role of radiologists was prepared and given to outpatients scheduled to undergo brain MRI examinations while in the waiting room. A survey composed mainly of yes/no and Likert scale questions pertaining to the leaflet, as well as patient demographics, was administered to the patients. RESULTS: A total of 147 patients completed the survey, of which 110 (75%) had undergone a prior MRI scan, 120 (82%) stated that their ordering provider explained the reason for the MRI scan, and less than 1% reported having referenced online resources related to MRI. The average score for how well patients understood the MRI scan procedure and how it is reviewed was 4.16/5 (standard deviation 1.18) before versus 4.39/5 (standard deviation 1.08) after reading the leaflet, which was a statistically significant improvement based on the Wilcoxon signed-rank test ( P < 0.01). The score for how helpful the reading material was for explaining what is MRI was 4.06/5 (standard deviation 1.02) and the score for how helpful the reading material was for explaining what is a radiologist was 4.18/5 (standard deviation 0.98). CONCLUSION: A printed leaflet about MRI and radiologists can serve as an opportunity to educate patients about certain aspects of their scans during their stay in the waiting room.

Fuzzy c-means segmentation of major vessels in angiographic images of stroke.

Patients suffering from ischemic stroke develop varying degrees of pial arterial supply (PAS), which can affect patient response to reperfusion therapy and risk of hemorrhage. Since vessel segmentation may be an important part in identifying PAS, we present a fuzzy c-means (FCM) clustering method to segment major vessels in x-ray angiograms. Our approach consists of semiautomatic region of interest (ROI) delineation, separation of major vessels from capillary blush and/or background noise through FCM clustering, and identification of the major vessel category. This method was applied to a database of x-ray angiograms of 24 patients acquired at various frame rates. The ground truth for performance evaluation was the designation by an expert radiologist selecting image pixels as being vessel or nonvessel. From receiver operating characteristic (ROC) analysis, area under the ROC curve (AUC) was the performance metric in the task of distinguishing between major vessels and blush or background. When clustering data into three categories and performing FCM segmentation on each ROI separately, the AUC was 0.89 for the entire database and [Formula: see text] for all examined frame-rates. In conclusion, our method showed promising performance in identifying major vessels and is anticipated to become an integral part of automatic quantification of PAS.

Quantitative susceptibility mapping as a monitoring biomarker in cerebral cavernous malformations with recent hemorrhage.

BACKGROUND: Quantitative Susceptibility Mapping (QSM) MRI allows accurate assessment of iron content in cerebral cavernous malformations (CCM), and a threshold increase by 6% in QSM has been shown to reflect new symptomatic hemorrhage (SH) in previously stable lesions. PURPOSE/HYPOTHESIS: It is unclear how lesional QSM evolves in CCMs after recent SH, and whether this could serve as a monitoring biomarker in clinical trials aimed at preventing rebleeding in these lesions. STUDY TYPE: This is a prospective observational cohort study. POPULATION: 16 CCM patients who experienced a SH within the past year, whose lesion was not resected or irradiated. FIELD STRENGTH/SEQUENCE: The data acquisition was performed using QSM sequence implemented on a 3T MRI system ASSESSMENT: The lesional QSM assessments at baseline and yearly during 22 patient-years of follow-up were performed by a trained research staff including imaging scientists. STATISTICAL TESTS: Biomarker changes were assessed in relation to clinical events. Clinical trial modeling was performed using two-tailed tests of time-averaged difference (assuming within-patient correlation of 0.8, power = 0.9 and alpha = 0.1) to detect 20%, 30% or 50% effects of intervention on clinical and biomarkers event rates during two years of follow-up. RESULTS: The change in mean lesional QSM of index hemorrhagic lesions was +7.93% per patient-year in the whole cohort. There were 5 cases (31%) of recurrent SH or lesional growth, and twice as many instances (62%) with a threshold (6%) increase in QSM. There were no instances of SH hemorrhage or lesional growth without an associated threshold increase in QSM during the same epoch. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:1133-1138.

Plasma Biomarkers of Inflammation Reflect Seizures and Hemorrhagic Activity of Cerebral Cavernous Malformations.

The clinical course of cerebral cavernous malformations (CCMs) is highly variable. Based on recent discoveries implicating angiogenic and inflammatory mechanisms, we hypothesized that serum biomarkers might reflect chronic or acute disease activity. This single-site prospective observational cohort study included 85 CCM patients, in whom 24 a priori chosen plasma biomarkers were quantified and analyzed in relation to established clinical and imaging parameters of disease categorization and severity. We subsequently validated the positive correlations in longitudinal follow-up of 49 subjects. Plasma levels of matrix metalloproteinase-2 and intercellular adhesion molecule 1 were significantly higher (P = 0.02 and P = 0.04, respectively, FDR corrected), and matrix metalloproteinase-9 was lower (P = 0.04, FDR corrected) in patients with seizure activity at any time in the past. Vascular endothelial growth factor and endoglin (both P = 0.04, FDR corrected) plasma levels were lower in patients who had suffered a symptomatic bleed in the prior 3 months. The hierarchical clustering analysis revealed a cluster of four plasma inflammatory cytokines (interleukin 2, interferon gamma, tumor necrosis factor alpha, and interleukin 1 beta) separating patients into what we designated "high" and "low" inflammatory states. The "high" inflammatory state was associated with seizure activity (P = 0.02) and more than one hemorrhagic event during a patient's lifetime (P = 0.04) and with a higher rate of new hemorrhage, lesion growth, or new lesion formation (P < 0.05) during prospective follow-up. Peripheral plasma biomarkers reflect seizure and recent hemorrhagic activity in CCM patients. In addition, four clustered inflammatory biomarkers correlate with cumulative disease aggressiveness and predict future clinical activity.