Blood-Brain Barrier Opening with MRI-guided Focused Ultrasound Elicits Meningeal Venous Permeability in Humans with Early Alzheimer Disease.

Background Opening of the blood-brain barrier (BBB) induced with MRI-guided focused ultrasound has been shown in experimental animal models to reduce amyloid-ß plaque burden, improve memory performance, and facilitate delivery of therapeutic agents to the brain. However, physiologic effects of this procedure in humans with Alzheimer disease (AD) require further investigation. Purpose To assess imaging effects of focused ultrasound-induced BBB opening in the hippocampus of human participants with early AD and to evaluate fluid flow patterns after BBB opening by using serial contrast-enhanced MRI. Materials and Methods Study participants with early AD recruited to a Health Insurance Portability and Accountability Act-compliant, prospective, ongoing phase II clinical trial (ClinicalTrials.gov identifier, NCT03671889) underwent three separate focused ultrasound-induced BBB opening procedures that used a 220-kHz transducer with a concomitant intravenous microbubble contrast agent administered at 2-week intervals targeting the hippocampus and entorhinal cortex between October 2018 and May 2019. Posttreatment effects and gadolinium-based contrast agent enhancement patterns were evaluated by using 3.0-T MRI. Results Three women (aged 61, 72, and 73 years) consecutively enrolled in the trial successfully completed repeated focused ultrasound-induced BBB opening of the hippocampus and entorhinal cortex. Postprocedure contrast enhancement was clearly identified within the targeted brain volumes, indicating immediate spatially precise BBB opening. Parenchymal enhancement resolved within 24 hours after all treatments, confirming BBB closure. Transient perivenous enhancement was consistently observed during the acute phase after BBB opening. Notably, contrast enhancement reappeared in the perivenular regions after BBB closure. This imaging marker is consistent with blood-meningeal barrier permeability and persisted for 24-48 hours before spontaneous resolution. No evidence of intracranial hemorrhage or other adverse effect was identified. Conclusion MRI-guided focused ultrasound-induced blood-brain barrier opening was safely performed in the hippocampi of three participants with Alzheimer disease without any adverse effects. Posttreatment MRI reveals a unique spatiotemporal contrast enhancement pattern that suggests a perivenular immunologic healing response downstream from targeted sites. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Klibanov in this issue.

Guanidinoacetate N-methyltransferase deficiency: Case report and brief review of the literature.

Guanidinoacetate N-methyltransferase (GAMT) deficiency is a rare autosomal recessive disorder characterized by a decrease in creatine synthesis, resulting in cerebral creatine deficiency syndrome (CCDS). GAMT deficiency is caused by mutations in the GAMT gene located on chromosome 19, which impairs the conversion of guanidinoacetic acid (GAA) to creatine. The resulting accumulation of the toxic metabolite GAA and the lack of creatine lead to various symptoms, including global developmental delays, behavioral issues, and epilepsy. The gold standard for diagnosis of GAMT deficiency is genetic testing. Treatment options for GAMT deficiency include creatine supplementation, ornithine supplementation, arginine restriction, and sodium benzoate supplementation. These treatment options have been shown to improve movement disorders and epileptic symptoms, but their impact on intellectual and speech development is limited. Early intervention has shown promising results in normalizing neurological development in a minor subgroup of patients. Therefore, there is a growing need for newborn screening techniques to detect GAMT deficiency early and prevent permanent neurological delays. Here we report a case of GAMT deficiency with emphasis on imaging presentation. Our case showed reduced brain parenchyma creatine stores on MR Spectroscopy, which may provide an avenue to aid in early diagnosis.

Ultrasound-mediated blood-brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer's disease.

BACKGROUND: Focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening is under investigation as a therapeutic modality for neurodegeneration, yet its effects in humans are incompletely understood. Here, we assessed physiologic responses to FUS administered in multifocal brain sites of persons with Alzheimer's disease (AD). METHODS: At a tertiary neuroscience institute, eight participants with AD (mean age 65, 38% F) enrolled in a phase 2 clinical trial underwent three successive targeted BBB opening procedures at 2 week intervals using a 220 kHz FUS transducer in combination with systemically administered microbubbles. In all, 77 treatment sites were evaluated and encompassed hippocampal, frontal, and parietal brain regions. Post-FUS imaging changes, including susceptibility effects and spatiotemporal gadolinium-based contrast agent enhancement patterns, were analyzed using serial 3.0-Tesla MRI. RESULTS: Post-FUS MRI revealed expected intraparenchymal contrast extravasation due to BBB opening at all targeted brain sites. Immediately upon BBB opening, hyperconcentration of intravenously-administered contrast tracer was consistently observed around intracerebral veins. Following BBB closure, within 24-48 h of FUS intervention, permeabilization of intraparenchymal veins was observed and persisted for up to one week. Notably, extraparenchymal meningeal venous permeabilization and associated CSF effusions were also elicited and persisted up to 11 days post FUS treatment, prior to complete spontaneous resolution in all participants. Mild susceptibility effects were detected, however no overt intracranial hemorrhage or other serious adverse effects occurred in any participant. CONCLUSIONS: FUS-mediated BBB opening is safely and reproducibly achieved in multifocal brain regions of persons with AD. Post-FUS tracer enhancement phenomena suggest the existence of a brain-wide perivenous fluid efflux pathway in humans and demonstrate reactive physiological changes involving these conduit spaces in the delayed, subacute phase following BBB disruption. The delayed reactive venous and perivenous changes are consistent with a dynamic, zonal exudative response to upstream capillary manipulation. Further preclinical and clinical investigations of these FUS-related imaging phenomena and of intracerebral perivenous compartment changes are needed to elucidate physiology of this pathway as well as biological effects of FUS administered with and without adjuvant neurotherapeutics. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03671889, registered 9/14/2018.

Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy.

Patients with metastatic breast cancer have high and continually increasing rates of brain metastases. During the course of the disease, brain metastases can occur in up to 30% of these patients. In most cases, brain metastases are diagnosed after significant disease progression. The blood-tumor barrier increases the difficulty of treating brain metastasis by preventing accumulation of chemotherapy within metastases at therapeutically effective concentrations. Traditional therapies, such as surgical resection, radiotherapy, and chemotherapy, have poor efficacy, as reflected by a low median survival rate of 5-8% after post-diagnosis. Low-intensity focused ultrasound (LiFUS) is a new treatment for enhancing drug accumulation within the brain and brain malignancies. In this study, we elucidate the effect of clinical LiFUS combined with chemotherapy on tumor survival and progression in a preclinical model of triple-negative breast cancer metastasis to the brain. LiFUS significantly increased the tumor accumulation of 14C-AIB and Texas Red compared to controls (p< 0.01). LiFUS-mediated opening of the BTB is size-dependent, which is consistent with our previous studies. Mice receiving LiFUS with combinatorial Doxil and paclitaxel showed a significant increase in median survival (60 days) compared to other groups. LiFUS plus combinatorial chemotherapy of paclitaxel and Doxil also showed the slowest progression of tumor burden compared to chemotherapy alone or individual chemotherapy and LiFUS combinations. This study shows that combining LiFUS with timed combinatorial chemotherapeutic treatment is a potential strategy for improving drug delivery to brain metastases.

CT perfusion imaging pitfall related to fetal posterior cerebral artery.

OBJECTIVE: The purpose of this article is to discuss how a unilateral fetal posterior cerebral artery (PCA) causes perfusion map asymmetry due to anteroposterior bolus arrival discrepancy. We performed region of interest analysis of asymmetric perfusion maps before and after delay correction was performed. CONCLUSION: Perfusion asymmetry becomes unapparent using a delay correction algorithm, indicating bolus arrival delay on the side opposite the fetal PCA. Delay correction algorithms can eliminate deconvolution errors related to bolus arrival delay.

Characterization of passive permeability after low intensity focused ultrasound mediated blood-brain barrier disruption in a preclinical model.

BACKGROUND: Systemic drug delivery to the central nervous system is limited by presence of the blood-brain barrier (BBB). Low intensity focused ultrasound (LiFUS) is a non-invasive technique to disrupt the BBB, though there is a lack of understanding of the relationship between LiFUS parameters, such as cavitation dose, time of sonication, microbubble dose, and the time course and magnitude of BBB disruption. Discrepancies in these data arise from experimentation with modified, clinically untranslatable transducers and inconsistent parameters for sonication. In this report, we characterize microbubble and cavitation doses as LiFUS variables as they pertain to the time course and size of BBB opening with a clinical Insightec FUS system. METHODS: Female Nu/Nu athymic mice were exposed to LiFUS using the ExAblate Neuro system (v7.4, Insightec, Haifa, Israel) following target verification with magnetic resonance imaging (MRI). Microbubble and cavitation doses ranged from 4-400 µL/kg, and 0.1-1.5 cavitation dose, respectively. The time course and magnitude of BBB opening was evaluated using fluorescent tracers, ranging in size from 105-10,000 Da, administered intravenously at different times pre- or post-LiFUS. Quantitative autoradiography and fluorescence microscopy were used to quantify tracer accumulation in brain. RESULTS: We observed a microbubble and cavitation dose dependent increase in tracer uptake within brain after LiFUS. Tracer accumulation was size dependent, with 14C-AIB (100 Da) accumulating to a greater degree than larger markers (~ 625 Da-10 kDa). Our data suggest opening of the BBB via LiFUS is time dependent and biphasic. Accumulation of solutes was highest when administered prior to LiFUS mediated disruption (2-fivefold increases), but was also significantly elevated at 6 h post treatment for both 14C-AIB and Texas Red. CONCLUSION: The magnitude of LiFUS mediated BBB opening correlates with concentration of microbubbles, cavitation dose as well as time of tracer administration post-sonication. These data help define the window of maximal BBB opening and applicable sonication parameters on a clinically translatable and commercially available FUS system that can be used to improve passive permeability and accumulation of therapeutics targeting the brain.

Neurovascular changes measured by time-of-flight MR angiography in cholesterol-fed rabbits with cortical amyloid beta-peptide accumulation.

PURPOSE: To test the hypothesis that narrowing of cranial blood vessels in cholesterol-fed rabbits is a function of the duration of the high cholesterol diet. Such neurovascular changes, caused by elevated serum cholesterol, are linked to stroke and Alzheimer's disease risk. MATERIALS AND METHODS: Four groups of New Zealand White rabbits were studied. Six were fed a normal diet, 19 were fed a 2% cholesterol diet with 0.12 ppm copper in the drinking water for 8 weeks, 10 weeks, or 12 weeks. Time-of-flight (TOF) MR angiography (MRA) at 3 Tesla was used to measure arterial diameters in 11 vessels. Previously published data for amyloid beta-peptide (Abeta) accumulation in the brains measured postmortem were correlated to vessel diameters. Ventricular volumes of rabbits were measured on group-averaged data. RESULTS: Several vessel diameters decreased with cholesterol diet duration. The posterior communicating arteries showed the largest significant effect. Abeta accumulation was inversely correlated with arterial diameter. Ventricular volumes between the normal diet and 12 weeks cholesterol-fed groups were not significantly different. CONCLUSION: Reduction in vessel diameter of medium-sized vessels but not large vessels was measured in these hypercholesterolemic rabbits. The vessel diameter narrowing and cortical Abeta deposition occurred before measurable ventricular enlargement.

Treatment of intracranial aneurysms with the Enterprise stent: a multicenter registry.

OBJECT: The development of self-expanding stents dedicated to intracranial use has significantly widened the applicability of endovascular therapy to many intracranial aneurysms that would otherwise have been untreatable by endovascular techniques. Recent Food and Drug Administration approval of the Enterprise Vascular Reconstruction Device and Delivery System (Cordis) has added a new option for self-expanding stent-assisted intracranial aneurysm coiling. METHODS: The authors established a collaborative registry across multiple institutions to rapidly provide largevolume results regarding initial experience in using the Enterprise in real-world practice. Ten institutions (University at Buffalo, Thomas Jefferson University, University of Florida, Cleveland Clinic, Northwestern University, West Virginia University, University of Puerto Rico, Albany Medical Center Hospital, the Neurological Institute of Savannah, and the Barrow Neurological Institute) have provided consecutive data regarding their initial experience with the Enterprise. RESULTS: In total, 141 patients (119 women) with 142 aneurysms underwent 143 attempted stent deployments. The use of Enterprise assistance with aneurysm coiling was associated with a 76% rate of > or = 90% occlusion. An inability to navigate or deploy the stent was experienced in 3% of cases, as well as a 2% occurrence of inaccurate deployment. Procedural data demonstrated a 6% temporary morbidity, 2.8% permanent morbidity, and 2% mortality (0.8% unruptured, 12% ruptured). CONCLUSIONS: The authors report initial results of the largest series to date in using the Enterprise for intracranial aneurysm treatment. The Enterprise is associated with a high rate of successful navigation and low occurrence of inaccurate stent deployment. The overall morbidity and mortality rates were low; however, caution should be exercised when considering Enterprise deployment in patients with subarachnoid hemorrhage as the authors' experience demonstrated a high rate of associated hemorrhagic complications leading to death.

The 'bendy' basilar: progressive aneurysm tilting and arterial deformation can be a delayed outcome after coiling of large basilar apex aneurysms.

BACKGROUND: Morphological changes in the basilar artery and the artery-aneurysm relationship following coiling of large basilar apex aneurysms may induce morbidity. METHODS: The basilar artery radius-of-curvature was measured along its center line on volumetrically reconstructed images formatted along the plane of curvature. The aneurysm-tilt-angle was measured between the distal basilar and the vertical long axis of the aneurysm. The measurements were compared between small (<10 mm) and large (≥10 mm) aneurysms on baseline and follow-up studies. The volume (mm3) and mass (g) of the deployed coils was also compared. RESULTS: Among 94 consecutive aneurysms, 62 (66%) were <10 mm and 32 (34%) were ≥10 mm. The mean aneurysm size and volume was 9 mm (±4) and 507 mm3(±1366) respectively. The median aneurysm follow-up was 24 months (IQR 6-59). There was no difference between the groups based on age, gender, or associated comorbidities. The coil mass was 0.4 g (±0.2) for aneurysms <10 mm and 1.9 g (±1.6) for aneurysms ≥10 mm (P<0.0001). The total coil volume was 32 (±20) mm3 for aneurysms <10 mm and 187 (±172) mm3 for aneurysms ≥10 mm (P<0.0001). Aneurysms ≥10 mm tilted 13.5o (±14.4) compared with 1.1o (±2.8) for aneurysms <10 mm (P<0.0001). The basilar artery became more curved by 1.3 (±9.4) mm for aneurysms ≥10 mm and 0.25 (±2.1) mm for aneurysms <10 mm (P=0.0002). Other than size of the coiled aneurysms no other factors correlated with the geometrical changes. CONCLUSION: Large coiled basilar apex aneurysms may be more prone to aneurysm tilting and bending of the basilar artery. Speculative causes include the weight of the coil mass and the biomechanical forces exerted on the coiled aneurysm.

The role of CT perfusion imaging in acute stroke diagnosis: a large single-center experience.

The objective of this study was to determine the utility of computed tomography perfusion (CTP) scans in diagnosing acute ischemic stroke (AIS). CTP abnormalities in two contiguous supratentorial levels were correlated with diffusion weighted image (DWI) abnormalities on magnetic resonance imaging (the standard for stroke diagnosis) performed within 1 week in 422 suspected acute ischemic strokes. Of 157 AIS confirmed by DWI, 78 showed CTP abnormalities (sensitivity 49.7%). All of these examinations were performed with a mean of 35 min from the initial emergency department neurological examination. Excluding small non-vascular territory strokes left 77 AIS with a total volume of infarcted tissue of more than 5 cc by DWI. Of these, 71 showed CTP abnormalities (sensitivity 92.2%). Of the 265 patients without AIS, none showed CTP abnormalities (specificity 100%). CTP is a rapid, readily available and effective method of diagnosing AIS in clinical practice, particularly the major intracranial vessel strokes that result in a more devastating outcome.

Gamma Knife Radiosurgery for Arteriovenous Malformations Using a Four-Dimensional Dynamic Volume Computed Tomography Angiography Planning System as an Alternative to Traditional Catheter Angiogram.

Background Gamma knife radiosurgery (GKRS) remains a critical intervention in the long-term management of arteriovenous malformations (AVMs). For planning a treatment, identification of the nidus is essential, and it is dependent on high-resolution blood flow imaging, usually in the form of a traditional angiogram. The development of dynamic 320-slice computed tomography (CT) angiography has offered a noninvasive alternative to intra-arterial fluoroscopic imaging, and it is capable of providing equivalent temporal resolution. In this study, we describe the feasibility of using four-dimensional CT angiography (4D-CTA) in GKRS planning for AVM treatment and a comparative analysis with a traditional angiogram. Methods A retrospective review was performed on AVM patients treated via GKRS with a 4D-CTA prior to the day of treatment, on the day of treatment, or with a day-of-treatment angiogram. Treatment times, along with total times in the Leksell® coordinate frame G, were obtained from the medical records. The frame-on time was calculated by subtracting the treatment time from the total time starting from application to removal, and the statistical analysis was performed across groups using analysis of variance (ANOVA). All treatments were performed on the Perfexion™ model with a dynamic flow imaging procured via a 320-slice CT scanner or traditional angiography platform. Results Some 27 patients underwent a total of 29 GKRS procedures for AVM treatment at our institution between September 2011 and January 2017. Mean age at the time of treatment was 35.5 (6-65) years, and male:female ratio was 5:4. Some 12 patients had 4D-CTA performed prior to the day of treatment, eight patients had the same CTA completed after frame placement on the day of treatment, while seven patients underwent traditional angiography. The mean frame-on times of each group were 190, 336, and 426 minutes, respectively (p < 0.0001). No procedures were aborted based on the image quality. Conclusions 4D-CTA is an effective tool in identifying the AVM nidus for GKRS planning. These studies can be performed prior to the day of treatment, allowing for a significant reduction in frame-on time and eliminating the risk of angiogram complication on the day of GKRS.

Intravenous thrombolysis before endovascular therapy for large vessel strokes can lead to significantly higher hospital costs without improving outcomes.

BACKGROUND: Limited efficacy of IV recombinant tissue plasminogen activator (rt-PA) for large vessel occlusions (LVO) raises doubts about its utility prior to endovascular therapy. PURPOSE: To compare outcomes and hospital costs for anterior circulation LVOs (middle cerebral artery, internal carotid artery terminus (ICA-T)) treated with either primary endovascular therapy alone (EV-Only) or bridging therapy (IV+EV)). METHODS: A single-center retrospective analysis was performed. Clinical and demographic data were collected prospectively and relevant cost data were obtained for each patient in the study. RESULTS: 90 consecutive patients were divided into EV-Only (n=52) and IV+EV (n=38) groups. There was no difference in demographics, stroke severity, or clot distribution. The mean (SD) time to presentation was 5:19 (4:30) hours in the EV-Only group and 1:46 (0:52) hours in the IV+EV group (p<0.0001). Recanalization: EV-Only 35 (67%) versus IV+EV 31 (81.6%) (p=0.12). Favorable outcome: EV-Only 26 (50%) versus IV+EV 22 (58%) (p=0.45). For patients presenting within 4.5 hours (n=64): Recanalization: EV-Only 21/26 (81%) versus IV+EV 31/38 (81.6%) (p=0.93). Favorable outcome: EV-Only 14/26 (54%) versus IV+EV 22/38 (58%) (p=0.75). There was no significant difference in rates of hemorrhage, mortality, home discharge, or length of stay. A stent retriever was used in 67 cases (74.4%), with similar recanalization, outcomes, and number of passes in the EV-Only and IV+EV groups. The mean (SD) total hospital cost was $33 810 (13 505) for the EV-Only group and $40 743 (17 177) for the IV+EV group (p=0.02). The direct cost was $23 034 (8786) for the EV-Only group and $28 711 (11 406) for the IV+EV group (p=0.007). These significantly higher costs persisted for the subgroup presenting in <4.5 hours and the stent retriever subgroup. IV rt-PA administration independently predicted higher hospital costs. CONCLUSIONS: IV rt-PA did not improve recanalization, thrombectomy efficacy, functional outcomes, or length of stay. Combined therapy was associated with significantly higher total and direct hospital costs than endovascular therapy alone.

A population-based incidence of M2 strokes indicates potential expansion of large vessel occlusions amenable to endovascular therapy.

BACKGROUND: M2 occlusions may result in poor outcomes and potentially benefit from endovascular therapy. Data on the rate of M2 strokes is lacking. METHODOLOGY: Patients with acute ischemic stroke discharged over a period of 3 years from a tertiary level hospital in the 'stroke belt' were evaluated for M2 occlusions on baseline vascular imaging. Regional and national incidence was calculated from discharge and multicounty data. RESULTS: There were 2739 ICD-9 based AIS discharges. M2 occlusions in 116 (4%, 95% CI 3.5% to 5%) patients constituted the second most common occlusion site. The median National Institute of Health Stroke Scale (NIHSS) score was 12 (IQR 5-18). Good outcomes were observed in 43% (95% CI 34% to 53%), poor outcomes in 57% (95% CI 47% to 66%), and death occurred in 27% (95% CI 19% to 37%) of patients. Receiver operating characteristics curves showed the NIHSS to be predictive of outcomes (area under the curve 0.829, 95% CI 0.745 to 0.913, p<0.0001). An NIHSS score ≥9 was the optimal cut-off point for predicting poor outcomes (sensitivity 85.7%, specificity 67.4%). 71 (61%) patients had an NIHSS score ≥9 and 45 (39%) an NIHSS score <9. The rate of good-outcome was 22.6% for NIHSS score ≥9 versus 78.4% for NIHSSscore <9 (OR=0.08, 95% CI 0.03 to 0.21, p<0.0001). Mortality was 42% for NIHSS score ≥9 versus 2.7% for NIHSS score <9 (OR=26, 95% CI 3.3 to 202, p<0.0001). Infarct volume was 57 (±55.7) cm3 for NIHSS score ≥9 versus 30 (±34)cm3 for NIHSS score <9 (p=0.003). IV recombinant tissue plasminogen activator (rtPA) administered in 28 (24%) patients did not affect outcomes. The rate of M2 occlusions was 7 (95% CI 5 to 9)/100 000 people/year (3%, 95% CI 2% to 4%), giving an incidence of 21 176 (95% CI 15 282 to 29 247)/year. Combined with M1, internal carotid artery terminus and basilar artery, this yields a 'large vessel occlusion (LVO)+M2' rate of 31 (95% CI 26 to 35)/100 000 people/year and a national incidence of 99 227 (95% CI 84 004 to 112 005) LVO+M2 strokes/year. CONCLUSION: M2 occlusions can present with serious neurological deficits and cause significant morbidity and mortality. Patients with M2 occlusions and higher baseline deficits (NIHSS score ≥9) may benefit from endovascular therapy, thus potentially expanding the category of acute ischemic strokes amenable to intervention.

A population-based incidence of acute large vessel occlusions and thrombectomy eligible patients indicates significant potential for growth of endovascular stroke therapy in the USA.

BACKGROUND: Data on large vessel strokes are important for resource allocation and infrastructure development. OBJECTIVE: To determine an annual incidence of large vessel occlusions (LVOs) and a thrombectomy eligible patient population. METHODS: All patients with acute ischemic stroke discharged over 3 years from a tertiary-level hospital serving a large geographic area were evaluated for an LVO (M1, internal carotid artery terminus, basilar artery). The incidence of LVO was determined for the hospital's 4-county primary service area (PSA, population 210 000) based on each county's discharges and extrapolated to the US population. 'Thrombectomy eligibility' for anterior circulation LVOs was based on time (onset <6 hours) and imaging (Alberta Stroke Program Early CT Score (ASPECTS) ≥6). The number of annual thrombectomy procedures was calculated for Medicare and private payer patients using federally available databases. RESULTS: 1157 patients were discharged from the hospital's PSA, of whom 129 (11.1%, 95% CI 9.5% to 13.1%) had an LVO. This translated into an LVO incidence of 24 per 100 000 people per year (95% CI 20 to 28). 20 per 100 000 people per year had anterior circulation LVOs (95% CI 19 to 22), of whom 10/100 000/year (95% CI 8 to 11) were 'thrombectomy eligible'. An additional 5/100 000/year (95% CI 3 to 6) presented with favorable ASPECTS after 6 hours of symptom onset. Basilar occlusion incidence was estimated at 4/100 000/year (95% CI 2 to 5). These rates yield 77 569 (95% CI 65 835 to 91 091) new LVOs per year in the USA. An estimated 10 284 mechanical thrombectomy procedures were performed in 2015. CONCLUSIONS: This study estimates an LVO incidence of 24 per 100 000 person-years (95% CI 20 to 28). A current estimated annual thrombectomy rate of three procedures per 100 000 people indicates significant potential increase in the volume of endovascular procedures and the need to develop systems of care.

Quantitative comparisons on hand motor functional areas determined by resting state and task BOLD fMRI and anatomical MRI for pre-surgical planning of patients with brain tumors.

For pre-surgical planning we present quantitative comparison of the location of the hand motor functional area determined by right hand finger tapping BOLD fMRI, resting state BOLD fMRI, and anatomically using high resolution T1 weighted images. Data were obtained on 10 healthy subjects and 25 patients with left sided brain tumors. Our results show that there are important differences in the locations (i.e., > 20 mm) of the determined hand motor voxels by these three MR imaging methods. This can have significant effect on the pre-surgical planning of these patients depending on the modality used. In 13 of the 25 cases (i.e., 52%) the distances between the task-determined and the rs-fMRI determined hand areas were more than 20 mm; in 13 of 25 cases (i.e., 52%) the distances between the task-determined and anatomically determined hand areas were > 20 mm; and in 16 of 25 cases (i.e., 64%) the distances between the rs-fMRI determined and anatomically determined hand areas were more than 20 mm. In just three cases, the distances determined by all three modalities were within 20 mm of each other. The differences in the location or fingerprint of the hand motor areas, as determined by these three MR methods result from the different underlying mechanisms of these three modalities and possibly the effects of tumors on these modalities.

The 'pit-crew' model for improving door-to-needle times in endovascular stroke therapy: a Six-Sigma project.

BACKGROUND: Delays in delivering endovascular stroke therapy adversely affect outcomes. Time-sensitive treatments such as stroke interventions benefit from methodically developed protocols. Clearly defined roles in these protocols allow for parallel processing of tasks, resulting in consistent delivery of care. OBJECTIVE: To present the outcomes of a quality-improvement (QI) process directed at reducing stroke treatment times in a tertiary level academic medical center. METHODS: A Six-Sigma-based QI process was developed over a 3-month period. After an initial analysis, procedures were implemented and fine-tuned to identify and address rate-limiting steps in the endovascular care pathway. Prospectively recorded treatment times were then compared in two groups of patients who were treated 'before' (n=64) or 'after' (n=30) the QI process. Three time intervals were measured: emergency room (ER) to arrival for CT scan (ER-CT), CT scan to interventional laboratory arrival (CT-Lab), and interventional laboratory arrival to groin puncture (Lab-puncture). RESULTS: The ER-CT time was 40 (±29) min in the 'before' and 26 (±15) min in the 'after' group (p=0.008). The CT-Lab time was 87 (±47) min in the 'before' and 51 (±33) min in the 'after' group (p=0.0002). The Lab-puncture time was 24 (±11) min in the 'before' and 15 (±4) min in the 'after' group (p<0.0001). The overall ER-arrival to groin-puncture time was reduced from 2 h, 31 min (±51) min in the 'before' to 1 h, 33 min (±37) min in the 'after' group, (p<0.0001). The improved times were seen for both working hours and off-hours interventions. CONCLUSIONS: A protocol-driven process can significantly improve efficiency of care in time-sensitive stroke interventions.