O-020 Modifying Flow in the ICA Bifurcation: Pipeline Deployment from the supraclinoid ICA Extending into the M1 Segment: Clinical and Anatomical Results

BACKGROUND: Utility of the pipeline embolization device (PED) extending to the M1 segment as well as its clinical and flow consequences at the ICA bifurcation, has not clearly described. We describe clinical and anatomical flow modifications results at the ICA bifurcation. METHODS: In this retrospective analysis of patients treated for distal supraclinoid carotid aneurysms, a single PED was deployed from the proximal M1 segment to the distal supraclinoid carotid. Flow assessment prior to the procedure, to predict the competence of the ACA/AcomA complex, was achieved by formal DSA angiography and occasional manual cross compression. In all cases a single PED was deployed over the ostium of the A1, while treating a single or multiple aneurysms. Anatomical vessels diameters and ratios between the size of the proximal segments of the A1 and M1 as well as the distal ICA were assessed. Relationships between the PED nominal diameter and the diameters of the vessels at the landing zones were obtained. All measurements were evaluated in respect to flow modifications and size regression of the A1 in the immediate postoperative images, at 3 month MRI/MRA and at 6-9 month formal DSA angiography. Immediate and mid-term clinical results were assessed. RESULTS: We treated seven patients using this technique. Median age was 62. Four patients were treated for multiple aneurysms. The following aneurysms were treated: 3 posterior communicating artery aneurysms, 3 anterior choroidal artery aneurysms, 4 ICA bifurcation aneurysms and one A1 segment aneurysm. 6/7 patients demonstrated no change of flow in ACA/AComA complex at the immediate post embolization angiography. One patient demonstrated immediate antegrade flow retardation in the ipsilateral A1 segment. Five patients underwent 3-4 month MRA follow up. All demonstrated size regression of the ipsilateral A1 segment and occlusion of the neurysms. Five patients underwent mid-term follow-up angiography (5.5-12 month). Complete reversal of flow in the ipsilateral A1, was noted in 4/5 patients (Figure 1). One patient did not demonstrate any flow modification. This patient had a dominant ipsilateral A1 segment. Interestingly, ratios of the vessels participating in this bifurcation demonstrated a unique configuration of a higher A1/M1, A1/ICA ratios and a lower M1/ICA ratio, possibly in favor of maintaining patency of the ipsilateral A1. In this specific patient, a minimal length (0.97 mm) of PED was deployed in the M1 segment. This was the most oversized PED in respect to the M1 segment. All patients were stable in the post-procedural period and with no new neurological deficits. There were no clinical nor radiographic signs of ischemia. One patient experienced asymptomatic angiographic in-stent stenosis at the M1 segment. CONCLUSIONS: We found that the deployment of PED from the distal supraclinoid carotid to the M1 segment may result in reversal of flow in the ACA/AcomA complex as well as regression of the ipsilateral A1 segment. Preoperative anatomical disposition and sizing of the PED may predict the flow modification results. This modification of flow is safe and effective, based on pre-embolization flow assessments, and may be useful in treating distal ICA aneurysm by a flow diverter. DISCLOSURES: E. Nossek: None. D. Chalif: None. S. Chakraborty: None. A. Setton: None

Internal Maxillary Artery-Middle Cerebral Artery Bypass: Infratemporal Approach for Subcranial-Intracranial (SC-IC) Bypass

BACKGROUND:Internal maxillary artery (IMax)-middle cerebral artery (MCA) bypass has been recently described as an alternative to cervical extracranial-intracranial bypass. This technique uses a keyhole craniectomy in the temporal fossa that requires a technically challenging end-to-side anastomosis.OBJECTIVE:To describe a lateral subtemporal craniectomy of the middle cranial fossa floor to facilitate wide exposure of the IMax to facilitate bypass.METHODS:Orbitozygomatic osteotomy is used followed by frontotemporal craniotomy and subsequently laterotemporal fossa craniectomy, reaching its medial border at a virtual line connecting the foramen rotundum and foramen ovale. The IMax was identified by using established anatomic landmarks, neuronavigation, and micro Doppler probe (Mizuho Inc. Tokyo, Japan). Additionally, we studied the approach in a cadaveric specimen in preparation for microsurgical bypass.RESULTS:There were 4 cases in which the technique was used. One bypass was performed for flow augmentation in a hypoperfused hemisphere. The other 3 were performed as part of treatment paradigms for giant middle cerebral artery aneurysms. Vein grafts were used in all patients. The proximal anastomosis was performed in an end-to-side fashion in 1 patient and end-to-end in 3 patients. Intraoperative graft flow measured with the Transonic flow probe ranged from 20 to 60 mL/min. Postoperative angiography demonstrated good filling of the graft with robust distal flow in all cases. All patients tolerated the procedure well.CONCLUSION:IMax to middle cerebral artery subcranial-intracranial bypass is safe and efficacious. The laterotemporal fossa craniectomy technique resulted in reliable identification and wide exposure of the IMax, facilitating the proximal anastomosis

Bioactive in situ crosslinkable polymer-peptide hydrogel for cell delivery to the intervertebral disc in a rat model

Degeneration of the intervertebral disc (IVD) is associated with significant biochemical and morphological changes that include a loss of disc height, decreased water content and decreased cellularity. Cell delivery has been widely explored as a strategy to supplement the nucleus pulposus (NP) region of the degenerated IVD in both pre-clinical and clinical trials, using progenitor or primary cell sources. We previously demonstrated an ability for a polymer-peptide hydrogel, serving as a culture substrate, to promote adult NP cells to undergo a shift from a degenerative fibroblast-like state to a juvenile-like NP phenotype. In the current study, we evaluate the ability for this peptide-functionalized hydrogel to serve as a bioactive system for cell delivery, retention and preservation of a biosynthetic phenotype for primary IVD cells delivered to the rat caudal disc in an anular puncture degeneration model. Our data suggest that encapsulation of adult degenerative human NP cells in a stiff formulation of the hydrogel functionalized with laminin-mimetic peptides IKVAV and AG73 can promote cell viability and increased biosynthetic activity for this population in 3D culture in vitro. Delivery of the peptide-functionalized biomaterial with primary rat cells to the degenerated IVD supported NP cell retention and NP-specific protein expression in vivo, and promoted improved disc height index (DHI) values and endplate organization compared to untreated degenerated controls. The results of this study suggest the physical cues of this peptide-functionalized hydrogel can serve as a supportive carrier for cell delivery to the IVD. STATEMENT OF SIGNIFICANCE: Cell delivery into the degenerative intervertebral disc has been widely explored as a strategy to supplement the nucleus pulposus. The current work seeks to employ a biomaterial functionalized with laminin-mimetic peptides as a cell delivery scaffold in order to improve cell retention rates within the intradiscal space, while providing the delivered cells with biomimetic cues in order to promote phenotypic expression and increase biosynthetic activity. The use of the in situ crosslinkable material integrated with the native IVD, presenting a system with adequate physical properties to support a degenerative disc

Star Formation Suppression by Tidal Removal of Cold Molecular Gas from an Intermediate-redshift Massive Post-starburst Galaxy

Observations and simulations have demonstrated that star formation in galaxies must be actively suppressed to prevent the formation of overly massive galaxies. Galactic outflows driven by stellar feedback or supermassive black hole accretion are often invoked to regulate the amount of cold molecular gas available for future star formation but may not be the only relevant quenching processes in all galaxies. We present the discovery of vast molecular tidal features extending up to 64 kpc outside of a massive z = 0.646 post-starburst galaxy that recently concluded its primary star-forming episode. The tidal tails contain (1.2 ± 0.1) × 1010 M⊙ of molecular gas, 47% ± 5% of the total cold gas reservoir of the system. Both the scale and magnitude of the molecular tidal features are unprecedented compared to all known nearby or high-redshift merging systems. We infer that the cold gas was stripped from the host galaxies during the merger, which is most likely responsible for triggering the initial burst phase and the subsequent suppression of star formation. While only a single example, this result shows that galaxy mergers can regulate the cold gas contents in distant galaxies by directly removing a large fraction of the molecular gas fuel, and plausibly suppress star formation directly, a qualitatively different physical mechanism than feedback-driven outflows

NF-κB-mediated effects on behavior and cartilage pathology in a non-invasive loading model of post-traumatic osteoarthritis

OBJECTIVE: This study aimed to examine the temporal activation of NF-κB and its relationship to the development of pain-related sensitivity and behavioral changes in a non-invasive murine knee loading model of PTOA. METHOD: Following knee injury NF-κB activity was assessed longitudinally via in vivo imaging in FVB. Cg-Tg (HIV-EGFP,luc)8Tsb/J mice. Measures of pain-related sensitivity and behavior were also assessed longitudinally for 16 weeks. Additionally, we antagonized NF-κB signaling via intra-articular delivery of an IκB kinase two antagonist to understand how local NF-κB inhibition might alter disease progression. RESULTS: Following joint injury NF-κB signaling within the knee joint was transiently increased and peaked on day 3 with an estimated 1.35 p/s/cm CONCLUSION: These findings underscore the development of behavioral changes in this non-invasive loading model of PTOA and their relationships to NF-κB activation and pathology. They also highlight the potential chondroprotective effects of NF-κB inhibition shortly following joint injury despite limitations in preventing the long-term development of joint degeneration in this model of PTOA

Development of a library of laminin-mimetic peptide hydrogels for control of nucleus pulposus cell behaviors

The nucleus pulposus (NP) of the intervertebral disc plays a critical role in distributing mechanical loads to the axial skeleton. Alterations in NP cells and, consequently, NP matrix are some of the earliest changes in the development of disc degeneration. Previous studies demonstrated a role for laminin-presenting biomaterials in promoting a healthy phenotype for human NP cells from degenerated tissue. Here we investigate the use of laminin-mimetic peptides presented individually or in combination on a poly(ethylene) glycol hydrogel as a platform to modulate the behaviors of degenerative human NP cells. Data confirm that NP cells attach to select laminin-mimetic peptides that results in cell signaling downstream of integrin and syndecan binding. Furthermore, the peptide-functionalized hydrogels demonstrate an ability to promote cell behaviors that mimic that of full-length laminins. These results identify a set of peptides that can be used to regulate NP cell behaviors toward a regenerative engineering strategy