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  • Salomonsen McElroy posted an update 3 months, 2 weeks ago

    This also provides a foundation for noninvasive intravenous delivery of therapeutic molecules to precise brain targets after transient disruption of the BBB. Certain chemotherapies for brain tumors, immunotherapies, gene, and cell therapies are all examples of therapeutic or even restorative agents that normally will not enter the brain without direct infusion but which have been shown in preclinical studies to effectively traverse the BBB after transient disruption with MRgFUS. Here we will review these novel applications of MRgFUS to provide an overview of the extraordinary potential of this technology to expand future neurosurgical treatments of brain diseases.Magnetic resonance-guided focused ultrasound is a powerful new technology that is enabling development of noninvasive applications for complex brain disorders. This is currently revolutionizing the treatment of tremor disorders, and a variety of experimental applications are under active investigation. To fully realize the potential of this disruptive technology, many challenges have been identified, some of which have been addressed and others remain to be solved. As an image-based technology, optimal intraoperative imaging can be difficult to achieve and several factors can influence the quality of these images. Technical issues with current devices can also limit the effective delivery of ultrasound technology to particular targets. While lesioning is the primary approved application of magnetic resonance-guided focused ultrasound at present, the ability to transient and precisely open the blood-brain barrier has the potential to clear brain pathologies and deliver restorative therapies, but this more experimental method presents unique difficulties to overcome. Finally, regulatory and reimbursement hurdles currently remain complex and continue to limit widespread application of even approved, effective applications. Here we review many of these challenges, discuss several solutions that have already been developed, and propose potential options for addressing some of these complexities in the future.The ability of ultrasonography to safely penetrate deeply into the brain has made it an attractive technology for neurological applications for almost 1 century. Having recognized that converging ultrasound waves could deliver high levels of energy to a target and spare the overlying and surrounding brain, early applications used craniotomies to allow transducers to contact the brain or dural surface. The development of transducer arrays that could permit the transit of sufficient numbers of ultrasound waves to deliver high energies to a target, even with the loss of energy from the skull, has now resulted in clinical systems that can permit noninvasive focused ultrasound procedures that leave the skull intact. Another major milestone in the field was the marriage of focused ultrasonography with magnetic resonance thermometry. This provides real-time feedback regarding the level and location of brain tissue heating, allowing for precise elevation of temperatures within a desired target to lead to focal therapeutic lesions. The major clinical use of this technology, at present, has been limited to treatment of refractory essential tremor and parkinsonian tremor, although the first study of this approach had targeted sensory thalamus for refractory pain, and new targets and disease indications are under study. Finally, focused ultrasonography can also be used at a lower frequency and energy level when combined with intravenous microbubbles to create cavitations, which will open the blood-brain barrier rather than ablate tissue. In the present review, we have discussed the historical and scientific foundations and current clinical applications of magnetic resonance-guided focused ultrasonography and the genesis and background that led to the use of this technique for focal blood-brain barrier disruption.Extradural anterior clinoidectomy is an important tool for neurovascular and skull base surgery. This technique is cardinal for expanding access to the proximal carotid artery, optic nerve, sella, and the central skull base. The goal of anterior clinoidectomy is to reveal the more proximal ophthalmic and clinoidal segments of the internal carotid artery (ICA) while skeletonizing the proximal optic nerve. CM272 This maneuver expands the opticocarotid and carotid-oculomotor windows and therefore the operative corridor to the interpeduncular cisterns; both the carotid artery and optic nerve are partially untethered or liberated and can be more safely mobilized.The benefits of deammonification to remove nitrogen from sidestreams, i.e., sludge dewatering liquors, in municipal wastewater treatment plants are well accepted. The ammonia removal from dewatering liquors originated from thermal hydrolysis/anaerobic digestion (THP/AD) are deemed challenging. Many different commercial technologies have been applied to remove ammonia from sidestreams, varying in reactor design, biomass growth form and instrumentation and control strategy. Four technologies were tested (a deammonification suspended sludge sequencing batch reactor (S-SBR), a deammonification moving bed biofilm reactor (MEDIA), a deammonification granular sludge sequencing batch reactor (G-SBR), and a nitrification suspended sludge sequencing batch reactor (N-SBR)). All technologies relied on distinct control strategies that actuated on the feed flow leading to a range of different ammonia loading rates. Periods of poor performance were displayed by all technologies and related to imbalances in the chain of deammonification reactions subsequently effecting both load and removal. The S-SBR was most robust, not presenting these imbalances. The S-SBR and G-SBR presented the highest nitrogen removal rates (NRR) of 0.58 and 0.56 kg N m-3 d-1, respectively. The MEDIA and the N-SBR presented an NRR of 0.17 and 0.07 kg N m-3 d-1, respectively. This study demonstrated stable ammonia removal from THP/AD dewatering liquors and did not observe toxicity in the nitrogen removal technologies tested. It was identified that instrumentation and control strategy was the main contributor that enabled higher stability and NRR. Overall, this study provides support in selecting a suitable biological nitrogen removal technology for the treatment of sludge dewatering liquors from THP/AD.

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