RESUMEN
The blood-brain barrier (BBB) poses a significant challenge to drug delivery for brain tumors, with most chemotherapeutics having limited permeability into non-malignant brain tissue and only restricted access to primary and metastatic brain cancers. Consequently, due to the drug's inability to effectively penetrate the BBB, outcomes following brain chemotherapy continue to be suboptimal. Several methods to open the BBB and obtain higher drug concentrations in tumors have been proposed, with the selection of the optimal method depending on the size of the targeted tumor volume, the chosen therapeutic agent, and individual patient characteristics. Herein, we aim to comprehensively describe osmotic disruption with intra-arterial drug administration, intrathecal/intraventricular administration, laser interstitial thermal therapy, convection-enhanced delivery, and ultrasound methods, including high-intensity focused and low-intensity ultrasound as well as tumor-treating fields. We explain the scientific concept behind each method, preclinical/clinical research, advantages and disadvantages, indications, and potential avenues for improvement. Given that each method has its limitations, it is unlikely that the future of BBB disruption will rely on a single method but rather on a synergistic effect of a combined approach. Disruption of the BBB with osmotic infusion or high-intensity focused ultrasound, followed by the intra-arterial delivery of drugs, is a promising approach. Real-time monitoring of drug delivery will be necessary for optimal results.
RESUMEN
The paradigm is gradually shifting, with radiosurgery and endovascular embolization being increasingly chosen over surgical resection in the selected cases of brain arteriovenous malformations. Routinely used X-ray monitoring of liquid embolic infusion has very good spatial and temporal resolution but is not without significant drawbacks regarding poor visualization of the complex AVM angioarchitecture, especially after many embolizations in the past and therefore limiting the technical ability of the embocure-total occlusion of the feeding arteries, nidus, and draining veins. The purpose of this study was to evaluate the use of real-time MRI guidance in endovascular embolization with Onyx (instead of X-ray) in a single swine rete mirabile (RM) AVM model in order to provide the scaffolding for the real-time MRI guidance method. Onyx propagation was observed in real-time dynamic GE-EPI scan with initial ipsilateral RM filling followed by main cerebral arterial branch distribution. The relatively bright signal within RM and the brain prior to Onyx injection provided a good background for the dark, low signal of the embolic agent spreading in rete mirabile and brain arteries. X-ray picture confirmed Onyx cast distribution at the end of the procedure. In this initial experience, real-time MRI seems to be a promising method that may significantly improve liquid embolic agent infusion monitoring in the future, although requiring further development before clinical use.
RESUMEN
As a significant cause of intracerebral hemorrhages, seizures, and neurological decline, brain arteriovenous malformations (bAVMs) are a rare group of complex vascular lesions with devastating implications for patients' quality of life. Although the concerted effort of the scientific community has improved our understanding of bAVM biology, the exact mechanism continues to be elucidated. Furthermore, to this day, due to the high heterogeneity of bAVMs as well as the lack of objective data brought by the lack of evaluative and comparative studies, there is no clear consensus on the treatment of this life-threatening and dynamic disease. As a consequence, patients often fall short of obtaining the optimal treatment. Endovascular embolization is an inherent part of multidisciplinary bAVM management that can be used in various clinical scenarios, each with different objectives. Well-trained neuro-interventional centers are proficient at curing bAVMs that are smaller than 3 cm; are located superficially in noneloquent areas; and have fewer, larger, and less tortuous feeding arteries. The transvenous approach is an emerging effective and safe technique that potentially offers a chance to cure previously untreatable bAVMs. This review provides the state of the art in all aspects of endovascular embolization in the management of bAVMs.
RESUMEN
Objective: To provide a comprehensive review of intra-arterial cerebral infusions of chemotherapeutics in glioblastoma multiforme treatment and discuss potential research aims. We describe technical aspects of the intra-arterial delivery, methods of blood-brain barrier disruption, the role of intraoperative imaging and clinical trials involving intra-arterial cerebral infusions of chemotherapeutics in the treatment of glioblastoma multiforme. Method: 159 articles in English were reviewed and used as the foundation for this paper. The Medline/Pubmed, Cochrane databases, Google Scholar, Scielo and PEDro databases have been used to select the most relevant and influential papers on the intra-arterial cerebral infusions of chemotherapeutics in the treatment of glioblastoma multiforme. Additionally, we have included some relevant clinical trials involving intra-arterial delivery of chemotherapeutics to other than GBM brain tumours. Conclusion: Considering that conventional treatments for glioblastoma multiforme fall short of providing a significant therapeutic benefit, with a majority of patients relapsing, the neuro-oncological community has considered intra-arterial administration of chemotherapeutics as an alternative to oral or intravenous administration. Numerous studies have proven the safety of IA delivery of chemotherapy and its ability to ensure higher drug concentrations in targeted areas, simultaneously limiting systemic toxicity. Nonetheless, the scarcity of phase III trials prevents any declaration of a therapeutic benefit. Given that the likelihood of a single therapeutic agent which will be effective for the treatment of glioblastoma multiforme is extremely low, it is paramount to establish an adequate multimodal therapy which will have a synergistic effect on the diverse pathogenesis of GBM. Precise quantitative and spatial monitoring is necessary to guarantee the accurate delivery of the therapeutic to the tumour. New and comprehensive pharmacokinetic models, a more elaborate understanding of glioblastoma biology and effective methods of diminishing treatment-related neurotoxicity are paramount for intra-arterial cerebral infusion of chemotherapeutics to become a mainstay treatment for glioblastoma multiforme. Additional use of other imaging methods like MRI guidance during the procedure could have an edge over X-ray alone and aid in selecting proper arteries as well as infusion parameters of chemotherapeutics making the procedure safer and more effective.
