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Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease.
Lancet Neurol
January 2025
Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK. Electronic address:
The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics.
View Article and Find Full Text PDFGene Therapy for Glioblastoma Multiforme.
Viruses
January 2025
Surgical Neurology Branch, NINDS, NIH 10 Center Drive, Bethesda, MD 20892, USA.
Glioblastoma multiforme (GBM) is a devastating, aggressive primary brain tumor with poor patient outcomes and a five-year survival of less than 10%. Significant limitations to effective GBM treatment include poor drug delivery across the blood-brain barrier, drug resistance, and complex genetic tumor alterations. Gene therapy uses a mechanism different from other GBM therapies to reduce tumor growth and enhance antitumor immunity.
View Article and Find Full Text PDFPathological diagnosis of central nervous system tumours in adults: what's new?
Pathology
December 2024
Department of Pathology, Amsterdam University Medical Centers/VUmc, Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
In the course of the last decade, the pathological diagnosis of many tumours of the central nervous system (CNS) has transitioned from a purely histological to a combined histological and molecular approach, resulting in a more precise 'histomolecular diagnosis'. Unfortunately, translation of this refinement in CNS tumour diagnostics into more effective treatment strategies is lagging behind. There is hope though that incorporating the assessment of predictive markers in the pathological evaluation of CNS tumours will help to improve this situation.
View Article and Find Full Text PDFNNFit: A Self-Supervised Deep Learning Method for Accelerated Quantification of High- Resolution Short Echo Time MR Spectroscopy Datasets.
Radiol Artif Intell
January 2025
From the Department of Radiation Oncology (A.S.G., V.H., H.S.) and Department of Radiology and Imaging Sciences (B.D.W.), Emory University School of Medicine, 1701 Uppergate Dr, C5008 Winship Cancer Institute, Atlanta, GA 30322; Department of Radiology, University of Miami {School of Medicine?}, Miami, Fla (S.S., A.A.M.); Department of {Radiology?} Northwestern University {Feinberg School of Medicine?}, Chicago, Ill (L.A.D.C.); Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, Ga (Y.L.); Department of Psychology, Emory University, Atlanta, Ga (M.T.); and Department of Radiology, Duke University Medical Center, Durham, NC (B.J.S.).
Purpose To develop and evaluate the performance of NNFit, a self-supervised deep-learning method for quantification of high-resolution short echo-time (TE) echo-planar spectroscopic imaging (EPSI) datasets, with the goal of addressing the computational bottleneck of conventional spectral quantification methods in the clinical workflow. Materials and Methods This retrospective study included 89 short-TE whole-brain EPSI/GRAPPA scans from clinical trials for glioblastoma (Trial 1, May 2014-October 2018) and major-depressive-disorder (Trial 2, 2022- 2023). The training dataset included 685k spectra from 20 participants (60 scans) in Trial 1.
View Article and Find Full Text PDFPhotosensitizer spatial heterogeneity and its impact on personalized interstitial photodynamic therapy treatment planning.
J Biomed Opt
January 2025
University of Toronto, University Health Network, Princess Margaret Cancer Centre, Department of Medical Biophysics, Toronto, Ontario, Canada.
Significance: Personalized photodynamic therapy (PDT) treatment planning requires knowledge of the spatial and temporal co-localization of photons, photosensitizers (PSs), and oxygen. The inter- and intra-subject variability in the photosensitizer concentration can lead to suboptimal outcomes using standard treatment plans.
Aim: We aim to quantify the PS spatial variation in tumors and its effect on PDT treatment planning solutions.
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