دورية أكاديمية
أعرض في EDS

Cochlear pharmacokinetics - Micro-computed tomography and learning-prediction modeling for transport parameter determination.

التفاصيل البيبلوغرافية
العنوان: Cochlear pharmacokinetics - Micro-computed tomography and learning-prediction modeling for transport parameter determination.
المؤلفون: Moudgalya SS; Chester F. Carlson Center for Imaging Science, Rochester Institute of Technology, Rochester, NY, USA., Wilson K; Department of Electrical and Microelectronic Engineering, Rochester Institute of Technology, Rochester, NY, USA., Zhu X; Department of Medical Engineering, University of Southern Florida, Tampa, FL, USA; Global Center for Hearing and Speech Research, University of Southern Florida, Tampa, FL, USA., Budzevich MM; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA., Walton JP; Department of Medical Engineering, University of Southern Florida, Tampa, FL, USA; Global Center for Hearing and Speech Research, University of Southern Florida, Tampa, FL, USA; Department of Communication Sciences and Disorders, University of Southern Florida, Tampa, FL, USA., Cahill ND; Chester F. Carlson Center for Imaging Science, Rochester Institute of Technology, Rochester, NY, USA; School of Mathematical Sciences, Rochester Institute of Technology, Rochester, NY, USA., Frisina RD; Department of Medical Engineering, University of Southern Florida, Tampa, FL, USA; Global Center for Hearing and Speech Research, University of Southern Florida, Tampa, FL, USA., Borkholder DA; Department of Electrical and Microelectronic Engineering, Rochester Institute of Technology, Rochester, NY, USA; Microsystems Engineering, Rochester Institute of Technology, Rochester, NY, USA. Electronic address: david.borkholder@rit.edu.
المصدر: Hearing research [Hear Res] 2019 Sep 01; Vol. 380, pp. 46-59. Date of Electronic Publication: 2019 Jun 01.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7900445 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-5891 (Electronic) Linking ISSN: 03785955 NLM ISO Abbreviation: Hear Res Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
مواضيع طبية MeSH: Models, Biological* , X-Ray Microtomography*, Cochlea/*diagnostic imaging , Cochlea/*metabolism , Contrast Media/*pharmacokinetics , Iopamidol/*pharmacokinetics, Animals ; Computer Simulation ; Contrast Media/administration & dosage ; Diffusion ; Infusions, Parenteral ; Iopamidol/administration & dosage ; Mice, Inbred CBA ; Tissue Distribution
مستخلص: Inner ear disorders such as sensorineural deafness and genetic diseases may one day be treated with local drug delivery to the inner ear. Current pharmacokinetic models have been based on invasive methods to measure drug concentrations, limiting them in spatial resolution, and restricting the research to larger rodents. We developed an intracochlear pharmacokinetic model based on an imaging, learning-prediction (LP) paradigm for learning transport parameters in the murine cochlea. This was achieved using noninvasive micro-computed tomography imaging of the cochlea during in vivo infusion of a contrast agent at the basal end of scala tympani through a cochleostomy. Each scan was registered in 3-D to a cochlear atlas to segment the cochlear regions with high accuracy, enabling concentrations to be extracted along the length of each scala. These spatio-temporal concentration profiles were used to learn a concentration dependent diffusion coefficient, and transport parameters between the major scalae and to clearance. The LP model results are comparable to the current state of the art model, and can simulate concentrations for cases involving different infusion molecules and different drug delivery protocols. Forward simulation results with pulsatile delivery suggest the pharmacokinetic model can be used to optimize drug delivery protocols to reduce total drug delivered and the potential for toxic side effects. While developed in the challenging murine cochlea, the processes are scalable to larger animals and different drug infusion paradigms.
(Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
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معلومات مُعتمدة: P30 CA076292 United States CA NCI NIH HHS; R01 DC014568 United States DC NIDCD NIH HHS
فهرسة مساهمة: Keywords: 3-D image registration; Cochlea; Contrast agent; Inner ear; Micro-computed tomography; Mouse; Optimization; Pharmacokinetics; Segmentation
المشرفين على المادة: 0 (Contrast Media)
JR13W81H44 (Iopamidol)
تواريخ الأحداث: Date Created: 20190611 Date Completed: 20210104 Latest Revision: 20210104
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6669082
DOI: 10.1016/j.heares.2019.05.009
PMID: 31181459
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-5891
DOI:10.1016/j.heares.2019.05.009