BACKGROUND: Intrathecal drug delivery is an attractive option to circumvent the blood-brain barrier for pain management through its increased efficacy of pain relief, reduction in adverse side effects, and cost-effectiveness. Unfortunately, there are limited guidelines for physicians to choose infusion or drug pump settings to administer therapeutic doses to specific regions of the spine or the brain. Although empiric trialing of intrathecal drugs is critical to determine the sustained side effects, currently there is no inexpensive in vitro method to guide the selection of spinal drug delivery parameters. The goal of this study is to demonstrate current computational capabilities to predict drug biodistribution while varying 3 parameters: (1) infusion settings, (2) drug chemistry, and (3) subject-specific anatomy and cerebrospinal fluid dynamics. We will discuss strategies to systematically optimize these 3 parameters to administer drug molecules to targeted tissue locations in the central nervous system. METHODS: We acquired anatomical data from magnetic resonance imaging (MRI) and velocity measurements in the spinal cerebrospinal fluid with CINE-MRI for 2 subjects. A bench-top surrogate of the subject-specific central nervous system was constructed to match measured anatomical dimensions and volumes. We generated a computational mesh for the bench-top model. Idealized simulations of tracer distribution were compared with bench-top measurements for validation. Using reconstructions from MRI data, we also introduced a subject-specific computer model for predicting drug spread for the human volunteer. RESULTS: MRI velocity measurements at 3 spinal regions of interest reasonably matched the simulated flow fields in a subject-specific computer mesh. Comparison between the idealized spine computations and bench-top tracer distribution experiments demonstrate agreement of our drug transport predictions to this physical model. Simulated multibolus drug infusion theoretically localizes drug to the cervical and thoracic region. Continuous drug pump and single bolus injection were successful to target the lumbar spine in the simulations. The parenchyma might be targeted suitably by multiple boluses followed by a flush infusion. We present potential guidelines that take into account drug specific kinetics for tissue uptake, which influence the speed of drug dispersion in the model and potentially influence tissue targeting. DISCUSSION: We present potential guidelines considering drug-specific kinetics of tissue uptake, which determine the speed of drug dispersion and influence tissue targeting. However, there are limitations to this analysis in that the parameters were obtained from an idealized healthy patient in a supine position. The proposed methodology could assist physicians to select clinical infusion parameters for their patients and provide guidance to optimize treatment algorithms. In silico optimization of intrathecal drug delivery therapies presents the first steps toward a possible care paradigm in the future that is specific to personalized patient anatomy and diseases. (C) 2017 International Anesthesia Research Society
http://ift.tt/2oaUe1G
Αρχειοθήκη ιστολογίου
-
►
2020
(289)
- ► Φεβρουαρίου (28)
-
►
2019
(9071)
- ► Δεκεμβρίου (19)
- ► Σεπτεμβρίου (54)
- ► Φεβρουαρίου (3642)
- ► Ιανουαρίου (3200)
-
►
2018
(39872)
- ► Δεκεμβρίου (3318)
- ► Σεπτεμβρίου (3683)
- ► Φεβρουαρίου (2693)
- ► Ιανουαρίου (3198)
-
▼
2017
(41099)
- ► Δεκεμβρίου (3127)
- ► Σεπτεμβρίου (2173)
-
▼
Απριλίου
(6024)
-
▼
Απρ 07
(222)
- Ten-year survival outcomes for patients with nasop...
- Viral Reactivations and Associated Outcomes in Con...
- Outcome of Hematopoietic Cell Transplantation for ...
- Interplay Between the Skin Barrier and Immune Cell...
- Is IL-1β inhibition the next therapeutic target in...
- Efficacy of tofacitinib for the treatment of nail ...
- The effectiveness of treatments for androgenetic a...
- Yellow Fever Virus Modulates the Expression of Key...
- Development of mPMab-1, a Mouse–Rat Chimeric Antib...
- LpMab-23: A Cancer-Specific Monoclonal Antibody Ag...
- The association of Enamelin, Lactoferrin, and Tumo...
- The Rosai–Dorfman Disease: A Differential Diagnosi...
- Acquired Angioedema: A Rare Manifestation of Angio...
- A Rare Case of Basal Cell Adenocarcinoma of Paroti...
- Managing the Dorsum in Rhinoplasty
- Cartilage Scales Embedded in Fibrin Gel
- Dorsal Augmentation Using Autologous Costal Cartil...
- Understanding Approaches to the Dorsal Hump
- Dorsal Augmentation with Homologous Rib
- Aesthetics of the Nasal Dorsum: Proportions, Light...
- Safety of 2-Octyl Cyanoacrylate in Spreader Grafting
- Midvault Reconstruction in Primary Rhinoplasty
- Facial Augmentation using Expanded Polytetrafluoro...
- Treating the Deviated or Wide Nasal Dorsum
- Revision of the Nasal Dorsum
- Correcting Deviations of the Lower Third of the Nose
- Rhinoplasty Results Are Influenced by Non-nasal Fe...
- Dorsal Augmentation-Diced Cartilage Techniques: Th...
- Interest in Aesthetic Rhinoplasty Scale
- Dorsal Augmentation using Alloplastic Implants
- Absorbable Implant to Treat Nasal Valve Collapse
- Erratum: Hyaluronic Acid Fillers in Soft Tissue Re...
- The Importance of Facts and the Role of Academic P...
- Detection of endolymphatic hydrops using tradition...
- Reduced post-tonsillectomy bleeding rates through ...
- Correction to: Viral Immunol 2013;26:259–267
- MicroRNA-155 Deficiency in Kupffer Cells Ameliorat...
- Human Herpesvirus 6 Reactivation in DRESS With Acu...
- Octogenarian Liver Grafts Reaching Centennial Age ...
- Sleep-Disordered Breathing, Postoperative Delirium...
- Computational and In Vitro Experimental Investigat...
- Total Spinal Anesthesia Failure: Have You Assessed...
- How Long Is Too Long? The Prespiked Intravenous De...
- The Association of Frailty With Outcomes and Resou...
- Creation and Validation of an Automated Algorithm ...
- Anesthesiologists and Disaster Medicine: A Needs A...
- Surveying the Literature: Synopsis of Recent Key P...
- Generative Retrieval Improves Learning and Retenti...
- It Takes a Village to Deliver Effective and Effici...
- Sevoflurane Posttreatment Attenuates Lung Injury I...
- Does Bariatric Surgery Decrease Levothyroxine Requ...
- Postoperative Thyroglobulin and Neck Ultrasound Ar...
- Thyroid Nodules Do Not Increase in Size During Pre...
- Intensity of 18F-FDG Uptake in Metastatic Differen...
- Levothyroxine Therapy of Subclinical Hypothyroidis...
- Rare Cases of Differentiated Thyroid Cancer with L...
- Hyperthyroidism with Severe Liver Dysfunction Can ...
- In Patients with Congenital Hypothyroidism, Prolon...
- Could Measuring a Spectrum of Metabolites and Prot...
- Novel Anticoagulant Agents in the Perioperative Se...
- Erratum
- General anesthetic actions on GABA A receptors in ...
- Diagnostic Tools in Ocular Allergy
- Work productivity in rhinitis using cell phones: T...
- Whipple’s disease in granulomatous disguise: a cha...
- Not little adults: The uniqueness of the pediatric...
- CARD14-Mediated Activation of Paracaspase MALT1 in...
- Type I lnterferons Modulate CD8(+) T Cell Immunity...
- Bioinspired, biomimetic, double-enzymatic minerali...
- Procedure of informed assent/consent for clinical ...
- Off-label and unlicensed use in a pediatric hemato...
- Predicting outcomes for children with neuroblastoma
- GATA4 and GATA5 are potential tumor suppressors an...
- Pharmacologic unmasking of epigenetically silenced...
- Transabdominal wall lipoma
- Otolaryngology: Open Access..................OMICS...
- Adolescent anxiety: The effectiveness of psycholog...
- The impact of a lack of medical explanation for pa...
- Generalisation in Named Entity Recognition: A Quan...
- The effect of brief mindfulness training on distre...
- Healthy adjustment for new residents with dementia...
- Benchmarking predictions of allostery in liver pyr...
- Biosecurity for Translocations: Cirl Bunting (Embe...
- Neural Correlates of Inhibition in Children and Ad...
- The Effect of Age on the Underlying Abilities of M...
- Pain part 9: Trigeminal autonomic cephalalgias
- Genetic evidence challenges the native status of a...
- Freud reads Krafft-Ebing : the case of sadism and ...
- Recht en geweld
- Freuds Gentse connectie: Juliaan Varendonck (1879-...
- Molybdenum(VI) Dioxo Complexes Supported on stable...
- Renal microRNA- and RNA-profiles in progressive ch...
- Positron emission tomography study of the human hy...
- Impact of Respiratory Virus Infections in Exacerba...
- An atypical form of infantile meningococcal mening...
- Aorto-right ventricular fistula following transcat...
- Impact of Respiratory Virus Infections in Exacerba...
- Johns Hopkins Researchers Win Top Prizes, Honors a...
- An NLRP3 inflammasome-triggered Th2-biased adaptiv...
- Neurophysiological and clinical investigation of p...
-
▼
Απρ 07
(222)
-
►
2016
(13807)
- ► Δεκεμβρίου (700)
- ► Σεπτεμβρίου (600)
- ► Φεβρουαρίου (1350)
- ► Ιανουαρίου (1400)
-
►
2015
(1500)
- ► Δεκεμβρίου (1450)
Ετικέτες
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου