139 results match your criteria infusate distribution


Evaluation of a patient-specific algorithm for predicting distribution for convection-enhanced drug delivery into the brainstem of patients with diffuse intrinsic pontine glioma.

J Neurosurg Pediatr 2021 May 14:1-9. Epub 2021 May 14.

2Department of Neurological Surgery, Weill Medical College of Cornell University, New York, New York.

Objective: With increasing use of convection-enhanced delivery (CED) of drugs, the need for software that can predict infusion distribution has grown. In the context of a phase I clinical trial for pediatric diffuse intrinsic pontine glioma (DIPG), CED was used to administer an anti-B7H3 radiolabeled monoclonal antibody, iodine-124-labeled omburtamab. In this study, the authors retrospectively evaluated a software algorithm (iPlan Flow) for the estimation of infusate distribution based on the planned catheter trajectory, infusion parameters, and patient-specific MRI. Read More

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Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler.

Front Physiol 2020 15;11:491. Epub 2020 May 15.

Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Background: We recently reported a method using positron emission tomography (PET) and the tracer F-labeled tetraphenylphosphonium (F-TPP) for mapping the tissue (i.e., cellular plus mitochondrial) membrane potential (ΔΨ) in the myocardium. Read More

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Evaluating infusate parameters for direct drug delivery to the brainstem: a comparative study of convection-enhanced delivery versus osmotic pump delivery.

Neurosurg Focus 2020 01;48(1):E2

1Department of Neurologic Surgery, Mayo Clinic.

Objective: Convection-enhanced delivery (CED) and osmotic pump delivery both have been promoted as promising techniques to deliver drugs to pediatric diffuse intrinsic pontine gliomas (DIPGs). Correspondingly, the aim of this study was to understand how infusate molecular weight (MW), duration of delivery, and mechanism of delivery (CED or osmotic pump) affect volume of distribution (Vd) in the brainstem, to better inform drug selection and delivery in future DIPG investigations.

Methods: A series of in vivo experiments were conducted using rat models. Read More

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January 2020

Time-Resolved MRI Assessment of Convection-Enhanced Delivery by Targeted and Nontargeted Nanoparticles in a Human Glioblastoma Mouse Model.

Cancer Res 2019 09 22;79(18):4776-4786. Epub 2019 Jul 22.

Department of Materials Science and Engineering, University of Washington, Seattle, Washington.

Convection-enhanced delivery (CED) provides direct access of infusates to brain tumors; however, clinical translation of this technology has not been realized because of the inability to accurately visualize infusates in real-time and lack of targeting modalities against diffuse cancer cells. In this study, we use time-resolved MRI to reveal the kinetics of CED processes in a glioblastoma (GBM) model using iron oxide nanoparticles (NP) modified with a glioma-targeting ligand, chlorotoxin (CTX). Mice bearing orthotopic human GBM tumors were administered a single dose of targeted CTX-conjugated NP (NPCP-CTX) or nontargeted NP (NPCP) via CED. Read More

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September 2019

ABC Transporter Inhibition Plus Dexamethasone Enhances the Efficacy of Convection Enhanced Delivery in H3.3K27M Mutant Diffuse Intrinsic Pontine Glioma.

Neurosurgery 2020 05;86(5):742-751

Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina.

Background: An impermeable blood-brain barrier and drug efflux via ATP-binding cassette (ABC) transporters such as p-glycoprotein may contribute to underwhelming efficacy of peripherally delivered agents to treat diffuse intrinsic pontine glioma (DIPG).

Objective: To explore the pharmacological augmentation of convection-enhanced delivery (CED) infusate for DIPG.

Methods: The efficacy of CED dasatinib, a tyrosine kinase inhibitor, in a transgenic H3. Read More

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Convection-Enhanced Delivery of a Virus-Like Nanotherapeutic Agent with Dual-Modal Imaging for Besiegement and Eradication of Brain Tumors.

Theranostics 2019 28;9(6):1752-1763. Epub 2019 Feb 28.

Institute of Medical Science and Technology, National Sun Yat-sen University, 70 Lienhai Rd., Kaohsiung 80424, Taiwan.

Convection-enhanced delivery (CED) is a promising technique for infusing a therapeutic agent directly into the brain, bypassing the blood-brain barrier (BBB) with a pressure gradient to increase drug concentration specifically around the brain tumor, thereby enhancing tumor inhibition and limiting the systemic toxicity of chemotherapeutic agents. Herein, we developed a dual-imaging monitored virus-like nanotherapeutic agent as an ideal CED infusate, which can be delivered to specifically besiege and eradicate brain tumors. We report one-pot fabrication of green-fluorescence virus-like particles (gVLPs) in () for epirubicin (EPI) loading, cell-penetrating peptide (CPP) modification, and Ga-DOTA labeling to form a positron emission tomography (PET)-fluorescence dual-imaging monitored virus-like nanotherapeutic agent (Ga-DOTA labeled [email protected]) combined with CED for brain tumor therapy and image tracking. Read More

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Treatment Strategies in Diffuse Midline Gliomas With the H3K27M Mutation: The Role of Convection-Enhanced Delivery in Overcoming Anatomic Challenges.

Front Oncol 2019 8;9:31. Epub 2019 Feb 8.

Department of Neurosurgery, Mayo Clinic, Rochester, MN, United States.

Diffuse midline gliomas harboring the H3 K27M mutation-including the previously named diffuse intrinsic pontine glioma (DIPG)-are lethal high-grade pediatric brain tumors that are inoperable and without cure. Despite numerous clinical trials, the prognosis remains poor, with a median survival of ~1 year from diagnosis. Systemic administration of chemotherapeutic agents is often hindered by the blood brain barrier (BBB), and even drugs that successfully cross the barrier may suffer from unpredictable distributions. Read More

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February 2019

Kinetics and MR-Based Monitoring of AAV9 Vector Delivery into Cerebrospinal Fluid of Nonhuman Primates.

Mol Ther Methods Clin Dev 2019 Jun 8;13:47-54. Epub 2018 Dec 8.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94103, USA.

Here we evaluated the utility of MRI to monitor intrathecal infusions in nonhuman primates. Adeno-associated virus (AAV) spiked with gadoteridol, a gadolinium-based MRI contrast agent, enabled real-time visualization of infusions delivered either via cerebromedullary cistern, lumbar, cerebromedullary and lumbar, or intracerebroventricular infusion. The kinetics of vector clearance from the cerebrospinal fluid (CSF) were analyzed. Read More

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Clinical tolerance of corticospinal tracts in convection-enhanced delivery to the brainstem.

J Neurosurg 2018 Dec;131(6):1812-1818

Departments of1Neurological Surgery and.

Objective: Convection-enhanced delivery (CED) has been explored as a therapeutic strategy for diffuse intrinsic pontine glioma (DIPG). Variables that may affect tolerance include infusate volume, infusion rate, catheter trajectory, and target position. Supratentorial approaches for catheter placement and infusate distribution patterns may conflict with corticospinal tracts (CSTs). Read More

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December 2018

Convection-Enhanced Delivery of Muscimol in Patients with Drug-Resistant Epilepsy.

Neurosurgery 2019 07;85(1):E4-E15

Electroencephalography Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.

Background: Minimally invasive therapies for drug-resistant epilepsy (DRE) have been advocated. A study of convection-enhanced delivery (CED) of muscimol, a GABAA receptor agonist, was previously completed in non-human primates.

Objective: To investigate the safety and anti-epileptic effects of intracerebral muscimol infusion into the epileptic focus of patients with DRE. Read More

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Maximising coverage of brain structures using controlled reflux, convection-enhanced delivery and the recessed step catheter.

J Neurosci Methods 2018 10 1;308:337-345. Epub 2018 Sep 1.

Functional Neurosurgery Research Group, University of Bristol, School of Clinical Sciences, Learning & Research Building, Southmead Hospital, UK; Neurological Applications Department, Renishaw PLC, New Mills, Wotton-Under-Edge, Gloucestershire, GL12, UK.

Background: The design and use of convection-enhanced delivery catheters remains an active field as clinical trials have highlighted suboptimal distribution as a contributory factor to the failure of those studies. Recent studies indicate limitations and challenges in achieving target coverage using conventional point source delivery.

New Method: The recessed step catheter(RSC), developed by this group, does not function as a point source delivery device, but instead uses 'controlled reflux' of the infusate to a flow inhibiting recess feature. Read More

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October 2018

Convection-Enhanced Delivery of Polymeric Nanoparticles Encapsulating Chemotherapy in Canines with Spontaneous Supratentorial Tumors.

World Neurosurg 2018 Sep 27;117:e698-e704. Epub 2018 Jun 27.

Section of Neurosurgery, Department of Surgery, The University of Chicago, Chicago, Illinois, USA. Electronic address:

Background: Despite aggressive multimodal treatment, survival for patients with glioblastoma remains dismal. One obstacle to improving patient outcomes is the difficulty in delivering adequate therapeutic to the central nervous system due to the presence of the blood-brain barrier. Although direct drug infusion by convection-enhanced delivery (CED) can bypass the blood-brain barrier and facilitate delivery to intracranial tumors, determining the distribution of delivered therapeutic remains problematic. Read More

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September 2018

Imaging of Convective Drug Delivery in the Nervous System.

Authors:
Russell R Lonser

Neurosurg Clin N Am 2017 Oct 19;28(4):615-622. Epub 2017 Aug 19.

Department of Neurological Surgery, The Ohio State University Wexner Medical Center, 410 West 10th Avenue, Doan 1047, Columbus, OH 43210, USA. Electronic address:

Convection-enhanced delivery permits the direct homogeneous delivery of small- and large-molecular-weight putative therapeutics to the nervous system in a manner that bypasses the blood-nervous system barrier. The development of co-infused surrogate imaging tracers (for computed tomography and MRI) allows for the real-time, noninvasive monitoring of infusate distribution during convective delivery. Real-time image monitoring of convective distribution of therapeutic agents insures that targeted structures/nervous system regions are adequately perfused, enhances safety, informs efficacy (or lack thereof) of putative agents, and provides critical information regarding the properties of convection-enhanced delivery in normal and various pathologic tissue states. Read More

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October 2017

Strategies to enhance the distribution of nanotherapeutics in the brain.

J Control Release 2017 Dec 21;267:232-239. Epub 2017 Jul 21.

Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States. Electronic address:

Convection enhanced delivery (CED) provides a powerful means to bypass the blood-brain barrier and drive widespread distribution of therapeutics in brain parenchyma away from the point of local administration. However, recent studies have detailed that the overall distribution of therapeutic nanoparticles (NP) following CED remains poor due to tissue inhomogeneity and anatomical barriers present in the brain, which has limited its translational applicability. Using probe NP, we first demonstrate that a significantly improved brain distribution is achieved by infusing small, non-adhesive NP via CED in a hyperosmolar infusate solution. Read More

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December 2017

Influence of an intratumoral cyst on drug distribution by convection-enhanced delivery: case report.

J Neurosurg Pediatr 2017 Sep 7;20(3):256-260. Epub 2017 Jul 7.

Department of Neurological Surgery, NewYork-Presbyterian Hospital, Weill Cornell Medicine.

Convection-enhanced delivery (CED) uses positive pressure to induce convective flow of molecules and maximize drug distribution. Concerns have been raised about the effect of cystic structures on uniform drug distribution with CED. The authors describe the case of a patient with a diffuse intrinsic pontine glioma (DIPG) with a large cyst and examine its effect on drug distribution after CED with a radiolabeled antibody. Read More

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September 2017

Insights from mathematical modeling for convection-enhanced intraputamenal delivery of GDNF.

Med Biol Eng Comput 2017 Dec 11;55(12):2069-2077. Epub 2017 May 11.

Worldwide Research & Development, Pfizer Inc., 1 Portland Street, Cambridge, MA, 02139, USA.

Glial cell line-derived neurotrophic factor (GDNF) is a potential therapy for Parkinson's disease (PD) promoting survival and functional recovery of dopaminergic neurons when delivered to the degenerated striatum. To study the aspects of intraputamenal delivery of GDNF, a mathematical model of recombinant methionyl human GDNF (r-metHuGDNF) convection in the human putamen has been developed. The convection-enhanced delivery infusions of r-metHuGDNF were simulated at rates up to 5 μL/min. Read More

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December 2017

Continuous intranigral infusion is not associated with observable behavioral deficits or marked pathology: a preclinical safety study.

J Neurosurg 2017 Apr 27;126(4):1253-1262. Epub 2016 May 27.

Departments of 1 Anatomy and Neurobiology and.

OBJECTIVE A better understanding of the effects of chronically delivering compounds to the substantia nigra and nearby areas is important for the development of new therapeutic approaches to treat alpha-synucleinopathies, like Parkinson's disease. Whether chronic intranigral delivery of an infusate could be achieved without causing motor dysfunction or marked pathology remains unclear. The authors evaluated the tolerability of continuously delivering an infusate directly into the rhesus monkey substantia nigra via a programmable pump coupled to a novel intraparenchymal needle-tip catheter surgically implanted using MRI-guided techniques. Read More

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Current and Future Issues in the Development of Spinal Agents for the Management of Pain.

Curr Neuropharmacol 2017 ;15(2):232-259

University of California, San Diego, Anesthesia Research Lab 0818, 9500 Gilman Dr. LaJolla, CA 92093, United States.

Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. Read More

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Chronic, intermittent convection-enhanced delivery devices.

J Neurosci Methods 2016 Feb 23;259:47-56. Epub 2015 Nov 23.

School of Medical Engineering, Queen's Building, Cardiff University, The Parade, Cardiff, CF24 3AA, UK.

Background: Intraparenchymal convection-enhanced delivery (CED) of therapeutics directly into the brain has long been endorsed as a medium through which meaningful concentrations of drug can be administered to patients, bypassing the blood brain barrier. The translation of the technology to clinic has been hindered by poor distribution not previously observed in smaller pre-clinical models. In part this was due to the larger volumes of target structures found in humans but principally the poor outcome was linked to reflux (backflow) of infusate proximally along the catheter track. Read More

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February 2016

Intraparenchymal ultrasound application and improved distribution of infusate with convection-enhanced delivery in rodent and nonhuman primate brain.

J Neurosurg 2016 May 23;124(5):1490-500. Epub 2015 Oct 23.

Department of Neurosurgery, Tohoku University Graduate School of Medicine;

OBJECT Convection-enhanced delivery (CED) is an effective drug delivery method that delivers high concentrations of drugs directly into the targeted lesion beyond the blood-brain barrier. However, the drug distribution attained using CED has not satisfactorily covered the entire targeted lesion in tumors such as glioma. Recently, the efficacy of ultrasound assistance was reported for various drug delivery applications. Read More

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Convection-enhanced delivery of MANF--volume of distribution analysis in porcine putamen and substantia nigra.

J Neurol Sci 2015 Oct 6;357(1-2):264-9. Epub 2015 Aug 6.

Functional Neurosurgery Research Group, University of Bristol, UK. Electronic address:

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a 20kDa human protein which has both neuroprotective and neurorestorative activity on dopaminergic neurons and therefore may have application for the treatment of Parkinson's Disease. The aims of this study were to determine the translational potential of convection-enhanced delivery (CED) of MANF for the treatment of PD by studying its distribution in porcine putamen and substantia nigra and to correlate histological distribution with co-infused gadolinium-DTPA using real-time magnetic resonance imaging. We describe the distribution of MANF in porcine putamen and substantia nigra using an implantable CED catheter system using co-infused gadolinium-DTPA to allow real-time MRI tracking of infusate distribution. Read More

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October 2015

Impaired upper esophageal sphincter reflexes in patients with supraesophageal reflux disease.

Gastroenterology 2015 Nov 17;149(6):1381-91. Epub 2015 Jul 17.

Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address:

Background & Aims: Normal responses of the upper esophageal sphincter (UES) and esophageal body to liquid reflux events prevent esophagopharyngeal reflux and its complications, however, abnormal responses have not been characterized. We investigated whether patients with supraesophageal reflux disease (SERD) have impaired UES and esophageal body responses to simulated reflux events.

Methods: We performed a prospective study of 25 patients with SERD (age, 19-82 y; 13 women) and complaints of regurgitation and supraesophageal manifestations of reflux. Read More

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November 2015

The Relation between Catheter Occlusion and Backflow during Intraparenchymal Cerebral Infusions.

Stereotact Funct Neurosurg 2015 18;93(2):102-109. Epub 2015 Feb 18.

Therataxis, LLC, Baltimore, Md., USA.

Background/Aims: The distribution of infusate into the brain by convection-enhanced delivery can be affected by backflow along the catheter shaft. This work assesses the following: (1) whether tissue coring and occlusion of the catheter lumen occurs when an open end-port catheter is inserted, (2) whether there is a relationship between intracatheter pressure and backflow, and (3) whether catheter occlusion increases backflow. Methods: Freshly excised monkey brains were used to assess tissue coring and its correlation with the behavior of the line pressure. Read More

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February 2015

Convection-enhanced delivery to the central nervous system.

J Neurosurg 2015 Mar 14;122(3):697-706. Epub 2014 Nov 14.

Department of Neurological Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio;

Convection-enhanced delivery (CED) is a bulk flow-driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. Read More

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Titer and product affect the distribution of gene expression after intraputaminal convection-enhanced delivery.

Stereotact Funct Neurosurg 2014 12;92(3):182-94. Epub 2014 Jun 12.

Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wis., USA.

Background: The efficacy and safety of intracerebral gene therapy for brain disorders like Parkinson's disease depends on the appropriate distribution of gene expression.

Objectives: To assess whether the distribution of gene expression is affected by vector titer and protein type.

Methods: Four adult macaque monkeys seronegative for adeno-associated virus 5 (AAV5) received a 30-µl inoculation of a high- or a low-titer suspension of AAV5 encoding glial cell line-derived neurotrophic factor (GDNF) or green fluorescent protein (GFP) in the right and left ventral postcommissural putamen. Read More

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February 2015

Distribution of nanoparticles throughout the cerebral cortex of rodents and non-human primates: Implications for gene and drug therapy.

Front Neuroanat 2014 17;8. Epub 2014 Mar 17.

Department of Neurological Surgery, University of California at San Francisco San Francisco, CA, USA.

When nanoparticles/proteins are infused into the brain, they are often transported to distal sites in a manner that is dependent both on the characteristics of the infusate and the region targeted. We have previously shown that adeno-associated virus (AAV) is disseminated within the brain by perivascular flow and also by axonal transport. Perivascular distribution usually does not depend strongly on the nature of the infusate. Read More

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Selective intra-arterial administration of ¹⁸F-FDG to the rat brain -- effects on hemispheric uptake.

Neuroradiology 2014 May 14;56(5):375-80. Epub 2014 Feb 14.

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Introduction: The purpose of this study was to investigate the radioligand uptake and iodine contrast distribution in the intra- and extracranial circulation of the rat, after intra-arterial injections to the common carotid artery and different parts of the internal carotid artery.

Methods: All animal experiments were carried out in accordance with Karolinska Institutet's guidelines and were approved by the local laboratory animal ethics committee. We used clinical neurointerventional systems to place microcatheters in the extra- or intracranial carotid artery of 15 Sprague-Dawley rats. Read More

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Differential effects of two MRI contrast agents on the integrity and distribution of rAAV2 and rAAV5 in the rat striatum.

Mol Ther Methods Clin Dev 2014 8;1. Epub 2014 Jan 8.

Department of Neurology, University of Wisconsin , Madison, Wisconsin, USA.

Intraoperative magnetic resonance imaging (MRI) has been proposed as a method to optimize intracerebral targeting and for tracking infusate distribution in gene therapy trials for nervous system disorders. We thus investigated possible effects of two MRI contrast agents, gadoteridol (Gd) and galbumin (Gab), on the distribution and levels of transgene expression in the rat striatum and their effect on integrity and stability of recombinant adeno-associated virus (rAAV) particles. MRI studies showed that contrast agent distribution did not predict rAAV distribution. Read More

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Influence of neuropathology on convection-enhanced delivery in the rat hippocampus.

PLoS One 2013 8;8(11):e80606. Epub 2013 Nov 8.

Department of Neuroscience, University of Florida, Gainesville, Florida, United States of America ; Wilder Center of Excellence for Epilepsy Research, University of Florida, Gainesville, Florida, United States of America ; Department of Pediatrics, Division of Pediatric Neurology, University of Florida, Gainesville, Florida, United States of America.

Local drug delivery techniques, such as convention-enhanced delivery (CED), are promising novel strategies for delivering therapeutic agents otherwise limited by systemic toxicity and blood-brain-barrier restrictions. CED uses positive pressure to deliver infusate homogeneously into interstitial space, but its distribution is dependent upon appropriate tissue targeting and underlying neuroarchitecture. To investigate effects of local tissue pathology and associated edema on infusate distribution, CED was applied to the hippocampi of rats that underwent electrically-induced, self-sustaining status epilepticus (SE), a prolonged seizure. Read More

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