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Evaluating differential nanoparticle accumulation and retention kinetics in a mouse model of traumatic brain injury via K^trans mapping with MRI.

ABSTRACT: Traumatic brain injury (TBI) is a leading cause of injury-related death worldwide, yet there are no approved neuroprotective therapies that improve neurological outcome post-injury. Transient opening of the blood-brain barrier following injury provides an opportunity for passive accumulation of intravenously administered nanoparticles through an enhanced permeation and retention-like effect. However, a thorough understanding of physicochemical properties that promote optimal uptake and retention kinetics in TBI is still needed. In this study, we present a robust method for magnetic resonance imaging of nanoparticle uptake and retention kinetics following intravenous injection in a controlled cortical impact mouse model of TBI. Three contrast-enhancing nanoparticles with different hydrodynamic sizes and relaxivity properties were compared. Accumulation and retention were monitored by modelling the permeability coefficient, K^trans, for each nanoparticle within the reproducible mouse model. Quantification of K^trans for different nanoparticles allowed for non-invasive, multi-time point assessment of both accumulation and retention kinetics in the injured tissue. Using this method, we found that 80 nm poly(lactic-co-glycolic acid) nanoparticles had maximal K^trans in a TBI when injected 3 hours post-injury, showing significantly higher accumulation kinetics than the small molecule, Gd-DTPA. This robust method will enable optimization of administration time and nanoparticle physicochemical properties to achieve maximum delivery.

SUBMITTER: Miller HA

PROVIDER: S-EPMC6834577 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Evaluating differential nanoparticle accumulation and retention kinetics in a mouse model of traumatic brain injury via K<sup>trans</sup> mapping with MRI.

Miller Hunter A HA Magsam Alexander W AW Tarudji Aria W AW Romanova Svetlana S Weber Laura L Gee Connor C CC Madsen Gary L GL Bronich Tatiana K TK Kievit Forrest M FM

Scientific reports 20191106 1

Traumatic brain injury (TBI) is a leading cause of injury-related death worldwide, yet there are no approved neuroprotective therapies that improve neurological outcome post-injury. Transient opening of the blood-brain barrier following injury provides an opportunity for passive accumulation of intravenously administered nanoparticles through an enhanced permeation and retention-like effect. However, a thorough understanding of physicochemical properties that promote optimal uptake and retention ...[more]

PMID: 31695100

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Project description:Magnetic resonance (MR) imaging and spectroscopy using dissolved hyperpolarized (HP) 129Xe have expanded the ability to probe lung function regionally and noninvasively. In particular, HP 129Xe imaging has been used to quantify impaired gas uptake by the pulmonary tissues. Whole-lung spectroscopy has also been used to assess global cardiogenic oscillations in the MR signal intensity originating from 129Xe dissolved in the red blood cells of pulmonary capillaries. Herein, we show that the magnitude of these cardiogenic dynamics can be mapped three dimensionally using radial MRI, because dissolved 129Xe dynamics are encoded directly in the raw imaging data. Specifically, 1-point Dixon imaging is combined with postacquisition keyhole image reconstruction to assess regional blood volume fluctuations within the pulmonary microvasculature throughout the cardiac cycle. This "oscillation mapping" was applied in healthy subjects (mean amplitude 9% of total RBC signal) and patients with pulmonary arterial hypertension (PAH; mean 4%) and idiopathic pulmonary fibrosis (IPF; mean 14%). Whole-lung mean values from these oscillation maps correlated strongly with spectroscopy and clinical pulmonary function testing, but exhibited significant regional heterogeneity, including gravitationally dependent gradients in healthy subjects. Moreover, regional oscillations were found to be sensitive to disease state. Greater percentages of the lungs exhibit low-amplitude oscillations in PAH patients, and longitudinal imaging shows high-amplitude oscillations increase significantly over time (4-14 mo, P = 0.02) in IPF patients. This technique enables regional dynamics within the pulmonary capillary bed to be measured, and in doing so, provides insight into the origin and progression of pathophysiology within the lung microvasculature.NEW & NOTEWORTHY Spatially heterogeneous abnormalities within the lung microvasculature contribute to pathology in various cardiopulmonary diseases but are difficult to assess noninvasively. Hyperpolarized 129Xe MRI is a noninvasive method to probe lung function, including regional gas exchange between pulmonary air spaces and capillaries. We show that cardiogenic oscillations in the raw dissolved 129Xe MRI signal from pulmonary capillary red blood cells can be imaged using a postacquisition reconstruction technique, providing a new means of assessing regional lung microvasculature function and disease state.

Dataset Information

Evaluating differential nanoparticle accumulation and retention kinetics in a mouse model of traumatic brain injury via K^trans mapping with MRI.

Publications

Evaluating differential nanoparticle accumulation and retention kinetics in a mouse model of traumatic brain injury via K<sup>trans</sup> mapping with MRI.

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Dataset Information

Evaluating differential nanoparticle accumulation and retention kinetics in a mouse model of traumatic brain injury via Ktrans mapping with MRI.

Publications

Evaluating differential nanoparticle accumulation and retention kinetics in a mouse model of traumatic brain injury via K<sup>trans</sup> mapping with MRI.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Evaluating differential nanoparticle accumulation and retention kinetics in a mouse model of traumatic brain injury via K^trans mapping with MRI.