Magnetic Resonance Lymphography at 9.4 T Using a Gadolinium-Based Nanoparticle in Rats

Müller, Andreas; Fries, Peter; Jelvani, Bijan; Lux, François; Rübe, Claudia E.; Kremp, Stephanie; Giovanoli, Pietro; Buecker, Arno; Menger, Michael D.; Laschke, Matthias W.; Frueh, Florian S.

doi:10.1097/rli.0000000000000398

Cited by 18 publications

(17 citation statements)

References 43 publications

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“…Imaging was performed with a three-dimensional time of flight gradient recalled echo sequence (3D-TOF-GRE) originally adapted for imaging of peripheral lymph vessels [41] with recovery time of 12.0 ms, echo time of 2.5 ms, flip angle 25 o , matrix 600 × 400 × 180, field of view 36.00 mm × 25.92 mm × 18.00 mm, zero fill 2, 1 average and a scan time of 4 min 19 s 200 ms. Signal intensity (SI) reduction in blood vessels was achieved by placement of a saturation slice over the mouse heart.…”

Section: Methodsmentioning

confidence: 99%

“…Animals were examined in a horizontal-bore 9.4 T animal scanner (BioSpec Avance III 94/20; Bruker Biospin GmbH, Ettlingen, Germany) with a BGA12S gradient system with ParaVision 6.0.1 (Bruker Biospin GmbH) and a linearly polarized coil with an inner diameter of 40 mm (Bruker Biospin GmbH). Imaging was performed with a three-dimensional time of flight gradient recalled echo sequence (3D-TOF-GRE) originally adapted for imaging of peripheral lymph vessels [ 41 ] with recovery time of 12.0 ms, echo time of 2.5 ms, flip angle 25 o , matrix 600 × 400 × 180, field of view 36.00 mm × 25.92 mm × 18.00 mm, zero fill 2, 1 average and a scan time of 4 min 19 s 200 ms. Signal intensity (SI) reduction in blood vessels was achieved by placement of a saturation slice over the mouse heart.…”

Section: Methodsmentioning

confidence: 99%

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Rapid lymphatic efflux limits cerebrospinal fluid flow to the brain

et al. 2018

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The relationships between cerebrospinal fluid (CSF) and brain interstitial fluid are still being elucidated. It has been proposed that CSF within the subarachnoid space will enter paravascular spaces along arteries to flush through the parenchyma of the brain. However, CSF also directly exits the subarachnoid space through the cribriform plate and other perineural routes to reach the lymphatic system. In this study, we aimed to elucidate the functional relationship between CSF efflux through lymphatics and the potential influx into the brain by assessment of the distribution of CSF-infused tracers in awake and anesthetized mice. Using near-infrared fluorescence imaging, we showed that tracers quickly exited the subarachnoid space by transport through the lymphatic system to the systemic circulation in awake mice, significantly limiting their spread to the paravascular spaces of the brain. Magnetic resonance imaging and fluorescence microscopy through the skull under anesthetized conditions indicated that tracers remained confined to paravascular spaces on the surface of the brain. Immediately after death, a substantial influx of tracers occurred along paravascular spaces extending into the brain parenchyma. We conclude that under normal conditions a rapid CSF turnover through lymphatics precludes significant bulk flow into the brain.Electronic supplementary materialThe online version of this article (10.1007/s00401-018-1916-x) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Rapid lymphatic efflux limits cerebrospinal fluid flow to the brain

et al. 2018

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“…A four–element receive–only cryogenic phased array coil (Bruker BioSpin GmbH) was used in combination with a linearly polarized room temperature volume resonator for transmission. Imaging was performed with a three-dimensional time of flight gradient recalled echo sequence (3D-TOF-GRE) 48 with an echo time/repetition time = 2.5/12.0 ms, flip angle 25°, matrix 480 × 360 × 180, field of view 36 mm × 27 mm × 18 mm, zero fill 2, 1 average and a scan time of 3 min 46 s. Both horizontal (dorsal to ventral) and sagittal (rostral to caudal) sections were scanned at t = 15 min, 25 min, 35 min, 45 min, 55 min after Gadospin D infusion. Signal intensity (SI) reduction in blood vessels was achieved by placement of a saturation slice over the mouse heart.…”

Section: Methodsmentioning

confidence: 99%

Lymphatic outflow of cerebrospinal fluid is reduced in glioma

Schlegel

Bachmann

et al. 2019

Sci Rep

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Glioblastoma is a malignant brain tumor with mean overall survival of less than 15 months. Blood vessel leakage and peritumoral edema lead to increased intracranial pressure and augment neurological deficits which profoundly decrease the quality of life of glioblastoma patients. It is unknown how the dynamics of cerebrospinal fluid (CSF) turnover are affected during this process. By monitoring the transport of CSF tracers to the systemic blood circulation after infusion into the cisterna magna, we demonstrate that the outflow of CSF is dramatically reduced in glioma-bearing mice. Using a combination of magnetic resonance imaging (MRI) and near-infrared (NIR) imaging, we found that the circulation of CSF tracers was hindered after cisterna magna injection with reduced signals along the exiting cranial nerves and downstream lymph nodes, which represent the major CSF outflow route in mice. Due to blockage of the normal routes of CSF bulk flow within and from the cranial cavity, CSF tracers were redirected into the spinal space. In some mice, impaired CSF clearance from the cranium was compensated by a lymphatic outflow from the sacral spine.

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“…administration, and they can be further tuned towards lymph node accumulation (Schudel, Francis, & Thomas, 2019). This nanoparticle‐based lymphatic imaging has been used to monitor the impact of disease upon the lymphatic system, as well as identify sentinel lymph nodes in cancer (Müller et al, 2017; Taruno et al, 2019). As discussed previously in this review, nanoparticles also have a tendency to be taken up by immune cells, and therefore it is not surprising that nanotechnology‐based imaging agents are in development for imaging inflammation associated with disease states.…”

Section: Future Directionsmentioning

confidence: 99%

Challenges in the development of nanoparticle‐based imaging agents: Characterization and biology

Crist

Dasa

Liu

et al. 2020

WIREs Nanomed Nanobiotechnol

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Despite imaging agents being some of the earliest nanomedicines in clinical use, the vast majority of current research and translational activities in the nanomedicine field involves therapeutics, while imaging agents are severely underrepresented. The reasons for this lack of representation are several fold, including difficulties in synthesis and scale‐up, biocompatibility issues, lack of suitable tissue/disease selective targeting ligands and receptors, and a high bar for regulatory approval. The recent focus on immunotherapies and personalized medicine, and development of nanoparticle constructs with better tissue distribution and selectivity, provide new opportunities for nanomedicine imaging agent development. This manuscript will provide an overview of trends in imaging nanomedicine characterization and biocompatibility, and new horizons for future development. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine

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Magnetic Resonance Lymphography at 9.4 T Using a Gadolinium-Based Nanoparticle in Rats

Cited by 18 publications

References 43 publications

Rapid lymphatic efflux limits cerebrospinal fluid flow to the brain

Rapid lymphatic efflux limits cerebrospinal fluid flow to the brain

Lymphatic outflow of cerebrospinal fluid is reduced in glioma

Challenges in the development of nanoparticle‐based imaging agents: Characterization and biology

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