Three-Dimensional Imaging of the Vertebral Lymphatic Vasculature and Drainage using iDISCO&lt;sup&gt;+&lt;/sup&gt; and Light Sheet Fluorescence Microscopy

Journal of Experimental Medicine

et al. 2022

Self Cite

Meningeal lymphatic vessels (MLVs) were identified in the dorsal and caudobasal regions of the dura mater, where they ensure waste product elimination and immune surveillance of brain tissues. Whether MLVs exist in the anterior part of the murine and human skull and how they connect with the glymphatic system and extracranial lymphatics remained unclear. Here, we used light-sheet fluorescence microscopy (LSFM) imaging of mouse whole-head preparations after OVA-A555 tracer injection into the cerebrospinal fluid (CSF) and performed real-time vessel-wall (VW) magnetic resonance imaging (VW-MRI) after systemic injection of gadobutrol in patients with neurological pathologies. We observed a conserved three-dimensional anatomy of MLVs in mice and humans that aligned with dural venous sinuses but not with nasal CSF outflow, and we discovered an extended anterior MLV network around the cavernous sinus, with exit routes through the foramina of emissary veins. VW-MRI may provide a diagnostic tool for patients with CSF drainage defects and neurological diseases.

Section: Introductionmentioning

confidence: 99%

Conserved meningeal lymphatic drainage circuits in mice and humans

Jacob

Neto

Journal of Experimental Medicine

et al. 2022

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“…The subsequent overflow of the lymphatic excretion of CSF can therefore progressively erode the skull base, especially at the cribriform plate, which is a hot spot of the lymphatic system. 23 As this disease process progresses, the osteodural erosion can eventually result in an active osteodural CSF leak. By restoring an effective venous CSF outflow pathway, VSS seems to lessen the pressure on the lymphatic drainage pathway as well as the ICP and induce the spontaneous resolution of this functional CSF leak in most cases.…”

Section: Discussionmentioning

confidence: 99%

Transverse sinus stenting without surgical repair in idiopathic CSF rhinorrhea associated with transverse sinus stenoses: a pilot study

Journal of Neurosurgery

Nouet

Shotar

et al. 2022

OBJECTIVE Based on their clinical and radiological patterns, idiopathic CSF rhinorrhea and idiopathic intracranial hypertension can represent different clinical expressions of the same underlying pathological process. Transverse sinus stenoses are associated with both diseases, resulting in eventual restriction of the venous CSF outflow pathway. While venous sinus stenting has emerged as a promising treatment for idiopathic intracranial hypertension, its efficiency on idiopathic CSF leaks has not been very well addressed in the literature so far. The purpose of this study was to report the results of transverse sinus stenting in patients with spontaneous CSF rhinorrhea associated with transverse sinus stenoses. METHODS From a prospectively collected database, the authors retrospectively collected the clinical and radiological features of the patients with spontaneous CSF leakage who were treated with venous sinus stenting. RESULTS Five female patients were included in this study. Transverse sinus stenoses were present in all patients, and other radiological signs of idiopathic intracranial hypertension were present in 4 patients. The median transstenotic pressure gradient was 6.5 mm Hg (range 3–9 mm Hg). Venous stenting resulted in the disappearance of the leak in 4 patients with no recurrence and no subsequent meningitis during the follow-up (median 12 months, range 6–63 months). CONCLUSIONS According to the authors’ results, venous sinus stenting may result in the disappearance of the leak in many cases of idiopathic CSF rhinorrhea. Larger comparative studies are needed to assess the efficiency and safety of venous stenting as a first-line approach in patients with spontaneous CSF rhinorrhea associated with transverse sinus stenoses.

“…In this work, we investigated CSF lymphatic drainage with sub-millimeter resolution by large field imaging of the whole head using postmortem light-sheet fluorescent microscopy (LSFM) imaging in mice (Jacob et al, 2019(Jacob et al, , 2020, and improved real-time magnetic resonance imaging (MRI) in humans (Absinta et al, 2017). Because both techniques preserved the vascular connections between the meninges and the collecting LNs, we were able to establish a 3D-map of the entire lymphatic CSF drainage network in mice and humans.…”

Section: Introductionmentioning

confidence: 99%

3D-imaging reveals conserved cerebrospinal fluid drainage via meningeal lymphatic vasculature in mice and humans

Jacob

Neto

et al. 2022

Preprint

Self Cite

Meningeal lymphatic vessels (MLVs) contribute to waste product elimination and immune surveillance in brain tissues. MLVs were identified in the dorsal and caudo-basal regions of the dura mater, where they ensure the clearance of cerebrospinal fluid (CSF). Whether MLVs exist in the complex anterior part of the murine and human skull, and how they connect with the glymphatic system and extracranial lymphatic vasculature remained unclear. Here, we generated three-dimensional (3D) maps of MLV drainage by light-sheet fluorescence microscopy (LSFM) imaging of mouse whole-head preparations following fluorescent OVA-A555 tracer injections into the CSF. In humans, we performed real-time magnetic resonance vessel wall imaging (MR-VWI) after systemic gadobutrol injections. We observed a conserved 3D-anatomy of MLVs in mice and humans, and we discovered an extended anterior network around the dural cavernous sinus including multiple capillary beds and exit routes through the foramina of emissary veins. MR-VWI may provide a diagnostic tool for patients with CSF drainage defects and neurological diseases.