MRI Parameters of 3D FLAIR T2 Imaging Technique for Visualization of the Brain Lymphatic Signals

doi:10.21203/rs.3.pex-2228/v1

Method Article

MRI Parameters of 3D FLAIR T2 Imaging Technique for Visualization of the Brain Lymphatic Signals

https://doi.org/10.21203/rs.3.pex-2228/v1

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Meningeal lymphatic vessels (MLVs) have been described in animal studies, but limited comparable data is available in human studies. Non-contrast 3D T2-Fluid Attenuated Inversion Recovery (FLAIR) magnetic resonance imaging relies on protein-rich lymphatic fluid internal signals rather than contrast media. Here, we outline our non-contrast 3D FLAIR MR method permitting visualization of dorsal-along the venous sinuses and ventral lymphatic structures-flow around perineural/peridural spaces of cranial nerves, cerebrospinal fluid (CSF) - interstitial fluid (ISF) drainage around nerves in the human brain in detail.

Neuroscience

Neurology

Human

Brain

Meningeal lymphatic

Fluid Attenuated Inversion Recovery Magnetic Resonance Imaging.

Meningeal lymphatic vessels have been described in animal studies, but limited comparable data is available in human studies. Disruption of glymphatic and MVLs functions likely underlies or contributes to many clinical conditions, such as traumatic brain injury, Alzheimer's disease, and multiple sclerosis [1]. While MRI can allow for noninvasive in vivo evaluation of MLVs for these pathologies, this has previously been achieved only through the use of intravenous and intrathecal Gadolinium (Gd) [2],[3],[4],[5]. Gd use is not entirely safe for healthy subjects or patients due to Gd retention in the body. In addition, the visualization of MLVs using this approach is limited to anatomic compartments physically accessible to Gd, as described above [6]. Therefore, additional noninvasive MR techniques that do not rely on Gd are needed to allow safer, more complete visualization of MVLs for further studies relating to MVLs or CSF-ISF drainage pathways.

We know from previous studies that albumin is the most abundant protein in the lymph, contributing to 65% of the total protein content of lymph in the body [7], and the albumin concentration in the ISF is up to 30% that in the plasma [8]. Notably, the albumin concentration in interstitial fluid is very similar to its concentration in lymph (~1.6–1.8 g/dl) [7], [9].

Fluid attenuated inversion recovery (FLAIR) imaging is more successful than other methods in showing meningitis, subarachnoid hemorrhage, and leptomeningeal metastatic involvement in the brain. It successfully differentiates inflammation in the brain and increases macromolecule-solute concentration or different protein concentrations [10], [11]. With the recent advances in MR technology, it has become possible to image the brain in 3D submillimeter resolution. This allowed the visualization of very small structures or fluids in the brain.

Here, we outline our non-contrast 3D FLAIR MR method permitting visualization of dorsal-along the venous sinuses and ventral lymphatic structures-flow around perineural/peridural spaces of cranial nerves, CSF-ISF drainage around nerves in the human brain in detail.

3D T2-FLAIR technique in a new generation 3 Tesla MR scanner (Prisma, Siemens, Erlangen, Germany) using a 20 or 32-channel array head coil. We performed our study with Prisma Scanner. However, we observed that 3 Tesla Skyra-Siemens and Verio-Siemens 3T machines also could show lymphatic structures-flow with the same MR protocol. Unfortunately, we don’t have any experience with other vendors such as GE or Philips 3 Tesla machines.

3D FLAIR imaging technique is very dependent on technical parameters for visualization of the different fluid contents. Technical factors such as IR time, T2 preparation pulses, TE, and TR times are essential, especially in demonstrating different macromolecular or protein concentrations. On December 20, 2021, Fukutomi et al. published "Visualization of the saccule and utricle with non-contrast-enhanced FLAIR sequences" [12]. This study described how conventional 3D FLAIR IR imaging techniques could not differentiate chemical differences between perilymphatic space (PLS) and endolymphatic space (ELS). When using T2 prep inversion pulse sequences, however, the PLS and ELS could be discerned. They concluded that a specific combination of T2 Prep time and TI from high-resolution 3D-FLAIR could differentiate ELS from PLS and even delineate the saccule from the utricle without gadolinium injection [12]. Therefore, with these findings, we believe that 3D FLAIR with a T2-selective inversion pulse allows for evaluating solute-protein-rich fluid, whereas 3D conventional IR imaging techniques do not. We also found that PLS and ELS can be differentiated using the 3D FLAIR technique without contrast during our data analyses. We used fat-saturation (FS) and T2-selective inversion pulse. Conventional inversion pulse cannot visualize the lymphatic structures in the brain.

Our MR protocol is given below (see Figure 1 for the table), with all its data in detail.

MR Vendors change their software from time to time, and with this, so do 3D FLAIR imaging parameters. Therefore, these new software versions should check TE, TR, TI, and T2-preparation pulses.

One would expect to observe visualization of dorsal-along the venous sinuses and ventral lymphatic structures-flow around perineural/peridural spaces of cranial nerves, and CSF-ISF drainage around nerves in the human by using non-contrast 3D FLAIR MR method.

References:

1. Benveniste, H. et al. The glymphatic system and waste clearance with brain aging: a review. Gerontology 65, 106–119 (2019).

2. Absinta, M. et al. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. eLife 6, e29738 (2017).

3. Ringstad, G. & Eide, P. K. Cerebrospinal fluid tracer efflux to parasagittal dura in humans. Nat. Commun. 11, (2020) https://doi.org/10.1038/s41467-019-14195-x

4. Zhou, Y. et al. Impairment of the glymphatic pathway and putative meningeal lymphatic vessels in the aging human. Ann. Neurol. 87, 357–369 (2020).

5. Wu, C. et al. Noninvasive characterization of human glymphatics and meningeal lymphatics in an in vivo model of blood–brain barrier leakage. Ann. Neurol.(2020) https://doi.org/10.1002/ana.25928.

6. Wu, C. et al. Noninvasive characterization of human glymphatics and meningeal lymphatics in an in vivo model of blood–brain barrier leakage. Ann. Neurol.(2020) https://doi.org/10.1002/ana.25928.

7. Rutili, G. & Arfors, K.-E. Protein concentration in interstitial and lymphatic fluids from the subcutaneous tissue. Acta Physiologica Scandinavica 99, 1–8 (1977).

8. Ellmere et al., Measurement of interstitial albumin in human skeletal muscle and adipose tissue by open-flow microperfusion. Am J Physiol Endocrinol Metab 278(2):E352-6 (2000)

9. Abdallah, M. et al. Lymphatic targeting by albumin-hitchhiking: applications and optimisation. J. Controlled Release 327, 117–128 (2020).

10. Melhem, E.R. et al., Fluid-attenuated inversion recovery MR imaging: identification of protein concentration thresholds for CSF hyperintensity. AJR Am J Roentgenol 169(3):859-62 (1997).

11. Albayram, M.S. et al., Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes. Nat Commun. 13(1):203 (2022).

12. Fukutomi, H. et al., Visualization of the saccule and utricle with non-contrast-enhanced FLAIR sequences. Eur Radiol. 32(5):3532-3540 (2022).

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MRI Parameters of 3D FLAIR T2 Imaging Technique for Visualization of the Brain Lymphatic Signals

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MRI Parameters of 3D FLAIR T2 Imaging Technique for Visualization of the Brain Lymphatic Signals

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