Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes

Meningeal lymphatic vessels have been described in animal studies, but limited comparable data is available in human studies. Here we show dural lymphatic structures along the dural venous sinuses in dorsal regions and along cranial nerves in the ventral regions in the human brain. 3D T2-Fluid Attenuated Inversion Recovery magnetic resonance imaging relies on internal signals of protein rich lymphatic fluid rather than contrast media and is used in the present study to visualize the major human dural lymphatic structures. Moreover we detect direct connections between lymphatic fluid channels along the cranial nerves and vascular structures and the cervical lymph nodes. We also identify age-related cervical lymph node atrophy and thickening of lymphatics channels in both dorsal and ventral regions, findings which reflect the reduced lymphatic output of the aged brain.


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No sample-size calculation was performed. the sample size 81. All eligible cases are included.
Patients were excluded from the study if the quality of imaging was insufficient to recognize the dural and subarachnoid spaces, if significant motion artifacts were present, if contrast administration occurred within a few weeks before 3D FLAIR series collection, or if imaging was performed under sedation or general anesthesia. Patients with previous surgery, additional diagnoses such as stroke, intracranial mass, multiple sclerosis, focal parenchymal disease, significant atrophy, significant small vessel disease, or congenital developmental abnormalities were excluded.
As this is a retrospective study, replication with the same patients is not possible. The phantom studies were carried out multiple times. The same imaging findings that we obtained can be obtained with our study MR parameters and protocols at any time or place. When we use the same MR parameters for brain MR imaging, we can detect dorsal and ventral lymphatic signals in different patients in our current clinical setting. For replication of the measurements, we assessed intra-observer variability to evaluate possibility for replication. S.A. made measurements in 10 of the patients on two different times and without seeing his previous measurements. However, it was not feasible to assess inter-observer variability because of the large work load.
Observational study design. The randomization was not done.
We evaluated anatomical structures including SI and thickness measurements. The measurements were performed on MR images on which age, gender and other identifying patient attributes were blinded.
We investigated patients referred for MR imaging due to clinical history of epilepsy or suspicion of epilepsy. A total of 81 subjects (45 females and 36 males) with a mean age of 41·7 (SD 20·4, range 15-80) years were included.
The subjects were selected from those who underwent MR imaging for clinical history of epilepsy or suspicion of epilepsy during a consecutive 13 month period. This is a retrospective study. We included all eligible subjects. We identify no selection biases. Exclusion criteria are given in the data exclusions section.
The study is registered in IRB-IRB201902528. This was not fMRI study.
This was not fMRI study.
No preprocessing performed, MR images directly analyzed in our PACS.
MRI signal units measured at areas of interest were normalized to the reference tissues. As reference tisssues, SI values of bilateral insula, caudate nucleus, bilateral superficial temporalis muscle at the level of frontal skull base, bilateral precentral frontal cortex, bilateral posterior centrum semiovale, bilateral central cerebellar white matter, and cortex at the level of the dentate nucleus were measured.
No template used.
Not used.
Not used.
Differences between continuous data were analyzed using univariate models. Correlations were tested using Spearman's correlation coefficient. Statistical significance was set at the 0.05 level (two-tailed).
We studied signal intensity and thickness by ROI measurement of normalized and standard MRI signal. We also assessed the visibility of specific anatomical structures.
Dorsal and Ventral anatomical structures were selected by visual inspection and assessed in part by ROI and thickness analyses. The atlases and algorithms were not used. The whole brain volumetric analysis were done.
Not relevant.
Multiple comparisons were not performed.