Iichiro Osawa1, Eito Kozawa1, Yuya Yamamoto1, Sayuri Tanaka1, Taira Shiratori1, Akane Kaizu1, Kaiji Inoue1, and Mamoru Niitsu1
1Saitama Medical University Hospital, Saitama, Japan
Synopsis
The infundibular
recess (IR) is a cerebrospinal fluid (CSF) space in the third ventricle floor,
and its function remains unclear. We retrospectively evaluated contrast
enhancement of the normal IR using heavily T2-weighted 3D FLAIR. The enhancement of IR was the strongest on post-contrast
images, followed by 4-h delayed post-contrast images. It was also stronger than
that of other CSF spaces. This is the first study to report the enhancement
of IR after an intravenous gadolinium injection. Evaluations of the enhancement
of IR may clarify substance transport, such as gadolinium or hormones into the CSF.
Introduction
The infundibular recess (IR) is a cerebrospinal fluid (CSF) space in the
third ventricle floor that is surrounded by the median eminence, one of the
circumventricular organs (CVOs) characterized by permeable fenestrated
capillaries lacking a blood-brain barrier (BBB). Therefore, substances may move
freely between the blood and CVOs. Previous studies demonstrated
that the median eminence was enhanced on T1-weighted or FLAIR imaging after the
intravenous administration of gadolinium [1, 2]. However,
enhancement of the normal IR has not yet been reported. In our clinical
practice, IR was enhanced on heavily T2-weighted 3D FLAIR (HT2-FLAIR). HT2-FLAIR
is a variant of the 3D FLAIR sequence with variable flip-angle refocusing
pulses [3].
This sequence increases sensitivity to low concentrations of contrast material over
that of conventional 3D FLAIR. A previous study showed enhancement
of the anterior eye segment and various areas of the cranial subarachnoid space
on HT2-FLAIR [4]. Although IR has been
linked to the endocrine system [5, 6], its
function remains unclear. Kanda et al. detected gadolinium deposits in the
brain after intravenous administration [7]. Although the exact mechanism remains
unclear, several hypotheses have been proposed, one of which is the glymphatic
system. The glymphatic system is a functional waste clearance pathway for the
central nervous system [8]. This system drives CSF into the interstitial space
of the brain along the perivascular spaces surrounding arteries and out along those
surrounding veins. Therefore, evaluations of IR enhancement may clarify
gadolinium transport into CSF and its deposition in the brain. The present study aimed to evaluate contrast enhancement of
the normal IR using HT2-FLAIR. Methods
Twenty-six
patients (mean 54 years, male/female 11/15) were retrospectively recruited. We
subjectively compared the overall enhancement of IR on post-contrast, 4-h delayed HT2-FLAIR, and pre-contrast
images. We also objectively conducted chronological and spatial comparisons by
measuring the signal intensity (SI) ratio (SIR). Chronological comparisons were
conducted by comparing SIR IR-MB (SI of IR/SI of the mid-brain) using the Friedman test followed by the Holm
correction. Spatial comparisons were performed by comparing the SIR Post-
Pre (SI on post-contrast HT2-FLAIR/SI on pre-contrast HT2-FLAIR) of IR with that of other CSF spaces,
including the superior part of the third ventricle, lateral ventricles, fourth
ventricle, and prepontine cistern, using the Kruskal-Wallis test followed by the
Steel test. p values < 0.05 were
considered to be significant.Results
In a subjective
analysis, the enhancement of IR on post-contrast and 4-h delayed post-contrast
HT2-FLAIR was observed in all cases, and enhancement was weaker on 4-h delayed
post-contrast HT2-FLAIR than on post-contrast HT2-FLAIR (Figure 1 and 2). In an
objective analysis, SIR IR-MB was the highest on post-contrast
images, followed by 4-h delayed post-contrast images (Figure 3). SIR Post-Pre
was significantly higher in IR than in other CSF spaces (Figure 4). Discussion
It is unknown why IR
showed contrast enhancement. One possible explanation is the leakage of
contrast material into CSF from the median eminence, a CVO. Although CVOs are functionally
and morphologically diverse, they have several common features: 1) fenestrated
capillaries lacking BBB, 2) specialized neuroglial cells (tanycytes and
pituicytes), and 3) an interface between the brain, blood, and CSF. These
organs play a critical role as a transducer of information between the brain,
blood, and CSF.
The median eminence is characterized
by permeable fenestrated capillaries lacking BBB. Therefore, substances may
move freely between the blood and extracellular space within the median
eminence. The dorsal wall of the median eminence bordering the floor of IR is
lined by β2 tanycytes. Tight junctions between β2 tanycytes at the ventricular
pole restrict the passage of substances between CSF and the extracellular space
within the median eminence.
However, previous studies reported
the transport of substances from the median eminence to CSF in the third
ventricle [5, 9, 10]. Caraty et al. demonstrated that gonadotropin-releasing
hormone (GnRH) was not uniformly distributed throughout the third ventricle and
was more concentrated in IR [5]. They hypothesized that the median eminence may
be the major, if not only, source of GnRH entering CSF. Other studies revealed
that peptide hormones, including leptin and ghrelin, were transported after
peripheral administration from the blood to CSF via tanycytes in the median
eminence [9, 10]. Therefore, tight junctions between β2 tanycytes may be leaky.
Gadolinium deposition in the brain
after intravenous administration was initially reported by Kanda et al. [7].
Recent findings suggest a role for the glymphatic system as one of the transport
pathways of gadolinium into the brain parenchyma [11-16]. Furthermore,
intravenously administered gadolinium was distributed to perivascular spaces [14]
as well as CSF spaces around various tissues, including the peripheral part of
the cranial nerves [4] and the cortical veins [16]. The perivascular space
comprising the glymphatic system functions as a transport conduit of CSF and
solutes in the brain. The constellation of these MR findings suggests the
involvement of the glymphatic system in the transportation and deposition of
gadolinium in the brain. Conclusion
The present results demonstrated that IR was enhanced on HT2-FLAIR. IR is a potential source of the leakage of intravenously administered
gadolinium into CSF.Acknowledgements
We express our
appreciation to all the technicians, nurses, and patients involved with the
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