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Purpose: To investigate whether deep cervical lymph node (DCLN) ligation alters intracranial cerebrospinal fluid (CSF) tracer dynamics and outflow using a rat model with intrathecal dynamic contrast-enhanced (DCE) MRI., Methods: Six bilateral DCLN-ligated and six sham-operated rats were subjected to DCE MRI with Gd-BTDO3A, and dynamic T1-weighted images were acquired. ROIs were collected from the CSF at the C1 level (CSF_C1), CSF between the olfactory bulbs (CSF_OB), CSF at the pituitary recess (CSF_PitR), and CSF at the pineal recess (CSF_PinR), upper nasal turbinate (UNT), olfactory bulbs, cerebrum, and the jugular region. Time-intensity curves were evaluated, and the maximum slope, peak timing, peak signal ratio, and elimination half-life for the four CSF ROIs and UNT were calculated and compared., Results: Delayed tracer arrival in the rostral CSF space and the nasal cavity with tracer retention in the ventral CSF space were observed in the ligation group. The maximum slopes were smaller in the ligation group at UNT (sham: 0.075 ± 0.0061, ligation: 0.044 ± 0.0086/min, P = 0.011). A significant difference was not detected in peak timings. The peak signal ratio values were lower in the ligation group at UNT (sham: 2.12 ± 0.19, ligation: 1.72 ± 0.11, P = 0.011). The elimination half-life was delayed in the ligation group at CSF_C1 (sham: 30.5 ± 2.70, ligation: 44.4 ± 12.6 min, P = 0.043), CSF_OB (sham: 30.2 ± 2.67, ligation: 44.8 ± 7.47 min, P = 0.021), and CSF_PitR (sham: 30.2 ± 2.49, ligation: 41.3 ± 7.57 min, P = 0.021)., Conclusion: The DCLN ligation in rats blocked CSF outflow into the nasal cavity and caused CSF retention.

Purpose: Clearance of cerebrospinal fluid (CSF) is important for the removal of toxins from the brain, with implications for neurodegenerative diseases. Imaging evaluation of CSF outflow in humans has been limited, relying on venous or invasive intrathecal injections of contrast agents. The objective of this study was to introduce a novel spin-labeling MRI technique to detect and quantify the movement of endogenously tagged CSF, and then apply it to evaluate CSF outflow in normal humans of varying ages., Methods: This study was performed on a clinical 3-Tesla MRI scanner in 16 healthy subjects with an age range of 19-71 years with informed consent. Our spin-labeling MRI technique applies a tag pulse on the brain hemisphere, and images the outflow of the tagged CSF into the superior sagittal sinus (SSS). We obtained 3D images in real time, which was analyzed to determine tagged-signal changes in different regions of the meninges involved in CSF outflow. Additionally, the signal changes over time were fit to a signal curve to determine quantitative flow metrics. These were correlated against subject age to determine aging effects., Results: We observed the signal of the tagged CSF moving from the dura mater and parasagittal dura, and finally draining into the SSS. In addition, we observed a possibility of another pathway which is seen in some young subjects. Furthermore, quantitative CSF outflow metrics were shown to decrease significantly with age., Conclusion: We demonstrate a novel non-invasive MRI technique identifying two intrinsic CSF clearance pathways, and observe an age-related decline of CSF flow metrics in healthy subjects. Our work provides a new opportunity to better understand the relationships of these CSF clearance pathways during the aging process, which may ultimately provide insight into the age-related prevalence of neurodegenerative diseases.

Purpose: The cardiac- and respiratory-driven components of cerebrospinal fluid (CSF) motion characteristics and bulk flow are not yet completely understood. Therefore, the present study aimed to characterize cardiac- and respiratory-driven CSF motions in the intracranial space using delay time, CSF velocity waveform correlation, and displacement., Methods: Asynchronous two-dimensional phase-contrast at 3T was applied to measure the CSF velocity in the inferior-superior direction in a sagittal slice at the midline (N = 12) and an axial slice at the foramen magnum (N = 8). Volunteers were instructed to engage in six-second respiratory cycles. The calculated delay time and correlation coefficients of the cardiac- and respiratory-driven velocity waveforms, separated in the frequency domain, were applied to evaluate the propagation of the CSF motion. The cardiac- and respiratory-driven components of the CSF displacement and motion volume were calculated during diastole and systole, and during inhalation and exhalation, respectively. The cardiac- and respiratory-driven components of the velocity, correlation, displacement, and motion volume were compared using an independent two-sample t-test., Results: The ratio of the cardiac-driven CSF velocity to the sum of the cardiac- and respiratory-driven CSF velocities was higher than the equivalent respiratory-driven ratio for all cases (P < 0.01). Delay time and correlation maps demonstrated that the cardiac-driven CSF motion propagated more extensively than the respiratory-driven CSF motion. The correlation coefficient of the cardiac-driven motion was significantly higher in the prepontine (P < 0.01), the aqueduct, and the fourth ventricle (P < 0.05). The respiratory-driven displacement and motion volume were significantly greater than the cardiac-driven equivalents for all observations (P < 0.01)., Conclusion: The correlation mapping technique characterized the cardiac- and respiratory-driven CSF velocities and their propagation properties in the intracranial space. Based on these findings, cardiac-driven CSF velocity is greater than respiratory-induced velocity, but the respiratory-driven velocity might displace farther.

Purpose: Although there is no lymphatic system in the central nervous system (CNS), there seems to be a mechanism to remove macro molecules from the brain. Cerebrospinal fluid (CSF) and interstitial fluid (ISF) are thought to be parts of this pathway, but the details are not known. In this study, MR signal of the extracellular water was decomposed into components with distinct T 2 's, to obtain some information about distribution of waste material in the brain., Methods: Images were acquired using a Curr, Purcell, Meiboom, Gill (CPMG) imaging sequence. In order to reduce T 1 contamination and the signal oscillation, hard pulses were used as refocusing pulses. The signal was then decomposed into many T 2 components using non-negative least squares (NNLS) in pixel-by-pixel basis. Finally, a color map was generated by assigning different color for each T 2 component, then adding them together., Results: From the multi-echo images, it was possible to decompose the decaying signal into separate T 2 components. By adjusting the color table to create the color map, it is possible to visualize the extracellular water distribution, as well as their T 2 values. Several observation points include: (1) CSF inside ventricles has very long T 2 (~2 s), and seems to be relatively homogeneous, (2) subarachnoid CSF also have long T 2 , but there are short T 2 component at the brain surface, at the surface of dura, at the blood vessels in the subarachnoid space, etc., (3) in the brain parenchyma, short T 2 components (longer than intracellular component but shorter than CSF) exists along the white matter, in the choroid plexus, etc. These can be considered as distribution of macromolecules (waste materials) in the brain., Conclusion: From T 2 component analysis it is possible to obtain some insight into pathways for the transport of large molecules in the CNS, where no lymphatic system is present.

The feasibility of the 3D dynamic improved motion-sensitized driven-equilibrium steady-state free precession (3D dynamic iMSDE SSFP) was evaluated for visualizing CSF motion and the appropriate parameters were determined. Both flow phantom and volunteer studies revealed that linear ordering and the shortest acquisition duration time were optimal. 3D dynamic iMSDE SSFP provides good quality imaging of CSF motion in the whole brain and enables visualization of flow in arbitrary planes from a single 3D volume scan.

Purpose: It has been reported that leakage of intravenously administered gadolinium-based contrast agents (IV-GBCAs) into the cerebrospinal fluid (CSF) from the cortical veins even in healthy subjects can be detected using a highly sensitive pulse sequence such as heavily T 2 -weighted 3D fluid-attenuated inversion recovery and 3D-real inversion recovery (IR). The purpose of this study was to evaluate the feasibility of MR fingerprinting to detect GBCA leakage from the cortical veins after IV-GBCA., Materials: Fourteen patients with suspected endolymphatic hydrops (EH) who received a single dose of IV-GBCA (39-79 years old) were included. The real IR images as well as MR fingerprinting images were obtained at 4 h after IV-GBCA. T 1 and T 2 values were obtained using MR fingerprinting and analyzed in ROIs covering intense GBCA leakage, and non-leakage areas of the CSF as determined on real IR images. The scan time for real IR imaging was 10 min and that for MR fingerprinting was 41 s., Results: The mean T 1 value of the ROI in the area of GBCA leakage was 2422 ± 261 ms and that in the non-leakage area was 3851 ± 235 ms (P < 0.01). There was no overlap between the T 1 values in the area of GBCA leakage and those in the non-leakage area.The mean T 2 value in the area of GBCA leakage was 319 ± 90 ms and that in the non-leakage area was 670 ± 166 ms (P < 0.01). There was some overlap between the T 2 values in the area of GBCA leakage and those in the non-leakage area., Conclusion: Leaked GBCA from the cortical veins into the surrounding CSF can be detected using MR fingerprinting obtained in <1 min.

Purpose: Since the first report on the deposition of gadolinium in the brain parenchyma after repeated intravenous administrations of gadolinium-based contrast agent GBCA (IV-GBCA), the mechanisms of penetration and retention are still remaining a hot topic of discussion and a target of investigation. We routinely obtain endolymphatic hydrops (EH) images at 4 h after IV administration of a single dose (SD) of GBCA (IV-SD-GBCA) using heavily T 2 -weighted three-dimensional fluid-attenuated inversion recovery imaging (hT 2 W-3D-FLAIR). Occasionally, we have encountered cases, which indicate high-signal intensity (SI) in the cerebrospinal fluid (CSF) surrounding the vein of Labbe. The purpose of the present study was to investigate the degree of contrast enhancement of the CSF surrounding the vein of Labbe on hT 2 W-3D-FLAIR after IV-SD-GBCA in comparison with other CSF spaces., Materials and Methods: In 25 patients with a suspicion of EH, a magnetic resonance cisternography (MRC) and an hT 2 W-3D-FLAIR were obtained at 4 h after IV-SD-GBCA. The perivascular space (PVS) in the basal ganglia, CSF spaces in the ambient cistern (CSF-Amb), the CSF surrounding the superficial middle cerebral vein (CSF-SMCV), and the CSF surrounding the vein of Labbe (CSF-VL) were segmented on MRC. The PVS and CSF regions were co-registered onto the hT 2 W-3D-FLAIR and the SI of the PVS and CSF spaces were measured. The SI ratio (SIR) of the post-contrast hT 2 W-3D-FLAIR to the pre-contrast hT 2 W-3D-FLAIR was measured. Significant differences were evaluated using Steel-Dwass's test for multiple comparisons., Results: The SIR of the CSF-VL was significantly higher than that of the PVS (P = 0.008), the CSF-Amb (P = 0.021), and the CSF-SMCV (P = 0.023)., Conclusion: The strong contrast enhancement of CSF space around the vein of Labbe was confirmed on hT 2 W-3D-FLAIR at 4 h after IV-GBCA compared to the PVS and the other CSF spaces.

Purpose: To elucidate differences between the perivascular space (PVS) in the basal ganglia (BG) versus that found in white matter (WM) using heavily T 2 -weighted FLAIR (hT 2 -FL) in terms of 1) signal intensity on non-contrast enhanced images, and 2) the degree of contrast enhancement by intravenous single dose administration of gadolinium based contrast agent (IV-SD-GBCA)., Materials and Methods: Eight healthy men and 13 patients with suspected endolymphatic hydrops were included. No subjects had renal insufficiency. All subjects received IV-SD-GBCA. MR cisternography (MRC) and hT 2 -FL images were obtained prior to and 4 h after IV-SD-GBCA. The signal intensity of the PVS in the BG, subinsular WM, and the cerebrospinal fluid (CSF) in Ambient cistern (CSF AC ) and CSF in Sylvian fissure (CSF Syl ) was measured as well as that of the thalamus. The signal intensity ratio (SIR) was calculated by dividing the intensity by that of the thalamus. We used 5% as a threshold to determine the significance of the statistical test., Results: In the pre-contrast scan, the SIR of the PVS in WM (Mean ± standard deviation, 1.83 ± 0.46) was significantly higher than that of the PVS in the BG (1.05 ± 0.154), CSF Syl (1.03 ± 0.15) and the CSF AC (0.97 ± 0.29). There was no significant difference between the SIR of the PVS in the BG compared to the CSF AC and CSF Syl . For the evaluation of the contrast enhancement effect, significant enhancement was observed in the PVS in the BG, the CSF AC and the CSF Syl compared to the pre-contrast scan. No significant contrast enhancement was observed in the PVS in WM., Conclusion: The signal intensity difference between the PVS in the BG versus WM on pre-contrast images suggests that the fluid composition might be different between these PVSs. The difference in the contrast enhancement between the PVSs in the BG versus WM suggests a difference in drainage function.

We measured the changes in the cerebrospinal fluid (CSF) flow dynamics after compression of the bilateral jugular veins using phase contrast-magnetic resonance imaging (PC-MRI). PC-MRI was performed in 10 healthy male volunteers using a 3T clinical scanner with a two-dimensional gradient echo sequence. We successfully measured the changes in CSF flow velocity using PC-MRI with and without compression of the bilateral jugular veins. The relative velocity range decreased by about 30% when the bilateral jugular veins were compressed.

We assessed labeling region selectivity on time-spatial labeling inversion pulse (Time-SLIP) with pencil beam pulse (PB Time-SLIP) for the use of visualizing cerebrospinal fluid (CSF) flow dynamics. We compared the selectivity of labeling to the third and fourth ventricles between PB Time-SLIP and conventional Time-SLIP (cTime-SLIP) in eight volunteers and one patient using a 1.5T MRI. PB Time-SLIP provided more selective labeling in CSF than cTime-SLIP, particularly in complex anatomical regions.

Purpose: Diffusion-weighted imaging (DWI) using readout-segmented EPI (rs-EPI) can minimize distortion and blurring artifacts; however, we sometimes encounter cerebrospinal fluid (CSF) pulsation artifacts on apparent diffusion coefficient (ADC) maps, especially when the number of readout segments (NRS) is increased. The purpose of this study was to evaluate the effect of the NRS on the CSF pulsation artifacts in the ADC maps of healthy volunteers., Methods: In 10 healthy volunteers, we obtained DWI from rs-EPI with a b-value of 0 and 1000 s/mm 2 . The NRS was set to 5, 7, or 9. An ADC map was generated from the trace image and the b = 0 image. Each scan was performed twice. A circular region of interest (ROI) was drawn in the pons and bilateral thalami. The standard deviation (SD) of the ROI was measured to assess the artifacts. Bilateral SD values were averaged for the ROIs in the thalami. The SD values from two successive scans of each NRS were averaged for the pons and thalami, respectively. For the qualitative analysis, the CSF pulsation artifacts on each ADC map were graded by two observers independently as 0, no artifact; 1, mild artifact; 2, moderate artifact; or 3, severe artifact., Results: In the quantitative analysis, the SD values tend to increase with the increasing of NRS in both thalami and pons; however, the difference in the SD values from each NRS did not reach a statistically significant level. In the qualitative analysis, there was a statistically significant difference in the scores between 5 and 9 segments and between 7 and 9 segments with both the observers, respectively (P < 0.05)., Conclusion: The CSF pulsation artifacts on ADC maps obtained with rs-EPI are affected by the NRS.