Table 2:
Overview of knowledge gained from glymphatic transport by DCE-MRI
| Species | Route of Contrast | Glymphatic Parameters Measured | Physiological State or Disease? | Knowledge Gained | References |
|---|---|---|---|---|---|
| Rat | Intracisternal | - Time-activity curve - Cluster analysis |
Physiological | - Visualized the paraarterial CSF pathways and areas of CSF-ISF exchange - Tracer size affects its distribution in the brain |
2013 (Iliff, et al., 2013) |
| Mouse | Intracisternal | Visualization of contrast distribution throughout the brain | Various vascular pathologies | Glymphatic impairment was evident following subarachnoid hemorrhage and ischemic stroke, but not after common carotid artery occlusion and intracerebral hemorrhage | 2014 (Gaberel, et al., 2014) |
| Rat | Intralumbar | Flow kinetics | Physiological | Utilized optimal mass transfer (OMT) method to create a glymphatic flow model | 2015 (Ratner et al., 2015) |
| Rat | Intracisternal | - Time-signal curve - Flow kinetics |
Physiological | Glymphatic transport was affected by body position and was most efficient in the right lateral decubitus position | 2015 (Lee, et al., 2015) |
| Human | Intralumbar | T1 signal intensities of ROIs | Intracranial hypotension caused by CSF leakage | Contrast-enhanced MRI may be a viable technique for glymphatic studies in humans | 2015 (Eide and Ringstad, 2015) |
| Human | Intravenous | T2 signal intensities of ROIs | Physiological | Intravenous contrast can enter the perivascular spaces via the CSF | 2017 (Naganawa et al., 2017) |
| Rat | Intracisternal | Flow kinetics | Physiological | Improved upon previous work (Ratner, et al., 2015) on an optimal mass transfer (OMT) method to model glymphatic flow | 2017 (Ratner, et al., 2017) |
| Rat | Intracisternal | - Time-evolution curve - Residual intensity - Clearance rate - Cluster analysis |
Type 2 diabetes mellitus | - Glymphatic transport was impaired in rats with type 2 diabetes mellitus - Increased retention of contrast in the hippocampus and hypothalamus of rats with type 2 diabetes mellitus |
2017 (Jiang et al., 2017) |
| Nonhuman Primate | Intracisternal | - Visualization of contrast distribution throughout the brain - T1 signal intensities of ROIs |
Subarachnoid hemorrhage | Subarachnoid hemorrhage significantly impaired circulation of CSF through the parenchyma | 2017 (Goulay et al., 2017) |
| Human | Intralumbar | - Time-signal curve - Clearance rate - T1 signal intensities of ROIs |
Idiopathic normal pressure hydrocephalus | - Distribution of contrast throughout the brain was slower in humans when compared to rats - Glymphatic transport was decreased in patients with idiopathic normal pressure hydrocephalus, possibly due to restricted arterial pulsation |
2017 (Ringstad, et al., 2017) |
| Rat | Intracisternal | - Time-signal curve - Clearance rate |
Physiological | Glymphatic transport was increased in rats anesthetized with lowdose isoflurane supplemented with dexmedetomidine when compared to rats anesthetized with only isoflurane | 2017 (Benveniste, et al., 2017) |
| Mouse | Intracisternal | - Visualization of contrast distribution throughout the brain - T1 signal intensities of ROIs |
Physiological | First study to show that glymphatic transport was decreased with anesthesia when compared to the awake state, in contrast to most other studies. | 2018 (Gakuba, et al., 2018) |
| Rat | Intracisternal | - Visualization of contrast distribution throughout the brain - T1 signal intensities of ROIs - Time-activity curve |
Physiological | Introduction of a B1+ correction factor for more accurate T1/contrast measurements | 2018 (Lee, et al., 2018) |
| Human | Intralumbar | T1 signal intensities of ROIs | Various CSF disorders | - Contrast drains from the CSF into the cervical lymph nodes - Drainage from nasal lymphatics and perineural pathways may be less pronounced in humans compared to rats |
2018 (Eide et al., 2018) |
| Human | Intralumbar | - Visualization of contrast distribution throughout the brain - Time-signal curve - Clearance rate - T1 signal intensities of ROIs |
Idiopathic normal pressure hydrocephalus | Clearance, but not uptake, of contrast was decreased in patients with idiopathic normal pressure hydrocephalus | 2018 (Ringstad, et al., 2018) |
| Rat | Intravenous | - Time-signal curve - T1 signal intensities of ROIs |
Physiological | - Signal intensity in the fourth ventricle increased immediately after intravenous contrast injection, suggesting the CSF as a potential intermediary pathway for contrast in the blood to reach the brain - Time-of-day of contrast injections may affect brain contrast concentrations |
2018 (Taoka et al., 2018) |
| Rat Mouse | Intracisternal | - Visualization of contrast distribution throughout the brain - T1 signal intensities of ROIs |
Physiological | Both flow and efflux of CSF increases as newborn rats and mice mature into adults | 2018 (Di Palma et al., 2018) |
| Mouse | Intracisternal | - Visualization of contrast distribution throughout the brain - T1 signal intensities of ROIs |
AQP4 knockout | A meta-analysis of five studies (using both microscopy and DCEMRI) strongly reinforced the theory that AQP4 facilitates the influx of CSF into the parenchyma | 2018 (Mestre, et al., 2018) |
| Rat | Intracisternal | - Time-evolution curve - T1 signal intensities of ROIs |
Physiological | - Described the effect of various contrast infusion rates on distribution and clearance Higher infusion rates show quicker distribution of contrast, but with a higher risk of disturbing CSF flow 2018 |
(Ding, et al., 2018) |
| Rat | Intracisternal | - Visualization of contrast distribution throughout the brain - Time-signal curve |
Physiological | Introduced a mathematical model of the glymphatic system using local, rather than global, input functions | 2019 (Davoodi-Bojd, et al., 2019) |
| Nonhuman Primate | - Intracisternal - Intralumbar - Intraventricular |
- Visualization of contrast distribution throughout the brain - Clearance rate |
Physiological | Distribution and clearance of tracer varies between different contrast delivery methods, with acute cisterna magna injection achieving the quickest and most extensive coverage of the brain | 2019 (Ohno, et al., 2019) |
| Rat | Intracisternal | - Visualization of contrast distribution throughout the brain - Time-signal curve - T1 signal intensities of ROIs |
Chronic liver disease with minimal hepatic encephalopathy | Both influx and clearance of contrast in the frontal brain was decreased in rats with chronic liver disease, possibly due to decreased expression of aquaporin-4 in this region | 2019 (Hadjihambi, et al., 2019) |
| Mouse | Intracisternal | - Visualization of contrast distribution throughout the brain and spinal cord - T1 signal intensities of ROIs |
Experimental autoimmune encephalomyelitis (multiple sclerosis model) | Parenchymal CSF circulation in the spinal cord, but not the brain, was decreased in mice with a model of multiple sclerosis, possibly due to leukocyte infiltration | 2019 (Fournier et al., 2019) |
| Phantom | N/A | T2 signal intensities of ROIs | N/A | Increasing repetition time (TR) helped increase the signal intensity of low concentration contrast, suggesting that higher TR may be utilized to detect low contrast concentrations in certain locations and after extended durations | 2019 (Kato et al., 2019) |
| Human | Intravenous | T2 signal intensities of ROIs | Blood-brain barrier damage | Contrast in the blood may enter the CSF by way of the choroid plexus, aqueous humour, and/or trigeminal nerve | 2019 (Deike-Hofmann et al., 2019) |
| Human | Intralumbar | - Visualization of contrast distribution throughout the brain - Concentrationtime curve |
Physiological | Quantified contrast concentration in the human brain over a period of 3 days | 2019 (Watts, et al., 2019) |
| Human | Intralumbar | T1 signal intensities of ROIs | Physiological | Contrast injected into the spinal subarachnoid space accessed the visual pathways, suggesting the existence of an ocular glymphatic system | 2019 (Jacobsen et al., 2019) |
| Rat | Intracisternal | - Visualization of contrast distribution throughout the brain -Timeconcentration curve -Flow kinetics |
Spontaneous hypertension | - Developed a new compartmental model to analyze contrast influx and efflux - Glymphatic influx and efflux was reduced in adult spontaneously hypertensive rats |
2019 (Mortensen, et al., 2019) |
| Human | Intralumbar | Time for contrast to reach level of the foramen magnum (spinal transit time) | Various CSF disorders | - Intrathecal contrast injection is safe in humans without allergies to contrast - Contrast in the spinal cord reached the intracranial CSF in 99 out of 100 patients |
2019 (Edeklev et al., 2019) |
| Human | Intravenous | Visualization of T1 signal intensities | Ultrasound-induced blood-brain barrier damage | Introduced a method of transient local blood-brain barrier opening to facilitate contrast penetration from the blood into the brain, allowing for local noninvasive visualization of the glymphatic system | 2019 (Meng et al., 2019) |
| Human | Intralumbar | T1 and T2 signal intensities of ROIs | Various neurological diseases | - Simultaneously imaged the brain, putative meningeal lymph vessels, and deep cervical lymph nodes in humans, allowing for visualization of the glymphatic clearance pathways - Showed that clearance through these pathways may be impaired with aging |
2020 (Zhou et al., 2020) |
| Human | Intravenous | Visualization of contrast distribution along vessels/sinuses | Physiological | The space under the pial sheath of cortical vessels may be connected with meningeal lymphatics | 2020 (Naganawa et al., 2020) |
| Rat | Intraventricular | T1 signal intensities of ROIs | Physiological | - Intraventricular injection of contrast may be plausible in glymphatic imaging - The distribution of contrast was more widespread during the dark phase of a light-dark cycle |
2020 (Cai et al., 2020) |
| Rat | Yes | - Visualization of contrast distribution throughout the brain - Flow kinetics |
Spontaneous hypertension | - Applied a novel method to reveal the contributions of advective and diffusive forces to glymphatic transport - Solute flow speed was reduced in spontaneously hypertensive rats |
2020 (Koundal, et al., 2020) |
| Human | Intralumbar | - Time-signal curve - T1 signal intensities of ROIs |
Physiological | Established a physiological baseline of CSF contrast kinetics in various cortical and subcortical areas of the human brain | 2020 (Dyke et al., 2020) |
| Rat | Intracisternal | - Time-evolution curve - T1 signal intensities of ROIs |
Ischemic stroke | - During the acute phase, clearance of contrast was slower in the hemisphere ipsilateral to ischemia - During the subacute phase, contrast’s time-to-peak was longer and its retention was increased ipsilateral to ischemia |
2020 (Lin et al., 2020) |
| Mouse | Intracisternal | - Visualization of contrast distribution throughout the brain - T1 signal intensities of ROIs |
Physiological | - Introduced a new method of glymphatic transport quantification and analysis - Contrast drains from the brain into the deep cervical and submandibular lymph nodes |
2020 (Xue, et al., 2020) |
| Rat | Intracisternal | - Time-signal curves - T1 signal intensities of ROIs |
AQP4 inhibition | - Inhibition of AQP4 led to decreased influx of contrast into the parenchyma | 2020 (Takano and Yamada, 2020) |
| Rat | Intracisternal | - Visualization of contrast distribution throughout the brain - Time-signal curves - Flow kinetics |
Mild traumatic brain injury | Both glymphatic influx and clearance was persistently impaired during the chronic time course following mild traumatic brain injury | 2020 (Li et al., 2020) |