Arun A. Joseph

Inspiration is the major regulator of human CSF flow.

The mechanisms behind CSF flow in humans are still not fully known. CSF circulates from its primary production sites at the choroid plexus through the brain ventricles to reach the outer surface of the brain in the subarachnoid spaces from where it drains into venous bloodstream and cervical lymphatics. According to a recent concept of brain fluid transport, established in rodents, CSF from the brain surface also enters the brain tissue along para-arterial routes and exits through paravenous spaces again into subarachnoid compartments. This unidirectional flow is mainly driven by arterial pulsation. To investigate how CSF flow is regulated in humans, we applied a novel real-time magnetic resonance imaging technique at high spatial (0.75 mm) and temporal (50 ms) resolution in healthy human subjects. We observed significant CSF flow exclusively with inspiration. In particular, during forced breathing, high CSF flow was elicited during every inspiration, whereas breath holding suppressed it. Only a minor flow component could be ascribed to cardiac pulsation. The present results unambiguously identify inspiration as the most important driving force for CSF flow in humans. Inspiratory thoracic pressure reduction is expected to directly modulate the hydrostatic pressure conditions for the low-resistance paravenous, venous, and lymphatic clearance routes of CSF. Furthermore, the experimental approach opens new clinical opportunities to study the pathophysiology of various forms of hydrocephalus and to design therapeutic strategies in relation to CSF flow alterations.

Real‐time phase‐contrast MRI of cardiovascular blood flow using undersampled radial fast low‐angle shot and nonlinear inverse reconstruction

Velocity‐encoded phase‐contrast MRI of cardiovascular blood flow commonly relies on electrocardiogram‐synchronized cine acquisitions of multiple heartbeats to quantitatively determine the flow of an averaged cardiac cycle. Here, we present a new method for real‐time phase‐contrast MRI that combines flow‐encoding gradients with highly undersampled radial fast low‐angle shot acquisitions and phase‐sensitive image reconstructions by regularized nonlinear inversion. Apart from calibration studies using steady and pulsatile flow, preliminary in vivo applications focused on through‐plane flow in the ascending aorta of healthy subjects. With bipolar velocity‐encoding gradients of alternating polarity that overlap the slice‐refocusing gradient, the method yields flow‐encoded images with an in‐plane resolution of 1.8 mm, section thickness of 6 mm and measuring time at 3 T of 24 ms (TR/TE = 3.44/2.76 ms; flip angle, 10º; seven radial spokes per image). Accordingly, phase‐contrast maps and corresponding velocity profiles achieve a temporal resolution of 48 ms. The evaluated peak velocities, stroke volumes, flow rates and respective variances over at least 20 consecutive heartbeats are in general agreement with literature data. Copyright

Real-time flow MRI of the aorta at a resolution of 40 msec.

To evaluate a novel real‐time phase‐contrast magnetic resonance imaging (MRI) technique for the assessment of through‐plane flow in the ascending aorta.

Identification of the upward movement of human CSF in vivo and its relation to the brain venous system.

CSF flux is involved in the pathophysiology of neurodegenerative diseases and cognitive impairment after traumatic brain injury, all hallmarked by the accumulation of cellular metabolic waste. Its effective disposal via various CSF routes has been demonstrated in animal models. In contrast, the CSF dynamics in humans are still poorly understood. Using novel real-time MRI, forced inspiration has been identified recently as a main driving force of CSF flow in the human brain. Exploiting technical advances toward real-time phase-contrast MRI, the current work analyzed directions, velocities, and volumes of human CSF flow within the brain aqueduct as part of the internal ventricular system and in the spinal canal during respiratory cycles. A consistent upward CSF movement toward the brain in response to forced inspiration was seen in all subjects at the aqueduct, in 11/12 subjects at thoracic level 2, and in 4/12 subjects at thoracic level 5. Concomitant analyses of CSF dynamics and cerebral venous blood flow, that is, in epidural veins at cervical level 3, uniquely demonstrated CSF and venous flow to be closely communicating cerebral fluid systems in which inspiration-induced downward flow of venous blood due to reduced intrathoracic pressure is counterbalanced by an upward movement of CSF. The results extend our understanding of human CSF flux and open important clinical implications, including concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and idiopathic intracranial hypertension. SIGNIFICANCE STATEMENT Effective disposal of brain cellular waste products via CSF has been demonstrated repeatedly in animal models. However, CSF dynamics in humans are still poorly understood. A novel quantitative real-time MRI technique yielded in vivo CSF flow directions, velocities, and volumes in the human brain and upper spinal canal. CSF moved upward toward the head in response to forced inspiration. Concomitant analysis of brain venous blood flow indicated that CSF and venous flux act as closely communicating systems. The finding of a human CSF–venous network with upward CSF net movement opens new clinical concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and ideopathic intracranial hypertension.

Advances in real-time phase-contrast flow MRI using asymmetric radial gradient echoes.

To provide multidimensional velocity compensation for real‐time phase‐contrast flow MRI.

Real-time phase-contrast flow MRI of the ascending aorta and superior vena cava as a function of intrathoracic pressure (Valsalva manoeuvre).

OBJECTIVE Real-time phase-contrast flow MRI at high spatiotemporal resolution was applied to simultaneously evaluate haemodynamic functions in the ascending aorta (AA) and superior vena cava (SVC) during elevated intrathoracic pressure (Valsalva manoeuvre). METHODS Real-time phase-contrast flow MRI at 3 T was based on highly undersampled radial gradient-echo acquisitions and phase-sensitive image reconstructions by regularized non-linear inversion. Dynamic alterations of flow parameters were obtained for 19 subjects at 40-ms temporal resolution, 1.33-mm in-plane resolution and 6-mm section thickness. Real-time measurements were performed during normal breathing (10 s), increased intrathoracic pressure (10 s) and recovery (20 s). RESULTS Real-time measurements were technically successful in all volunteers. During the Valsalva manoeuvre (late strain) and relative to values during normal breathing, the mean peak flow velocity and flow volume decreased significantly in both vessels (p < 0.001) followed by a return to normal parameters within the first 10 s of recovery in the AA. By contrast, flow in the SVC presented with a brief (1-2 heartbeats) but strong overshoot of both the peak velocity and blood volume immediately after pressure release followed by rapid normalization. CONCLUSION Real-time phase-contrast flow MRI may assess cardiac haemodynamics non-invasively, in multiple vessels, across the entire luminal area and at high temporal and spatial resolution. ADVANCES IN KNOWLEDGE Future clinical applications of this technique promise new insights into haemodynamic alterations associated with pre-clinical congestive heart failure or diastolic dysfunction, especially in cases where echocardiography is technically compromised.

Model-based reconstruction for real-time phase-contrast flow MRI: Improved spatiotemporal accuracy.

To develop a model‐based reconstruction technique for real‐time phase‐contrast flow MRI with improved spatiotemporal accuracy in comparison to methods using phase differences of two separately reconstructed images with differential flow encodings.

High-speed real-time magnetic resonance imaging of fast tongue movements in elite horn players

This paper describes the use of high-speed real-time (RT) magnetic resonance imaging (MRI) in quantifying very rapid motor function within the oropharyngeal cavity of six elite horn players. Based on simultaneous sound recordings, the efficacy of RT-MRI films at 30 and 100 frames per second (fps) was assessed for tongue movements associated with double tonguing performance. Serial images with a nominal temporal resolution of 10.0 and 33.3 ms were obtained by highly undersampled radial fast low-angle shot (FLASH) sequences (5 and 17 spokes, respectively) using complementary sets of spokes for successive acquisitions (extending over 9 and 5 frames, respectively). Reconstructions of high-speed images were obtained by temporally regularized nonlinear inversion (NLINV) as previously described. A customized MATLAB toolkit was developed for the extraction of line profiles from MRI films to quantify temporal phenomena associated with task performance. The analyses reveal that for the present setting, which required the use of a temporal median filter to optimize image quality, acquisition rates of 30 fps are inadequate to accurately detect tongue movements during double tonguing, but that rates of 100 fps do allow for a precise quantification of movement. These data for the first time demonstrate the extreme performance of elite horn players. High-speed RT-MRI offers so far unavailable opportunities to study the oropharyngeal movements during brass playing with future potential for teaching and the treatment of patients suffering from dystonia.

Real-time magnetic resonance imaging of cardiac function and flow—Recent progress

Cardiac structure, function and flow are most commonly studied by ultrasound, X-ray and magnetic resonance imaging (MRI) techniques. However, cardiovascular MRI is hitherto limited to electrocardiogram (ECG)-synchronized acquisitions and therefore often results in compromised quality for patients with arrhythmias or inabilities to comply with requested protocols-especially with breath-holding. Recent advances in the development of novel real-time MRI techniques now offer dynamic imaging of the heart and major vessels with high spatial and temporal resolution, so that examinations may be performed without the need for ECG synchronization and during free breathing. This article provides an overview of technical achievements, physiological validations, preliminary patient studies and translational aspects for a future clinical scenario of cardiovascular MRI in real time.

Diagnosis of Gastroesophageal Reflux Disease Using Real-time Magnetic Resonance Imaging

A small angle (His angle) between the oesophagus and the fundus of the stomach is considered to act as flap valve and anti-reflux barrier. A wide angle results in dysfunction of the oesophagogastric junction and subsequently in gastroesophageal reflux disease (GERD). Here, we used real-time magnetic resonance imaging (MRI) at 50 ms resolution (20 frames per second) in 12 volunteers and 12 patients with GERD to assess transport of pineapple juice through the oesophagogastric junction and reflux during Valsalva. We found that the intra-abdominal part of the oesophagus was bended towards the left side resulting in an angle of 75.3 ± 17.4, which was significantly larger during Valsava (P = 0.017). Reflux and several underlying pathologies were detected in 11 out of 12 patients. Our data visualize oesophagogastric junction physiology and disprove the flap valve hypothesis. Further, non-invasive real-time MRI has considerable potential for the diagnosis of causative pathologies leading to GERD.