Multimodal analysis of the effects of dexamethasone on high-altitude cerebral oedema: protocol for a pilot study.

BACKGROUND: Acute mountain sickness (AMS) is a cluster of symptoms that commonly occur in those ascending to high altitudes. Symptoms can include headaches, nausea, insomnia and fatigue. Exposure to high altitude can also lead to high-altitude cerebral oedema (HACE), which is a potential cause of death whilst mountaineering. Generally, AMS precedes the development of HACE. Historical studies have demonstrated the effectiveness of regular dexamethasone administration in reducing the symptoms of AMS. However, the mechanism by which dexamethasone works to reduce symptoms AMS remains poorly understood. Further studies, simulating altitude using hypoxic tents, have characterised the effect of prolonged exposure to normobaric hypoxia on cerebral oedema and blood flow using MRI. This randomised trial assesses the effect of dexamethasone on hypoxia-induced cerebral oedema in healthy adult volunteers. METHODS/DESIGN: D4H is a double-blind placebo-controlled randomised trial assessing the effect of dexamethasone on hypoxia-induced cerebral oedema. In total, 20 volunteers were randomised in pairs to receive either 8.25 mg dexamethasone or normal saline placebo intravenously after 8 h of hypoxia with an FiO2 of 12%. Serial MRI images of the brain and spinal cord were obtained at hours 0, 7, 11, 22 and 26 of the study along with serum and urinary markers to correlate with the severity of cerebral oedema and the effect of the intervention. DISCUSSION: MRI has been used to identify changes in cerebral vasculature in the development of AMS and HACE. Dexamethasone is effective at reducing the symptoms of AMS; however, the mechanism of this effect is unknown. If this study demonstrates a clear objective benefit of dexamethasone in this setting, future studies may be able to demonstrate that dexamethasone is an effective therapy for oedema associated with brain and spinal cord ischaemia beyond AMS. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03341676 . Registered on 14 November 2017.

Chiari malformation: CSF flow dynamics in the craniocervical junction and syrinx.

BACKGROUND: A CSF flow study in patients with Chiari malformation (ChM) who undergo craniocervical junction decompression (CCJD). METHODS: Using spatial modulation of magnetization (SPAMM), cerebrospinal fluid (CSF) flow velocities were measured at the prepontine (PP), anterior cervical (AC), and posterior cervical (PC) subarachnoid spaces (SAS) in healthy subjects (n = 11) and patients with Chiari malformation (ChM) before and/or after CCJD (n = 15). In the syringes, the intrasyrigeal pulsatile CSF motion was estimated qualitatively as present or absent. FINDINGS: In normal subjects, the mean CSF velocities were 2.4 +/- 0.2 cm/s (PP), 2.8 +/- 0.3 cm/s (AC), and 2.4 +/- 0.2 cm/s (PC). Velocities were significantly lower than normal in patients with ChM prior to CCJD, reduced by 38%, 25%, and 79% in the 3 regions, respectively (P<0.001). Post-CCJD, velocities were 20% (PP), 100% (AC), and 40% (PC) greater than preoperatively (P<0.001). CONCLUSIONS: In ChM, the posterior cervical CSF flow velocity was low, increased minimally after CCJD and, by itself, had limited predictive value. Post-CCJD, an increase of the sum of anterior and posterior cervical CSF flow velocities by more than 20% consistently preceded or coincided with marked headache improvement. After CCJD, the finding that the intrasyringeal CSF pulsatile motion had become absent was an earlier and more sensitive predictor of motor or sensory improvement than a reduction in syrinx's size. SPAMM can be used to assess whether CCJD has restored CSF flow, predict outcome and provide pathophysiological insights in ChM and syringomyelia.

Estimating spatial resolution of in vivo MR images using spatial modulation of magnetization.

Spatial Modulation of Magnetization is shown to provide a means of estimating perceived spatial resolution directly in vivo. On the first magnetic resonance system tested, resolution in conventional spin echo images was found to be stability limited in the phase encoding direction and voxel limited (via the Nyquist sampling theorem) in the frequency encoding direction both in vitro and in vivo. As the voxel size approaches half the stripe separation, fringes of resolved and unresolved stripes are formed across the image. This phenomenon is explained and described mathematically. On a second magnetic resonance scanner, resolution in the phase encoding direction of fast spin echo images with centrically ordered phase encoding is shown to be voxel limited in substances with long T2, with poorer resolution in substances with short T2. Resolution in fast spin echo images with linearly ordered phase encoding was shown to be voxel limited in the phase encoding direction.

Cine magnetic resonance imaging of pulsatile cerebrospinal fluid flow using CSPAMM.

Spatial modulation of magnetization (SPAMM) is a well established imaging technique which superimposes a tagging pattern on conventional magnetic resonance (MR) images, allowing movement to be visualized. A modification to the SPAMM technique, called complementary spatial modulation of magnetization (CSPAMM), which improves the contrast of the tagging pattern is explained. The application of CSPAMM to the visualization of pulsatile cerebrospinal fluid flow (CSF) using an 8 frame cardiac-gated cine sequence is described. Various combinations of binomial pulses, up to the fifth order, were investigated to see which produces the optimum tagging pattern in the CSPAMM images. The flip angles of the imaging RF pulses were studied to see which would give equal maximum CSF signal intensity in all the cine images. The optimized cine CSPAMM technique was compared in vivo with SPAMM and CSF motion was found to be more easily visualized in the CSPAMM images.

Fat suppressed magnetic resonance imaging at 0.5 T using binomial radiofrequency pulses.

Fat suppressed MR imaging can be achieved by selectively saturating lipid protons, just before applying a conventional spin-echo rf pulse sequence. The difference in the Larmor frequency between fat and water protons is only 3.5 ppm, so that the frequency response of the suppressing pulse, or pulses, has to be carefully designed. The choice of suitable binomial and modified trains of hard rf pulses was investigated by computer simulation, phantom testing and T1 weighted spin-echo imaging of a normal volunteer's optic nerve at 0.5 T.

Use of the linear quadratic model in order to accommodate a small reduction in the number of fractions of a standard radiotherapy treatment regime.

Use of the linear quadratic model is considered for reduction, by one or two fractions, of the number of fractions in a daily fractionated reference schedule while maintaining a continuous regime. The cases of maintaining late or early tumour reacting tissue are considered with the inclusion of time effects. The reduction of biologically effective dose (BED) to early-tumour type tissue is shown to be overestimated for both cases if time effects are not taken into account. A third option is outlined, which equates the magnitude of the fractional reduction of BED for early-tumour-reacting tissue to the fractional increase in BED for late-reacting tissue without accounting for time effects. Using this option, the resulting variations in BED for late- and early-tumour tissue are compared with the accepted tolerances in physical dose delivery and some examples presented. The overestimated prediction of the variation in BED for early-tumour tissue still applies in this option, suggesting that this is the way the linear quadratic model should be applied to such a schedule change.

A cine-SPAMM sequence for NMR imaging of pulsatile cerebrospinal fluid flow.

The technical difficulties in designing a SPAMM sequence to image pulsatile cerebrospinal fluid (CSF) flow at different phases of the cardiac cycle are described. The criteria used to select the most appropriate order of binomial SPAMM sequence are outlined. Data collection times required to view both cephalad and caudad flow for all R-R intervals were considered. The flip angles of the RF pulses required to produce images with equal CSF intensity throughout the cardiac cycle were investigated in detail.

Magnetic resonance imaging of pulsatile cerebrospinal fluid flow by spatial modulation of magnetization.

Various orders of binomial spatial modulation of magnetization sequences up to (1 4 6 4 1) have been tested to find the optimum sequence for clinical application. Stripe width, stripe sharpness and the tolerance of the sequences to radiofrequency non-linearity have been investigated. The (1 3 3 1) sequence was found to be a good compromise between competing design criteria, and its application to viewing pulsatile cerebrospinal fluid motion is described.