Estimating the arterial input function from dynamic contrast-enhanced MRI data with compensation for flow enhancement (II): Applications in spine diagnostics and assessment of crohn's disease.

BACKGROUND: Pharmacokinetic (PK) models can describe microvascular density and integrity. An essential component of PK models is the arterial input function (AIF) representing the time-dependent concentration of contrast agent (CA) in the blood plasma supplied to a tissue. PURPOSE/HYPOTHESIS: To evaluate a novel method for subject-specific AIF estimation that takes inflow effects into account. STUDY TYPE: Retrospective study. SUBJECTS: Thirteen clinical patients referred for spine-related complaints; 21 patients from a study into luminal Crohn's disease with known Crohn's Disease Endoscopic Index of Severity (CDEIS). FIELD STRENGTH/SEQUENCE: Dynamic fast spoiled gradient echo (FSPGR) at 3T. ASSESSMENT: A population-averaged AIF, AIFs derived from distally placed regions of interest (ROIs), and the new AIF method were applied. Tofts' PK model parameters (including vp and Ktrans ) obtained with the three AIFs were compared. In the Crohn's patients Ktrans was correlated to CDEIS. STATISTICAL TESTS: The median values of the PK model parameters from the three methods were compared using a Mann-Whitney U-test. The associated variances were statistically assessed by the Brown-Forsythe test. Spearman's rank correlation coefficient was computed to test the correlation of Ktrans to CDEIS. RESULTS: The median vp was significantly larger when using the distal ROI approach, compared to the two other methods (P < 0.05 for both comparisons, in both applications). Also, the variances in vp were significantly larger with the ROI approach (P < 0.05 for all comparisons). In the Crohn's disease study, the estimated Ktrans parameter correlated better with the CDEIS (r = 0.733, P < 0.001) when the proposed AIF was used, compared to AIFs from the distal ROI method (r = 0.429, P = 0.067) or the population-averaged AIF (r = 0.567, P = 0.011). DATA CONCLUSION: The proposed method yielded realistic PK model parameters and improved the correlation of the Ktrans parameter with CDEIS, compared to existing approaches. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2018;47:1197-1204.

ENerGetIcs in hypertrophic cardiomyopathy: traNslation between MRI, PET and cardiac myofilament function (ENGINE study).

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant heart disease mostly due to mutations in genes encoding sarcomeric proteins. HCM is characterised by asymmetric hypertrophy of the left ventricle (LV) in the absence of another cardiac or systemic disease. At present it lacks specific treatment to prevent or reverse cardiac dysfunction and hypertrophy in mutation carriers and HCM patients. Previous studies have indicated that sarcomere mutations increase energetic costs of cardiac contraction and cause myocardial dysfunction and hypertrophy. By using a translational approach, we aim to determine to what extent disturbances of myocardial energy metabolism underlie disease progression in HCM. METHODS: Hypertrophic obstructive cardiomyopathy (HOCM) patients and aortic valve stenosis (AVS) patients will undergo a positron emission tomography (PET) with acetate and cardiovascular magnetic resonance imaging (CMR) with tissue tagging before and 4 months after myectomy surgery or aortic valve replacement + septal biopsy. Myectomy tissue or septal biopsy will be used to determine efficiency of sarcomere contraction in-vitro, and results will be compared with in-vivo cardiac performance. Healthy subjects and non-hypertrophic HCM mutation carriers will serve as a control group. ENDPOINTS: Our study will reveal whether perturbations in cardiac energetics deteriorate during disease progression in HCM and whether these changes are attributed to cardiac remodelling or the presence of a sarcomere mutation per se. In-vitro studies in hypertrophied cardiac muscle from HOCM and AVS patients will establish whether sarcomere mutations increase ATP consumption of sarcomeres in human myocardium. Our follow-up imaging study in HOCM and AVS patients will reveal whether impaired cardiac energetics are restored by cardiac surgery.

First-line erlotinib and bevacizumab in patients with locally advanced and/or metastatic non-small-cell lung cancer: a phase II study including molecular imaging.

BACKGROUND: Both bevacizumab and erlotinib have clinical activity in non-small-cell lung cancer (NSCLC). Preclinical data suggest synergistic activity. PATIENTS AND METHODS: Chemonaive patients with stage IIIb or IV non-squamous NSCLC were treated with bevacizumab 15 mg/kg every 3 weeks and erlotinib 150 mg daily until progression. Primary end point was non-progression rate (NPR) at 6 weeks. Tumor response was measured with computed tomography, 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG-PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). KRAS and EGFR mutations were assessed in tumor samples. RESULTS: Forty-seven patients were included. Median follow-up was 15.2 months. NPR at 6 weeks was 75%. Median progression-free survival (PFS) was 3.8 [95% confidence interval (CI) 2.3-5.4] months and median overall survival (OS) was 6.9 (95% CI 5.5-8.4) months. Toxicity was mainly mild. The presence of KRAS (n = 10) or EGFR mutations (n = 5) did not influence outcome. After 3 weeks of treatment, >20% decrease in standard uptake value as measured with positron emission tomography predicted for longer PFS (9.7 versus 2.8 months; P = 0.01) and >40% decrease in K(trans) as assessed by DCE-MRI did not predict for longer PFS. CONCLUSIONS: First-line treatment with bevacizumab and erlotinib in stage IIIb/IV NSCLC resulted in an NPR of 75%. OS was however disappointing. Early response evaluation with FDG-PET is the best predictive test for PFS.

RC time constant of single lung equals that of both lungs together: a study in chronic thromboembolic pulmonary hypertension.

The product of resistance, R, and compliance, C (RC time), of the entire pulmonary circulation is constant. It is unknown if this constancy holds for individual lungs. We determined R and C in individual lungs in chronic thromboembolic pulmonary hypertension (CTEPH) patients where resistances differ between both lungs. Also, the contribution of the proximal pulmonary arteries (PA) to total lung compliance was assessed. Patients (n=23) were referred for the evaluation of CTEPH. Pressure was measured by right heart catheterization and flows in the main, left, and right PA by magnetic resonance imaging. Total, left, and right lung resistances were calculated as mean pressure divided by mean flow. Total, left, and right lung compliances were assessed by the pulse pressure method. Proximal compliances were derived from cross-sectional area change DeltaA and systolic-diastolic pressure difference DeltaP (DeltaA/DeltaP) in main, left, and right PA, multiplied by vessel length. The lung with the lowest blood flow was defined "low flow" (LF), the contralateral lung "high flow" (HF). Total resistance was 0.57+/-0.28 mmHg.s(-1).ml(-1), and resistances of LF and HF lungs were 1.57+/-0.2 vs. 1.00+/-0.1 mmHg.s(-1).ml(-1), respectively, P<0.0001. Total compliance was 1.22+/-1.1 ml/mmHg, and compliances of LF and HF lung were 0.47+/-0.11 and 0.62+/-0.12 ml/mmHg, respectively, P=0.01. Total RC time was 0.49+/-0.2 s, and RC times for the LF and HF lung were 0.45+/-0.2 and 0.45+/-0.1 s, respectively, not different. Proximal arterial compliance, given by the sum of main, right, and left PA compliances, was only 19% of total lung compliance. The RC time of a single lung equals that of both lungs together, and pulmonary arterial compliance comes largely from the distal vasculature.

Sildenafil treatment in COPD does not affect stroke volume or exercise capacity.

In chronic obstructive pulmonary disease (COPD) patients, stroke volume response to exercise is impaired. The aim of the present study was to investigate whether 3 months of sildenafil treatment improves stroke volume and, if so, whether this improvement is related to the pulmonary artery pressure and translated into an improved exercise capacity. A total of 15 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) underwent right heart catheterisation at rest and during exercise. Stroke volume was assessed by magnetic resonance imaging (MRI) at rest and during submaximal exercise in the supine position and compared with eight age-matched controls. Additionally, a cardiopulmonary exercise test and a 6-min walking distance test were performed. Exercise tests and MRI were repeated after 12 weeks of oral therapy with 50 mg sildenafil three times daily. Stroke volume in COPD patients was significantly lower than in healthy controls (62+/-12 versus 81+/-22 mL at rest and 70+/-15 versus 101+/-28 mL during exercise). Pulmonary hypertension (PH) was diagnosed in nine patients and was absent in six. Treatment with sildenafil had no effect on stroke volume or exercise capacity. Although the stroke volume was lower in COPD patients with associated PH in comparison with non-PH patients, there was no difference in treatment response between both groups. In the present group of 15 chronic obstructive pulmonary disease patients, a reduced stroke volume was found at rest and during exercise. Neither stroke volume nor exercise capacity were improved by 3 months of sildenafil therapy.

MRI protocol optimization for quantitative DCE-MRI of the spine.

PURPOSE: In this study we systematically investigated different Dynamic Contrast Enhancement (DCE)-MRI protocols in the spine, with the goal of finding an optimal protocol that provides data suitable for quantitative pharmacokinetic modelling (PKM). MATERIALS AND METHODS: In 13 patients referred for MRI of the spine, DCE-MRI of the spine was performed with 2D and 3D MRI protocols on a 3T Philips Ingenuity MR system. A standard bolus of contrast agent (Dotarem - 0.2ml/kg body weight) was injected intravenously at a speed of 3ml/s. Different techniques for acceleration and motion compensation were tested: parallel imaging, partial-Fourier imaging and flow compensation. The quality of the DCE MRI images was scored on the basis of SNR, motion artefacts due to flow and respiration, signal enhancement, quality of the T1 map and of the arterial input function, and quality of pharmacokinetic model fitting to the extended Tofts model. RESULTS: Sagittal 3D sequences are to be preferred for PKM of the spine. Acceleration techniques were unsuccessful due to increased flow or motion artefacts. Motion compensating gradients failed to improve the DCE scans due to the longer echo time and the T2* decay which becomes more dominant and leads to signal loss, especially in the aorta. The quality scoring revealed that the best method was a conventional 3D gradient-echo acquisition without any acceleration or motion compensation technique. The priority in the choice of sequence parameters should be given to reducing echo time and keeping the dynamic temporal resolution below 5s. Increasing the number of acquisition, when possible, helps towards reducing flow artefacts. In our setting we achieved this with a sagittal 3D slab with 5 slices with a thickness of 4.5mm and two acquisitions. CONCLUSION: The proposed DCE protocol, encompassing the spine and the descending aorta, produces a realistic arterial input function and dynamic data suitable for PKM.

Quantification of regional contractile function after infarction: strain analysis superior to wall thickening analysis in discriminating infarct from remote myocardium.

OBJECTIVES: Using two-dimensional wall thickening (WT) (expressed as percentage) and strain analysis, regional contractile myocardial function was quantified and compared in 13 control subjects and 13 patients with a first myocardial infarction (MI). The findings in the patient group were related to global ventricular function and infarct size. BACKGROUND: In patients with coronary artery disease, regions with dysfunctional myocardium cannot be differentiated easily from regions with normal function by planar WT analysis. Physiologic factors, in combination with limitations of conventional imaging techniques, affect the calculation of WT. Quantitative assessment of contractile function by magnetic resonance (MR) tissue tagging and strain analysis may be less affected by these factors. METHODS: Two-dimensional regional WT and strain were calculated in three short-axis MR cine and tagged images, respectively. Left ventricular volumes and ejection fraction (EF) were obtained from a series of contiguous short-axis cine images. RESULTS: In patients with infarct-related ventricles, WT and strain analysis both revealed reduced myocardial function, as compared with control subjects (p < 0.005 and p < 0.001, respectively). However, WT analysis yielded no significant regional differences in function between infarct-related and remote myocardium (p = 0.064), whereas strain analysis did (p < 0.005). For detecting dysfunctional myocardium of electrocardiographically and angiographically defined infarct areas, WT analysis had a sensitivity of 69% and a specificity of 92%, whereas strain analysis demonstrated a sensitivity of 92% and a specificity of 99%. The EF correlated with WT (r = 0.76, p < 0.005) and strain (r = 0.89, p < 0.001). CONCLUSIONS: Two-dimensional strain analysis is more accurate than planar WT analysis in discriminating dysfunctional from functional myocardium, and it provides a strong correlation between regional myocardial and global ventricular function.

Impaired left ventricular filling due to right ventricular pressure overload in primary pulmonary hypertension: noninvasive monitoring using MRI.

OBJECTIVE: To analyze the effect of primary pulmonary hypertension (PPH) on cardiac function using MRI. METHODS: In 12 patients (9 women; age range, 30 to 56 years), the diagnosis of PPH had been established by catheterization (mean +/- SD pulmonary artery pressure [PAP] was 56 +/- 8 mm Hg). With breath-hold cine MRI, a series of short-axis images was acquired covering the whole left ventricle (LV) and right ventricle (RV). The curvature, defined as 1 divided by the radius of curvature in centimeters, was calculated for the septum and the LV free wall in early diastole. Leftward ventricular septal bowing (LVSB) is denoted by a negative curvature. For the LV and the RV, the end-diastolic volume (EDV), stroke volume (SV), and volumetric filling rate were calculated. The control subjects were all healthy (n = 14; 11 women; age range, 20 to 57 years). RESULTS: In the patients, LVSB was quantified in early diastole by the septal curvature of - 0.14 +/- 0.07 cm(-1), and the septal to free-wall curvature ratio of - 0.42 +/- 0.21. LV EDV and LV SV correlated negatively with diastolic PAP (p = 0.004 and p = 0.04, respectively). In patients vs control subjects, RV SV was reduced (52 +/- 12 mL vs 82 +/- 11 mL, p < 0.0001); LV peak filling rate was smaller (2.2 +/- 0.7 EDV/s vs 3.3 +/- 0.5 EDV/s, p < 0.001); LV EDV was smaller (81 +/- 23 mL vs 117 +/- 19 mL, p = 0.001); and LV SV was smaller (49 +/- 18 mL vs 83 +/- 13 mL, p < 0.0001). CONCLUSION: In PPH, RV pressure overload leads to LVSB and reduced RV output. By decreased blood delivery, LV filling is reduced, which results in decreased LV SV by the Frank-Starling mechanism.

The effect of right ventricular hypertrophy on left ventricular ejection fraction in pulmonary emphysema.

STUDY OBJECTIVE: The development of right ventricular (RV) hypertrophy in emphysema is accompanied by involvement of the left ventricle (LV) and its systolic function. Our objective was to study the relation between RV hypertrophy and LV ejection fraction in emphysema by means of MRI. PATIENTS: Ten emphysematous patients (FEV1, 0.99+/-0.32 L; FEV1/vital capacity (VC), 0.32+/-0.11 [mean+/-SD]) and 10 age-matched control subjects were included. Exclusion criteria were any history of systemic hypertension, ischemic or valvular heart disease, or episodes of right- and/or left-sided cardiac failure. MEASUREMENTS AND RESULTS: Rapid scout imaging was used to measure RV and LV wall mass, wall thickness, and end-diastolic volume. Stroke volume was derived from the main pulmonary artery flow. RV wall volume, RV wall thickness, and the ratio of RV to LV wall thickness were significantly larger in the patient group than in the control group (p<0.01). Furthermore, patients had significantly lower values of LV ejection fraction (p<0.01) than the control subjects. A flattening or leftward displacement of the ventricular septum during systole was observed. In addition, our study showed an increase of LV ejection fraction proportional with the RV wall thickness (r=0.78, p<0.01) in severely emphysematous patients. CONCLUSION: These data are in support of the hypothesis that flattening of the interventricular septum explains the relatively normal LV ejection fraction in emphysematous patients with severe RV hypertrophy.

Noninvasive assessment of right ventricular diastolic function by electrical impedance tomography.

STUDY OBJECTIVES: Electrical impedance tomography (EIT) offers the possibility to study blood volume changes within the right atrium during the cardiac cycle. The aim of this study was to determine the applicability of EIT in the assessment of right ventricular diastolic function in COPD. DESIGN: By means of region of interest analysis, impedance changes within the right atrium during the cardiac cycle were plotted as a function of time. As a diastolic index of the right ventricle, the right atrium emptying volume (RAEV), defined as the ratio between the volume change during the rapid filling phase relative to the total ventricular filling volume, was calculated. In a first study, the validity of the EIT method was assessed by comparison of the RAEV measured by EIT and MRI in a group of eight patients with severe COPD and seven control subjects. A second study was undertaken to assess the relation between RAEV and pulmonary artery pressure in a group of 27 patients measured by right-sided heart catheterization. RESULTS: The correlation coefficient between RAEV measured with MRI and EIT was 0.78. The difference between RAEV measured by MRI and EIT was 8.3 +/- 15.7% (mean +/- SD) for the control subjects and 3.5 +/- 10.9% for the COPD patients. RAEV values measured by EIT and MRI were larger in the control group (47.1 +/- 7.6%) compared with the patient group (38.1 +/- 10.4%). There was a clear nonlinear relationship between RAEV and the pulmonary artery pressure (y = 315 x-0.64, r = 0.83, p < 0.001). CONCLUSION: Our results indicate that RAEV measured by EIT is a useful noninvasive and inexpensive method for assessing right ventricular diastolic function in COPD patients.

Spatiotemporal representation of moving luminance edges in human vision.

The edges of straight bars in a square-wave luminance grating appear undulating to an observer when the retinal image of this pattern is in motion. The amplitude of the perceived undulations increases linearly with retinal image speed with an average slope of 30 +/- 4 ms. The period of the motion-induced bulges is 2.5 +/- 0.5 degree and shows no consistent variation with the retinal image velocity of the pattern. The close quantitative agreement between the spatiotemporal extent of this effect and recent estimates of the spatiotemporal parameters of human motion-sensitive mechanisms suggests the existence of motion-sensitive cells in the central nervous system that have a fixed time constant but change the shape and size of their retinal support with retinal image velocity.

Imaging of thoracic blood volume changes during the heart cycle with electrical impedance using a linear spot-electrode array.

Electrical impedance (EI) measurements conducted on the thorax contain useful information about the changes in blood volume that occur in the thorax during the heart cycle. The aim of this paper is to present a new (tomographic-like) method to obtain this relevant information with electrical impedance measurements, using a linear electrode array. This method is tested on three subjects and the results are compared with results, obtained from magnetic resonance cine-images showing the cross-sectional surface area changes of the aorta, the vena cava, the carotid arteries, and the heart. This paper shows that the different sources of the thoracic EI waveform may be separated in time and location on the thoracic surface and that aortic volume changes may be estimated accurately.

Three-dimensional myocardial strain analysis based on short- and long-axis magnetic resonance tagged images using a 1D displacement field.

A robust algorithm to estimate three-dimensional strain in the left-ventricular heart wall, based on magnetic resonance (MR) grid-tagging in two sets of orthogonal image planes, is presented. Starting-point of this study was to minimize global interpolation and smoothing. Only the longitudinal displacement was interpolated between long-axis images. Homogeneous strain analysis was performed using small tetrahedrons. The method was tested using a stack of short-axis images and three long-axis images in six healthy volunteers. In addition, the method was subjected to an analytical test case, in which the effect of noise in tag point position on the observed strains was explored for normally distributed noise (0.5 mm RMS). In volunteers, the error in the longitudinal displacement due to interpolation between the long-axis image planes was -0.10 +/- 0. 48 mm (mean +/- SD). The resulting error in the longitudinal strain epsilon(l) was -0.003 +/- 0.02. The analytical test case was used to quantify the effects of three sources of errors on the observed strain. The SD of the difference between homogeneous strain and true strain was 0.06 for epsilon(r.) The error due to the 3-D reconstruction was 0.004 for epsilon(r.) The error in epsilon(r) resulting from simulated noise in the tag point position was 0.10. Equivalent results were obtained for all other strain parameters; thus, the error resulting from noise in the tag point position dominates the error introduced by approximations in the method. Because the proposed method uses a minimum of global interpolation and smoothing, it offers the prospect to detect small regions of aberrant contraction.

Improvement of cardiac imaging in electrical impedance tomography by means of a new electrode configuration.

Until now, electrical impedance tomography (EIT) has been used for cardiac imaging with the electrodes attached transversally at the level of the fourth intercostal space at the anterior side. However, the results obtained with this electrode configuration have been disappointing. The aim of the present study was to improve the measurement design of EIT for cardiac imaging. Therefore, magnetic resonance imaging (MRI) scans were analysed in two healthy subjects to determine the optimum anatomical plane in which atria and ventricles are clearly visually separated. From these findings, we proposed a new oblique plane at the level of the ictus cordis anteriorly and 10 cm higher posteriorly. EIT pictures obtained in the oblique plane revealed a better visual separation between the ventricles and atria than with the electrodes attached in the transverse plane. Comparison between volume changes measured by means of MRI and impedance changes in different regions of interest measured with EIT were performed with the electrodes in the proposed oblique plane. Ventricular and atrial volume changes measured by MRI show the same pattern as do impedance changes measured by EIT. Furthermore, we assessed the reproducibility and validity of the oblique electrode configuration in ten healthy mate volunteers during rest and during exercise compared with the currently used transverse electrode configuration. The reproducibility coefficient assessed from repeated measurements with the electrodes attached in the oblique plane was 0.98 at rest and 0.85 during exercise. For the transverse plane the reproducibility coefficient was 0.96 at rest and 0.66 during exercise. The well-known increase in stroke volume during exercise is 40% in healthy subjects. The increase in impedance change during exercise compared with rest was 34 +/- 13% (20-59%) for the oblique plane and 68 +/- 57% (13-140%) for the transverse plane. From these results we infer that the stroke volume is assessed more accurately by using the oblique plane. From these findings, we conclude that the oblique plane improved the cardiac measurements, because (i) a better spatial separation of the heart compartments is obtained, (ii) the results are more reliable and (iii) measurements during exercise are more accurate with the electrodes attached in an oblique plane.

Determination of stroke volume by means of electrical impedance tomography.

ECG-gated electrical impedance tomography (EIT) is a non-invasive imaging technique, developed to monitor blood volume changes. This study is the first in comparing this non-invasive technique in measuring stroke volume with established techniques. The objective of this study was to validate EIT variables derived from the EIT images with paired obtained stroke volume measurements by thermodilution and MRI. After right cardiac catheterization, EIT measurements were performed in 25 patients. Regression analysis was used to analyse the relation between the EIT results and stroke volume determined by thermodilution. From the regression line an equation was derived to estimate stroke volume (in ml) by EIT. A strong correlation was found between EIT and stroke volume measured by the thermodilution method (r = 0.86). In a group of 11 healthy subjects this equation was validated to MRI. The mean and standard deviation of the difference between EIT and MRI was 0.7 ml and 5.4 ml respectively. These data indicate that EIT is a valid and reproducible method for the assessment of stroke volume.

Pulmonary perfusion measured by means of electrical impedance tomography.

Electrical impedance tomography (EIT) is a recent imaging technique based on electrical impedance, offering the possibility of measuring pulmonary perfusion. In the present study the influence of several pulmonary haemodynamical parameters on the EIT signal were investigated. First, the influence on the systolic wave of the EIT signal (delta Zsys) of stroke volume, large pulmonary artery distensibility (both assessed by means of MRI) and the extent of the pulmonary peripheral vascular bed in 11 emphysematous patients (reduced peripheral vascular bed) and 9 controls (normal peripheral vascular bed) was investigated. Second, the influence of hypoxic pulmonary vasoconstriction on delta Zsys was examined in 14 healthy subjects. Finally, the origin of the diastolic wave was examined in three patients with atrioventricular dissociation. Multiple regression analysis showed that delta Zsys was only dependent on the variable emphysema (p < 0.02), but not dependent on stroke volume (p < 0.3) or pulmonary artery distensibility (p > 0.9). The mean value of delta Zsys for emphysematous patients (131 +/- 32 arbitrary units (AU)) was significantly lower (p < 0.001) than in the control group (200 +/- 39). In the group of healthy subjects delta Zsys decreased significantly (p < 0.001) during hypoxia (193 +/- 38 AU) compared with rest measurements (260 +/- 62 AU). The absence of the diastolic wave in the cardiological patients suggests the influence of reverse venous blood flow on the EIT signal. It is concluded that volume changes in the small pulmonary vessels contribute significantly to the EIT signal. Moreover, the hypoxia induced decrease in delta Zsys indicates the potential of EIT for measuring pulmonary vascular responses to external stimuli.

Influence of gravitoinertial force on vestibular nystagmus in man observed in a centrifuge.

The influence of gravity load on the vestibular system in man was investigated in a centrifuge operating on the free swing principle. The vertical vestibular nystagmus induced by acceleration to 3G was analyzed and compared with reference measurements during 1G. Our data indicate that the effects of increased gravity load include a prolonged decay time constant of upbeat nystagmus and a subject-dependent persisting upbeat nystagmus. In an attempt to explain these findings, an extension of the velocity storage model is proposed, with gravity as a second stimulus function in addition to angular acceleration.

Vestibulo-ocular responses in man to +Gz hypergravity.

The influence of high +Gz gravito-inertial force on the vestibular system in man was investigated in a 4-m centrifuge with a freely swinging gondola. The Gz profile was: acceleration +0.2 Gz/s, +3 Gz sustained for 3 min, deceleration -0.2 Gz/s. The subject was exposed to this profile under two conditions in randomized order: facing forward and facing backward. Under these conditions, the effective angular velocity in the plane of the vertical semicircular canals is opposed. Adding the slow phase velocity responses from these conditions yields the Gz effect only; subtracting yields the angular velocity effect only. Vertical vestibular nystagmus was analysed in five subjects. Results indicate that +3 Gz induced a subject-dependent vertical nystagmus with slow phase downwards. The average amplitude of this nystagmus reached a maximum of 27 degrees/s at 16 s from G onset, and was 11 degrees/s after 3 min of sustained +3 Gz. The vestibular stimulation by +Gz could result in false subjective perception of attitude, and play a major role in spatial disorientation in flight.