Quantitative BOLD imaging at 3T: Temporal changes in hepatocellular carcinoma and fibrosis following oxygen challenge.

PURPOSE: To evaluate the utility of oxygen challenge and report on temporal changes in blood oxygenation level-dependent (BOLD) contrast in normal liver, hepatocellular carcinoma (HCC) and background fibrosis. MATERIALS AND METHODS: Eleven volunteers (nine male and two female, mean age 33.5, range 27-41 years) and 10 patients (nine male and one female, mean age 68.9, range 56-87 years) with hepatocellular carcinoma on a background of diffuse liver disease were recruited. Imaging was performed on a 3T system using a multiphase, multiecho, fast gradient echo sequence. Oxygen was administered via a Hudson mask after 2 minutes of free-breathing. Paired t-tests were performed to determine if the mean pre- and post-O2 differences were statistically significant. RESULTS: In patients with liver fibrosis (n = 8) the change in T2* following O2 administration was elevated (0.88 ± 0.582 msec, range 0.03-1.69 msec) and the difference was significant (P = 0.004). The magnitude of the BOLD response in patients with HCC (n = 10) was larger, however the response was more variable (1.07 ± 1.458 msec, range -0.93-3.26 msec), and the difference was borderline significant (P = 0.046). The BOLD response in the volunteer cohort was not significant (P = 0.121, 0.59 ± 1.162 msec, range -0.81-2.44 msec). CONCLUSION: This work demonstrates that the BOLD response following oxygen challenge within cirrhotic liver is consistent with a breakdown in vascular autoregulatory mechanisms. Similarly, the elevated BOLD response within HCC is consistent with the abnormal capillary vasculature within tumors and the arterialization of the blood supply. Our results suggest that oxygen challenge may prove a viable BOLD contrast mechanism in the liver. J. Magn. Reson. Imaging 2016;44:739-744.This study was supported by the Addenbrooke’s Charitable Trust, Cambridge’s Experimental Cancer Medicine Centre and a NIHR comprehensive Biomedical Research Centre award to Cambridge University Hospitals NHS Foundation Trust in partnership with the University of Cambridge.This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/jmri.2518

Errors of Measurement for Blood Parameters and Physiological and Performance Measures After the Decay of Short-Term Heat Acclimation

Introduction: It is important to determine the accuracy of measurements relative to potential treatment effects, with time intervals between tests. Purpose: The aim of this study was to assess the error of measurement for blood parameters, physiological, and performance measures after the decay of short-term heat acclimation. Methods: Ten trained males (Mean±SD: age 28±7 y; body mass 74.6±4.4 kg; 4.26±0.37 L.min-1; peak power output (PPO) 329±42 W) completed an exercising heat stress test (HST) at baseline, 2nd day after acclimation and then during decay at 1, 2, 3 and 5-6 wks. CoV (95% CI), SE (95% CI) and Pearsons (r) were used for analysis of blood volume (blood, plasma, red cell volume, mean hemoglogin mass); plasma (aldosterone, arginine vasopressin [AVP], total protein, albumin, sodium); physiological (rectal temperature, cardiac frequency) and performance (exercise performance capacity, PPO). Results: The CoV (95% CI), SE (95% CI) and r with a 1-wk interval for blood volume was 2.3% (1.6 to 4.3; 1.9 [1.3 to 3.4 mL.Kg-1]; r=0.93; n=10). After 2-wk and 5-6 wks this had increased to 4.9% (3.4 to 9.3; 3.8 [2.6 to 7.0 mL.Kg-1]; r=0.76; n=9) and 5.5% (3.6 to 12.8; 4.5 [2.9 to 10.0 mL.Kg-1]; r=0.65; n=7) respectively. Conclusions: Blood volume and physiological measures demonstrated the least error one week apart but increased thereafter. Plasma concentrations and performance markers had the greatest error with repeat measures after one week. Therefore, for greater reliability and low measurement error measures should be taken no more than one week a part in repeated experimentation

Errors of measurement for blood parameters, physiological and performance measures after the decay of short-term heat acclimation

Introduction: It is important to determine the accuracy of measurements relative to potential treatment effects, with time intervals between tests. Purpose: The aim of this study was to assess the error of measurement for blood parameters, physiological, and performance measures after the decay of short-term heat acclimation. Methods: Ten trained males (Mean±SD: age 28±7 y; body mass 74.6±4.4 kg; 4.26±0.37 L.min-1; peak power output (PPO) 329±42 W) completed an exercising heat stress test (HST) at baseline, 2nd day after acclimation and then during decay at 1, 2, 3 and 5-6 wks. CoV (95% CI), SE (95% CI) and Pearsons (r) were used for analysis of blood volume (blood, plasma, red cell volume, mean hemoglogin mass); plasma (aldosterone, arginine vasopressin [AVP], total protein, albumin, sodium); physiological (rectal temperature, cardiac frequency) and performance (exercise performance capacity, PPO). Results: The CoV (95% CI), SE (95% CI) and r with a 1-wk interval for blood volume was 2.3% (1.6 to 4.3; 1.9 [1.3 to 3.4 mL.Kg-1]; r=0.93; n=10). After 2-wk and 5-6 wks this had increased to 4.9% (3.4 to 9.3; 3.8 [2.6 to 7.0 mL.Kg-1]; r=0.76; n=9) and 5.5% (3.6 to 12.8; 4.5 [2.9 to 10.0 mL.Kg-1]; r=0.65; n=7) respectively. Conclusions: Blood volume and physiological measures demonstrated the least error one week apart but increased thereafter. Plasma concentrations and performance markers had the greatest error with repeat measures after one week. Therefore, for greater reliability and low measurement error measures should be taken no more than one week a part in repeated experimentation

The use of error-category mapping in pharmacokinetic model analysis of dynamic contrast-enhanced MRI data.

This study introduces the use of 'error-category mapping' in the interpretation of pharmacokinetic (PK) model parameter results derived from dynamic contrast-enhanced (DCE-) MRI data. Eleven patients with metastatic renal cell carcinoma were enrolled in a multiparametric study of the treatment effects of bevacizumab. For the purposes of the present analysis, DCE-MRI data from two identical pre-treatment examinations were analysed by application of the extended Tofts model (eTM), using in turn a model arterial input function (AIF), an individually-measured AIF and a sample-average AIF. PK model parameter maps were calculated. Errors in the signal-to-gadolinium concentration ([Gd]) conversion process and the model-fitting process itself were assigned to category codes on a voxel-by-voxel basis, thereby forming a colour-coded 'error-category map' for each imaged slice. These maps were found to be repeatable between patient visits and showed that the eTM converged adequately in the majority of voxels in all the tumours studied. However, the maps also clearly indicated sub-regions of low Gd uptake and of non-convergence of the model in nearly all tumours. The non-physical condition ve ≥ 1 was the most frequently indicated error category and appeared sensitive to the form of AIF used. This simple method for visualisation of errors in DCE-MRI could be used as a routine quality-control technique and also has the potential to reveal otherwise hidden patterns of failure in PK model applications.This work was supported by GlaxoSmithKline UK, Wellcome Trust, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Cancer Research UKThis is the published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0730725X1400321X

Safe Supervisory Control of Soft Robot Actuators

Although soft robots show safer interactions with their environment than traditional robots, soft mechanisms and actuators still have significant potential for damage or degradation particularly during unmodeled contact. This article introduces a feedback strategy for safe soft actuator operation during control of a soft robot. To do so, a supervisory controller monitors actuator state and dynamically saturates control inputs to avoid conditions that could lead to physical damage. We prove that, under certain conditions, the supervisory controller is stable and verifiably safe. We then demonstrate completely onboard operation of the supervisory controller using a soft thermally-actuated robot limb with embedded shape memory alloy (SMA) actuators and sensing. Tests performed with the supervisor verify its theoretical properties and show stabilization of the robot limb's pose in free space. Finally, experiments show that our approach prevents overheating during contact (including environmental constraints and human contact) or when infeasible motions are commanded. This supervisory controller, and its ability to be executed with completely onboard sensing, has the potential to make soft robot actuators reliable enough for practical use