MR-compatible Ergometer Research Articles

Correlation between skeletal muscle acetylcarnitine and phosphocreatine metabolism during submaximal exercise and recovery: interleaved 1H/31P MRS 7 T study

Acetylcarnitine is an essential metabolite for maintaining metabolic flexibility and glucose homeostasis. The in vivo behavior of muscle acetylcarnitine content during exercise has not been shown with magnetic resonance spectroscopy. Therefore, this study aimed to explore the behavior of skeletal muscle acetylcarnitine during rest, plantar flexion exercise, and recovery in the human gastrocnemius muscle under aerobic conditions. Ten lean volunteers and nine overweight volunteers participated in the study. A 7 T whole-body MR system with a double-tuned surface coil was used to acquire spectra from the gastrocnemius medialis. An MR-compatible ergometer was used for the plantar flexion exercise. Semi-LASER-localized 1H MR spectra and slab-localized 31P MR spectra were acquired simultaneously in one interleaved exercise/recovery session. The time-resolved interleaved 1H/31P MRS acquisition yielded excellent data quality. A between-group difference in acetylcarnitine metabolism over time was detected. Significantly slower τPCr recovery, τPCr on-kinetics, and lower Qmax in the overweight group, compared to the lean group was found. Linear relations between τPCr on-kinetics, τPCr recovery, VO2max and acetylcarnitine content were identified. In conclusion, we are the first to show in vivo changes of skeletal muscle acetylcarnitine during acute exercise and immediate exercise recovery with a submaximal aerobic workload using interleaved 1H/31P MRS at 7 T.

P047 Deconditioning in quiescent Crohn’s Disease patients with heightened fatigue perception

Abstract Background Heightened fatigue perception and premature exercise fatigue are common in inflammatory bowel disease (IBD). Physical deconditioning is greater in patients with increased fatigue perception relative to patients with a lower perception of fatigue, implicating deconditioning as an aetiological factor. This study used physiology and multiparametric Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) during exercise to comprehensively phenotype quiescent IBD fatigue. Methods Participant body mass and regional body composition was assessed by DEXA, and tknee extensor strength and fatiguability using isokinetic dynamometry (Cybex, USA). A supine CPET was performed using an MR-compatible Ergometer (Cardiostepper, Ergospect) to standardize relative exercise intensity for in-bore 1H MRI measures. 1H MRI data were collected on a Philips 3T Ingenia wide bore scanner using a Philips Head/Neck coil and in-built posterior coil. Across rest, steady-state exercise (50% VO2 peak) and recovery, Phase Contrast-MRI was used to compute cardiac output and cerebral blood flow (CBF), and T2 Relaxation under spin tagging (TRUST-MRI) to measure brain oxygen extraction fraction (OEF). 31P MRS data was collected on a 3T Philips Achieva using a 14cm 31P coil over the medial gastrocnemius. Ischaemic plantar flexion exercise was performed at 50% maximum voluntary contraction (MVC) using an MR-compatible ergometer (Trispect, Ergospect) during non-localized pulse-acquire 31P-MRS. 31P spectra were analysed using the AMARES function in jMRUI Beta 6.0. In vivo muscle mitochondrial flux during post-exercise PCr recovery (VPCr = kPCr * ΔPCr) where ΔPCr is PCrendrecovery –PCrendex) was quantified after reinstating limb blood flow and fitting PCr recovery to a mono-exponential function in GraphPad prism (PCr(t) = PCrinitial+(PCrend – PCrinitial)(1-exp(-k.t) where t is time from start of non-ischaemic recovery). Results 16 quiescent CD patients and 12 age and BMI matched HV’s completed the study. General fatigue score was greater in CD relative to HV (P = 0.001, Table 1). Body composition, isometric strength, fatigue development were not different between groups (Table 1). CBF response to steady-state exercise was less in CD (P = 0.003) alongside the maintenance of cardiac output and brain OEF in HV (Figure 1). VPCr following ischemic plantar flexion exercise was less in CD than HV (P = 0.02, Figure 1) (Figure 1). Conclusion Greater fatigue perception in CD was accompanied by lower CBF on exercise and blunted post-exercise PCr resynthesis, but no differences in body composition, strength and fatiguability relative to HV. These finding point to greater deconditioning in CD, corroborated by their lower daily step count relative to HV.

Alteration of skeletal muscle energy metabolism assessed by 31 P MRS in clinical routine: Part 2. Clinical application.

In this second part of a two-part paper, we intend to demonstrate the impact of the previously proposed advanced quality control pipeline. To understand its benefit and challenge the proposed methodology in a real scenario, we chose to compare the outcome when applying it to the analysis of two patient populations with significant but highly different types of fatigue: COVID-19 and multiple sclerosis (MS). 31 P-MRS was performed on a 3 T clinical MRI, in 19 COVID-19 patients, 38 MS patients, and 40 matched healthy controls. Dynamic acquisitions using an MR-compatible ergometer ran over a rest (40 s), exercise (2 min), and a recovery phase (6 min). Long and short TR acquisitions were also made at rest for T1 correction. The advanced data quality control pipeline presented in Part 1 is applied to the selected patient cohorts to investigate its impact on clinical outcomes. We first used power and sample size analysis to estimate objectively the impact of adding the quality control score (QCS). Then, comparisons between patients and healthy control groups using the validated QCS were performed using unpaired t tests or Mann-Whitney tests (p < 0.05). The application of the QCS resulted in increased statistical power, changed the values of several outcome measures, and reduced variability (standard deviation). A significant difference was found between the T1PCr and T1Pi values of MS patients and healthy controls. Furthermore, the use of a fixed correction factor led to systematically higher estimated concentrations of PCr and Pi than when using individually corrected factors. We observed significant differences between the two patient populations and healthy controls for resting [PCr]-MS only, [Pi ], [ADP], [H2 PO4 - ], and pH-COVID-19 only, and post-exercise [PCr], [Pi ], and [H2 PO4 - ]-MS only. The dynamic indicators τPCr , τPi , ViPCr , and Vmax were reduced for COVID-19 and MS patients compared with controls. Our results show that QCS in dynamic 31 P-MRS studies results in smaller data variability and therefore impacts study sample size and power. Although QCS resulted in discarded data and therefore reduced the acceptable data and subject numbers, this rigorous and unbiased approach allowed for proper assessment of muscle metabolites and metabolism in patient populations. The outcomes include an increased metabolite T1 , which directly affects the T1 correction factor applied to the amplitudes of the metabolite, and a prolonged τPCr , indicating reduced muscle oxidative capacity for patients with MS and COVID-19.

Alteration of skeletal muscle energy metabolism assessed by phosphorus-31 magnetic resonance spectroscopy in clinical routine, part 1: Advanced quality control pipeline.

Implementing a standardized phosphorus-31 magnetic resonance spectroscopy (31 P-MRS) dynamic acquisition protocol to evaluate skeletal muscle energy metabolism and monitor muscle fatigability, while being compatible with various longitudinal clinical studies on diversified patient cohorts, requires a high level of technicality and expertise. Furthermore, processing data to obtain reliable results also demands a great degree of expertise from the operator. In this two-part article, we present an advanced quality control approach for data acquired using a dynamic 31 P-MRS protocol. The aim is to provide decision support to the operator to assist in data processing and obtain reliable results based on objective criteria. We present here, in part 1, an advanced data quality control (QC) approach of a dynamic 31 P-MRS protocol. Part 2 is an impact study that will demonstrate the added value of the QC approach to explore data derived from two clinical populations that experience significant fatigue, patients with coronavirus disease 2019 and multiple sclerosis. In part 1, 31 P-MRS was performed using 3-T clinical MRI in 175 subjects from clinical and healthy control populations conducted in a University Hospital. An advanced data QC score (QCS) was developed using multiple objective criteria. The criteria were based on current recommendations from the literature enriched by new proposals based on clinical experience. The QCS was designed to indicate valid and corrupt data and guide necessary objective data editing to extract as much valid physiological data as possible. Dynamic acquisitions using an MR-compatible ergometer ran over a rest (40 s), exercise (2 min), and a recovery phase (6 min). Using QCS enabled rapid identification of subjects with data anomalies, allowing the user to correct the data series or reject them partially or entirely, as well as identify fully valid datasets. Overall, the use of the QCS resulted in the automatic classification of 45% of the subjects, including 58 participants who had data with no criterion violation and 21 participants with violations that resulted in the rejection of all dynamic data. The remaining datasets were inspected manually with guidance, allowing acceptance of full datasets from an additional 80 participants and recovery phase data from an additional 16 subjects. Overall, more anomalies occurred with patient data (35% of datasets) compared with healthy controls (15% of datasets). In conclusion, the QCS ensures a standardized data rejection procedure and rigorous objective analysis of dynamic 31 P-MRS data obtained from patients. This methodology contributes to efforts made to standardize 31 P-MRS practices that have been underway for a decade, with the goal of making it an empowered tool for clinical research.

Technical note: MR-compatible pedal ergometer with electromechanical pedal resistance and exercise triggering enhanced by visual feedback via video display.

During and after exercise, dynamic 31 P MR parameters are typically measured using an MR-compatible ergometer. Self-built equipment for local condition can be constructed where possible. To develop a pedal resistance ergometer with rocker arm based on a system that combines electric weight displacement, visual self-monitoring, and exercise triggering. The repeatability and reproducibility were tested. The hardware and software for the ergometer were constructed from commercial components in a home laboratory. Twelve volunteers participated in the testing of the ergometer. A fully automated ergometer system was developed, allowing the pedal resistance to be adjusted during the examination. The system includes a self-monitoring and triggering mechanism that enables both the operator and subject to monitor pedal frequency and force. The operator can modify the pedal resistance as desired during the exercise. This self-monitoring solution is simple and cost-effective, requiring only a commercial potentiometer, an Arduino converter, and a conventional video projector with a personal computer (PC). Additionally, all system components are located outside the magnetic resonance (MR) room, avoiding interference with the MR system. Results of several test of the reproducibility/repeatability of power at three pedal resistance values (15%, 24%, 25% maximal voluntary force) were expressed both as a coefficient of variation ranging from 6% to 3.1% and as an intraclass correlation of coefficient ranging from 0.96 to 0.99. Similar values were also found for other dynamic parameters of 31 P MR spectroscopy. These findings are similar to published data obtained on different types of ergometers. Based on more than 1 year of usage, the ergometer proved successful in handling stationary and variable loads, and can be easily operated by a single user.

P062 31P MRS and MRI phenotyping of muscle metabolic quality in IBD fatigue

Abstract Background Fatigue perception and exercise intolerance are common in inflammatory bowel disease (IBD). The mechanisms are unknown, although physical deconditioning is greater in fatigued relative to non-fatigued patients, suggesting an aetiological role for deconditioning. To assess peripheral muscle quality in Crohn’s disease (CD), we quantified the time-course of muscle phosphocreatine (PCr) recovery, which is wholly mitochondrial dependent, following ischaemic high-intensity exercise in fatigued CD and HV. Methods Participant body mass and regional body composition was assessed by DEXA. All MR data was collected using a 3T Philips Achieva scanner and a 14cm 31P coil on the medial gastrocnemius muscle. 1H mDIXON scans were acquired to image the calf prior to ischaemic plantar flexion exercise at 50% maximum voluntary contraction (MVC) using an MR-compatible ergometer (Trispect, Ergospect) during non-localized pulse-acquire 31P-MRS. 31P spectra were analysed using jMRUI Beta 6.0 using the AMARES function with prior knowledge. Cytosolic pH was estimated using the chemical shift difference between Pi and PCr peaks. Post exercise PCr recovery was quantified after reinstating limb blood flow. PCr recovery was expressed relative to baseline (non-ischaemic) signal amplitude and fit to a mono-exponential function in GraphPad prism. (PCr(t) = PCrinitial+(PCrend – PCrinitial)(1-exp(-k.t)) where t is the time from the start of non-ischaemic recovery, PCrinitial and PCrend is the PCr signal at the initial and end of recovery phases. An FSL and Matlab pipeline was used to obtain calf muscle volume and fat fraction from 1H mDIXON images. Results 13 quiescent CD patients (7 female, HBI 1±2, CRP &amp;lt;5) and 9 HVs (4 female) were matched for age (P = 0.986) and BMI (P = 0.845). General fatigue score was greater in CD (13 ± 4) relative to HV (8 ± 3) (t19=3.08, P = 0.006) (Table 1.) End-exercise muscle PCr depletion (%) (85.25 ± 10.12 vs 83.28 ± 7.8%, P = 0.639) and estimated end-exercise muscle pH (6.6 ± 0.2 vs 6.5 ± 0.2, P = 0.320) was consistent between HV and CD. The mean rate constant of PCr resynthesis (kPCr min-1) in CD (0.76 ± 0.23) was significantly less (t20 = 2.6, P = 0.016) than HV (1.03 ± 0.23). PCr recovery curves were well described using a mono-exponential function in CD (R2=0.98 ± 0.01, R2value) and HV (R2=0.96 ± 0.03) (Table 3). Conclusion The PCr resynthesis rate following intensity matched ischemic exercise was less in fatigued CD patients relative to HV. This points to peripheral muscle deconditioning and associated loss of mitochondrial mass as a driver of exercise intolerance in IBD. This may be amenable to exercise training intervention.

Hemodynamic and Ventilatory Responses during Exercise in Pediatric Patients with Pulmonary Embolism

Background Pediatric patients with pulmonary embolism (PE) suffer from exercise intolerance and dyspnea on exertion, often without right heart dysfunction or pulmonary hypertension - at least at rest. The pathophysiology of the exercise limitation following pediatric PE therefore remains incompletely understood. Objectives To extend our understanding of exercise intolerance in pediatric patients with PE by examining ventilatory and hemodynamic responses to exercise. Methods To accomplish our goal, we instituted a standardized institutional protocol to systematically assess exercise capacity in pediatric PE patients in the first 3 months following diagnosis. Between February 2019- June 2020, 15 patients underwent resting pulmonary function tests and an incremental symptom-limited cardiopulmonary exercise testing (CPET) to obtain peak exercise in 8-12 minutes. All patients had received anticoagulation for at least 3 months. In all patients, right and left ventricular systolic and/or diastolic dysfunction at rest was ruled out by transthoracic echocardiography. Continuous measurements were made of minute ventilation (VE), oxygen uptake (VO2), carbon dioxide production (VCO2), heart rate (HR), and blood pressure. Predicted values for peak VO2 and work rate were generated from predictive equations. Patients with impaired exercise capacity, defined as &amp;lt;80% of age-, sex- and ideal lean body mass predicted, and dyspnea on exertion underwent further exercise cardiac magnetic resonance (exCMR) imaging using an MR compatible ergometer. Biventricular volumes and contractility, RV longitudinal strain, and RV to pulmonary artery coupling were assessed at rest and with exercise. Results Baseline, clinical characteristics, and CPET data are shown in Tables 1 and 2. Forced Vital Capacity was normal without signs of airway obstruction. Three patients failed to reach their predicted physiologic limits during exercise, and CPET was terminated by the patient prematurely (e.g., muscular exertion, fatigue, &amp; dyspnea, respectively). The mean exercise duration was 9.85 min. The mean ventilatory reserve was within normal limits (&amp;gt;15%) in all but 1 patient. VO2/work rate was normal with normal VO2 at the anaerobic threshold (mean 1541ml/kg/min, SD:731). Exercise capacity, as measured by peak VO2 was reduced, that is, &amp;lt;80% of predicted, in 5 out of the 15 patients (30%). Of these, three patients had echocardiography evidence of RV dysfunction at PE diagnosis, which had resolved at the time of CPET. There were no differences in the mean exercise time and maximal work rate achieved in those with low exercise capacity relative to normal capacity. The ventilatory equivalent for CO2 (VE/VCO2) at peak exercise was elevated (&amp;gt;35) in three of the five patients with decreased exercise capacity. The O2 pulse was attenuated in patients with decreased exercise capacity when compared to those with normal exercise capacity (7.5 mL.beat -1 vs. 12.9-1; p=0.037). Of the two patients who underwent exCMR; one showed reduced right ventricular ejection fraction (38%), abnormal RV strain (-11.3%), elevated right sided pressures signified by interventricular flattening upon inspiration during free breathing scan and an uncoupled RV to the pulmonary circulation. Conclusions Reduced exercise capacity is common after PE and not evident by resting evaluations. Pediatric PE patients with low exercise capacity and dyspnea seem to be characterized by either an abnormal pulmonary vascular response to exercise or decreased ventilatory efficiency. Larger studies are needed to better understand exercise pathophysiology after pediatric PE. Disclosures No relevant conflicts of interest to declare.

Energy Expenditure of Dynamic Submaximal Human Plantarflexion Movements: Model Prediction and Validation by in-vivo Magnetic Resonance Spectroscopy

To understand the organization and efficiency of biological movement, it is important to evaluate the energy requirements on the level of individual muscles. To this end, predicting energy expenditure with musculoskeletal models in forward-dynamic computer simulations is currently the most promising approach. However, it is challenging to validate muscle models in-vivo in humans, because access to the energy expenditure of single muscles is difficult. Previous approaches focused on whole body energy expenditure, e.g., oxygen consumption (VO2), or on thermal measurements of individual muscles by tracking blood flow and heat release (through measurements of the skin temperature). This study proposes to validate models of muscular energy expenditure by using functional phosphorus magnetic resonance spectroscopy (31P-MRS). 31P-MRS allows to measure phosphocreatine (PCr) concentration which changes in relation to energy expenditure. In the first 25 s of an exercise, PCr breakdown rate reflects ATP hydrolysis, and is therefore a direct measure of muscular enthalpy rate. This method was applied to the gastrocnemius medialis muscle of one healthy subject during repetitive dynamic plantarflexion movements at submaximal contraction, i.e., 20% of the maximum plantarflexion force using a MR compatible ergometer. Furthermore, muscle activity was measured by surface electromyography (EMG). A model (provided as open source) that combines previous models for muscle contraction dynamics and energy expenditure was used to reproduce the experiment in simulation. All parameters (e.g., muscle length and volume, pennation angle) in the model were determined from magnetic resonance imaging or literature (e.g., fiber composition), leaving no free parameters to fit the experimental data. Model prediction and experimental data on the energy supply rates are in good agreement with the validation phase (<25 s) of the dynamic movements. After 25 s, the experimental data differs from the model prediction as the change in PCr does not reflect all metabolic contributions to the energy expenditure anymore and therefore underestimates the energy consumption. This shows that this new approach allows to validate models of muscular energy expenditure in dynamic movements in vivo.

Magnetic Resonance Compatible Knee Extension Ergometer.

A magnetic resonance (MR) compatible ergometer has been developed to study contracting lower limb muscles during acquisition of MR spectroscopy data, a technique to noninvasively measure metabolic energy in muscle tissue. Current active and passive MR-compatible ergometer designs lack torque or velocity control to allow precise mechanical measurements during isotonic and isokinetic contractions; incorporating load and velocity controllers while maintaining MR-compatibility is the main challenge. Presented in this paper is the design and evaluation of an MR-compatible ergometer designed to control knee torque or velocity up to 420 N·m and 270 deg/s and is able to operate in a 3 Tesla magnetic field. The ergometer comprising of a passive component with no electronics or ferrous materials is located inside the bore of the scanner. The active component with the electronics and actuator located outside of the magnetic field in an adjacent room. The active components connect to the passive components via a cable that passes through the waveguide, a hole in the wall of the scanner room. System evaluations were performed and human subject evaluations were performed that measured the mechanical performance and show the mean percent errors below 9% in isotonic and 2% in isokinetic conditions.

Diffusion‐weighted MRI with intravoxel incoherent motion modeling for assessment of muscle perfusion in the thigh during post‐exercise hyperemia in younger and older adults

Aging is associated with impaired endothelium-dependent vasodilation that leads to muscle perfusion impairment and contributes to organ dysfunction. Impaired muscle perfusion may result in inadequate delivery of oxygen and nutrients during and after muscle contraction, leading to muscle damage. The ability to study the relationship between perfusion and muscle damage has been limited using traditional muscle perfusion measures, which are invasive and risky. To overcome this limitation, we optimized a diffusion-weighted MRI sequence and validated an intravoxel incoherent motion (IVIM) analysis based on Monte Carlo simulation to study muscle perfusion impairment with aging during post-exercise hyperemia. Simulation results demonstrated that the bias of IVIM-derived perfusion fraction (fp ) and diffusion of water molecules in extra-vascular tissue (D) ranged from -3.3% to 14% and from -16.5% to 0.002%, respectively, in the optimized experimental condition. The dispersion in fp and D ranged from 3.2% to 9.5% and from 0.9% to 1.1%, respectively. The mid-thigh of the left leg of four younger (21-30year old) and four older (60-90year old) healthy females was studied using the optimized protocol at baseline and at seven time increments occurring every 3.25min following in-magnet dynamic knee extension exercise performed using a MR-compatible ergometer with a workload of 0.4bar for 2.5min. After exercise, both fp and D significantly increased in the rectus femoris (active muscle during exercise) but not in adductor magnus (inactive muscle), reflecting the fact that the local increase in perfusion with both groups showed a maximum value in the second post-exercise time-point. A significantly greater increase in perfusion from the baseline (p<0.05) was observed in the younger group (37±12.05%) compared with the older group (17.57±15.92%) at the first post-exercise measurement. This work establishes a reliable non-invasive method that can be used to study the effects of aging on dynamic changes in muscle perfusion as they relate to important measures of physical function.

Spatially resolved kinetics of skeletal muscle exercise response and recovery with multiple echo diffusion tensor imaging (MEDITI): a feasibility study.

We describe measurement of skeletal muscle kinetics with multiple echo diffusion tensor imaging (MEDITI). This approach allows characterization of the microstructural dynamics in healthy and pathologic muscle. In a Siemens 3-T Skyra scanner, MEDITI was used to collect dynamic DTI with a combination of rapid diffusion encoding, radial imaging, and compressed sensing reconstruction in a multi-compartment agarose gel rotation phantom and within in vivo calf muscle. An MR-compatible ergometer (Ergospect Trispect) was employed to enable in-scanner plantar flexion exercise. In a HIPAA-compliant study with written informed consent, post-exercise recovery of DTI metrics was quantified in eight volunteers. Exercise response of DTI metrics was compared with that of T2-weighted imaging and characterized by a gamma variate model. Phantom results show quantification of diffusivities in each compartment over its full dynamic rotation. In vivo calf imaging results indicate larger radial than axial exercise response and recovery in the plantar flexion-challenged gastrocnemius medialis (fractional response: nT2w = 0.385 ± 0.244, nMD = 0.163 ± 0.130, nλ1 = 0.110 ± 0.093, nλrad = 0.303 ± 0.185). Diffusion and T2-weighted response magnitudes were correlated (e.g., r = 0.792, p = 0.019 for nMD vs. nT2w). We have demonstrated the feasibility of MEDITI for capturing spatially resolved diffusion tensor data in dynamic systems including post-exercise skeletal muscle recovery following in-scanner plantar flexion.

A low-cost Mr compatible ergometer to assess post-exercise phosphocreatine recovery kinetics

To develop a low-cost pedal ergometer compatible with ultrahigh (7 T) field MR systems to reliably quantify metabolic parameters in human lower leg muscle using phosphorus magnetic resonance spectroscopy. We constructed an MR compatible ergometer using commercially available materials and elastic bands that provide resistance to movement. We recruited ten healthy subjects (eight men and two women, mean age±standard deviation: 32.8±6.0years, BMI: 24.1±3.9kg/m2). All subjects were scanned on a 7 T whole-body magnet. Each subject was scanned on two visits and performed a 90s plantar flexion exercise at 40% maximum voluntary contraction during each scan. During the first visit, each subject performed the exercise twice in order for us to estimate the intra-exam repeatability, and once during the second visit in order to estimate the inter-exam repeatability of the time constant of phosphocreatine recovery kinetics. We assessed the intra and inter-exam reliability in terms of the within-subject coefficient of variation (CV). We acquired reliable measurements of PCr recovery kinetics with an intra- and inter-exam CV of 7.9% and 5.7%, respectively. We constructed a low-cost pedal ergometer compatible with ultrahigh (7 T) field MR systems, which allowed us to quantify reliably PCr recovery kinetics in lower leg muscle using 31P-MRS.

134 MR Augmented Cardiopulmonary Exercise Testing – a Novel Way of Assessing Cardiovascular Function

Introduction Reduced exercise capacity is a common feature of many cardiovascular diseases. Quantitative assessment of exercise capacity is usually achieved by measuring peak oxygen consumption (VO2). However, measuring peak VO2 alone neglects the different components of reduced exercise capacity: namely reduced cardiac output (CO) and oxygen extraction (ΔcO2). A better approach would be to simultaneously measure VO2 and CO and then calculate ΔcO2. This could be achieved using MR augmented cardiopulmonary exercise testing (MR-CPET). The aims of this study were to demonstrate: 1) MR-CPET is feasible and well tolerated, 2) peak VO2 in the MR scanner correlates with conventional peak VO2 and 3) variation in peak VO2 is related to both peak CO and peak oxygen extraction (ΔcO2) as calculated by the Fick equation. Method 17 healthy volunteers (21–55 years) underwent MR-CPET. Exercise was performed on an MR-compatible ergometer (Lode, Groningen, The Netherlands) and VO2 was assessed using a commercial respiratory gas analyser (Ultima, MedGraphics, St. Paul, USA) with a modified sampling tube that was MR compatible. Set-up for MR-CPET is shown in [Figure 1][1]. Aortic flow was continuously measured using a previously validated UNFOLD-SENSE spiral PCMR sequence. Images were reconstructed using a graphical processing unit card and analysed using an in-house plug-in for OsiriX software. Conventional CPET was also performed within 2 weeks of MR-CPET. For both tests, participants were asked to rate i) concern ii) comfort and iii) perceived helplessness. ![Abstract 134 Figure 1][2] Abstract 134 Figure 1 Set-up for MR-CPET: a) subject in exercise position on MR compatible ergometer b) subject with facemask attached to MR compatible umbilicus passing through the wave-guide Results 15 out of 17 volunteers completed exercise; exclusions were due to claustrophobia (n = 1) and inability to master exercise technique (n = 1). Reported concern and discomfort was higher with MR-CPET, although still within acceptable limits. Peak VO2, peak VCO2 and VE showed strong correlation between conventional CPET and MR-CPET: VO2 peak (r = 0.94, p < 0.001); VCO2 (r = 0.87, p < 0.001); VE (r = 0.88, p < 0.001). Resting and peak values VO2, CO, HR, SV and ΔcO2 are shown in [Table 1][3]. Multiple linear regression analysis demonstrated that both peak CO and ΔcO2 were independent predictors of peak VO2 measured during MR-CPET (beta = 0.73 and 0.38 respectively, p < 0.001) and conventional CPET (beta = 0.78 and 0.28 respectively, p < 0.001). ![Abstract 134 Table 1][2] Abstract 134 Table 1 Values at rest and Peak VO2 obtained at MR-CPET Conclusion MR-CPET is feasible, well tolerated and demonstrates physiology not apparent with conventional CPET. In this study, we have shown that MR-CPET allows assessment of the differing contributions of CO and ΔcO2 to variation in peak VO2. We believe that will be useful in understanding the origin of reduced exercise capacity in cardiac disease. [1]: #F1 [2]: pending:yes [3]: #F2

Efficiency of energy transfer during exercise: what are the limiting factors?

Efficiency of energy transfer during exercise: what are the limiting factors?

MR augmented cardiopulmonary exercise testing—a novel approach to assessing cardiovascular function

The purposes of this study were: (1) to evaluate feasibility and acceptability of MRI augmented cardiopulmonary exercise testing (MR-CPET) in healthy adults and (2) to test whether peak values obtained at conventional and MR-CPET correlate and to demonstrate variation in peak oxygen consumption (VO2) relates to both peak cardiac output (CO) and peak oxygen extraction (ΔcO2). Seventeen healthy adults underwent CPET and MR-CPET using an MR compatible ergometer and CPET system customised for MR use. Continuous aortic flow measurement used a validated UNFOLD-SENSE spiral phase contrast magnetic resonance (PCMR) sequence.Fifteen of 17 volunteers completed exercise; exclusions were due to claustrophobia and inability to effectively master exercise technique. Measures of acceptability were lower but still satisfactory for MR-CPET.There were strong correlations between conventional and MR-CPET for peak VO2 (r = 0.94, p < 0.001); VCO2 (r = 0.87, p < 0.001) and VE (r = 0.88, p < 0.001).Multiple linear regression analysis demonstrated peak CO and ΔcO2 were independent predictors of peak VO2 measured during MR-CPET (β = 0.73 and 0.38 p < 0.0001) and conventional CPET (β = 0.78, 0.28 p < 0.0001).MR-CPET is feasible, acceptable and demonstrates physiology not apparent with conventional CPET. MR-CPET allows differentiation of the contributions of CO and ΔcO2 to variation in peak VO2. We believe that this will be useful in understanding the origin of reduced exercise capacity in cardiac disease.

MRI assessment of aortic flow and pulse wave velocity in response to exercise

Background The effect of exercise on cardiac function is important in the diagnosis of cardiovascular disease [1], yet is clinically not available with MRI. Instead, pharmacological agents are used, which have several disadvantages [2]. Recent work has addressed this shortcoming with an MR compatible ergometer next to the magnet [3], albeit with an unavoidable time delay between exercising and actual scanning, which can reduce the measured effect. In this pilot study, we investigated flow and area changes in the aorta with customized exercise equipment that functions in the bore.

AB1170 Clinical whole-body exercise testing in a magnetic resonance scanner: A feasibility study in children with chronic inflammatory myopathy

BackgroundExercise is increasingly utilized as a non-pharmacological intervention in the clinical management of patients with chronic inflammatory conditions. Availability of more objective microscopic outcome measures that provide functional information at...

Towards a more comprehensive assessment of cardiovascular fitness - magnetic resonance augmented cardiopulmonary exercise testing (MR-CPEX)

Background Assessment of exercise intolerance is important in patients with cardiovascular disease. Traditionally, this is achieved by measuring maximum VO2 during cardiopulmonary exercise testing (CPEX). However, this cannot discriminate between cardiac output and tissue extraction problems. A better approach may be to assess VO2 and cardiac output simultaneously (which also allows calculation of tissue extraction). Thus, we developed MR augmented CPEX in which real- time PCMR is performed at the same time as respiratory gas analysis. The purpose of this study was to validate this novel technology. Methods Ten volunteers underwent MR-CPEX in a 1.5T scanner using a ramped protocol on an MR compatible Ergometer. All volunteers exercised till exhaustion and the total test period was 9 minutes. Expired gases and respiratory flow data were collected with a calibrated MR compatible respiratory analysis system. Using this data continuous VO2, VCO2 and Ve were calculated for the whole test period. Aortic flow was measured continuously during the test period using real-time UNFOLD-SENSE spiral PCMR (spatial resolution: 2.5x2.5 mm, temporal resolution: 30 ms, 16000 frames). Flow data was segmented using a semi-automated technique to calculate cardiac output during exercise. Cardiac output and VO2 were used to calculate arterio-venous oxygen content gradient (tissue oxygen extraction). All volunteers also underwent traditional bicycle CPEX for comparison. Results MR augmented CPEX was successful in all volunteers with 40% of participants reaching their anaerobic threshold. The maximum workload reached during MR and conventional CPEX was strongly correlated. (r=0.76). Mean peak VO2 during MR-CPEX was 19.3±5.1ml/min/kg and peak VCO2 was 19.6±5.5ml /min/kg. There was an excellent correlation between MR-CPEX peak VO2 and conventional CPEX (r=0.84). During MR-CPEX, mean heart rate rose from 76±14 to 151±25 bpm, with no change in stroke volume. This resulted in mean cardiac output increasing from 3.2±0.5 l/min/m2 to 6.6±1.2 l/min/m2. Mean peak arterio-venous oxygen gradient calculated from the cardiac output and VO2 during MR-CPEX was 12ml O2 per 100ml of blood. Representative ventilation, cardiac output and tissue arterio-venous oxygen gradient curves are shown in figures 1 &2. Conclusions

An MR‐compatible bicycle ergometer for in‐magnet whole‐body human exercise testing

An MR-compatible ergometer was developed for in-magnet whole-body human exercise testing. Designed on the basis of conventional mechanically braked bicycle ergometers and constructed from nonferrous materials, the ergometer was implemented on a 1.5-T whole-body MR scanner. A spectrometer interface was constructed using standard scanner hardware, complemented with custom-built parts and software to enable gated data acquisition during exercise. High-quality 31P NMR spectra were reproducibly obtained from the medial head of the quadriceps muscle of the right leg of eight healthy subjects during two-legged high-frequency pedaling (80 revolutions per minute) at three incremental workloads, including maximal. Muscle phosphocreatine content dropped 82%, from 32.2+/-1.0 mM at rest to 5.7+/-1.1 mM at maximal workload (mean+/-standard error; n=8), indicating that the majority of quadriceps motor units were recruited. The cardiovascular load of the exercise was likewise significant, as evidenced by heart rates of 150 (+/-10%) beats per minute, measured immediately afterward. As such, the newly developed MR bicycling exercise equipment offers a powerful new tool for clinical musculoskeletal and cardiovascular MR investigation. The basic design of the ergometer is highly generic and adaptable for application on a wide selection of whole-body MR scanners.

Calf muscle perfusion at peak exercise in peripheral arterial disease: Measurement by first‐pass contrast‐enhanced magnetic resonance imaging

To develop a contrast-enhanced magnetic resonance (MR) technique to measure skeletal muscle perfusion in peripheral arterial disease (PAD). A total of 11 patients (age = 61 +/- 11 years) with mild to moderate symptomatic PAD (ankle-brachial index [ABI] = 0.75 +/- 0.08) and 22 normals were studied using an MR-compatible ergometer. PAD and normal(max) (Nl(max); N = 11) exercised to exhaustion. Nl(low) (N = 11) exercised to the same workload achieved by PAD. At peak exercise, 0.1 mm/kg of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) was infused at 3-4 cm(3)/second followed by a saline flush at the same rate. A dual-contrast gradient echo (GRE) sequence enabled simultaneous acquisition of muscle perfusion and arterial input function (AIF). The perfusion index (PI) was defined as the slope of the time-intensity curve (TIC) in muscle divided by the arterial TIC slope. Median workload was 120 Joules in PAD, 210 Joules in Nl(low), and 698 Joules in Nl(max) (P < 0.001 vs. Nl(low) and PAD). Median PI was 0.29 in PAD (25th and 75th percentiles [%] = 0.20, 0.40), 0.48 in Nl(low) (25th, 75th % = 0.36, 0.62; P < 0.02 vs. PAD), and 0.69 in Nl(max) (25th, 75th % = 0.5, 0.77; P < 0.001 vs. PAD). Area under the ROC-curve for PI differentiating patients from Nl(max) was 0.95 (95% confidence interval [CI] = 0.77-0.99). Peak-exercise measurement of lower limb perfusion with dual-contrast, first-pass MR distinguishes PAD from normals. This method may be useful in the study of novel therapies for PAD.