Grzegorz T Kowalik

Adiposity Is Associated with Blunted Cardiovascular, Neuroendocrine and Cognitive Responses to Acute Mental Stress

Obesity and mental stress are potent risk factors for cardiovascular disease but their relationship with each other is unclear. Resilience to stress may differ according to adiposity. Early studies that addressed this are difficult to interpret due to conflicting findings and limited methods. Recent advances in assessment of cardiovascular stress responses and of fat distribution allow accurate assessment of associations between adiposity and stress responsiveness. We measured responses to the Montreal Imaging Stress Task in healthy men (N = 43) and women (N = 45) with a wide range of BMIs. Heart rate (HR) and blood pressure (BP) measures were used with novel magnetic resonance measures of stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and arterial compliance to assess cardiovascular responses. Salivary cortisol and the number and speed of answers to mathematics problems in the task were used to assess neuroendocrine and cognitive responses, respectively. Visceral and subcutaneous fat was measured using T2 *-IDEAL. Greater BMI was associated with generalised blunting of cardiovascular (HR:β = −0.50 bpm.unit−1, P = 0.009; SV:β = −0.33 mL.unit−1, P = 0.01; CO:β = −61 mL.min−1.unit−1, P = 0.002; systolic BP:β = −0.41 mmHg.unit−1, P = 0.01; TPR:β = 0.11 WU.unit−1, P = 0.02), cognitive (correct answers: r = −0.28, P = 0.01; time to answer: r = 0.26, P = 0.02) and endocrine responses (cortisol: r = −0.25, P = 0.04) to stress. These associations were largely determined by visceral adiposity except for those related to cognitive performance, which were determined by both visceral and subcutaneous adiposity. Our findings suggest that adiposity is associated with centrally reduced stress responsiveness. Although this may mitigate some long-term health risks of stress responsiveness, reduced performance under stress may be a more immediate negative consequence.

Habitual alcohol consumption is associated with lower cardiovascular stress responses – a novel explanation for the known cardiovascular benefits of alcohol?

Abstract In contrast to heavy alcohol consumption, which is harmful, light to moderate drinking has been linked to reduced cardiovascular morbidity and mortality. Effects on lipid status or clotting do not fully explain these benefits. Exaggerated cardiovascular responses to mental stress are detrimental to cardiovascular health. We hypothesized that habitual alcohol consumption might reduce these responses, with potential benefits. Advanced magnetic resonance techniques were used to accurately measure cardiovascular responses to an acute mental stressor (Montreal Imaging Stress Task) in 88 healthy adults (∼1:1 male:female). Salivary cortisol and task performance measures were used to assess endocrine and cognitive responses. Habitual alcohol consumption and confounding factors were assessed by questionnaire. Alcohol consumption was inversely related to responses of heart rate (HR) (r = −0.31, p = 0.01), cardiac output (CO) (r = −0.32, p = 0.01), vascular resistance (r = 0.25, p = 0.04) and mean blood pressure (r = −0.31, p = 0.01) provoked by stress, but not to stroke volume (SV), or arterial compliance changes. However, high alcohol consumers had greater cortisol stress responses, compared to moderate consumers (3.5 versus 0.7 nmol/L, p = 0.04). Cognitive measures did not differ. Findings were not explained by variations in age, sex, social class, ethnicity, physical activity, adrenocortical activity, adiposity, smoking, menstrual phase and chronic stress. Habitual alcohol consumption is associated with reduced cardiac responsiveness during mental stress, which has been linked to lower risk of hypertension and vascular disease. Consistent with established evidence, our findings suggest a mechanism by which moderate alcohol consumption might reduce cardiovascular disease, but not high consumption, where effects such as greater cortisol stress responses may negate any benefits.

Assessment of cardiac time intervals using high temporal resolution real‐time spiral phase contrast with UNFOLDed‐SENSE

To develop a real‐time phase contrast MR sequence with high enough temporal resolution to assess cardiac time intervals.

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

Physiological adaptations to chronic stress in healthy humans – why might the sexes have evolved different energy utilisation strategies?

The human stress response activates the autonomic nervous system and endocrine systems to increase performance during environmental challenges. This response is usually beneficial, improving the chance of overcoming environmental challenges, but costs resources such as energy. Humans and other animals are known to adapt their responses to acute stress when they are stimulated chronically, presumably to optimise resource utilisation. Characterisation of these adaptations has been limited. Using advanced imaging techniques, we show that cardiovascular and endocrine physiology, reflective of energy utilisation during acute stress, and energy storage (fat) differ between the sexes when they are exposed to chronic stress. We examine possible evolutionary explanations for these differences, related to energy use, and point out how these physiological differences could underpin known disparities between the sexes in their risk of important cardiometabolic disorders such as obesity and cardiovascular disease.

Implementation of a generalized heterogeneous image reconstruction system for clinical magnetic resonance

This paper describes the development of a novel online, heterogeneous image reconstruction system for magnetic resonance data. The system integrates an external computer equipped with a graphic processing unit card into the magnetic resonance scanners image reconstruction pipeline. The system promotes fast online reconstruction for computationally intensive algorithms making them feasible in a busy clinical service. Analysis and improvement of execution time of the complex, iterative reconstruction algorithm is presented. Specifically, optimizations were examined that allowed fast reconstruction of data that were acquired in an arbitrary manner. The system was successfully used in research and clinical studies requiring high data throughput. Copyright

Tissue phase mapping using breath-hold 4D PCMR

Methods An undersampled, prospectively triggered, stack-of-spirals, 4D PCMR sequence was developed, and reconstructed using SENSE-UNFOLD. A uniform-density spiral trajectory was used in kx-ky with 8 interleaves required to fill k-space, with acceleration of R = 4 (resulting in 2 spiral interleaves acquired per kz position). In kz, 16 slices were used, with acceleration of R = 2, resulting in 9 kz positions being acquired for each cardiac phase (calculated as 16÷2 plus one to ensure that the middle kz position is always acquired). The other sequence parameters were; TE/TR:4.0/14.4 ms, matrix size:160 × 160, FOV:500 × 500 mm, slices:16, slice thickness:8 mm, venc(x/y/z):30/30/ 30 cm/s. This resulted in a temporal resolution of 57.5 ms,

Golden ratio stack of spirals for flexible angiographic imaging: Proof of concept in congenital heart disease

In this study, a golden ratio stack of spiral (GRASS) sequence that used both golden step and golden angle ordering was implemented. The aim was to demonstrate that GRASS acquisitions could be flexibly reconstructed as both cardiac‐gated and time‐resolved angiograms.

MR-Augmented Cardiopulmonary Exercise Testing- a proof of concept in Sickle Cell Disease (SCD)

Background Exercise intolerance is a common feature of many noncardiac and non-respiratory diseases. The causes are often multifactorial and include secondary cardiac-respiratory dysfunction, as well as skeletal muscle abnormalities. Unfortunately, it is difficult to determine the exact cause using conventional cardiopulmonary exercise testing (CPET). Therefore, we have developed MR augmented CPET that allows simultaneous evaluation of cardiac output and tissue oxygen extraction in addition to conventional CPET measures. To demonstrate the utility of this technique we performed MR-CPET on patients with sickle cell disease (SCD). The aim of this study was to demonstrate that MR-CPET could be used to define the physiological factors associated with their poorly understood exercise intolerance.

MR augmented cardiopulmonary exercise testing - a novel method of assessing cardiovascular function

Background 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 cardio-pulmonary exercise testing (MR-CPET) The aims of this study were to demonstrate: 1) MRCPET 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.