Quantification of aortic stenosis diagnostic parameters: comparison of fast 3 direction and 1 direction phase contrast CMR and transthoracic echocardiography.

BACKGROUND: Aortic stenosis (AS) is a common valvular disorder, and disease severity is currently assessed by transthoracic echocardiography (TTE). However, TTE results can be inconsistent in some patients, thus other diagnostic modalities such as cardiovascular magnetic resonance (CMR) are demanded. While traditional unidirectional phase-contrast CMR (1Dir PC-CMR) underestimates velocity if the imaging plane is misaligned to the flow direction, multi-directional acquisitions are expected to improve velocity measurement accuracy. Nonetheless, clinical use of multidirectional techniques has been hindered by long acquisition times. Our goal was to quantify flow parameters in patients using 1Dir PC-CMR and a faster multi-directional technique (3Dir PC-CMR), and compare to TTE. METHODS: Twenty-three patients were prospectively assessed with TTE and CMR. Slices above the aortic valve were acquired for both PC-CMR techniques and cine SSFP images were acquired to quantify left ventricular stroke volume. 3Dir PC-CMR implementation included a variable density sampling pattern with acceleration rate of 8 and a reconstruction method called ReVEAL, to significantly accelerate acquisition. 3Dir PC-CMR reconstruction was performed offline and ReVEAL-based image recovery was performed on the three (x, y, z) encoding pairs. 1Dir PC-CMR was acquired with GRAPPA acceleration rate of 2 and reconstructed online. CMR derived flow parameters and aortic valve area estimates were compared to TTE. RESULTS: ReVEAL based 3Dir PC-CMR derived parameters correlated better with TTE than 1Dir PC-CMR. Correlations ranged from 0.61 to 0.81 between TTE and 1Dir PC-CMR and from 0.61 to 0.87 between TTE and 3Dir-PC-CMR. The correlation coefficients between TTE, 1Dir and 3Dir PC-CMR Vpeakwere 0.81 and 0.87, respectively. In comparison to ReVEAL, TTE slightly underestimates peak velocities, which is not surprising as TTE is only sensitive to flow that is parallel to the acoustic beam. CONCLUSIONS: By exploiting structure unique to PC-CMR, ReVEAL enables multi-directional flow imaging in clinically feasible acquisition times. Results support the hypothesis that ReVEAL-based 3Dir PC-CMR provides better estimation of hemodynamic parameters in AS patients in comparison to 1Dir PC-CMR. While TTE can accurately measure velocity parallel to the acoustic beam, it is not sensitive to the other directions of flow. Therefore, multi-directional flow imaging, which encodes all three components of the velocity vector, can potentially outperform TTE in patients with eccentric or multiple jets.

Rapid assessment of quantitative T1, T2 and T2* in lower extremity muscles in response to maximal treadmill exercise.

MRI provides a non-invasive diagnostic platform to quantify the physical and physiological attributes of skeletal muscle at rest and in response to exercise. MR relaxation parameters (T1, T2 and T2*) are characteristic of tissue composition and metabolic properties. With the recent advent of quantitative techniques that allow rapid acquisition of T1, T2 and T2* maps, we posited that an integrated treadmill exercise-quantitative relaxometry paradigm can rapidly characterize exercise-induced changes in skeletal muscle relaxation parameters. Accordingly, we investigated the rest/recovery kinetics of T1, T2 and T2* in response to treadmill exercise in the anterior tibialis, soleus and gastrocnemius muscles of healthy volunteers, and the relationship of these parameters to age and gender. Thirty healthy volunteers (50.3 ± 16.6 years) performed the Bruce treadmill exercise protocol to maximal exhaustion. Relaxometric maps were sequentially acquired at baseline and for approximately 44 minutes post-exercise. Our results show that T1, T2 and T2* are significantly and differentially increased immediately post-exercise among the leg muscle groups, and these values recover to near baseline within 30-44 minutes. Our results demonstrate the potential to characterize the kinetics of relaxation parameters with quantitative mapping and upright exercise, providing normative values and some clarity on the impact of age and gender.

Comparison of treadmill exercise stress cardiac MRI to stress echocardiography in healthy volunteers for adequacy of left ventricular endocardial wall visualization: A pilot study.

PURPOSE: To compare exercise stress cardiac magnetic resonance (cardiac MR) to echocardiography in healthy volunteers with respect to adequacy of endocardial visualization and confidence of stress study interpretation. MATERIALS AND METHODS: Twenty-eight healthy volunteers (age 28 ± 11 years, 15 males) underwent exercise stress echo and cardiac MR one week apart assigned randomly to one test first. Stress cardiac MR was performed using an MRI-compatible treadmill; stress echo was performed as per routine protocol. Cardiac MR and echo images were independently reviewed and scored for adequacy of endocardial visualization and confidence in interpretation of the stress study. RESULTS: Heart rate at the time of imaging was similar between the studies. Average time from cessation of exercise to start of imaging (21 vs. 31 s, P < 0.001) and time to acquire stress images (20 vs. 51 s, P < 0.001) was shorter for cardiac MR. The number of myocardial segments adequately visualized was significantly higher by cardiac MR at rest (99.8% vs. 96.4%, P = 0.002) and stress (99.8% vs. 94.1%, P = 0.001). The proportion of subjects in whom there was high confidence in the interpretation was higher for cardiac MR than echo (96% vs. 60%, P = 0.005). CONCLUSION: Exercise stress cardiac MR to assess peak exercise wall motion is feasible and can be performed at least as rapidly as stress echo.

Comparison of Ketogenic Diets with and without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in Overweight Adults.

Ketogenic diets (KDs) often contain high levels of saturated fat, which may increase liver fat, but the lower carbohydrate intake may have the opposite effect. Using a controlled feeding design, we compared liver fat responses to a hypocaloric KD with a placebo (PL) versus an energy-matched low-fat diet (LFD) in overweight adults. We also examined the added effect of a ketone supplement (KS). Overweight adults were randomized to a 6-week KD (KD + PL) or a KD with KS (KD + KS); an LFD group was recruited separately. All diets were estimated to provide 75% of energy expenditure. Weight loss was similar between groups (p > 0.05). Liver fat assessed by magnetic resonance imaging decreased after 6 week (p = 0.004) with no group differences (p > 0.05). A subset with nonalcoholic fatty liver disease (NAFLD) (liver fat > 5%, n = 12) showed a greater reduction in liver fat, but no group differences. In KD participants with NAFLD, 92% of the variability in change in liver fat was explained by baseline liver fat (p < 0.001). A short-term hypocaloric KD high in saturated fat does not adversely impact liver health and is not impacted by exogenous ketones. Hypocaloric low-fat and KDs can both be used in the short-term to significantly reduce liver fat in individuals with NAFLD.

The Effects of a 6-Week Controlled, Hypocaloric Ketogenic Diet, With and Without Exogenous Ketone Salts, on Body Composition Responses.

Background: Ketogenic diets (KDs) that elevate beta-hydroxybutyrate (BHB) promote weight and fat loss. Exogenous ketones, such as ketone salts (KS), also elevate BHB concentrations with the potential to protect against muscle loss during caloric restriction. Whether augmenting ketosis with KS impacts body composition responses to a well-formulated KD remains unknown. Purpose: To explore the effects of energy-matched, hypocaloric KD feeding (<50 g carbohydrates/day; 1.5 g/kg/day protein), with and without the inclusion of KS, on weight loss and body composition responses. Methods: Overweight and obese adults were provided a precisely defined hypocaloric KD (~75% of energy expenditure) for 6 weeks. In a double-blind manner, subjects were randomly assigned to receive ~24 g/day of a racemic BHB-salt (KD + KS; n = 12) or placebo (KD + PL; n = 13). A matched comparison group (n = 12) was separately assigned to an isoenergetic/isonitrogenous low-fat diet (LFD). Body composition parameters were assessed by dual x-ray absorptiometry and magnetic resonance imaging. Results: The KD induced nutritional ketosis (>1.0 mM capillary BHB) throughout the study (p < 0.001), with higher fasting concentrations observed in KD + KS than KD + PL for the first 2 weeks (p < 0.05). There were decreases in body mass, whole body fat and lean mass, mid-thigh muscle cross-sectional area, and both visceral and subcutaneous adipose tissues (p < 0.001), but no group differences between the two KDs or with the LFD. Urine nitrogen excretion was significantly higher in KD + PL than LFD (p < 0.01) and trended higher in KD + PL compared to KD + KS (p = 0.076), whereas the nitrogen excretion during KD + KS was similar to LFD (p > 0.05). Conclusion: Energy-matched hypocaloric ketogenic diets favorably affected body composition but were not further impacted by administration of an exogenous BHB-salt that augmented ketosis. The trend for less nitrogen loss with the BHB-salt, if manifested over a longer period of time, may contribute to preserved lean mass.

Mitral annular velocity measurement with cardiac magnetic resonance imaging using a novel annular tracking algorithm: Validation against echocardiography.

BACKGROUND: Doppler based mitral annular velocities are an integral part of echocardiographic left ventricular diastolic function assessment. Although these measurements can be obtained by phase contrast cardiac magnetic resonance imaging (PC-CMR), this approach has limitations. The aims of this study were to assess the accuracy and reproducibility of a high temporal resolution steady-state free precession (SSFP) cine acquisition coupled with semi-automated mitral annular tracking to measure tissue velocity, and compare to echocardiography as the reference method. METHODS: High temporal resolution (17 ms) 4-chamber cines were acquired in 25 volunteers using retrospective and prospective gating on a 3.0 T magnet. Mitral annular early (e') and late (a') tissue velocities were derived using a novel algorithm to semi-automatically detect the mitral valve insertion points and track its motion. Additionally, PC-CMR was used to measure mitral inflow early diastolic (E) velocity. Those measurements were also obtained using echocardiography based pulsed and tissue Doppler techniques, on the same day. RESULTS: Subjects were on average 34 ±â€¯14 years-old (48% male). The lateral annulus e' measurements had the best agreement with echocardiography with a concordance correlation coefficient (CCC) of 0.76 and 0.75 for prospectively and retrospectively gated cine CMR respectively. There was no significant difference in the lateral annular tissue velocities between echocardiography (13.8 ±â€¯3.7 cm/s) and prospective (13.4 ±â€¯3.7 cm/s) or retrospective (14.0 ±â€¯3.7) acquisitions. Similarly, CMR measurement of E/e' (a surrogate marker for LV filling pressures) using the lateral e' velocity showed moderate agreement with echocardiography (CCC of 0.56 and 0.51 for prospective and retrospective acquisitions respectively) without a significant difference in ratios (5.3 ±â€¯1.6 and 5.0 ±â€¯1.3) compared to echocardiography (5.2 ±â€¯1.4). Intra- and inter-observer reproducibility of the CMR-based annular velocity measurements was good. CONCLUSION: Measurements of mitral annular tissue velocities can be obtained from SSFP 4-chamber cine images using a semi-automated annular tracking algorithm, and demonstrates moderate agreement with echocardiography. The semi-automated method can provide quantitative mitral annular velocity measurements directly from conventional cine images, thereby providing additional clinically relevant information. The accuracy of this method in patients with diastolic dysfunction remains to be determined.

Quantification of Human Central Adipose Tissue Depots: An Anatomically Matched Comparison Between DXA and MRI.

Excess visceral adipose tissue (VAT) and VAT volume relative to subcutaneous adipose tissue (SAT) are associated with elevated health risks. This study compares fat measurements by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). In total, 21 control subjects (Control) and 16 individuals with metabolic syndrome (MetSyn) were scanned by DXA and MRI. The region measured by MRI was matched to the android region defined by DXA, and MRI reproducibility was also evaluated. In addition, liver fat fraction was quantified via MRI and whole-body fat by DXA. VAT measurements are interchangeable between DXA and MRI in the Control (R = 0.946), MetSyn (R = 0.968), and combined cohort (R = 0.983). VAT/SAT ratio did not differ in the Control group (P = .10), but VAT/SAT ratio measured by DXA was significantly higher in the MetSyn group (P < .01) and the combined (P = .03) cohort. Intraobserver (ICC = 0.998) and interobserver (ICC = 0.977) reproducibility of MRI VAT measurements was excellent. Liver fat fraction by MRI was higher (P = .001) in MetSyn (12.4% ± 7.6%) than in controls (2.6% ± 2.2%), as was whole-body fat percentage by DXA (P = .001) between the MetSyn (42.0% ± 8.1%) and Control groups (26.7% ± 6.9%). DXA and MRI VAT are interchangeable when measured over an anatomically matched region of the abdomen, while SAT and VAT/SAT ratio differ between the 2 modalities.

Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss.

BACKGROUNDMetabolic syndrome (MetS) is highly correlated with obesity and cardiovascular risk, but the importance of dietary carbohydrate independent of weight loss in MetS treatment remains controversial. Here, we test the theory that dietary carbohydrate intolerance (i.e., the inability to process carbohydrate in a healthy manner) rather than obesity per se is a fundamental feature of MetS.METHODSIndividuals who were obese with a diagnosis of MetS were fed three 4-week weight-maintenance diets that were low, moderate, and high in carbohydrate. Protein was constant and fat was exchanged isocalorically for carbohydrate across all diets.RESULTSDespite maintaining body mass, low-carbohydrate (LC) intake enhanced fat oxidation and was more effective in reversing MetS, especially high triglycerides, low HDL-C, and the small LDL subclass phenotype. Carbohydrate restriction also improved abnormal fatty acid composition, an emerging MetS feature. Despite containing 2.5 times more saturated fat than the high-carbohydrate diet, an LC diet decreased plasma total saturated fat and palmitoleate and increased arachidonate.CONCLUSIONConsistent with the perspective that MetS is a pathologic state that manifests as dietary carbohydrate intolerance, these results show that compared with eucaloric high-carbohydrate intake, LC/high-fat diets benefit MetS independent of whole-body or fat mass.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT02918422.FUNDINGDairy Management Inc. and the Dutch Dairy Association.

Cardiopulmonary exercise testing in the MRI environment.

Maximal oxygen consumption ([Formula: see text]max) measured by cardiopulmonary exercise testing (CPX) is the gold standard for assessment of cardiorespiratory fitness. Likewise, cardiovascular magnetic resonance (CMR) is the gold standard for quantification of cardiac function. The combination of CPX and CMR may offer unique insights into cardiopulmonary pathophysiology; however, the MRI-compatible equipment needed to combine these tests has not been available to date. We sought to determine whether CPX testing in the MRI environment, using equipment modified for MRI yields results equivalent to those obtained in standard exercise physiology (EP) lab. Ten recreationally trained subjects completed [Formula: see text]max tests in different locations; an EP laboratory and an MRI laboratory, using site specific equipment. CMR cine images of the heart were acquired before and immediately after maximal exercise to measure cardiac function. Subjects in all tests met criteria indicating that peak exercise was achieved. Despite equipment modifications for the MRI environment, [Formula: see text]max was nearly identical between tests run in the different labs (95% lower confidence limit (LCL) = 0.8182). The mean difference in [Formula: see text]max was less than 3.40 ml (kg/min)(-1), within the variability expected for tests performed on different days, in different locations, using different metabolic carts. MRI performed at rest and following peak exercise stress indicated cardiac output increased from 5.1 ± 1.0 l min(-1) to 16.4 ± 5.6 l min(-1), LVEF increased from 65.2 ± 3.3% to 78.4 ± 4.8%, while RVEF increased from 52.8 ± 5.3% to 63.4 ± 5.3%. Regression analysis revealed a significant positive correlation between [Formula: see text]max and stroke volume (R = 0.788, P = 0.006), while the correlation with cardiac output did not reach statistical significance (R = 0.505, P = 0.137). [Formula: see text]max CPX testing can be effectively performed in the MRI environment, enabling direct combination of physiological data with advanced post-exercise imaging in the same test session.

Diagnostic Performance of Treadmill Exercise Cardiac Magnetic Resonance: The Prospective, Multicenter Exercise CMR's Accuracy for Cardiovascular Stress Testing (EXACT) Trial.

BACKGROUND: Stress cardiac magnetic resonance (CMR) has typically involved pharmacologic agents. Treadmill CMR has shown utility in single-center studies but has not undergone multicenter evaluation. METHODS AND RESULTS: Patients referred for treadmill stress nuclear imaging (SPECT) were prospectively enrolled across 4 centers. After rest (99m)Tc SPECT, patients underwent resting cine CMR. In-room stress was then performed using an MR-compatible treadmill with continuous 12-lead electrocardiogram monitoring. At peak stress, (99m)Tc was injected, and patients rapidly returned to the MR scanner isocenter for real-time, free-breathing stress cine and perfusion imaging. After recovery, cine and rest perfusion followed by late gadolinium enhancement acquisitions concluded CMR imaging. Stress SPECT was then acquired in adjacent nuclear laboratories. A subset of patients not referred for invasive coronary angiography within 2 weeks of stress underwent coronary computed tomography angiography. Angiographic data available in 94 patients showed sensitivity of 79%, specificity of 99% for exercise CMR with positive predictive value of 92% and negative predictive value of 96%. Agreement between treadmill stress CMR and angiography was strong (κ=0.82), and moderate between SPECT and angiography (κ=0.46) and CMR versus SPECT (κ=0.48). CONCLUSIONS: The multicenter EXACT trial indicates excellent diagnostic value of treadmill stress CMR in typical patients referred for exercise SPECT.