Background
Proton magnetic resonance spectroscopy (1H‐MRS) of the human heart is deemed to be a quantitative method to investigate myocardial metabolite content, but thorough validations of in vivo ...measurements against invasive techniques are lacking.
Purpose
To determine measurement precision and accuracy for quantifications of myocardial total creatine and triglyceride content with localized 1H‐MRS.
Study type
Test–retest repeatability and measurement validation study.
Subjects
Sixteen volunteers and 22 patients scheduled for open‐heart aortic valve replacement or septal myectomy.
Field Strength/Sequence
Prospectively ECG‐triggered respiratory‐gated free‐breathing single‐voxel point‐resolved spectroscopy (PRESS) sequence at 3 T.
Assessment
Myocardial total creatine and triglyceride content were quantified relative to the total water content by fitting the 1H‐MR spectra. Precision was assessed with measurement repeatability. Accuracy was assessed by validating in vivo 1H‐MRS measurements against biochemical assays in myocardial tissue from the same subjects.
Statistical Tests
Intrasession and intersession repeatability was assessed using Bland–Altman analyses. Agreement between 1H‐MRS measurements and biochemical assay was tested with regression analyses.
Results
The intersession repeatability coefficient for myocardial total creatine content was 41.8% with a mean value of 0.083% ± 0.020% of the total water signal, and 36.7% for myocardial triglyceride content with a mean value of 0.35% ± 0.13% of the total water signal. Ex vivo myocardial total creatine concentrations in tissue samples correlated with the in vivo myocardial total creatine content measured with 1H‐MRS: n = 22, r = 0.44; P < 0.05. Likewise, ex vivo myocardial triglyceride concentrations correlated with the in vivo myocardial triglyceride content: n = 20, r = 0.50; P < 0.05.
Data Conclusion
We validated the use of localized 1H‐MRS of the human heart at 3 T for quantitative assessments of in vivo myocardial tissue metabolite content by estimating the measurement precision and accuracy.
Level of Evidence
2
Technical Efficacy Stage
2
Background
Renal steatosis (fatty kidney) is a potential biomarker for obesity‐related renal disease; however, noninvasive assessment of renal fat content remains a technical challenge.
Purpose
To ...evaluate reproducibility and explore clinical application of renal metabolic imaging for the quantification of renal triglyceride content (TG) using proton magnetic resonance spectroscopy (1H‐MRS).
Study type
Reproducibility and clinical cohort study.
Population
Twenty‐three healthy volunteers (mean age 30.1 ± 13.4 years) and 15 patients with type 2 diabetes mellitus (T2DM) (mean age 59.3 ± 7.0 years).
Field Strength/Sequence
3T, single‐voxel point resolved spectroscopy (PRESS).
Assessment
Intra‐ and interexamination reproducibility of renal TG was assessed in healthy volunteers, and compared to T2DM patients. Intraexamination differences were obtained by repeating the 1H‐MRS measurement directly after the first 1H‐MRS without repositioning of the subject or changing surface coil and measurement volumes. Interexamination variability was studied by repeating the scan protocol after removal and replacement of the subject in the magnet, and subsequent repositioning of body coil and measurement volumes.
Statistical Tests
Reproducibility was determined using Pearson's correlation and Bland–Altman analyses. Differences in TG% between healthy volunteers and T2DM patients were assessed using the Mann–Whitney U‐test.
Results
After logarithmic (log) transformation, both intraexamination (r = 0.91, n = 19) and interexamination (r = 0.73, n = 9) measurements of renal TG content were highly correlated with the first renal TG measurements. Intraexamination and interexamination limits of agreement of renal log TG% were respectively −1.36%, + 0.84% and −0.77%, + 0.62%. Backtransformed limits of agreement were −0.89%,+0.57% and −0.55%, + 0.43% multiplied by mean TG for intra‐ and interexamination measurements. Overall median renal TG content was 0.12% 0.08, 0.22; 25th percentile, 75th percentile in healthy volunteers and 0.20% 0.13, 0.22 in T2DM patients (P = 0.08).
Data Conclusion
Renal metabolic imaging using 3T 1H‐MRS is a reproducible technique for the assessment of renal triglyceride content.
Level of Evidence: 3
Technical Efficacy: Stage 1
J. MAGN. RESON. IMAGING 2018;48:507–513.
Obesity and type 2 diabetes have not only been linked to fatty liver, but also to fatty kidney and chronic kidney disease. Since non-invasive tools are lacking to study fatty kidney in clinical ...studies, we explored agreement between proton magnetic resonance spectroscopy (1H-MRS) and enzymatic assessment of renal triglyceride content (without and with dietary intervention). We further studied the correlation between fatty kidney and fatty liver.
Triglyceride content in the renal cortex was measured by 1H-MRS on a 7-Tesla scanner in 27 pigs, among which 15 minipigs had been randomized to a 7-month control diet, cafeteria diet (CAF) or CAF with low-dose streptozocin (CAF-S) to induce insulin-independent diabetes. Renal biopsies were taken from corresponding MRS-voxel locations. Additionally, liver biopsies were taken and triglyceride content in all biopsies was measured by enzymatic assay.
Renal triglyceride content measured by 1H-MRS and enzymatic assay correlated positively (r = 0.86, P < 0.0001). Compared with control diet-fed minipigs, renal triglyceride content was higher in CAF-S-fed minipigs (137 ± 51 nmol/mg protein, mean ± standard error of the mean, P < 0.05), but not in CAF-fed minipigs (60 ± 10 nmol/mg protein) compared with controls (40 ± 6 nmol/mg protein). Triglyceride contents in liver and kidney biopsies were strongly correlated (r = 0.97, P < 0.001).
Non-invasive measurement of renal triglyceride content by 1H-MRS closely predicts triglyceride content as measured enzymatically in biopsies, and fatty kidney appears to develop parallel to fatty liver. 1H-MRS may be a valuable tool to explore the role of fatty kidney in obesity and type 2 diabetic nephropathy in humans in vivo.
Purpose
To optimize data acquisition parameters in cardiac proton MR spectroscopy, and to evaluate the intra‐ and intersession variability in myocardial triglyceride content.
Materials and Methods
...Data acquisition parameters at 3 Tesla (T) were optimized and reproducibility measured using, in total, 49 healthy subjects. The signal‐to‐noise‐ratio (SNR) and the variance in metabolite amplitude between averages were measured for: (i) global versus local power optimization; (ii) static magnetic field (B0) shimming performed during free‐breathing or within breathholds; (iii) post R‐wave peak measurement times between 50 and 900 ms; (iv) without respiratory compensation, with breathholds and with navigator triggering; and (v) frequency selective excitation, Chemical Shift Selective (CHESS) and Multiply Optimized Insensitive Suppression Train (MOIST) water suppression techniques. Using the optimized parameters intra‐ and intersession myocardial triglyceride content reproducibility was measured. Two cardiac proton spectra were acquired with the same parameters and compared (intrasession reproducibility) after which the subject was removed from the scanner and placed back in the scanner and a third spectrum was acquired which was compared with the first measurement (intersession reproducibility).
Results
Local power optimization increased SNR on average by 22% compared with global power optimization (P = 0.0002). The average linewidth was not significantly different for pencil beam B0 shimming using free‐breathing or breathholds (19.1 Hz versus 17.5 Hz; P = 0.15). The highest signal stability occurred at a cardiac trigger delay around 240 ms. The mean amplitude variation was significantly lower for breathholds versus free‐breathing (P = 0.03) and for navigator triggering versus free‐breathing (P = 0.03) as well as for navigator triggering versus breathhold (P = 0.02). The mean residual water signal using CHESS (1.1%, P = 0.01) or MOIST (0.7%, P = 0.01) water suppression was significantly lower than using frequency selective excitation water suppression (7.0%). Using the optimized parameters an intrasession limits of agreement of the myocardial triglyceride content of ‐0.11% to +0.04%, and an intersession of ‐0.15% to +0.9%, were achieved. The coefficient of variation was 5% for the intrasession reproducibility and 6.5% for the intersession reproducibility.
Conclusion
Using approaches designed to optimize SNR and minimize the variation in inter‐average signal intensities and frequencies/phases, a protocol was developed to perform cardiac MR spectroscopy on a clinical 3T system with high reproducibility. J. Magn. Reson. Imaging 2016;44:1151–1158.
South Asians have a high risk to develop type 2 diabetes, which may be related to substantial ectopic fat deposition. Since glucagon-like peptide-1 analogues can reduce ectopic fat accumulation, the ...aim of the present study was to assess the effect of treatment with liraglutide for 26 weeks on ectopic fat deposition and HbA1c in South Asian patients with type 2 diabetes.
In a placebo-controlled trial, 47 South Asian patients with type 2 diabetes were randomly assigned to treatment with liraglutide (1.8 mg/day) or placebo added to standard care. At baseline and after 26 weeks of treatment we assessed abdominal subcutaneous, visceral, epicardial and paracardial adipose tissue volume using MRI. Furthermore, myocardial and hepatic triglyceride content were examined with proton magnetic resonance spectroscopy.
In the intention-to-treat analysis, liraglutide decreased body weight compared to placebo (- 3.9 ± 3.6 kg vs - 0.6 ± 2.2 kg; mean change from baseline (liraglutide vs placebo): - 3.5 kg; 95% CI - 5.3, - 1.8) without significant effects on the different adipose tissue compartments. HbA1c was decreased in both groups without between group differences. In the per-protocol analysis, liraglutide did decrease visceral adipose tissue volume compared to placebo (- 23 ± 27 cm
vs - 2 ± 17 cm
; mean change from baseline (liraglutide vs placebo): - 17 cm
; 95% CI - 32, - 3). Furthermore, HbA1c was decreased by liraglutide compared to placebo (- 1.0 ± 0.8% (- 10.5 ± 9.1 mmol/mol)) vs (- 0.6 ± 0.8% (- 6.1 ± 8.8 mmol/mol)), with a between group difference (mean change from baseline (liraglutide vs placebo): - 0.6% (- 6.5 mmol/mol); 95% CI - 1.1, - 0.1 (- 11.5, - 1.5)). Interestingly, the decrease of visceral adipose tissue volume was associated with the reduction of HbA1c (β: 0.165 mmol/mol (0.015%) per 1 cm
decrease of visceral adipose tissue volume; 95% CI 0.062, 0.267 (0.006, 0.024%)).
While the intention-to-treat analysis did not show effects of liraglutide on ectopic fat and HbA1c, per-protocol analysis showed that liraglutide decreases visceral adipose tissue volume, which was associated with improved glycaemic control in South Asians. Trial registration NCT02660047 (clinicaltrials.gov). Registered 21 January 2016.
The pathogenesis and cardiovascular impact of type 2 diabetes (T2D) may be different in South Asians compared with other ethnic groups. The phenotypic characterization of diabetic cardiomyopathy ...remains debated and little is known regarding differences in T2D-related cardiovascular remodeling across ethnicities. We aimed to characterize the differences in left ventricular (LV) diastolic and systolic function, LV structure, myocardial tissue characteristics and aortic stiffness between T2D patients and controls and to assess the differences in T2D-related cardiovascular remodeling between South Asians and Europeans.
T2D patients and controls of South Asian and European descent underwent 3 Tesla cardiovascular magnetic resonance imaging (CMR) and cardiac proton-magnetic resonance spectroscopy (
H-MRS). Differences in cardiovascular parameters between T2D patients and controls were examined using ANCOVA and were reported as mean (95% CI). Ethnic group comparisons in the association of T2D with cardiovascular remodeling were made by adding the interaction term between ethnicity and diabetes status to the model.
A total of 131 individuals were included (54 South Asians 50.1 ± 8.7 years, 33% men, 33 patients vs. 21 controls) and 77 Europeans (58.8 ± 7.0 years, 56% men, 48 patients vs. 29 controls). The ratio of the transmitral early and late peak filling rate (E/A) was lower in T2D patients compared with controls, in South Asians - 0.20 (- 0.36; - 0.03), P = 0.021 and Europeans - 0.20 (- 0.36; - 0.04), P = 0.017, whereas global longitudinal strain and aortic pulse wave velocity were similar. South Asian T2D patients had a higher LV mass + 22 g (15; 30), P < 0.001 (P for interaction by ethnicity = 0.005) with a lower extracellular volume fraction - 1.9% (- 3.4; - 0.4), P = 0.013 (P for interaction = 0.114), whilst European T2D patients had a higher myocardial triglyceride content + 0.59% (0.35; 0.84), P = 0.001 (P for interaction = 0.002) than their control group.
Diabetic cardiomyopathy was characterized by impaired LV diastolic function in South Asians and Europeans. Increased LV mass was solely observed among South Asian T2D patients, whereas differences in myocardial triglyceride content between T2D patients and controls were only present in the European cohort. The diabetic cardiomyopathy phenotype may differ between subsets of T2D patients, for example across ethnicities, and tailored strategies for T2D management may be required.
To assess the feasibility of renal proton magnetic resonance spectroscopy for quantification of triglyceride content and to compare spectral quality and reproducibility without and with respiratory ...motion compensation in vivo.
The Institutional Review Board of our institution approved the study protocol, and written informed consent was obtained. After technical optimization, a total of 20 healthy volunteers underwent renal proton magnetic resonance spectroscopy of the renal cortex both without and with respiratory motion compensation and volume tracking. After the first session the subjects were repositioned and the protocol was repeated to assess reproducibility. Spectral quality (linewidth of the water signal) and triglyceride content were quantified. Bland-Altman analyses and a test by Pitman were performed.
Linewidth changed from 11.5±0.4 Hz to 10.7±0.4 Hz (all data pooled, p<0.05), without and with respiratory motion compensation respectively. Mean % triglyceride content in the first and second session without respiratory motion compensation were respectively 0.58±0.12% and 0.51±0.14% (P = NS). Mean % triglyceride content in the first and second session with respiratory motion compensation were respectively 0.44±0.10% and 0.43±0.10% (P = NS between sessions and P = NS compared to measurements with respiratory motion compensation). Bland-Altman analyses showed narrower limits of agreement and a significant difference in the correlated variances (correlation of -0.59, P<0.05).
Metabolic imaging of the human kidney using renal proton magnetic resonance spectroscopy is a feasible tool to assess cortical triglyceride content in humans in vivo and the use of respiratory motion compensation significantly improves spectral quality and reproducibility. Therefore, respiratory motion compensation seems a necessity for metabolic imaging of renal triglyceride content in vivo.
The metabolic syndrome (MetS) is characterized by ectopic lipid accumulation. Magnetic resonance (MR) imaging and spectroscopy can quantify ectopic lipid accumulation. Consequences of MetS can be ...evaluated with MR on a whole-body level. In the liver, several techniques are used to quantify hepatic steatosis and differentiate stages of nonalcoholic fatty liver disease. Cardiac MR can quantify myocardial steatosis and associated complications. In the brain, magnetization transfer imaging and diffusion tensor imaging can detect microstructural brain damage. Various other organs can be assessed with MR. MR is a powerful tool to unravel whole-body MetS pathophysiology, monitor therapeutic efficacy, and establish prognosis.
Aims/hypothesis
The aim of this work was to assess the effect of liraglutide on ectopic fat accumulation in individuals with type 2 diabetes mellitus.
Methods
This study is a pre-specified ...subanalysis of the MAGNetic resonance Assessment of VICTOza efficacy in the Regression of cardiovascular dysfunction In type 2 diAbetes mellitus (MAGNA VICTORIA) study, with primary endpoints being the effects of liraglutide on left ventricular diastolic and systolic function. The MAGNA VICTORIA study was a single-centre, parallel-group trial in 50 individuals with type 2 diabetes mellitus (BMI >25 kg/m
2
) who were randomly assigned (1:1, stratified for sex and insulin use) to receive liraglutide 1.8 mg once daily or placebo for 26 weeks, added to standard care. Participants, study personnel and outcome assessors were blinded to treatment allocation. The secondary endpoints of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT) and epicardial fat were measured with MRI. Hepatic triacylglycerol content (HTGC) and myocardial triacylglycerol content (MTGC) were quantified with proton MR spectroscopy. Between-group differences (change from baseline) were tested for significance using ANCOVA. Mean differences with 95% CIs were reported.
Results
The trial was completed in 2016. Twenty-four participants were randomised to receive liraglutide and 26 to receive placebo. One patient in the liraglutide group withdrew consent before having received the study drug and was not included in the intention-to-treat analysis. Liraglutide (
n
= 23) vs placebo (
n
= 26) significantly reduced body weight (liraglutide 98.4 ± 13.8 kg to 94.3 ± 14.9 kg; placebo 94.5 ± 13.1 kg to 93.9 ± 13.2 kg; estimated treatment effect −4.5 95% CI −6.4, −2.6 kg). HbA
1c
declined in both groups without a significant treatment effect of liraglutide vs placebo (liraglutide 66.7 ± 11.5 mmol/mol to 55.0 ± 13.2 mmol/mol 8.4 ± 1.1% to 7.3 ± 1.2%; placebo 64.7 ± 10.2 mmol/mol to 56.9 ± 6.9 mmol/mol 8.2 ± 1.0% to 7.5 ± 0.7%; estimated treatment effect −2.9 95% CI −8.1, 2.3 mmol/mol or −0.3 95% CI −0.8, 0.2%). VAT did not change significantly between groups (liraglutide 207 ± 87 cm
2
to 203 ± 88 cm
2
; placebo 204 ± 63 cm
2
to 200 ± 55 cm
2
; estimated treatment effect −7 95% CI −24, 10 cm
2
), while SAT was reduced by a significantly greater extent with liraglutide than with placebo (liraglutide 361 ± 142 cm
2
to 339 ± 131 cm
2
; placebo 329 ± 107 cm
2
to 333 ± 125 cm
2
; estimated treatment effect −29 95% CI −51, −8 cm
2
). Epicardial fat did not change significantly between groups (liraglutide 8.9 ± 4.3 cm
2
to 9.1 ± 4.7 cm
2
; placebo 9.6 ± 4.1 cm
2
to 9.6 ± 4.6 cm
2
; estimated treatment effect 0.2 95% CI −1.5, 1.8 cm
2
). Change in HTGC was not different between groups (liraglutide 18.1 ± 11.2% to 12.0 ± 7.7%; placebo 18.4 ± 9.4% to 14.7 ± 10.0%; estimated treatment effect −2.1 95% CI −5.3, 1.0%). MTGC was not different after treatment with liraglutide (1.5 ± 0.6% to 1.2 ± 0.6%) vs placebo (1.3 ± 0.5% to 1.2 ± 0.6%), with an estimated treatment effect of −0.1 (95% CI −0.4, 0.2)%. There were no adjudicated serious adverse events.
Conclusions/interpretation
Compared with placebo, liraglutide-treated participants lost significantly more body weight. Liraglutide primarily reduced subcutaneous fat but not visceral, hepatic, myocardial or epicardial fat. Future larger studies are needed to confirm the results of this secondary endpoint study.
Trial registration
ClinicalTrials.gov
NCT01761318.
Funding
This study was funded by Novo Nordisk A/S (Bagsvaerd, Denmark).
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