Accuracy of Liver Fat Quantification With Advanced CT, MRI, and Ultrasound Techniques: Prospective Comparison With MR Spectroscopy.

OBJECTIVE: The purpose of this study was to prospectively evaluate the accuracy of proton-density fat-fraction, single- and dual-energy CT (SECT and DECT), gray-scale ultrasound (US), and US shear-wave elastography (US-SWE) in the quantification of hepatic steatosis with MR spectroscopy (MRS) as the reference standard. SUBJECTS AND METHODS: Fifty adults who did not have symptoms (23 men, 27 women; mean age, 57 ± 5 years; body mass index, 27 ± 5) underwent liver imaging with un-enhanced SECT, DECT, gray-scale US, US-SWE, proton-density fat-fraction MRI, and MRS for this prospective trial. MRS voxels for the reference standard were colocalized with all other modalities under investigation. For SECT (120 kVp), attenuation values were recorded. For rapid-switching DECT (80/140 kVp), monochromatic images (70-140 keV) and fat density-derived material decomposition images were reconstructed. For proton-density fat fraction MRI, a quantitative chemical shift-encoded method was used. For US, echogenicity was evaluated on a qualitative 0-3 scale. Quantitative US shear-wave velocities were also recorded. Data were analyzed by linear regression for each technique compared with MRS. RESULTS: There was excellent correlation between MRS and both proton-density fat-fraction MRI (r2 = 0.992; slope, 0.974; intercept, -0.943) and SECT (r2 = 0.856; slope, -0.559; intercept, 35.418). DECT fat attenuation had moderate correlation with MRS measurements (r2 = 0.423; slope, 0.034; intercept, 8.459). There was good correlation between qualitative US echogenicity and MRS measurements with a weighted kappa value of 0.82. US-SWE velocity did not have reliable correlation with MRS measurements (r2 = 0.004; slope, 0.069; intercept, 6.168). CONCLUSION: Quantitative MRI proton-density fat fraction and SECT fat attenuation have excellent linear correlation with MRS measurements and can serve as accurate noninvasive biomarkers for quantifying steatosis. Material decomposition with DECT does not improve the accuracy of fat quantification over conventional SECT attenuation. US-SWE has poor accuracy for liver fat quantification.

Longitudinal Monitoring of Hepatic Blood Flow before and after TIPS by Using 4D-Flow MR Imaging.

Purpose To demonstrate the feasibility of four-dimensional (4D)-flow magnetic resonance (MR) imaging for noninvasive longitudinal hemodynamic monitoring of hepatic blood flow before and after transjugular intrahepatic portosystemic shunt (TIPS) placement. Materials and Methods The institutional review board approved this prospective Health Insurance Portability and Accountability Act compliant study with written informed consent. Four-dimensional-flow MR imaging was performed in seven patients with portal hypertension and refractory ascites before and 2 and 12 weeks after TIPS placement by using a time-resolved three-dimensional radial phase-contrast acquisition. Flow and peak velocity measurements were obtained in the superior mesenteric vein (SMV), splenic vein (SV), portal vein (PV), and the TIPS. Flow volumes and peak velocities in each vessel, as well as the ratio of in-stent to PV flow, were compared before and after TIPS placement by using analysis of variance. Results Flow volumes significantly increased in the SMV (0.24 L/min; 95% confidence interval [CI]: 0.07, 0.41), SV (0.31 L/min; 95% CI: 0.07, 0.54), and PV (0.88 L/min; 95% CI: 0.06, 1.70) after TIPS placement (all P < .05), with no significant difference between the first and second post-TIPS placement acquisitions (all P > .11). Ascites resolved in six of seven patients. In those with resolved ascites, the TIPS-to-PV flow ratio was 0.8 ± 0.2 and 0.9 ± 0.2 at the two post-TIPS time points, respectively, while the observed ratios were 4.6 and 4.3 in the patient with refractory ascites at the two post-TIPS time points, respectively. In this patient, 4D-flow MR imaging demonstrated arterio-portal-venous shunting, with draining into the TIPS. Conclusion Four-dimensional-flow MR imaging is feasible for noninvasive longitudinal hemodynamic monitoring of hepatic blood flow before and after TIPS placement. © RSNA, 2016 Online supplemental material is available for this article.

Quantitative magnetic resonance imaging of hepatic steatosis: Validation in ex vivo human livers.

UNLABELLED: Emerging magnetic resonance imaging (MRI) biomarkers of hepatic steatosis have demonstrated tremendous promise for accurate quantification of hepatic triglyceride concentration. These methods quantify the proton density fat-fraction (PDFF), which reflects the concentration of triglycerides in tissue. Previous in vivo studies have compared MRI-PDFF with histologic steatosis grading for assessment of hepatic steatosis. However, the correlation of MRI-PDFF with the underlying hepatic triglyceride content remained unknown. The aim of this ex vivo study was to validate the accuracy of MRI-PDFF as an imaging biomarker of hepatic steatosis. Using ex vivo human livers, we compared MRI-PDFF with magnetic resonance spectroscopy-PDFF (MRS-PDFF), biochemical triglyceride extraction, and histology as three independent reference standards. A secondary aim was to compare the precision of MRI-PDFF relative to biopsy for the quantification of hepatic steatosis. MRI-PDFF was prospectively performed at 1.5 Tesla in 13 explanted human livers. We performed colocalized paired evaluation of liver fat content in all nine Couinaud segments using single-voxel MRS-PDFF (n=117) and tissue wedges for biochemical triglyceride extraction (n=117), and five core biopsies performed in each segment for histologic grading (n=585). Accuracy of MRI-PDFF was assessed through linear regression with MRS-PDFF, triglyceride extraction, and histology. Intraobserver agreement, interobserver agreement, and repeatability of MRI-PDFF and histologic grading were assessed through Bland-Altman analyses. MRI-PDFF showed an excellent correlation with MRS-PDFF (r=0.984, confidence interval 0.978-0.989) and strong correlation with histology (r=0.850, confidence interval 0.791-0.894) and triglyceride extraction (r=0.871, confidence interval 0.818-0.909). Intraobserver agreement, interobserver agreement, and repeatability showed a significantly smaller variance for MRI-PDFF than for histologic steatosis grading (all P<0.001). CONCLUSION: MRI-PDFF is an accurate, precise, and reader-independent noninvasive imaging biomarker of liver triglyceride content, capable of steatosis quantification over the entire liver.

Feasibility of a three-step magnetic resonance imaging approach for the assessment of hepatic steatosis in an asymptomatic study population.

OBJECTIVES: To determine the feasibility of a multi-step magnetic resonance imaging (MRI) approach for comprehensive assessment of hepatic steatosis defined as liver fat content of ≥5 % in an asymptomatic population. METHODS: The study was approved by the institutional review board and written informed consent of all participants was obtained. Participants of a population-based study cohort underwent a three-step 3-T MRI-based assessment of liver fat. A dual-echo Dixon sequence was performed to identify subjects with hepatic steatosis, followed by a multi-echo Dixon sequence with proton density fat fraction estimation. Finally, single-voxel T2-corrected multi-echo spectroscopy was performed. RESULTS: A total of 215 participants completed the MRI protocol (56.3 % male, average age 57.2 ± 9.4 years). The prevalence of hepatic steatosis was 55 %. Mean liver proton density fat fraction was 9.2 ± 8.5 % by multi-echo Dixon and 9.3 ± 8.6 % by multi-echo spectroscopy (p = 0.51). Dual-echo Dixon overestimated liver fat fraction by 1.4 ± 2.0 % (p < 0.0001). All measurements showed excellent correlations (r ≥ 0.9, p < 0.001). Dual-echo Dixon was highly sensitive for the detection of hepatic steatosis (sensitivity 0.97, NPV 0.96) with good specificity and PPV (0.75 and 0.81, respectively). CONCLUSIONS: A multi-step MRI approach may enable rapid and accurate identification of subjects with hepatic steatosis in an asymptomatic population. KEY POINTS: • Dual-echo Dixon can rapidly and reliably exclude hepatic steatosis without complex post-processing. • Multi-echo Dixon and multi-echo spectroscopy yield similar results regarding hepatic fat quantification. • Each sequence can be performed in one breath-hold. • These sequences can be implemented in routine abdominal MRI protocols. • Thus hepatic fat can be evaluated without relevant increase in scan time.

On the confounding effect of temperature on chemical shift-encoded fat quantification.

PURPOSE: To characterize the confounding effect of temperature on chemical shift-encoded (CSE) fat quantification. METHODS: The proton resonance frequency of water, unlike triglycerides, depends on temperature. This leads to a temperature dependence of the spectral models of fat (relative to water) that are commonly used by CSE-MRI methods. Simulation analysis was performed for 1.5 Tesla CSE fat-water signals at various temperatures and echo time combinations. Oil-water phantoms were constructed and scanned at temperatures between 0 and 40°C using spectroscopy and CSE imaging at three echo time combinations. An explanted human liver, rejected for transplantation due to steatosis, was scanned using spectroscopy and CSE imaging. Fat-water reconstructions were performed using four different techniques: magnitude and complex fitting, with standard or temperature-corrected signal modeling. RESULTS: In all experiments, magnitude fitting with standard signal modeling resulted in large fat quantification errors. Errors were largest for echo time combinations near TEinit ≈ 1.3 ms, ΔTE ≈ 2.2 ms. Errors in fat quantification caused by temperature-related frequency shifts were smaller with complex fitting, and were avoided using a temperature-corrected signal model. CONCLUSION: Temperature is a confounding factor for fat quantification. If not accounted for, it can result in large errors in fat quantifications in phantom and ex vivo acquisitions.

Magnetic resonance angiography of the carotid arteries: comparison of unenhanced and contrast enhanced techniques.

OBJECTIVE: To compare different techniques for carotid imaging including contrast-enhanced, unenhanced and dynamic techniques to find an alternative to contrast-enhanced MRA. METHODS: 43 patients referred for imaging of the carotids were enrolled in this IRB-approved study. Imaging included dark-blood, time-of-flight, ECG-gated SSFP and dynamic and static contrast-enhanced MRA. Two radiologists evaluated all datasets in terms of image quality (vessel lumen, signal homogeneity, diagnostic confidence, preferred technique) on a four-point Likert-scale and in measuring the vessel area. RESULTS: Of the 43 included patients the first 8 subjects served for protocol optimisation and 4 individuals discontinued the examination. Thus 31 datasets served for evaluation. CE-MRA revealed best results for delineation of vessel lumen, signal homogeneity and diagnostic confidence with values of 3.61, 3.42 and 3.77. It was also rated as the most preferred technique. SSFP-MRA was rated second in all categories with values of 3.1, 2.9 and 3.11. This unenhanced technique was the only one showing non-significantly different results in quantitative analysis. CONCLUSION: SSFP-MRA, an unenhanced form of MRA, represents an alternative to CE-MRA, particularly in patients where administration of gadolinium for CE-MRA may be contraindicated. In contrast to other techniques, SSFP-MRA serves with not significant different results compared to standard CE-MRA.

Cost comparison of transcatheter and operative closures for patients with secundum atrial septal defects in Vietnam.

We aim to estimate and compare the costs of operative and transcatheter closure for patients with secundum atrial septal defect (ASD) in Vietnam. This was a retrospective cross-sectional study based on medical records of congenital heart diseases (CHD) patients in Da Nang Hospital, Vietnam from 2010 through 2015. All costs in this study were calculated according to a provider's perspective. All pricing data were converted into USD at the 2015 exchange rate. A total of 258 patients with secundum ASD were recruited in the study, including 35 patients treated by operative closure and 223 patients treated by transcatheter closure. The total treatment costs of the transcatheter closure group (US $3,107.9) were higher than those of the operative closure group (US $2,080.5). The cost of the procedure and medical supplies accounted for 67.3% of the total treatment cost in the operative closure group, while the cost of occlusion devices accounted for 62.2% of the total cost in the transcatheter closure group. Given the advantages of the transcatheter closure procedure, reducing occlusion device costs may increase the proportion of patients treated with this technique.

Measuring HCC Tumor Size in MRI-The Sequence Matters!

BACKGROUND: The aim of this paper was to assess and compare the accuracy of common magnetic resonance imaging (MRI) pulse sequences in measuring the lesion sizes of hepatocellular carcinomas (HCCs) with respect to the Milan criteria and histopathology as a standard of reference. METHODS: We included 45 patients with known HCC who underwent contrast-enhanced MRI of the liver prior to liver transplantation or tumor resection. Tumor size was assessed pathologically for all patients. The MRI protocol contained axial T2-weighted images as well as T1-weighted imaging sequences before and after application of Gd-EOB-DTPA. Tumor diameters, the sharpness of lesions, and the presence of artifacts were evaluated visually on all available MRI sequences. MRI measurements and pathologically assessed tumor dimensions were correlated using Pearson's correlation coefficient and Bland-Altman plots. The rate of misclassifications following Milan criteria was assessed. RESULTS: The mean absolute error (in cm) of MRI size measurements in comparison to pathology was the smallest for the hepatobiliary phase T1-weighted acquisition (0.71 ± 0.70 cm, r = 0.96) and largest for the T2w turbo-spin-echo (TSE) sequence (0.85 ± 0.78 cm, r = 0.94). The misclassification rate regarding tumor size under the Milan criteria was lowest for the T2w half-Fourier acquisition single-shot turbo spin-echo sequence and the hepatobiliary phase T1w acquisition (each 8.6%). The highest rate of misclassification occurred in the portal venous phase T1w acquisition and T2w TSE sequence (each 14.3%). CONCLUSIONS: The hepatobiliary phase T1-weighted acquisition seems to be most accurate among commonly used MRI sequences for measuring HCC tumor size, resulting in low rates of misclassification with respect to the Milan criteria.

Multicenter, double-blind, randomized, intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for MR angiography of peripheral arteries.

PURPOSE: To prospectively compare the image quality and diagnostic performance achieved with doses of gadobenate dimeglumine and gadopentetate dimeglumine of 0.1 mmol per kilogram of body weight in patients undergoing contrast material-enhanced magnetic resonance (MR) angiography of the pelvis, thigh, and lower-leg (excluding foot) for suspected or known peripheral arterial occlusive disease. MATERIALS AND METHODS: Institutional review board approval was granted from each center and informed written consent was obtained from all patients. Between November 2006 and January 2008, 96 patients (62 men, 34 women; mean age, 63.7 years +/- 10.4 [standard deviation]; range, 39-86 years) underwent two identical examinations at 1.5 T by using three-dimensional spoiled gradient-echo sequences and randomized 0.1-mmol/kg doses of each agent. Images were evaluated on-site for technical adequacy and quality of vessel visualization and offsite by three independent blinded readers for anatomic delineation and detection/exclusion of pathologic features. Comparative diagnostic performance was determined in 31 patients who underwent digital subtraction angiography. Data were analyzed by using the Wilcoxon signed-rank, McNemar, and Wald tests. Interreader agreement was determined by using generalized kappa statistics. Differences in quantitative contrast enhancement were assessed and a safety evaluation was performed. RESULTS: Ninety-two patients received both agents. Significantly better performance (P < .0001; all evaluations) with gadobenate dimeglumine was noted on-site for technical adequacy and vessel visualization quality and offsite for anatomic delineation and detection/exclusion of pathologic features. Contrast enhancement (P < or = .0001) and detection of clinically relevant disease (P < or = .0028) were significantly improved with gadobenate dimeglumine. Interreader agreement for stenosis detection and grading was good to excellent (kappa = 0.749 and 0.805, respectively). Mild adverse events were reported for four (six events) and five (eight events) patients after gadobenate dimeglumine and gadopentetate dimeglumine, respectively. CONCLUSION: Higher-quality vessel visualization, greater contrast enhancement, fewer technical failures, and improved diagnostic performance are obtained with gadobenate dimeglumine, relative to gadopentetate dimeglumine, when compared intraindividually at 0.1-mmol/kg doses in patients undergoing contrast-enhanced MR angiography for suspected peripheral arterial occlusive disease.

Diagnostic value of time-resolved CT angiography for the lower leg.

OBJECTIVE: The aim of this study was to test the feasibility of time-resolved computed tomography angiography (TR-CTA) for use in the lower leg. METHODS: Fifty-nine patients with suspected peripheral arterial occlusive disease were examined with a standard CTA (S-CTA) of the lower run-off and with an additional TR-CTA of the calves (12 phases; 2.5 s/phase, 80 kV, 120 mAs, volume of contrast medium 50 mL, flow rate 5.0 mL/s). For seven lower-leg artery segments, arterial contrast and the presence of venous overlay were tested for S-CTA and TR-CTA. Stenoses were classified on a three-point scale separately for S-CTA and TR-CTA, and diagnostic confidence for stenosis assessment was evaluated for both datasets. Contrast arrival times and HU values were evaluated in patients with asymmetric proximal stenoses. RESULTS: TR-CTA resulted in significantly higher contrast enhancement (P < 0.0001) and less venous overlay as compared to S-CTA (P < 0.05). Diagnostic confidence for stenosis rating was significantly higher in TR-CTA (P < 0.0001). Asymmetric proximal stenoses lead to significantly delayed and diminished contrast enhancement on the stenotic side. CONCLUSION: TR-CTA of the calves is feasible and provides higher enhancement and higher diagnostic confidence as compared to monophasic CTA of the lower legs.

Brain MRI with single-dose (0.1 mmol/kg) Gadobutrol at 1.5 T and 3 T: comparison with 0.15 mmol/kg Gadoterate meglumine.

OBJECTIVE: The purpose of this article is to evaluate the efficacy of a single dose of gadobutrol (0.1 mmol/kg of body weight) compared with that of a substantially higher dose of gadoterate meglumine (0.15 mmol/kg of body weight) in a rat brain tumor model at 1.5 and 3 T. MATERIALS AND METHODS: A cohort of 20 Fischer rats with a surgically implanted plastic brain cannula for glioma cell injection was divided into two groups. Group A underwent MRI at 1.5 T, and group B underwent MRI at 3 T. All rats were implanted with 10 microL of C6/lacZ glioma cells. Seven days after tumor cell implantation, MRI was performed with the first of two contrast agents in randomized order. Twenty-four hours later, MRI was performed with the second contrast agent. Both contrast agents were macrocyclic but differed in concentration. All rats were sacrificed after the second MRI scan was obtained, and brains were harvested for histopathologic assessment. For evaluation of image quality, signal-to-noise ratio, contrast-to-noise ratio, and lesion enhancement were evaluated. RESULTS: Two rats in each group died before the imaging protocol was completed. Thus, 16 rats could be evaluated. At both 1.5 and 3 T, no significant differences between the two contrast agents were found in terms of signal-to-noise ratio, contrast-to-noise ratio, and lesion enhancement, although the contrast agents were applied at substantially different dosages. CONCLUSION: The amount of gadobutrol needed to reach the same efficacy as gadoterate meglumine is substantially lower, which may be beneficial for patients with impaired renal function. In addition, increasing the dose of gadobutrol to 0.15 mmol/kg of body weight can potentially lead to better delineation of lesions.

Prospective evaluation of left atrial function and late gadolinium enhancement with 3 T MRI in patients with atrial fibrillation before and after catheter ablation.

In a prospective, randomized study we performed left atrial (LA) functional imaging and late gadolinium enhancement (LGE) in patients undergoing pulmonary vein isolation with ablation of the anterior mitral line to evaluate LA function and visibility of the anterior mitral line and to explore the relationship of these factors to short- and long-term procedural success. Functional imaging of the LA and LGE-visualization 15 min post i.v. administration of gadobutrol was performed on a 3 T MRI system before and after ablation. Patients were grouped in (a) subjects with sinus rhythm, and (b) subjects without sinus rhythm at the follow-up-MRI. Eight patients were excluded due to poor image quality. 37 patients were allotted to group a, 4 patients to group b. Group a showed a significant improvement in ejection fraction (22.3 ± 7.1% vs. 27.2 ± 5.5%; p < 0.001), end-systolic volume (111.6 ± 48.3 ml vs. 96.9 ± 37.2 ml; p = 0.002), stroke volume (30.2 ± 12.6 ml vs. 35.6 ± 12.6 ml; p = 0.003) and LGE (12.5% vs. 83.7%; p < 0.001). Group b showed no significant changes in functional parameters or LGE. Patients with successful therapy at 12 months showed significantly lower volumes in the baseline MRI. Scarring along the ablation pathways could be visualized with LGE. Patients with successful CA showed a significant improvement in LA cardiac parameters. Pre-ablation atrial volume seems to be a predictor for long-term success.

Noncontrast Chest Computed Tomographic Imaging of Obesity and the Metabolic Syndrome: Part II Noncardiovascular Findings.

The purpose of this review article is to acquaint the reader with the current state of the art for the noncardiovascular imaging biomarkers of metabolic syndrome found on noncontrast computed tomography (NCCT) of the chest and their prognostic significance. Routine chest NCCT includes quantitative information with regard to tissue density and organ volumes in the neck, chest, and upper abdomen. The specific imaging biomarkers that may be seen in association with metabolic syndrome include low thyroid iodine organification, hepatic steatosis, sarcopenia (muscle volume and density), demineralization of the thoracic and upper lumbar vertebral bodies, loss of axial skeletal muscle mass, premature lung inflammation, and an increased deposition of subcutaneous and visceral fat. These easily identified imaging biomarkers can have prognostic implications, which include nonalcoholic steatohepatitis, cirrhosis, hypothyroidism, early lung fibrosis with interstitial abnormalities, sarcopenia, and osteoporotic thoracic and lumbar spine vertebral body compression fractures. NCCT examinations of the chest have the opportunity to become an important imaging tool for outcomes research.

Benefit of Contact Force Sensing Catheter Technology for Successful Left Atrial Anterior Line Formation: A Prospective Randomized Trial.

INTRODUCTION: The value of contact force information for ablation of LA anterior line is unknown. In a prospective randomized clinical trial, we investigated if information on contact force during left atrial (LA) anterior line ablation reduces total radiofrequency time and results in higher rates of bidirectional line block in patients undergoing pulmonary vein isolation (PVI) plus substrate modification. METHODS: We included patients with indication for pulmonary vein isolation (PVI) and additional substrate modification. For LA anterior line ablation, patients were randomized to contact force information visible (n=35) or blinded (n=37). Patients received contrast enhanced cardiac magnetic resonance imaging (cMRI) before and 3-6 months after ablation to visualize the LA anterior line. Primary endpoint was radiofrequency time to achieve bidirectional line block. Secondary endpoints were completeness of the LA anterior line on cMRI, distribution of contact force, procedural data, adverse events, and 12 months success rate. RESULTS: In 72 patients (64±9 years, 68% male), bidirectional LA anterior line block was achieved in 70 (97%) patients. Radiofrequency time to bidirectional block did not differ significantly across groups (contact force information visible 23±18min versus contact force information blinded 21±15min, p=0.50). The LA anterior line was discernable on cMRI in 40 patients (82%) without significant differences across randomization groups (p=0.46). No difference in applied contact force was found depending on cMRI line visibility. Twelve-month success and adverse event rates were comparable across groups. CONCLUSION: Information on contact force does not significantly improve the ablation of LA anterior lines. CLINICAL TRIAL REGISTRATION: The trial was registered at http://www.clinicaltrials.gov by identifier: NCT02217657.

Intraindividual comparison of MR-renal perfusion imaging at 1.5 T and 3.0 T.

PURPOSE: The purpose of this study was to intraindividually compare fast gradient-echo semiquantitative renal perfusion measurements at 1.5 Tesla (T) and 3.0 Tesla. MATERIALS AND METHODS: Fifteen healthy male volunteers underwent renal perfusion measurements at 1.5 T and 3.0 T after the bolus injection of 7 mL of Gd-BOPTA. At both field strengths a Saturation-Recovery-fast gradient echo sequence (SR-TurboFLASH) with a temporal resolution of 4 (1.5 T) and 5 (3.0 T) simultaneously acquired slices per second was used. At 3.0 T, a parallel-imaging factor 2 was applied. For postprocessing, semiquantitative perfusion parameters including mean transit time (MTT), time to peak (TTP), and maximal signal intensity (SMax) were determined. The signal-to-noise ratios (SNR) of kidneys and aorta were determined precontrast and after enhancement. The image quality was rated by 2 radiologists. After Bonferroni correction paired t-tests were performed for statistical analysis. RESULTS: All measurements were successfully performed. At 3.0 T, a significant 63% increase in the baseline SNR (P = 0.00005) of the kidneys was found, the peak SNR was also increased though not statistically significant. Because of the higher SNR, the SMax was also significantly (P = 0.005) increased from 406 A.U. to 522 A.U., whereas MTT and TTP were not significantly changed. The image quality was rated very good to good for the 3.0 T images but only good to moderate at 1.5 T. CONCLUSION: Renal perfusion measurements at 3.0 T are feasible and directly benefit from the inherently higher SNR at 3.0 T. The higher SNR also translates into an increased SMax, whereas MTT and TTP are independent of the field strength.