Abstract
Objectives:
Liver T1 is a potential magnetic resonance imaging biomarker for liver diseases. This study aimed to determine the T1 relaxation time of the normal liver (PDFF<5%) in healthy Asian volunteers using modified look-locker inversion recovery (MOLLI) and B1 inhomogeneity-corrected variable flip angle (B1-corrected VFA).
Methods:
60 healthy Asian volunteers without focal or diffuse liver disease underwent a liver scan at 3T magnetic resonance. Proton density fat fraction (PDFF) and liver stiffness measurements were applied for the quantification of liver fat and fibrosis. T1 mapping was performed with MOLLI and B1-corrected VFA sequences. Bland-Altman, linear regression, Student t-test, and one-way analysis of variance were used for statistical analysis.
Results:
The mean T1 relaxation times of the whole liver were 901 ± 34 ms by MOLLI, and 948 ± 29 ms by B1-corrected VFA in healthy volunteers. There was a strong correlation (r = 0.86, p < 0.0001) for liver T1 between two T1 mapping methods. There were significant differences between the right and left lobes in liver T1 relaxation times using both methods (p < 0.05). Gender and Asian ethnic disparities had no impact on liver T1 relaxation times.
Conclusion:
T1 relaxation times of the normal liver (PDFF<5%) in healthy volunteers were established by MOLLI and B1-corrected VFA T1 mapping methods at 3T. It may provide suitable and robust baseline values for the assessment of liver diseases.
Advances in knowledge:
Gender and Asian ethnic disparities do not impact liver T1 relaxation time measurements.
Introduction
Quantitative MRI is becoming increasingly common in modern radiology research and practice, assisting in the clinical assessment of many patients with a variety of diseases. 1 The liver T1 relaxation time obtained by MR T1 mapping has been reported as a reliable and accurate biomarker for noninvasively assessing patients with liver disease. 2–4 Among the T1 mapping techniques, the modified look-locker inversion recovery sequence (MOLLI) combines images from two consecutive inversion-recovery experiments into a single T1 map, providing excellent T1 accuracy and reproducibility. 5 However, it scans only one high-resolution slice of the liver within one breath-hold and allows a limited coverage of the liver due to the long acquisition time. 3 While the MOLLI method has shown to be beneficial in predicting disease outcomes, 6,7 it is influenced by confounding factors such as excess iron, fat deposition, heart rate, the sequence parameters in liver T1 measurements, and magnetization transfer. 8 In the meantime, the variable flip angle (VFA) T1 mapping technique can cover the whole liver within one breath-hold. 9 But scanning a vast field of view at 3T strength or more, has a higher sensitivity to B1 inhomogeneity, leading to spatial variations of measured flip angles and T1 values. Additionally, B1 variation influences flip angles, leading to a knock-on effect on reconstructed T1 values. 10 To overcome this problem, B1 inhomogeneity correction has become available in the VFA technique by applying the B1 mapping pulse sequence before T1 mapping. 11
As a specific criterion, measurements of T1 relaxation time in ‘normal liver’ require proton density fat fraction (PDFF)<5% among the study population. 12 For this purpose, the application of MRI-PDFF is viewed as a noninvasive accurate method for liver fat quantification. 2 In addition, PDFF obtained by multiecho Dixon 13 is strongly correlated with liver T1 mapping. 14
To date, the clinical application of liver T1 mapping has largely been reported and gained acceptance for the evaluation of chronic liver disease. 7 However, most of the recent T1 mapping studies have focused on liver disease patient groups. 14–17 To the best of our knowledge, there is limited information about the evaluation of T1 relaxation time in ‘normal liver’ with MOLLI 7 and B1-corrected VFA T1 mapping methods among the healthy volunteers at 3T. Furthermore, there are insufficient data on quantitative liver T1 relaxation time and its correlation with gender and ethnic background. This study aimed to determine the T1 relaxation time of the ‘normal liver’ in healthy volunteers (PDFF<5%) using MOLLI and B1-corrected VFA and to evaluate whether gender, Asian ethnic disparities would impact liver T1 relaxation times.
Methods and materials
Subjects
In this observational, cross-sectional study, a total number of 60 healthy adult volunteers (mean age of 24.3 ± 2.1 years) were enrolled for obtaining liver T1 relaxation times, during October 2019 and April 2021. All the subjects underwent FibroScan (US transient elastography) for evaluation of liver disease. Healthy volunteers were placed in inclusion criteria if: (a) liver function was normal, based on a negative history of liver disease, serologic findings, and normal liver function tests; (b) they were medication-free, had no history of alcohol abuse (mean ethanol consumption should be ≤140 g/week in males and ≤70 g/week in females) or drug toxicity (e.g., methotrexate or hypervitaminosis A), and no history of abdominal surgery; (c) they were without focal or diffuse liver disease (based on MRI); (d) they had BMI <25 kg/m2 and liver PDFF <5%. (e) R2* (iron deposition)<126 sec−1 at 3T 18 ; (f) Liver stiffness measurements (LSM) by FibroScan were less than 7.3 kPa. 19
Subjects who had at least three of the five following criteria were diagnosed with metabolic syndrome: (a) triglycerides ≥ 150 mg dl−1 (1.7 mmol l−1); (b) blood pressure ≥130/85 mmHg; (c) HDL cholesterol <40 mg dl−1 (1.03 mmol l−1); (d) fasting plasma glucose ≥110 mg dl−1 (5.6 mmol l−1); (e) waist circumference >80 cm based on specificity of ethnicity. Volunteers diagnosed with metabolic syndrome were excluded from this study. Moreover, hydration status and glycogen concentration can affect T1 mapping results. 8 Hence, all the subjects were asked not to drink or eat 6 h before the scan.
The healthy volunteers included East (Chinese, n = 35), South (Indian, n = 15), and West (Iran, n = 10) Asians. Additional baseline characteristics are summarized in Table 1. This study was approved by Shandong Provincial Hospital Institutional Review Board and all participants provided written informed consent.
Table 1.
Characteristics of the study population
| Characteristic | Healthy volunteers |
|---|---|
| Number of participants | 60 |
| Age | 24.3 ± 2.1 |
| Male/Female | 26/34 |
| BMI (kg/m²) | 24.5 ± 3.1 |
| Total Cholesterol level (mg/dL) | 177.3 ± 29.4 |
| Fasting glucose (mg/dl) | 90.1 ± 10.2 |
| HDL cholesterol (mg/dl) | 49.2 ± 9.1 |
| LDL cholesterol (mg/dl) | 121 ± 12.3 |
| GGT (IU/L) | 24.2 ± 23.1 |
| Triglyceride (mmol/l) | 100.1 ± 46.4 |
| AST (IU/L) | 21.06 ± 8.9 |
| ALT (IU/L) | 20.1 ± 15.1 |
| PDFF (%) | 2.19 ± 2.1 |
| R2* (sec−1) | 34.3 to 59.4 |
| Liver stiffness (kPa) | 4.6 ± 0.5 |
| Heart rate (bpm) | 81.6 ± 14.8 |
ALT, Alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; GGT, gamma-glutamyl transpeptidase; PDFF, proton density fat fraction.
Data are means ± standard deviation (M ± SD).
MR imaging
All subjects underwent MRI scan at 3T (MAGNETOM PRISMA, Siemens Healthineers) to obtain T1 maps with an 18-channel body spine matrix coil, using MOLLI sequence and B1-corrected VFA sequence. For the MOLLI-T1 map, 2D (two-dimensional) TRUFI (two-dimensional True Fast Imaging with Steady-State Free Precession) sequences were obtained within one breath-hold. 20 Three axial slices were acquired at the levels of the intrahepatic inferior vena cava confluence, portal hilum, and gallbladder fossa. MOLLI technique uses electrocardiogram gated image acquisition at end-diastole. 21 We applied a 5 (3)3 MOLLI scheme that provides eight images with an initial inversion time of 180 (ms). The number of heartbeats for the total scan duration is 11 in this scheme. With acquisition time depending on heart rate, the longitudinal magnetization recovery has extra time by moving the 5-beat image acquisition to the 5 (3)three scheme beginning. 22 Using the B1-corrected VFA sequence, T1 maps spatial homogeneity were refined by B1 corrections. Moreover, inline T1 maps were built by vendor-provided software. To account for B1 field variations, the B1 mapping of the whole liver was obtained before the acquisition of the VIBE sequence to correct B1 inhomogeneity. 23
Quantification and evaluation of liver R2* (iron deposition) and PDFF values were performed by the vendor-supplied package (LiverLab), using a single breath-hold multiecho Dixon sequence with six echoes (composed of VIBE e-Dixon and VIBE q-Dixon sequences). 24 The detailed sequence parameters can be found in Table 2. T1 relaxation times of the liver were acquired without administration of contrast material.
Table 2.
Pulse sequence parameters
| Parameter | MOLLI 5 (3)3 |
B1 map | B1-corrected VFA T1 map VIBE (3D) | Multiple-echo Dixon VIBE (3D) |
|---|---|---|---|---|
| Matrix size | 256 × 168 | 64 × 64 | 224 × 175 | 160 × 126 |
| Slice Thickness (mm) | 5 | 8 | 5 | 3.5 |
| Distance factor % | 30 | 50 | 20 | 20 |
| Inversion time (ms) | 180 | - | - | - |
| Repetition time (ms) | 285.6 | 5050 | 5.02 | 9 |
| Echo time (ms) | 1.2 | 1.83 | 2.3 | 1.05, 2.46, 3.69, 4.92, 6.15, 7.38 |
| Acquisition time (s) | 15 a | 10 | 15 | 14 |
| Flip angle (degrees) | 35 | 8 | three and 15 | 4 |
| FOV (mm) | 360 | 381 | 380 | 450 |
| Averages | 1 | 1 | 1 | 1 |
| Cardiac gating | Yes | No | No | No |
| Orientation | Transverse | Transverse | Transverse | Transverse |
| Bandwidth (Hz/Px) | 1085 | 490 | 300 | 1080 |
| Acceleration factor | 2 b | 2 | 2 c | 2 c |
3D, three-dimensional; FOV, field of view; MOLLI, modified Look-Locker inversion recovery; VFA, variable flip angle; VIBE, volumetric interpolated breath-hold examination.
Acquisition time is heart rate dependent.
Applied Parallel acquisition technique GRAPPA (GeneRalized Autocalibrating Partial Parallel Acquisition).
Used CAIPIRINHA (Controlled Aliasing In Parallel Imaging Results IN Higher Acceleration) technique.
Imaging analysis of T1 maps
Two radiologists (10 and 15 years of experience) drew regions of interest (ROIs) along the margins of the liver manually, including as much available parenchyma while keeping away from the biliary tract and blood vessels. The readers were blinded to the volunteers’ clinical history. Major branches of the vessels were cautiously avoided and mean values of the ROIs were considered as T1 relaxation time (Figure 1). The T1 relaxation time of the whole liver is represented by the average T1 values of the right (segment VII-VIII) and left (segment II-IV) lobes. For R2* and PDFF measurements, ROIs were placed manually on the right and left lobes and the mean values averaged across the two lobes were recorded. ROIs for R2* and PDFF measurements were matched to those on single-slice T1 maps, avoiding major vessels and bile ducts. Liver stiffness measurement was performed by a physician blinded to clinical data. Finally, MOLLI liver T1 relaxation times do not need to be corrected for fat or iron, as all subjects have normal levels of hepatic fat and iron concentration. 7,8,25
Figure 1.
Liver T1 maps using (a) MOLLI sequence and (b) B1-corrected VFA sequence in a healthy 23-year-old female. The manually drawn regions of interest were placed at the anatomic level of portal hilum on both T1 maps with distance to the liver border. Large blood vessels and bile ducts were avoided.
Statistical analysis
Normally distributed continuous data were summarized as means and standard deviations (SDs). The intraclass correlation coefficient (ICC) of quantitative data between the two methods was calculated (poor: <0.40; fair: 0.40 to 059; good: 0.6 to 0.74; excellent: 0.75 to 1.00).
Bland-Altman plot 26 was constructed to evaluate the consistency of MOLLI and B1-corrected VFA sequences. Paired t-tests (student’s t-test) were conducted to compare the T1 relaxation times. Independent t-tests (student’s t-test) were performed to compare the T1 relaxation times between males and females. We also applied one-way analysis of variance (ANOVA) for multiple comparisons among the Asian ethnic groups. p < 0.05 was considered statistically significant for all statistical testing. Statistical analyses were performed by commercially available software (MedCalc Software version 19.2; and IBM SPSS Statistics, version 26.0, SPSS Inc).
Results
All of the 60 healthy participants underwent FibroScan and 3T MRI with MOLLI and B1-corrected VFA T1 mapping sequences. Mean value for liver stiffness was 4.6 ± 0.5 (kPa). Liver T1 relaxation times acquired by MOLLI sequence indicated excellent intraobserver agreement in right lobe (ICC: 0.923, 95% CI: 0.868 to 0.956) and left lobe (ICC: 0.906, 95% CI: 0.835 to 0.942). Liver T1 relaxation times acquired by B1-corrected VFA sequence also showed excellent agreement in right lobe (ICC: 0.914, 95% CI: 0.858 to 0.953) and left lobe (ICC: 0.935, 95% CI: 0.901 to 0.965).
Comparison of T1 relaxation times in the whole liver between MOLLI and B1-corrected VFA T1 mapping methods
Liver T1 relaxation times of healthy subjects using both methods are reported in Table 3. The mean T1 relaxation times (ms) in the whole liver were 901 ± 34 by MOLLI and 948 ± 29 by B1-corrected VFA. The correlation coefficient was 0.86 (p < 0.0001). Regression analysis displayed a strong correlation between the two methods in the whole liver (R2 = 0.75, p < 0.0001) (Figure 2). Paired t-test showed a significant difference between the two methods in the whole liver (p < 0.0001). The Bland-Altman plot revealed the mean difference of −46 ms (Figure 3).
Table 3.
Liver T1 values and the correlation coefficient between MOLLI and B1 -corrected VFA
| MOLLI | B1-correced VFA | Correlation coefficient | P value | |
|---|---|---|---|---|
| Healthy volunteers (n=60) | ||||
| Whole liver | 901.98±34.82 | 948.26±29.20 | 0.86 | 0.0001 |
| Right lobe | 909.9±36.42 | 954.5±32.37 | 0.9 | 0.0001 |
| Left lobe | 894.6±40.84 | 941.9±34.44 | 0.76 | 0.0001 |
| Gender | ||||
| Men (n=26) | 897±35.38 | 943.1±29.67 | 0.91 | 0.0001 |
| Female (n=34) | 905.4±34.52 | 952.56±28.54 | 0.88 | 0.0001 |
| Ethnic groups | ||||
| East Asia (n=35) | 899.55±40.08 | 943.94±33.34 | 0.94 | 0.0001 |
| West Asia (n=10) | 898.56±24.24 | 948.56±5.34 | 0.79 | 0.0001 |
| South Asia (n=15) | 915.91±29.41 | 960.82±20.03 | 0.73 | 0.0001 |
MOLLI, modified look-locker inversion recovery; VFA, variable flip angle.
Data are means standard deviation (M SD). P value less than 0.05 indicates a statistically significant difference between the two T1 mapping techniques.
Figure 2.
Regression lines and scatter diagram of liver T1 relaxation times between MOLLI and B1-corrected VFA sequences. Diverging dashed lines = 95% confidence interval, solid parallel lines = 95% prediction interval and thick solid lines = regression line. Diagonal line represents the ideal identity line. Regression equation in the whole liver is as follows: MOLLI (ms) = −94.440 (ms) + [1.049 × B1-corrected VFA (ms)]. The slope of the regression was close to 1. The intercept was statistically different from zero and had statistical significance (p < 0.05)
Figure 3.
Bland-Altman plot shows the mean bias and 95% limits of agreement between MOLLI and B1-corrected VFA T1 mapping methods.
Comparison of liver T1 relaxation times, R2*, and PDFF values between the right and left liver lobes
The mean T1 relaxation times (ms) of the liver in the right lobe were 909 ± 36 by MOLLI and 954 ± 32 by B1-corrected VFA in healthy volunteers. The mean liver T1 relaxation times (ms) of the liver in the left lobe were 894 ± 40 by MOLLI and 941 ± 34 by B1-corrected VFA sequences. R2* (sec−1) values were 43 ± 5 and 41 ± 4 in the right and left lobes, respectively. PDFF (%) values were 2.1 ± 0.8 and 1.7 ± 0.6 in the right and left lobes, respectively. There were significant differences in T1 relaxation times using both methods (Figure 4), R2*, and PDFF values between right and left lobes, (p < 0.05).
Figure 4.
Boxplots of liver T1 using MOLLI and B1-corrected VFA T1 mapping techniques based on (a) the whole liver, right and left lobes; (b) gender; (c) Asian ethnic groups.
T1 relaxation times of the liver based on gender, ethnic groups, using two T1 mapping methods
There was no significant difference of liver T1 relaxation times in healthy volunteers between males and females, using MOLLI (897 ± 35 ms vs 905 ± 34 ms, p = 0.23) or B1-corrected VFA (943 ± 29 ms vs 952 ± 28 ms, p = 0.19) (Table 3, Figure 4). ANOVA test indicated no association of liver T1 relaxation times among Asian ethnic groups, using MOLLI (p = 0.4) or B1-corrected VFA sequences (p = 0.8) (Table 4).
Table 4.
One-way ANOVA for comparison of liver T1 in each Asian ethnic group
| Asian Ethnic groups | Mean difference | 95% CI of difference | P-value |
|---|---|---|---|
| MOLLI | |||
| East (n = 35) vs West (n = 10) | −9.01 | −43.87 to 25.85 | 0.92 |
| East (n = 35) vs South (n = 15) | −26.36 | −55.12 to 2.40 | 0.18 |
| West (n = 10) vs South (n = 15) | −17.35 | −57.32 to 23.01 | 0.53 |
| B1-corrected VFA | |||
| East (n = 35) vs West (n = 10) | −4.63 | −32.21 to 22.96 | 0.89 |
| East (n = 35) vs South (n = 15) | −16.88 | −39.64 to 5.88 | 0.17 |
| West (n = 10) vs South (n = 15) | −12.26 | −44.19 to 19.68 | 0.65 |
MOLLI (modified look-locker inversion recovery), B1-corrected VFA (variable flip angle). p < 0.05 indicates a statistically significant difference between the two groups. East ethnic group: China; West ethnic group: Iran, South ethnic group: India.
Discussion
In the era of T1 mapping techniques, many studies have figured out the use of T1 mapping in patients with chronic liver disease, 4,27 however, these studies lacked the viewpoint to clarify T1 relaxation times for ‘normal liver’. Liver T1 relaxation times are influenced by the liver fat. 13,28,29 Therefore, it remains essential to establish the ‘normal liver’ T1 relaxation times in healthy subjects without focal or diffused liver disease (PDFF<5%). In this study, all of the volunteers were identified to have ‘normal liver’ by 3T MR examination, blood test, and FibroScan results.
Our findings indicated that T1 relaxation time in the normal liver has a strong correlation between the two T1 mapping methods (r = 0.86). It was consistent with the findings of a previous study that measured T1 relaxation time in patients with chronic liver disease. 3 We also found that liver T1 relaxation times by MOLLI were shorter with a larger variance than those of B1-corrected VFA (Figure 4). VFA T1 mapping unlike MOLLI applies consecutive spoiled GRE sequences with at least two different flip angles and can cover the entire liver within a single breath-hold. However, it is more vulnerable to incomplete spoiling and B1 inhomogeneity. We performed B1 inhomogeneity correction before VFA T1 mapping to overcome B1 inhomogeneity. 30 The difference between the two T1 mapping methods can be explained by incomplete spoiling and B1 bias that is not fully fixed in the B1-corrected VFA method. 3,30 Moreover, MOLLI is influenced by the contribution of confounding technical/physical factors, 31,32 is less sensitive to B1 inhomogeneity. 30 In comparison with previous studies that applied the MOLLI method, 7,28 our results showed higher liver T1 relaxation times. This difference can be based on the subject’s heart rate, RR time interval, inversion times, and the type of used MOLLI scheme. 8,33 In addition, the difference in liver T1 relaxation times between Asian and non-Asian healthy controls might be linked to diet-related factors which requires further evaluation.
Our study also indicated that the liver T1 relaxation times obtained by both T1 mapping methods had weak correlations with liver R2* and PDFF values < 5%. It is known that liver T1 relaxation times are influenced by liver fat and iron concentration 14 which might have contributed to these weak correlations. Further studies are needed to investigate the weak correlations of R2* and PDFF values in both T1 mapping techniques.
Differences between T1 relaxation times in lobes of ‘normal liver’ have not been extensively investigated yet. In a recent study of patients with chronic liver disease, the authors indicated a significant difference in T1 relaxation times between the right and left lobes. 9 Among healthy volunteers, we found that the liver T1 relaxation times using both T1 mapping methods, R2*, and PDFF values in the right lobe were higher than those of the left lobe. This difference might be related to B0/B1 inhomogeneity and portal perfusion between the lobes that accounts for higher fat fraction values in the right lobe. 34 Due to B0/B1 inhomogeneity issues, it is unlikely that this difference represents a true difference in liver T1 relaxation times between the two lobes. Significant higher R2* values in the right lobe compared with the left lobe (p < 0.001) could be partially explained by the possible iron-rich blood flow that predominantly streamlines to the right lobe. 35
Determination of liver T1 relaxation times among the various populations may be essential where reference values frequently involve various populations and ethnicities, influencing different measured biological values. In this study, we investigated liver T1 relaxation times in different Asian ethnic groups. The obtained results indicated that liver T1 relaxation times do not differ among Asian ethnic groups. Therefore, by applying ‘normal liver’ T1 relaxation times, clinicians can identify the population with potential liver disease which is useful for further evaluation and follow-ups.
In the present study, we found that although females had longer T1 relaxation times than males, the gender difference in both methods does not affect liver T1 relaxation times in healthy population. However, characteristics of T1 relaxation times among healthy females and males have been discussed controversially in the literature: Contrary to our findings, Mojtahed et al 12 used the concept of the fibro-suppressive effect of female estrogen, to explain the inconsistency and significant difference in liver T1 relaxation times between genders. However, the female estrogen influence on postponing of liver fibrosis progress is important only when pathological conditions, such as HCV-related advanced fibrosis (≥3 fibrosis) were present in the liver, 36 or when females with chronic liver disease were compared before and after menopause. 37 Furthermore, several factors between genders, such as habitual differences 38 and metabolic syndrome, 39 were not correctly adjusted in the article by Mojtahed et al. Thus, variations in liver T1 relaxation times between the genders might not be explained by gender alone. To clarify if estrogen has any influence on histology and the T1 relaxation time of the healthy liver, further studies that focus on a strict selection of participants with ‘normal liver’ are still in need.
In comparison with previous studies, 6,17,40 ours has distinctive features. This is the first study performed in 60 healthy Asian population (PDFF<5%) with two T1 mapping methods (MOLLI and B1-corrected VFA). Although the ideal approach to gain normal liver T1 relaxation times is to recruit subjects with histologically normal livers, liver biopsy is not always available based on its invasiveness. Therefore, a multiparametric approach using FibroScan and MRI-PDFF for recruiting healthy population was necessary for this study. Consequently, with a strict selection of subjects, the healthy participants were separated from those with potential liver diseases.
There are several limitations to our study. First, a larger sample size is required to investigate the positive trend between liver T1 relaxation time and Asian ethnicities (Figure 4), and also for better evaluation of the liver T1 relaxation time with other T1 mapping methods. Second, this study was performed in one institution, on the same MR machine over one field of strength. Third, based on the dependency on the confounding factors in the MOLLI method, 31,32 the liver T1 measurements are “apparent” and not “true” T1 values. 41 Further prospective studies are needed to compare T1 of the normal liver with different MOLLI variants. In the future, more research is required for the establishment of normal reference values and evaluation of the mapping techniques' reproducibility with different scanners at various imaging centers. In addition, we used a multiecho Dixon sequence with six echoes to evaluate R2* (R2*=1 /T2*), the longest echo time of 7.38 ms might not be long enough to accurately measure T2* values near 20 ms at 3T and additional studies on accurate measurement of T2* are needed.
Conclusion
The T1 relaxation times of the normal liver (PDFF <5%) in healthy population were established by two T1 mapping methods. It may provide suitable and robust baseline values for the assessment of liver diseases.
Footnotes
Acknowledgements: This work was supported by Natural Science Foundation of Shandong Province (No. ZR2020MH285) and Academic promotion program of Shandong First Medical University (No. 2019QL023). The authors thank Mengxiao Liu from Siemens Healthineers Ltd (Shanghai 201318, China) for the incredible editorial assistance.
Funding: This work was supported by the Natural Science Foundation of Shandong Province (No. ZR2020MH285) and the Academic promotion program of Shandong First Medical University (No. 2019QL023).
Ethical Approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Disclosures: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. All authors have read and approved this version of the article. No part of this paper has been published or submitted elsewhere.
Contributor Information
Armin Ghavamian, Email: armin.ghavamian@gmail.com, Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong, China .
Cuihong Liu, Email: 1395032209@qq.com, Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong, China ; Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong University, Shandong, China .
Bing Kang, Email: kangbing0228@163.com, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong University, Shandong, China .
Xianshun Yuan, Email: yuanxianshun@163.com, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong University, Shandong, China .
Ximing Wang, Email: WANGXMSLYY@163.com, Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong, China ; Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong University, Shandong, China .
Ling Gao, Email: linggao@sdu.edu.cn, Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Shandong Clinical Medical Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Shandong, China .
Xinya Zhao, Email: zhaoxinya2000@126.com, Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong, China ; Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong University, Shandong, China .
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