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Li Q, Zhang T, Yao S, Gao F, Nie L, Tang H, Song B, Wei Y. Preoperative assessment of liver regeneration using T1 mapping and the functional liver imaging score derived from Gd-EOB-DTPA-enhanced magnetic resonance for patient with hepatocellular carcinoma after hepatectomy. Front Immunol 2025; 16:1516848. [PMID: 39949770 PMCID: PMC11821634 DOI: 10.3389/fimmu.2025.1516848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 01/02/2025] [Indexed: 02/16/2025] Open
Abstract
Objectives To explore whether T1 mapping parameters and the functional liver imaging score (FLIS) based on Gd-EOB-DTPA MRI could evaluate liver regeneration after hepatectomy for HCC patient. Methods This retrospective study finally included 60 HCC patients (48 men and 12 women, with a median age of 53 years). T1 relaxation time of liver before gadoxetic acid injection (T1pre) and during the hepatobiliary phase (T1HBP), reduction rate (Δ%) and FLIS were calculated, their correlations with liver fibrosis stage, hepatic steatosis, and liver regeneration, quantified as regeneration index (RI), were assessed by Kendall's tau-b correlation test or Spearman's correlation test. Multivariate linear regression analyses were used to explore the indicator of RI. Results T1pre, T1HBP, Δ%, and FLIS manifested significant correlation with fibrosis stage (r = 0.434, P =0.001; r = 0.546, P < 0.001; r = -0.356, P =0.005; r = -0.653, P <0.001, respectively). T1pre showed significant correction with steatosis grade (r = 0.415, P =0.001). Fibrosis stage and steatosis grade were associated with RI (r = -0.436, P<0.001; r = -0.338, P =0.008). Accordingly, T1pre, T1HBP and FLIS were the significant predictors (P<0.05) of RI in multivariate analysis. Similarly, in the patients undergoing minor hepatectomy (n=35), T1HBP, Δ% and FLIS were related to RI (P<0.05) in multivariate analysis. Nevertheless, in the patients undergoing major hepatectomy (n=25), no T1 mapping parameter and FLIS was the independent predictor of RI. Conclusions T1 mapping parameters and FLIS were the potential noninvasive indicators of liver regeneration, except for HCC patients undergoing major hepatectomy. Clinical relevance statement The value of T1 mapping and FLIS with Gd-EOB-DTPA MRI for accurate preoperative evaluation of liver regeneration is critical to prevent liver failure and improve prognosis of HCC patients.
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Affiliation(s)
- Qian Li
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Tong Zhang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Shan Yao
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Feifei Gao
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Lisha Nie
- MRI Research, GE Healthcare (China), Beijing, China
| | - Hehan Tang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Radiology, Sanya People’s Hospital, Sanya, China
| | - Yi Wei
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
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Chen YY, Yang L, Li J, Rao SX, Ding Y, Zeng MS. Gadoxetic acid-enhanced magnetic resonance imaging in the assessment of hepatic sinusoidal obstruction syndrome in a mouse model. World J Hepatol 2024; 16:1167-1176. [PMID: 39221094 PMCID: PMC11362905 DOI: 10.4254/wjh.v16.i8.1167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 07/13/2024] [Accepted: 08/02/2024] [Indexed: 08/21/2024] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy can cause hepatic sinusoidal obstruction syndrome (SOS) in patients with colorectal cancer liver metastases and increases postoperative morbidity and mortality. AIM To evaluate T1 mapping based on gadoxetic acid-enhanced magnetic resonance imaging (MRI) for diagnosis of hepatic SOS induced by monocrotaline. METHODS Twenty-four mice were divided into control (n = 10) and experimental (n = 14) groups. The experimental groups were injected with monocrotaline 2 or 6 days before MRI. MRI parameters were: T1 relaxation time before enhancement; T1 relaxation time 20 minutes after enhancement (T1post); a reduction in T1 relaxation time (△T1%); and first enhancement slope percentage of the liver parenchyma (ESP). Albumin and bilirubin score was determined. Histological results served as a reference. Liver parenchyma samples from the control and experimental groups were analyzed by western blotting, and organic anion transporter polypeptide 1 (OATP1) was measured. RESULTS T1post, △T1%, and ESP of the liver parenchyma were significantly different between two groups (all P < 0.001) and significantly correlated with the total histological score of hepatic SOS (r = -0.70, 0.68 and 0.79; P < 0.001). △T1% and ESP were positively correlated with OATP1 levels (r = 0.82, 0.85; P < 0.001), whereas T1post had a negative correlation with OATP1 levels (r = -0.83; P < 0.001). CONCLUSION T1 mapping based on gadoxetic acid-enhanced MRI may be useful for diagnosis of hepatic SOS, and MRI parameters were associated with OATP1 levels.
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Affiliation(s)
- Yuan-Yuan Chen
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Li Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jun Li
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Sheng-Xiang Rao
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Ying Ding
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
| | - Meng-Su Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Gunwhy ER, Hines CDG, Green C, Laitinen I, Tadimalla S, Hockings PD, Schütz G, Kenna JG, Sourbron S, Waterton JC. Assessment of hepatic transporter function in rats using dynamic gadoxetate-enhanced MRI: a reproducibility study. MAGMA (NEW YORK, N.Y.) 2024; 37:697-708. [PMID: 39105950 PMCID: PMC11417070 DOI: 10.1007/s10334-024-01192-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 07/19/2024] [Accepted: 07/23/2024] [Indexed: 08/07/2024]
Abstract
OBJECTIVE Previous studies have revealed a substantial between-centre variability in DCE-MRI biomarkers of hepatocellular function in rats. This study aims to identify the main sources of variability by comparing data measured at different centres and field strengths, at different days in the same subjects, and over the course of several months in the same centre. MATERIALS AND METHODS 13 substudies were conducted across three facilities on two 4.7 T and two 7 T scanners using a 3D spoiled gradient echo acquisition. All substudies included 3-6 male Wistar-Han rats each, either scanned once with vehicle (n = 76) or twice with either vehicle (n = 19) or 10 mg/kg of rifampicin (n = 13) at follow-up. Absolute values, between-centre reproducibility, within-subject repeatability, detection limits, and effect sizes were derived for hepatocellular uptake rate (Ktrans) and biliary excretion rate (kbh). Sources of variability were identified using analysis of variance and stratification by centre, field strength, and time period. RESULTS Data showed significant differences between substudies of 31% for Ktrans (p = 0.013) and 43% for kbh (p < 0.001). Within-subject differences were substantially smaller for kbh (8%) but less so for Ktrans (25%). Rifampicin-induced inhibition was safely above the detection limits, with an effect size of 75 ± 3% in Ktrans and 67 ± 8% in kbh. Most of the variability in individual data was accounted for by between-subject (Ktrans = 23.5%; kbh = 42.5%) and between-centre (Ktrans = 44.9%; kbh = 50.9%) variability, substantially more than the between-day variation (Ktrans = 0.1%; kbh = 5.6%). Significant differences in kbh were found between field strengths at the same centre, between centres at the same field strength, and between repeat experiments over 2 months apart in the same centre. DISCUSSION Between-centre bias caused by factors such as hardware differences, subject preparations, and operator dependence is the main source of variability in DCE-MRI of liver function in rats, closely followed by biological between-subject differences. Future method development should focus on reducing these sources of error to minimise the sample sizes needed to detect more subtle levels of inhibition.
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Affiliation(s)
- Ebony R Gunwhy
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Polaris, 18 Claremont Crescent, Sheffield, S10 2TA, UK.
| | | | - Claudia Green
- MR & CT Contrast Media Research, Bayer AG, Berlin, Germany
| | - Iina Laitinen
- Antaros Medical, GoCo House, Mölndal, Sweden
- Sanofi-Aventis GmbH, Frankfurt, Germany
| | - Sirisha Tadimalla
- Institute of Medical Physics, University of Sydney, Sydney, Australia
| | - Paul D Hockings
- Antaros Medical, GoCo House, Mölndal, Sweden
- Chalmers University of Technology, Gothenburg, Sweden
| | - Gunnar Schütz
- MR & CT Contrast Media Research, Bayer AG, Berlin, Germany
| | | | - Steven Sourbron
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Polaris, 18 Claremont Crescent, Sheffield, S10 2TA, UK
| | - John C Waterton
- Bioxydyn Ltd, St. James Tower, Manchester, UK
- Centre for Imaging Sciences, Division of Informatics Imaging & Data Sciences, School of Health Sciences, Faculty of Biology Medicine & Health, University of Manchester, Manchester, UK
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Li S, Xu X, Li C, Xu Z, Wu K, Ye Q, Zhang Y, Jiang X, Cang C, Tian C, Wen J. In vivo labeling and quantitative imaging of neuronal populations using MRI. Neuroimage 2023; 281:120374. [PMID: 37729795 DOI: 10.1016/j.neuroimage.2023.120374] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 08/30/2023] [Accepted: 09/10/2023] [Indexed: 09/22/2023] Open
Abstract
The study of neural circuits, which underlies perception, cognition, emotion, and behavior, is essential for understanding the mammalian brain, a complex organ consisting of billions of neurons. To study the structure and function of the brain, in vivo neuronal labeling and imaging techniques are crucial as they provide true physiological information that ex vivo methods cannot offer. In this paper, we present a new strategy for in vivo neuronal labeling and quantification using MRI. We demonstrate the efficacy of this method by delivering the oatp1a1 gene to the target neurons using rAAV2-retro virus. OATP1A1 protein expression on the neuronal membrane increased the uptake of a specific MRI contrast agent (Gd-EOB-DTPA), leading to hyperintense signals on T1W images of labeled neuronal populations. We also used dynamic contrast enhancement-based methods to obtain quantitative information on labeled neuronal populations in vivo.
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Affiliation(s)
- Shana Li
- The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, PR China
| | - Xiang Xu
- The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, PR China
| | - Canjun Li
- School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, PR China
| | - Ziyan Xu
- School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, PR China
| | - Ke Wu
- The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, PR China
| | - Qiong Ye
- Key Laboratory of High Field Magnetic Resonance Image of Anhui Province, High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, PR China
| | - Yan Zhang
- The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, PR China
| | - Xiaohua Jiang
- The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, PR China
| | - Chunlei Cang
- School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, PR China
| | - Changlin Tian
- The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, PR China; School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, PR China; Key Laboratory of High Field Magnetic Resonance Image of Anhui Province, High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, PR China.
| | - Jie Wen
- The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, PR China.
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Xue Y, Xiao B, Xia Z, Dai L, Xia Q, Zhong L, Zhu C, Zhu J. A New OATP-Mediated Hepatobiliary-Specific Mn(II)-Based MRI Contrast Agent for Hepatocellular Carcinoma in Mice: A Comparison With Gd-EOB-DTPA. J Magn Reson Imaging 2023; 58:926-933. [PMID: 36609994 DOI: 10.1002/jmri.28590] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/27/2022] [Accepted: 12/27/2022] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Growing concerns about the safety of gadolinium (Gd)-based contrast agents have reinforced the need for the development of Gd-free MRI contrast agents (CAs) that are effective in imaging liver tumors. PURPOSE To evaluate the ability of Mn-BnO-TyEDTA MRI CA to detect hepatocellular carcinoma in a mouse model of implanted liver tumor. STUDY TYPE Prospective. ANIMAL MODEL Thirteen orthotopically implanted liver tumor mice. FIELD STRENGTH/SEQUENCE 3.0 T/precontrast and postcontrast T1-weighted fast spoiled gradient recalled echo and T2-weighted fast recovery fast spin-echo imaging with fat suppression. ASSESSMENT The relative enhancement ratio was calculated and statistically compared. Lesion detection in postcontrast images was analyzed by calculations of area under the curve (AUC, the increases in liver-to-tumor contrast-to-noise ratio [∆CNR] vs. time curve). Mn or Gd levels were measured in the liver and tumoral tissues by inductively coupled plasma-mass spectrometry. Tumor specimens were stained with hematoxylin and eosin (H&E) and the expression of organic anion transfer peptide (OATP)1B1 was evaluated by immunofluorescence (IF) staining and mean fluorescence intensity (MFI) was calculated. STATISTICAL TESTS Unpaired t-test and two-tailed paired t-test. P < 0.05 was considered statistical significance. RESULTS Mn-BnO-TyEDTA and Gd-EOB-DTPA demonstrated nearly identical enhancement patterns in the liver, tumor, and psoas muscle and no difference in lesion detection (AUC10-30, Mn = 851 ∆CR·min, AUC10-30, Gd = 823 ∆CR·min). A Significant higher concentration of metal (Mn or Gd) was found in the liver compared to the tumor ([Mn]liver = 0.88 ± 0.07 μmmol/g, [Mn]tumor = 0.49 ± 0.05 μmmol/g, [Gd]liver = 0.65 ± 0.07 μmmol/g, [Gd]tumor = 0.27 ± 0.04 μmmol/g). IF staining showed significantly decreased expression of OATP1B1 in the tumor core compared to the liver (MFItumor = 5.28 ± 1.54, MFIliver = 25.49 ± 3.41). DATA CONCLUSION Mn-BnO-TyEDTA can provide comparable hepatobiliary tumor contrast enhancement to Gd-EOB-DTPA. EVIDENCE LEVEL 1 TECHNICAL EFFICACY: Stage 1.
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Affiliation(s)
- Yuan Xue
- Medical Imaging Key Laboratory of Sichuan Province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
- School of Basic Medical Sciences and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Bin Xiao
- Medical Imaging Key Laboratory of Sichuan Province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Zhiyang Xia
- Medical Imaging Key Laboratory of Sichuan Province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
- School of Basic Medical Sciences and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Lixiong Dai
- Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China
| | - Qian Xia
- Medical Imaging Key Laboratory of Sichuan Province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Lei Zhong
- Medical Imaging Key Laboratory of Sichuan Province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Chunrong Zhu
- Medical Imaging Key Laboratory of Sichuan Province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
- School of Basic Medical Sciences and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Jiang Zhu
- Medical Imaging Key Laboratory of Sichuan Province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
- School of Pharmacy, North Sichuan Medical College, Nanchong, Sichuan, China
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Im WH, Song JS, Jang W. Noninvasive staging of liver fibrosis: review of current quantitative CT and MRI-based techniques. Abdom Radiol (NY) 2022; 47:3051-3067. [PMID: 34228199 DOI: 10.1007/s00261-021-03181-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 06/12/2021] [Accepted: 06/14/2021] [Indexed: 01/18/2023]
Abstract
Liver fibrosis features excessive protein accumulation in the liver interstitial space resulting from repeated tissue injury due to chronic liver disease. Liver fibrosis eventually proceeds to cirrhosis and associated complications. So, early diagnosis and staging of liver fibrosis are of vital importance for clinical treatment. Liver biopsy remains the gold standard for the diagnosing and staging of fibrosis, but it is suboptimal due to various limitations. Recently, efforts have been made to migrate toward noninvasive techniques for assessing liver fibrosis. CT is relatively easy to perform, relatively standardized for different scanners, and does not require additional hardware in liver fibrosis staging. MRI is frequently performed to characterize indeterminate liver lesions. Because it does not use ionizing radiation and features high image contrast, its role has increased in the staging of liver fibrosis. More recently, several studies on liver fibrosis staging using deep learning algorithms in CT or MRI have been proposed and have shown meaningful results. In this review, we summarize the basic concept, diagnostic performance, and advantages and limitations of each technique to noninvasively stage liver fibrosis.
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Affiliation(s)
- Won Hyeong Im
- Department of Radiology, The 3rd Flying Training Wing, Sacheon, 52516, South Korea
| | - Ji Soo Song
- Department of Radiology, Jeonbuk National University Medical School and Hospital, 20 Geonji-ro, Deokjin-gu, Jeonju, 54907, Jeonbuk, South Korea.
- Research Institute of Clinical Medicine of Jeonbuk National University, Jeonju, South Korea.
- Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea.
| | - Weon Jang
- Department of Radiology, Jeonbuk National University Medical School and Hospital, 20 Geonji-ro, Deokjin-gu, Jeonju, 54907, Jeonbuk, South Korea
- Research Institute of Clinical Medicine of Jeonbuk National University, Jeonju, South Korea
- Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea
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Monocrotaline Toxicity Alters the Function of Hepatocyte Membrane Transporters in Rats. Int J Mol Sci 2022; 23:ijms23147928. [PMID: 35887275 PMCID: PMC9323134 DOI: 10.3390/ijms23147928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/13/2022] [Accepted: 07/16/2022] [Indexed: 12/10/2022] Open
Abstract
Pyrrolizidine alkaloid monocrotaline (MCT) induces sinusoidal obstruction syndrome (SOS) in rats characterised by a sinusoidal congestive obstruction. Additionally, MCT administration decreases the biliary excretion of gadobenate dimeglumine (BOPTA), a hepatobiliary substrate used in clinical imaging. BOPTA crosses hepatocyte membranes through organic anion transporting polypeptides, multidrug-resistance-associated protein 2, and Mrp3/4 transporters, and a modified function of these transporters is likely to explain the decreased biliary excretion. This study compared BOPTA transport across hepatocytes in livers isolated from normal (Nl) rats and rats with intragastric administration of MCT. BOPTA hepatocyte influx clearance was similar in both groups, while biliary clearance and bile concentrations were much lower in MCT than in Nl livers. BOPTA efflux clearance back to the sinusoids compensated for the low biliary excretion, and hepatocyte concentrations remained similar in both groups. This SOS-associated changes of transporter functions might impact the pharmacokinetics of numerous drugs that use similar transporters to cross hepatocytes.
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Obmann VC, Catucci D, Berzigotti A, Gräni C, Ebner L, Heverhagen JT, Christe A, Huber AT. T1 reduction rate with Gd-EOB-DTPA determines liver function on both 1.5 T and 3 T MRI. Sci Rep 2022; 12:4716. [PMID: 35304554 PMCID: PMC8933426 DOI: 10.1038/s41598-022-08659-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 02/01/2022] [Indexed: 11/10/2022] Open
Abstract
Magnetic resonance T1 mapping before and after Gd-EOB-DTPA administration allows quantification of the T1 reduction rate as a non-invasive surrogate marker of liver function. A major limitation of T1 relaxation time measurement is its dependency on MRI field strengths. Since T1 reduction rate is calculated as the relative shortening of T1 relaxation time before and after contrast administration, we hypothesized that the T1 reduction rate is comparable between 1.5 and 3 T. We thus compared liver T1 relaxation times between 1.5 and 3 T in a total of 243 consecutive patients (124, 1.5 T and 119, 3 T) between 09/2018 and 07/2019. T1 reduction rates were compared between patients with no cirrhosis and patients with cirrhosis Child-Pugh A-C. There was no significant difference of T1 reduction rate between 1.5 and 3 T in any patient group (p-value 0.126-0.861). On both 1.5 T and 3 T, T1 reduction rate allowed to differentiate between patients with no cirrhosis and patients with liver cirrhosis Child A-C (p < 0.001). T1 reduction rate showed a good performance to predict liver cirrhosis Child A (AUC = 0.83, p < 0.001), Child B (AUC = 0.83, p < 0.001) and Child C (AUC = 0.92, p < 0.001). In conclusion, T1 reduction rate allows to determine liver function on Gd-EOB-DTPA MRI with comparable values on 1.5 T and 3 T.
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Affiliation(s)
- Verena Carola Obmann
- Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 10, 3010, Bern, Switzerland
| | - Damiano Catucci
- Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 10, 3010, Bern, Switzerland
| | - Annalisa Berzigotti
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Christoph Gräni
- Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Lukas Ebner
- Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 10, 3010, Bern, Switzerland
| | - Johannes Thomas Heverhagen
- Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 10, 3010, Bern, Switzerland
| | - Andreas Christe
- Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 10, 3010, Bern, Switzerland
| | - Adrian Thomas Huber
- Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 10, 3010, Bern, Switzerland.
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Liu HF, Xu YS, Liu Z, Che KY, Sheng Y, Ding JL, Zhang JG, Lei JQ, Xing W. Value of Gd-EOB-DTPA-Enhanced MRI and Diffusion-Weighted Imaging in Detecting Residual Hepatocellular Carcinoma After Drug-Eluting Bead Transarterial Chemoembolization. Acad Radiol 2021; 28:790-798. [PMID: 32414638 DOI: 10.1016/j.acra.2020.04.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 04/04/2020] [Accepted: 04/04/2020] [Indexed: 02/07/2023]
Abstract
RATIONALE AND OBJECTIVES To investigate the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in diagnosing residual hepatocellular carcinoma (HCC) after drug-eluting bead transarterial chemoembolization (DEB-TACE). MATERIALS AND METHODS Sixty-two patients (50 men, 12 women; mean age, 56.8 ± 1.4 years) with 74 HCCs who underwent Gd-EOB-DTPA-enhanced MRI and DWI in 1-2-month intervals after DEB-TACE were retrospectively studied. Imaging features derived from Gd-EOB-DTPA-enhanced MRI and DWI were analyzed and compared between residual HCCs and necrotic tumors. The sensitivity and specificity of Gd-EOB-DTPA-enhanced MRI and DWI with quantitative apparent diffusion coefficient (ADC) values in diagnosing residual HCCs were calculated and compared, based on the reference standard of pathology and/or angiography. RESULTS Thirty-three residual HCCs and 41 necrotic tumors were diagnosed. Residual HCCs presented characteristics of arterial hypervascularity (90.91%) and DWI hyperintensity (78.78%), which were of importance in differentiating necrotic tumors (p< 0.05). DWI showed lower sensitivity (78.79% vs. 96.97%, p< 0.001) and specificity (78.05% vs. 100%, p< 0.001) than Gd-EOB-DTPA-enhanced MRI in diagnosing residual HCCs after DEB-TACE. Residual HCCs had a significantly higher mean ADC value than necrotic tumors (1.30 ± 0.32 × 10-3 mm2/s vs. 1.55 ± 0.50 × 10-3 mm2/s, p< 0.001). Receiver operating characteristic curve analysis for identifying residual HCCs demonstrated that the threshold ADC value of 1.25 × 10-3 mm2/s had 84.85% sensitivity and 87.80% specificity. CONCLUSION Gd-EOB-DTPA-enhanced MRI is superior to DWI in diagnosing residual HCCs after DEB-TACE, and arterial hypervascularity and DWI hyperintensity are important imaging features in distinguishing residual HCCs from necrotic tumors.
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T2 mapping in gadoxetic acid-enhanced MRI: utility for predicting decompensation and death in cirrhosis. Eur Radiol 2021; 31:8376-8387. [PMID: 33782768 DOI: 10.1007/s00330-021-07805-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 12/21/2020] [Accepted: 02/17/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVES To determine whether T2 mapping in liver MRI can predict decompensation and death in cirrhotic patients. METHODS This retrospective study included 292 cirrhotic patients who underwent gadoxetic acid-enhanced MRI, including T1 and T2 mapping at 10-min hepatobiliary phase by using the Look-Locker and radial turbo spin-echo sequences, respectively. T1 and T2 values of the liver and spleen were measured. The association of MR parameters and serum markers with decompensation and death was investigated. Risk models combining T2Liver, serum albumin level, and Model for End-Stage Liver Disease (MELD) score were created for predicting decompensation (T2Liver, < 49.3 versus ≥ 49.3 ms) and death (< 57.4 versus ≥ 57.4 ms). RESULTS In patients with compensated cirrhosis at baseline and in the full patient cohort, 9.6% (19 of 197) and 5.1% (15 of 292) developed decompensation and died during the mean follow-up periods of 18.7 and 19.2 months, respectively. A prolonged T2Liver (hazard ratio (HR), 2.59; 95% confidence interval (CI), 1.26, 5.31) was independently predictive of decompensation along with the serum albumin level (HR, 0.28; 95% CI, 0.12, 0.68) and MELD score (HR, 1.34; 95% CI, 1.08, 1.66). T2Liver (HR, 2.61; 95% CI, 1.19, 5.72) and serum albumin level (HR, 0.46; 95% CI, 0.19, 1.14) were independent predictors of death. The mean times to decompensation (12.9 versus 29.2 months) and death (16.5 versus 29.6 months) were significantly different between the high- and low-risk groups (p < 0.001). CONCLUSION T2Liver from T2 mapping can predict decompensation and death in patients with cirrhosis. KEY POINTS • Liver T2 values from the radial turbo spin-echo (TSE) T2 mapping sequence with tiered echo sharing and pseudo golden-angle (pGA) reordering were significantly higher in decompensated cirrhosis than compensated cirrhosis. • Liver T2 values from the radial TSE T2 mapping sequence with tiered echo sharing and pGA reordering can predict decompensation and death in patients with cirrhosis. • T2 mapping is recommended as part of liver MRI examinations for cirrhotic patients because it can provide a noninvasive prognostic marker for the development of decompensation and death.
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Abstract
Perfusion imaging allows for the quantitative extraction of physiological perfusion parameters of the liver microcirculation at levels far below the spatial the resolution of CT and MR imaging. Because of its peculiar structure and architecture, perfusion imaging is more challenging in the liver than in other organs. Indeed, the liver is a mobile organ and significantly deforms with respiratory motion. Moreover, it has a dual vascular supply and the sinusoidal capillaries are fenestrated in the normal liver. Using extracellular contrast agents, perfusion imaging has shown its ability to discriminate patients with various stages of liver fibrosis. The recent introduction of hepatobiliary contrast agents enables quantification of both the liver perfusion and the hepatocyte transport function using advanced perfusion models. The purpose of this review article is to describe the characteristics of liver perfusion imaging to assess chronic liver disease, with a special focus on CT and MR imaging.
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Zhou IY, Catalano OA, Caravan P. Advances in functional and molecular MRI technologies in chronic liver diseases. J Hepatol 2020; 73:1241-1254. [PMID: 32585160 PMCID: PMC7572718 DOI: 10.1016/j.jhep.2020.06.020] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 06/11/2020] [Accepted: 06/15/2020] [Indexed: 02/06/2023]
Abstract
MRI has emerged as the most comprehensive non-invasive diagnostic tool for liver diseases. In recent years, the value of MRI in hepatology has been significantly enhanced by a wide range of contrast agents, both clinically available and under development, that add functional information to anatomically detailed morphological images, or increase the distinction between normal and pathological tissues by targeting molecular and cellular events. Several classes of contrast agents are available for contrast-enhanced hepatic MRI, including i) conventional non-specific extracellular fluid contrast agents for assessing tissue perfusion; ii) hepatobiliary-specific contrast agents that are taken up by functioning hepatocytes and excreted through the biliary system for evaluating hepatobiliary function; iii) superparamagnetic iron oxide particles that accumulate in Kupffer cells; and iv) novel molecular contrast agents that are biochemically targeted to specific molecular/cellular processes for staging liver diseases or detecting treatment responses. The use of different functional and molecular MRI methods enables the non-invasive assessment of disease burden, progression, and treatment response in a variety of liver diseases. A high diagnostic performance can be achieved with MRI by combining imaging biomarkers.
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Affiliation(s)
- Iris Y. Zhou
- Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States.,Harvard Medical School, Boston, MA, USA,Institute for Innovation in Imaging (i3), Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
| | - Onofrio A. Catalano
- Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States.,Harvard Medical School, Boston, MA, USA,Division of Abdominal Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, United States
| | - Peter Caravan
- Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States; Harvard Medical School, Boston, MA, USA; Institute for Innovation in Imaging (i(3)), Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA.
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13
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Yang L, Ding Y, Rao S, Chen C, Zeng M. T 1 Mapping on Gd-EOB-DTPA-Enhanced MRI for the Prediction of Oxaliplatin-Induced Liver Injury in a Mouse Model. J Magn Reson Imaging 2020; 53:896-902. [PMID: 32979019 DOI: 10.1002/jmri.27377] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 09/06/2020] [Accepted: 09/08/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Oxaliplatin-induced liver injury (OILI) not only impairs hepatic regeneration but also increases postoperative morbidity and mortality. Therefore, noninvasive, accurate, and early diagnosis of OILI is mandatory. PURPOSE To evaluate the potential of T1 mapping on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI for assessing OILI in a mouse model. STUDY TYPE Case control, animal model. ANIMAL MODEL Thirty oxaliplatin-treated mice and 10 control mice were included. FIELD STRENGTH Volumetric interpolated breath-hold examination sequence: 3T scanner with a phased-array animal 8-channel coil. T1 mapping before and at hepatobiliary phase (HBP) after injection of Gd-EOB-DTPA were undertaken. ASSESSMENT T1 relaxation times of the liver parenchyma were measured and the reduction rate (ΔT1 %) was calculated. Histological findings were used as a standard reference. STATISTICAL TESTS The Kruskal-Wallis test with pairwise comparisons using the Mann-Whitney U-test were applied to compare the parameters across groups. Spearman's rank correlation test and receiver operating characteristics (ROC) analyses were performed. Areas under the curves (AUCs) were compared using the DeLong method. RESULTS Histologically, mice were classified as normal (n = 10), hepatocellular degeneration without fibrosis (n = 16), and hepatocellular degeneration with fibrosis (n = 14). HBP T1 relaxation time increased with the severity of OILI (rho = 0.60, P < 0.05), and ΔT1 % decreased with the severity of OILI (rho = -0.78, P < 0.05). AUC was 0.92 for ΔT1 % in differentiating hepatocellular degeneration without fibrosis from normal liver, but HBP T1 relaxation time could not distinguish them (P = 0.09). AUCs were 0.96 and 0.95 for HBP T1 relaxation time, and 0.90 and 0.84 for ΔT1 % in discriminating OILI with fibrosis from normal liver and OILI without fibrosis. DATA CONCLUSION HBP T1 relaxation time and ΔT1 % of Gd-EOB-DTPA enhanced MRI was useful for assessing OILI. ΔT1 % may be more sensitive than HBP T1 relaxation time in detecting early stage of liver injury. LEVEL OF EVIDENCE 2. TECHNICAL EFFICACY STAGE 5.
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Affiliation(s)
- Li Yang
- Department of Radiology, Zhongshan, Hospital of Fudan University, Shanghai, China
| | - Ying Ding
- Department of Radiology, Zhongshan, Hospital of Fudan University, Shanghai, China
| | - Shengxiang Rao
- Department of Radiology, Zhongshan, Hospital of Fudan University, Shanghai, China
| | - Caizhong Chen
- Department of Radiology, Zhongshan, Hospital of Fudan University, Shanghai, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan, Hospital of Fudan University, Shanghai, China
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Hernández Lozano I, Langer O. Use of imaging to assess the activity of hepatic transporters. Expert Opin Drug Metab Toxicol 2020; 16:149-164. [PMID: 31951754 PMCID: PMC7055509 DOI: 10.1080/17425255.2020.1718107] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 01/15/2020] [Indexed: 12/13/2022]
Abstract
Introduction: Membrane transporters of the SLC and ABC families are abundantly expressed in the liver, where they control the transfer of drugs/drug metabolites across the sinusoidal and canalicular hepatocyte membranes and play a pivotal role in hepatic drug clearance. Noninvasive imaging methods, such as PET, SPECT or MRI, allow for measuring the activity of hepatic transporters in vivo, provided that suitable transporter imaging probes are available.Areas covered: We give an overview of the working principles of imaging-based assessment of hepatic transporter activity. We discuss different currently available PET/SPECT radiotracers and MRI contrast agents and their applications to measure hepatic transporter activity in health and disease. We cover mathematical modeling approaches to obtain quantitative parameters of transporter activity and provide a critical assessment of methodological limitations and challenges associated with this approach.Expert opinion: PET in combination with pharmacokinetic modeling can be potentially applied in drug development to study the distribution of new drug candidates to the liver and their clearance mechanisms. This approach bears potential to mechanistically assess transporter-mediated drug-drug interactions, to assess the influence of disease on hepatic drug disposition and to validate and refine currently available in vitro-in vivo extrapolation methods to predict hepatic clearance of drugs.
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Affiliation(s)
| | - Oliver Langer
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
- Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
- Preclinical Molecular Imaging, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria
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15
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Application Value of Magnetic Resonance Perfusion Imaging in the Early Diagnosis of Rat Hepatic Fibrosis. BIOMED RESEARCH INTERNATIONAL 2019; 2019:5095934. [PMID: 31950040 PMCID: PMC6949670 DOI: 10.1155/2019/5095934] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 11/24/2019] [Accepted: 12/09/2019] [Indexed: 12/17/2022]
Abstract
Objective To assess the application value of perfusion-weighted imaging (PWI) in early diagnosis, quantitation, and hepatic fibrosis staging by analyzing the related parameters in hepatic fibrosis. Methods A total of 60 rats were randomly divided into the hepatic fibrosis and control groups, and carbon tetrachloride (CCL4) was used to establish the liver fibrosis model. All rats underwent PWI examination, and the trend of the time-signal intensity curve (TIC, automatically generated by the software) was observed. Also, the perfusion parameters, maximum signal reduction ratio (SRRmax), time to peak (TTP), and mean transit time (MTT), were analyzed and compared with pathological staging. Results The TIC curve was characterized by slow wash-in and wash-out with a low and wide peak. The PWI perfusion parameters were statistically significant in specific groups (P < 0.05): SRRmax values (control group and F3, F4), TTP, and MTT values (control group and F2–F4, F1 and F3, F1 and F4, and F2 and F4 in addition to TTP values for F1 and F2). Pearson's correlation analysis showed a negative correlation of SRRmax with hepatic fibrosis stage (r = −0.439, P < 0.05), while TTP and MTT values were positively correlated with hepatic fibrosis stage (TTP, r = 0.798; MTT, r = 0.647; all P < 0.001). Conclusions PWI perfusion parameters reflect the degree of hepatic fibrosis, especially TTP and MTT, and PWI is recommended for the early diagnosis of liver fibrosis for timely intervention and treatment of the disease and delaying its progression.
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16
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Forsgren MF, Karlsson M, Dahlqvist Leinhard O, Dahlström N, Norén B, Romu T, Ignatova S, Ekstedt M, Kechagias S, Lundberg P, Cedersund G. Model-inferred mechanisms of liver function from magnetic resonance imaging data: Validation and variation across a clinically relevant cohort. PLoS Comput Biol 2019; 15:e1007157. [PMID: 31237870 PMCID: PMC6613709 DOI: 10.1371/journal.pcbi.1007157] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 07/08/2019] [Accepted: 06/06/2019] [Indexed: 12/11/2022] Open
Abstract
Estimation of liver function is important to monitor progression of chronic liver disease (CLD). A promising method is magnetic resonance imaging (MRI) combined with gadoxetate, a liver-specific contrast agent. For this method, we have previously developed a model for an average healthy human. Herein, we extended this model, by combining it with a patient-specific non-linear mixed-effects modeling framework. We validated the model by recruiting 100 patients with CLD of varying severity and etiologies. The model explained all MRI data and adequately predicted both timepoints saved for validation and gadoxetate concentrations in both plasma and biopsies. The validated model provides a new and deeper look into how the mechanisms of liver function vary across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate. These mechanisms are shared across many liver functions and can now be estimated from standard clinical images. Being able to accurately and reliably estimate liver function is important when monitoring the progression of patients with liver disease, as well as when identifying drug-induced liver injury during drug development. A promising method for quantifying liver function is to use magnetic resonance imaging combined with gadoxetate. Gadoxetate is a liver-specific contrast agent, which is taken up by the hepatocytes and excreted into the bile. We have previously developed a mechanistic model for gadoxetate dynamics using averaged data from healthy volunteers. In this work, we extended our model with a non-linear mixed-effects modeling framework to give patient-specific estimates of the gadoxetate transport-rates. We validated the model by recruiting 100 patients with liver disease, covering a range of severity and etiologies. All patients underwent an MRI-examination and provided both blood and liver biopsies. Our validated model provides a new and deeper look into how the mechanisms of liver function varies across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate.
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Affiliation(s)
- Mikael F. Forsgren
- Wolfram MathCore AB and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
| | - Markus Karlsson
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
- Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
| | - Olof Dahlqvist Leinhard
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
- Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
| | - Nils Dahlström
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
- Department of Radiology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
| | - Bengt Norén
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
| | - Thobias Romu
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
- Department of Biomedical Engineering, Linköping University, Linköping, Sweden
| | - Simone Ignatova
- Department of Clinical Pathology and Clinical Genetics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Mattias Ekstedt
- Department of Gastroenterology and Hepatology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
| | - Stergios Kechagias
- Department of Gastroenterology and Hepatology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
| | - Peter Lundberg
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
- Department of Radiation Physics, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
- * E-mail: (PL); (GC)
| | - Gunnar Cedersund
- Department of Biomedical Engineering, Linköping University, Linköping, Sweden
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
- * E-mail: (PL); (GC)
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Ghanem CI, Manautou JE. Modulation of Hepatic MRP3/ABCC3 by Xenobiotics and Pathophysiological Conditions: Role in Drug Pharmacokinetics. Curr Med Chem 2019; 26:1185-1223. [PMID: 29473496 DOI: 10.2174/0929867325666180221142315] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 01/17/2018] [Accepted: 02/05/2018] [Indexed: 12/13/2022]
Abstract
Liver transporters play an important role in the pharmacokinetics and disposition of pharmaceuticals, environmental contaminants, and endogenous compounds. Among them, the family of ATP-Binding Cassette (ABC) transporters is the most important due to its role in the transport of endo- and xenobiotics. The ABCC sub-family is the largest one, consisting of 13 members that include the cystic fibrosis conductance regulator (CFTR/ABCC7); the sulfonylurea receptors (SUR1/ABCC8 and SUR2/ABCC9) and the multidrug resistanceassociated proteins (MRPs). The MRP-related proteins can collectively confer resistance to natural, synthetic drugs and their conjugated metabolites, including platinum-containing compounds, folate anti-metabolites, nucleoside and nucleotide analogs, among others. MRPs can be also catalogued into "long" (MRP1/ABCC1, -2/C2, -3/C3, -6/C6, and -7/C10) and "short" (MRP4/C4, -5/C5, -8/C11, -9/C12, and -10/C13) categories. While MRP2/ABCC2 is expressed in the canalicular pole of hepatocytes, all others are located in the basolateral membrane. In this review, we summarize information from studies examining the changes in expression and regulation of the basolateral hepatic transporter MPR3/ABCC3 by xenobiotics and during various pathophysiological conditions. We also focus, primarily, on the consequences of such changes in the pharmacokinetic, pharmacodynamic and/or toxicity of different drugs of clinical use transported by MRP3.
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Affiliation(s)
- Carolina I Ghanem
- Instituto de Investigaciones Farmacologicas (ININFA), Facultad de Farmacia y Bioquimica. CONICET. Universidad de Buenos Aires, Buenos Aires, Argentina.,Catedra de Fisiopatologia. Facultad de Farmacia y Bioquimica. Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Jose E Manautou
- Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, United States
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18
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T1 mapping for liver function evaluation in gadoxetic acid–enhanced MR imaging: comparison of look-locker inversion recovery and B1 inhomogeneity–corrected variable flip angle method. Eur Radiol 2019; 29:3584-3594. [DOI: 10.1007/s00330-018-5947-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 10/27/2018] [Accepted: 12/04/2018] [Indexed: 02/06/2023]
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Shuboni-Mulligan DD, Parys M, Blanco-Fernandez B, Mallett CL, Schnegelberger R, Takada M, Chakravarty S, Hagenbuch B, Shapiro EM. Dynamic Contrast-Enhanced MRI of OATP Dysfunction in Diabetes. Diabetes 2019; 68:271-280. [PMID: 30487262 PMCID: PMC6341305 DOI: 10.2337/db18-0525] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 11/10/2018] [Indexed: 12/19/2022]
Abstract
Diabetes is associated with hepatic metabolic dysfunction predisposing patients to drug-induced liver injury. Mouse models of type 2 diabetes (T2D) have dramatically reduced expression of organic anion transporting polypeptide (OATP)1A1, a transporter expressed in hepatocytes and in the kidneys. The effects of diabetes on OATP1B2 expression are less studied and less consistent. OATP1A1 and OATP1B2 both transport endogenous substrates such as bile acids and hormone conjugates as well as numerous drugs including gadoxetate disodium (Gd-EOB-DTPA). As master pharmacokinetic regulators, the altered expression of OATPs in diabetes could have a profound and clinically significant influence on drug therapies. Here, we report a method to noninvasively measure OATP activity in T2D mice by quantifying the transport of hepatobiliary-specific gadolinium-based contrast agents (GBCAs) within the liver and kidneys using dynamic contrast-enhanced MRI (DCE-MRI). By comparing GBCA uptake in control and OATP knockout mice, we confirmed liver clearance of the hepatobiliary-specific GBCAs, Gd-EOB-DTPA, and gadobenate dimeglumine, primarily though OATP transporters. Then, we measured a reduction in the hepatic uptake of these hepatobiliary GBCAs in T2D ob/ob mice, which mirrored significant reductions in the mRNA and protein expression of OATP1A1 and OATP1B2. As these GBCAs are U.S. Food and Drug Administration-approved agents and DCE-MRI is a standard clinical protocol, studies to determine OATP1B1/1B3 deficiencies in human individuals with diabetes can be easily envisioned.
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Affiliation(s)
- Dorela D Shuboni-Mulligan
- Department of Radiology, Michigan State University, East Lansing, MI
- Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI
| | - Maciej Parys
- Department of Comparative Medicine and Integrative Biology Program, Michigan State University, East Lansing, MI
| | - Barbara Blanco-Fernandez
- Department of Radiology, Michigan State University, East Lansing, MI
- Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI
| | - Christiane L Mallett
- Department of Radiology, Michigan State University, East Lansing, MI
- Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI
| | - Regina Schnegelberger
- Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, MO
| | - Marilia Takada
- Department of Comparative Medicine and Integrative Biology Program, Michigan State University, East Lansing, MI
| | - Shatadru Chakravarty
- Department of Radiology, Michigan State University, East Lansing, MI
- Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI
| | - Bruno Hagenbuch
- Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, MO
| | - Erik M Shapiro
- Department of Radiology, Michigan State University, East Lansing, MI
- Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI
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Sheng RF, Jin KP, Yang L, Wang HQ, Liu H, Ji Y, Fu CX, Zeng MS. Histogram Analysis of Diffusion Kurtosis Magnetic Resonance Imaging for Diagnosis of Hepatic Fibrosis. Korean J Radiol 2018; 19:916-922. [PMID: 30174481 PMCID: PMC6082766 DOI: 10.3348/kjr.2018.19.5.916] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Accepted: 02/09/2018] [Indexed: 12/22/2022] Open
Abstract
Objective To investigate the diagnostic value of diffusion kurtosis imaging (DKI) histogram analysis in hepatic fibrosis staging. Materials and Methods Thirty-six rats were divided into carbon tetrachloride-induced fibrosis groups (6 rats per group for 2, 4, 6, and 8 weeks) and a control group (n = 12). MRI was performed using a 3T scanner. Histograms of DKI were obtained for corrected apparent diffusion (D), kurtosis (K) and apparent diffusion coefficient (ADC). Mean, median, skewness, kurtosis and 25th and 75th percentiles were generated and compared according to the fibrosis stage and inflammatory activity. Results A total of 35 rats were included, and 12, 5, 5, 6, and 7 rats were diagnosed as F0–F4. The mean, median, 25th and 75th percentiles, kurtosis of D map, median, 25th percentile, skewness of K map, and 75th percentile of ADC map demonstrated significant correlation with fibrosis stage (r = −0.767 to 0.339, p < 0.001 to p = 0.039). The fibrosis score was the independent variable associated with histogram parameters compared with inflammatory activity grade (p < 0.001 to p = 0.041), except the median of K map (p = 0.185). Areas under the receiver operating characteristic curve of D were larger than K and ADC maps in fibrosis staging, although no significant differences existed in pairwise comparisons (p = 0.0512 to p = 0.847). Conclusion Corrected apparent diffusion of DKI histogram analysis provides added value and better diagnostic performance to detect various liver fibrosis stages compared with ADC.
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Affiliation(s)
- Ruo-Fan Sheng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai 200032, China
| | - Kai-Pu Jin
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai 200032, China
| | - Li Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai 200032, China
| | - He-Qing Wang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai 200032, China
| | - Hao Liu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai 200032, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Cai-Xia Fu
- MR Collaboration NEA, Siemens Ltd. China, Shanghai 201318, China
| | - Meng-Su Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai 200032, China
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Assessment of Liver Function Using Pharmacokinetic Parameters of Gd-EOB-DTPA: Experimental Study in Rat Hepatectomy Model. CONTRAST MEDIA & MOLECULAR IMAGING 2018; 2018:6321316. [PMID: 29713251 PMCID: PMC5866904 DOI: 10.1155/2018/6321316] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Accepted: 02/12/2018] [Indexed: 12/17/2022]
Abstract
Objectives To determine whether the pharmacokinetic parameters of Gd-EOB-DTPA can identify the difference in liver function in a rat hepatectomy model. Methods A total of 56 eight-week-old male Sprague-Dawley rats were divided into the following groups: control group without hepatectomy (n = 16), 70% hepatectomy group (n = 14), and 90% hepatectomy group (n = 26). On postoperative day 2, Gd-EOB-DTPA (0.1 mmol/kg) was injected intravenously and serial blood samples were obtained. Pharmacokinetic analysis was performed using a noncompartmental method. Statistical analysis was performed using one-way analysis of variance and post hoc pairwise group comparisons. Results After excluding 6 rats that died unexpectedly, blood samples were obtained from 16, 14, and 20 rats in the control group, 70% hepatectomy group, and 90% hepatectomy group. There was a significant increase in area under the concentration-time curve from time zero to the time of the last measurable concentration between the 70% and 90% hepatectomy group (P < 0.001). The volume of distribution at steady state was significantly decreased between the control and 70% hepatectomy group (P < 0.001). The clearance was significantly different in all pairwise group comparisons (P < 0.001). Conclusions The vascular clearance of Gd-EOB-DTPA can identify the difference in liver function in a rat hepatectomy model.
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Abstract
Transporter systems involved in the permeation of drugs and solutes across biological membranes are recognized as key determinants of pharmacokinetics. Typically, the action of membrane transporters on drug exposure to tissues in living organisms is inferred from invasive procedures, which cannot be applied in humans. In recent years, imaging methods have greatly progressed in terms of instruments, synthesis of novel imaging probes as well as tools for data analysis. Imaging allows pharmacokinetic parameters in different tissues and organs to be obtained in a non-invasive or minimally invasive way. The aim of this overview is to summarize the current status in the field of molecular imaging of drug transporters. The overview is focused on human studies, both for the characterization of transport systems for imaging agents as well as for the determination of drug pharmacokinetics, and makes reference to animal studies where necessary. We conclude that despite certain methodological limitations, imaging has a great potential to study transporters at work in humans and that imaging will become an important tool, not only in drug development but also in medicine. Imaging allows the mechanistic aspects of transport proteins to be studied, as well as elucidating the influence of genetic background, pathophysiological states and drug-drug interactions on the function of transporters involved in the disposition of drugs.
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Affiliation(s)
- Nicolas Tournier
- Imagerie Moléculaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France
| | - Bruno Stieger
- Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Oliver Langer
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; Biomedical Systems, Center for Health & Bioresources, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria; Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
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Quantification of hepatic perfusion and hepatocyte function with dynamic gadoxetic acid-enhanced MRI in patients with chronic liver disease. Clin Sci (Lond) 2018; 132:813-824. [PMID: 29440620 DOI: 10.1042/cs20171131] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 02/05/2018] [Accepted: 02/09/2018] [Indexed: 02/06/2023]
Abstract
The purpose of the present study was to develop and perform initial validation of dynamic MRI enhanced with gadoxetic acid as hepatobiliary contrast agent to quantify hepatic perfusion and hepatocyte function in patients with chronic liver disease. Free-breathing, dynamic gadoxetic acid-enhanced MRI was performed at 3.0 T using a 3D time-resolved angiography sequence with stochastic trajectories during 38 min. A dual-input three-compartment model was developed to derive hepatic perfusion and hepatocyte function parameters. Method feasibility was assessed in 23 patients with biopsy-proven chronic liver disease. Parameter analysis could be performed in 21 patients (91%). The hepatocyte function parameters were more discriminant than the perfusion parameters to differentiate between patients with minimal fibrosis (METAVIR F0-F1), intermediate fibrosis (F2-F3) and cirrhosis (F4). The areas under the receiver operating characteristic curves (ROCs) to diagnose significant fibrosis (METAVIR F ≥ 2) were: 0.95 (95% CI: 0.87-1; P<0.001) for biliary efflux, 0.88 (95% CI: 0.73-1; P<0.01) for sinusoidal backflux, 0.81 (95% CI: 0.61-1; P<0.05) for hepatocyte uptake fraction and 0.75 (95% CI: 0.54-1; P<0.05) for hepatic perfusion index (HPI), respectively. These initial results in patients with chronic liver diseases show that simultaneous quantification of hepatic perfusion and hepatocyte function is feasible with free breathing dynamic gadoxetic acid-enhanced MRI. Hepatocyte function parameters may be relevant to assess liver fibrosis severity.
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Can functional parameters from hepatobiliary phase of gadoxetate MRI predict clinical outcomes in patients with cirrhosis? Eur Radiol 2018; 28:4215-4224. [DOI: 10.1007/s00330-018-5366-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 01/12/2018] [Accepted: 02/01/2018] [Indexed: 12/26/2022]
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Lee JH, Kim YR, Lee GM, Ryu JH, Cho EY, Lee YH, Yoon KH. Coefficient of variation on Gd-EOB MR imaging: Correlation with the presence of early-stage hepatocellular carcinoma in patients with chronic hepatitis B. Eur J Radiol 2018; 102:95-101. [PMID: 29685552 DOI: 10.1016/j.ejrad.2018.02.032] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Revised: 02/23/2018] [Accepted: 02/26/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE To study whether the measurement of hepatic fibrosis on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) magnetic resonance (MR) imaging using the coefficient of variation (CV) might be correlated with the presence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). MATERIALS AND METHODS This study included 104 patients with and without CHB, who were divided into 4 groups: control group, CHB without liver cirrhosis (LC; Group I), CHB with LC (Group II), and CHB with LC and HCC (Group III). MR images were analyzed to measure the inhomogeneity of signal intensities calculated using the CV map of the liver parenchyma. Intergroup comparisons of CV values were performed using ANOVA. The diagnostic performance of the CV map and alpha-fetoprotein (AFP) for diagnosing HCC was evaluated using the receiver operating characteristic (ROC) curve. RESULTS On the hepatobiliary phase of Gd-EOB-DTPA-enhanced T1-weighted imaging, the mean CV values of the control group and Groups I, II, and III were 3.9 ± 0.99, 3.97 ± 1.09, 5.58 ± 2.05, and 6.80 ± 2.34, respectively (P = 0.000). On ROC analysis of the CV value for predicting HCC, the value of the area under the curve (AUC) on Gd-EOB-DTPA MR imaging was 0.788 (95% CI: 0.697-0.862). The sensitivity and specificity were 84.2% and 63.6%, respectively, at a CV cutoff value >4.75. The value of AUC determined using AFP was 0.766. CONCLUSION The CV value for hepatic fibrosis on Gd-EOB-DTPA MR imaging may be correlated with the presence of HCC in patients with CHB, and shows comparable diagnostic performance to AFP analysis.
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Affiliation(s)
- Jung Hun Lee
- Department of Radiology, Wonkwang University School of Medicine, Iksan, Republic of Korea
| | - Youe Ree Kim
- Department of Radiology, Wonkwang University School of Medicine, Iksan, Republic of Korea
| | - Guy Mok Lee
- Department of Radiology, Wonkwang University School of Medicine, Iksan, Republic of Korea
| | - Jong Hyun Ryu
- Imaging Science Research Center, Wonkwang University Hospital, Iksan, Republic of Korea
| | - Eun Young Cho
- Department of Gastroenterology, Wonkwang University School of Medicine, Iksan, Republic of Korea
| | - Young Hwan Lee
- Department of Radiology, Wonkwang University School of Medicine, Iksan, Republic of Korea
| | - Kwon-Ha Yoon
- Department of Radiology, Wonkwang University School of Medicine, Iksan, Republic of Korea; Imaging Science Research Center, Wonkwang University Hospital, Iksan, Republic of Korea.
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Marie S, Cisternino S, Buvat I, Declèves X, Tournier N. Imaging Probes and Modalities for the Study of Solute Carrier O (SLCO)-Transport Function In Vivo. J Pharm Sci 2017; 106:2335-2344. [DOI: 10.1016/j.xphs.2017.04.031] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 04/04/2017] [Accepted: 04/17/2017] [Indexed: 01/26/2023]
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Sheng RF, Wang HQ, Yang L, Jin KP, Xie YH, Fu CX, Zeng MS. Assessment of liver fibrosis using T1 mapping on Gd-EOB-DTPA-enhanced magnetic resonance. Dig Liver Dis 2017; 49:789-795. [PMID: 28237298 DOI: 10.1016/j.dld.2017.02.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Revised: 02/02/2017] [Accepted: 02/06/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Few studies have investigated the value of Gd-EOB-DTPA-enhanced T1 mapping in exact fibrosis staging, especially its correlation with hepatic molecular transporters. AIMS To investigate the diagnostic value of Gd-EOB-DTPA-enhanced T1 mapping in staging liver fibrosis and its relationship with hepatic molecular transporters. METHODS Thirty rats were divided into the carbon tetrachloride-induced fibrosis groups and a control group. T1-mapping was performed before and 20min after administration of Gd-EOB-DTPA. The T1 relaxation time and reduction rate (Δ%) were calculated, and their correlations with the degree of fibrosis, necroinflammatory activity, iron load and hepatic molecular transporters were assessed and compared. RESULTS Hepatobiliary phase T1 relaxation time (HBP) and Δ% were different between each adjacent fibrosis subgroups(P=0.000-0.042). Very strong correlations existed between fibrosis and both HBP and Δ% (r=0.960/-0.952), and multivariate analyses revealed that fibrosis was the only factor independently predicted by HBP (P=0.000) and Δ% (P=0.001), comparing to necroinflammatory activity and iron load. The expression of the organic anion transporting polypeptide1a1 (Oatp1a1) was significantly correlated with HBP and Δ% at both mRNA (r=-0.741/0.697) and protein (r=-0.577/0.602) levels. Weaker correlations were found for multidrug resistance associated protein2 (Mrp2). Generally, both transporters showed decreasing levels with increasing degrees of fibrosis. CONCLUSION Gd-EOB-DTPA-enhanced T1 mapping may provide a reliable diagnostic tool in staging liver fibrosis, and can be regarded as a useful imaging biomarker of hepatocyte transporter function.
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Affiliation(s)
- Ruo Fan Sheng
- Department of Radiology, Zhongshan Hospital, Fudan University, Xuhui District, Shanghai, China; Shanghai Institute of Medical Imaging, Xuhui District, Shanghai, China
| | - He Qing Wang
- Department of Radiology, Zhongshan Hospital, Fudan University, Xuhui District, Shanghai, China; Shanghai Institute of Medical Imaging, Xuhui District, Shanghai, China
| | - Li Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Xuhui District, Shanghai, China; Shanghai Institute of Medical Imaging, Xuhui District, Shanghai, China
| | - Kai Pu Jin
- Department of Radiology, Zhongshan Hospital, Fudan University, Xuhui District, Shanghai, China; Shanghai Institute of Medical Imaging, Xuhui District, Shanghai, China
| | - Yan Hong Xie
- Department of Pathology, Zhongshan Hospital, Fudan University, Xuhui District, Shanghai 200032, China
| | - Cai Xia Fu
- MR Collaboration NEA, Siemens Ltd. China, Shanghai, China
| | - Meng Su Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Xuhui District, Shanghai, China; Shanghai Institute of Medical Imaging, Xuhui District, Shanghai, China.
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Sheng RF, Wang HQ, Yang L, Jin KP, Xie YH, Chen CZ, Zeng MS. Diffusion kurtosis imaging and diffusion-weighted imaging in assessment of liver fibrosis stage and necroinflammatory activity. Abdom Radiol (NY) 2017; 42:1176-1182. [PMID: 27866239 DOI: 10.1007/s00261-016-0984-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
PURPOSE To investigate and compare the diagnostic value of diffusion kurtosis imaging (DKI) with diffusion-weighted imaging (DWI) in assessing and quantifying hepatic fibrosis. METHODS Thirty rats were divided into the control group (n = 6) and the fibrosis experimental groups (n = 6 per group) with CCl4 administration for 2, 4, 6, and 8 weeks. Liver fibrosis stage (S) and necroinflammatory activity grade (G) were histopathologically determined. DKI and DWI were performed; mean apparent diffusion (MD), mean kurtosis (MK), and apparent diffusion coefficient (ADC) values were calculated. DKI parameters were compared with ADC values according to G/S scores. RESULTS Strong inverse correlations were found between the degree of fibrosis and both MD and ADC (r = -0.840 and r = -0.760), while only weak correlation existed in MK (r = 0.405). ROC analyses demonstrated the AUC in MD, MK, and ADC of 0.862, 0.684, 0.817 for identifying mild and severe fibrosis, and 0.757, 0.675, 0.733 for non-cirrhosis and cirrhosis, respectively. The degree of fibrosis was significantly correlated with α-smooth muscle actin (α-SMA) (P < 0.0001); α-SMA had strong inverse correlation with MD (r = -0.723), moderate inverse correlation with ADC (r = -0.613), and very weak correlation with MK (r = 0.175). Additionally, MD was strongly correlated with the necroinflammatory activity (r = -0.758), ADC was moderately correlated (r = -0.492), and MK was weakly correlated (r = 0.254). CONCLUSION DKI may provide added information and serve as a valuable tool for the characterization and surveillance of liver fibrosis in a non-invasive manner.
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Affiliation(s)
- Ruo Fan Sheng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - He Qing Wang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Li Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Kai Pu Jin
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Yan Hong Xie
- Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Cai Zhong Chen
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Meng Su Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
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Yoon JH, Choi JI, Jeong YY, Schenk A, Chen L, Laue H, Kim SY, Lee JM. Pre-treatment estimation of future remnant liver function using gadoxetic acid MRI in patients with HCC. J Hepatol 2016; 65:1155-1162. [PMID: 27476767 DOI: 10.1016/j.jhep.2016.07.024] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Revised: 05/25/2016] [Accepted: 07/20/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS This study aimed to determine whether the predicted remnant liver function on dynamic hepatocyte-specific contrast media-enhanced magnetic resonance (DHCE-MR) imaging correlates with the results of the indocyanin green retention test (ICG R15) after hepatic resection or radiofrequency ablation (RFA). METHODS This prospective multicenter study was approved by the Institutional Review Boards of each hospital. Informed consents were obtained from all. DHCE-MRI and ICG R15 were performed in 57 patients scheduled to undergo hepatectomy or RFA for hepatocellular carcinoma, once before treatment and repeated on post-treatment day 3. In nine donors and three recipients, DHCE-MRI and ICG R15 were performed only preoperatively. The predicted remnant liver function (HEFml) was estimated using the hepatic extraction fraction (HEF) multiplied by the remnant liver volume, and compared with post-treatment ICG R15. Intra-individual heterogeneity of HEF was assessed using pooled coefficients of variation (CV) among hepatic segments. Finally, development of post-treatment hepatic failure was assessed according to the 50-50 criteria on post-treatment day 5. RESULTS Predicted remnant HEFml showed a negative correlation with post-treatment ICG R15 (r=-0.45, p=0.001), whereas liver volume did not (p>0.05). There were significant correlations between pre-treatment HEFml and pre-treatment ICG R15 (r=-0.33, p=0.006) and between post-treatment HEFml and post-treatment ICG R15 (r=-0.54, p<0.001). Pooled CV among segmental HEFs was 12.6%. No patients showed post-treatment liver failure on post-treatment day 5. CONCLUSIONS DHCE-MRI using Gd-EOB-DTPA was able to provide both global and segmental liver function information, and post-treatment remnant liver function predicted on pre-treatment DHCE-MRI showed a significant negative correlation with post-treatment ICG R15. LAY SUMMARY Post-treatment liver function could be predicted at pre-treatment DHCE-MRI. Liver function was heterogeneous among the liver segments. Liver anatomy, disease extent, and underlying liver function can be assessed in one DHCE-MRI examination. CLINICAL TRIAL NUMBER ClinicalTrials.gov number, NCT01490203.
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Affiliation(s)
- Jeong Hee Yoon
- Radiology, Seoul National University Hospital, Seoul, Republic of Korea; College of Medicine, Seoul, Republic of Korea
| | - Joon-Il Choi
- Radiology, Catholic Medical Center, Seoul, Republic of Korea
| | - Yong Yeon Jeong
- Chonnam National University Hwasun Hospital and Medical School, Gwang-Ju, Republic of Korea
| | | | | | | | - So Yeon Kim
- Radiology, Asan Medical Center, Seoul, Republic of Korea.
| | - Jeong Min Lee
- Radiology, Seoul National University Hospital, Seoul, Republic of Korea; College of Medicine, Seoul, Republic of Korea; Institute of Radiation Medicine, Seoul National University Medical Research Center, 103 Daehak-ro, Jongno-gu, Seoul 03087, Republic of Korea.
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Ba-Ssalamah A, Bastati N, Wibmer A, Fragner R, Hodge JC, Trauner M, Herold CJ, Bashir MR, Van Beers BE. Hepatic gadoxetic acid uptake as a measure of diffuse liver disease: Where are we? J Magn Reson Imaging 2016; 45:646-659. [PMID: 27862590 DOI: 10.1002/jmri.25518] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Accepted: 10/05/2016] [Indexed: 02/06/2023] Open
Abstract
MRI has emerged as the most comprehensive noninvasive diagnostic tool for focal liver lesions and diffuse hepatobiliary disorders. The introduction of hepatobiliary contrast agents, most notably gadoxetic acid (GA), has expanded the role of MRI, particularly in the functional imaging of chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD). GA-enhanced MRI (GA-MRI) may help to distinguish between the two subgroups of NAFLD, simple steatosis and nonalcoholic steatohepatitis. Furthermore, GA-MRI can be used to stage fibrosis and cirrhosis, predict liver transplant graft survival, and preoperatively estimate the risk of liver failure should major resection be undertaken. The amount of GA uptake can be estimated, using static images, by the relative liver enhancement, hepatic uptake index, and relaxometry of T1-mapping during the hepatobiliary phase. On the contrary, the hepatic extraction fraction and liver perfusion can be measured on dynamic imaging. Importantly, there is currently no clear consensus as to which of these MR-derived parameters is the most suitable for assessing liver dysfunction. This review article aims to describe the current role of GA-enhanced MRI in quantifying liver function, primarily in diffuse hepatobiliary disorders. LEVEL OF EVIDENCE 3 J. Magn. Reson. Imaging 2017;45:646-659.
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Affiliation(s)
- Ahmed Ba-Ssalamah
- Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Austria
| | - Nina Bastati
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, General Hospital of Vienna (AKH), Austria
| | - Andreas Wibmer
- Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Austria
| | - Romana Fragner
- Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Austria
| | - Jacqueline C Hodge
- Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, General Hospital of Vienna (AKH), Austria
| | - Christian J Herold
- Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Austria
| | - Mustafa R Bashir
- Department of Radiology and Center for Advanced Magnetic Resonance Development, Duke University Medical Center, Durham, North Carolina, USA.,Center for Advanced Magnetic Resonance Development, Duke University Medical Center, Durham, North Carolina, USA
| | - Bernard E Van Beers
- Laboratory of Imaging Biomarkers, UMR 1149, INSERM - University Paris Diderot and Department of Radiology, University Hospital Paris Nord - Beaujon, France
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Kim J, Kim T, Hong KS, Moon H, Oh IK, Lee SM, Hohenwalter MD, Zimmerman MA, Cronin DC, Hong JC. Pre-Hepatectomy Assessment of Bile Transporter Expression by Gadoxetic Acid-Enhanced MRI in a Rat Model of Liver Cirrhosis. J INVEST SURG 2016; 30:265-271. [PMID: 27780379 DOI: 10.1080/08941939.2016.1238983] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Gadoxetic acid is a liver-specific intravenous T1 magnetic resonance (MR) contrast agent that is excreted via the hepatobiliary system. We hypothesize that hepatocyte expressions of bile transporters (OATP1 and MRP2) correlate with dynamic profile of Gadoxetic acid enhanced (GE)-MR imaging (MRI). METHODS Two groups of rats, control (n = 6) and cirrhosis (n = 12), received gadoxetic acid enhanced MRI followed by 70% hepatectomy. The change in MR signal intensity from the baseline before the contrast injection (ΔSI) was analyzed every minute for 30 min. Dynamic signal intensity retention ratio (DSR) was defined as the mean ΔSI of the third 10-minmin period divided by the first 10-minmin period. Real-time PCR was utilized to quantify mRNA expressions. RESULTS Compared to the control, cirrhosis group demonstrated lower mRNA levels of OATP1 (0.038 ± 0.020 vs. 0.232 ± 0.0979; p = 0.004), MRP2 (0.201 ± 0.084 vs. 0.7567 ± 0.254; p = 0.002), and OATP1/MRP2 mRNA ratio (0.193 ± 0.065 vs. 0.342 ± 0.206; p = 0.032). DSR was higher in the cirrhosis group (0.678 ± 0.554 vs -0.125 ± 0.839; p = 0.033). In the cirrhosis group, there was an inverse correlation between the ratios of OATP1/MRP2 mRNA and DSR (R = -0.709, p = 0.01). CONCLUSION Bile transporters OATP1/MRP2 mRNA expression ratio in rat liver tissue decreased with DMN-induced liver injury. The expressions of bile transporters correlated with GE-MRI DSR. The GE-MRI DSR has potential utility in qualifying OATP1/MRP2 mRNA expression.
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Affiliation(s)
- Joohyun Kim
- a Division of Transplant Surgery, Department of Surgery , Medical College of Wisconsin , Milwaukee , Wisconsin , USA.,b The Transplant Center at Froedtert and Medical College of Wisconsin , Children's Hospital of Wisconsin and The Blood Center of Wisconsin , Milwaukee , Wisconsin , USA
| | - Tae Kim
- c Department of Biomedical Science and Engineering , Gwangju Institute of Science and Technology , Gwangju , South Korea
| | - Kwan Soo Hong
- d Division of MR Research , Korea Basic Science Institute , Cheongwon , South Korea
| | - Hyeyoung Moon
- d Division of MR Research , Korea Basic Science Institute , Cheongwon , South Korea
| | - In-Kyung Oh
- e Department of Surgery , College of Medicine, Kyung Hee University , Seoul , South Korea
| | - Sang Mok Lee
- e Department of Surgery , College of Medicine, Kyung Hee University , Seoul , South Korea
| | - Mark D Hohenwalter
- f Department of Radiology , Medical College of Wisconsin , Wisconsin , USA
| | - Michael A Zimmerman
- a Division of Transplant Surgery, Department of Surgery , Medical College of Wisconsin , Milwaukee , Wisconsin , USA.,b The Transplant Center at Froedtert and Medical College of Wisconsin , Children's Hospital of Wisconsin and The Blood Center of Wisconsin , Milwaukee , Wisconsin , USA
| | - David C Cronin
- a Division of Transplant Surgery, Department of Surgery , Medical College of Wisconsin , Milwaukee , Wisconsin , USA.,b The Transplant Center at Froedtert and Medical College of Wisconsin , Children's Hospital of Wisconsin and The Blood Center of Wisconsin , Milwaukee , Wisconsin , USA
| | - Johnny C Hong
- a Division of Transplant Surgery, Department of Surgery , Medical College of Wisconsin , Milwaukee , Wisconsin , USA.,b The Transplant Center at Froedtert and Medical College of Wisconsin , Children's Hospital of Wisconsin and The Blood Center of Wisconsin , Milwaukee , Wisconsin , USA
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Yoon JH, Lee JM, Kim E, Okuaki T, Han JK. Quantitative Liver Function Analysis: Volumetric T1 Mapping with Fast Multisection B 1 Inhomogeneity Correction in Hepatocyte-specific Contrast-enhanced Liver MR Imaging. Radiology 2016; 282:408-417. [PMID: 27697007 DOI: 10.1148/radiol.2016152800] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Purpose To determine whether B1 inhomogeneity-corrected volumetric T1 maps of gadoxetic acid-enhanced liver magnetic resonance (MR) imaging are able to demonstrate global liver function and functional heterogeneity in patients with cirrhosis and to investigate their relationship with the development of hepatic insufficiency and decompensation. Materials and Methods This institutional review board-approved retrospective study with waiver of informed consent included 234 consecutive patients who underwent gadoxetic acid-enhanced liver MR imaging, including B1 inhomogeneity-corrected volumetric T1 mapping. For all patients, T1 relaxation times of the liver and liver volumes were measured on T1 maps. Liver T1 and functional liver volume-to-weight ratio (liver volume divided by liver T1 and the patient's weight) were compared between Child-Pugh class A and class B cirrhosis. Associations between serum markers, MR parameters, hepatic insufficiency, and decompensation were investigated by using Cox proportional hazards analysis. Results Patients with Child-Pugh class B disease showed significantly longer liver T1 (548.2 msec ± 257.7 vs 372.2 msec ± 77.5, P < .0001) and lower kurtosis of liver T1 (29.1 ± 39.6 vs 43.9 ± 64.9, P = .016) than patients with Child-Pugh class A disease. Prolonged liver T1 (≥462 msec) (hazard ratio [HR], 5.9; 95% confidence interval [CI]: 1.1, 62.8) and an albumin level of less than 3.5 g/dL (HR, 20.7; 95% CI: 3.9, 221.9) were independently associated with the development of hepatic insufficiency. Functional liver volume-to-weight ratio was associated with the development of hepatic decompensation in patients with Child-Pugh class A disease (HR, 0.03; 95% CI: 0.004, 0.23). Conclusion B1 inhomogeneity-corrected volumetric T1 mapping provided information on global liver function and demonstrated functional heterogeneity. In addition, prolonged liver T1 (≥462 msec) was associated with the development of hepatic insufficiency, and functional liver volume-to-weight ratio was negatively related with the development of decompensation in compensated cirrhosis. © RSNA, 2016 Online supplemental material is available for this article.
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Affiliation(s)
- Jeong Hee Yoon
- From the Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea (J.H.Y., J.M.L., J.K.H.); Department of Radiology, Seoul National University College of Medicine, Seoul, Korea (J.H.Y., J.M.L., J.K.H.); Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea (J.M.L., J.K.H.); Philips Healthcare Korea, Seoul, Korea (E.K.); and Philips Healthcare Japan, Tokyo, Japan (T.O.)
| | - Jeong Min Lee
- From the Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea (J.H.Y., J.M.L., J.K.H.); Department of Radiology, Seoul National University College of Medicine, Seoul, Korea (J.H.Y., J.M.L., J.K.H.); Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea (J.M.L., J.K.H.); Philips Healthcare Korea, Seoul, Korea (E.K.); and Philips Healthcare Japan, Tokyo, Japan (T.O.)
| | - Eunju Kim
- From the Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea (J.H.Y., J.M.L., J.K.H.); Department of Radiology, Seoul National University College of Medicine, Seoul, Korea (J.H.Y., J.M.L., J.K.H.); Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea (J.M.L., J.K.H.); Philips Healthcare Korea, Seoul, Korea (E.K.); and Philips Healthcare Japan, Tokyo, Japan (T.O.)
| | - Tomoyuki Okuaki
- From the Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea (J.H.Y., J.M.L., J.K.H.); Department of Radiology, Seoul National University College of Medicine, Seoul, Korea (J.H.Y., J.M.L., J.K.H.); Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea (J.M.L., J.K.H.); Philips Healthcare Korea, Seoul, Korea (E.K.); and Philips Healthcare Japan, Tokyo, Japan (T.O.)
| | - Joon Koo Han
- From the Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea (J.H.Y., J.M.L., J.K.H.); Department of Radiology, Seoul National University College of Medicine, Seoul, Korea (J.H.Y., J.M.L., J.K.H.); Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea (J.M.L., J.K.H.); Philips Healthcare Korea, Seoul, Korea (E.K.); and Philips Healthcare Japan, Tokyo, Japan (T.O.)
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Yang L, Ding Y, Rao S, Chen C, Wu L, Sheng R, Fu C, Zeng M. Staging liver fibrosis in chronic hepatitis B with T 1 relaxation time index on gadoxetic acid-enhanced MRI: Comparison with aspartate aminotransferase-to-platelet ratio index and FIB-4. J Magn Reson Imaging 2016; 45:1186-1194. [PMID: 27563840 DOI: 10.1002/jmri.25440] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Accepted: 08/08/2016] [Indexed: 12/17/2022] Open
Abstract
PURPOSE To assess the accuracy of the T1 relaxation time index on gadoxetic acid-enhanced magnetic resonance imaging (MRI) for staging liver fibrosis in chronic hepatitis B (CHB), in comparison and combination with the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4). MATERIALS AND METHODS A retrospective study of gadoxetic acid-enhanced T1 mapping and serum biochemical tests was performed on 126 CHB patients who underwent gadoxetic acid-enhanced 1.5T MRI, and the histological score used as the gold standard. The reduction rate of T1 relaxation time before and 20 minutes after gadoxetic acid injection (ΔT1 , ΔR1%), the contrast uptake rate (KHep ), APRI, and FIB-4 were calculated. The diagnostic efficacy of ΔT1 , ΔR1%, KHep , APRI, and FIB-4 for predicting stage 2 or greater (≥S2), stage 3 or greater (≥S3), and stage 4 (S4) was compared. RESULTS ΔT1 (r = -0.513, P < 0.001), ΔR1% (r = -0.626, P < 0.001), KHep (r = -0.527, P < 0.001), APRI (r = 0.519, P < 0.001), and FIB-4 (r = 0.476, P < 0.001) correlated significantly with fibrosis stages. Areas under the curves (AUCs) of ΔR1% for detecting ≥S2, ≥S3, and S4 were 0.849, 0.827, and 0.809, which were greater than that of APRI (0.763, 0.745, 0.787) and FIB-4 (0.727, 0.738, 0.772), but significant difference was found only in discriminating ≥S2 between ΔR1% and FIB-4 (P = 0.027). The combination of all five indices performed best, with AUC, sensitivity, and specificity of 0.860, 87.21%, and 72.50% for diagnosing ≥S2, 0.878, 82.81%, and 85.48% for ≥S3, and 0.867, 80.00%, and 83.95% for S4. CONCLUSION The gadoxetic acid-enhanced T1 relaxation time index appears to be superior to APRI and FIB-4 for predicting hepatic fibrosis. The combined use of gadoxetic acid-enhanced T1 mapping, APRI, and FIB-4 may be more reliable for staging liver fibrosis in CHB. LEVEL OF EVIDENCE 4 J. Magn. Reson. Imaging 2017;45:1186-1194.
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Affiliation(s)
- Li Yang
- Department of Radiology, Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | - Ying Ding
- Department of Radiology, Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.,Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | - Shengxiang Rao
- Department of Radiology, Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.,Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | - Caizhong Chen
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | - Lifang Wu
- Department of Radiology, Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | - Ruofan Sheng
- Department of Radiology, Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.,Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
| | - Caixia Fu
- Siemens Healthcare, Shanghai, P.R. China
| | - Mengsu Zeng
- Department of Radiology, Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.,Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
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Giraudeau C, Leporq B, Doblas S, Lagadec M, Pastor CM, Daire JL, Van Beers BE. Gadoxetate-enhanced MR imaging and compartmental modelling to assess hepatocyte bidirectional transport function in rats with advanced liver fibrosis. Eur Radiol 2016; 27:1804-1811. [PMID: 27553933 DOI: 10.1007/s00330-016-4536-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Revised: 07/27/2016] [Accepted: 08/01/2016] [Indexed: 12/18/2022]
Abstract
OBJECTIVES Changes in the expression of hepatocyte membrane transporters in advanced fibrosis decrease the hepatic transport function of organic anions. The aim of our study was to assess if these changes can be evaluated with pharmacokinetic analysis of the hepatobiliary transport of the MR contrast agent gadoxetate. METHODS Dynamic gadoxetate-enhanced MRI was performed in 17 rats with advanced fibrosis and 8 normal rats. After deconvolution, hepatocyte three-compartmental analysis was performed to calculate the hepatocyte influx, biliary efflux and sinusoidal backflux rates. The expression of Oatp1a1, Mrp2 and Mrp3 organic anion membrane transporters was assessed with reverse transcription polymerase chain reaction. RESULTS In the rats with advanced fibrosis, the influx and efflux rates of gadoxetate decreased and the backflux rate increased significantly (p = 0.003, 0.041 and 0.010, respectively). Significant correlations were found between influx and Oatp1a1 expression (r = 0.78, p < 0.001), biliary efflux and Mrp2 (r = 0.50, p = 0.016) and sinusoidal backflux and Mrp3 (r = 0.61, p = 0.002). CONCLUSION These results show that changes in the bidirectional organic anion hepatocyte transport function in rats with advanced liver fibrosis can be assessed with compartmental analysis of gadoxetate-enhanced MRI. KEY POINTS • Expression of hepatocyte transporters is modified in rats with advanced liver fibrosis. • Kinetic parameters at gadoxetate-enhanced MRI are correlated with hepatocyte transporter expression. • Hepatocyte transport function can be assessed with compartmental analysis of gadoxetate-enhanced MRI. • Compartmental analysis of gadoxetate-enhanced MRI might provide biomarkers in advanced liver fibrosis.
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Affiliation(s)
- Céline Giraudeau
- Laboratory of Imaging Biomarkers, UMR1149 Inserm, University Paris Diderot, Sorbonne Paris Cité, Hôpital Beaujon, 100 boulevard du général Leclerc, 92110, Clichy, France.
| | - Benjamin Leporq
- Laboratory of Imaging Biomarkers, UMR1149 Inserm, University Paris Diderot, Sorbonne Paris Cité, Hôpital Beaujon, 100 boulevard du général Leclerc, 92110, Clichy, France
| | - Sabrina Doblas
- Laboratory of Imaging Biomarkers, UMR1149 Inserm, University Paris Diderot, Sorbonne Paris Cité, Hôpital Beaujon, 100 boulevard du général Leclerc, 92110, Clichy, France
| | - Matthieu Lagadec
- Laboratory of Imaging Biomarkers, UMR1149 Inserm, University Paris Diderot, Sorbonne Paris Cité, Hôpital Beaujon, 100 boulevard du général Leclerc, 92110, Clichy, France.,Department of Radiology, Beaujon University Hospital Paris Nord, Clichy, France
| | - Catherine M Pastor
- Laboratory of Imaging Biomarkers, UMR1149 Inserm, University Paris Diderot, Sorbonne Paris Cité, Hôpital Beaujon, 100 boulevard du général Leclerc, 92110, Clichy, France.,Département d'imagerie et des sciences de l'information médicale, Hôpitaux Universitaires de Genève, Geneva, Switzerland
| | - Jean-Luc Daire
- Laboratory of Imaging Biomarkers, UMR1149 Inserm, University Paris Diderot, Sorbonne Paris Cité, Hôpital Beaujon, 100 boulevard du général Leclerc, 92110, Clichy, France.,Department of Radiology, Beaujon University Hospital Paris Nord, Clichy, France
| | - Bernard E Van Beers
- Laboratory of Imaging Biomarkers, UMR1149 Inserm, University Paris Diderot, Sorbonne Paris Cité, Hôpital Beaujon, 100 boulevard du général Leclerc, 92110, Clichy, France.,Department of Radiology, Beaujon University Hospital Paris Nord, Clichy, France
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Ding Y, Rao S, Yang L, Chen C, Zeng M. Comparison of the effect of region-of-interest methods using gadoxetic acid-enhanced MR imaging with diffusion-weighted imaging on staging hepatic fibrosis. Radiol Med 2016; 121:821-827. [PMID: 27449761 DOI: 10.1007/s11547-016-0669-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Accepted: 07/12/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the utility of T1 mapping on gadoxetic acid-enhanced MRI and DWI for staging liver fibrosis and assess the influence of ROI positioning on interobserver variability, T1 relaxation time and ADC value. METHODS This retrospective study was approved by the institutional review board and included 150 patients (mean age 58 years old; 91 men and 59 women). Liver fibrosis stages (S) were histopathologically determined. T1 relaxation time and ADC value of liver were measured by three distinct ROI protocols (the whole left lobe liver, the whole right lobe liver and the individual ROIs). T1 relaxation time measurements were compared with ADC values according to S scores. Interobserver variability for the T1 relaxation times and ADC values by the three distinct ROI protocols was analyzed by calculating the ICC. RESULTS T1 relaxation time measurements by the three distinct ROI protocols on severe fibrosis stage were significantly higher than the relative values on mild fibrosis stage. The mean ADC values on severe fibrosis stage showed no significantly different when measured by means of the whole right lobe liver (p = 0.057) and the individual ROIs (p = 0.10), compared with the relative values on mild fibrosis stage. AUCs of T1 relaxation time and ADC value by the means of the three distinct ROI protocols were 0.614, 0.676, 0.677 and 0.656, 0.585, 0.575 for identification of severe fibrosis stage. The interobserver reproducibility was excellent for measuring the right lobe liver T1 relaxation time and the individual ROIs T1 relaxation time (ICC 0.814, 0.883, respectively). CONCLUSIONS T1 relaxation time measurements by means of the three distinct ROI protocols on gadoxetic acid-enhanced MR imaging were a potential biomarker in staging of hepatic fibrosis, which were more accuracy than DWI-ADC measurements. The more reproducible results were obtained when measuring T1 relaxation time of the whole right lobe liver and the individual ROIs.
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Affiliation(s)
- Ying Ding
- Department of Radiology, Zhongshan Hospital Fudan University, Shanghai Medical Imaging Institute, No 138, Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Shengxiang Rao
- Department of Radiology, Zhongshan Hospital Fudan University, Shanghai Medical Imaging Institute, No 138, Fenglin Road, Xuhui District, Shanghai, 200032, China.
| | - Li Yang
- Department of Radiology, Zhongshan Hospital Fudan University, Shanghai Medical Imaging Institute, No 138, Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Caizhong Chen
- Department of Radiology, Zhongshan Hospital Fudan University, Shanghai Medical Imaging Institute, No 138, Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital Fudan University, Shanghai Medical Imaging Institute, No 138, Fenglin Road, Xuhui District, Shanghai, 200032, China
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