| 1. |
- Forsgren, Mikael F, 1983-, et al.
(författare)
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Biomarkers of liver fibrosis : prospective comparison of multimodal magnetic resonance, serum algorithms and transient elastography.
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:7, s. 848-859
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Accurate biomarkers for quantifying liver fibrosis are important for clinical practice and trial end-points. We compared the diagnostic performance of magnetic resonance imaging (MRI), including gadoxetate-enhanced MRI and 31P-MR spectroscopy, with fibrosis stage and serum fibrosis algorithms in a clinical setting. Also, in a subset of patients, MR- and transient elastography (MRE and TE) was evaluated when available.METHODS: Patients were recruited prospectively if they were scheduled to undergo liver biopsy on a clinical indication due to elevated liver enzyme levels without decompensated cirrhosis. Within a month of the clinical work-up, an MR-examination and liver needle biopsy were performed on the same day. Based on late-phase gadoxetate-enhanced MRI, a mathematical model calculated hepatobiliary function (relating to OATP1 and MRP2). The hepatocyte gadoxetate uptake rate (KHep) and the normalised liver-to-spleen contrast ratio (LSC_N10) were also calculated. Nine serum fibrosis algorithms were investigated (GUCI, King's Score, APRI, FIB-4, Lok-Index, NIKEI, NASH-CRN regression score, Forns' score, and NAFLD-fibrosis score).RESULTS: The diagnostic performance (AUROC) for identification of significant fibrosis (F2-4) was 0.78, 0.80, 0.69, and 0.78 for MRE, TE, LSC_N10, and GUCI, respectively. For the identification of advanced fibrosis (F3-4), the AUROCs were 0.93, 0.84, 0.81, and 0.82 respectively.CONCLUSION: MRE and TE were superior for non-invasive identification of significant fibrosis. Serum fibrosis algorithms developed for specific liver diseases are applicable in this cohort of diverse liver diseases aetiologies. Gadoxetate-MRI was sufficiently sensitive to detect the low function losses associated with fibrosis. None was able to efficiently distinguish between stages within the low fibrosis stages.Lay summaryExcessive accumulation of scar tissue, fibrosis, in the liver is an important aspect in chronic liver disease. To replace the invasive needle biopsy, we have explored non-invasive methods to assess liver fibrosis. In our study we found that elastographic methods, which assess the mechanical properties of the liver, are superior in assessing fibrosis in a clinical setting. Of interest from a clinical trial point-of-view, none of the tested methods was sufficiently accurate to distinguish between adjacent moderate fibrosis stages.
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| 2. |
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| 3. |
- Karlsson, Markus, et al.
(författare)
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Diffuse Liver Disease: Measurements of Liver Trace Metal Concentrations and R2* Relaxation Rates
- 2016
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Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer. - 0968-5243 .- 1352-8661. ; 29:1, s. S395-S395
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionOver the past decade, several methods for measuring of liver iron content (LIC) non-invasively with MRI have been developed and verified. The most promising methods uses relaxometry, measuring either R2- or R2* relaxation rate in the liver1,2. For instance, several studies have shown that there seems to be a linear relationship between R2* and LIC1. However, few of these studies have measured the liver content of other metals, which could also affect the relaxation rates. The goal of this study was to investigate if any trace metals, other than iron could affect the R2* relaxation rate in liver tissue in a patients with diffuse liver disease.Subjects and methods75 patients with suspected diffuse liver disease underwent an MRI examination followed by a liver biopsy the same day. The R2* relaxation rate of the water protons in the liver was measured using an axial 3D multi-slice fat-saturated multi-echo turbo field echo sequence (TE=4.60/9.20/13.80/18.40/23.00ms). Regions of interest (ROI) were drawn and R2* was estimated by fitting the mean signal intensity from the ROIs to a mono-exponential decay model. The biopsies were freeze dried and the concentrations of iron, manganese, copper, cobalt and gadolinium were measured using Inductively Coupled Plasma Sector Field Mass Spectrometry (ICP-SFMS). A multiple linear regression analysis was applied to determine which of the measured metals significantly affected the relaxation rate.ResultsA linear regression with the LIC and R2* showed a reasonable fit (Figure 1). The multiple linear regression analysis (Table 1) showed that iron as well as manganese had a significant affect on R2*. Unlike iron however, the regression coefficient of manganese was negative, meaning that an increasing manganese concentration gave a shorter R2* relaxation rate. The same trend can be seen when plotting the manganese concentration against R2* (Figure 2).
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| 4. |
- Karlsson, Markus, et al.
(författare)
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Increased bile excretion of Gd-EOB-DTPA in diffuse liver disease : mechanistic modeling of qDCE-MRI in patients with severe fibro-sis
- 2016
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Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer. - 0968-5243 .- 1352-8661. ; 29:1, s. S272-S273
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionOver the past decades, several different non-invasive methods for staging hepatic fibrosis have been proposed. One such method is dynamic contrast enhanced MRI (DCE-MRI) using the contrast agent (CA) Gd-EOB-DTPA. Gd-EOB-DTPA is liver specific, which means that it is taken up specifically by the hepatocytes via the OATP3B1/B3 transporters and excreted into the bile via the MRP2 transporter. Several studies have shown that DCE-MRI and Gd-EOBDTPA can separate patients with advanced (F3-F4) from mild (F0-F2) hepatic fibrosis by measuring the signal intensity, where patients with advanced fibrosis have a lower signal intensity than the mild fibrosis cases.1 However, none of the studies up to date have been able to differentiate if the reduced signal intensity in the liver is because of an decreased uptake of CA or an increased excretion. Analyzing the DCE-MRI data with mechanistic mathematical modelling has the possibility of investigating such a differentiation.Subjects and methods88 patients with diffuse liver disease were examined using DCE-MRI (1.5 T Philips Achieva, two-point Dixon, TR=6.5 ms, TE=2.3/4.6 ms, FA=13) after a bolus injection of Gd-EOB-DTPA, followed by a liver biopsy. Regions of interest were placed within the liver, spleen and veins and a whole-body mechanistic pharmacokinetic model2 was fitted to the data. The fitted parameters in the model correspond to the rate of CA transport between different compartments, e.g. hepatocytes, blood plasma, and bile (Fig. 1).ResultsAs can be seen in Fig. 2, the parameter corresponding to the transport of CA from the blood plasma to the hepatocytes, kph, is lower for patients with advanced fibrosis (p=0.01). Fig. 3 shows that the parameter corresponding to the CA excretion into the bile, khb, is higher for patients with advanced fibrosis (p<0.01).Discussion/ConclusionThis work shows that the decreased signal intensity in DCE-MRI images in patients with advanced fibrosis depends on both a decreased uptake of CA in the hepatocytes and an increased excretion into the bile. Similar results have also been observed in a rat study3. In that study, rats with induced cirrhosis had a higher MRP2-activity than the healthy control rats.References1Norén et al: Eur. Radiol, 23(1), 174-181, 2013.2Forsgren et al: PloS One, 9(4): e95700, 2014.3Tsuda & Matsui: Radiol, 256(3): 767-773, 2010.
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| 5. |
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| 6. |
- Norén, Bengt, 1955-, et al.
(författare)
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Absolute quantification of human liver metabolite concentrations by localized in vivo 31P NMR spectroscopy in diffuse liver disease
- 2005
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 15:1, s. 148-157
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorus-31 NMR spectroscopy using slice selection (DRESS) was used to investigate the absolute concentrations of metabolites in the human liver. Absolute concentrations provide more specific biochemical information compared to spectrum integral ratios. Nine patients with histopathologically proven diffuse liver disease and 12 healthy individuals were examined in a 1.5-T MR scanner (GE Signa LX Echospeed plus). The metabolite concentration quantification procedures included: (1) determination of optimal depth for the in vivo measurements, (2) mapping the detection coil characteristics, (3) calculation of selected slice and liver volume ratios using simple segmentation procedures and (4) spectral analysis in the time domain. The patients had significantly lower concentrations of phosphodiesters (PDE), 6.3±3.9 mM, and ATP-β, 3.6±1.1 mM, (P<0.05) compared with the control group (10.0±4.2 mM and 4.2±0.3 mM, respectively). The concentrations of phosphomonoesters (PME) were higher in the patient group, although this was not significant. Constructing an anabolic charge (AC) based on absolute concentrations, [PME]/([PME] + [PDE]), the patients had a significantly larger AC than the control subjects, 0.29 vs. 0.16 (P<0.005). Absolute concentration measurements of phosphorus metabolites in the liver are feasible using a slice selective sequence, and the technique demonstrates significant differences between patients and healthy subjects.
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| 7. |
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| 8. |
- Norén, Bengt, 1955-
(författare)
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MECP möjligheter, begränsningar, utveckling
- 2002
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Ingår i: Läkarmöte "ERCP-Nyheter inom gallvägsdiagnostik och handläggning", Norrköping 24 sept 2002,2002.
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Konferensbidrag (refereegranskat)
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| 9. |
- Norén, Bengt, 1955-
(författare)
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Non-Invasive Assessment of Liver Fibrosis with 31P-Magnetic Resonance Spectroscopy and Dynamic Contrast Enhanced Magnetic Resonance Imaging
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present study aims at demonstrating phosphorus metabolite concentration changes and alterations in uptake/excretion of a hepatocyte specific contrast agent in patients with diffuse - or suspected diffuse - liver disease by applying two non-invasive quantitative MR techniques and to compare the results with histo-pathological findings, with focus on liver fibrosis.In the first study phosphorus-31 MR spectroscopy using slice selection (DRESS) was implemented. Patients with histopathologically proven diffuse liver disease (n = 9) and healthy individuals (n = 12) were examined. The patients had significantly lower concentrations of phosphodiesters (PDE) and ATP compared with controls. Constructing an ‘anabolic charge’ (AC) based on absolute concentrations, [PME] / ([PME] + [PDE]), the patients had a significant larger AC than the control subjects.The MRS technique was then, in a second study, applied on two distinct groups of patients, one group with steatosis and none-to-moderate inflammation (n = 13) and one group with severe fibrosis or cirrhosis (n = 16). A control group (n = 13) was also included. Lower concentrations of PDE and a higher AC were found in the cirrhosis group compared to the control group. Also compared to the steatosis group, the cirrhosis group had lower concentrations of PDE and a higher AC. A significant correlation between fibrosis stage and PDE and fibrosis stage and AC was found. Using an AC cut-off value of 0.27 to discriminate between mild (stage 0-2) and advanced (stage 3-4) fibrosis yielded an AUROC value of 0.78, similar as for discriminating between F0-1 vs. F2-4.Dynamic contrast enhanced MRI (DCE-MRI) was performed prospectively in a third study on 38 patients referred for evaluation of elevated serum alanine aminotransferase (ALT) and/or alkaline phosphatase (ALP) levels. Data were acquired from regions of interest in the liver and spleen by using single-breath-hold symmetrically sampled two-point Dixon 3D images time-series (non-enhanced, arterial and venous portal phase; 3, 10, 20 and 30 min) following a bolus injection of Gd-EOB-DTPA (0.025 mmol/kg). A new quantification procedure for calculation of the ‘hepatocyte specific uptake rate’, KHep, was applied on a two-compartment pharmacokinetic model. Liver-to-spleen contrast ratios (LSC_N) were also calculated. AUROC values of 0.71, 0.80 and 0.78, respectively, were found for KHep, LSC_N10 and LSC_N20 with regard to severe versus mild fibrosis. Significant group differences were found for KHep (borderline), LSC_N10 and LSC_N20.In study four no significant correlation between visual assessments of bile ducts excretion of Gd-EOB-DTPA and histo-pathological grading of fibrosis or the quantified uptake of Gd-EOB-DTPA defined as KHep and LSC_N.In conclusion 31P-MRS and DCE-MRI show promising results for achieving a non-invasive approach in discriminating different levels of fibrosis from each other.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Norén, Bengt, 1955-
(författare)
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Quantitative 31P magnetic resonance spectroscopy in diffuse liver disease
- 2006
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The studies in this thesis were delineated to evaluate the diagnostic possibilities in patients with diffuse liver disease by using phosphorus-31 MR spectroscopy and comparing the results with clinical, laboratory and histopathological findings. For this purpose in all 38 patients and 25 controls without evidence of liver disease were examined.In the first study 31P-MRS using slice selection (DRESS) was implemented to investigate the absolute concentrations of metabolites in human liver. The metabolite concentration quantification procedures included: 1. Determination of optimal depth for the in vivo measurements, 2. Mapping the detection coil characteristics, 3. Calculation of selected slice and liver volume ratios using simple segmentation procedures, and 4. Spectral analysis in the time domain. Patients with histopathologically proven diffuse liver disease (n = 9) and healthy individuals (n = 12) were examined. The patients had significantly lower concentrations of phosphodiesters (PDE) and ATP-ß compared with the control group. Constructing an anabolic charge (AC) based on absolute concentrations, [PME] / ([PME] + [PDE]), the patients had a significant larger AC than the control subjects, 0.29 vs. 0.16 (p < 0.005).In the second study the MRS technique was applied on two distinct groups of patients with diffuse chronic liver disorders, one group with steatosis and none-to-moderate inflammation (n = 13) and one group with severe fibrosis or cirrhosis (n = 16). All patients underwent liver biopsy and extensive biochemical evaluation. A control group (n = 13) was also included. Lower concentrations of PDE (p = 0.025) and a higher AC (p = 0.001) were found in the cirrhosis group compared to the control group.Using a PDE concentration of 10.5 mM as a cut-off value to discriminate between mild (stage 0-2) and advanced (stage 3-4) fibrosis the sensitivity and specificity were 81% and 69% respectively. An AC cut-off value of 0.27 showed a sensitivity of 93% and a specificity of 54%.In conclusion the results indicates that a decrease in PDE concentration is a marker of liver fibrosis and that AC is a potentially clinically useful parameter indiscriminating mild fibrosis from advanced. No significant relationship between the MRS data and the degree of steatosis or inflammation was found.
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| 14. |
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| 15. |
- Norén, Bengt, 1955-, et al.
(författare)
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Separation of advanced from mild fibrosis in diffuse liver disease using 31P magnetic resonance spectroscopy
- 2008
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Ingår i: European Journal of Radiology. - : Elsevier. - 0720-048X .- 1872-7727. ; 66:2, s. 313-320
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Tidskriftsartikel (refereegranskat)abstract
- 31P-MRS using DRESS was used to compare absolute liver metabolite concentrations (PME, Pi, PDE, γATP, αATP, βATP) in two distinct groups of patients with chronic diffuse liver disorders, one group with steatosis (NAFLD) and none to moderate inflammation (n = 13), and one group with severe fibrosis or cirrhosis (n = 16). All patients underwent liver biopsy and extensive biochemical evaluation. A control group (n = 13) was also included. Absolute concentrations and the anabolic charge, AC = {PME}/({PME} + {PDE}), were calculated.Comparing the control and cirrhosis groups, lower concentrations of PDE (p = 0.025) and a higher AC (p < 0.001) were found in the cirrhosis group. Also compared to the NAFLD group, the cirrhosis group had lower concentrations of PDE (p = 0.01) and a higher AC (p = 0.009). No significant differences were found between the control and NAFLD group. When the MRS findings were related to the fibrosis stage obtained at biopsy, there were significant differences in PDE between stage F0–1 and stage F4 and in AC between stage F0–1 and stage F2–3.Using a PDE concentration of 10.5 mM as a cut-off value to discriminate between mild, F0–2, and advanced, F3–4, fibrosis the sensitivity and specificity were 81% and 69%, respectively. An AC cut-off value of 0.27 showed a sensitivity of 93% and a specificity of 54%.In conclusion, the results suggest that PDE is a marker of liver fibrosis, and that AC is a potentially clinically useful parameter in discriminating mild fibrosis from advanced.
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| 16. |
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| 17. |
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| 18. |
- Rundblad, Bengt, et al.
(författare)
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Politiskt ledarskap i en kommun
- 1992
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Ingår i: Schaller, J., & Johansson, J., (red), Ledarskap och arbetsmiljö.. - Göteborg : Akademiförlaget. - 9124165557
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 19. |
- Sörstedt, Erik, 1980-, et al.
(författare)
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Computed tomographic colonography : Comparison of two workstations
- 2005
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 46:7, s. 671-678
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare two commercially available computed tomography (CT) colonography systems with respect to interobserver variability, the influence of level of expertise, and the gradual reduction of reviewing time for each system. Material and Methods: Two residents and two radiologists using Siemens CTAPP Colography software and Viatronix V3DColon software reviewed supine and prone CT acquisitions from 24 patients in a primary 3D endoluminal view. The observers graded each case with respect to technical quality and diagnostic value, assessed the presence of pathology, and indicated the time spent on the viewing. Results: Significant differences were found in technical quality ( P <0.001) and diagnostic value ( P <0.001) depending on which system was used, with higher scores for the Viatronix software. The agreement between specialists tended to be higher than that between residents (κ = 0.63 (0.30-0.95) vs. κ = 0.51 (0.21-0.81)), and the residents gave significantly ( P <0.001) higher scores of technical quality. However, the level of expertise had no significant impact on the assessments. We noted extensive variability in pathological lesions found by the different observers. The number of findings did not differ between workstations, but the viewers tended to report larger polyp sizes with the Viatronix software. The time needed for viewing decreased significantly from the first to the last examination viewed by each observer. Conclusion: Both the evaluated systems present trustworthy images of the human colon, but in a primary 3D setting the Viatronix software is favored owing to the userfriendly interface, higher experienced technical quality, and better diagnostic value. © 2005 Taylor & Francis.
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