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Absolute quantification of human liver metabolite concentrations by localized in vivo 31P NMR spectroscopy in diffuse liver disease
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Medical Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology UHL.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radiation Physics. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).ORCID iD: 0000-0001-8661-2232
Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Center for Medical Image Science and Visualization (CMIV).
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Medical Radiology.
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2005 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 15, no 1, 148-157 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2005. Vol. 15, no 1, 148-157 p.
Keyword [en]
phosphorus MR spectroscopy, absolute concentrations, diffuse liver disease
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-24421DOI: 10.1007/s00330-004-2434-xISI: 000227354900022Local ID: 6524OAI: oai:DiVA.org:liu-24421DiVA: diva2:244739
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
In thesis
1. Non-Invasive Assessment of Liver Fibrosis with 31P-Magnetic Resonance Spectroscopy and Dynamic Contrast Enhanced Magnetic Resonance Imaging
Open this publication in new window or tab >>Non-Invasive Assessment of Liver Fibrosis with 31P-Magnetic Resonance Spectroscopy and Dynamic Contrast Enhanced Magnetic Resonance Imaging
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. 72 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1351
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90154 (URN)978-91-7519-705-0N (print) (ISBN)
Public defence
2013-03-15, Eken, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Funder
Swedish Research Council
Available from: 2013-06-04 Created: 2013-03-20 Last updated: 2014-10-02Bibliographically approved
2. Quantitative 31P magnetic resonance spectroscopy in diffuse liver disease
Open this publication in new window or tab >>Quantitative 31P magnetic resonance spectroscopy in diffuse liver disease
2006 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2006. 41 p.
Series
Linköping Studies in Health Sciences. Thesis, ISSN 1100-6013 ; 77
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-34266 (URN)21190 (Local ID)91-85497-88-6 (ISBN)21190 (Archive number)21190 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2013-09-18

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Norén, BengtLundberg, PeterRessner, MarcusWirell, StaffanAlmer, SvenSmedby, Örjan

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Faculty of Health SciencesMedical RadiologyDepartment of Radiology UHLRadiation PhysicsDepartment of Radiation PhysicsCenter for Medical Image Science and Visualization (CMIV)The Institute of TechnologyPhysiological MeasurementsGastroenterology and HepatologyDepartment of Endocrinology and Gastroenterology UHL
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