T2 relaxation time is related to liver fibrosis severity

Alexander Guimaraes, Luiz Siqueira, Ritika Uppal, Jamu Alford, Bryan C. Fuchs, Suguru Yamada, Kenneth Tanabe, Raymond T. Chung, Gregory Lauwers, Michael L. Chew, Giles W. Boland, Duhyant V. Sahani, Mark Vangel, Peter F. Hahn, Peter Caravan

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: The grading of liver fibrosis relies on liver biopsy. Imaging techniques, including elastography and relaxometric, techniques have had varying success in diagnosing moderate fibrosis. The goal of this study was to determine if there is a relationship between the T2-relaxation time of hepatic parenchyma and the histologic grade of liver fibrosis in patients with hepatitis C undergoing both routine, liver MRI and liver biopsy, and to validate our methodology with phantoms and in a rat model of liver fibrosis. Methods: This study is composed of three parts: (I) 123 patients who underwent both routine, clinical liver MRI and biopsy within a 6-month period, between July 1999 and January 2010 were enrolled in a retrospective study. MR imaging was performed at 1.5 T using dual-echo turbo-spin echo equivalent pulse sequence. T2 relaxation time of liver parenchyma in patients was calculated by mono-exponential fit of a region of interest (ROI) within the right lobe correlating to histopathologic grading (Ishak 0-6) and routine serum liver inflammation [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)]. Statistical comparison was performed using ordinary logistic and ordinal logistic regression and ANOVA comparing T2 to Ishak fibrosis without and using AST and ALT as covariates; (II) a phantom was prepared using serial dilutions of dextran coated magnetic iron oxide nanoparticles. T2 weighed imaging was performed by comparing a dual echo fast spin echo sequence to a Carr-Purcell-Meigboom-Gill (CPMG) multi-echo sequence at 1.5 T. Statistical comparison was performed using a paired t-test; (III) male Wistar rats receiving weekly intraperitoneal injections of phosphate buffer solution (PBS) control (n=4 rats); diethylnitrosamine (DEN) for either 5 (n=5 rats) or 8 weeks (n=4 rats) were MR imaged on a Bruker Pharmascan 4.7 T magnet with a home-built bird-cage coil. T2 was quantified by using a mono-exponential fitting algorithm on multislice multi echo T2 weighted data. Statistical comparison was performed using ANOVA. Results: (I) Histopathologic evaluation of both rat and human livers demonstrated no evidence of steatosis or hemochromatosis There was a monotonic increase in mean T2 value with increasing degree of fibrosis (control 65.4±2.9 ms, n=6 patients); mild (Ishak 1-2) 66.7±1.9 ms (n=30); moderate (Ishak 3-4) 71.6±1.7 ms (n=26); severe (Ishak 5-6) 72.4±1.4 ms (n=61); with relatively low standard error (∼2.9 ms). There was a statistically significant difference between degrees of mild (Ishak <4) vs. moderate to severe fibrosis (Ishak >4) (P=0.03) based on logistic regression of T2 and Ishak, which became insignificant (P=0.07) when using inflammatory markers as covariates. Expanding on this model using ordinal logistic regression, there was significance amongst all 4 groups comparing T2 to Ishak (P=0.01), with significance using inflammation as a covariate (P=0.03) and approaching statistical significance amongst all groups by ANOVA (P=0.07); (II) there was a monotonic increase in T2 and statistical significance (ANOVA P<0.0001) between each rat subgroup [phosphate buffer solution (PBS) 25.2±0.8, DEN 5-week (31.1±1.5), and DEN 9-week (49.4±0.4) ms]; (III) the phantoms that had T2 values within the relevant range for the human liver (e.g., 20-100 ms), demonstrated no statistical difference between two point fits on turbo spin echo (TSE) data and multi-echo CPMG data (P=0.9). Conclusions: The finding of increased T2 with liver fibrosis may relate to inflammation that may be an alternative or adjunct to other noninvasive MR imaging based approaches for assessing liver fibrosis.

Original languageEnglish (US)
Pages (from-to)103-114
Number of pages12
JournalQuantitative Imaging in Medicine and Surgery
Volume6
Issue number2
DOIs
StatePublished - 2016

Fingerprint

Liver Cirrhosis
Liver
Diethylnitrosamine
Analysis of Variance
Fibrosis
Logistic Models
Aspartate Aminotransferases
Inflammation
Alanine Transaminase
Biopsy
Buffers
Phosphates
Elasticity Imaging Techniques
Hemochromatosis
Magnets
Hepatitis C
Dextrans
Intraperitoneal Injections
Nanoparticles
Birds

Keywords

  • Fibrosis imaging biomarkers
  • Liver fibrosis
  • MRI
  • Quantitative Imaging
  • T2 relaxation time

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Guimaraes, A., Siqueira, L., Uppal, R., Alford, J., Fuchs, B. C., Yamada, S., ... Caravan, P. (2016). T2 relaxation time is related to liver fibrosis severity. Quantitative Imaging in Medicine and Surgery, 6(2), 103-114. https://doi.org/10.21037/qims.2016.03.02

T2 relaxation time is related to liver fibrosis severity. / Guimaraes, Alexander; Siqueira, Luiz; Uppal, Ritika; Alford, Jamu; Fuchs, Bryan C.; Yamada, Suguru; Tanabe, Kenneth; Chung, Raymond T.; Lauwers, Gregory; Chew, Michael L.; Boland, Giles W.; Sahani, Duhyant V.; Vangel, Mark; Hahn, Peter F.; Caravan, Peter.

In: Quantitative Imaging in Medicine and Surgery, Vol. 6, No. 2, 2016, p. 103-114.

Research output: Contribution to journalArticle

Guimaraes, A, Siqueira, L, Uppal, R, Alford, J, Fuchs, BC, Yamada, S, Tanabe, K, Chung, RT, Lauwers, G, Chew, ML, Boland, GW, Sahani, DV, Vangel, M, Hahn, PF & Caravan, P 2016, 'T2 relaxation time is related to liver fibrosis severity', Quantitative Imaging in Medicine and Surgery, vol. 6, no. 2, pp. 103-114. https://doi.org/10.21037/qims.2016.03.02
Guimaraes, Alexander ; Siqueira, Luiz ; Uppal, Ritika ; Alford, Jamu ; Fuchs, Bryan C. ; Yamada, Suguru ; Tanabe, Kenneth ; Chung, Raymond T. ; Lauwers, Gregory ; Chew, Michael L. ; Boland, Giles W. ; Sahani, Duhyant V. ; Vangel, Mark ; Hahn, Peter F. ; Caravan, Peter. / T2 relaxation time is related to liver fibrosis severity. In: Quantitative Imaging in Medicine and Surgery. 2016 ; Vol. 6, No. 2. pp. 103-114.
@article{2170523b20544aa18e0532006eb0c8a4,
title = "T2 relaxation time is related to liver fibrosis severity",
abstract = "Background: The grading of liver fibrosis relies on liver biopsy. Imaging techniques, including elastography and relaxometric, techniques have had varying success in diagnosing moderate fibrosis. The goal of this study was to determine if there is a relationship between the T2-relaxation time of hepatic parenchyma and the histologic grade of liver fibrosis in patients with hepatitis C undergoing both routine, liver MRI and liver biopsy, and to validate our methodology with phantoms and in a rat model of liver fibrosis. Methods: This study is composed of three parts: (I) 123 patients who underwent both routine, clinical liver MRI and biopsy within a 6-month period, between July 1999 and January 2010 were enrolled in a retrospective study. MR imaging was performed at 1.5 T using dual-echo turbo-spin echo equivalent pulse sequence. T2 relaxation time of liver parenchyma in patients was calculated by mono-exponential fit of a region of interest (ROI) within the right lobe correlating to histopathologic grading (Ishak 0-6) and routine serum liver inflammation [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)]. Statistical comparison was performed using ordinary logistic and ordinal logistic regression and ANOVA comparing T2 to Ishak fibrosis without and using AST and ALT as covariates; (II) a phantom was prepared using serial dilutions of dextran coated magnetic iron oxide nanoparticles. T2 weighed imaging was performed by comparing a dual echo fast spin echo sequence to a Carr-Purcell-Meigboom-Gill (CPMG) multi-echo sequence at 1.5 T. Statistical comparison was performed using a paired t-test; (III) male Wistar rats receiving weekly intraperitoneal injections of phosphate buffer solution (PBS) control (n=4 rats); diethylnitrosamine (DEN) for either 5 (n=5 rats) or 8 weeks (n=4 rats) were MR imaged on a Bruker Pharmascan 4.7 T magnet with a home-built bird-cage coil. T2 was quantified by using a mono-exponential fitting algorithm on multislice multi echo T2 weighted data. Statistical comparison was performed using ANOVA. Results: (I) Histopathologic evaluation of both rat and human livers demonstrated no evidence of steatosis or hemochromatosis There was a monotonic increase in mean T2 value with increasing degree of fibrosis (control 65.4±2.9 ms, n=6 patients); mild (Ishak 1-2) 66.7±1.9 ms (n=30); moderate (Ishak 3-4) 71.6±1.7 ms (n=26); severe (Ishak 5-6) 72.4±1.4 ms (n=61); with relatively low standard error (∼2.9 ms). There was a statistically significant difference between degrees of mild (Ishak <4) vs. moderate to severe fibrosis (Ishak >4) (P=0.03) based on logistic regression of T2 and Ishak, which became insignificant (P=0.07) when using inflammatory markers as covariates. Expanding on this model using ordinal logistic regression, there was significance amongst all 4 groups comparing T2 to Ishak (P=0.01), with significance using inflammation as a covariate (P=0.03) and approaching statistical significance amongst all groups by ANOVA (P=0.07); (II) there was a monotonic increase in T2 and statistical significance (ANOVA P<0.0001) between each rat subgroup [phosphate buffer solution (PBS) 25.2±0.8, DEN 5-week (31.1±1.5), and DEN 9-week (49.4±0.4) ms]; (III) the phantoms that had T2 values within the relevant range for the human liver (e.g., 20-100 ms), demonstrated no statistical difference between two point fits on turbo spin echo (TSE) data and multi-echo CPMG data (P=0.9). Conclusions: The finding of increased T2 with liver fibrosis may relate to inflammation that may be an alternative or adjunct to other noninvasive MR imaging based approaches for assessing liver fibrosis.",
keywords = "Fibrosis imaging biomarkers, Liver fibrosis, MRI, Quantitative Imaging, T2 relaxation time",
author = "Alexander Guimaraes and Luiz Siqueira and Ritika Uppal and Jamu Alford and Fuchs, {Bryan C.} and Suguru Yamada and Kenneth Tanabe and Chung, {Raymond T.} and Gregory Lauwers and Chew, {Michael L.} and Boland, {Giles W.} and Sahani, {Duhyant V.} and Mark Vangel and Hahn, {Peter F.} and Peter Caravan",
year = "2016",
doi = "10.21037/qims.2016.03.02",
language = "English (US)",
volume = "6",
pages = "103--114",
journal = "Quantitative Imaging in Medicine and Surgery",
issn = "2223-4292",
publisher = "AME Publishing Company",
number = "2",

}

TY - JOUR

T1 - T2 relaxation time is related to liver fibrosis severity

AU - Guimaraes, Alexander

AU - Siqueira, Luiz

AU - Uppal, Ritika

AU - Alford, Jamu

AU - Fuchs, Bryan C.

AU - Yamada, Suguru

AU - Tanabe, Kenneth

AU - Chung, Raymond T.

AU - Lauwers, Gregory

AU - Chew, Michael L.

AU - Boland, Giles W.

AU - Sahani, Duhyant V.

AU - Vangel, Mark

AU - Hahn, Peter F.

AU - Caravan, Peter

PY - 2016

Y1 - 2016

N2 - Background: The grading of liver fibrosis relies on liver biopsy. Imaging techniques, including elastography and relaxometric, techniques have had varying success in diagnosing moderate fibrosis. The goal of this study was to determine if there is a relationship between the T2-relaxation time of hepatic parenchyma and the histologic grade of liver fibrosis in patients with hepatitis C undergoing both routine, liver MRI and liver biopsy, and to validate our methodology with phantoms and in a rat model of liver fibrosis. Methods: This study is composed of three parts: (I) 123 patients who underwent both routine, clinical liver MRI and biopsy within a 6-month period, between July 1999 and January 2010 were enrolled in a retrospective study. MR imaging was performed at 1.5 T using dual-echo turbo-spin echo equivalent pulse sequence. T2 relaxation time of liver parenchyma in patients was calculated by mono-exponential fit of a region of interest (ROI) within the right lobe correlating to histopathologic grading (Ishak 0-6) and routine serum liver inflammation [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)]. Statistical comparison was performed using ordinary logistic and ordinal logistic regression and ANOVA comparing T2 to Ishak fibrosis without and using AST and ALT as covariates; (II) a phantom was prepared using serial dilutions of dextran coated magnetic iron oxide nanoparticles. T2 weighed imaging was performed by comparing a dual echo fast spin echo sequence to a Carr-Purcell-Meigboom-Gill (CPMG) multi-echo sequence at 1.5 T. Statistical comparison was performed using a paired t-test; (III) male Wistar rats receiving weekly intraperitoneal injections of phosphate buffer solution (PBS) control (n=4 rats); diethylnitrosamine (DEN) for either 5 (n=5 rats) or 8 weeks (n=4 rats) were MR imaged on a Bruker Pharmascan 4.7 T magnet with a home-built bird-cage coil. T2 was quantified by using a mono-exponential fitting algorithm on multislice multi echo T2 weighted data. Statistical comparison was performed using ANOVA. Results: (I) Histopathologic evaluation of both rat and human livers demonstrated no evidence of steatosis or hemochromatosis There was a monotonic increase in mean T2 value with increasing degree of fibrosis (control 65.4±2.9 ms, n=6 patients); mild (Ishak 1-2) 66.7±1.9 ms (n=30); moderate (Ishak 3-4) 71.6±1.7 ms (n=26); severe (Ishak 5-6) 72.4±1.4 ms (n=61); with relatively low standard error (∼2.9 ms). There was a statistically significant difference between degrees of mild (Ishak <4) vs. moderate to severe fibrosis (Ishak >4) (P=0.03) based on logistic regression of T2 and Ishak, which became insignificant (P=0.07) when using inflammatory markers as covariates. Expanding on this model using ordinal logistic regression, there was significance amongst all 4 groups comparing T2 to Ishak (P=0.01), with significance using inflammation as a covariate (P=0.03) and approaching statistical significance amongst all groups by ANOVA (P=0.07); (II) there was a monotonic increase in T2 and statistical significance (ANOVA P<0.0001) between each rat subgroup [phosphate buffer solution (PBS) 25.2±0.8, DEN 5-week (31.1±1.5), and DEN 9-week (49.4±0.4) ms]; (III) the phantoms that had T2 values within the relevant range for the human liver (e.g., 20-100 ms), demonstrated no statistical difference between two point fits on turbo spin echo (TSE) data and multi-echo CPMG data (P=0.9). Conclusions: The finding of increased T2 with liver fibrosis may relate to inflammation that may be an alternative or adjunct to other noninvasive MR imaging based approaches for assessing liver fibrosis.

AB - Background: The grading of liver fibrosis relies on liver biopsy. Imaging techniques, including elastography and relaxometric, techniques have had varying success in diagnosing moderate fibrosis. The goal of this study was to determine if there is a relationship between the T2-relaxation time of hepatic parenchyma and the histologic grade of liver fibrosis in patients with hepatitis C undergoing both routine, liver MRI and liver biopsy, and to validate our methodology with phantoms and in a rat model of liver fibrosis. Methods: This study is composed of three parts: (I) 123 patients who underwent both routine, clinical liver MRI and biopsy within a 6-month period, between July 1999 and January 2010 were enrolled in a retrospective study. MR imaging was performed at 1.5 T using dual-echo turbo-spin echo equivalent pulse sequence. T2 relaxation time of liver parenchyma in patients was calculated by mono-exponential fit of a region of interest (ROI) within the right lobe correlating to histopathologic grading (Ishak 0-6) and routine serum liver inflammation [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)]. Statistical comparison was performed using ordinary logistic and ordinal logistic regression and ANOVA comparing T2 to Ishak fibrosis without and using AST and ALT as covariates; (II) a phantom was prepared using serial dilutions of dextran coated magnetic iron oxide nanoparticles. T2 weighed imaging was performed by comparing a dual echo fast spin echo sequence to a Carr-Purcell-Meigboom-Gill (CPMG) multi-echo sequence at 1.5 T. Statistical comparison was performed using a paired t-test; (III) male Wistar rats receiving weekly intraperitoneal injections of phosphate buffer solution (PBS) control (n=4 rats); diethylnitrosamine (DEN) for either 5 (n=5 rats) or 8 weeks (n=4 rats) were MR imaged on a Bruker Pharmascan 4.7 T magnet with a home-built bird-cage coil. T2 was quantified by using a mono-exponential fitting algorithm on multislice multi echo T2 weighted data. Statistical comparison was performed using ANOVA. Results: (I) Histopathologic evaluation of both rat and human livers demonstrated no evidence of steatosis or hemochromatosis There was a monotonic increase in mean T2 value with increasing degree of fibrosis (control 65.4±2.9 ms, n=6 patients); mild (Ishak 1-2) 66.7±1.9 ms (n=30); moderate (Ishak 3-4) 71.6±1.7 ms (n=26); severe (Ishak 5-6) 72.4±1.4 ms (n=61); with relatively low standard error (∼2.9 ms). There was a statistically significant difference between degrees of mild (Ishak <4) vs. moderate to severe fibrosis (Ishak >4) (P=0.03) based on logistic regression of T2 and Ishak, which became insignificant (P=0.07) when using inflammatory markers as covariates. Expanding on this model using ordinal logistic regression, there was significance amongst all 4 groups comparing T2 to Ishak (P=0.01), with significance using inflammation as a covariate (P=0.03) and approaching statistical significance amongst all groups by ANOVA (P=0.07); (II) there was a monotonic increase in T2 and statistical significance (ANOVA P<0.0001) between each rat subgroup [phosphate buffer solution (PBS) 25.2±0.8, DEN 5-week (31.1±1.5), and DEN 9-week (49.4±0.4) ms]; (III) the phantoms that had T2 values within the relevant range for the human liver (e.g., 20-100 ms), demonstrated no statistical difference between two point fits on turbo spin echo (TSE) data and multi-echo CPMG data (P=0.9). Conclusions: The finding of increased T2 with liver fibrosis may relate to inflammation that may be an alternative or adjunct to other noninvasive MR imaging based approaches for assessing liver fibrosis.

KW - Fibrosis imaging biomarkers

KW - Liver fibrosis

KW - MRI

KW - Quantitative Imaging

KW - T2 relaxation time

UR - http://www.scopus.com/inward/record.url?scp=84994713301&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994713301&partnerID=8YFLogxK

U2 - 10.21037/qims.2016.03.02

DO - 10.21037/qims.2016.03.02

M3 - Article

VL - 6

SP - 103

EP - 114

JO - Quantitative Imaging in Medicine and Surgery

JF - Quantitative Imaging in Medicine and Surgery

SN - 2223-4292

IS - 2

ER -