Rationale and Objectives
Water molecule motion has been shown to be isotropic in healthy liver as assessed by diffusion-weighted imaging (DWI). The purpose of this study was to investigate whether this assumption is still valid in the cirrhotic liver.
Materials and Methods
Twelve cirrhotic patients and 12 controls underwent DWI on a 3.0T-system. We used an echo-planar sequence independently applying unidirectional motion-probing gradients along read-(x), phase-(y), and slice-(z) directions, respectively. Liver apparent diffusion coefficient (ADC) and perfusion fraction ( f ) were calculated along each gradient direction, based on two b-values sets (0–400 and 0–800 seconds/mm 2 ). Measurement was repeated at two different axial slices of the liver.
Results
No significant difference among x, y, and z- ADC (and f ) of the liver was found within controls and cirrhotic patients ( P > .01), regardless of the set of b-values or the slice of measurement. ADC was lower in cirrhotic patients than in controls (difference of 0.24–0.39 × 10 −3 mm 2 /seconds at b = 800 seconds/mm 2 ; P = .000–.0139). Perfusion fraction f was lower in cirrhotics than in controls, irrespective of the b-values set or the slice of measurement (difference of 0.05–0.15; P < .0001–.0885).
Conclusion
The liver shows isotropic water diffusion in cirrhotics, despite fibrotic distortion leading to decreased ADC as compared to controls. Our results emphasize that the correlation between parenchymal changes in liver fibrosis and the ADC estimate remains an elusive goal based on the state-of-the-art DWI technique.
Over the last years, diffusion-weighted Imaging (DWI) has been investigated as a tool to provide noninvasive detection and quantification of liver fibrosis . Fibrosis results from the accumulation of extracellular matrix components, which causes distortion of the parenchymal architecture , and leads to the restriction of water diffusion . As expected, the hepatic apparent diffusion coefficient (ADC), measured by means of DWI, has been shown to decrease proportionally to the degree of fibrosis and/or inflammation . Nonetheless, the mechanism underlying the decrease of the ADC is not completely understood, and probably depends more on alterations in liver perfusion rather than in actual diffusion . Thus, the radiopathologic correlation of what DWI measures in liver fibrosis must be further elucidated.
In addition, several concerns still limit DWI clinical applications for liver fibrosis. Among them, technical issues like the choice of b-values, sequence design and ADC assessment optimization are those mainly affecting the reproducibility of results . In this scenario, the most appropriate direction of DWI motion-probing gradients is still undetermined. In previous studies, gradients have been applied multi- or mono-directionally, based on the assumption that the liver shows isotropic water diffusion . To our knowledge, this assumption has been investigated on humans only by Taouli et al on a 1.5-T system . No previous studies were aimed to assess liver isotropy at higher magnetic field strength, and whether isotropy is lost (or not) in liver fibrosis.
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Materials and methods
Patients
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DWI Protocol
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Image Analysis and ADC Determination
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ADC=1/bi×ln(S0/Si) ADC
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f=1−exp[−b(ADC−D)] f
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Data Analysis
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Results
Image Quality and Homogeneity of Measurements
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Table 1
P Value of the Differences between Liver Apparent Diffusion Coefficient (ADC) and Perfusion Fraction f Along Each Diffusion Gradient Direction Applied (Unpaired t -Test)
ADC at 0–400 seconds/mm 2 ADC at 0–800 seconds/mm 2 Perfusion Fraction f x y z x y z x y z CONTROLS
Slice 1 vs. slice 2 ( P ) 0.7436 0.6975 0.8739 0.5768 0.3412 0.6274 0.9105 1.000 0.4599 CIRRHOTICS
Slice 1 vs. slice 2 ( P ) 0.2113 0.1912 0.0369 0.8156 0.4055 0.4164 0.1297 0.3097 0.0626
Measurements are consistent in our model. Range, mean, and standard deviation of ADC and f values are detailed in Tables 2 and 3 .
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Patterns of Water Diffusion within the Liver
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Table 2a
ADC and Perfusion Fraction f in Controls and Cirrhotic Patients Measured on slice 1 (1 cm Above the Level of the Hepatic Hilum)
Diffusion Gradient Direction_P_ x y z Controls ADC at 0–400 second/mm 2 Range 1.32–2.60 1.22–2.50 1.42–2.91 .990 Mean ± SD 1.95 ± 0.41 1.96 ± 0.34 1.97 ± 0.43 95% CI 1.69–2.21 1.74–2.17 1.69–2.25 ADC at 0–800 seconds/mm 2 P = .0001P = .0001P = .0001 Range 1.05–2.06 0.86–1.62 1.10–1.70 .597 Mean ± SD 1.42 ± 0.25 1.33 ± 0.24 1.40 ± 0.20 95% CI 1.26–1.59 1.18–1.48 1.27–1.53f Range 0.03–0.35 0.05–0.35 0.09–0.38 .635 Mean ± SD 0.18 ± 0.10 0.21 ± 0.08 0.20 ± 0.08 95% CI 0.11–0.24 0.16–0.26 0.15–0.25 Cirrhotics ADC at 0–400 seconds/mm 2 Range 0.96–1.91 0.99–1.75 0.89–1.46 .082 Mean ± SD 1.35 ± 0.25 1.27 ± 0.23 1.15 ± 0.17 95% CI 1.19–1.52 1.07–1.52 1.03–1.25 ADC at 0–800 seconds/mm 2 P = .0012P = .0039P = .0006 Range 0.63–1.69 0.63–1.48 0.64–1.31 .057 Mean ± SD 1.13 ± 0.28 1.06 ± 0.22 1.01 ± 0.19 95% CI 0.94–1.31 0.92–1.21 0.89–1.13f Range 0.01–0.21 0.01–0.23 0.01–0.13 .363 Mean ± SD 0.08 ± 0.06 0.07 ± 0.07 0.05 ± 0.03 95% CI 0.04–0.12 0.03–0.12 0.03–0.12
Table 2b
ADC and Perfusion Fraction f in Controls and Cirrhotic Patients Measured on slice 2 (1 cm Below the Level of the Hepatic Hilum)
Diffusion Gradient Direction_P_ x y z Controls ADC at 0–400 seconds/mm 2 Range 1.38–2.84 1.49–2.72 1.35–2.76 .857 Mean ± SD 2.00 ± 0.40 2.03 ± 0.40 1.94 ± 0.42 95% CI 1.75–2.26 1.78–2.29 1.65–2.21 ADC at 0–800 seconds/mm 2 P < .0001P < .0001P = .0001 Range 1.09–1.80 1.1–1.73 1.15–1.82 .719 Mean ± SD 1.48 ± 0.19 1.41 ± 0.17 1.44 ± 0.20 95% CI 1.35–1.60 1.30–1.52 1.31–1.57f Range 0.09–0.34 0.12–0.34 0.04–0.31 .662 Mean ± SD 0.18 ± 0.07 0.21 ± 0.07 0.16 ± 0.09 95% CI 0.13–0.22 0.16–0.26 0.12–0.23 Cirrhotics ADC at 0–400 seconds/mm 2 Range 1.10–2.11 1.04–2.12 1.00–1.89 .376 Mean ± SD 1.52 ± 0.35 1.43 ± 0.34 1.33 ± 0.23 95% CI 1.29–1.74 1.21–1.65 1.18–1.48 ADC at 0–800 seconds/mm 2 P = .0002P = .0001P = .0004 Range 0.43–1.54 0.80–1.57 0.77–1.35 .657 Mean ± SD 1.16 ± 0.31 1.14 ± 0.22 1.07 ± 0.16 95% CI 0.95–1.36 1.00–1.28 0.96–1.18f Range 0.03–0.24 0.01–0.20 0.01–0.27 .534 Mean ± SD 0.13 ± 0.11 0.10 ± 0.07 0.09 ± 0.07 95% CI 0.08–0.18 0.06–0.15 0.05–0.14
ADC, apparent diffusion coefficient; SD, standard deviation; x, read-encoding direction; y, phase-encoding direction; z, slice-select direction.
No significant difference in ADC and f was observed along different diffusion gradient directions x, y, and z within controls and cirrhotics. Both in controls and cirrhotic patients, ADCs decreased by increasing maximum b-value from 400 to 800 seconds/mm 2 ( P values shown across table cells). ADCs are expressed in × 10 −3 mm 2 /seconds.
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Diagnosis of Cirrhosis
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Table 3
Difference between Liver ADC of Controls vs. Cirrhotics (Expressed in ×10 −3 mm 2 /second), with the Statistical Significance Expressed by the P Value
ADC at 0–400 seconds/mm 2 ADC at 0–800 seconds/mm 2 Perfusion Fraction f x y z x y z x y z Slice 1 Difference 0.60 0.69 0.82 0.29 0.27 0.39 0.10 0.14 0.15P .0003 <.0001 <.0001 .0139 .0107 .0001 .0106 .0002 <.0001 Slice 2 Difference 0.48 0.60 0.61 0.32 0.24 0.37 0.05 0.11 0.08P .0050 .0007 .0003 .0084 .0045 .0001 .0885 .0016 .0255
ADC, apparent diffusion coefficient; x, read-encoding direction; y, phase-encoding direction; z, slice-select direction.
Data are reported for every diffusion gradient direction, at both slices 1 and 2.
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Discussion
Liver Isotropy at 3.0T
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Liver Isotropy in Cirrhotic Patients
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Limitations
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Conclusion
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