Table 2.

Imaging based quantitative methods for evaluation of liver fibrosis

Method	Parameter (s) evaluated	Confounding factors	Advantages	Limitations
Ultrasound based
Vibration controlled transient elastography (VCTE or Fibroscan®) [81, 82, 95, 96]	Bulk modulus @50Hz	Fatty liver Inflammation Biliary obstruction Venous congestion Diffuse infiltrative disorders Post prandial state Excessive alcohol	Rapid, easy to perform Repeatable Widely available Validated in all common CLDs Excellent for distinguishing advanced fibrosis from mild or no fibrosis Shown to be useful for predicting outcome and complications	Dependent on operator’s experience Limited depth of penetration Patient factors-small intercostal space, excessive visceral fat, obesity, and ascites Blinded technique and region of interest cannot be chosen
Point shear wave elastography (pSWE) and two-dimensional shear wave elastography (2D-SWE) [72, 83, 84, 95, 96, 112]	Shear stiffness at variable frequencies	Fatty liver Inflammation Biliary obstruction Venous congestion Diffuse infiltrative disorders Post prandial state Excessive alcohol	Can be performed with routine ultrasound of liver Region of interest (ROI) can be chosen Measures stiffness in real time High performance for diagnosis of significant fibrosis and cirrhosis	Operator dependent Patient factors-obesity and ascites
CT based
Dual energy CT	Extracellular volume (ECV) Iodine washout rate (IWR) Parenchymal iodine density	Portal flow Inflammation Congestion	Can be performed easily on dual energy CT scanners	Prospective evaluation results are lacking Intravenous contrast Exposure to radiation No standardized acquisition Unknown reproducibility across vendors Availability of dual energy CT technique is limited
MRI based
Magnetic resonance elastography (MRE) [81–83, 87, 89, 94, 95, 97, 112]	Shear stiffness @60 Hz	Inflammation Biliary obstruction Venous congestion Diffuse infiltrative disorders	High repeatability and reproducibility Whole liver evaluation possible High diagnostic performance for early stages of fibrosis Not affected by obesity or fatty change in the liver Validated in all common CLDs Useful for predicting outcome and complications	Needs dedicated hardware and software Not widely available Moderate to severe iron deposition
Diffusion weighted imaging (DWI) and Intravoxel incoherent imaging (IVIM) [89, 99]	Apparent diffusion coefficient (ADC) Diffusion coefficient (D) Pseudo-diffusion coefficient (D*) Perfusion fraction (f)	Fatty liver Iron deposition Inflammation	DWI widely available in all clinical MR scanners No intravenous contrast required High performance differentiating advanced fibrosis/cirrhosis from normal liver	Motion sensitive Lack of standardized acquisition parameters Poor repeatability and reproducibility Low to moderate performance for intermediate stages IVIM not widely available
T1-mapping [89, 104, 105]	T1-relaxation time	Iron Fatty change Acute liver disease	Can be performed with or without intravenous contrast	No standardization of acquisition parameters and analysis Repeatability and reproducibility across scanners not widely established
T1ρ [103, 105]	Spin–lattice relaxation time	Magnetic field inhomogeneities	No additional hardware required No contrast required	Sensitive to B0 and B1 field inhomogeneities High specific absorption rate Research studies and not validated for clinical use
Hepatobiliary contrast uptake on MRI	Gadoxetate uptake ratio	Genetic variability of expression of proteins Competing drugs for uptake	Can be performed on any available clinical scanner Short post processing calculation	Specific use of hepatobiliary contrast agent Needs longer imaging time for the hepatobiliary phase Decreased enhancement in fatty or iron loaded livers
CT or MRI
Surface nodularity score (CT or MRI) [106, 107, 110, 111]	Nodularity of the surface	Disease that can mimic cirrhosis such as nodular regenerative hyperplasia and treated multifocal metastases	Semiautomatic Performed on existing or previously acquired CT/MRI Relatively less affected by inflammation, acute biliary obstruction, and hepatic congestion	Computation time Not validated in all etiologies May be less accurate in NAFLD May be difficult to evaluate in patients with ascites and very thin patients
CT volumetric assessment [89]	Caudate to right lobe ratio (CRL) Liver segment volume ratio (LSVR) Splenic volume (SV)	Volumetric changes without fibrosis can occur. For example, from portal vein occlusion in perihilar cholangiocarcinoma or severe biliary strictures in PSC	No special technique required Performed on existing CT studies Can be performed on MRI as well	Computation of volumes take time Ionizing radiation with CT Low sensitivity for early fibrosis Other causes of organomegaly may confound volumetry
Fractional extracellular space (CT or MRI)	Extracellular space which becomes wider or larger in LF due to deposition of fibrosis in extracellular space	Edema Congestion	Can be performed with CT or MRI	Need prospective evaluation Specific phases of contrast need to be obtained such as equilibrium phases Motion artifacts Not validated in all etiologies Poor discrimination between intermediate stages of fibrosis
Perfusion CT/MRI	Mean transit time (MTT) Portal venous perfusion Hepatic arterial perfusion Arterial perfusion fraction	Inflammation may increase blood flow Passive venous congestion may reduce portal flow	Applicable to any contrast enhanced studies Can be incorporate into any existing CT or MRI scanners	Need prospective evaluation Fasting is essential Prone for motion artifacts Acquisition protocols and reconstruction methods are not standardized Additional computation and complex modeling required Software not available widely