<p>Non-invasive imaging is central to the diagnosis and staging of metabolic dysfunction-associated steatotic liver disease (MASLD). Various non-invasive means are used to reliably diagnose steatosis, whereas liver biopsy remains the gold standard for MASLD staging, as it enables assessment of the severity of fibrosis and inflammation. Importantly, imaging modalities have the potential to serve as non-invasive alternatives to biopsy in the future. This review summarises established and emerging imaging techniques for the diagnosis and staging of MASLD, focusing on their measurement principles, diagnostic performance and practical limitations. Conventional ultrasound remains the most widely used first-line modality for steatosis screening owing to its low cost and broad availability, but it lacks sensitivity for mild steatosis and is strongly operator and body habitus dependent. Quantitative ultrasound extensions such as the controlled attenuation parameter improve steatosis assessment, while transient elastography additionally measures liver stiffness, which is a surrogate marker for fibrosis. Computed tomography permits density-based assessment of steatosis and focal lesions but is limited by radiation exposure and poor sensitivity for low hepatic lipid (HL) content. MRI-derived proton density fat fraction and proton magnetic resonance spectroscopy are considered non-invasive reference standards for quantifying HL content, with high sensitivity and specificity even at low fat fractions, albeit at a higher cost and with more restricted availability. For fibrosis staging based on liver stiffness, magnetic resonance elastography currently offers the highest non-invasive accuracy across fibrosis stages and reduces sampling error by probing large liver volumes, whereas transient elastography is more widely implemented in routine care owing to its broader availability. Additional MRI-based approaches, including diffusion-weighted imaging and T<sub>1</sub>-based mapping techniques, provide complementary information on tissue microstructure, reflecting inflammatory and fibrotic processes, although their specificity and standardisation are still under evaluation. Nuclear imaging with positron emission tomography and single-photon emission computed tomography enables functional and molecular characterisation. Novel tracers targeting fibroblast activation protein, macrophage subsets or activated hepatic stellate cells, together with targeted MRI contrast agents and nanoparticle-based probes, hold promise for more specific imaging of fibrogenesis and inflammation. Beyond structural changes, multinuclear magnetic resonance spectroscopy and specialised positron emission tomography tracers allow in vivo assessment of hepatic energy metabolism, mitochondrial function, glycogen dynamics and substrate fluxes, which is particularly relevant for mechanistic studies, increasing our understanding of MASLD pathology, but are currently confined to research settings. Future developments will likely emphasise multiparametric and multimodal strategies integrating quantitative imaging biomarkers with clinical and biochemical data to refine risk stratification, enable sensitive treatment monitoring and support precision medicine approaches in MASLD.</p> Graphical Abstract <p></p>

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Imaging of MASLD: clinical standards and novel methods

  • Marc Jonuscheit,
  • Vera B. Schrauwen-Hinderling

摘要

Non-invasive imaging is central to the diagnosis and staging of metabolic dysfunction-associated steatotic liver disease (MASLD). Various non-invasive means are used to reliably diagnose steatosis, whereas liver biopsy remains the gold standard for MASLD staging, as it enables assessment of the severity of fibrosis and inflammation. Importantly, imaging modalities have the potential to serve as non-invasive alternatives to biopsy in the future. This review summarises established and emerging imaging techniques for the diagnosis and staging of MASLD, focusing on their measurement principles, diagnostic performance and practical limitations. Conventional ultrasound remains the most widely used first-line modality for steatosis screening owing to its low cost and broad availability, but it lacks sensitivity for mild steatosis and is strongly operator and body habitus dependent. Quantitative ultrasound extensions such as the controlled attenuation parameter improve steatosis assessment, while transient elastography additionally measures liver stiffness, which is a surrogate marker for fibrosis. Computed tomography permits density-based assessment of steatosis and focal lesions but is limited by radiation exposure and poor sensitivity for low hepatic lipid (HL) content. MRI-derived proton density fat fraction and proton magnetic resonance spectroscopy are considered non-invasive reference standards for quantifying HL content, with high sensitivity and specificity even at low fat fractions, albeit at a higher cost and with more restricted availability. For fibrosis staging based on liver stiffness, magnetic resonance elastography currently offers the highest non-invasive accuracy across fibrosis stages and reduces sampling error by probing large liver volumes, whereas transient elastography is more widely implemented in routine care owing to its broader availability. Additional MRI-based approaches, including diffusion-weighted imaging and T1-based mapping techniques, provide complementary information on tissue microstructure, reflecting inflammatory and fibrotic processes, although their specificity and standardisation are still under evaluation. Nuclear imaging with positron emission tomography and single-photon emission computed tomography enables functional and molecular characterisation. Novel tracers targeting fibroblast activation protein, macrophage subsets or activated hepatic stellate cells, together with targeted MRI contrast agents and nanoparticle-based probes, hold promise for more specific imaging of fibrogenesis and inflammation. Beyond structural changes, multinuclear magnetic resonance spectroscopy and specialised positron emission tomography tracers allow in vivo assessment of hepatic energy metabolism, mitochondrial function, glycogen dynamics and substrate fluxes, which is particularly relevant for mechanistic studies, increasing our understanding of MASLD pathology, but are currently confined to research settings. Future developments will likely emphasise multiparametric and multimodal strategies integrating quantitative imaging biomarkers with clinical and biochemical data to refine risk stratification, enable sensitive treatment monitoring and support precision medicine approaches in MASLD.

Graphical Abstract