Quantitative imaging in medicine and surgery · 2025
T1rho MRI as a quantitative biomarker of radiation-induced liver disease in normal and fibrotic rat models.
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Wang Yiqi, Wen Junjie, Zhong Weixiang, He Wenguang, Wang Jili, Lu Zhongjie, Zhang Yi, Yan Senxiang, Wang Yi Xiang J, Zhao Feng
Аннотация
BACKGROUND: Stereotactic body radiotherapy (SBRT) is used for inoperable hepatocellular carcinoma (HCC) patients, yet radiation-induced liver disease (RILD) poses risks, particularly in fibrotic livers. T1rho imaging, which allows high scan-rescan stability and high sensitivity to changes from baseline measure, has emerged as a promising noninvasive biomarker for liver injury but its utility in RILD remains underexplored. This study characterizes liver T1rho change in rat models of RILD with/without pre-existing fibrosis.
METHODS: Male Sprague-Dawley (SD) rats were divided into radiation therapy (RT) (n=41; 25 Gy right liver irradiation) and thioacetamide (TAA) + RT (n=46; 6-week TAA-induced fibrosis + 20 Gy RT) groups. Nine control rats, and each experimental rat at the endpoint had in vivo T1rho MRI and followed by histology. Pathological assessments [hematoxylin-eosin (HE), Masson's trichrome (MT), Picro-Sirius Red (PSR), transforming growth factor-beta (TGF-β), and alpha-smooth muscle actin (α-SMA)] were performed at 2, 4, 8, and 12 weeks post-RT to quantify fibrosis, collagen, inflammation, and ballooning degeneration.
RESULTS: The control rats had normal liver T1rho value of 37.2±0.93 ms. An RT of 25 Gy led to an elevated liver T1rho of 40.14±1.06 ms 2 weeks post-RT (P<0.001). With TAA pre-treatment, 20 Gy RT led to an elevated liver T1rho of 45.24±1.24 ms 2 weeks post-RT, which is statistically significantly higher than the liver T1rho 2 weeks post-RT with the dosage of 25 Gy (P<0.001), suggesting pre-existing liver injury by TAA sensitizing liver to RT injury. For both the RT and TAA + RT model, there was a treatment-duration dependent elongation of liver T1rho value. Liver T1rho values were strongly correlated with collagen-based histological markers (mostly, Pearson r>0.9). Tentatively Inflammation contributed to T1rho elongation beyond collagen deposition, while ballooning degeneration did not show a notable effect on liver T1rho.
CONCLUSIONS: This study demonstrates that T1rho MRI is a sensitive and noninvasive biomarker of RILD severity in rat models, reflecting both fibrosis and inflammation. These findings support its potential utility for early detection, individualized risk assessment, and mechanistic studies of RILD, particularly in clinical settings where histological validation is not feasible.
METHODS: Male Sprague-Dawley (SD) rats were divided into radiation therapy (RT) (n=41; 25 Gy right liver irradiation) and thioacetamide (TAA) + RT (n=46; 6-week TAA-induced fibrosis + 20 Gy RT) groups. Nine control rats, and each experimental rat at the endpoint had in vivo T1rho MRI and followed by histology. Pathological assessments [hematoxylin-eosin (HE), Masson's trichrome (MT), Picro-Sirius Red (PSR), transforming growth factor-beta (TGF-β), and alpha-smooth muscle actin (α-SMA)] were performed at 2, 4, 8, and 12 weeks post-RT to quantify fibrosis, collagen, inflammation, and ballooning degeneration.
RESULTS: The control rats had normal liver T1rho value of 37.2±0.93 ms. An RT of 25 Gy led to an elevated liver T1rho of 40.14±1.06 ms 2 weeks post-RT (P<0.001). With TAA pre-treatment, 20 Gy RT led to an elevated liver T1rho of 45.24±1.24 ms 2 weeks post-RT, which is statistically significantly higher than the liver T1rho 2 weeks post-RT with the dosage of 25 Gy (P<0.001), suggesting pre-existing liver injury by TAA sensitizing liver to RT injury. For both the RT and TAA + RT model, there was a treatment-duration dependent elongation of liver T1rho value. Liver T1rho values were strongly correlated with collagen-based histological markers (mostly, Pearson r>0.9). Tentatively Inflammation contributed to T1rho elongation beyond collagen deposition, while ballooning degeneration did not show a notable effect on liver T1rho.
CONCLUSIONS: This study demonstrates that T1rho MRI is a sensitive and noninvasive biomarker of RILD severity in rat models, reflecting both fibrosis and inflammation. These findings support its potential utility for early detection, individualized risk assessment, and mechanistic studies of RILD, particularly in clinical settings where histological validation is not feasible.