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Changes in dynamic and static brain fluctuation distinguish minimal hepatic encephalopathy and cirrhosis patients and
Jiang Ji1,2, Yi-Yang Liu3, Guo-Wei Wu4
1Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, China.
Purpose:
Minimal hepatic encephalopathy (MHE) is characterized by mild neuropsychological and neurophysiological alterations that are not detectable by routine clinical examination. Abnormal brain activity (in terms of the amplitude of low-frequency fluctuation (ALFF) has been observed in MHE patients. However, little is known concerning temporal dynamics of intrinsic brain activity. The present study aimed to investigate the abnormal dynamics of brain activity (dynamic ALFF; dALFF) and static measures [static ALFF; (sALFF)] in MHE patients and to strive for a reliable imaging neuromarkers for distinguishing MHE patients from cirrhosis patients. In addition, the present study also investigated whether intrinsic brain activity predicted the severity of liver damage.
Methods:
Thirty-four cirrhosis patients with MHE, 28 cirrhosis patients without MHE, and 33 age-, sex-, and education-matched healthy controls (HCs) underwent resting-state magnetic resonance imaging (rs-fMRI). dALFF was estimated by combining the ALFF method with the sliding-window method, in which temporal variability was quantized over the whole-scan timepoints and then compared among the three groups. Additionally, dALFF, sALFF and both two features were utilized as classification features in a support vector machine (SVM) to distinguish MHE patients from cirrhosis patients. The severity of liver damage was reflected by the Child-Pugh score. dALFF, sALFF and both two features were used to predict Child-Pugh scores in MHE patients using a general linear model.
Results:
Compared with HCs, MHE patients showed significantly increased dALFF in the left inferior occipital gyrus, right middle occipital gyrus, and right insula; increased dALFF was also observed in the right posterior lobe of the cerebellum (CPL) and right thalamus. Compared with HCs, noMHE patients exhibited decreased dALFF in the right precuneus. In contrast, compared with noMHE patients, MHE patients showed increased dALFF in the right precuneus, right superior frontal gyrus, and right superior occipital gyrus. Furthermore, the increased dALFF values in the left precuneus were positively associated with poor digit-symbol test (DST) scores (r = 0.356, p = 0.038); however, dALFF in the right inferior temporal gyrus (ITG) was negatively associated with the number connection test-A (NCT-A) scores (r = -0.784, p = 0.000). A significant positive correlation was found between dALFF in the left inferior occipital gyrus (IOG) and high blood ammonia levels (r = 0.424, p = 0.012). Notably, dALFF values yielded a higher classification accuracy than sALFF values in distinguishing MHE patients from cirrhosis patients. Importantly, the dALFF values predicted the Child-Pugh score (r = 0.140, p = 0.030), whereas sALFF values did not in the current dataset. Combining two features had high accuracy in classification in distinguishing MHE patients from cirrhotic patients and yielded prediction in the severity of liver damage.
Conclusion:
These findings suggest that combining dALFF and sALFF features is a useful neuromarkers for distinguishing MHE patients from cirrhosis patients and highlights the important role of dALFF feature in predicting the severity of liver damage in MHE.
Insights
Dynamic amplitude of low-frequency fluctuation (dALFF) and static ALFF (sALFF) show promise as imaging biomarkers. Combining dALFF and sALFF effectively distinguishes minimal hepatic encephalopathy (MHE) patients from cirrhosis patients and predicts liver damage severity.
Area of Science:
- Neuroimaging
- Hepatology
- Neurology
Background:
- Minimal hepatic encephalopathy (MHE) presents subtle neuropsychological deficits not evident in routine exams.
- Previous studies noted abnormal intrinsic brain activity (ALFF) in MHE, but temporal dynamics remain under-explored.
- Identifying reliable imaging markers for MHE is crucial for early diagnosis and management.
Purpose of the Study:
- To investigate dynamic ALFF (dALFF) and static ALFF (sALFF) in MHE patients.
- To establish reliable imaging neuromarkers for differentiating MHE from cirrhosis.
- To explore the predictive value of intrinsic brain activity for liver damage severity.
Main Methods:
- Resting-state fMRI was performed on 34 MHE patients, 28 non-MHE cirrhosis patients, and 33 healthy controls.
- Dynamic ALFF (dALFF) was calculated using a sliding-window approach; static ALFF (sALFF) was also measured.
- Support vector machine (SVM) was employed for classification, and general linear models assessed prediction of Child-Pugh scores.
Main Results:
- MHE patients exhibited significantly altered dALFF in various brain regions (e.g., occipital gyrus, insula, cerebellum, thalamus) compared to controls and non-MHE patients.
- dALFF showed significant correlations with neuropsychological test scores (DST, NCT-A) and blood ammonia levels.
- dALFF demonstrated higher classification accuracy than sALFF in distinguishing MHE from cirrhosis and predicted liver damage severity (Child-Pugh score).
Conclusions:
- Combined dALFF and sALFF serve as valuable neuromarkers for differentiating MHE from cirrhosis.
- dALFF plays a significant role in predicting the severity of liver damage in MHE patients.
- These findings underscore the potential of dynamic brain activity measures in understanding and diagnosing MHE.
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