Projects / Programmes
Role of MRI in detection of minimal hepatic encephalopathy
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
hepatic encephalopathy, magnetic resonance, DWI, DKI, QSM, MRS, MEGA-PRESS
Researchers (9)
Organisations (2)
Abstract
SUMMARY
Background:
Most common cause of liver cirrhosis (LC) is alcohol overconsumption and its incidence increases. One of the complications of the cirrhosis is hepatic encephalopathy (HE), defined as brain dysfunction caused by liver insufficiency. Since HE is potentially reversible, the recognition of early stages is crucial. Minimal HE (mHE) is defined as HE without symptoms on clinical examination, but can be detected by psychometric testing. Early recognition of mHE is pivotal as early treatment improves the quality of life of patients.
Pathophysiological mechanisms of HE are complex. Ammonia, cytokines, manganese deposition and neurotransmitters are involved in malfunctioning of neuronal cells, but exact mechanisms are poorly understood.
2. Problem and objectives of the proposed research
This study will address the following problems:
Diagnosis of mHE
Diagnosis of mHE is challenging, time-consuming and subjective. MRI and MRS are non-invasive and objective methods that produce quantifiable results. This project will assess the role of MRI in mHE diagnosis with emphasis on multimodal imaging technique. The correlation of physcometric testing with MRI data will improve the sensitivity and specificity of mHE diagnosis.
Pathophysiology of HE
The exact mechanisms of neuron and astrocyte damage in HE are poorly understood. Advanced MRI and MRS techniques will provide new answers to these questions.
3. The originality of the expected results
Multimodal MRI approach as we propose in this application has not been yet performed. We will use advanced MRI techniques which are currently not available in clinical setting. QSM requires multicenter collaboration.
4. Methods
Patients with hyperammonemia and mHE and patients with HE will be studied. Diagnosis of HE will be based on results of validated neuropsychiatric test listed below. Age-matched and gender- matched volunteers will serve as the control group.
Patients with contraindications for MRI scanning will be excluded. The study protocol will include: 1) short description and the aim of the study and patient’s written-consent, 2) scoring according to WH and CP classifications, 3) liver function tests, ammonia levels, 4) Critical Flicker Frequency test, 5) neuropsychiatric tests and 6) MRI scanning.
Standard safety questionnaire will be used before the scanning. MRI scanning will involve: T1- and T2-weighted MRI, MRS (MEGA-PRESS and PRESS), high resolution diffusion weighted imaging (DWI), diffusion kurtosis imaging (DKI), quantitative susceptibility mapping (QSM). Liver QSM will be executed to assess iron load. The same tests will be performed on control subjects. The advanced MRI, with emphasis on complex analysis, will be done with collaboration of Neuroimaging Research Unit, Medical University Graz.
This protocol was approved by the Republic of Slovenia National Medical Ethics Committee.
6. Relevance and potential impact of the results
This project will explore mechanisms that are complex and still poorly understand in humans. Multimodal MR approach that will be used in protocol is novel approach to study HE. Moreover, as the diagnosis of mHE is time-consuming and often delayed or even unrecognized, MR could be used as method in a process of diagnostic process of mHE.
7. Organisational structure and feasibility of the project
Acquisition of MRI and MRS will be performed at ULMF, analysis of QSM results will be done in collaboration with MedUni Graz and optimization of protocols and analysis of structural data jointly with Academic Research Centre of SZD.
8. Comments
QSM data analysis can be performed in collaboration with Austrian partner.
Significance for science
Development of HE in patients with LC is not fully understood due to complex pathogenesis. Besides osmotic effects chronic ammonia exposure also causes a shift in the balance between inhibitory and excitatory neurotransmission towards a net increase in inhibitory neurotransmission. Most data came from studies on cell cultures and animal models and only a few studies have been performed using non-invasive magnetic resonance (MR) imaging and spectroscopy (MRS) on patients with HE. Therefore the exact mechanisms of impairment of neurons and glial cells in mHE/HE remains poorly understood.
The results of this project are relevant for providing the following answers:
Detection of minimal brain water shifts, paramagnetic deposits in mHE and HE involved in pathophysiological mechanisms of HE development. With advanced MR techniques such as DKI and QSM, in-vivo detections of small water shifts content, intracerebral edema and brain deposits are feasible. This will also offer the possibility to compare and evaluate the results from previous studies on animal models and cell cultures
Assessment of the role of GABA in in mHE and HE. Striatum has a crucial role in movement planning, decision-making, motivation and reward processes With MEGA-PRESS, millimolar concertation of GABA, the most important inhibitory neurotransmitter in the brain, can be reliably detected. This will provide evidence for early and late impairment of striatum in mHE/HE.
The potential use of various MR techniques in detecting mHE in clinical environment. MR is a non-invasive and safe method that could have an essential role in detecting mHE. We will assess the sensitivity and specificity of MR imaging in mHE diagnosis with emphasis on multimodal imaging technique.
Significance for the country
Development of HE in patients with LC is not fully understood due to complex pathogenesis. Besides osmotic effects chronic ammonia exposure also causes a shift in the balance between inhibitory and excitatory neurotransmission towards a net increase in inhibitory neurotransmission. Most data came from studies on cell cultures and animal models and only a few studies have been performed using non-invasive magnetic resonance (MR) imaging and spectroscopy (MRS) on patients with HE. Therefore the exact mechanisms of impairment of neurons and glial cells in mHE/HE remains poorly understood.
The results of this project are relevant for providing the following answers:
Detection of minimal brain water shifts, paramagnetic deposits in mHE and HE involved in pathophysiological mechanisms of HE development. With advanced MR techniques such as DKI and QSM, in-vivo detections of small water shifts content, intracerebral edema and brain deposits are feasible. This will also offer the possibility to compare and evaluate the results from previous studies on animal models and cell cultures
Assessment of the role of GABA in in mHE and HE. Striatum has a crucial role in movement planning, decision-making, motivation and reward processes With MEGA-PRESS, millimolar concertation of GABA, the most important inhibitory neurotransmitter in the brain, can be reliably detected. This will provide evidence for early and late impairment of striatum in mHE/HE.
The potential use of various MR techniques in detecting mHE in clinical environment. MR is a non-invasive and safe method that could have an essential role in detecting mHE. We will assess the sensitivity and specificity of MR imaging in mHE diagnosis with emphasis on multimodal imaging technique.
