Multispectral Optoacoustic Tomography in Patients With Cystic Fibrosis

Study Overview
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Brief Summary
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Cystic fibrosis (CF) is the most common hereditary disease in Central Europe. The disease is caused by a mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR). In the liver, fibrotic remodeling can lead to liver cirrhosis in the long term. Early detection of CF hepatopathy is essential to therapeutically slow down the progression of fibrotic remodeling mechanisms. Newborns suffering from CF have a significantly increased risk for the occurrence of meconium ileus and also with advancing age there are symptoms ranging from chronic constipation to Distal Intestinal Obstruction Syndrome (DIOS), due to a reduction of intestinal motility. In this study, the degree of liver fibrosis will now be investigated in adult patients with cystic fibrosis using Multispectral Optoacoustic Imaging (MSOT). In addition, gastrointestinal passage will be studied non-invasively to investigate another affection of the gastrointestinal system.

Detailed Description
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Cystic fibrosis (CF) is the most common hereditary disease in Central Europe, with an incidence of approximately 3,300 to 4,800 new cases. The disease follows an autosomal recessive pattern of inheritance, the cause being a mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR). In the liver, fibrotic remodeling can lead to liver cirrhosis in the long term. Early detection of CF hepatopathy is essential to therapeutically slow down the progression of fibrotic remodeling mechanisms. Over the past decade, measurements of liver stiffness using Acoustic Radiation Force Impulse Imaging (ARFI) have proven to be a valid tool for measuring fibrotic tissue remodeling in CF in adults and children. Furthermore, in the gastrointestinal tract, serious consequences result from the absence of the CFTR channel. Newborns suffering from CF have a significantly increased risk for the occurrence of meconium ileus and also with advancing age there are symptoms ranging from chronic constipation to DIOS (Distal Intestinal Obstruction Syndrome), due to a reduction of intestinal motility. By means of new imaging methods, such as multispectral optoacoustic tomography, it is possible to examine not only the body's own substances but also substances foreign to the body. With Multispectral Optoacoustic Imaging (MSOT), similar to conventional sonography, a transducer is placed on the skin and instead of sound, energy is applied to the tissue by means of light flashes. This leads to a constant alternation of minimal expansions and contractions (thermoelastic expansion) of individual tissue components or molecules. Previous studies have shown that quantitative determination of hemoglobin can provide information on blood flow and inflammatory activity in the intestines of adult patients with Crohn's disease. Also, fibrotic changes in the liver can probably be detected with this method, similar to that in muscle tissue. Furthermore, we have recently shown that orally ingested Indocyanine green (ICG) can be detected in the small intestine and thus conclusions can be drawn about gastrointestinal passage, without the use of ionizing radiation. In this study, the degree of liver fibrosis will now be investigated in adult patients with cystic fibrosis using MSOT. In addition, gastrointestinal passage will be studied non-invasively to investigate another affection of the gastrointestinal system.

Official Title
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Multispectral Optoacoustic Tomography for the Assessment of Liver Fibrosis and Gastrointestinal Transit in Patients With Cystic Fibrosis

Conditions
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Cystic Fibrosis, Liver Fibrosis, Gastrointestinal Transport Disorder, Dios

Intervention / Treatment
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* Diagnostic Test: Acoustic Radiation Forced Impulse Imaging
* Diagnostic Test: Multispectral Optoacoustic Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient cohort Cystic Fibrosis without CF-related liver disease: Molecular genetic confirmed diagnosis of cystic fibrosis. Age over 18 years Written informed consent Patient cohort Cystic Fibrosis with CF-related liver disease: Molecular genetic confirmed diagnosis of cystic fibrosis Presence of CF-related liver disease based on Colombo criteria: Hepato- and/or splenomegaly Persistent elevation of transaminases in the serum Sonographic evidence of liver involvement Age over 18 years Written informed consent Volunteer Subjects: Age over 18 years Written informed consent Exclusion Criteria: General: Pregnancy Breastfeeding mothers Tattoo in the area of the examination Subcutaneous fat tissue over 3 cm Patient cohort Cystic fibrosis without CF-related liver disease: Taking systemic glucocorticoids or immunosuppressants as part of a permanent medication regimen. Presence of CF-related liver disease based on Colombo criteria: Hepato- and/or splenomegaly. Persistent elevation of transaminases in the serum Sonographic evidence of liver involvement. Acute exacerbation of infection Patient cohort Cystic fibrosis with CF-related liver disease: Taking systemic glucocorticoids or immunosuppressants as part of a permanent medication regimen. Decompensation of CF-related liver disease Acute exacerbation of infection volunteer subjects: Presence of liver disease Use of systemic glucocorticoids or immunosuppressants in the context of permanent medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CF with liver affection<br>CF patients with proven CF hepatopathy | Diagnostic Test: Acoustic Radiation Forced Impulse Imaging<br>* Measurement of Liver stiffness<br>* Other names: ARFI;Diagnostic Test: Multispectral Optoacoustic Tomography<br>* Measurement of optoacoustic spectra in liver and gastrointestinal tract<br>* Other names: MSOT;|
| CF without liver affection<br>CF patients without proven CF hepatopathy | Diagnostic Test: Acoustic Radiation Forced Impulse Imaging<br>* Measurement of Liver stiffness<br>* Other names: ARFI;Diagnostic Test: Multispectral Optoacoustic Tomography<br>* Measurement of optoacoustic spectra in liver and gastrointestinal tract<br>* Other names: MSOT;|
| Healthy volunteers<br>Healthy volunteers without liver affection | Diagnostic Test: Acoustic Radiation Forced Impulse Imaging<br>* Measurement of Liver stiffness<br>* Other names: ARFI;Diagnostic Test: Multispectral Optoacoustic Tomography<br>* Measurement of optoacoustic spectra in liver and gastrointestinal tract<br>* Other names: MSOT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative collagen signal (Liver) | in arbitrary units | Day 1 | 
| Quantitative Indocyanine Green (ICG) signal (Intestinal) | Day 1 | 0, 60, 90, 120, 180, 240, 300min post ICG intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative oxy/deoxygenated hemoglobin signal (Liver) | in arbitrary units | Day 1 | 
| Quantitative oxy/deoxygenated hemoglobin signal (Intestinal) | in arbitrary units | 0, 60, 90, 120, 180, 240, 300min post ICG intake | 
| Quantitative single wave lengths (Intestinal) | in arbitrary units | 0, 60, 90, 120, 180, 240, 300min post ICG intake | 
| Quantitative single wave lengths (Liver) | in arbitrary units | Day 1 | 
| Optoacoustic spectrum (Intestinal) | in arbitrary units, normalized | 0, 60, 90, 120, 180, 240, 300min post ICG intake | 
| Optoacoustic spectrum (Liver) | in arbitrary units, normalized | Day 1 | 
| Shear wave velocity (Liver) | in m/s | Day 1 | 
| Attenuation coefficient (Liver) | in dB/cm/MHz | Day 1 | 
| Chenodeoxycholic acid (CDCA) and respective glycine and taurine conjugates | µmol/l and /g stool | Day 1 | 
| Cholic acid (CA) and respective glycine and taurine conjugates | µmol/l and /g stool | Day 1 | 
| Deoxycholic acid (DCA) and respective glycine and taurine conjugates | µmol/l and /g stool | Day 1 | 
| Lithocholic acid (LCA) and respective glycine and taurine conjugates | µmol/l and /g stool | Day 1 | 
| Ursodeoxycholic acid (UDCA) and respective glycine and taurine conjugates | µmol/l and /g stool | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, MSOT, Liver Fibrosis, Gastrointestinal Transit