Clinical Validation of High Throughput Raman Fiber Optic Probe to Determine Hepatic Fat Content

Currently there are three main methods reported to assess liver steatosis before deceased donor liver retrieval: Noninvasive imaging techniques, evaluation of a liver biopsy sample by an experienced pathologist and assessment by transplant surgeon.

Imaging techniques that are currently in use include ultrasonography (USG) , computerized tomography (CT) and magnetic resonance imaging (MRI). Although it has an acceptable level of sensitivity, USG does not provide reproducible quantitative information. It can be used in most centers but it is operator dependent. Likewise, the diagnostic performance of non-enhanced CT scan for the accurate quantification of steatosis is unreliable. MRI is highly sensitive and specific in diagnosing hepatic steatosis and it has been reported that fat quantification using a 3.0-T MRI can provide sufficient sensitivity to detect and quantify steatosis in live liver donor candidates. However, this complex technology limits its use in routine organ procurement.

The microscopic evaluation of a liver biopsy sample by an expert pathologist is the gold standard for steatosis assessment. The presence and type of steatosis can be determined by microscopic evaluation. The grade of steatosis can be determined according to the international standards.

Despite being gold standard, biopsies are recorded for only 23% of transplanted livers in United States. Since a pathologist is not always available at the time of procurement, many centers rely mainly on the assessment of steatosis and organ quality by the procurement surgeon (i.e. transplant surgeon). During this assessment the donor liver is evaluated according to parenchymal texture criteria such as degree of yellowness (normal, mild, moderate, severe) and degree of firmness (soft, normal; mild, moderate, severe). However, studies which investigated how accurately a transplant surgeon could predict hepatic steatosis concluded that these assessments could be significantly misleading even in experienced hands.

Since all these three methods have their limitations, there is a need for a convenient and simple technique to better assess hepatic fat content prior to transplantation. Raman spectroscopy is an inelastic light scattering technique that is sensitive to molecular vibrations, the symmetry and frequencies of which are unique to the type of atoms and their spatial arrangement. Sensitivity to these properties is the basis of its ability to provide a spectral fingerprint of molecules in the illuminated region. It has been used to detect amino acids, nucleotide bases, fatty acids, saccharides, primary metabolites and other constituents that form the protein, carbohydrates, fats and DNA/RNA of biological tissues. It is an attractive technology for bioanalysis because no sample preparation is needed.