Metabolic viability assessment of cystic echinococcosis using high-field 1H MRS of cyst contents

Cystic echinococcosis is a worldwide disease caused by larval stages of the parasite Echinococcus granulosus (canine tapeworm). In clinical practice, staging of cyst development by ultrasonography (US) has allowed treatment options to be tailored to individual patient needs. However. the empirical correlation between cyst morphology and parasite viability is not always dependable and has, until now,. required confirmation by invasive assessment of cyst content by light microscopy (LM), for example. Alternatively. high-field H-1 MRS may be used to examine cyst fluid ex vivo and prepare detailed quantitative metabolite profiles. enabling a multivariate metabolomics approach to cyst staging. One-dimensional and two-dimensional H-1 and H-1/C-13 MRS at 600 MHz (14.1 T) was used to analyze 50 cyst aspirates of various US and LM classes. MR parameters and concentrations relative to internal valine were determined for 44 metabolites and four substance classes. The high concentrations of succinate, fumarate, malate, acetate, alanine, and lactate found in earlier studies of viable cysts were confirmed, and additional metabolites such as myo-inositol, sorbitol, 1.5-anhydro-D-glucitol, betaine, and 2-hydroxyisovalerate were identified. Data analysis and cyst classification were performed using univariate (succinate), bivariate (succinate VS fumarate), and multivariate partial least squares discriminant analysis (PSL-DA) methods (With LIP to 48 metabolite variables). Metabolic classification of 23 viable and 18 nonviable cysts oil the basis of succinate alone a,reed with LM results. However. for seven samples, I-M and MRS gave opposing results. Reclassification of these samples and two unclassified samples by PLS-DA prediction techniques led to a set of 50 samples that could be completely separated into viable and nonviable MRS classes with no overlap, using as few as nine variables: succinate. formate, malate, 2-hydroxyisovalerate, acetate, total protein content. 1.5-anhydro-D-glucitol alanine, and betaine. Thus. future noninvasive in vivo applications of MRS would appear promising. Copyright (C) 2008 John Wiley & Sons, Ltd.