Time

Prog #

Sonali S. De Silva¹, Geoffery S. Payne¹, Valerie A. Thomas², Thomas E. Ind², Nandita M. deSouza¹

¹Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK; ²St Georges Hospital NHS Trust, Tooting Broadway, UK

The development of invasive cervical cancer is preceded by a well-defined pre-invasive stage, cervical intraepithelial neoplasia (CIN). Elevated levels of choline have previously been identified in a number of tumours including cervical cancer [1] but whether these metabolites are elevated in CIN tissue is still unclear. The study investigates the metabolic changes in the transition from normal-to-pre-invasive, and from pre-invasive to invasive cervical cancer using 1H and 31P HR-MAS MRS of intact tissues in which the tissue content was subsequently confirmed with histology. Targeted biopsies were obtained on colposcopy in cervical intraepithelial neoplasia, CIN, (low-grade n=5, high-grade n=40) and on visual inspection when invasive disease was clinically obvious (n=23). Cervical tissues were also obtained from women with normal smears undergoing hysterectomy for benign uterine disease (n=5). Mean concentrations of Aln, Cr, Cho, PC, Tau in 1H HR-MAS and PC, PE and Pi in 31P HR-MAS were calculated. HR-MAS spectral analysis shows significant differences between  invasive cervical cancer and high-grade CIN. Increased levels of choline-containing compounds are observed in cancer tissue. Our findings also suggest that normal tissue adjacent to tumour shows some metabolite depletion, while concentration of choline-containing metabolites is increased in CIN tissue adjacent to a malignancy.  Changes in choline metabolism may be a useful biomarker in identifying the transition of pre-invasive to invasive disease.

Brad R. Cohn¹, Bonnie N. Joe¹, Shoujun Zhao¹, John Kornak¹, Vickie Yi Zhang¹, Rahwa Iman¹, John Kurhanewicz¹, Jingwei Yu¹, Aaron B. Caughey¹, Mark G. Swanson¹

¹UCSF, San Francisco, California , USA

High-resolution MR spectroscopy was used to quantify 21 metabolites in second and third trimester human amniotic fluid samples (N=50). Significant differences were found for 15 of 21 metabolites.  Glucose and several amino acid concentrations decreased, while creatinine and betaine increased with gestational age.  Stepwise linear regression models suggested that gestational age could be accurately predicted using combinations of alanine, glucose, and creatinine concentrations. This study provides normative data for assessing fetal development, evidence of pulmonary and renal maturation, and may aid in the application of in vivo MRS as a future non-invasive test for evaluating fetal development.

Rahwa Iman¹, Mark Swanson¹, Paul J. Turek¹, David Aaronson¹, Helena Gurascier¹, Dan Vigneron¹, Sarah Nelson¹, John Kurhanewicz¹

¹University of California San Francisco, San Francisco, California , USA

1H high resolution magic angle spinning (HR-MAS) spectroscopy was used to determine the metabolic profiles of normal, maturation arrested, and azoospermatic human testicular biopsy tissues.  Fourteen 1H HR-MAS spectra were acquired and quantified using the electronic standard ERETIC and the algorithm QUEST.  Phosphocholine (PC) concentrations were significantly higher in normal versus azoospermatic testes and there was no overlap between the two groups.  However, PC concentrations in maturation arrested testes overlapped both normal and azoospermatic testes.  This study suggests that PC could serve as a specific in vivo marker for fertility in 1H MRSI studies of human testes.

William E. Hull¹, Waldemar Hosch², Günter W. Kauffmann², Thomas Junghanss²

¹German Cancer Research Center (DKFZ), Heidelberg, Germany; ²University Clinic Heidelberg, Heidelberg, Germany

Cystic echinococcosis (CE) or hydatid disease is caused by larval stages of the cestode parasite Echinococcus granulosus (canine tapeworm) and is a zoonosis of worldwide distribution. Clinical staging of cyst development by ultrasonography (US) requires accurate assessment of cyst viability, assuming a correlation between cyst morphology and parasite viability (light microscopy). Using high-field 1H-MRS of 50 cyst biopsies, 48 metabolite parameters were determined, and multivariate analysis provided excellent discrimination between viable and nonviable cysts, regardless of US class, as well as a rationale for discriminating between individual US classes.

Sveva Grande¹, Anna Maria Luciani¹, Antonella Rosi¹, Laura Guidoni¹, Vincenza Viti¹

¹Istituto Superiore di Sanita', Roma, Italy

MRS can be used to monitor intracellular pH in in vitro and in vivo samples. Amide signals were chosen to this purpose, because their intensity is related to pH value. The origin of these signals is not yet clear. In the present work, through the comparison of spectra from tumor cells and from GSH solution, we assign two main peaks of the 1H MR cell spectra to NH protons of gly and cys of GSH. Assignment is confirmed by treatment of cells with buthionine sulfoximine (BSO), that inhibits the activity of the enzyme γ-glutamyl cysteine synthetase.

Tedros Bezabeh¹, Celia Marginean², Garth Nicholas², Omkar B. Ijare¹

¹National Research Council Institute for Biodiagnostics, Winnipeg, Canada; ²The Ottawa Hospital, Ottawa, Canada

Application of ¹H MR spectroscopy for the detection of lung cancer has been investigated. Sputum samples from lung cancer patients and normal controls were analyzed by ¹H MRS. Glucose was found to be absent in sputum samples obtained from lung cancer patients. The absence of glucose could be due to an increased rate of glycolysis in the lung cancer cells in these patients. Cancer cells rely heavily on glycolysis for their metabolic demands since they cannot produce energy from pyruvate, due to a defective Krebs cycle. This observation may have a diagnostic potential for the rapid and non-invasive diagnosis of lung cancer.

Daniel Valverde-Saubí¹, ², Ana Paula Candiota, ¹², Maria Antonia Molins³, Miguel Feliz³, Oscar Godino⁴, Juan Martino⁴, Juan José Acebes⁴, Carles Arús¹, ²

¹Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain; ²Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Cerdanyola del Vallès, Spain; ³Universitat de Barcelona, Barcelona, Spain; ⁴Hospital Universitari de Bellvitge, L'Hospitalet del Llobregat, Spain

We investigated the recording temperature effects on the HRMAS spectral pattern and on supervised classifier development. HRMAS spectra were acquired at 0ºC and 37ºC and analysed using  pattern recognition techniques. Post-HRMAS histopathology was carried out. Major reversible temperature dependent changes were detected on the spectral pattern of the samples analysed. A better classification was achieved using the spectra acquired at 0ºC. Sample morphology was essentially not affected by 37ºC HRMAS analysis. The temperature dependent changes explain the better classification at 0ºC. Higher dispersion of data at 37ºC could be due to the existence of molecular subtypes of glioblastoma.