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Trehalose as quantitative biomarker for in vivo diagnosis and treatment follow-up in cryptococcomas.

  • Vanherp, Liesbeth1
  • Poelmans, Jennifer1
  • Weerasekera, Akila2
  • Hillen, Amy1
  • Croitor-Sava, Anca R3
  • Sorrell, Tania C4
  • Lagrou, Katrien5
  • Vande Velde, Greetje1
  • Himmelreich, Uwe6
  • 1 Biomedical MRI, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. , (Belgium)
  • 2 Biomedical MRI, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium; A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School (MGH/HMS), Boston, Massachusetts, USA. , (Belgium)
  • 3 Biomedical MRI, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium; STADIUS, Department of Electrical Engineering (ESAT), KU Leuven, Leuven, Belgium. , (Belgium)
  • 4 Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, and Westmead Institute for Medical Research, Centre for Infectious Diseases and Microbiology, Sydney, Australia. , (Australia)
  • 5 Laboratory of Clinical Bacteriology and Mycology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium; National Reference Centre for Mycosis, Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium. , (Belgium)
  • 6 Biomedical MRI, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. Electronic address: [email protected] , (Belgium)
Published Article
Translational research : the journal of laboratory and clinical medicine
Publication Date
Apr 01, 2021
DOI: 10.1016/j.trsl.2020.11.001
PMID: 33166695


Brain lesions caused by Cryptococcus neoformans or C. gattii (cryptococcomas) are typically difficult to diagnose correctly and treat effectively, but rapid differential diagnosis and treatment initiation are crucial for good outcomes. In previous studies, cultured cryptococcal isolates and ex vivo lesion material contained high concentrations of the virulence factor and fungal metabolite trehalose. Here, we studied the in vivo metabolic profile of cryptococcomas in the brain using magnetic resonance spectroscopy (MRS) and assessed the relationship between trehalose concentration, fungal burden, and treatment response in order to validate its suitability as marker for early and noninvasive diagnosis and its potential to monitor treatment in vivo. We investigated the metabolites present in early and late stage cryptococcomas using in vivo 1H MRS in a murine model and evaluated changes in trehalose concentrations induced by disease progression and antifungal treatment. Animal data were compared to 1H and 13C MR spectra of Cryptococcus cultures and in vivo data from 2 patients with cryptococcomas in the brain. In vivo MRS allowed the noninvasive detection of high concentrations of trehalose in cryptococcomas and showed a comparable metabolic profile of cryptococcomas in the murine model and human cases. Trehalose concentrations correlated strongly with the fungal burden. Treatment studies in cultures and animal models showed that trehalose concentrations decrease following exposure to effective antifungal therapy. Although further cases need to be studied for clinical validation, this translational study indicates that the noninvasive MRS-based detection of trehalose is a promising marker for diagnosis and therapeutic follow-up of cryptococcomas. Copyright © 2020 Elsevier Inc. All rights reserved.

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