Abstract
In pediatric brain tumours, dissemination of malignant cells within the central nervous system confers poor prognosis and determines treatment intensity, but is often undetectable by imaging or cytology. This study describes the use of fluorescence lifetime (FLT) imaging microscopy (FLIM), a novel diagnostic tool, for detection of metastatic spread. The study group included 15 children with medulloblastoma and 2 with atypical teratoid/rhabdoid tumour. Cells extracted from the tumour and the cerebrospinal fluid (CSF) 2 weeks postoperatively and repeatedly during chemo/radiotherapy were subjected to nuclear staining followed by FLT measurement and cytological study. Control CSF samples were collected from patients with infectious/inflammatory disease attending the same hospital. Median FLT was prolonged in tumour cells (4.27 ± 0.28 ns; P < 2.2*10−16) and CSF metastatic cells obtained before chemo/radiotherapy (6.28 ± 0.22 ns; P < 2.2*10−16); normal in inflammatory control cells (2.6 ± 0.04 ns) and cells from children without metastasis before chemo/radiotherapy (2.62 ± 0.23 ns; P = 0.858) and following treatment (2.62 ± 0.21 ns; P = 0.053); and short in CSF metastatic cells obtained after chemo/radiotherapy (2.40 ± 0.2 ns; P < 2.2*10−16). FLIM is a simple test that can potentially identify CSF spread of brain tumours. FLT changes in accordance with treatment, with significant prolonged median values in tumours and metastases. More accurate detection of metastatic cells may guide personalised treatment and improve the therapeutic outcome.
Highlights
Krieger Eye Research Laboratory, Felsenstein Medical Research Center, Beilinson Hospital, Petach Tikva 4941492, affiliated to Tel Aviv University, Tel Aviv, 6997801, Israel. 3Faculty of Engineering and Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, 5290002, Israel. 4Department of Pediatric Neurosurgery, Schneider Children’s Medical Center of Israel, Petach Tikva, 4920235, Israel. 5Department of Pediatric Oncology, Schneider Children’s Medical Center of Israel, Petach Tikva, 4920235, Israel. 6Department of Ophthalmology, Bnai Zion Medical Center, Haifa, 3339419, Israel. 7Laboratory of Microbiology, Rabin Medical Center – Beilinson Hospital, Petach Tikva, 4941492, Israel. 8Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6997801, Israel. 9Department of Oral Pathology and Oral Medicine, Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv, 6997801, Israel
Malignant brain tumours usually metastasize within the central nervous system (CNS) and very rarely to extraneural sites
Seventeen children were included in the study group: 15 with medulloblastoma and 2 with atypical teratoid/rhabdoid tumour (ATRT)
Summary
Despite recent advances in treatment, 30% to 40% of children experience tumour recurrence, and most of them die from disease especially if previously irradiated[6] Another highly malignant tumour of childhood is atypical teratoid/rhabdoid tumour (ATRT), usually diagnosed in the first 2 years of life[7]. Current means of detection of CNS disease, mainly preoperative imaging and postoperative cytologic study of the cerebrospinal fluid (CSF), are limited and reviewer-dependent. This is crucial, because diagnostic errors may lead to under-treatment, which may be life-threatening, or over-treatment, which places patients at unnecessary risk of severe adverse effects and future disability. It differs from the earlier steady-state fluorescence techniques used in the bio-sciences which are not useful for quantitative investigation of cellular function at the molecular level
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