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Rapid determination of medulloblastoma subgroup affiliation with mass spectrometry using a handheld picosecond infrared laser desorption probe.

ABSTRACT: Medulloblastoma (MB), the most prevalent malignant childhood brain tumour, consists of at least 4 distinct subgroups each of which possesses a unique survival rate and response to treatment. To rapidly determine MB subgroup affiliation in a manner that would be actionable during surgery, we subjected murine xenograft tumours of two MB subgroups (SHH and Group 3) to Mass Spectrometry (MS) profiling using a handheld Picosecond InfraRed Laser (PIRL) desorption probe and interface developed by our group. This platform provides real time MS profiles of tissue based on laser desorbed lipids and small molecules with only 5-10 seconds of sampling. PIRL-MS analysis of ex vivo MB tumours offered a 98% success rate in subgroup determination, observed over 194 PIRL-MS datasets collected from 19 independent tumours (?10 repetitions each) utilizing 6 different established MB cell lines. Robustness was verified by a 5%-leave-out-and-remodel test. PIRL ablated tissue material was collected on a filter paper and subjected to high resolution LC-MS to provide ion identity assignments for the m/z values that contribute most to the statistical discrimination between SHH and Group 3 MB. Based on this analysis, rapid classification of MB with PIRL-MS utilizes a variety of fatty acid chains, glycerophosphates, glycerophosphoglycerols and glycerophosphocholines rapidly extracted from the tumours. In this work, we provide evidence that 5-10 seconds of sampling from ex vivo MB tissue with PIRL-MS can allow robust tumour subgroup classification, and have identified several biomarker ions responsible for the statistical discrimination of MB Group 3 and the SHH subgroup. The existing PIRL-MS platform used herein offers capabilities for future in vivo use.

SUBMITTER: Woolman M

PROVIDER: S-EPMC5628578 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Rapid determination of medulloblastoma subgroup affiliation with mass spectrometry using a handheld picosecond infrared laser desorption probe.

Woolman Michael M Ferry Isabelle I Kuzan-Fischer Claudia M CM Wu Megan M Zou Jing J Kiyota Taira T Isik Semra S Dara Delaram D Aman Ahmed A Das Sunit S Taylor Michael D MD Rutka James T JT Ginsberg Howard J HJ Zarrine-Afsar Arash A

Chemical science 20170721 9

Medulloblastoma (MB), the most prevalent malignant childhood brain tumour, consists of at least 4 distinct subgroups each of which possesses a unique survival rate and response to treatment. To rapidly determine MB subgroup affiliation in a manner that would be actionable during surgery, we subjected murine xenograft tumours of two MB subgroups (SHH and Group 3) to Mass Spectrometry (MS) profiling using a handheld Picosecond InfraRed Laser (PIRL) desorption probe and interface developed by our g ...[more]

PMID: 28989676

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Project description:SignificanceMeasurements of auditory ossicles displacement are commonly carried out by means of laser-Doppler vibrometry (LDV), which is considered to be a gold standard. The limitation of the LDV method, especially for in vivo measurements, is the necessity to expose an object in a straight line to a laser beam operating from a distance. An alternative to this approach is the use of a handheld laser-fiber vibrometry probe (HLFVP) with a curved tip.AimWe evaluate the feasibility of an HLFVP with a curved tip for measuring sound-induced displacement of the auditory ossicles.ApproachA handheld vibrometer probe guiding the laser beam with a fiber-optic cable was used for displacement measurements of the incus body and the posterior crus of the stapes. Tonal stimuli at frequencies of 0.5, 1, 2, and 4 kHz were presented by means of an insert earphone positioned in the outer ear canal. The probe was fixed at the measurement site using a tripod or hand-held by one of the two surgeons.ResultsThe measurements were carried out on six fresh temporal bones. Multivariate analysis of variance showed statistically significant differences for stimulus frequency (F3,143 = 29.37, p < 0.001, and η2 = 0.35), bone (F5,143 = 4.61, p = 0.001, and η2 = 0.01), and measurement site (F1,143 = 4.74, p = 0.03, and η2 = 0.02) in the absence of statistically significant differences for the probe fixation method (F2,143 = 0.15, p = 0.862, and η2 = 0.001). Standard deviations of the means were 6.9, 2.6, 1.9, and 0.6 nm / Pa for frequency, bone, site, and fixation, respectively. Ear transfer functions were found to be consistent with literature data.ConclusionsThe feasibility of applying HLFVP to measure the displacement of auditory ossicles has been confirmed. HLFVP offers the possibility of carrying out measurements at various angles; however, this needs to be standardized taking into account anatomical limitations and surgical convenience.

Dataset Information

Rapid determination of medulloblastoma subgroup affiliation with mass spectrometry using a handheld picosecond infrared laser desorption probe.

Publications

Rapid determination of medulloblastoma subgroup affiliation with mass spectrometry using a handheld picosecond infrared laser desorption probe.

Similar Datasets

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