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Evaluation of the added value of 1H-magnetic resonance spectroscopy for the diagnosis of pediatric brain lesions in clinical practice.

ABSTRACT: Magnetic resonance spectroscopy (MRS) aids noninvasive diagnosis of pediatric brain tumors, but use in clinical practice is not well documented. We aimed to review clinical use of MRS, establish added value in noninvasive diagnosis, and investigate potential impact on patient care.Sixty-nine children with lesions imaged using MRS and reviewed by the tumor board from 2014 to 2016 met inclusion criteria. Contemporaneous MRI diagnosis, spectroscopy analysis, histopathology, and clinical information were reviewed. Final diagnosis was agreed on by the tumor board at study end.Five cases were excluded for lack of documented MRI diagnosis. The principal MRI diagnosis by pediatric radiologists was correct in 59%, increasing to 73% with addition of MRS. Of the 73%, 19.1% (95% CI, 9.1%-33.3%) were incorrectly diagnosed with MRI alone. MRS led to a significant improvement in correct diagnosis over all tumor types (P = .012). Of diagnoses correctly made with MRI, confidence increased by 37% when adding MRS, with no patients incorrectly re-diagnosed. Indolent lesions were diagnosed noninvasively in 85% of cases, with MRS a major contributor to 91% of these diagnoses. Of all patients, 39% were managed without histopathological diagnosis. MRS contributed to diagnosis in 68% of this group, modifying it in 12%. MRS influenced management in 33% of cases, mainly through avoiding and guiding biopsy and aiding tumor characterization.MRS can improve accuracy and confidence in noninvasive diagnosis of pediatric brain lesions in clinical practice. There is potential to improve outcomes through avoiding biopsy of indolent lesions, aiding tumor characterization, and facilitating earlier family discussions and treatment planning.

SUBMITTER: Manias K

PROVIDER: S-EPMC5909808 | biostudies-other | 2018 Mar

REPOSITORIES: biostudies-other

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Evaluation of the added value of <sup>1</sup>H-magnetic resonance spectroscopy for the diagnosis of pediatric brain lesions in clinical practice.

Manias Karen K Gill Simrandip K SK Zarinabad Niloufar N Davies Paul P English Martin M Ford Daniel D MacPherson Lesley L Nicklaus-Wollenteit Ina I Oates Adam A Solanki Guirish G Adamski Jenny J Wilson Martin M Peet Andrew C AC

Neuro-oncology practice 20170513 1

<h4>Background</h4>Magnetic resonance spectroscopy (MRS) aids noninvasive diagnosis of pediatric brain tumors, but use in clinical practice is not well documented. We aimed to review clinical use of MRS, establish added value in noninvasive diagnosis, and investigate potential impact on patient care.<h4>Methods</h4>Sixty-nine children with lesions imaged using MRS and reviewed by the tumor board from 2014 to 2016 met inclusion criteria. Contemporaneous MRI diagnosis, spectroscopy analysis, histo ...[more]

PMID: 29692921

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Project description:Can 1H Magnetic Resonance Spectroscopy (MRS) be used to obtain information about the molecules and metabolites in live human spermatozoa?Percoll-based density gradient centrifugation (DGC) followed by a further two washing steps, yielded enough sperm with minimal contamination (<0.01%) from seminal fluid to permit effective MRS which detected significant differences (P < 0.05) in the choline/glycerophosphocholine (GPC), lipid and lactate regions of the 1H MRS spectrum between sperm in the pellet and those from the 40%/80% interface.Current methods to examine sperm are either limited in their value (e.g. semen analysis) or are destructive (e.g. immunohistochemistry, sperm DNA testing). A few studies have previously used MRS to examine sperm, but these have either looked at seminal plasma from men with different ejaculate qualities or at the molecules present in pooled samples of lyophilized sperm.Sperm suspended in phosphate buffered saline (PBS) at 37°C were examined by 1H MRS scanning using a 1H excitation-sculpting solvent suppression sequence after recovery from fresh ejaculates by one of three different methods: (i) simple centrifugation; (ii) DGC with one wash; or (iii) DGC with two washes. In the case of DGC, sperm were collected both from the pellet ('80%' sperm) and the 40/80 interface ('40%' sperm). Spectrum processing was carried out using custom Matlab scripts to determine; the degree of seminal plasma/Percoll contamination, the minimum sperm concentration for 1H MRS detection and differences between the 1H MRS spectra of '40%' and '80%' sperm.DGC with two washes minimized the 1H MRS peak intensity for both seminal plasma and Percoll/PBS solution contamination while retaining sperm specific peaks. For the MRS scanner used in this study, the minimum sperm concentration required to produce a choline/GPC 1H MRS peak greater than 3:1 signal to noise ratio (SNR) was estimated at ~3 × 106/ml. The choline/GPC and lactate/lipid regions of the 1H spectrum were significantly different by two-way ANOVA analysis (P < 0.0001; n = 20). ROC curve analysis of these region showed significant ability to distinguish between the two sperm populations: choline/GPC ROC AUC = 0.65-0.67, lactate/lipid ROC AUC = 0.86-0.87.Only 3-4 semen samples were used to assess the efficacy of each sperm washing protocol that were examined. The estimated minimum sperm concentration required for MRS is specific to the hardware used in our study and may be different in other spectrometers. Spectrum binning is a low resolution analysis method that sums MRS peaks within a chemical shift range. This can obscure the identity of which metabolite(s) are responsible for differences between sperm populations. Further work is required to determine the relative contribution of somatic cells to the MRS spectrum from the '40%' and '80%' sperm.1H MRS can provide information about the molecules present in live human sperm and may therefore permit the study of the underlying functional biology or metabolomics of live sperm. Given the relatively low concentration of sperm required to obtain a suitable MRS signal (~3 × 106/ml), this could be carried out on sperm from men with oligo-, astheno- or teratozoospermia. This may lead to the development of new diagnostic tests or ultimately novel treatments for male factor infertility.This work was supported by the Medical Research Council Grant MR/M010473/1. The authors declare no conflicts of interest.

Project description:Background and purposeOur goal is to determine the added value of intracranial vessel wall magnetic resonance imaging (IVWI) in differentiating nonocclusive vasculopathies compared with luminal imaging alone.MethodsWe retrospectively reviewed images from patients with both luminal and IVWI to identify cases with clinically defined intracranial vasculopathies: atherosclerosis (intracranial atherosclerotic disease), reversible cerebral vasoconstriction syndrome, and inflammatory vasculopathy. Two neuroradiologists blinded to clinical data reviewed the luminal imaging of defined luminal stenoses/irregularities and evaluated the pattern of involvement to make a presumed diagnosis with diagnostic confidence. Six weeks later, the 2 raters rereviewed the luminal imaging in addition to IVWI for the pattern of wall involvement, presence and pattern of postcontrast enhancement, and presumed diagnosis and confidence. Analysis was performed on per-lesion and per-patient bases.ResultsThirty intracranial atherosclerotic disease, 12 inflammatory vasculopathies, and 12 reversible cerebral vasoconstriction syndrome patients with 201 lesions (90 intracranial atherosclerotic disease, 64 reversible cerebral vasoconstriction syndrome, and 47 inflammatory vasculopathy lesions) were included. For both per-lesion and per-patient analyses, there was significant diagnostic accuracy improvement with luminal imaging+IVWI when compared with luminal imaging alone (per-lesion: 88.8% versus 36.1%; P<0.001 and per-patient: 96.3% versus 43.5%; P<0.001, respectively). There was substantial interrater diagnostic agreement for luminal imaging+IVWI (κ=0.72) and only slight agreement for luminal imaging (κ=0.04). Although there was a significant correlation for both luminal and IVWI pattern of wall involvement with diagnosis, there was a stronger correlation for IVWI finding of lesion eccentricity and intracranial atherosclerotic disease diagnosis than for luminal imaging (κ=0.69 versus 0.18; P<0.001).ConclusionsIVWI can significantly improve the differentiation of nonocclusive intracranial vasculopathies when combined with traditional luminal imaging modalities.

Project description:Medulloblastoma (MB) is the most common malignant brain tumor occurring in childhood and rarely found in adult. Based on transcriptome profile MB are currently classified into four major molecular groups reflecting a considerable biological heterogeneity: WNT-activated, SHH-activated, group 3 and group 4. Recently, DNA methylation profiling allowed the identification of additional subgroups within the four major molecular groups associated with different clinic-pathological and molecular features. Isocitrate Dehydrogenase-1 (IDH1) mutations have been described in several tumours, including gliomas, while in MB are exceptionally reported and not routinely investigated. By mean of magnetic resonance spectroscopy (MRS) we unequivocally assessed the presence the oncometabolite D-2-Hydroxyglutarate (2HG), a marker of IDH1 and IDH2 mutation, in a case of adult MB. Immunophenotypical work-up and methylation profiling assigned the diagnosis of MB, subclass SHH-A, and molecular testing revealed the presence of the non-canonical somatic IDH1(p.R132C) mutation and an additional GNAS mutation, also exceptionally described in MB. To our knowledge this is the first reported case of MB harboring both mutations together. Of note, tumour exhibited a heterogeneous phenotype with a tumour component displaying glial differentiation, with robust GFAP expression, and a component with conventional MB features and selective presence of GNAS mutation, suggesting coexistence of two different major tumour clones. These findings draw attention to the need of a deeper genetic characterization of MB in order to get insights into their biology and improve stratification and clinical management of the patients. Moreover, reported data underling the importance of performing MRS for the identification of IDH mutations in non-glial tumours. The use of throughput molecular profiling analysis and advanced medical imaging technology will certainly increase the frequency with which rare tumour entities will be identified. Whether they have any particular therapeutic implications or prognostic relevance requires further investigations.

Dataset Information

Evaluation of the added value of 1H-magnetic resonance spectroscopy for the diagnosis of pediatric brain lesions in clinical practice.

Publications

Evaluation of the added value of <sup>1</sup>H-magnetic resonance spectroscopy for the diagnosis of pediatric brain lesions in clinical practice.

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