Added value of magnetic resonance spectroscopy for diagnosing childhood cerebellar tumours.

1 H-magnetic resonance spectroscopy (MRS) provides noninvasive metabolite profiles with the potential to aid the diagnosis of brain tumours. Prospective studies of diagnostic accuracy and comparisons with conventional MRI are lacking. The aim of the current study was to evaluate, prospectively, the diagnostic accuracy of a previously established classifier for diagnosing the three major childhood cerebellar tumours, and to determine added value compared with standard reporting of conventional imaging. Single-voxel MRS (1.5 T, PRESS, TE 30 ms, TR 1500 ms, spectral resolution 1 Hz/point) was acquired prospectively on 39 consecutive cerebellar tumours with histopathological diagnoses of pilocytic astrocytoma, ependymoma or medulloblastoma. Spectra were analysed with LCModel and predefined quality control criteria were applied, leaving 33 cases in the analysis. The MRS diagnostic classifier was applied to this dataset. A retrospective analysis was subsequently undertaken by three radiologists, blind to histopathological diagnosis, to determine the change in diagnostic certainty when sequentially viewing conventional imaging, MRS and a decision support tool, based on the classifier. The overall classifier accuracy, evaluated prospectively, was 91%. Incorrectly classified cases, two anaplastic ependymomas, and a rare histological variant of medulloblastoma, were not well represented in the original training set. On retrospective review of conventional MRI, MRS and the classifier result, all radiologists showed a significant increase (Wilcoxon signed rank test, p < 0.001) in their certainty of the correct diagnosis, between viewing the conventional imaging and MRS with the decision support system. It was concluded that MRS can aid the noninvasive diagnosis of posterior fossa tumours in children, and that a decision support classifier helps in MRS interpretation.

Diffusion-weighted MRI and intravoxel incoherent motion model for diagnosis of pediatric solid abdominal tumors.

BACKGROUND: Pediatric retroperitoneal tumors in the renal bed are often large and heterogeneous, and their diagnosis based on conventional imaging alone is not possible. More advanced imaging methods, such as diffusion-weighted (DW) MRI and the use of intravoxel incoherent motion (IVIM), have the potential to provide additional biomarkers that could facilitate their noninvasive diagnosis. PURPOSE: To assess the use of an IVIM model for diagnosis of childhood malignant abdominal tumors and discrimination of benign from malignant lesions. STUDY TYPE: Retrospective. POPULATION: Forty-two pediatric patients with abdominal lesions (n = 32 malignant, n = 10 benign), verified by histopathology. FIELD STRENGTH/SEQUENCE: 1.5T MRI system and a DW-MRI sequence with six b-values (0, 50, 100, 150, 600, 1000 s/mm2 ). ASSESSMENT: Parameter maps of apparent diffusion coefficient (ADC), and IVIM maps of slow diffusion coefficient (D), fast diffusion coefficient (D*), and perfusion fraction (f) were computed using a segmented fitting model. Histograms were constructed for whole-tumor regions of each parameter. STATISTICAL TESTS: Comparison of histogram parameters of and their diagnostic performance was determined using Kruskal-Wallis, Mann-Whitney U, and receiver-operating characteristic (ROC) analysis. RESULTS: IVIM parameters D* and f were significantly higher in neuroblastoma compared to Wilms' tumors (P < 0.05). The ROC analysis showed that the best diagnostic performance was achieved with D* 90th percentile (area under the curve [AUC] = 0.935; P = 0.002; cutoff value = 32,376 × 10-6 mm2 /s) and f mean values (AUC = 1.00; P < 0.001; cutoff value = 14.7) in discriminating between neuroblastoma (n = 11) and Wilms' tumors (n = 8). Discrimination between tumor types was not possible with IVIM D or ADC parameters. Malignant tumors revealed significantly lower ADC, D, and higher D* values than in benign lesions (all P < 0.05). DATA CONCLUSION: IVIM perfusion parameters could distinguish between malignant childhood tumor types, providing potential imaging biomarkers for their diagnosis. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1475-1486.

Prospective multicentre evaluation and refinement of an analysis tool for magnetic resonance spectroscopy of childhood cerebellar tumours.

BACKGROUND: A tool for diagnosing childhood cerebellar tumours using magnetic resonance (MR) spectroscopy peak height measurement has been developed based on retrospective analysis of single-centre data. OBJECTIVE: To determine the diagnostic accuracy of the peak height measurement tool in a multicentre prospective study, and optimise it by adding new prospective data to the original dataset. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) and single-voxel MR spectroscopy were performed on children with cerebellar tumours at three centres. Spectra were processed using standard scanner software and peak heights for N-acetyl aspartate, creatine, total choline and myo-inositol were measured. The original diagnostic tool was used to classify 26 new tumours as pilocytic astrocytoma, medulloblastoma or ependymoma. These spectra were subsequently combined with the original dataset to develop an optimised scheme from 53 tumours in total. RESULTS: Of the pilocytic astrocytomas, medulloblastomas and ependymomas, 65.4% were correctly assigned using the original tool. An optimized scheme was produced from the combined dataset correctly assigning 90.6%. Rare tumour types showed distinctive MR spectroscopy features. CONCLUSION: The original diagnostic tool gave modest accuracy when tested prospectively on multicentre data. Increasing the dataset provided a diagnostic tool based on MR spectroscopy peak height measurement with high levels of accuracy for multicentre data.

What is MR spectroscopy?

1H-Magnetic Resonance Spectroscopy (MRS) is a novel advanced imaging technique used as an adjunct to MRI to reveal complementary non-invasive information about the biochemical composition of imaged tissue. Clinical uses in paediatrics include aiding diagnosis of brain tumours, neonatal disorders such as hypoxic-ischaemic encephalopathy, inherited metabolic diseases, traumatic brain injury, demyelinating conditions and infectious brain lesions. MRS has potential to improve diagnosis and treatment monitoring of childhood brain tumours and other CNS diseases, facilitate biopsy and surgical planning, and provide prognostic biomarkers. MRS is employed as a research tool outside the brain in liver disease and disorders of muscle metabolism. The range of clinical uses is likely to increase with growing evidence for added value. Multicentre trials are needed to definitively establish the benefits of MRS in specific clinical scenarios and integrate this promising new technique into routine practice to improve patient care. This article gives a brief overview of MRS and its potential clinical applications, and addresses challenges surrounding translation into practice.

Multiclass imbalance learning: Improving classification of pediatric brain tumors from magnetic resonance spectroscopy.

PURPOSE: Classification of pediatric brain tumors from 1 H-magnetic resonance spectroscopy (MRS) can aid diagnosis and management of brain tumors. However, varied incidence of the different tumor types leads to imbalanced class sizes and introduces difficulties in classifying rare tumor groups. This study assessed different imbalanced multiclass learning techniques and compared the use of complete spectra and quantified metabolite profiles for classification of three main childhood brain tumor types. METHODS: Single-voxel, Short echo time MRS data were collected from 90 patients with pilocytic astrocytoma (n = 42), medulloblastoma (n = 38), or ependymoma (n = 10). Both spectra and metabolite profiles were used to develop the learning algorithms. The borderline synthetic minority oversampling technique and AdaboostM1 were used to correct for the skewed distribution. Classifiers were trained using five different pattern recognition algorithms. RESULTS: Use of imbalanced learning techniques improved the balanced accuracy rate (BAR) of all classification methods (average BAR over all classification methods for spectra: oversampled data = 0.81, original = 0.63, P < 0.001; metabolite concentration: oversampled-data = 0.91, original = 0.75, P < 0.0001). Performance of all classifiers in discriminating ependymomas increased when oversampled data were used compared with original data for both complete spectra (F-measure P < 0.01) and metabolite profile (F-measure P < 0.001). CONCLUSION: Imbalanced learning techniques improve the classification accuracy of childhood brain tumors from MRS where group sizes differ and facilitate the inclusion of rarer tumor types into clinical decision support systems. Magn Reson Med 77:2114-2124, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Prediction of severe bacterial infection in children with an emergency department diagnosis of infection.

OBJECTIVE: To determine the relationship between near-patient-test (NPT) lactate, white blood cell count (WBC) and C-reactive protein (CRP) and severe bacterial infection (SBI) in children presenting to the emergency department (ED) with infection. METHODS: An observational cohort study was undertaken in a paediatric emergency department of a large urban teaching hospital. Data were collected from January 2007 until December 2007. Inclusion criteria were age <16 years, blood test including NPT lactate obtained in the ED and infection-related ED diagnosis. Patients were pre-assigned to risk groups according to their NPT lactate, WBC and CRP. RESULTS: 506 children were included in the study, of which 42 (8.3%) had SBI. NPT lactate, WBC and CRP were significantly higher in the SBI cohort. High-risk NPT lactate (≥4 mmol/l) had a sensitivity of 38.1% (95% CI 23.6% to 54.4%) and a specificity of 89.7% (95% CI 86.5% to 92.3%); high-risk WBC (<5 or ≥15×10(9)/l) had a sensitivity of 51.2% (95% CI 35.1% to 67.1%) and a specificity of 73.8% (95% CI 69.4% to 77.8%); and high-risk CRP (≥50 mg/l) had a sensitivity of 36.8% (95% CI 21.8% to 54.1%) and a specificity of 83.6% (95% CI 79.4% to 87.2%) for SBI. All three high-risk markers combined yielded a sensitivity of 5.3% (95% CI 1.5% to 17.3%) and a specificity of 99.2% (95% CI 97.6% to 99.7%) for SBI. CONCLUSION: The data from our study suggest that NPT lactate provides early diagnostic information about the risk of SBI in children presenting to the ED with a suspected infection. Combining NPT lactate with WBC and CRP resulted in a promising rule-in-tool for SBI in children in the ED which, with prospective validation, has the potential to aid early identification of SBI in children.

Survey of neonatal resuscitation equipment in emergency departments in the UK.

OBJECTIVE: All emergency departments (EDs) should be adequately equipped and prepared to deal with unexpected neonatal deliveries and resuscitation. A study was undertaken to determine what neonatal resuscitation equipment is available in EDs in the UK and to formulate recommendations for improvement. METHODS: A prospective telephone survey of all UK EDs was conducted between November 2008 and February 2009 to determine the type of neonatal resuscitation equipment available as recommended in the fourth edition of the APLS guidelines. RESULTS: 169 EDs were identified, 137 (81%) of which successfully completed the survey. The majority of EDs followed APLS recommendations for provision of neonatal resuscitation equipment. There was a particularly good availability of basic airway equipment (99%), but 11% did not have a source of warmth, 5% lacked advanced airway equipment and 31% had no equipment for obtaining umbilical access. A Resuscitaire was present in 47% of EDs surveyed. CONCLUSION: There is a good level of provision of neonatal resuscitation equipment in UK EDs, although certain areas need to be addressed. There is a particular need for improving the provision of warming and advanced airway equipment. The authors consider that it is not necessary to have a neonatal Resuscitaire in the ED provided other equipment is readily available. The findings of this survey prompt the recommendation that all EDs should review their neonatal resuscitation equipment in accordance with APLS guidance, and ensure that staff have immediate access to this equipment and are comfortable with its use.

Diagnostic accuracy and added value of qualitative radiological review of 1H-magnetic resonance spectroscopy in evaluation of childhood brain tumors.

BACKGROUND: 1H-magnetic resonance spectroscopy (MRS) facilitates noninvasive diagnosis of pediatric brain tumors by providing metabolite profiles. Prospective studies of diagnostic accuracy and comparisons with conventional MRI are lacking. We aimed to evaluate diagnostic accuracy of MRS for childhood brain tumors and determine added clinical value compared with conventional MRI. METHODS: Children presenting to a tertiary pediatric center with brain lesions from December 2015 through 2017 were included. MRI and single-voxel MRS were acquired on 52 tumors and sequentially interpreted by 3 radiologists, blinded to histopathology. Proportions of correct diagnoses and interrater agreement at each stage were compared. Cases were reviewed to determine added value of qualitative radiological review of MRS through increased certainty of correct diagnosis, reduced number of differentials, or diagnosis following spectroscopist evaluation. Final diagnosis was agreed by the tumor board at study end. RESULTS: Radiologists' principal MRI diagnosis was correct in 69%, increasing to 77% with MRS. MRI + MRS resulted in significantly more additional correct diagnoses than MRI alone (P = .035). There was a significant increase in interrater agreement when correct with MRS (P = .046). Added value following radiologist interpretation of MRS occurred in 73% of cases, increasing to 83% with additional spectroscopist review. First histopathological diagnosis was available a median of 9.5 days following imaging, with 25% of all patients managed without conclusive histopathology. CONCLUSIONS: MRS can improve the accuracy of noninvasive diagnosis of pediatric brain tumors and add value in the diagnostic pathway. Incorporation into practice has the potential to facilitate early diagnosis, guide treatment planning, and improve patient care.

Automated Modular Magnetic Resonance Imaging Clinical Decision Support System (MIROR): An Application in Pediatric Cancer Diagnosis.

BACKGROUND: Advances in magnetic resonance imaging and the introduction of clinical decision support systems has underlined the need for an analysis tool to extract and analyze relevant information from magnetic resonance imaging data to aid decision making, prevent errors, and enhance health care. OBJECTIVE: The aim of this study was to design and develop a modular medical image region of interest analysis tool and repository (MIROR) for automatic processing, classification, evaluation, and representation of advanced magnetic resonance imaging data. METHODS: The clinical decision support system was developed and evaluated for diffusion-weighted imaging of body tumors in children (cohort of 48 children, with 37 malignant and 11 benign tumors). Mevislab software and Python have been used for the development of MIROR. Regions of interests were drawn around benign and malignant body tumors on different diffusion parametric maps, and extracted information was used to discriminate the malignant tumors from benign tumors. RESULTS: Using MIROR, the various histogram parameters derived for each tumor case when compared with the information in the repository provided additional information for tumor characterization and facilitated the discrimination between benign and malignant tumors. Clinical decision support system cross-validation showed high sensitivity and specificity in discriminating between these tumor groups using histogram parameters. CONCLUSIONS: MIROR, as a diagnostic tool and repository, allowed the interpretation and analysis of magnetic resonance imaging images to be more accessible and comprehensive for clinicians. It aims to increase clinicians' skillset by introducing newer techniques and up-to-date findings to their repertoire and make information from previous cases available to aid decision making. The modular-based format of the tool allows integration of analyses that are not readily available clinically and streamlines the future developments.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Magnetic resonance imaging based functional imaging in paediatric oncology.

Imaging is central to management of solid tumours in children. Conventional magnetic resonance imaging (MRI) is the standard imaging modality for tumours of the central nervous system (CNS) and limbs and is increasingly used in the abdomen. It provides excellent structural detail, but imparts limited information about tumour type, aggressiveness, metastatic potential or early treatment response. MRI based functional imaging techniques, such as magnetic resonance spectroscopy, diffusion and perfusion weighted imaging, probe tissue properties to provide clinically important information about metabolites, structure and blood flow. This review describes the role of and evidence behind these functional imaging techniques in paediatric oncology and implications for integrating them into routine clinical practice.

Fractures and recurrent fractures in children; varying effects of environmental factors as well as bone size and mass.

BACKGROUND: Fractures are frequent in childhood and cause considerable morbidity. Previous reports have indicated a variety of potential contributors to fracture risk including low bone mineral content and density, milk avoidance, lack of exercise, asthma, obesity, and a high consumption of carbonated beverages. AIMS: We wished to test the hypothesis that children who sustain recurrent fractures have a lower bone mass and a higher prevalence of underlying risk factors for fracture than those who fracture once or not at all. METHODS: We studied 150 children aged 4-16 years: 50 who had suffered recurrent fractures, 50 who had fractured for the first time, and 50 fracture-free controls. Subjects underwent assessment of bone size and mass by total body (TB) and lumbar spine (L2-4) dual energy X-ray absorptiometry (DXA). Values were adjusted for body size, based on the control group measurements as unadjusted DXA values are substantially influenced by size in children. Anthropometry and grip dynamometry were carried out, and information about factors implicated in fracture aetiology such as milk intake, physical activity levels, asthma prevalence and carbonated beverage consumption were recorded using questionnaires. RESULTS: Children who had sustained one or more fractures had a significantly lower BMC and aBMD at all sites than controls after conversion to size adjusted z scores (L2-4 BMC P = 0.0002; L2-4 aBMD P < 0.0001; TB BMC P < 0.0001; TB aBMD P < 0.0001); estimates for TB excluded fracture sites. There was, however, no difference in adjusted bone mass between children with one and those with recurrent fractures. Children with recurrent fractures had a significantly lower milk intake, lower levels of physical activity, a higher BMI, and a higher consumption of carbonated beverages than controls. The prevalence of risk factors was not, however, significantly higher than controls in children with a single fracture. CONCLUSIONS: Children with fractures have a lower bone mass for body size than children without fractures. Modifiable risk factors such as diet and exercise increase the risk of recurrent fractures.