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.

Machine learning-based radiomic, clinical and semantic feature analysis for predicting overall survival and MGMT promoter methylation status in patients with glioblastoma.

INTRODUCTION: Survival varies in patients with glioblastoma due to intratumoral heterogeneity and radiomics/imaging biomarkers have potential to demonstrate heterogeneity. The objective was to combine radiomic, semantic and clinical features to improve prediction of overall survival (OS) and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status from pre-operative MRI in patients with glioblastoma. METHODS: A retrospective study of 181 MRI studies (mean age 58 ± 13 years, mean OS 497 ± 354 days) performed in patients with histopathology-proven glioblastoma. Tumour mass, contrast-enhancement and necrosis were segmented from volumetric contrast-enhanced T1-weighted imaging (CE-T1WI). 333 radiomic features were extracted and 16 Visually Accessible Rembrandt Images (VASARI) features were evaluated by two experienced neuroradiologists. Top radiomic, VASARI and clinical features were used to build machine learning models to predict MGMT status, and all features including MGMT status were used to build Cox proportional hazards regression (Cox) and random survival forest (RSF) models for OS prediction. RESULTS: The optimal cut-off value for MGMT promoter methylation index was 12.75%; 42 radiomic features exhibited significant differences between high and low-methylation groups. However, model performance accuracy combining radiomic, VASARI and clinical features for MGMT status prediction varied between 45 and 67%. For OS predication, the RSF model based on clinical, VASARI and CE radiomic features achieved the best performance with an average iAUC of 96.2 ± 1.7 and C-index of 90.0 ± 0.3. CONCLUSIONS: VASARI features in combination with clinical and radiomic features from the enhancing tumour show promise for predicting OS with a high accuracy in patients with glioblastoma from pre-operative volumetric CE-T1WI.

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.

Magnetic resonance spectroscopy metabolite profiles predict survival in paediatric brain tumours.

BACKGROUND: Brain tumours cause the highest mortality and morbidity rate of all childhood tumour groups and new methods are required to improve clinical management. (1)H magnetic resonance spectroscopy (MRS) allows non-invasive concentration measurements of small molecules present in tumour tissue, providing clinically useful imaging biomarkers. The primary aim of this study was to investigate whether MRS detectable molecules can predict the survival of paediatric brain tumour patients. PATIENTS AND METHODS: Short echo time (30ms) single voxel (1)H MRS was performed on children attending Birmingham Children's Hospital with a suspected brain tumour and 115 patients were included in the survival analysis. Patients were followed-up for a median period of 35 months and Cox-Regression was used to establish the prognostic value of individual MRS detectable molecules. A multivariate model of survival was also investigated to improve prognostic power. RESULTS: Lipids and scyllo-inositol predicted poor survival whilst glutamine and N-acetyl aspartate predicted improved survival (p<0.05). A multivariate model of survival based on three MRS biomarkers predicted survival with a similar accuracy to histologic grading (p<5e-5). A negative correlation between lipids and glutamine was found, suggesting a functional link between these molecules. CONCLUSIONS: MRS detectable biomolecules have been identified that predict survival of paediatric brain tumour patients across a range of tumour types. The evaluation of these biomarkers in large prospective studies of specific tumour types should be undertaken. The correlation between lipids and glutamine provides new insight into paediatric brain tumour metabolism that may present novel targets for therapy.

Accurate classification of childhood brain tumours by in vivo ¹H MRS - a multi-centre study.

AIMS: To evaluate the accuracy of single-voxel Magnetic Resonance Spectroscopy ((1)H MRS) as a non-invasive diagnostic aid for paediatric brain tumours in a multi-national study. Our hypotheses are (1) that automated classification based on (1)H MRS provides an accurate non-invasive diagnosis in multi-centre datasets and (2) using a protocol which increases the metabolite information improves the diagnostic accuracy. METHODS: Seventy-eight patients under 16 years old with histologically proven brain tumours from 10 international centres were investigated. Discrimination of 29 medulloblastomas, 11 ependymomas and 38 pilocytic astrocytomas (PILOAs) was evaluated. Single-voxel MRS was undertaken prior to diagnosis (1.5 T Point-Resolved Spectroscopy (PRESS), Proton Brain Exam (PROBE) or Stimulated Echo Acquisition Mode (STEAM), echo time (TE) 20-32 ms and 135-136 ms). MRS data were processed using two strategies, determination of metabolite concentrations using TARQUIN software and automatic feature extraction with Peak Integration (PI). Linear Discriminant Analysis (LDA) was applied to this data to produce diagnostic classifiers. An evaluation of the diagnostic accuracy was performed based on resampling to measure the Balanced Accuracy Rate (BAR). RESULTS: The accuracy of the diagnostic classifiers for discriminating the three tumour types was found to be high (BAR 0.98) when a combination of TE was used. The combination of both TEs significantly improved the classification performance (p<0.01, Tukey's test) compared with the use of one TE alone. Other tumour types were classified accurately as glial or primitive neuroectodermal (BAR 1.00). CONCLUSION: (1)H MRS has excellent accuracy for the non-invasive diagnosis of common childhood brain tumours particularly if the metabolite information is maximised and should become part of routine clinical assessment for these children.

Appraisal of the current staging system for residual medulloblastoma by volumetric analysis.

AIM: This study aims to investigate the accuracy of the current staging system of childhood medulloblastoma by using volumetric image analysis on immediate post-operative MRI scans. MATERIAL AND METHODS: Tumour volume and maximum cross area of residual medulloblastoma were measured on immediate post-operative MR scans of 37 children operated between 1999 and 2005. RESULTS: Mean preoperative volume was 32 cm(3) (range 4.5-71.9 cm(3)). Mean post-operative volume was 3.3 cm(3) (range 0-23.3 cm(3)). At mean follow-up of 50.08 months (range 6-129), 15 (40%) patients had died. Cut-off limit for residual post-operative tumour volume employed was maximum cross section of 1.5 cm(2), which corresponds to volume of 1.376 cm(3); 14 patients (38%) had no residual tumour, 7 patients (19%) had less than 1.5 cm(2) and 16 patients (43%) had more than 1.5 cm(2) residual tumour in its maximum cross section area. In three patients (8.2%) there was mismatch between the measured maximum cross section area and volume. In particular, in two patients, the cross section areas were more than 1.5 cm(2) but the residual tumour volumes were less than 1.376 cm(3) (the cross section area overestimated the residual volume) and in one case, the cross section area was less than 1.5 cm(2) but the residual tumour volume was more than 1.376 cm(3) (the cross section area underestimated the residual volume; difference statistically significant, Fisher's exact test, p < 0.01). CONCLUSIONS: It appears that volumetric measurement of residual medulloblastoma on immediate post-operative MRI scans may further improve the accuracy of staging process.

Short echo time single voxel 1H magnetic resonance spectroscopy in the diagnosis and characterisation of pineal tumours in children.

BACKGROUND: Magnetic resonance spectroscopy (MRS) has been successful in characterising a range of brain tumours and is a useful aid to non-invasive diagnosis. The pineal region poses considerable surgical challenges and a major surgical resection is not required in the management of all tumours. Improved non-invasive assessment of pineal region tumours would be of considerable benefit. METHODS: Single voxel MRS (TE 30 ms, TR 1500, 1.5 T) was performed on 15 pineal tumours: 5 germinomas, 1 non-germinomatous secreting germ cell tumour (GCT), 2 teratomas, 5 pineoblastomas, 1 pineal parenchymal tumour (PPT) of intermediate differentiation and 1 pineocytoma. Two germinomas outside the pineal gland were also studied. Metabolite, lipid and macromolecule concentrations were determined with LCModel™. RESULTS: Germ cell tumours had significantly higher lipid and macromolecule concentrations than other tumours (t-test; P < 0.05). The teratomas had significantly lower total choline and creatine levels than germinomas (z test; P < 0.05). Taurine was convincingly detected in germinomas as well as PPTs. CONCLUSIONS: Magnetic resonance spectroscopy is useful for characterising pineal region tumours, aiding the non-invasive diagnosis and giving additional biological insight.

A comparison between simulated and experimental basis sets for assessing short-TE in vivo ¹H MRS data at 1.5 T.

A number of algorithms designed to determine metabolite concentrations from in vivo (1)H MRS require a collection of single metabolite spectra, known as a basis set, which can be obtained experimentally or by simulation. It has been assumed that basis sets can be used interchangeably, but no systematic study has investigated the effects of small variations in basis functions on the metabolite values obtained. The aim of this study was to compare the results of simulated with experimental basis sets when used to fit short-TE (1)H MRS data of variable quality at 1.5 T. Two hundred and twelve paediatric brain tumour spectra were included in the analysis, and each was analysed twice with LCModel™ using a simulated and experimental basis set. To determine the influence of data quality on quantification, each spectrum was assessed and 152 were classified as being of 'good' quality. Bland-Altman statistics were used to measure the agreement between the two basis sets for all available spectra and only 'good'-quality spectra. Monte-Carlo simulations were performed to investigate the influence of minor shifts in metabolite frequencies on metabolite concentration estimates. All metabolites showed good agreement between the two basis sets, and the average metabolite limits of agreement were approximately ±3.84 mM for all available data and ±0.99 mM for good-quality data. Errors obtained from the Monte-Carlo analysis were found to be more accurate than the Cramer-Rao lower bounds (CRLB) for 12 of 15 metabolites when metabolite frequency shifting was considered. For the majority of purposes, a level of agreement of ±0.99 mM between simulated and experimental basis sets is sufficiently small for them to be used interchangeably. Multiple analyses using slightly modified basis sets may be useful in estimating fitting errors, which are not predicted by CRLBs.

Magnetic resonance spectroscopy in the assessment of pilocytic astrocytomas.

BACKGROUND: Pilocytic astrocytomas (PA) are common childhood brain tumours whose management and prognosis vary widely depending on location. (1)H magnetic resonance spectroscopy (MRS) measures biochemistry in vivo and shows promise for characterising brain tumours and aiding management. METHODS: Single voxel MRS (1.5 Tesla, TE 30 ms, TR 1500 ms) was performed on 27 children with PAs. Cases were designated 'progressors' if tumour progression led to their clinical management plan being altered. RESULTS: Prior to treatment, supratentorial tumours had significantly higher myo-inositol (p<0.01, t-test) and glutamate plus glutamine (p=0.02, t-test) than cerebellar tumours. Optic pathway or thalamic tumours that progressed had a significantly (p=0.04, t-test) lower myo-inositol at initial MRS than those with stable disease. Myo-inositol levels decreased significantly in progressors between the initial and subsequent MRS (p=0.03, paired t-test). Changes in myo-inositol occurred before clinical and radiological progression. CONCLUSIONS: MRS identifies differences with anatomical location in PAs and yields potential non-invasive biomarkers of prognosis.

Predictive value of preoperative ventricular volume on the need for permanent hydrocephalus treatment immediately after resection of posterior fossa medulloblastomas in children.

OBJECT: In this study, the authors investigated whether preoperative ventricular volume can be used to predict the need for permanent treatment of hydrocephalus in children with posterior fossa medulloblastomas. METHODS: Ventricular volumes were measured on magnetic resonance imaging studies obtained preoperatively and immediately postoperatively in 20 children who had undergone resection for medulloblastomas between 1999 and 2007. Comparison of mean values was performed using the one-way analysis of variance test. The association between ventricular and tumor volume was also investigated. RESULTS: All patients had obstructive hydrocephalus preoperatively, and 4 patients required postoperative shunt placement. The mean preoperative ventricular volume was 252 ml for those who required shunt placement, and 106 ml for those who did not (p = 0.000). The postoperative ventricular volume was 157 and 78 ml, respectively (p = 0.039), larger than normal in both groups. The mean postoperative and preoperative ratios were 0.69 and 0.70, respectively (p = 0.932). There was no correlation of ventricular volumes with age at operation (older or younger than 3 years), presence of metastasis, or amount of residual tumor. There was a statistical correlation between the preoperative ventricular volume and the tumor volume, related to the need for permanent shunt placement. CONCLUSIONS: Preoperative ventricular volume has predictive value for the later need for shunt placement, but in clinical practice this may be difficult to appreciate because all patients have significant hydrocephalus at presentation. The rate of ventricular size reduction in response to tumor excision does not have predictive value because ventricular volume is related to tumor volume. It appears that the removal of cerebellar medulloblastoma converts hydrocephalus from obstructive to communicating, which requires surgical treatment if it exceeds a certain level of cerebrospinal fluid volume.

The use of short-echo-time 1H MRS for childhood cerebellar tumours prior to histopathological diagnosis.

BACKGROUND: Proton magnetic resonance spectroscopy (MRS) measures concentrations of metabolites in vivo and provides a powerful method for identifying tumours. MRS has not entered routine clinical use partly due to the difficulty of analysing the spectra. OBJECTIVE: To create a straightforward method for interpreting short-echo-time MRS of childhood cerebellar tumours. MATERIALS AND METHODS: Single-voxel MRS (1.5-T Siemens Symphony NUM4, TR/TE 1,500/30 ms) was performed at presentation in 30 children with cerebellar tumours. The MRS results were analysed for comparison with histological diagnosis. Peak heights for N-acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mIns) were determined and receiver operator characteristic curves used to select ratios that best discriminated between the tumour types. The method was implemented by a group of clinicians and scientists, blinded to the results. RESULTS: A total of 27 MRS studies met the quality control criteria. NAA/Cr >4.0 distinguished all but one of the astrocytomas from the other tumours. A combination of Cr/Cho <0.75 and mIns/NAA <2.1 separated all the medulloblastomas from the ependymomas. CONCLUSION: Peak height ratios from short-echo-time MRS can accurately predict the histopathology of childhood cerebellar tumours.

Magnetic resonance spectroscopy suggests key differences in the metastatic behaviour of medulloblastoma.

BACKGROUND: Metastatic medulloblastoma has a poorer prognosis than localised disease in part due to inherent properties of the tumour. 1H magnetic resonance spectroscopy (MRS) provides a powerful method for investigating tumour metabolism in vivo. METHODS: Magnetic resonance imaging and short echo time (Te 30 ms) single voxel MRS were performed on the primary tumour of 16 children with medulloblastoma prior to surgical resection. Tumour volumes were calculated using a segmentation technique and the MRS was analysed using LCModel. RESULTS: Patients with metastatic disease had primary tumours which were smaller (p=0.01), had higher levels of total choline (p=0.03) and lower levels of mobile lipids (p=0.04). CONCLUSION: Metastatic medulloblastomas have metabolite profiles indicative of increased cell growth and decreased cell death compared with localised tumours reflecting intrinsic differences in underlying biology. Localised tumours with an MRS metabolite profile similar to those with metastatic disease may be at increased risk of metastatic relapse.

Posterior fossa volume in children with Chiari malformation Type I.

OBJECT: The authors sought to establish whether the volume of the posterior fossa in children suffering from Chiari malformation Type I (CM-I) is smaller than normal, as has been suggested previously. They also investigated the role of syringomyelia in posterior fossa development. METHODS: Both posterior fossa volume (PFV) and intracranial volume (ICV) were measured using segmentation techniques on preoperative magnetic resonance images obtained in 42 children who underwent surgery for CM-I (mean age 127 months, range 36-204 months); 25 (59%) of the patients had syringomyelia. The PFV/ICV ratio was calculated to eliminate differential supratentorial growth. Patients who had deformities potentially interfering with skull growth or who had undergone a shunt insertion procedure prior to craniovertebral decompression were excluded. The results were compared with measurements of 51 healthy children using one-way analysis of variance. In patients with CM-I only, the mean PFV and PFV/ICV ratios were not statistically different than those for healthy children. In patients with both CM-I and syringomyelia (CM-S), the mean PFV and PFV/ICV ratios were statistically smaller than those for healthy children. The ICV was 1383 cm3 in the healthy group, 1459 cm3 in the CM-I only group, and 1400 cm3 in the CM-S group (p = 0.363); the PFV was 186 cm3 in the healthy group, 196 cm3 in the CM-I only group, and 171 cm3 in the CM-S group (p = 0.036); the PFV/ICV ratio was 0.135 in the healthy group, 0.134 in the CM-I only group, and 0.122 in the CM-S group (p = 0.004). These differences were more prominent in the first 10 years of life. CONCLUSIONS: Children with isolated CM-I do not have a PFV smaller than normal, whereas children with both CM-I and syringomyelia have a PFV significantly smaller than normal. This result indicates that the two subgroups may represent different phenotypic expression or even a different pathogenesis.

Changes in ventricular and intracranial volume in hydrocephalic children following succesful endoscopic third ventriculostomy / Changes in ventricular and intracranial volume in hydrocephalic children following succesful endoscopic third ventriculostomy

Objective: comunicar la aparicion y crecimiento progresivo de un dermoide intramedular. Descripcion: paciente de 16 meses de edad con un cuadro de compresion medular y meningitis secundaria a un quiste dermoide intramedular. Estudios previos realizados al paciente no mostraron la presencia de una lesion expansiva intramedular. Intervencion: la cirugia permitio resecar en su totalidad un quiste dermoide abscedado intramedular. Conclusion: los pacientes con estigmas cutaneos deben ser controlados periodicamente por la posible presencia, aparicion tardia o progresion de lesiones intrarraquideas