After entering the Computer Tomography (CT) and, subsequently, Magnetic Resonance Imaging (MRI), as a routine examination,  the diagnosis of intracranial tumors has became much faster and more accurately, bringing direct information about their location and morphology.

Beyond the CT and MRI routine sequences, new techniques have been perfected in the last years (spectroscopy, diffusion, perfusion, tractography and functional MRI) with a major impact in the differential diagnosis and management of brain tumors.

In this paper we present the theoretical and neuro-imaging aspects of the most common primitive brain tumors in children and adolescents

Paper presented at the XIV Congress of the Society of Neurology and Psychiatry of Child and Adolescent from Romania (SNPCAR) on October 11, 2013, Alba Iulia. Scientific Coordinator: Axinia Corcheş, MD, Chief of Neurology and Psychiatry Clinic for Child and Adolescent, Timisoara.

Introduction

After computer tomography (CT) and, subsequently, magnetic resonance imaging (MRI), became routine examination, the diagnosis of intracranial tumours has become much faster and more accurate. These examinations bring direct information about the location and morphology of the tumours compared to classical radiological methods that used to characterize the lesions only indirectly, through the effect of compression which the tumours exerted on surrounding brain structures (vessels, ventricles).

Computer tomography (CT) is one of the most accurate methods of neuro – diagnosis to reveal any  anatomical alterations. It is based on the quantitative determination of absorption of Roetgen radiation into small volumes of tissues. The most commonly used slice thickness is 5 mm in the axial plane. Native CT highlights acute haemorrhages, calcification and intratumoural cystic and necrotic degenerations, mass effect on adjacent brain structures, secondary hydrocephalus by obstruction of the ventricular system. CT with contrast reveals tissue density in pathological conditions and contours of brain damage; it increases the ability to locate and accurately describe the nature and extent of the tumour mass. The advantages of this method derive from its short time of examination, which allows the diagnosis in the acute stage, from the possibility to view bony structures and from the lower cost compared to other methods for neuro – imaging. As with any diagnostic method, there are also disadvantages: contrast resolution is insufficient for white matter pathology, contrast is insufficient for the posterior fossa, the formations of medial line and the spinal cord and, of course, irradiation is another disadvantage. (8, 33)

Magnetic Resonance Imaging (MRI) is the method of choice in the detection, localization and characterization of brain tumours. It is based on the property of human body to release electromagnetic waves under the action of a radio frequency impulse at the time of its placement under the influence of an external magnetic field. The use of contrast substance highlights the integrity of the hematoencephalic barrier; the separation of solid elements from cystic formations; the differentiation of oedema zone and of necrosis areas from the tumour tissue itself; the differentiation of postoperative tumour residue from the granulation tissue; the differentiation between postoperative scar lesions from tumour relapse; highlights the invasion of the leptomeninges and of the spinal metastases. The increased time of examination, the need for anaesthesia in children, increased cost and contraindication in patients with metallic implants and metallic foreign bodies, are disadvantages of this method of diagnosis. ( 5, 8, 33 )

The central nervous system is the second site, as frequency, of paediatric malignant neoplasms after hematologic diseases. They can be located supra or infratentorial. The supratentorial ones are more common in infants and children under 3 years, and the infratentorial ones in children between 4 and 11 years old. Approximately, half of brain tumours are located in the posterior fossa. (7, 22, 24)

I. POSTERIOR FOSSA TUMOURS

From the point of view of the anatomic location, these tumours can be divided into the following categories: tumours of the cerebellar hemispheres, of the midline (vermis, fourth ventricle), of the brainstem and extraparenchymatous. More than 80 % of posterior fossa tumours are located in the cerebellum and fourth ventricle, and of these, the most common are medulloblastoma, astrocytoma and ependymoma. (2, 7, 15, 22)

1. Medulloblastomas are malignant primitive neuroectodermal tumours that represent about 25 % of all paediatric brain tumours. They are the most common posterior fossa tumours in children and occur most frequently in the first 10 years of life. The location is predominant in the cerebral vermis with extension to fourth ventricle. Medulloblastoma is a tumour that metastasizes the most frequently at the level of the meninges, about 40 % of them showing meningeal and intracerebral metastases at diagnosis. (7, 10, 31)

On the CT, they appear as iso- or slightly hyperdense spontaneous formations of homogeneous charge. Calcifications appear in 10-20% of cases (Figure 1) . On MRI they have a more variable aspect. Typically, on  the sequence T1 they are in hyposignal and on the T2 sequence they have a heterogeneous appearance due to calcification, haemorrhage, necrosis, cysts and blood flow artefacts (Figure 2). The charge with contrast of these formations is marked. ( 25 )

Figure 1. Native axial CT image of brain: solid tumoural formation situated at the level of fourth ventricle (hyper dense compared to the cerebral parenchyma (Rossi A., 2009)

Figure 2. Brain MRI images in axial section: solid tumour formation in hyposignal T1, T2 iso-signal with heterogeneous contrast outlet (T1+C) located in the fourth ventricle (Rossi A., 2009)

2. Cerebellar Astrocytomas are in second place as the frequency of all posterior fossa tumours. 75 % of them are juvenile pilocytic astrocytomas, are benign and the remaining are fibrillar and diffuse astrocytomas. The pilocytic ones occur more frequently in the first decade of life, and the fibrillar after 10 years and in adolescence. Because they are benign tumours that grow slowly, they are big at diagnosis and are accompanied by hydrocephalus. Intra-tumoural calcifications are rare . 50 % are cystic with a solid mural nodule (the tumour) that is loaded with contrast. Of the pilocytic astrocytomas, 40% are solid tumours with cystic or necrotic central areas. (7, 9 , 10, 22)

On the CT, the cystic component has more increased densities than the cerebrospinal fluid (CSF )
due to higher proteinaceous content, while the solid component appears hyperdense to normal brain parenchyma (Figure 3). On MRI, the T1 and T2 sequences, there is a higher signal than the one of the CSF’s for the same reason. The mural nodule is loaded with contrast. After administration of contrast, solid tumours present a heterogeneous load. ( 25 )

Figure 3. Native axial CT image of brain: solid-cystic tumour formation located in the left cerebellar hemisphere (Rossi A., 2009)

Figure 4. Brain MRI images in axial section (T1, T2) and coronal section (T1 + C) Solid-cystic tumor formations located in the left cerebellar hemisphere. The solid part of tumor formation is in isosignal T2, T1 and shows homogenous contrast of the outlet while the cystic formation is in heavy T2 hypersignal and T1 hyposignal without this contrast outlet (Rossi A., 2009)

3. Ependymomas represent 10% of childhood brain tumours and are the third as frequent as fourth ventricle tumours. Most commonly they are encountered at the age of 5 years. About 70% are infratentorial. They develop from the epithelial cells of the fourth ventricle floor, extending to the lateral recesses, and, through the foramen of Luschca, they enter into the pontocerebellar angle. They may also extend below the foramen of Magendie to posterior cisterna magna. Meningeal metastases are usually more frequent intraspinally. (7, 19, 20, 28)

On the CT, they appear as iso or hyper dense intraventricular formations with multifocal calcifications and contrast moderate intakes. On MRI, they appear in heterogeneous hyposignal T1 and iso /
hyposignal T2. There may be areas of necrosis or cystic (T2 hyper signal intensity) and calcification (hyposignal T2). Following administration of a contrast agent they have a heterogeneous charge. (25)

Figure 5.Native axial CT image of brain. Tumour formation developed in the fourth ventricle of the brain, iso dense with cerebral parenchyma with inside micro-calcifications (Rossi A., 2009)

Figure 6. MRI brain image in axial plane (T1, T2) and sagittal plane (T1 + C). Tumour formation in iso signal T1, T2 with heterogeneous contrast outlet located in the fourth ventricle, comprising the basilar artery (arrow) and having a lateral plastic development through the ventricular foramens into the cervical spinal canal (Rossi A., 2009)

4. Brain stem gliomas are most commonly located in the pons. They may be associated with type I neurofibromatosis and represent 30% of posterior fossa tumours. Clinical symptoms are associated with hydrocephalus and cranial nerve paresis. Peak of incidence is less than 10 years. Brain stem gliomas are most commonly pilocytic and fibrillary astrocytomas and less frequently anaplastic astrocytomas or glioblastomas. Some of these astrocytomas may have necrotic or hemorrhagic areas. The imaging appearance is that of a ballooned pons that obliterates the cisterns and the fourth ventricle, causing secondary hydrocephalus. Invasion of the basilar artery is rare. (1, 7, 10, 22)

On CT they appear as hypodense lesions with minimum load (50 % ) or without loading with contrast substance. More than half of tumours have an exophytic development at the level of the cisterns of the pontocerebellar angle. MRI is superior in the detection of pontine gliomas. The native sequence they appear in hyposignal T1 and hyperintense on T2 and Flair sequences. ( 25 )

Figure 7. Native axial CT image of brain. Iso dense tumour formation located in the pons (ballooning the pons and developing towards the fourth ventricle) (Rossi A., 2009)

Figure 8. MRI brain images in the axial (T1, T1 + C) and sagittal plane (T2). Tumour formation in T2 hyperintensity, T1 isosignal with discrete contrast outlet located at pontine level(diffuse astrocytoma) (Rossi A., 2009)

II.  SUPRATENTORIAL TUMOURS

The most common supratentorial tumours are gliomas and gangliogliomas. Intra-nevraxial brain tumours fall into hemispherical (of glial origin) which include astrocytomas, oligodendrogliomas, ependymomas and Pleomorphic xanthoastrocytomas and intra-nevraxiale tumours localized to the level of basal nuclei, including lymphomas and gliomas. Extra-nevraxial tumours can be located in the sellar region (pituitary tumour) suprasellar region (Craniopharyngioma, germ tumours, epidermoid cyst, dermoid cyst, teratoma tumours of the optic chiasm and hypothalamus), pineal and intraventricular. (2, 7, 14, 15, 23, 27)

1. Glioblastoamas: 3% of all glioblastomas occur in children. However, in children there is a biphasic distribution with two peaks of incidence: 4-5 years and 11-12 years. 90 % of diagnosed glioblastomas are located in the cerebral hemispheres. The most common location is the frontal lobe followed by the parietal lobes, as compared to the location where the front is followed by adults as well as the temporal frequency. They are usually solitary tumours, with loading in a ring, characterised by a pronounced peritumoural vasogenic oedema. Moreover, tumours are rich in neo vasculature that has a high permeability. (4, 22, 23)

The CT and MRI appearance of this lesion is the one of an almost completely necrosed formation with a strong load in ring . They are usually diffuse infiltrative forms involving possibly the corpus callosum and the contralateral hemisphere. Calcifications rarely occur in these tumours and meningeal metastases are very common. ( 18 )

Figure 9. MRI images in the axial plane. Necrotic tumour formation located in the left occipital white matter in hyposignal T1, T2 hyperintense contrast outlet ring with perilesional oedema and mass effect on midline structures (Ketonen L.M. 2005)

2. Brain astrocytomas have as a peak incidence at 7-8 years of age (more than locating the cerebellar and brainstem level). Supratentorial pilocytic astrocytomas are either cystic / multicystic with a mural nodule (55%) or solid (45%). The solid portion can sometimes show calcification or bleeding. (9, 21) On MRI image they usually appear as cystic or solid formations, well defined in hyposignal T1, T2 hyperintensity, which is loaded with contrast agent in the solid portion. (18)

Figure 10. Brain MRI in the axial plane. Solid formation located on the right temporal part of the brain in T2 hypersignal, T1 hyposignal with contrast outlet centre with minimal oedema around it, encompassing the right middle cerebral artery. (Ketonen L.M. 2005)

3. Oligodendrogliomas are glial tumours that originate in oligodendrocyte cells. These tumours are uncommon in children, they are more common in adolescent population. They grow very slowly or not at all. Imaged tumours are well circumscribed, peripheral, located in the white matter of the cerebral hemispheres, involving the cortex. (6, 23, 30)

The CT appears as iso or hypodense formations with nodular or granular calcifications. Cystic degeneration and bleeding may also be present. Heterogeneous appearances on MRI were: hypo and hypersignal T1 and T2 iso signal, moderate loading of contrast. The differential diagnosis should be considered for low-grade astrocytomas, gangliogliomas and neurocytomas. (18)

Figure 11. MRI brain images in the axial plane. Cerebral formation in hyposignal T1, T2 hyperintensity without contrast outlet, located at cortical and left frontal subcortical level (Ketonen L.M. 2005)

4. Primitive neuroectodermal tumours (PNET) are the most frequently encountered malignant tumours of the nervous system in children. They are a group of primary undifferentiated tumours arising in the brain hemispheres and include tumours that have common primitive neuroepithelial precursors in the  brainstem, cerebellum and the spinal cord. They tend to spread to the subarachnoid level, that is why the examination of the entire skull and spine is recommended. The peak incidence is at the age of over 5 years old. (16, 22, 23)

CT reveals hyperdense tumours with variable load. Calcification may occur, asymmetry of the upper brain and bone erosions. On MRI they appear as formations in hyposignal T1 and in iso or hypersignal T2 with uneven loading after administration of contrast. (13)

Figure 12. MRI brain images in the axial plane. Solid-necrotic tumour formation located in the left parietal lobe with surrounding oedema with contrast outlet in the solid part (Jurkiewicz E. 2010)

5. Craniopharyngiomas are benign tumours representing 6-9% of paediatric intracranial tumours and have a suprasellar typical location. Suprasellar tumours are most common in childhood. Calcifications are characteristic of this type of tumour, which can be distinguished from other suprasellar tumours based on this criterion; approximately 80% of childhood Craniopharyngiomas show calcification. (22, 26, 32)  On CT they look like heterogeneous solid-cystic formations, the solid part uploading itself with contrast. On MRI they are present in hypersignal T1 and T2, while the solid part is loaded with contrast. (18)

Figura13.  Native axial CT image of brain. Hyperdense polilobed tumour formation, located suprasellarly with extension to the pons and to the left pontocerebellar angle (Ketonen L.M. 2005)

Figure 14. MRI brain images in the axial plane. Multiloculated solid-cystic formation located suprasellarly and parasellarly to the left, in hypersignal T1, T2, FLAIR, having compressive effect on the pituitary gland and affecting the left internal carotid bifurcation and a proximal portion of the left MCA (Ketonen L.M. 2005)

NEW FRONTIERS IN NEUROIMAGING

The advent of advanced techniques of magnetic resonance such as spectroscopy, diffusion and perfusion allows the assessment of tumour formations from a functional point of view, complementing the information provided by conventional MRI that assesses tumours only morphologically.

Also, the use of functional MRI and of tractography led to a new vision of neurosurgical approach, the information provided by these methods helping to preserve the healthy peri-tumour tissues, thus reducing the incidence of postoperative disabling injuries.

1. CEREBRAL SPECTROSCOPY  is a new, special sequence of magnetic resonance which is based on the 21 metabolites that were detected at the level of the brain substance to determine the chemical composition of metabolic brain damage. Integral values ​​of these metabolites and their relationships lesion detected at lesion level can differentiate between different types of such lesions and can differentiate brain tumours from infectious, ischemic or demyelinating lesions. ( 1, 3 , 17, 18 , 29) )

2. CEREBRAL DIFFUSION is a special sequence which assesses the movement of water molecules in the tissue, bringing information about tumour cellularity. If the tumour cellularity is increased, as in the case of malignant tumours, the extracellular space is limited thereby restricting the movement of water molecules. (10, 11, 13, 16)

3. CEREBRAL PERFUSION CT is a special sequence of magnetic resonance that brings functional information about tumour angiogenesis, reflecting the tumour vasculature by the blood-brain barrier permeability (broken or intact). Also, the calculation of certain perfusion parameters allows their correlation with tumour grading. (5)

4. TRACTOGRAPHY is an MRI technique that highlights white matter tracts. It is used in pre-surgery assessment of their relationship with tumour formation, helping to establish neurosurgical approach. (3)

5. FUNCTIONAL MRI is a special MRI technique which provides a map of functional cortical areas, particularly the primary sensory and motor ones and of cortical areas involved in language and memory. It plays an important role in the preoperative assessment of brain tumours, bringing important related information to the neurosurgeon in connection to the anatomical relationship of the tumour formation with the cortical areas involved. (12)

Figure 15. Images of cerebral spectroscopy. Malignant intracranial tumour (suggested by the increased level of  choline) (Delgado, 2010)

Figure 16. Cerebral diffusion sequence. Restriction to cerebral diffusion and hypersignal (suggesting a malignant tumor) (Garcia Figueredo 2012)

Figure 17. Cerebral perfusion sequence. The increase in cerebral perfusion corresponding to highly malignant glioma (Edelman R. 2005)

Figure 18. Tractography sequence (Delgado 2010)

Figure 19. Functional MRI sequence. The proximity of the motor centre of the right hand compared to a low grade malignant lymphoma (Jiang Z. 2009)

Conclusions

CT scans and MRI in particular have been found to be extraordinarily useful in the detection and differential diagnosis of brain neoplasms. In recent years, they have perfected techniques (spectroscopy, diffusion, perfusion, tractography and functional MRI) that promise to significantly improve the accuracy, sensitivity and specificity of preoperative diagnosis of primary intra-nevraxial tumours bringing additional important data on the peritumoural brain parenchyma.

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