A protocol for imaging paediatric brain tumours

Clinical

Radiolog~~

( 1999) 54, 558-562

Review A Protocol for Imaging Paediatric Brain Tumours PAUL D. GRIFFITHS AND (UKCCSG) AND SOCIfiTI? Depat-trnent

of Radiology.

THE UNITED FRANCAISE

The Univer-sig

KINGDOM CHILDREN’S CANCER STUDY GROUP D’ONCOLOGIE PBDIATRIQUE (SFOP) PANELISTS

of Sheffield,

Royal

Hallamshir-e

Hospital.

Slwffield.

SlO 2JF. U.K.

Received: 17 September 1998 Revised: 4 November 1998 Accepted: 17 November 1998

Childhood cancer affects one in 600 children, tumours of the brain and spine accounting for up to 25% of these in population-based registries [ 1.21 and 20 per cent of intracranial tumours have presented by the age of 15 years. Overall survival rates of brain and spinal tumours are 50% and have not substantially improved in the last 20 years [3]. Currently. national and international efforts are being made to improve the standards of care for children with brain and spinal tumours [4,5]. These efforts are directed through the organization of national and international clinical trials of novel therapeutic approaches in the hope that the dramatic improvements seen in leukaemia and tumours outside the brain will be mirrored in brain and spinal tumours. This expansion of trial-led therapies is already underway in the United Kingdom through the activities of the United Kingdom Children’s Cancer Study Group (UKCCSG). The number of children in the U.K. with brain tumours involved in phase II/III clinical trials, has tripled in the past 6 years. These trials involve multidisciplinary strategies which require standardized approaches for imaging at diagnosis and after each phase of treatment in order to stratify patients for risk and evaluate the impact of each modality of treatment. The considerable variations in imaging practice can serve as confounding variables in these studies. The purpose of this report is to propose a set of standard diagnostic imaging guidelines that can be included in future clinical trials and act as a standard for audit of clinical practice in paediatric neuro-oncology centres. Imaging the child with a newly diagnosed primary neural tumour is directed at defining the anatomical relationships of the tumour and providing information necessary for tumour staging. The anatomical relationships assist in predicting the histological diagnosis, help the neurosurgeon in planning surgical approaches for biopsy or resection, assist the chemotherapist by allowing the tumour to be measured for response Correspondence to: Dr Paul D Grifliths. The University of Sheffield. Academic Department of Radiology. Floor C, Royal Hallamshire Hospital. Glossop Road, Sheffield SIO 2JF. U.K. Tel: 01 14-271-3207 Fax: 0 114-272-4760 E-mail: [email protected]

0009-9260/99/090558+05

$12.0010

assessment.assistthe radiotherapist in planning radiation fields and assist the neurologist in predicting disability and need for rehabilitation. Obtaining information about the degree of resection and the presence of disseminated tumour helps predict histology. define risk status with respect to survival, assess degree of resection and plan optimal imaging strategies for future follow-up. Standardized criteria for defining tumour stage by virtue of grading of response. degree of resection and presence or absence of metastases have been previously published as a result of clinical trials carried out by the Societe Franqaise d’Oncologie Pediatrique [6]. These criteria remain in current use and their concepts have been included in the development of these guidelines. The diagnosis and assessment of paediatric brain tumours has been greatly improved by the introduction of magnetic resonance imaging (MRI) into clinical practice. Cranial computed tomography (CT) is often the first imaging investigation in children with brain tumours but it is widely accepted that MRI is invaluable before treatment. Although CT often gives more clues to the tumour histology when compared with MRI [7]. MRI evaluates the full extent of the tumour. assisting surgical or radiotherapeutic management. MRI is also the most efficient way of detecting meningeal spread [8]. Children with brain tumours will require follow-up imaging to judge the effectiveness of treatment and MR is the imaging method of choice for this on the basis of improved sensitivity and specificity when compared with CT, and from the point of view of radiation protection. The serial evaluation of brain tumours in the clinical setting is usually made by subjective assessment by the reporting radiologist. In order to do this reliably, it is important to have a standardized imaging protocol so that interval MR examinations are as closely matched as possible. Relatively minor alterations in the plane of imaging, sequence parameters and intravenous contrast agent dose can have significant effects on tumour assessment.Many children with brain tumours are entered into national or international clinical trials and in the research setting, effectiveness of treatment is often judged by objective measurements. The variability of imaging techniques between centres often makes this difficult. 0

1999 The Royal

College

of Radiologists.

PAEDIATRIC

559

BRAIN TUMOURS

The aim of this editorial is to present guidelines to standardize the approach to MRI of paediatric brain tumours in the U.K. and in France. This document is the result of discussion between the UKCCSG neuroradiology panelists and their French counterparts, Socittt Franqaise d’Oncologie Pkdiatrique (SFOP). We believe that this will assist the interpretation of examinations performed for clinical and research purposes. The approach outlined below is considered to be the best practice for MRI although it is appreciated that other methods such as spectroscopy, perfusion imaging and image registration techniques are currently under evaluation. It is our intention to produce a protocol that can be performed on every MR system allowing accurate and reliable comparison of examinations performed at different centres and at different times within the same centre. It is important that any protocol can be performed within a reasonable investigation time. This will be variable depending on the MR system used but ideally should not be more than 30 min. MRI PROTOCOL Most children referred to the tertiary centre will have already undergone CT examination of the brain. This may well provide valuable information but CT should not be taken as the only or primary pre-operative imaging method. A pre-operative/therapy MR examination should be performed if at all possible. The protocols outlined below are straightforward multiplanar, multisequence investigations that are always supplemented with TI-weighted imaging after the intravenous administration of Gadolinium DTPA. It is preferable to have intravenous access sited in a child before coming to the MR department unless the examination is to be performed under general anaesthetic. This is particularly the case in younger children or those who are being examined under oral or rectal sedation where on-table siting of the canula is likely to wake the child. It is also important to know the weight of the child before MR as the dose of Gadolinium DTPA is weight dependent (0. I mmol/kg). Wherever possible MRI of the spine should be undertaken at the same time as imaging of the head at initial presentation. Follow-up imaging of the spine may be excluded if histology has indicated a tumour type that is unlikely to seed throughout the cerebrospinal fluid (CSF). The existence of seeding can be difticult to predict as radiological appearances are often not specific for a particular histological type and even histologically low grade gliomas may have seeded into the CSF spaces at presentation. Therefore. spinal imaging is performed at the end of most examinations at initial presentation. The usual sequence parameters and sequences are presented in Appendices 1 and 2. Axial images are aligned parallel to the anterior commissure/posterior commissure line (Fig. 1) and coronal sections are taken at 90” to that axis. If those landmarks are not apparent the plane of the hard palate is a good approximation. It is true that the precise imaging plan is not relevant for interpretation. but consistency between examinations is very important. It is good practice to copy a scout image showing the orientation of images on each sheet of hard copy so these can be reviewed and reproduced by the MR radiographers at subsequent appointments. It is also useful to start the image

Fig. I - Sagittal TI-weighted image with ;I constructionline centredon the anterior and posterior commisures.This plane is used ils the standardfor axial imaging. Note that the plane is close to that of the anterior cranial fossa,which can be used if the commisurescan not be located. acquisition at the same level and copy comparable sections onto the same position on the film. We recommend filming to proceed: axial-caudal to cranial; sagittal - right to left; and coronal - anterior to posterior. This assists the interpretation of serial examinations. When images are passed on to UKCCSG groups for assessment it is desirable to send copies reprinted from the archive not photographic reproductions of the originals. The most appropriate sequences and planes are driven by the need to evaluate the full anatomical extent and size of the tumour and to give the neurosurgeon information as to the best approach to the tumour within the time constraints of the MR department. Tumours are usually measured in the three natural orthogonal axes which requires imaging in at least two planes. Infratentorially the axial and sagittal planes usually provide all the information required although coronal imaging may be useful to assesstumour extension into the adjacent cisterns. Supratentorially. midline hemispheric tumours are best appreciated in the axial and sagittal planes while lateral tumours are best assessed by axial and coronal imaging. However, many neurosurgeons value parasagittal imaging to plan their approach. In post-operative patients Tl-weighted imaging should be performed before and after intravenous Gadolinium. This will detect haemorrhage and artefactual Tl shortening from ferromagnetic fragments resulting from surgery that may otherwise be misidentified as residual tumour [9]. A further important point for T2-weighted images is that the echo time may have to be altered depending on the age of the child. The high water content of the neonatal brain usually requires longer echo time (e.g. 30 ms for the first echo and 130 ms for the second echo). ISSUES Non-enhancing

Tumour

Tumour extent is usually estimated by the distribution

of

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CLINICAL

. abnormal enhancement after intravenous administration of gadolinium, therefore, measurements are made on post-contrast images. However, a surprisingly high proportion of paediatric primary brain tumours show little or no enhancement particularly infiltrating astrocytomas of the brainstem and hypothalamus. If there is no enhancement seen on the first post-contrast sequence, further T2-weighted imaging in different planes should be performed to assess the full extent of tumour judged by margins of T2 signal abnormality. 3D FT Gradient Echo Imaging Most modem MR systemscan perform 3D Ff Gradient Echo sequences (eg MPRAGE) which produce high resolution Tlweighted images as spoiled gradient echo technique with very short echo time providing excellent grey white matter contrast. These can be used either with or without intravenous gadolinium DTPA. The major advantage of this technique is that any plane can be constructed from the base data and the acquisition time is comparable to performing spin echo TIweighted sequences in two planes. These have been used successfully in many neuropaediatric situations and are particularly good in assessing subtle cortical malformations and looking for hippocampal volume change in mesial temporal sclerosis. However, these sequences do have pitfalls. Flowrelated enhancement is found both in the arteries and venous structures of the brain when performing gradient echo techniques which is a potential source of false positives when looking for tumour recurrence. The experience of the UKCCSG Brain Tumour Panel is that tumour enhancement is less pronounced, and less consistent, when compared with multi-slice spin echo techniques. In addition, spurious meningeal enhancement is common with 3D FT gradient echo techniques. Therefore, we recommend spin echo TI-weighted imaging in (at least) two planes instead of 3D FI gradient echo techniques in spite of the time penalties. Other problems with 3D FT techniques include the presence of aliasing of outer views into the central slices and changes in contrast due to imperfect spoiling of T2 coherence. Flow compensation techniques are useful in gadolinium enhanced examinations because spatial misregistration occurs in the vicinity of blood vessels containing high concentrations of gadolinium. This is often particularly marked in the posterior fossa. Alternatively imaging could be delayed for 15-20 min after injection of gadolinium [7]. Immediate

Post-operative

Imaging of Brain and Spine

The first post-operative brain MR examination will assess the amount of residual tumour. In some cases it can be difficult to distinguish between residual tumour and iatrogenic change such as gliosis/fibrosis. It has been suggested that iatrogenic enhancement does not occur within the first 3 post-operative days, therefore, any enhancement in the first 3 days must be due to residual tumour [IO]. It does appear that iatrogenic enhancement is lesslikely to be seen in the first 3 days but recent studies have shown exceptions [ I I, 121. Surgical enhancement appears soon after the original procedure, becomes maximal at about 6 weeks post-operatively and usually has disappeared by I2 months. An immediate post-operative MR examination is

RADIOLOGY

considered best practice by many centres and is performed usually just before the child is to come off the ventilator to avoid a later general anaesthetic. However, not all centres have adopted this policy, primarily due to limited MR time. However. it has proved practical to perform MR examinations in children who have come off the ventilator under light sedation within 72 h of surgery and every effort should be made to perform MRI within that time frame. It should be noted that intracranial dural enhancement is often seen following tumour surgery, biopsy or even lumbar puncture and this can be generalized and may persist for many months or years [9]. It is important to distinguish post-operative pachymeningeal (dural) enhancement from tumour enhancement of the leptomeninges (pia and arachnoid). The latter will follow the brain surface into the depths of the cortical sulci while dural enhancement does not follow the subarachnoid space and remains over the surface of the brain. The presence of leptomeningeal enhancement implies either leptomeningeal tumour, infection ]9] or localized ischaemia/infarction. The situation with post-operative spinal imaging is different. Ideally post-gadolinium imaging of the spine should be performed before surgery. If this was not done. it should be performed after surgery. However. in the first 2 weeks after surgery the MR results are difficult to interpret. Blood products can produce high signal on Tl-weighted images, therefore, this is a potential pitfall in performing only post-gadolinium imaging in this situation. The blood products and tumour cells dispersed from tumour operation often produce enhancement of the meninges and on the surface of the cord. This subsequently disappears and, therefore, does not represent leptomeningeal spread of viable tumour. Therefore, post-operative spinal imaging should not be performed in the first 2 weeks. In summary, we describe a simple, standardized protocol for MR imaging of children with brain tumours at presentation and post-therapy. It is hoped that this approach will assist interpretation of MR examinations in the routine clinical situation and in trials. REFERENCES Suller CA. Allen MB, Eatock EM. Childhood cancer in Britain: the nalional registry of childhood tumours and incidence rates 197% 1987. Eur J Cmcrr I995;3 I A:2028-2034. Stiller CA. Nectoux J. International incidence of childhood brain and spinal turnours. fin J Epidentiol 199423 3:458-463. Lannering B. Marky I, Nordborg C. Brain tumors in childhood and adolescence in West Sweden l970- 1984. Cancer 1990: I :604-609. Lashford L. Walker DA. Improving care for central nervous system tumours: a mood for change. Arch Dis Childhood. 1997;76:88-89. Walker DA. Hockley A, Taylor R, et cl/. Guidance for services for children and young people with brain and spinal turnours. Royal College of Paediatrics and Child Health 1997. Gnekow A. On behalf of the SIOP Brain Tumor Sub-Committee. Recommendations of the brain tumor sub-commitlee for the reporting of trials. Med P edicrrr Oncol I995;24: IO& 108. Barkovich AJ. Brain tumours in childhood. In: Barkovich AJ, ed. Pedicrtric Neumimugin,g 2nd ed. New York: Raven Press, 1995:321438. Barkovich AJ. Neuroimaging of pediatric brain turnours. In: Winn HR, Mayberg MR. eds. Nerrrosnrge~ Clinics r~f Norrh America Philadelphia: W.B. Saunders. 1992;739-770. Hudgins PA, Davis PC. Huffman Jr. JC. Gadopenetrate Dimeglumineenhanced MR imaging in children following surgery for brain tumor: spectrum of meningeal findings. Am J Neurorudiol I99 I: I2:301-307.

PAEDIATRIC IO Albert FK. Forsring M. Sartor K, Adams HP, Kunzc S. Early posloperalivc magnetic resonance imaging after resection of malignant glioma: objective evaluation of residual’ tumour and its influence on regrowth and prognosis. Ne~rnsrcr~e~ 1994:34:4.5-60. I I Rollins NK. Nisen P. Shapiro KN. The use of early post-operative MR in detecting residual juvenile cerebellar pilocytic astrocytoma. Am J Neworadiol 1998: 19: I5 I - 156. I7 Sato N. Bronen RA. Sze G, Kawamura Y. CI al. Post-operative changes in the brain: MR imaging findings in patients without neoplasms. Rodiolo,q~ 1997;204:839-85 I.

APPENDIX

1 - SUPRATENTORIAL

BRAIN

561

TUMOURS

Spine:

Pnrometers,

Post-contrast whole spine sagittal Tl SE (dependent on tumour type. If histology indicates tumour type with potential to seed through the CSF).- contrast medium: As before

APPENDIX

2 - INFRATENTORIAL

Presentation

TUMOURS Sequences:

Presentation

Cranial:

Whole brain axial coronal Tl SE Whole brain T2 SE/FSE axial Sagittal T2 through brainstem for brain stem glioma Post-contrast T I SE in at least two orthogonal planes Post-contrast whole spine sagittal Tl SE

Sequences:

Cranial - Axial dual echo SE (spin echo) or FSE (fast spin echo) Coronal TI SE Post contrast (i.v. gadolinium DTPA) Tl SE in at least two orthogonal planes. Spinal Guideline

Post contrast whole spine sagittal Tl SE Axial TI SE if equivocal

T2 SE T2 FSE Spinal -

Tl SE Slice thickness

Cottrrcrsr

Spinal: Poramerers:

parameters:

Cranial - Slice thickness FOV (field of view) Matrix Tl SE

Timing: Sequences:

Post Surgery - (Assessment of Residual Tumour) Within 72 h Cranial

Spinal Parameters.

TR: ~600 msec, TE: ~25 msec <4 mm

cottlro.lsI

medium:

As for supratentorial lesions Slice thickness <5 mm slice thickness

Immediately Titning: Sequences:

i.v. line to be placed prior to attending MR department, when possible. i.v. Gadolinium DTPA 0. I mmol/kg

tnediutn:

Post-surgery (Assessment of Residual Tumour)

Within 72 h Cranial: Whole brain coronal Tl SE Axial T2 SE/FSE Post contrast Tl SE in two orthogonal planes Spinal:

Parnmeters,

conwcIsI

Not recommended, see text medium:

As before

Late Follow-up Coronal Tl SE Axial dual echo SEffSE Post-contrast Tl SE in the least two orthogonal planes Not recommended, see text As before

Late Follow-up MRI Timing: Sequences:

Conrrusr

i.v. line to be placed prior to attending MR department, where possible i.v. Gadolinium DTPA 0.1 mmol/kg

tnediutn:

Immediate

4 mm 180-230 cm ~256x256 (effective) TR:<800 msec. TE: ~25 msec TR:2,000-2,600 msec, TE:20/90 msec TR:3,000-4,000 msec, TE: 20190 msec

Protocol driven - dependent on tumour type Cranial: Coronal Tl SE Axial dual echo SE/FSE Post-contrast Tl SE in at least two orthogonal planes

TUMOURS

Titning: Sequence:

Protocol driven (dependent on tumour type) Cranial: Whole brain coronal Tl SE Whole brain axial T2 SE/FSE Post contrast Tl SE in two orthogonal planes Spinal:

Pnrntnerers: Contrast

MRI

Post contrast sagittal Tl SE

As before tnedium:

As before

Abbreviations used in the appendix: FSE SE TE TR

Fast Spin Echo Spin Echo Time to Echo Time to Repeat

562

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APPENDIX

3: UK AND FRENCH

Hopital Saint-Julien, Nancy Atkinson Morley’s Hospital, Wimbledon Great Ormond Street Hospital, London Institute Gustave Roussy, Villejuif Guys and St Thomas’s Hospital, London Newcastle General Hospital, Newcastle University of Sheffield, Sheffield Institute of Neurological Sciences, Glasgow Queen’s Medical Centre. Nottingham T. Jaspan L. Lashford Christie Hospital NHS Trust, Manchester N. McConachie Queen’s Medical Centre. Nottingham S. Neuenschwander Institute Curie. Paris Centre Regional Leon Berard, Lyon P. Thiesse D. Walker Queen’s Medical Centre. Nottingham

Prof. S. Braccard Dr J. B&ton Dr W. K. Chong Dr D. Couanet Dr T. Cox Dr A. Gholkar Prof. P. D. Griffiths Dr D. Hadley Dr Dr Dr Dr Dr Dr

PANELISTS

RADIOLOGY