eduRAD syllabus 69 28 Diffusion imaging Apparent diffusion coefficient (ADC) values as measured with DWI are inversely related to cellularity, i.e. increased cellularity restricts diffusion and reduces ADC values. As increased cellularity is considered an indication of high grade tumour, it is expected that ADC may be useful for radiological tumour grading. Findings, however, are inconsistent and conflicting, with some authors reporting decrease of ADC in high grade tumours, as would be expected with increased cellularity (3), but others reporting increased ADC (4). The source of such discrepancies may, at least partially, be found in tumour heterogeneity. High grade tumours contain (micro)necrotic components in which diffusion is increased. Furthermore, diffusion is also increased in the peritumoural vasogenic oedema. MR spectroscopy Proton MR spectroscopy shows a correlation of the choline (Cho) peak with cell density and the lipid peak with proliferation (5). With increasing tumour grade there is generally an increase in the Cho/Creatine (Cr) ratio, a reduction in N-acetylaspartate (NAA) and an increase in the lactate/lipid peak (5-8). MR spectroscopy may be of particular use in the grading of oligodendrogliomas, in which contrast enhancement and increased rCBV ratios may be observed both in low and in high grades (7-9). Guiding neurosurgical intervention Among the commonly performed neurosurgical interventions we can distinguish diagnostic and therapeutic procedures. During either intervention damage to eloquent brain regions needs to be avoided. While eloquent brain regions can readily be identified on the basis of anatomical landmarks in the normal brain, such landmarks may be obscured in the presence of brain tumour with considerable mass effect. Advanced MR imaging techniques may be used to provide such information preoperatively. Furthermore, advanced MR imaging may also be used to identify the optimal target for diagnostic procedures. MR perfusion and spectroscopy Tumour grading is based on the highest malignancy grade identified within a tumour. Especially with stereotactic biopsy, sampling error is a real issue, when the tumour is under graded if the most malignant part of the tumour is not biopsied. With conventional MR imaging, stereotactic biopsy is generally targeted at the enhancing part of the tumour, which does not necessarily correspond with the most malignant part of the tumour. Such sampling errors may be avoided with the use of MR perfusion imaging or MR spectroscopy, with which the most vascular or malignant regions are readily identified. I n s c h r i j v e n v i a w w w . c o n g r e s s c o m p a n y . c o m o f w w w . r a d i o l o g e n . n l Figure 1. Combined fMRI and DTI-tractography indicating displacement of both the primary motor cortex and the corticospinal tract by the tumour mass effect. Functional and diffusion tensor MR imaging The aim of neurosurgical therapy is maximum tumour resection, while at the same time avoiding new functional deficit. In cases of tumour localisation in or near eloquent brain areas, such the motor cortex or language areas, additional advanced imaging may be advantageous to guide the neurosurgical approach, shorten surgery duration and obtain prognostic information prior to surgery. Functional MR imaging (fMRI) is used increasingly to assess the relationship between functionally eloquent cortex and brain pathology. Such information is particularly useful when normal anatomy is obscured by tumour mass effect or in cases of cortical plasticity. In an elegant study of 39 brain tumour patients, Petrella et al. demonstrated that treatment plans were altered based on information obtained with fMRI in 19 patients (10). Most notably, out of 9 patients who were considered inoperable based on information from conventional imaging, 7 were in fact considered operable upon assessment of the additional fMRI findings. While fMRI provides valuable information on eloquent cortex, with diffusion tensor MR imaging (DTI) the anatomy and involvement of white matter tracts may be evaluated. Inadvertent transection of white matter tracts during surgery leads to severe neurological deficit. DTI-tractography offers attractive visualisation of the major white matter tracts such as the corticospinal tract and the arcuate fasciculus (figure 1), and offers valuable preoperative information on their relationships with the brain tumour to be resected (11-13). As well as providing such anatomical information, colour coded eigenvector maps obtained with DTI can be used to categorise involvement of the white matter tracts by brain tumour (14). Four patterns of such involvement can be distinguished, indicating whether a tract is only displaced but not infiltrated, is altered due to vasogenic oedema, is infiltrated by tumour or is completely destroyed.
Especially in the last case this information is extremely useful preoperatively, allowing the surgeon to aim at gross total resection without concern for risking postoperative functional deficit. Follow-up Both low and high grade gliomas are followed-up with high frequency. In principle, all low grade (WHO grade II) gliomas undergo malignant transformation, mandating a change in therapy. Traditionally, the MacDonald criteria are used to monitor gliomas radiologically, in which the enhancing tumour is measured as the product of the maximum perpendicular diameters (15). With current and emerging therapeutic algorithms, which may on the one hand induce treatment-related enhancement (pseudoprogression) and on the other hand rapid reduction of enhancement (pseudoresponse), the MacDonald criteria may no longer be valid. These, and other limitations have led the Response Assessment in Neuro-Oncology (RANO) working group to define new standardised response assessment criteria for high grade glioma, in which most notably the non-enhancing tumour components are taken into account (16). In addition to the RANO criteria, advanced MR imaging techniques are expected to play an increasingly prominent role in both low and high grade glioma monitoring. This has led to the recent development of an imaging protocol by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumour Group (BTG), which includes diffusion and perfusion MR imaging (table). Malignant transformation It is not known how, why and when low grade gliomas undergo their transition from silent to aggressive tumours. The radiological hallmark of malignant transformation is the appearance of contrast enhancement in a previously non-enhancing tumour. An important concept in this context is the so-called angiogenic switch, indicating the transition of an avascular to a vascular tumour. It is this angiogenic switch that is assumed to underlie the finding by Danchaivijitr et al. of a progressive increase of maximum rCBV ratios in low grade transforming to high grade gliomas (17). Using longitudinal rCBV ratio measurements, they were able to predict malignant transformation as early as 18 months before transformation became apparent as determined by the current clinical and radiological criteria. The mean rCBV ratio at the point of transformation (i.e. appearance of contrast enhancement) was 5.4 ± 3.0, while mean rCBV ratios in the transformer group were 3.1 and 3.7 at 6 and 12 months respectively before enhancement became apparent. Not only can MR perfusion imaging be used to predict malignant transformation in non-enhancing tumours prior to the appearance of enhancement, it can also aid in establishing malignant transformation in those neuroradiologie tumours that already show enhancement in their low grade stages. Radiation necrosis and pseudoprogression Radiation-induced injury can be divided into acute (1-6 weeks during or after treatment), early delayed (after 3 weeks to several months) and late delayed (after months to years) injury (18). Histopathologically there is a vascular, endothelial injury resulting in endothelial proliferation with occlusive vasculopathy and stroke like episodes. Furthermore, there is a neurotoxic effect, resulting in white matter and glial damage. On conventional MR imaging, changes related to radiation necrosis are generally indistinguishable from tumour recurrence or progression. A separate entity, known as pseudoprogression, has emerged with the introduction of temozolomide combined with radiotherapy as the standard of care for newly diagnosed glioblastoma multiforme. Such chemoradiation therapy for high grade gliomas may result in asymptomatic pseudoprogressive lesions and increased necrosis in the peritumoural region, which is also indistinguishable from tumour progression or recurrence. It usually occurs soon after end of therapy (within 3 months of treatment) and subsides over the course of 6 to 9 months after start of treatment. This is earlier than the delayed radionecrosis. It is probably due to a subacute radiation encephalitis and treatment-related necrosis, with a higher degree of tumour cell and endothelial cell killing resulting in secondary reactions such as oedema and abnormal vessel permeability mimicking tumour (1). Such treatment related effects hinder the adequate adjustment of therapeutic strategy. Attempts are made with advanced MR imaging techniques to aid differentiating tumour progression/recurrence from treatment effects, but so far no unequivocal method or combination of methods is available. Such attempts are further complicated by the fact that histopathological correlation is problematic due to sampling bias as well as the general co-existence of radiation necrosis and vital tumour. MR perfusion imaging DSC perfusion imaging studies show low rCBV ratios in areas of radiation necrosis with reported thresholds of 0.7 and 0.6 (20) (figure 2). At such thresholds sensitivity is >90% and specificity approaches 100% (19). As with initial tumour staging, rCBV ratios are high in progressive tumour, with reported values of >2.6 (20) (figure 2). An accurate threshold, however, remains to be established. With steady-state dynamic contrast enhanced (DCE) perfusion a measure of vascular permeability (Ktrans) is obtained. Although there is contrast enhancement, indicating increased vascular permeability, in both radiation necrosis and recurrent tumour, enhancement is slow in radiation necrosis. K trans is therefore low in areas of radiation necrosis e d u r a d 6 9 - 2 1 - 2 2 e n 2 3 - 2 4 j u n I 2 0 1 1 29