Glial Neoplasms

Gliomas are the most common brain tumours [25] and are divided into astrocytomas, oligodendrogliomas and ependymomas. Astrocytomas are the most frequent type of glioma and present different grades of malignancy: grades I-IV. Grades I and II are classified as low-grade gliomas, while grades III (anaplastic as-trocytomas) and IV (glioblastomas) are classified as high-grade gliomas. Malignant astrocytomas (grades III and IV) are the most common subtypes, and glio-blastoma multiforme, in particular, represents approximately 51 % of all CNS tumours [26]. Gliomas are extremely heterogeneous in terms of imaging appearance. They are infiltrative lesions with margins often poorly defined on both T1- and T2-weighted images [27]. Low-grade gliomas are typically non-enhancing after injection of gadolinium and are identified as a region of hypointensity on T1-weighted images and of hyperintensity on T2-weighted images. Grade III glio-mas have large regions of hypointensity on T1-weight-ed images but may also have regions which appear bright on postcontrast T1-weighted images. Grade IV gliomas may be non-enhancing, but more frequently they have substantial regions of contrast enhancement with a central area of hypointensity that corresponds to necrosis. However, gadolinium-enhancing lesion is not always a reliable indicator of active tumour. This is due partly to the existence of tumour tissue which does not enhance, and partly to the presence of contrast-enhancing necrosis [28]. Of the astrocytic tumours, glio-matosis cerebri is a peculiar clinical and histopatholog-

ical entity, characterized by diffuse overgrowth of glial elements with infiltration of at least two and sometimes three contiguous areas of brain [29]. The distinction between gliomatosis cerebri and other diffuse infiltrating gliomas, such as multicentric glioma, has been debated [30]. However, gliomatosis cerebri refers to tumour with contiguous involvement of different regions, whereas multicentric glioma is defined as distinct foci of tumour in different sites [31]. Furthermore, glioma-tosis cerebri typically lacks features found in highgrade gliomas, especially vascular proliferation and necrosis, and shows no mass effect [32].

In recent years, the combination of 1H-MRSI, DWI and/or PWI in addition to conventional MRI has improved the ability to differentiate solid tumour from other intratumoral or peritumoral components [33-36]. Most of these studies have been performed at a magnetic field strength of 1.5 T. We applied such a multiparametric MR approach using a 3 T MR scanner to better characterize the large heterogeneity of brain gliomas. We evaluated 30 patients, 20 with high- and 10 with low-grade gliomas, before undergoing surgery and histologic confirmation. Normalized metabolite signals, including choline (Cho), N-acetylaspartate (NAA), creatine (Cr) and lactate/lipids (LL), were obtained by 'H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI. We carefully examined the regions of interest (ROIs) surrounding the enhanced margins of tumours (perienhancing ROIs) and those surrounding the non-enhancing tumours (peritumoral ROIs), identifying peculiar multiparametric MR patterns. We divided perienhancing ROIs into two groups: ROI with abnormal signal on conventional MRI (perienhancing abnormal ROIs) and normal-appearing ROIs (perienhancing normal ROIs). The first group was further divided into three groups: presumed tumour or tumour-infiltrated („tumour") ROIs, presumed vasogenic oedema („oedema") ROIs and presumed tumour-infiltrated oedema („tumour/oedema") ROIs. Perienhancing and peritumoral normal-appearing ROIs were further divided into two groups: presumed tumour-infiltrated („infiltrated") ROIs and „normal" ROIs.

In high-grade gliomas, „tumour" ROIs showed an abnormal Cho/NAA ratio (> 1), with an ADC lower and rCBV higher than „oedema" ROIs. These latter showed a normal Cho/NAA ratio, low or normal metabolite levels, and an ADC higher and rCBV lower than „tumour" ROIs. „Tumour/oedema" ROIs showed an abnormal Cho/NAA ratio, low metabolite levels and intermediate ADC andrCBVvalues (Figs. 18.1,18.2). „Tumour", „tu-mour/oedema" and „oedema" patterns were frequently present in the same tumour. In effect, regions of altered signal outside the enhancing margins of highgrade gliomas represent a variable combination of va-sogenic oedema and infiltrating tumour cells [37]. The predominance of tumour cells produces spectra with the typical tumour pattern (i.e. with high Cho peaks and abnormal Cho/NAA ratios) [5-8], reduces ADC because of augmented cellularity [12], and increases rCBV because of incremented size and/or number of vessels [38]. If vasogenic oedema is prominent, the increase of interstitial water in normal brain [39] „di-lutes" the signal of metabolites producing normal spectra with reduced metabolite peaks [34], increases the extracellular spaces and the diffusion of water [40], and compresses the blood vessels reducing rCBV [34]. If va-sogenic oedema and neoplastic cells are both predominant, spectra have the typical tumour pattern, but the metabolite signals are „diluted", and ADC and rCBV assume intermediate values. „Infiltrated" ROIs showed the typical tumour spectra with a high Cho and/or abnormal Cho/NAA ratio (Fig. 18.2). The finding of peri-enhancing tumour-infiltrated ROIs is in agreement with neuropathological studies showing tumour cells in areas well beyond the tumour margins as depicted on conventional MRI [8].

In low grade gliomas, the mass usually showed all metabolite peaks except for LL, but Cho and less frequently Cr were generally higher and NAA lower than normal (Figs. 18.3,18.4). Peritumour „infiltrated" ROIs showing a high Cho peak and/or an abnormal Cho/ NAA and no abnormalities on conventional MRI (Fig. 18.3) were found in three patients.

We also observed a case of gliomatosis cerebri in a 43-year-old patient (Figs. 18.5, 18.6). The tumour appeared on T2-weighted images as a diffuse hyperinten-sity that involved the splenium of corpus callosum, and the cortex and white matter of mesial temporal lobes. In the affected ROIs, 1H-MRSI showed spectra with the typical „tumour" pattern (Fig. 18.5). After 3 months, the lesion acquired the features of malignant glioma in the right occipital lobe, with diffuse contrast enhancement and evidence of necrotic core. The multiparame-tric approach, with 1H-MRSI, DWI and PWI, allowed the identification of areas with „tumour" and „oede-ma" patterns (Fig. 18.6).

Fig. 18.1. FLAIR (a), contrast-enhanced T1-weighted (b) and T2-weighted (e) images, ADC (c), rCBV (d), Cho (f), NAA (g), Cr (h) and LL (i) maps, and proton MR spectra (1-9) from selected ROIs in a 58-year-old woman with a right temporal glioblastoma. ROIs are those with a necrotic aspect (1, 2); perienhancing ROIs with abnormal signal on T2-weighted images and „tumour" (3, 5), „tumour/oedema" (4) and „oedema" (6) multiparametric patterns; and homolateral (7) and contralateral (8, 9) normal ROIs. On the colour scale, H indicates the strongest signal intensity and L the weakest (Cho choline, NAA N-acetylaspartate, Cr creatine, LL lactate and/or lipids, ADC apparent diffusion coefficient, rCBV relative cerebral blood volume). The lesion shows two apparently necrotic regions surrounded by a ring enhancement (b): the medial region, which presents high signal intensity on T2-weighted and FLAIR images (e) and high ADC (c), likely represents a colliquative necrosis. Note that „tumour" ROIs show an abnormal Cho/NAA ratio (> 1), Cho and rCBV higher, and ADC lower than „oedema" ROI, while „tumour/oedema" ROI presents an abnormal Cho/NAA ratio, low metabolite peaks and intermediate ADC and rCBV; necrotic ROIs show a variable level of Cho and a high LL peak

Fig. 18.2. Contrast-enhanced T1-weighted (a) and T2-weighted (b, e) images, ADC (c), rCBV (d), Cho (f), NAA (g), Cr (h) and LL (i) maps, and proton MR spectra (1-9) from selected ROIs in a 64-year-old man with a right frontal glioblastoma. ROIs are those with a necrotic aspect (1,2); tumour margin (4); perienhancing ROIs with „tumour" (3) and „infiltrated" (5) pattern; and homolateral (6, 7) and contralateral (8,9) normal ROIs. On the colour scale, H indicates the strongest signal intensity and L the weakest (Cho choline, NAA N-acetylaspartate, Cr creatine, LL lactate and/or lipids, ADC apparent diffusion coefficient, rCBV relative cerebral blood volume). Note that the „tumour" ROI presents multiparametric MR characteristics similar to „tumour" ROIs in Fig. 18.1 (i.e. high Cho peak, abnormal Cho/NAA ratio, low ADC and high rCBV) and an abnormal signal on T2-weighted image; the „infiltrated" ROI presents an abnormal Cho/NAA ratio (> 1), a Cho peak higher than normal ROIs and no signal abnormality on T1- and T2-weighted images; necrotic ROIs show a variable level of Cho and a high LL peak

Fig. 18.2. Contrast-enhanced T1-weighted (a) and T2-weighted (b, e) images, ADC (c), rCBV (d), Cho (f), NAA (g), Cr (h) and LL (i) maps, and proton MR spectra (1-9) from selected ROIs in a 64-year-old man with a right frontal glioblastoma. ROIs are those with a necrotic aspect (1,2); tumour margin (4); perienhancing ROIs with „tumour" (3) and „infiltrated" (5) pattern; and homolateral (6, 7) and contralateral (8,9) normal ROIs. On the colour scale, H indicates the strongest signal intensity and L the weakest (Cho choline, NAA N-acetylaspartate, Cr creatine, LL lactate and/or lipids, ADC apparent diffusion coefficient, rCBV relative cerebral blood volume). Note that the „tumour" ROI presents multiparametric MR characteristics similar to „tumour" ROIs in Fig. 18.1 (i.e. high Cho peak, abnormal Cho/NAA ratio, low ADC and high rCBV) and an abnormal signal on T2-weighted image; the „infiltrated" ROI presents an abnormal Cho/NAA ratio (> 1), a Cho peak higher than normal ROIs and no signal abnormality on T1- and T2-weighted images; necrotic ROIs show a variable level of Cho and a high LL peak

Fig. 18.3. Contrast-enhanced T1-weighted (a), FLAIR (b) and T2-weighted (e) images, ADC (c), rCBV (d), Cho (f),NAA (g), Cr (h) and LL (i) maps, and proton MR spectra (1-9) from selected ROIs in a 36-year-old woman with a grade II fronto-parieto-tempo-ral oligodendroglioma. ROIs are tumour mass (1-3), peritumour „infiltrated" ROI (4), homolateral (5) and contralateral (6-9) normal ROIs. Note that the „infiltrated" ROI presents an abnormal Cho/NAA ratio (> 1), a Cho peak higher than normal ROIs and no signal abnormality on T1- and T2-weighted images; the tumour mass shows all the metabolite peaks, except LL, and an abnormal Cho/NAA ratio; ADC values are higher than and rCBV values are similar to those of normal white matter

Fig. 18.4. Contrast-enhanced T1-weighted (a), T2-weighted (b) and FLAIR (e) images, ADC (c), rCBV (d), Cho (f ),NAA (g), Cr (h) and LL (i) maps, and proton MR spectra (1 -9) from selected ROIs in a 49-year-old man with parietal fibrillary astrocytoma of grade II. ROIs are tumour mass (1,2) andmargin (3), homolateral (4,5) andcontralateral (6-9) normal ROIs.Noteinthetumour mass the presence of all the metabolite peaks except LL, and the abnormal Cho/NAA ratio; ADC values are higher than and rCBV values are similar to those of normal white matter

Fig. 18.4. Contrast-enhanced T1-weighted (a), T2-weighted (b) and FLAIR (e) images, ADC (c), rCBV (d), Cho (f ),NAA (g), Cr (h) and LL (i) maps, and proton MR spectra (1 -9) from selected ROIs in a 49-year-old man with parietal fibrillary astrocytoma of grade II. ROIs are tumour mass (1,2) andmargin (3), homolateral (4,5) andcontralateral (6-9) normal ROIs.Noteinthetumour mass the presence of all the metabolite peaks except LL, and the abnormal Cho/NAA ratio; ADC values are higher than and rCBV values are similar to those of normal white matter

Fig. 18.5. FLAIR images and proton MR spectra (1 -9) from selected ROIs in a 42-year-old man with a gliomatosis cerebri. ROIs are those with the typical tumour spectra (2, 3, 6-8); ROIs with artefactual spectra (1, 4) in the region that will develop malignant features after 3 months (see Fig. 18.6); and normal ROIs (5,9). Note the diffuse hyper-intensity involving the splenium of corpus cal-losum, and the cortex and white matter of mesial temporal lobes

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