Книги по МРТ КТ на английском языке / MR Imaging in White Matter Diseases of the Brain and Spinal Cord - K Sartor Massimo Filippi Nicola De Stefano Vincent Dou

Metastatic Tumours

Gliomas are classified by their histologic features, according to the presumptive “cell of origin,” differentiation and malignancy grade. At the current state of knowledge, cytogenesis is more a theoretical concept than a definitive basis for tumour classification. In the near future the further discovery of molecular and cytogenetic features will form the basis of more objective tumour classification.

Age of the patient and anatomic location are also very important diagnostic and prognostic criteria. According to the WHO system or the St. Anne-Mayo system, glial tumours are graded on the basis of the most malignant area identified on the histopathologic specimens (Fig. 28.2.1). Fibrillary (grade II) astrocytoma is characterised by increased cellularity, with a monomorphic population of cells infiltrating the neuropil. Anaplastic (grade III) astrocytoma is characterised by nuclear polymorphism and mitoses. The pres-

ence of microvascular proliferation and necrosis are features of the (grade IV) glioblastoma. They can arise either alone (primary glioblastoma) or from a preexisting low-grade glioma (secondary glioblastoma).All gliomas are histologically and genetically heterogeneous. When a small specimen is taken for histopathology, it could not reflect the most malignant biology of the entire tumour.Among low grade astrocytomas the fibrillary (WHO grade II) must be distinguished from more benign tumours such as pilocytic astrocytoma (WHO I) and pleomorphic xanthoastrocytoma (WHO grade II). While fibrillary astrocytomas have a tendency to change their biologic behaviour with time and evolve into high-grade gliomas, the latter two types maintain a benign prognosis despite the presence of contrast enhancement on CT and MR imaging. The radiologist must be able to recognise promptly these true benign enhancing tumours!

Oligodendrogliomas are tumours originating from oligodendrocytes or their precursors. Oligoastrocytomas have composite histologic features, reflecting both oligodendrocytic and astrocytic cells. With the recognition that these tumours may be particularly sensitive to chemotherapy, neuropathologists have made a greater effort to identify them. The recent demonstration that many oligodendrogliomas and oligoastrocytomas have deletion of 1p and 19q chromosomes, and that these molecular changes are linked to chemosensitivity (Smith et al. 2000), has enhanced the efforts to identify them. An estimate suggests that they represent approximately 20% of glial neoplasms (Fortin et al. 1999). Oligodendrogliomas

are moderately cellular and composed of monotonous round, homogeneous nuclei with a clear cytoplasm. They have a dense network of branching capillaries. It is not rare for oligodendrogliomas to bleed, and they may present as an intracranial haemorrhage. Additional features include microcalcifications and macrocalcifications, and mucoid/cystic degeneration. The appearance of significant mitotic activity, prominent microvascular proliferation or necrosis indicates progression to high-grade oligodendroglioma (WHO grade III). Oligodendrogliomas grow diffusely in the cortex and white matter. Circumscribed leptomeningeal infiltration may induce a marked desmoplastic reaction.

The median survival of patients with low-grade astrocytomas is 5 years. However, the range of survival is broad and unpredictable (Bauman et al. 1999). Most patients die from progression to high-grade glioma. Studies of patients with oligodendrogliomas reported a median survival of about 10 years. A recent series of 106 patients yielded a median survival of 16 years (Olson et al. 2000), probably due to earlier diagnosis after the advent of MRI.

28.3

Conventional MR Imaging

In the last three decades the development of more sophisticated and advanced imaging techniques has led to improved diagnostic accuracy. CT and MR imaging enable doctors to diagnose brain tumours that previously might have been incorrectly diagnosed as strokes, senile dementia, multiple sclerosis or other neurologic disorders. The sensitivity of MR imaging to detect intracranial neoplasms is very high, and it has been generally recognised as the imaging study of choice. When a large lesion is detected,this is the first question to be answered: “Is it a tumour?” The recognition of mechanical effects and structural deformities that can be explained as infiltration of brain tissue or growth of the lesion are summarised in one sentence: “There is a mass.” The second question is: “What type of tumour is it?” Characterisation of the lesion includes distinction between intra-axial and extra-axial masses. The former is growing from inside,infiltrates and swells the brain tissue. The latter is growing from cells that are outside of the brain tissue, such as meninges (meningioma), nerve sheaths (schwannoma, neurofibroma), hypophysis (adenoma and craniopharyngioma), pineal gland (pineocytoma, pineoblastoma), germ cells (germinoma, teratoma, dermoid, epidermoid). Other tumours such as lymphoma and metastasis can grow as extra-axial as well as intra-axial masses.

The multiplanar capability of MR imaging has certainly improved our ability to localise a lesion and make that distinction. Unfortunately, the progress of MR imaging in specificity of brain tumour evaluation still has not paralleled its gains in sensitivity and anatomic localisation. Notwithstanding, MR imaging provides significant information about intrinsic tissue characterisation that the radiologist should exploit for determining tumour type and biological grade. The ability of MRI to discriminate differences in tissue by variations in signal intensities with multiple contrast techniques (i.e., T1, T2, PD, diffusion) parallels at least

gross pathology examination in the majority of cases. The identification of haemorrhagic or necrotic components within the tumour is an important diagnostic and prognostic sign. The association of cysts with certain neoplasms may be helpful for the diagnosis and for planning surgical approach. The presence of fat (hyperintense on T1-weighted images) is specific for certain neoplasms: teratoma, dermoid, lipoma). There are clues and tricks that aid in the diagnosis of fat in tumours. One clue is the recognition of “chemical shift artefact” that is an artefact displayed as signal void at fat–water interfaces and hyperintensity at water–fat interfaces, along the frequency-encoding axis. One trick is the use of fat-selective suppression methods. The recognition of anomalous blood vessels within a presumed neoplasm is another important prognostic sign, because it is diagnostic of a high-grade tumour.

28.3.1

Growth and Signal Intensity Patterns

A very important distinction is made evaluating signal changes at the boundary of the mass: some in- tra-axial CNS tumours are relatively discrete; others are infiltrative. A discrete mass will show a defined transition zone between the lesion and the presumed adjacent brain tissue. An infiltrating mass will have a smoother and ill-defined transition zone with areas with subtle signal abnormalities in the presumed adjacent normal brain tissue. Most CNS tumours express one of these two growth patterns.A list of intraaxial brain tumours subdivided according to their prevalent growth pattern is reported in Table 28.2.

Table 28.2 A list of brain tumours divided according to infiltrative or circumscribed pattern of growth

The characteristic appearance of an astrocytoma (WHO grade II) is that of a diffuse, non-enhanc- ing mass that is hypointense on T1-weighted images and hyperintense on PD-weighted and T2-weighted images. The hallmark of an astrocytoma is that of a highly infiltrative and non-destructive neoplasm with radiologically distinct borders. In young adults an astrocytoma frequently involves the fronto-insu- lar-temporal crossroad (Fig. 28.4.1). Oedema is virtually absent. In those astrocytomas that infiltrate the cortex, the use of fluid attenuated inversion recovery (FLAIR) images better outlines the mass against normal brain cortex, disclosing abnormal signal that reaches the surface of the brain. The distinction between astrocytoma and oligodendrogliomas is often difficult: signal intensity pattern and location are not distinguishing features. The presence of intra-tumoral haemorrhages and/or areas of cystic degeneration in a well-demarcated benign-appear- ing mass are suggestive of oligodendroglioma. The occasional finding of scalloping in the overlying cal-

varia is suggestive of a relatively slow-growing mass. Calcification is more common in oligodendroglioma than astrocytoma,but it is not diagnostic (Fig. 28.4.2). Contrast enhancement is usually mild and poorly defined. It is found in nearly half the cases of low-grade oligodendroglioma (Lee and van Tassel 1989).

28.3.2

Blood–Brain Barrier Integrity Evaluation

The next step in evaluating the signal features of a mass is whether there are signs of blood–brain barrier disruption and immaturity. The brain interstitium is highly dependent on a constant internal milieu. The concept of blood–brain barrier was postulated by Goldmann in 1913 and only later confirmed by electron microscopy studies in 1960. Cerebral endothelial cells have highly differentiated features: tight junctions, continuous basement membranes,

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Fig. 28.4.1a–c. Axial T2-weighted (a) and coronal FLAIR (b) MR images showing a mass located in the left frontal, insular and temporal region. There is no enhancement on post-gadolinium axial T1-weighted MR image (c). The 33-year-old male patient presented with an isolated seizure. The lesion is very close to eloquent language areas. The diagnosis of oligoastrocytoma (WHO II) was made on the neuropathologic specimen after surgery

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narrow intercellular gaps and a paucity of pinocytosis. Endothelial cells are also closely enveloped by astrocytic foot processes.Altogether, these structures form a continuous wall that prevents undesired protein molecules from diffusing from the bloodstream into the interstitium.The capillaries are impermeable to intravascularly injected contrast agents in normal brain and areas of intact blood–brain barrier.

Most discrete intra-axial masses show typically intense “enhancement” after injection of contrast agents, with only few exceptions. The presence of enhancement is not necessarily a sign of poor prognosis in this group. There is a long list of circumscribed masses that show variable degrees of enhancement: pilocytic astrocytoma (Fig.28.4.3),pleomorphic xan-

thoastrocytoma (Fig.28.4.4),subependymal giant cell astrocytoma, dysembryoplastic neuroepithelial tumour (DNET), ganglioglioma, central neurocytoma. It is mandatory to recognise these tumours that have a benign prognosis.

On the other hand, diffuse infiltrating neoplasms start showing scattered signs of enhancement when they are shifting to a higher grade of malignancy. Evidence of blood–brain barrier immaturity often correlates with shorter survival and shorter time to recurrence after surgery. This is particularly true for astrocytoma. Enhancement is present in over 95% of glioblastoma, in over 60% of anaplastic astrocytoma and in less than 10% of grade II astrocytoma. The presence of tumour capillaries deficient in blood–

brain barrier constituents in zones where angiogenesis is most active, rather than destruction of the blood–brain barrier is the most likely explanation for tumour enhancement in glioma. Enhancement is almost always present in metastasis and meningioma. The former enhances since its own capillaries do not have tight junctions and continuous basement membranes. Metastases usually grow at the grey–white matter junction and tend to cavitate when the blood supply becomes insufficient, causing nutrient depletion, and a necrotic core develops. Metastasis is the second most common tumour of the brain, accounting for 30% of intracerebral tumours. In order of

prevalence,the most common primary sites are: bronchogenic carcinoma (50%), breast (20%), colon and rectum (15%), kidney (10%) and melanoma (10%). In about 40% of intracerebral metastasis cases the primary location is unknown at time of diagnosis. In one-third of these cases, the primary site remains unknown despite extensive work-up. Metastases usually present as a ring-enhancing mass lesion (Fig. 28.4.5). They must be differentiated from glioblastoma, lymphoma and abscess.

Meningiomas are generally slow-growing tumours originating from meningothelial arachnoid cap cells. They virtually always enhance, because their capil-

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laries do not have a blood–brain barrier. They are easier to diagnose since they are extra-axial masses that imprint the brain. They account for about 20% of intracerebral tumours. Those with low risk of recurrence and aggressive growth may displace the adjacent brain tissue without inducing any signal change in the brain tissue. The appearance of T2-weighted signal abnormality in the adjacent brain tissue suggests a more aggressive type of meningioma, and this aspect is often observed in “atypical” meningiomas). The hyperintensity is due to the formation of vasogenic oedema with diffusion of serum proteins, probably induced by the metalloproteinases. These proteins are endopeptidases that can degrade the extracellular matrix, break the basal membrane and alter the blood–brain barrier. Thus, they can play a role in tumour invasion and oedema (Nordqvist et al. 2001; Paek et al. 2002).

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Fig. 28.4.4a–c. Axial CT (a) showing a small, round hypodense mass in the cortex in the temporal-parietal region with macroscopic calcification in a 32-year-old female. The discrete, superficial mass shows homogeneous enhancement after contrast injection in the axial (b) SE T1-weighted MR image. The superficial position of this lesion, often invading the leptomeninges, is a diagnostically important feature. The finding of large pleomorphic cells with low mitotic activity, focal xanthomatous changes and vessels with hyalinized walls on the histopathological H&E staining (c) confirmed the diagnosis of pleomorphic xanthoastrocytoma (WHO I)

28.3.3

Tumour Size and Survival

Measuring a mass is often considered a secondary task for most radiologists. However, it is important for evaluating tumour growth and response to multiple treatment strategies. Assessing prognostic variables, tumour size, in particular, is essential to ongoing clinical trials. Patients likely to benefit from a given treatment can be included, while those who may not could avoid receiving related toxicities. The ideal measuring technique should be accurate, easy and low time-consuming to perform, allowing low intra-observer and inter-observer variations. It’s intuitive that a three-dimensional (3D) volumetric measurement method obtained calculating tumour size on all sections would be more accurate than 1D or 2D methods obtained on a single selected section.

However, it is time-consuming. Most internationally accepted protocols devised to standardise response assessment in solid tumours and in supratentorial glioma advise using one-dimensional or two-dimen- sional measurement of tumour size. The 1D technique measures the longest diameter through the enhancing area on the slice showing the largest area of enhancement. The 2D technique measures the 1D measurement multiplied by the longest perpendicular diameter to this through the area of enhancement. Both techniques are indirect measures of tumour bulk and have largely been adopted on the basis of neoplasms’ roughly spherical shape. While this may be the case for most soft-tissue neoplasms, highgrade gliomas are very infiltrating, heterogeneous lesions with irregular shape. Warren et al. investigated

whether 3D rather than 1D or 2D measurements better correlated with responses to treatment in 32 children with primary brain tumours (Warren et al. 2001). They found little difference in the detection of partial responses to treatment, although the results suggested volumetric estimates agreed more closely with clinical estimates of progression-free survival than either 1D or 2D measures.

The prognosis of many systemic solid tumours is inversely related to the size of the original lesion. This is not often the case for brain tumours. The low predictive value of size in high-grade glioma has important implications also to justify indication of surgical cytoreduction. Factors such as age, histologic grade and preoperative Karnofsky performance status can exert a fourfold change in survival, and the potential

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benefit of surgery cannot compensate for a difference of this magnitude. In the literature there are few studies that have determined the relationship between tumour size and prognosis in primary brain tumours. Most of them have evaluated the enhancing component of the mass on T1-weighted MR images of highgrade glioma (Reeves and Marks 1979; Chow et al. 2000; Warren et al. 2001). The findings of these few studies are inconsistent. In 1979 Reeves and Marks (1979) found that lesion size did not predict survival in a population of 56 glioblastoma multiforme (GBM). In 2000 Chow et al. found that enhancing tumour size at the time of recurrence diagnosis was significant for predicting survival following intra-ar- terial chemotherapy in a population of 41 recurrent high grade glioma (Chow et al. 2000). These controversial results might be due to inherent errors of the 1D and 2D methods. Nevertheless, mass size (or volume) will remain one of the most accessible pieces of information provided by neuroimaging. What the neuro-oncologist really needs to know is whether there is evidence of response to chemotherapy in a defined population. For example, if only smaller tumours respond, the maximum size we should treat with a specific chemotherapy protocol has to be determined. These considerations emphasize the need of optimising a standard, accurate, fast and possibly automated technique to include reliable tumour size as an outcome measure.

28.4

MR Spectroscopic Imaging

The excellent soft-tissue contrast of MR makes it the modality of choice for evaluation of mass lesions in the brain.A conventional MR imaging study confirms the presence of an abnormality, determines the location and apparent size of the tumour and assesses the integrity of the blood–brain barrier. In most medical centres neurosurgeons and neuro-oncologists make their management decisions or plan their therapeutic intervention after carefully reviewing anatomical MR images. Although this may be adequate for some lesions, it is recognised that conventional MRI has several limitations: it cannot distinguish tumour from oedema, since they both appear bright on T2weighted images. It cannot accurately define the boundary that separates infiltrating tumour from adjacent functional reactive brain tissue; and it cannot rank in order of malignancy the zones of a heterogeneous tumour.

A. Bizzi et al.

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Fig. 28.7.1 a–c