Radiologic Features of Central Nervous System Tumors

Tumor Permeability

Vascular permeability can be affected by the presence of tumor, due either to direct breakdown of the blood-brain barrier (BBB) or to indirect effect from tumor-related vasoactive secretions. These physiologic changes are responsible for the qualitative lesion enhancement observed on CT scans or T1-weighted MR images obtained after administration of a contrast agent, as a result of extravascular leakage of the contrast agent. Among intra-axial tumors, most aggressive tumors, including metastases, higher-grade astrocytomas, primitive neuroectodermal tumors (PNETs), and lymphomas, enhance. On the other hand, nonenhancing tumors tend to be observed among low-grade tumors such as low-grade astrocytoma and subependymoma. Also, a number of nonaggressive tumors can enhance, including many extra-axial tumors, such as meningiomas and schwannomas, and some intra-axial tumors, including pilocytic astrocytoma, glioneuronal tumors, and a small subset of low-grade gliomas. Contrast enhancement is not specific to brain tumors; other pathologic processes, including infarct, inflammation, and infection, can also affect the integrity of the BBB and thus cause leakage of contrast material to interstitial space. Finally, many high-grade gliomas demonstrate heterogeneous contrast enhancement, with both enhancing and nonenhancing components, as a manifestation of their genetic heterogeneity. The enhancing component typically correlates with more aggressive, high-grade tumor components that should therefore be targets for biopsy or resection in order to optimize treatment planning and achieve the best outcome.

Perilesional Edema

Increase in interstitial water content is one consequence of greater vascular permeability and can manifest as either decreased attenuation on CT or hyperintense signal on T2-weighted or T2–fluid-attenuated inversion recovery (FLAIR) MRI. Evaluation of the edema pattern surrounding brain lesions can also be very helpful in making a diagnosis, because a vasogenic pattern is most commonly observed in peritumoral edema. This pattern is characterized by edema that does not violate the boundary at the gray matter–white matter junction and is easily discernable by visual inspection, because the difference in image intensity between gray matter and white matter is greater on both CT and MRI. This is in contradistinction to the cytotoxic edema pattern, such as in cases of ischemic infarction, in which gray matter is also affected, causing a reduction in contrast (blurring) at the gray matter–white matter junction. Extra-axial tumors, primarily meningiomas and schwannomas, are less frequently associated with edema in adjacent brain parenchyma. Intratumor hemorrhage can also cause rapid expansion of tumor volume and thereby cause secondary edema from compressive effect. Among intra-axial primary brain tumors, edema is typically absent with low-grade astrocytomas, oligodendrogliomas, gangliogliomas, ependymomas, and hemangioblastomas. Although low-grade gliomas typically lack surrounding edema, these tumor tissues can be difficult to distinguish from edema on conventional MRI sequences because of their similarities in high T2 signal. Furthermore, infiltrative tumor and edema can coexist within the same image pixels, such that it is often difficult to determine whether high T2 signal is due to edema or an infiltrative lesion. Nonetheless, low-grade infiltrative tumors tend to have a more indolent clinical course, with slow change in imaging appearance on serial MRI examinations. Edema associated with higher-grade intra-axial brain tumors often evolves rapidly, causes associated symptoms, and may be modulated by therapeutic interventions including administration of steroids. Intra-axial metastases almost always exhibit peritumoral edema, the extent of which is often significantly greater than the actual tumor size. When untreated brain metastases are observed without associated edema, involvement of extra-axial space (i.e., leptomeninges) must be suspected. Finally, edema that occurs in response to radiation therapy is often indistinguishable from edema induced by tumor.

Tumor Vascularity

In addition to increases in vascular permeability observed in a number of brain tumors, intravascular blood volume, or tumor vascularity, can be augmented as a result of tumor-induced angiogenesis. This augmentation creates an increase in tissue microvessel density (MVD) within the tumor that corresponds to greater regional cerebral blood volume (rCBV) on the perfusion imaging study. Estimation of intravascular volume in tumors requires use of dynamic imaging methods, such as dynamic contrast-enhanced MRI (DCE-MRI), dynamic susceptibility contrast MRI (DSC-MRI), arterial spin-labeled MRI (ASL-MRI), and dynamic contrast-enhanced CT. Correlation between rCBV and tumor histologic grades has been demonstrated in astrocytic tumors, but there is wide variability in sensitivity, specificity, and scanning techniques. rCBV maps can help identify focal regions within a brain tumor for biopsy. Perfusion data can be used to differentiate glioma from metastasis and to differentiate tumor recurrence or progression from the similar-looking enhancement that is secondary to posttherapy radiation necrosis. Care must be given to consider vascular lesions such as arteriovenous malformation or venous varix, which can mimic mass lesions with elevated blood volume but often can be differentiated on the basis of morphologic characteristics. Among extra-axial tumors, lower- grade meningiomas often demonstrate markedly elevated cerebral blood volume (CBV) ( Fig. 144.1 ), consistent with its typical angiographic features: early arterial blush and delayed washout.

Tumor Cellularity

Tumor cellularity, or the density of tumor cells per unit volume they occupy, is a prognostic histologic marker. The tumor cell density has been shown to directly correlate with CT attenuation values, with regions of hypercellularity demonstrating hyperdensity. On MRI, apparent diffusion coefficient (ADC) values derived from diffusion-weighted imaging (DWI) have also been correlated with cell density. Hypercellularity typically manifests as reduced diffusivity on the ADC map. In the setting of gliomas, higher-grade tumors typically demonstrate hypercellularity. Tumor cellularity also has diagnostic value in differentiating lesion types, selecting biopsy sites, and evaluating treatment response. For example, central nervous system (CNS) lymphoma is well known for its higher cellularity than other common CNS tumor types ^, ; moreover, management of CNS lymphoma is nonsurgical and based primarily on chemoradiation regimens. Therefore preoperative assessment of tumor cellularity can help define surgical goals in terms of both making the decision regarding biopsy versus resection and determining the biopsy site by targeting the hypercellular component of the tumor. Germinomas and medulloblastomas are also hypercellular, a feature that can aid their diagnoses when patient demographics and tumor locations are considered. ^,

It is important to recognize that these imaging markers of cellularity have limitations—namely, recent intratumor hemorrhage can appear as hyperdensity on CT and, depending on the age of the blood products, the attenuation values may overlap with those of hypercellular tumor. Lack of contrast enhancement can be a useful sign to distinguish between the two. Calcifications can also appear as increased densities within tumor, although in most cases these calcifications are either coarse or stippled and readily distinguished from hypercellular tumors. ADC values of tumor can also be decreased by the presence of blood products and can also be observed in several nontumor processes, such as abscess and infarct, requiring correlation with presenting clinical signs and symptoms, as well as other imaging features.

Tumor Necrosis

Necrosis, generally seen as nonenhancing tissue with irregular and sometimes nodular rim enhancement, is a common imaging feature in high-grade gliomas, particularly in glioblastomas, although necrosis observed in histologic specimens of glioblastomas may not be evident on imaging. Metastasis also frequently demonstrates necrosis and appears similar to glioma when manifesting as a solitary mass. Necrosis is uncommon in lymphomas among immunocompetent patients; in the immunocompromised population, tumor necrosis is much more common and can mimic other brain lesions, such as toxoplasmosis. Following chemotherapy or radiation therapy, necrosis can commonly occur within and around tumor tissues, occasionally accompanied by enlargement of overall tumor size, requiring close imaging follow-up to determine durability of treatment response.

Tumor-Associated Cysts

Cysts are frequently observed in a number of primary brain tumors, including hemangioblastoma, pilocytic astrocytoma, desmoplastic infantile ganglioglioma (DIG), dysembryoplastic neuroepithelial tumor (DNET), ganglioglioma, and craniopharyngioma. Identification of cysts can often narrow the diagnosis to include these tumors when combined with patient’s age, tumor location, and presenting symptoms. When cystic lesions are encountered, it is important to consider infectious causes such as brain abscesses, particularly when the content of cysts shows low diffusivity (hyperintensity) on DWI. Unlike postchemotherapy or postradiation necrosis, which typically indicates treatment response, growth of cysts is often a sign of tumor growth and treatment resistance.

Calcifications

Intratumoral calcifications are frequently found in a number of intracranial tumors, most notably meningiomas, oligodendrogliomas, neurocytomas, and craniopharyngiomas. On CT, calcifications tend to exhibit density greater than 100 HU, and this threshold allows differentiation of calcification from other dense materials including fibrosis and blood products. The signal characteristics of calcification are variable on MRI sequences depending on its chemical environment, but it is often faintly hyperintense on T1-weighted imaging and hypointense on T2-weighted imaging. Calcification is commonly observed in meningiomas and is an imaging marker of lower tumor grade and longer survival. ^, Presence of calcification in an extra-axial mass is also a helpful sign to distinguish meningioma from other extra-axial tumors such as dural metastases. The calcifications of oligodendrogliomas tend to be coarse and, when combined with the typical cortical involvement, allow these tumors to be diagnosed with high specificity. Among brain metastases, mucinous adenocarcinomas from genitourinary or gastrointestinal origins, osteosarcomas, and chondrosarcomas are sometimes associated with intratumoral calcifications. Untreated lymphomas rarely calcify; yet, as with many other tumor types, calcifications commonly occur after lymphoma treatment.

Meningioma

Meningiomas are the most common intracranial extra-axial neoplasm in adults, accounting for about one-third of primary CNS neoplasms in the United States. Meningiomas typically have higher density than normal brain parenchyma on CT, although the difference is small and these tumors can be difficult to differentiate from adjacent cortex without intravenous contrast. On MRI, meningiomas are typically isointense on T1-weighted images relative to gray matter, are slightly hyperintense on T2-weighted images, and demonstrate avid homogeneous enhancement ( Fig. 144.3 ). However, the signal characteristics of meningiomas can be highly variable, occasionally having cystic or necrotic components ( Fig. 144.4 ) and at times exhibiting fatty degeneration ( Fig. 144.5 ). Some reports suggest that syncytial, transitional, and angioimmunoblastic meningiomas may have differing signal intensity characteristics depending on their internal histology. Meningiomas may show stippled or coarse calcifications, which can be an important diagnostic clue for differentiating meningiomas from other malignant extra-axial lesions such as metastasis and lymphoma.

A widely discussed feature of meningiomas is the dural tail (see Fig. 144.3 ), which although highly sensitive for meningioma is not very specific, as it can be see with other neoplasms, such as dural-based metastasis and lymphoma, as well as nontumor etiologies, including sarcoidosis.

Bony hyperostosis can be observed adjacent to many meningiomas, best depicted on CT scans (see Fig. 144.3 ). Although these areas usually represent a reaction by osteoblasts to the tumor, in some cases meningiomas may permeate and expand the adjacent bones. Primarily lytic or destructive bony changes can occur with meningiomas, although these features are more commonly seen with other extra-axial neoplasms, such as hemangiopericytoma/solitary fibrous tumor and metastasis. Meningiomas can rarely invade brain parenchyma directly. The presence of vasogenic edema in association with meningiomas has been correlated with the lesion size as well as the degree of parasitization of dural venous structures.

The proton MRS features of meningiomas include absence of NAA and elevations of choline peaks. Alanine has been suggested to be a specific marker for meningiomas, but with variable sensitivities. On dynamic perfusion MRI, meningiomas typically show slow uptake of the contrast agent followed by its delayed clearance. This prolonged passage of contrast agent results in elevated CBV measurement, which can help differentiate meningiomas from dural metastases.

The blood supply of meningiomas can be evaluated by catheter angiography during preoperative planning. Meningiomas are typically supplied by branches of the external carotid arteries, including the middle meningeal arteries and the stylomastoid branches of the occipital arteries. At certain locations, meningiomas can receive additional blood supply from pial vessels. For example, tentorial arteries from the petrous internal carotid artery (ICA) may supply petroclival meningiomas. Meningiomas adjacent to cavernous sinuses may receive direct blood supply from branches of the cavernous ICAs, whereas those at the foramen magnum may be supplied by branches of the vertebral arteries or posterior inferior cerebellar arteries.

Schwannoma

Schwannomas are the second most common intracranial extra-axial tumor. The majority of intracranial schwannomas occur in the cerebellopontine angle near the internal auditory canal (IAC), arising most often from one of the vestibular branches of the eighth cranial nerve. In this location, meningiomas are the other common tumor type that can have MR signal characteristics similar to those of vestibular schwannomas and can occasionally extend into the IAC, although they can be distinguished by the presence of dural tails. Vestibular schwannomas typically have components both within the IAC and within the posterior fossa cerebellopontine angle. They occasionally cause characteristic smooth widening of the IAC ( Fig. 144.6 ). In addition, vestibular schwannomas can contain cyst(s), necrosis, or hemorrhage and occasionally cause edema in adjacent brain tissue. Vestibular schwannomas can be discovered incidentally as small enhancing nodules within the IAC, although these small schwannomas are difficult to distinguish from other cause of perineural enhancement, such as neuritis, meningitis, and leptomeningeal metastases, requiring clinical correlation and often follow-up imaging. Occasionally, vascular loops or aneurysm formed by anterior inferior cerebellar arteries in the IAC can mimic tumor, particularly on low-resolution imaging, but can be distinguished by high-resolution MR or CT angiography.

Schwannomas of other cranial nerves have imaging characteristics similar to those of vestibular schwannomas, but they can be distinguished by location and by the orientation of tumor growth. For example, trigeminal schwannomas track along a horizontal course from the lateral pons toward the Meckel cave inferolateral to the cavernous sinus. When these tumors extend extracranially through the foramen ovale, smooth widening of the bony foramen is typical. Schwannomas of the third, fourth, and sixth cranial nerves may manifest in the basal cisterns or within the cavernous sinus. When confined to the cavernous sinus, schwannomas can be difficult to distinguish from cavernous sinus meningiomas. Seventh cranial nerve schwannomas may occur in the cerebellopontine angle cistern, the IAC, or the temporal bone. They rarely are seen at the stylomastoid foramen region or in the parotid gland. Schwannomas of the 9th, 10th, and 11th cranial nerves are rarely seen in the intracranial compartment, but when they occur, they usually erode portions of the jugular foramen. Ninth cranial nerve schwannomas, in particular, occur more frequently in the intracranial compartment than in the head and neck region. Schwannomas of the 12th cranial nerves can cause widening of the hypoglossal canal and can be associated with clinical symptoms of tongue weakness as well as imaging findings of tongue atrophy. When multiple intracranial schwannomas are identified, neurofibromatosis type 2 should be highly suspected, and efforts should be made to search for other potentially associated intracranial tumor types, including meningiomas and ependymomas. This disease is termed MISME (multiple inherited schwannomas, meningiomas, and ependymomas) syndrome.