Advanced Imaging Techniques

Determining where an intracranial lesion is located is fundamentally important to both the neuroradiologist and the neurosurgeon because it is often the case that the histologic category of the lesion can be accurately predicted on the basis of its location. In recent years, however, it has also become possible to localize the regions of likely maximal malignancy within the lesion as well as to depict with increasing accuracy the relationship of the lesion to surrounding structures. These efforts are typically undertaken to optimize the surgical path to the mass and to reduce or at least to predict surgically related morbidity.

The fundamentals of lesion localization have not changed very much over the years, although the tools for doing so have made the task easier. The fundamental determination to be made remains whether the lesion is within the brain parenchyma or is extra-axial.

Beyond standard computed tomography (CT) and magnetic resonance imaging (MRI), techniques for characterizing the nature of the lesion include magnetic resonance spectroscopy (MRS) and regional cerebral blood flow and blood volume estimates. Functional MRI (fMRI) and more recently developed diffusion tensor imaging (DTI)-based techniques such as magnetic resonance tractography have been shown to be helpful for depiction of functionally important cortical regions and white matter tracts in the vicinity of either the lesion itself or the surgical path toward the lesion.

Spectroscopy

MRS provides information regarding the biochemical milieu within a relatively small volume of interest. Although it began, and is often still used, as a single voxel technique—gathering data from a usually cubic volume measuring between 1 and 2 cm—more modern implementations of MRS allow for acquisition of MRS data from arrays of smaller voxels (usually about 1 cm³ depending on the technical attributes of the imaging system) localized in multiple coplanar sections. These MRS imaging techniques can provide information on spatial variation in biochemical markers that can be used to distinguish among different types of tumors, and that can roughly index a lesion’s degree of malignancy (Fig. 109-1). Among the major markers are N-acetyl aspartate (NAA), choline, creatine, myoinositol, lactate, and lipid. Relevant spectroscopic features of different lesions are discussed throughout this chapter, but a general rule of thumb is that the more malignant the lesion, the lower the NAA and the higher the choline concentrations.

FIGURE 109-1 Spectroscopic analysis of a left periatrial glioblastoma multiforme (GBM). A, Axial fluid-attenuated inversion recovery (FLAIR) images demonstrate elevated signal in the left periatrial region. The choline (Cho) and creatine (Cr) maps show hyperintensity in this region, corresponding to elevated levels of these metabolites, whereas the N-acetyl aspartate (NAA) map shows collocated signal hypointensity, reflecting reduced NAA. B, Individual voxels from the spectroscopic imaging maps, with one voxel over the region of abnormality on the left and the other over the contralateral, normal, right periatrial white matter. C, A normal spectrum. D, Characteristic spectrum from a high-grade tumor, with marked elevation of choline, lesser elevation of creatine, and marked reduction in NAA.

(Spectroscopic data courtesy of Dr. Peter Barker, Johns Hopkins University.)

Cerebral Blood Flow and Volume Estimates

Measures of cerebral blood flow (CBF) and cerebral blood volume (CBV) within tumors using MRI^1–4 or, more recently, CT^5,6 provide quantitative correlates of what has been known since cerebral angiography as one of the mainstays for brain tumor localization and characterization, that is, that tumors frequently contain dysplastic blood vessels that exhibit blood (contrast) transit time that is markedly slower than is that within the surrounding parenchyma. In the case of many tumors, catheter angiography would demonstrate a tumor blush, indicative of an abnormally enlarged blood pool. MRI or CT perfusion data correlate reasonably well with tumor grade, with higher grade tumors exhibiting greater CBV.^1,7–9 There is also some evidence that blood volume measurements have prognostic value, with low-grade tumors that have higher blood volumes advancing in grade more rapidly than tumors with similar histology but lower blood volumes.¹⁰

Functional Magnetic Resonance Imaging

The early 1990s saw the development of imaging techniques which could assay dynamic changes in blood flow and blood oxygen extraction as a proxy for regional brain neural activity.^11,12 These techniques became known as fMRI and were based on the observations that the concentration of deoxyhemoglobin in blood affected the nuclear magnetic resonance parameter known as T2*—with a higher concentration being associated with a shorter T2*¹³—and that with brain activation, there is an increase in regional cerebral blood flow out of proportion to the increase in oxygen extraction.¹⁴ With regional brain activation, the disproportionate increase in blood flow compared with oxygen extraction leads to a higher concentration of oxyhemoglobin in the venous efflux and thus a reduced concentration of venous deoxyhemoglobin. The reduced concentration of deoxyhemoglobin and concomitant prolongation of T2* leads to a regional task-related increase in signal.

Fundamentally, all fMRI experiments rely on comparing signal intensities measured with and without presumed brain activation and mapping those regions where signal changes correlate with the temporal profile of the activation paradigm. In most cases, the experiments are set up in a so-called block design, in which epochs or blocks of task (e.g., finger movement or speech-related tasks) are alternated with epochs of rest, or at least activity not directly related to the task.

Soon after its introduction, investigators proposed fMRI as a tool in preneurosurgical planning¹⁵ and established that its ability to localize primary sensorimotor cortex compared reasonably well with electrophysiologic techniques.^16–19 In the neurosurgical setting, the earliest and probably still most common applications of fMRI have been in localizing the hand-arm representation in the primary sensorimotor regions, although with the development of a broad array of paradigms, interrogation of language-related brain regions has become virtually as common (Fig. 109-2). fMRI has been shown useful in demonstrating the degree to which regions of eloquent cortex have been displaced by tumors or have undergone reorganization because of regional cortical dysplasia or dysfunction.^20,21 In 1999, Lee and colleagues at the Mayo Clinic published a summary of their experience using fMRI in the setting of presurgical evaluation of tumor and seizure patients.²¹ They found that they were able to use fMRI to identify the primary sensorimotor region in 70% of patients; their success rate was close to 90% when they considered only the patients they evaluated using more recently developed data acquisition techniques.

FIGURE 109-2 Functional MRI results obtained with cued bilateral finger movements (A) and verb generation (B) in a 22-year-old patient with a left parietal giant cell ependymoma (white arrow in left upper image).

Like any technique, fMRI does not always work; the patients who are being evaluated frequently move more than healthy volunteers, which will almost certainly have an adverse effect on the quality of the data,²² as will reduced vasoreactivity in the vicinity of tumors or vascular malformations. As techniques have improved over time, especially for rapid data acquisition and for patient motion correction, the applicability of fMRI as a neurosurgical planning tool has increased.

Diffusion Tensor Imaging and Tractography

Although fMRI to estimate the proximity of functional cortex to a tumor has been available since the mid-1990s, techniques for estimating the proximity of major white matter tracts have developed much more recently, and as of this writing (mid-2008) remain under active development. These techniques are based on the biophysical observation that water molecules within axons move in a relatively unconstrained manner longitudinally along the length of the axon, whereas those molecules can move only a short distance radially before they encounter either microtubules or the axonal membrane.^23–26 Thus, if one were to measure and plot within any given imaging voxel the ability of water molecules to move in a relatively unconstrained way, one would end up with a blimp or cigar-shaped plot, oriented roughly along the axes of the axons that run through that voxel. This plot represents graphically what is known mathematically as the diffusion tensor. Conceptually, by assessing the directionality of water diffusivity in each small imaging voxel and then linking the measures of maximal diffusivity end to end, one can begin to discern the trajectories of white matter tracts as they run through the brain (Fig. 109-3, and Fig. 109-4 for a clinical example). Ongoing technical developments include improvements in tracking white matter bundles through edema surrounding tumors (and even through tumors) and in separating white matter tracts that closely approximate one another, or that cross one another within a group of voxels.^27–31

FIGURE 109-3 Diffusion tensor imaging (DTI) and tractography. A, Spherical representation of the diffusion tensor that one would find without the directionality imposed by a white matter tract. B, Elongated diffusion tensor representation, with the long axis of the ellipse corresponding to the dominant direction of the axons (thin tubes) within the voxel. C, Approximate trajectory of a white matter tract (red line) estimated by linking end to end a series of elongated diffusion tensor representations such as depicted in B.

FIGURE 109-4 Tractography in a patient with a right cerebral hemisphere glioblastoma multiforme. A, Axial T2-weighted images showing cross sections of the tractographic representations of the left (pink) and right (blue) corticospinal tracts at the level of the mass. Note the medial and anterior displacement of the right tract due to mass effect from the tumor. B, Reconstruction of the tracts, showing medial displacement of that on the right due to the mass.

Often fMRI and DTI-tractography results can be used complementarily because in the vicinity of brain tumors or vascular malformations, the coupling between neural activity and the reactive changes in blood flow on which fMRI signal changes depend is often impaired. In such cases, the fMRI data may be of reduced utility, whereas the tractographic data may still be quite robust (Fig. 109-5). Conversely, extensive edema may render the tractographic data suboptimal, whereas the fMRI signal changes in the overlying cortex remain relatively unaffected.

FIGURE 109-5 Functional magnetic resonance imaging (fMRI) (A) and DTI-based tractography (B) in a patient with a left occipital arteriovenous malformation. The patient’s visual fields are completely intact bilaterally, yet multiple visual fMRI tasks resulted in markedly asymmetric signal change, presumably because of impaired vasoreactivity in the vicinity of the lesion. The tractographic data, however, show slight lateral displacement of the optic radiations. These data aided in surgical planning for lesion resection.

The additions of advanced neuroimaging techniques notwithstanding, the first decision a neuroradiologist must make when evaluating an intracranial mass is whether the lesion is intraparenchymal or extra-axial. Extra-axial masses frequently exhibit at least some of the following characteristics:

Although each of these findings may also be identified with lesions that are intracranial (especially infiltration of or reaction by the overlying bone and relative absence of vasogenic edema), a combination of these features would suggest an extra-axial process.

Among the extra-axial processes, five are most common: meningioma, schwannoma, lymphoma, metastases, and granulomatous diseases (most notably sarcoidosis). Schwannomas occur in stereotypical locations associated with cranial nerves and rarely have dural tails of enhancing tissue arising from the margins of the lesion. In the case of dural or epidural metastases and dural lymphoma, the clinical picture usually suggests the diagnosis because of prior histories of a primary malignancy, systemic lymphoma, or HIV disease (although intraparenchymal central nervous system [CNS] lymphoma is far more common than dural-based lymphoma in the AIDS setting). Sarcoidosis may affect the pia, dura, or parenchyma and will commonly have pulmonary manifestations. It may elicit more of a parenchymal inflammatory and edematous reaction than the other diagnoses. Other granulomatous diseases such as tuberculosis or fungal infection are differentiated based on systemic symptoms. In the end, meningiomas still predominate in the extra-axial compartment, and unless there are unusual features as described previously, this is the most likely diagnosis to consider. Particularly with a dural tail and fine calcification or bony reaction, meningioma is the top choice.

Features that suggest that masses are intra-axial include the following:

When lesions grow through the margins of the dura, as in some aggressive meningiomas or cases of glioblastoma multiforme (GBM), the analysis of these lesions becomes much more difficult.

These caveats aside, the presence of necrosis, edema, and calcification and the location are the main factors that suggest a specific histologic classification. Most higher grade astrocytomas, primitive neuroectodermal tumors (PNETs), and lymphomas enhance. If a lesion does not enhance, one is likely to be dealing with a low-grade astrocytoma (pilocytic astrocytomas excluded), ganglioglioma, or subependymoma. Absence of enhancement virtually excludes metastases, hemangioblastomas, and GBM.

Necrosis is often evident in high-grade astrocytomas and usually implies a GBM. Although lymphomas in the non-AIDS population rarely show necrosis, such necrosis is much more often seen in AIDS-related CNS lymphomas. Metastases often demonstrate central necrosis. Often one must distinguish among cyst formation (seen frequently in hemangioblastoma, pilocytic astrocytoma, desmoplastic infantile ganglioglioma [DIG], dysembryoplastic neuroectodermal tumor [DNET], and ganglioglioma) and necrosis. The latter is usually much more irregular and elicits more edema in the surrounding tissue.

Edema may be absent with low-grade astrocytomas, gangliogliomas, DIGs, ependymomas, hemangioblastomas, some PNETs, and some DNETs. The lesions with the greatest degree of edema are the lymphomas, glioblastomas, and metastases. A lesion such as gliomatosis cerebri may infiltrate without evoking edema. Most lesions that evoke edema also produce mass effect unless they are merely infiltrating the cortex like gangliogliomas and DNETs.

Calcification occurs frequently with oligodendrogliomas, neurocytomas, and craniopharyngiomas. Nonetheless, by virtue of their higher incidence, astrocytomas still represent the most common calcified tumor. The calcification of an oligodendroglioma tends to be coarser than the more stippled calcification of astrocytomas. The metastases that calcify include mucinous adenocarcinomas, osteosarcomas, and chondrosarcomas.

Finally one must assess location. A lesion confined to or based predominantly in the gray matter likely represents a ganglioglioma, DNET, cortical dysplasia, or pleomorphic xanthoastrocytoma. Lesions that cross the corpus callosum are usually high-grade astrocytomas or lymphoma. Metastases do not as a rule cross the corpus callosum. Hemangioblastomas usually occur in the cerebellum, often bordering on the pia. Neurocytomas are found most commonly along the septum pellucidum. Oligodendrogliomas favor the temporal lobes, as do DNETs, DIGs, and pleomorphic xanthoastrocytoma. Clearly, the differential diagnosis of a pineal region mass differs from one in the suprasellar region (although germinomas and meningiomas may break that rule) or one that is in the ventricle. Location is a critical piece of the analysis.

This initial review offers insight into the framework that is used to diagnose most intracranial masses, with the understanding that radiology rarely preempts a histologic specimen, particularly for the intra-axial masses.

Meningioma

By far, the most common extra-axial neoplasm to affect the intracranial compartment is the meningioma. This tumor is characterized by hyperdensity relative to normal brain parenchyma on CT, isointensity on T1-weighted images relative to gray matter, and slight hyperintensity on T2-weighted images (Fig. 109-6). It should be noted, however, that there is a wide variety of signal intensity characteristics associated with meningiomas, and in fact, some reports suggest that syncytial, transitional, and angioimmunoblastic meningiomas may have differing signal intensity characteristics depending on their internal histology. Nearly all meningiomas show strong contrast enhancement on either CT or MRI. Meningiomas may show stippled or confluent calcification. If the meningioma is extensively calcified, enhancement may be less evident.

FIGURE 109-6 Planum sphenoidale meningioma. A, Much of the mass on this unenhanced sagittal T1-weighted image demonstrates signal that is close to isointense to brain parenchyma (arrow) but is sharply demarcated from the immediately overlying rostrum and genu of the corpus callosum. B, On the axial T2-weighted image, the mass is again seen to displace (arrows) rather than invade or arise from the brain parenchyma. Except for the center of the mass, much of it exhibits T2-weighted signal close to that of the surrounding brain. C, Coronal postgadolinium T1-weighted image shows the marked enhancement and a small dural tail (arrow) projecting leftward from the base of the mass.

Meningiomas also have a characteristic “dural tail,” which represents contrast enhancement extending along the margins of the tumor affecting the pachymeninges (Fig. 109-7). Some histologic studies have suggested that the entirety of the dural tail represents meningioma tumor, whereas others have suggested that this may represent reactive change adjacent to neoplasm.³²

FIGURE 109-7 Convexity meningioma. This lesion, which has extended extracranially (black arrow), as well as intracranially, demonstrates a “dural tail” (white arrows) that extends down over the right hemispheric convexity.

Bony lysis or sclerosis may be seen in about 30% of patients who have meningiomas. Viewing the CT scans using bone windows may be useful in detecting the increased density and overgrowth of the bone and the lytic areas adjacent to the meningioma. Although these areas usually represent a reaction by osteoblasts to the tumor, in some cases the meningioma may permeate the bone.

The spectroscopic features of meningioma on proton spectroscopy include absence of NAA and elevations of choline peaks. The height of the NAA and creatine peaks may be markedly reduced. Alanine has been suggested to be a specific marker for meningiomas, but its presence is variable.^33–35 Although this may help differentiate a meningioma from an intra-axial mass, many other extra-axial masses (see later) have a similar spectroscopic signature.

Meningiomas may deviate from the characteristic benign appearance in many different ways and on occasion demonstrate necrosis, fatty degeneration, cystic areas, infiltration into the brain, infiltration into the bone, and marked vasogenic edema.³⁶ The presence of vasogenic edema associated with meningiomas has been correlated with the lesion size as well as the degree of parasitization of dural venous structures.

On dynamic imaging with contrast agents, the meningiomas show slow uptake of the contrast agent in a continuous fashion followed by a lengthy period of stable enhancement and a delayed clearance of the contrast agent. MRI-based estimates of CBV has been shown to help differentiate between meningioma and dural-based metastatic deposits, with the meningiomas typically showing substantially greater CBV.³⁷ Angiographically, dural vessels generally supply the lesions. This usually means that the branches of the external carotid artery, including the middle meningeal artery or stylomastoid branches of the occipital artery, supply the mass. Nonetheless, branches of the tentorial artery from petrous carotid meningeal branches may be responsible for the primary supply of tentorial meningiomas. Similarly, meningiomas around the cavernous sinus may have direct carotid branches supplying the lesion. Meningiomas at the foramen magnum may receive blood supply from branches of the vertebral artery or posterior inferior cerebellar artery.

Schwannoma

The next most common extra-axial mass is the schwannoma, dominated by those that occur in and around the internal auditory canal. This lesion characteristically resides in the cerebellopontine angle or in the internal auditory canal, arising most often from the vestibular branches of the 8th cranial nerve (Fig. 109-8). Its imaging characteristics are similar to those of a meningioma from the standpoint of being relatively isointense to gray matter, but the absence of a dural tail usually helps to distinguish these two lesions. Vestibular schwannomas, however, may show cystic degeneration as well as hemorrhage and occasionally cause edema in adjacent brain tissue. As opposed to meningiomas, it would be highly unusual for an acoustic schwannoma to cause bony lysis or bony sclerosis. In particular, if a cerebellopontine angle lesion shows enhancing tumor entering the internal auditory canal, one would favor vestibular schwannoma over meningioma.

FIGURE 109-8 Vestibular schwannomas. A, T2-weighted axial image showing small soft tissue intensity mass (arrow) near the fundus of the left internal auditory canal, along with axial (B) and coronal (C) postgadolinium T1-weighted images. D, Axial T2-weighted image of a vestibular schwannoma from another patient, showing the widened cerebrospinal fluid spaces around the lesion, characteristic of an extra-axial mass, as well as the foci of elevated signal within the mass representing cystic degeneration.

Schwannomas of other cranial nerves, particularly of either the 7th or the 5th cranial nerve, are the next most likely extra-axial masses to arise from the cerebellopontine angle region or from the lateral pons. They have imaging characteristics similar to those of vestibular schwannomas, but they may be distinguished by virtue of their location and plane of growth. Schwannomas of the 5th cranial nerve will, as expected, track along this nerve on its trajectory from the lateral aspect of the pons and are oriented toward the Meckel’s cave region inferolateral to the cavernous sinus. Some branches of the 5th cranial nerve may show contrast enhancement within the cavernous sinus or the pterygopalatine fossa. The 7th cranial nerve schwannomas may occur in the cerebellopontine angle cistern, the internal auditory canal, 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, present more frequently in the intracranial compartment than in the head and neck region. Schwannomas of the 3rd, 4th, and 6th cranial nerves may present in the basal cisterns or within the cavernous sinus. In the cavernous sinus, these are difficult to distinguish from cavernous sinus meningiomas. All schwannomas tend to enhance avidly.

Epidermoid

Epidermoid tumors may arise in the cerebellopontine angle, the suprasellar cistern, the diploic space, the peripineal region, or the middle cranial fossa. These lesions do not as a rule exhibit contrast enhancement. Epidermoids have signal intensity appearances that are pathognomonic: (1) very high signal intensity on T2-weighted images, (2) signal intensity close to that of cerebrospinal fluid (CSF) on T1-weighted images, (3) higher signal intensity than CSF on fluid-attenuated inversion recovery (FLAIR) MRI and diffusion-weighted imaging (DWI), (4) restricted diffusion that typically is depicted as low signal on apparent diffusion coefficient (ADC) images, and (5) absence of enhancement (Fig. 109-9). Epidermoid lesions tend to have a crenated margin and will infiltrate adjacent structures, particularly along the brainstem. The usual differential diagnosis with the epidermoid is the arachnoid cyst. Epidermoids can be distinguished from the latter because arachnoid cysts are as dark as CSF on FLAIR, diffusion, and steady-state free precession imaging. The signal intensity of epidermoids will not simulate CSF on these sequences.³⁸ The arachnoid cyst is also more sharply delineated than is the epidermoid.

FIGURE 109-9 Epidermoid. A, Contrast-enhanced axial T1-weighted image demonstrates right cerebellopontine angle mass (arrow), showing close to cerebrospinal fluid (CSF) intensity signal on this sequence, and no postcontrast enhancement. B, Fluid-attenuated inversion recovery (FLAIR) image, showing the same lesion demonstrating signal intensity somewhat higher than CSF. C, On diffusion-weighted image, the lesion is hyperintense, whereas on the apparent diffusion coefficient map calculated from the diffusion data (D), the lesion (short arrow) is significantly lower in intensity than is the CSF in the fourth ventricle (long arrow).

Proton spectroscopy may help in some instances of cystic masses in the brain. Although cystic astrocytomas show NAA, choline, and creatine peaks (with or without lactate), epidermoid cysts show only lactate signal. There are no identifiable resonances from arachnoid and porencephalic cysts.³⁹

Arachnoid Cyst

Arachnoid cysts tend to occur in a similar location as epidermoid tumors, but they are relatively frequently seen in the anterior aspect of the middle cranial fossa. In this location, they must be distinguished from atrophy-related dilation of the subarachnoid space. In many instances, this can be determined merely by the displacement of the blood vessels associated with an arachnoid cyst, whereas dilation of the subarachnoid space does not displace the vessels, which are seen coursing through the CSF. Additionally, arachnoid cysts may remodel and thin the bone, which would not be seen with atrophy and subarachnoid space dilation (in fact, the bone may become thicker in younger subjects). Its CSF density and intensity on all pulse sequences distinguishes the arachnoid cyst from the epidermoid tumor. It also does not enhance. One may see pulsation artifacts within an arachnoid cyst, which are not seen in an epidermoid tumor.

Germinomas and Germ Cell Tumors

More than half of germinomas are denser than normal brain tissue on CT, and the remainder are isodense. Sometimes, the tumoral tissue surrounds the normal pineal gland, resulting in an engulfed appearance to the calcification (Fig. 109-10). Isointensity to low intensity on T1- and T2-weighted MRI is also the norm. Avid homogeneous enhancement characterizes germinomas. Cystic change occurs in 33% of pineal region, 28% of suprasellar, and 80% of basal ganglionic germinomas.^40,41 CSF seeding occurs in 50% of pineal region, 28% of suprasellar, and 30% of basal ganglionic germinoma. Response to radiation therapy may be dramatic, with scans showing no evidence of tumor within 2 weeks after completion of radiation therapy.⁴⁰ In some instances, complete resolution may not take place for 6 months after radiation. With treatment, the tumor may become hypodense and brighter on T2-weighted and FLAIR images. The presence of cystic change portends a worse response to radiation therapy (33% complete resolution if the mass is cystic, versus 90% without a cyst).

FIGURE 109-10 Germinoma. This CT scan shows a hyperdense mass (black arrows) in the pineal region engulfing the calcified pineal (white arrow). There is mild ventricular prominence, probably on the basis of obstruction of the cerebral aqueduct.

Teratomas, choriocarcinomas, endodermal sinus tumors, and embryonal cell tumors are also among the germ cell line tumors occurring around the pineal gland. Fat characterizes the teratoma and dermoid tumors—low in density on CT and bright on T1-weighted MRI. Choriocarcinomas have a high rate of hemorrhage, both in primary sites and in metastatic deposits. These lesions may also be distinguished based on serology and hormonal markers.

Pineal Cell Tumors

Pineocytomas and pineoblastomas are the primary pineal cell tumors of the CNS. Pineoblastomas are sometimes placed in the classification of primitive neuroectodermal tumors. They are often slightly hyperdense on CT and of low intensity on long repetition time (TR) MRI sequences, similar to germinomas. This low signal intensity on T2-weighted imaging probably reflects some combination of hypercellularity and calcification. Calcification is much more common with pineal cell tumors than with germinomas. Both enhance avidly. Subarachnoid seeding may occur with pineoblastomas but is uncommon with pineocytomas, which take a less malignant course. Pineocytomas may have cystic components and may appear like a complex benign congenital pineal cyst.

Sellar Lesions

Pituitary adenomas are tumors that arise in the sella and are typified by their characteristic location within or engulfing the pituitary gland. Although microadenomas (<10 mm) may not show bony abnormalities and may present purely as an intrapituitary area of abnormal density or intensity, a pituitary macroadenoma usually depresses the floor of the sella or extends upward into the suprasellar cistern. Both microadenomas and macroadenomas may show hemorrhagic transformation, appearing bright on T1-weighted MRI. On administration of gadolinium, most pituitary microadenomas show decreased enhancement amid the highly enhancing pituitary gland. Macroadenomas, however, enhance slightly throughout. When evaluating a patient for a pituitary adenoma, one should always examine the optic apparatus to determine whether it is compressed by the tumor. This may occur at the prechiasmal, chiasmal, or postchiasmal level. In addition, one should evaluate the cavernous sinuses. Invasion of the cavernous sinus may be associated with higher hormonal levels and a more difficult surgical approach. Tumors that project laterally to a vertically oriented line bisecting the two turns of the ipsilateral cavernous carotid artery are likely to have invaded the cavernous sinus. To make this evaluation, the unenhanced MRI is usually the most appropriate study. In the parasellar region, pituitary adenomas may encircle the internal carotid arteries. They are distinguished from meningiomas that do the same by the fact that pituitary adenomas, because they are relatively soft, generally do not decrease the size of the lumen of the vessel, whereas meningiomas often narrow the carotid artery.

The most common suprasellar lesion is extension of a large pituitary macroadenoma out of the sella through the diaphragma sella. Nonetheless, one should consider a craniopharyngioma in this location. Craniopharyngiomas often have cystic degeneration or calcification (with a higher rate in the adult population than in the younger age group). The cyst of the craniopharyngioma may be hyperintense on T1-weighted scans. This may be due to the high protein content associated with the cyst or to hemorrhage. When one does not see a solid nodule or calcification, Rathke’s cleft cysts enter the differential diagnosis.

Other sellar/suprasellar neoplasms include diaphragma sella meningiomas, germ cell tumors, hypothalamic and chiasmatic astrocytomas, and Langerhans’ cell histiocytosis. It is also important to consider the possibility of a cavernous carotid artery aneurysm, especially if the lesion is eccentric or exhibits the signal characteristics suggestive of turbulent flow. Mixed signal intensity in a partially thrombosed aneurysm may be confusing. Phase-related ghosting artifact, signifying flow, may be a helpful subtle finding to that end.

Choroid Plexus Papilloma

The choroid plexus papilloma is characterized by its frond-like borders, avid contrast enhancement, and characteristic location at the glomus of the lateral ventricle (80% of childhood choroid plexus papillomas).⁴² In patients younger than 2 months, choroid plexus papillomas account for 42% of brain tumors. Hydrocephalus is the norm from overproduction of CSF, gross obstruction of outlets, or arachnoidal adhesions from high protein or blood associated with the mass. Choroid plexus papillomas are hyperdense on unenhanced CT and demonstrate calcification in nearly 25% of cases.⁴² Fourth ventricular choroid plexus papillomas also may occur and are generally seen in an older population than are the lateral ventricular ones. These lesions are highly vascular, and one can see flow voids or calcifications as low signal intensity areas within the lesions.⁴²

The differential diagnosis of choroid plexus papilloma should include meningioma of the glomus region. The two have similar imaging characteristics, but meningiomas usually occur in elderly patients and usually have more homogeneous signal intensity. In the differential diagnosis of lesions around the glomus of the lateral ventricle, one should also consider metastases, and rarely lymphoma and astrocytoma.

Ependymoma

Ependymomas arise from the ependyma of the ventricular system. These are most frequently seen in the posterior fossa associated with the fourth ventricle. They tend to fill the fourth ventricle and enlarge it (as well as the foramina of Luschka and Magendie), which distinguishes them from medulloblastomas, which tend to displace the fourth ventricle and efface it. Ependymomas may grow through the exits of the ventricle, a feature that is unusual for medulloblastomas. From the posterior fossa, the tumor may grow into the cerebellopontine angle cisterns, the cisterna magna, or the foramen magnum to get to the cervical region.

As many as 40% of ependymomas in the pediatric population calcify. Although the noncalcified portion of the tumor is usually isodense to brain tissue on CT, stippled calcification may create the appearance of hyperdensity. Cyst formation is unusual, but ependymomas may show intratumoral hemorrhage. Their contrast enhancement is usually mild.

When ependymomas arise in the supratentorial compartment, they may appear in the peripheral parenchyma unassociated with the ventricular system. In the supratentorial compartment, the lesions may show ring enhancement with central necrosis and may simulate a higher grade astrocytoma. Thus, ependymoma is a tumor that may grow intra-axially (supratentorial) or extra-axially (infratentorial).

Ependymomas have lower NAA-to-choline ratios than do astrocytomas, but the creatine-to-choline ratio is higher for ependymomas (0.60 ± 0.20) than for astrocytomas (0.27 ± 0.12) and primitive neuroectodermal tumors.⁴³ Elevated lactate levels are not uncommon in ependymomas.

Subependymomas

Subependymomas are benign tumors, which again may be seen in association with the ventricular system. They may have signal intensity and density similar to that of gray matter. As opposed to ependymomas, these lesions do not routinely show contrast enhancement, although they can.⁴⁴ They may have focal mass effect but usually do not elicit vasogenic edema. Characteristic locations include in the floor of the fourth ventricle, along the septum pellucidum, or along the lateral ventricular ependyma. Calcification is rare.

Neurocytomas

Neurocytomas usually arise along the septum pellucidum and previously were often misclassified as intraventricular oligodendrogliomas. They show a high rate of calcification and have variable enhancement (Fig. 109-11). Their course is usually benign. Rare extraventricular neurocytomas have been reported in the temporal lobe.⁴⁵

FIGURE 109-11 Neurocytoma. Magnetic resonance image of central neurocytoma. Fluid-attenuated inversion recovery (A) and postcontrast T1-weighted (B) axial images of a central neurocytoma projecting from the septum pellucidum into the anterior body of the left lateral ventricle.

Other Intraventricular Lesions

Lesions such as intraventricular oligodendrogliomas, metastases, and germinomas may arise in the ventricles or along the septum pellucidum.

Miscellaneous Extra-axial Lesions

The less common causes of extra-axial lesions in the intracranial compartment include subarachnoid seeding (which may be from a primary CNS lesion, the lymphoma-leukemia spectrum of lesions, or a primary tumor outside the CNS), lipomas (more accurately a congenital lesion rather than a neoplasm), dermoid tumors (characterized by fatty density and a propensity for rupture and seeding fat droplets into the CSF space; Fig. 109-12), and hemangiopericytoma (effectively an aggressive malignant meningioma). Sarcoidosis may mimic an extra-axial tumor and has the same imaging features as most lymphomas and meningiomas.

FIGURE 109-12 Dermoid. This axial T1-weighted image shows a large right inferior frontal mass (white arrow) demonstrating predominantly signal hyperintensity, which is also evident in the anterior aspects of both lateral ventricles (black asterisks). This high signal represents fat that is floating on the water-density cerebrospinal fluid in the more posterior parts of the ventricles, as the patient is supine.

Astrocytomas

The recent World Health Organization (WHO) classification of astrocytomas separates the lesions into focal (benign) astrocytomas, nonfocal astrocytomas, anaplastic astrocytomas, and GBM. Such distinctions are rarely this clear based on neuroradiology studies. In many ways, the best way to grade a tumor by imaging is to check the patient’s age, the presence or absence of necrosis, the degree of vascularity, and the margins of the mass.

Glioblastoma Multiforme

GBM is characterized by irregular infiltrating margins, poor demarcation, extensive edema, necrosis, and hypervascularity (seen as flow voids on standard imaging or high perfusion on gadolinium-enhanced CBV studies; Fig. 109-13).⁴⁶ Others have found that intratumoral hemorrhage correlates well with histologic grade.⁴⁷ The aggressiveness of a GBM may be suggested by its infiltration through white matter bundles (particularly the corpus callosum) and its growth into the ependyma or subarachnoid space, or both. Nearly all GBMs show contrast enhancement, but that enhancement may be irregular, nodular, or ring-like in its appearance. The absence of enhancement would argue against GBM in all but the gliomatosis cerebri forms of this tumor.⁴⁸

FIGURE 109-13 Glioblastoma multiforme (GBM). Axial T2-weighted image (A) demonstrates a large centrally necrotic mass that extends into and expands the splenium of the corpus callosum (arrow). Axial (B) and coronal (C) postgadolinium T1-weighted images show the irregular peripheral enhancement frequently seen in GBM.

Gliomatosis cerebri is often multilobar with associated involvement and enlargement of deep gray structures.⁴⁸ Brainstem and cervical cord extension may be present. Underlying structures show preservation of overall shape with a paucity of edema. CT studies may appear normal,⁴⁹ but MRI demonstrates abnormal signal on long TR (T2-weighted, proton density weighted, and FLAIR) sequences (Fig. 109-14). Necrosis and significant contrast enhancement are absent.

FIGURE 109-14 Gliomatosis cerebri. Axial fluid-attenuated inversion recovery image showing diffuse infiltration of the left temporal lobe, with involvement of the brainstem, hypothalamus, and right hippocampal region as well. Postgadolinium images showed no enhancement. This pattern is compatible with gliomatosis cerebri.

Anaplastic Astrocytoma and Low-Grade Astrocytoma

An enhancing lesion that does not show necrosis yet is infiltrative suggests an anaplastic astrocytoma. Absence of contrast enhancement and edema suggests a low-grade astrocytoma (Fig. 109-15). The more infiltrative the margins and the more extensive the edema, the more likely a non-necrotic mass will be graded an anaplastic astrocytoma. The blood flow, measured by perfusion-weighted MRI studies, is higher in anaplastic astrocytomas than in low-grade tumors.

FIGURE 109-15 Low-grade astrocytoma. A, Note the slight outward bulging of the cortex and adjacent remodeling of the bone (arrows) by this mass on the fluid-attenuated inversion recovery image. B, The absence of enhancement and the remodeling of the bone seen in A suggests that this is a low-grade lesion. Histology was low-grade astrocytoma.

Pleomorphic xanthoastrocytoma is a lesion that favors the frontal and temporal lobes. It has a benign appearance with expansion of gray and white matter. The lesion’s contrast enhancement characteristics are variable. Because it has an indolent growth pattern, one may see remodeling of bone adjacent to the xanthoastrocytoma. The lesion may be cystic with a mural nodule, or it may have a diffuse form, which infiltrates the gyri.

Subependymal giant cell astrocytomas often occur in the setting of tuberous sclerosis. They arise at the foramen of Monro and often show both calcification and strong enhancement. When coupled with subependymal nodules or cortical tubers, the diagnosis is clear, particularly if growth can be demonstrated. Rarely, subependymal nodules themselves enhance, so the documentation of growth aids in this diagnosis.

Benign Astrocytomas

Of the benign astrocytomas, pilocytic astrocytomas of the cerebellum (typically seen as tumors with cysts and mural nodules) break the rules that enhancement tends to correlate with grade (Fig. 109-16). Despite their benign appearance, they invariably demonstrate a lactate doublet on proton spectra, a finding usually seen in higher grade tumors.⁵⁰ Pilocytic astrocytomas of the optic nerve or optic pathway are often detected in patients who have neurofibromatosis type I. This lesion may or may not show contrast enhancement and may exhibit an infiltrative growth pattern. The astrocytomas that infiltrate the brainstem (so-called brainstem gliomas) are typically fibrillary and have a more malignant course than do the pilocytic variety. They may show anaplastic transformation with time. MRI is superior to CT in identifying brainstem gliomas because this is often a region where CT suffers from beam-hardening artifacts arising from the petrous bones. Also, because the lesions may not enhance, long TR (FLAIR; T2-weighted) MRI is needed to show the full extent of the mass, seen as high signal intensity.⁵¹

FIGURE 109-16 Pilocytic astrocytoma. A, T1-weighted sagittal image demonstrates a cystic mass in the posterior fossa with herniation of the cerebellar tonsils (arrow) through the foramen magnum due to the mass effect. There is hydrocephalus present. B, T2-weighted image demonstrates the predominantly cystic lesion as well as two lower intensity solid components to the right (arrows). C, The post–gadolinium-enhanced T1-weighted image shows the enhancing portion of the mass (arrow) and evidence of hydrocephalus by virtue of the dilation of the atria of the lateral ventricles. Findings are pathognomonic for a pilocytic astrocytoma in a child, although a hemangioblastoma in the adult can have a similar appearance.

Perfusion scanning with maps of relative CBV of tumors with respect to white matter have been used to assess the grade of tumors.^3,52,53 Relative CBV appears to correlate directly with histologic grade because the relative CBV of GBM is nearly 3 to 5 times higher than that of low-grade astrocytomas. The CBV also correlates with histologic vascularity.⁵² These findings make sense with respect to the propensity of GBM for recruiting and developing a vascular network and the known vascular (angiogenesis) growth factors in malignancies. The area of a tumor with the highest CBV may be the best target for biopsy.

On spectroscopy, higher grade astrocytomas sometimes show elevated lactic acid, perhaps indicative of anaerobic metabolism. Some cystic low-grade tumors may have lactate build-up in the cyst. NAA, although present, will be depressed, but there is an abundance of choline (see Fig. 109-1). The adage that the higher the choline-to-NAA ratio, the more likely one is dealing with a high-grade neoplasm tends to hold with respect to astrocytomas. A choline-to-creatine ratio of greater than 1 suggests a tumor. The lactate-to-water ratio can be used to distinguish all three astrocytoma groups, whereas the choline-to-water ratio distinguished low-grade astrocytomas from the two high-grade groups. Both the choline and lactate ratios can be used to separate the high-grade from the low-grade tumors.⁵⁴

It has also been reported that MRS of intermediate-grade (WHO grade II) astrocytomas demonstrates elevated levels of myoinositol^55,56; this chemical moiety does not appear to be present in as high concentrations in either lower or higher grade astrocytic lesions.

The differential diagnosis of high-grade astrocytomas includes abscess. Although the clinical picture may clearly differentiate the two, DWI has been helpful in this regard. Pyogenic abscesses tend to be bright on diffusion-weighted imaging and dark on ADC maps, indicating restricted diffusion, whereas tumoral cysts and necrosis are dark on DWI⁵⁷ and bright on ADC maps because the diffusion of the water molecules in the cyst fluid is not as restricted as it is in pus. Enhancement characteristics may also be useful because abscesses have thin rims, thinner toward the ventricles. Abscesses may have high signal intensity rims on T1-weighted MRI before contrast. This has been attributed to the superoxide radicals elaborated by activated macrophages in the walls of an abscess.

Ganglioglioma

Gangliogliomas are tumors that are usually cortically based, favoring the frontal and temporal lobes.⁵⁸ These well-demarcated lesions often contain cysts (Fig. 109-17). Enhancement is inconsistent. Given their cortical bases, there may be bony remodeling secondary to their slow indolent growth pattern. Calcification may be present. As opposed to gangliogliomas, which may show differentiation into a more aggressive lesion, ganglioneuromas and gangliocytomas are nonaggressive, nonprogressive lesions that often appear as a cross between a dysplasia of the brain and a neoplasm.

FIGURE 109-17 Ganglioglioma. A, Axial fluid-attenuated inversion recovery image demonstrating a cortically based mildly expansile mass at the medial aspect of the left temporal lobe. B, Coronal postgadolinium T1-weighted image demonstrates substantial signal enhancement in this case, and a small cystic region (arrow).

Recently, both positron-emission tomography (PET) and thallium-201 single-photon emission CT have been shown to be useful in predicting grades of ganglioglioma (lower activity in lower grade tumors).⁵⁹ The only CT or MRI feature suggestive of higher grade is the presence of edema.

Oligodendrogliomas

These tumors are often located in the frontal and temporal lobes and have a higher rate of calcification than the classic astrocytoma series; they also have a greater propensity for cortical involvement than do astrocytomas (Fig. 109-18). Nonetheless, because astrocytomas far outnumber oligodendrogliomas, a calcified intra-axial lesion in the brain is more likely a calcified astrocytoma than an oligodendroglioma. Oligodendrogliomas may also show cystic areas as well as hemorrhagic areas. Therefore, their density and signal intensity characteristics may be heterogeneous. Enhancement is variable.

FIGURE 109-18 Axial fluid-attenuated inversion recovery (A) and postcontrast T1-weighted (B) images of a left frontal grade II oligodendroglioma, showing cortical involvement (white arrows in A) as well a central cystic region (dashed white arrow in A).

Part of the difficulty in describing a characteristic appearance of an oligodendroglioma is that in more than 50% of the cases, the tumor has a hybrid form, with histologic elements of an astrocytoma. Nonetheless, in general, the oligodendrogliomas are better defined than are the high-grade astrocytomas.

The proton spectroscopic maps of oligodendrogliomas show depressed NAA values. Lactate is usually absent.

Primitive Neuroectodermal Tumors

The primitive neuroectodermal tumor cell line (formerly medulloblastomas, ependymoblastomas, pineoblastomas, and primary cerebral neuroblastomas) usually includes hypercellular lesions, which correspond to an intermediate (isointense) signal intensity on T2-weighted scans when compared with overlying gray matter. Their enhancement, although usually present, is less avid than is that exhibited by pilocytic astrocytomas or the walls of GBM. The diagnosis is usually made by virtue of the location of the tumor as well as its occurrence in the pediatric age group.

Medulloblastomas are the classic intraparenchymal PNET. These tumors are often hyperdense on noncontrast CT. Ten percent to 20% of medulloblastomas have calcification or cystic or hemorrhagic change.⁶⁰ Medulloblastomas do sometimes occur in adults and in that patient group often simulate extra-axial tumors such as meningiomas in the posterior fossa. The finding of a well-demarcated, mild to moderately enhancing hemispheric mass involving the cerebellar surface in a young adult is suggestive of medulloblastoma (Fig. 109-19).⁶¹

FIGURE 109-19 Medulloblastoma. A, Sagittal T1-weighted image shows a large well-demarcated mass in the posterior fossa of a 15-year-old boy, mildly impinging the lower end of the sylvian aqueduct (white arrow) and the superior aspect of the fourth ventricle. The mass effect is associated with marked cerebellar tonsillar descent through the foramen magnum (black arrow). B, Axial T2-weighted image shows that the lesion has relatively low signal and also demonstrates well the cystic component. C, Peripheral patchy irregular enhancement (arrows) is present. D, The hypercellularity of the tumor contributes to low signal (restricted diffusion; arrows) on the apparent diffusion coefficient map derived from the diffusion-weighted scan.

The spectroscopic appearances of PNETs are different than those of the astrocytoma series in that there is an absence (as opposed to a variable degree of reduction) of NAA. Both classes of lesions show elevation of choline peaks. The NAA-to-choline and creatine-to-choline ratios are lower in PNETs than astrocytomas.⁴³ Myoinositol, taurine, glutamate, and glutamine may be evident on proton MRS maps of these tumors.

Germinomas and medulloblastomas usually are hyperdense on noncontrast CT studies, and this finding may suggest the specific diagnosis. The other intra-axial lesion to do this is lymphoma (see Fig. 109-23, later). All these lesions are likely hyperdense on CT on the basis of their dense cellularity; this hypercellularity also contributes to restricted diffusion, evidenced as low signal on ADC maps (see Fig. 109-19).

Dysembryoplastic Neuroepithelial Tumors

Dysembryoplastic neuroepithelial tumors are lesions that are hypodense on CT, hypointense on T1-weighted images, and hyperintense on T2-weighted images. Although some may infiltrate the cortex and appear as cortical thickening, most (>80%) show cyst formation, which may be solitary or multiple (Fig. 109-20).⁶² There may be ipsilateral temporal lobe atrophy with indistinct gray-white matter boundaries.⁶³ Subcortical white matter involvement is seen in most cases. Invariably, there are areas of hemorrhage identified if one employs gradient-echo MRI scanning sequences. Contrast enhancement and edema are variable.⁶² This is a tumor that has variable aggressiveness and may simulate pleomorphic xanthoastrocytoma or gangliogliomas. Some lesions simulate CSF in their T1- and T2-weighted signal characteristics and may show calcification and bony remodeling of the calvarium.⁶⁴

FIGURE 109-20 Dysembryoplastic neuroepithelial tumor. This left frontal mass demonstrates many variably sized cysts (arrows) but exhibits no substantial postgadolinium T1-weighted signal enhancement.

Desmoplastic Infantile Ganglioglioma

Desmoplastic infantile ganglioglioma (DIG) is a variant of the ganglioglioma that is usually seen in the first 2 years of life. The tumors typically occur in the frontal and parietal lobes and have a meningeal base. Cyst formation is the rule and peripheral rim enhancement usually is present as well. Some may show a calcified rim. Although this lesion may look like a huge necrotic GBM in an infant, it has a good prognosis, with benign histology. The desmoplasia accounts for the rim of low signal intensity tissue on T2-weighted images (Fig. 109-21). The differential diagnosis includes PNETs, but the incidence of calcification and hemorrhage is higher in cortical PNETS. Desmoplastic cerebral astrocytoma of infancy (DCAI) may also occur in the same aged children and look similarly. Absence of neuronal components histologically distinguishes this tumor from a DIG.

FIGURE 109-21 Desmoplastic infantile ganglioglioma (DIG). Axial noncontrast CT section (A) demonstrates large centrally cystic mass with speckled calcium (arrows) in a thick hyperdense and hypercellular rim that shows low signal on T2-weighted images (arrows in B). The asterisk in B is positioned in the central cyst. The thick rim of the lesion enhances after intravenous gadolinium administration (C).

Hemangioblastoma

Hemangioblastoma is the second most common posterior fossa tumor in the adult after metastases. It has a characteristic appearance with a markedly enhancing mural nodule associated with a cystic mass seen in the cerebellum (Fig. 109-22). The cyst wall does not enhance.⁶⁵ It looks similar to a juvenile pilocytic astrocytoma, although in a different age group. The nodule may have flow voids within it, owing to the vascular nature of the tumor, which may help differentiate between hemangioblastoma and pilocytic astrocytoma. Solid hemangioblastomas may occur in up to 40% to 45% of those masses in the cerebellum and is the rule in the cord and medulla.⁶⁶ Presence of multiple hemangioblastomas implies von Hippel-Lindau (VHL) disease, and the tumors may be found in the brainstem or spinal cord with this lesion. The lesions may be pial based.

FIGURE 109-22 Hemangioblastoma. Axial postgadolinium T1-weighted image through the posterior fossa demonstrating multiple nodular lesions with associated cysts, the walls of which do not enhance.

On angiography, these tumors show dense staining and may be supplied by a dilated tortuous artery. Dilated veins may coexist. If a cyst is present, it may displace vessels accordingly. Four percent to 40% of patients with hemangioblastomas have VHL disease, and 45% to 83% of patients with VHL have cerebellar hemangioblastomas.⁶⁶

Lymphoma

Before the HIV-AIDS era, lymphoma was an unusual diagnosis to make on neurological imaging. It also had a reasonably characteristic appearance of being hyperdense on unenhanced CT and demonstrating avid contrast enhancement in a homogeneous fashion (Fig. 109-23); the hypercellularity of the lesions also is often reflected as restricted diffusion. In all, more than 90% of lymphomas enhance,⁶⁷ and those that do not are often affected by steroid therapy, which suppresses the enhancement. Lymphoma may coat the ventricles and ependymal surfaces. Multiple lesions are present in more than half of all cases and even higher in patients with AIDS. On T2-weighted MRI, the lesion is isointense to hypointense in most cases.⁶⁷ Growth across the corpus callosum is not uncommon.

FIGURE 109-23 Lymphoma. A, Axial noncontrast CT section demonstrates a radiodense lesion (arrows) surrounded by edema in the right frontal lobe white matter. B, Axial T2-weighted image at roughly the same level as that depicted in A shows a relatively low signal intensity lesion (arrows), which demonstrates avid postgadolinium enhancement (C) and restricted diffusion (arrows in D).

Although histologically the diffuse histiocytic lymphoma of elderly patients and that of AIDS patients is similar, the imaging characteristics of these processes differ markedly. The absence of hyperdensity, the presence of necrosis, and the multifocal nature of the lymphoma seen in patients who have AIDS have led to difficulties in distinguishing this lesion from GBM and toxoplasmosis. Peripheral rather than solid enhancement (and necrosis) is often seen in lymphomas of patients who are not immunocompetent.⁶⁷ Fortunately, GBM can be distinguished from lymphoma in that it is not thallium-avid, whereas lymphoma is. This nuclear medicine study, therefore, is useful in patients who have equivocal lesions and in those who have AIDS.

Lymphoma in the brain can have a number of characteristic appearances, including a solitary lesion, a lesion infiltrating the leptomeninges or pachymeninges, lesions outlining the ventricles, multiple lesions both intraparenchymally and extra-axially, and osseous lesions. Almost always, these lesions enhance unless steroid therapy has been instituted. In addition, lymphoma may involve the subarachnoid space and be completely invisible to imaging, being detectable only on CSF evaluation.

The proton MRS pattern of lymphoma is characterized by elevated choline peaks with reductions in creatine and NAA residues. Lipid peaks are elevated dramatically.

Metastasis

Metastatic disease of the CNS may present in an intra-axial or extra-axial location. Metastatic disease to the calvaria may be either lytic, blastic, or mixed patterns, with lung and breast carcinomas being the most frequent primary tumors. Similarly, lung and breast cancers have the highest rate of intraparenchymal metastases to the brain. Classically, metastatic foci tend to deposit at the gray-white junction of the brain, where the neoplastic emboli get caught in the vasculature. Metastases most often manifest as well-defined enhancing lesions with surrounding vasogenic edema (Fig. 109-24). Multiplicity is helpful in making the diagnosis, but in many series, a solitary metastasis is still the most common intraparenchymal lesion in an adult.

FIGURE 109-24 Metastasis. A, Relatively low-signal-intensity gray matter–white matter junction lesion on fluid-attenuated inversion recovery image (arrow), surrounded by disproportionate edema given the size of the underlying lesion. Metastatic deposits frequently elicit a great deal of surrounding edema. This lesion demonstrates marked enhancement (B, arrow) and hyperemia (arrow in C), as evidenced by cerebral blood volume determination.

Hemorrhagic metastases are more commonly seen in patients with melanoma, renal cell carcinoma, and thyroid carcinoma. Nonetheless, because of the overwhelming higher prevalence of lung and breast cancer, one should consider these primary tumors as well. Although nonhemorrhagic metastases are usually hypodense on CT, hemorrhagic metastases are hyperdense. The highly cellular neoplasms (small cell carcinoma, renal cell carcinoma, and some adenocarcinomas) show signal intensity that may be isointense to normal gray matter.

Melanoma is unique in that if the tumor has a significant melanin content, it may appear hyperintense on T1-weighted images even without the presence of blood. The signal intensity on the T2-weighted image may be dark secondary to the paramagnetic effects (shortening T1 and T2) of the melanin. In contrast, melanoma may be amelanotic or hemorrhagic, which may account for a mixed signal intensity pattern of the lesion.

Metastatic disease may also be found with dural masses, subarachnoid seeding, and intraventricular lesions. Rarely, one may see metastatic deposits arising on nerve roots that span from the intraparenchymal compartment to the extracranial head and neck. One should also consider lymphoma, sarcoidosis, and inflammatory or infectious lesions in this scenario.

Metastases show greatly reduced NAA and creatine-phosphocreatine peaks on spectroscopy as opposed to primary glial tumors. Lipids and lactate are frequently seen in metastases. The larger the metastasis and the more heterogeneous the enhancement, the lower the choline and the higher the lipid and lactate resonances.⁶⁸

Posttherapeutic Imaging

Determining whether there is residual neoplasm in the immediate postoperative setting is usually predicated on the persistence of enhancing nodular tumor in the operative bed within 48 hours after the operation. In most instances, postoperative granulation tissue should not be enhancing in that short time frame. Unfortunately, in situations in which the original tumor was nonenhancing, the problem of differentiating between postoperative edema and neoplasm is made more challenging. Growth over time may be the only means for assessing this course.

On follow-up images, enhancement is again the key to distinguishing posttherapy changes from tumoral recurrences. Pial recurrences may be present with some histologies such as medulloblastoma or other forms of PNET.⁶⁹ Dural enhancement, however, is the norm for nearly all postoperative cases, whether after neoplasm resection, shunting, or epilepsy surgery. Dural enhancement does not imply residual or recurrent tumor.

Hudgins and colleagues studied patterns of dural enhancement in the postoperative setting.⁷⁰ Absent, mild focal, or diffuse dural enhancement was considered a normal finding, and in fact, moderate dural or subdural enhancement may be seen in clinically well children who have a history of postsurgical subdural collections or a history of superimposed meningitis. Nodular dural, pial, or ependymal enhancement suggested recurrent local tumor, leptomeningeal metastases, or active infection.⁶⁹

Radiation Effects

The challenge in the postradiotherapy evaluation is to differentiate residual or recurrent tumor from radionecrosis. Several factors influence the development of radiation necrosis. These include total dose, overall time of administration, size of each fraction of irradiation, number of fractions per irradiation, patient age, and survival time of patients. As patients survive longer with more effective treatment, the incidence of radiation necrosis will rise because it is usually a late effect of treatment. The signs and symptoms of radiation necrosis are nonspecific and do not differentiate it from recurrent tumor.

The effects of irradiation have been separated into those occurring early (within weeks) and late (4 months to many years later). The former is transient, may actually occur during radiotherapy, and is usually manifested by high signal intensity on T2-weighted and FLAIR imaging in the white matter caused by increased edema (beyond that associated with the tumor). The delayed effects are separated into early delayed injury (within months after therapy) or late injury (months to years after therapy). Early delayed injury is also a transient effect and is of little consequence other than recognizing it as such (as opposed to tumor growth) directly after therapy. The late effects are usually irreversible, affect white matter to a much greater extent than gray matter, and may be focal or diffuse. Seventy percent of focal late radiation injuries occur within 2 years after therapy.

Unfortunately, it is exceedingly difficult to make the diagnosis of focal radiation injury. CT or MRI may demonstrate a mass lesion associated with edema, low in attenuation on CT and high in signal on T2-weighted imaging, which usually enhances. The possibility of focal radiation injury needs to be raised when the lesion is found in the appropriate temporal sequence to treatment. If the lesion is remote from the primary tumor site, the diagnosis is more easily suggested. Unfortunately, radiation necrosis favors the primary tumor site, probably because of predisposing vascular effects. The diagnosis of radiation necrosis may be suggested by PET. With residual or recurrent tumor, [18]fluorodeoxyglucose PET has increased activity (greater than normal brain tissue), whereas radiation necrosis shows low activity (Fig. 109-25). Overall accuracy of PET is about 85% for distinguishing residual or recurrent tumor from radiation necrosis. The accuracy rates are better for high-grade tumors than for low-grade tumors, probably because of inherent differences in tumor growth activity, but even with high-grade tumors, the results are not always easy to interpret because biopsy of PET-hypometabolic regions often demonstrates a mixture of treatment effect and isolated foci of residual or regrowing tumor. Focal hemorrhage without necrosis also occurs as a result of radiation.

FIGURE 109-25 Left temporal astrocytoma, after radiation treatment. A, Axial image from fluorodeoxyglucose positron-emission tomography scan after surgery, chemotherapy, and radiation treatment shows markedly reduced tracer uptake in the left temporal region (arrows), with the postgadolinium T1-weighted (B) and T2-weighted (C) images demonstrating nonspecific signal changes in the same region. Histologic analysis of a repeat biopsy showed predominantly treatment effect with small foci of admixed tumor.

Diffuse late injury takes the form of severe demyelination, particularly in periventricular and posterior centrum semiovale regions. CT demonstrates decreased white matter density, but T2-weighted imaging is more sensitive and shows high signal intensity in the white matter. Usually, the abnormality does not show enhancement. It is estimated that with whole-brain irradiation, diffuse white matter changes may occur in 38% to 50% of patients. The incidence increases with increasing patient age. Clinical findings do not correlate well with severity of white matter injuries.

Radiation-induced telangiectasias and cavernomas have recently been reported as a late phenomenon after therapy. These are characterized by hemosiderin deposition (low in signal intensity on T2-weighted and gradient-echo images) without surrounding edema.⁷¹ They may be multiple or solitary.

Spectroscopy may show some utility in the distinction between recurrent tumor and radiation effects. Choline residues are expected to be depressed with radiation injury to the brain, in contradistinction to recurrent neoplasms, in which choline is elevated. Creatine is also lower in radiation damage than in actively proliferating tumors, and lipid signals may be present as well in radiated brain.⁷²

Some have advocated using perfusion MRI to assess for radiation necrosis. Radiation causes a decline in CBV, whereas recurrent tumor tissue leads to an increase in relative CBV by virtue of the tumor’s angiogenesis factors.^73–75