Imaging in Glioblastoma Multiforme 

Glioblastomas (malignant glioma) are the most common adult malignant brain tumors,^{[1, 2, 3]} and 20% of all primary brain neoplasms are glioblastoma multiforme tumors. Glioblastoma multiforme (GBM; malignant glioma) is the highest-grade form of astrocytoma and makes up about two thirds of all brain astrocytomas. The prognosis for this tumor is at the extreme worst end because of its high-grade status.^{[1, 4]} See the images below

Preferred examination

Computed tomography (CT) scanning can demonstrate the tumor and associated findings; however, in making the glioblastoma multiforme (GBM; malignant glioma) diagnosis, CT scanning may cause small tumors to be missed. A small low-grade glioma that is missed with a screening study may eventually progress to glioblastoma multiforme (GBM; malignant glioma). In addition, this modality may not depict all multifocal lesions. Cerebrospinal fluid (CSF) spread, particularly early spread, may also be difficult to diagnose with CT scanning.

Magnetic resonance imaging (MRI) is significantly more sensitive to the presence of tumor, as well as its associated findings, in the inclusion of peritumoral edema, and is the modality of choice for the examination of a patient with suspected or confirmed glioblastoma multiforme (GBM; malignant glioma). This lesion is a highly infiltrative tumor; thus, tumor cells are usually found beyond the margins of an area of abnormal signal intensity on MRIs. Central nervous system (CNS) metastases are frequent, but extracerebral metastases are rare.

After surgery, differentiating between recurrent tumor and scar tissue on the basis of MRI findings alone may be difficult. Positron emission tomography (PET) scanning is useful in this regard.^{[5, 6, 7, 8, 9, 10, 11, 12]}

Because of the highly variable appearance of the tumor, it may sometimes mimic other conditions, such as an infarct, an abscess, or even a tumefactive plaque in multiple sclerosis, and thereby delay diagnosis. In terms of the imaging appearance and the appearance of a mass in the spectrum from low-grade astrocytoma to glioblastoma multiforme (GBM; malignant glioma), the following generalizations can be made (although some exceptions apply):

• The incidence of calcification decreases in the spectrum from low-grade astrocytoma to glioblastoma multiforme (GBM; malignant glioma).
• The incidence of enhancement increases in the spectrum from low-grade astrocytoma (preserved blood-brain barrier [BBB], low enhancement frequency) to glioblastoma multiforme (GBM; malignant glioma) (disrupted BBB).
• Hemorrhage, necrosis, mass effect, and edema incidence patterns are the same as those for enhancement.
• Unless hemorrhagic changes are present, most tumors are hypointense on T1-weighted MRIs and hyperintense on T2-weighted MRI.
• Enhancement on CT scans means enhancement on MRIs.

Some forms of glioblastoma multiforme (GBM; malignant glioma) are considered variants. Giant cell glioblastoma (monstrocellular GBM) is a variant of GBM but has the same imaging findings as those of GBM.

Radiographs are not used in the evaluation of the primary tumor. However, in cases of tumors that invade the calvarium, x-ray studies may demonstrate skull erosion changes. In the uncommon case with distant skeletal metastases, radiographs may demonstrate these as well.

CT scan results offer a relatively high degree of confidence for the diagnosis of glioblastoma multiforme (GBM; malignant glioma). However, some lesions may mimic glioblastoma multiforme (GBM; malignant glioma), such as space-occupying lesions including brain abscess, infarct with hemorrhagic transformation, and neoplasms of a lower grade than that of glioblastoma multiforme (GBM; malignant glioma). In addition, some types of demyelinating lesions (eg, giant multiple sclerosis plaques) may mimic glioblastoma multiforme (GBM; malignant glioma), and the multifocal form of GBM may be indistinguishable from diffuse multiple sclerosis.

With gliomatosis cerebri, CT scan findings may be normal, or images can show widespread low-attenuating regions, with no focal mass and no enhancement.

Nonenhanced CT scan findings may include a heterogeneous poorly marginated mass; internal areas of low or fluid attenuation that are the foci of necrosis (present in as many as 95% of GBMs); internal areas of high attenuation that are the foci of hemorrhage or, rarely, calcifications (more common if GBM is the result of transformation of a low-grade astrocytoma or after therapy); and a significant mass effect and edema (vasogenic distribution of the edema).

Enhanced CT scans include significant enhancement of findings such as irregularity and inhomogeneity; possible ring enhancement; possible, but uncommon, solid enhancement; possible little enhancement possible in diffuse forms.

MRI has a high degree of confidence in the diagnosis of glioblastoma multiforme (GBM; malignant glioma). In fact, it has the highest degree of confidence of any imaging modality. Some lesions, mainly space-occupying lesions with hemorrhagic components, may mimic glioblastoma multiforme (malignant glioma) on MRIs. These include abscesses and infarcts.

MRI findings demonstrate a heterogeneous mass that is generally of low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.^[13] There are internal cystic areas, internal flow voids representing prominent vessels, internal areas of high signal intensity on T1 (hemorrhagic foci), neovascularity, necrotic foci, significant peritumoral vasogenic edema, and significant mass effect. Irregular but intense enhancement after the administration of gadolinium-based contrast material (same pattern as with enhanced CT scanning) is also found, as are metastatic foci of intracerebral metastasis that are common with GBM (MRI has a higher sensitivity to these lesions than CT scanning.)

Gliomatosis cerebri is seen as a diffuse white-matter abnormality with signs of increased intracranial pressure, including ventricular compression and subarachnoid space obliteration (the differential diagnosis includes normal pressure hydrocephalus).

Gliosarcoma are usually well-circumscribed, sarcomatous or infiltrative gliomatous elements that possibly resemble meningiomas. Other imaging findings are similar to those of glioblastoma multiforme (GBM; malignant glioma).

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], and gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.

NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

Positron emission tomography (PET) scanning is a useful adjunct to the evaluation of glioblastoma multiforme (GBM; malignant glioma), particularly after resection. In this setting, differentiation of residual or recurrent tumor and postoperative edema or scarring is often difficult on MRIs or CT scans. PET scanning with 18-fluorodeoxyglucose (FDG) is useful in cases of active tumor, which shows high metabolic activity and glucose utilization, and in cases of simple postoperative edema or scars, which usually have no increased activity.

In the setting of resection for known tumor, the finding of increased tracer uptake at the surgical site is a reliable indicator of recurrent disease. However, after radiotherapy, increased activity may be seen at the surgical site without tumor recurrence. False-positive findings occur after radiation therapy, when active granulation tissue can metabolize FDG, which may limit the sensitivity of the study in this setting. An epileptogenic focus near the surgical site may show increased uptake on PET scanning, particularly if epileptic activity is high.

Angiographic findings associated with glioblastoma multiforme (GBM; malignant glioma) include the following: hypervascular mass with tumor blush; prominent feeding and draining vessels, as well as arteriovenous shunting (this may mimic an arteriovenous malformation); aberrant vessels and vascular pooling and stasis (common); and mass effect, which is seen as displacement of vessels.

Angiography has low specificity for the diagnosis of glioblastoma multiforme (GBM; malignant glioma). Although images may show vascular displacement on the basis of the mass effect of the tumor, virtually any other space-occupying lesion may have similar findings. In addition, the hypervascularity of glioblastoma multiforme (GBM; malignant glioma) may mimic vascular malformations. Thus, any space-occupying lesion or vascular malformation with hypervascularity may cause a false-positive finding. Small tumors or those with a high infiltrative component and little or no vascular displacement may cause a false-negative finding.