Glioblastoma (Multiforme) Imaging 

Updated: Jun 14, 2022
Author: Alex Lobera, MD; Chief Editor: L Gill Naul, MD 

Practice Essentials

Glioblastomas (malignant glioma) are the most common adult malignant brain tumors, and 20% of all primary brain neoplasms are glioblastoma tumors. Glioblastoma (GBM; malignant glioma) is the highest-grade form (grad IV) of astrocytoma and makes up about two thirds of all brain astrocytomas.[1, 2] Mortality associated with GBM is greater than 90% at 5 years, with a median survival of 12.6 months.[3]  The prognosis for this tumor is at the extreme worst end because of its high-grade status.[3]

(See the images below.)

T1-weighted axial gadolinium-enhanced magnetic res T1-weighted axial gadolinium-enhanced magnetic resonance image demonstrates an enhancing tumor of the right frontal lobe. Image courtesy of George Jallo, MD.
T2-weighted image demonstrates the same lesion as T2-weighted image demonstrates the same lesion as in the previous image, with notable edema and midline shift. This finding is consistent with a high-grade or malignant tumor. Image courtesy of George Jallo, MD.

In the fifth edition of the WHO classification of CNS tumors, glioblastomas are classified as a grade 4 diffuse astrocytic tumor in adults that must be IDH-wildtype. The term ''glioblastoma' is no longer applied to pediatric tumors.[4]

The WHO further recognizes 3 glioblastoma histologic variants[4, 5] :

  • Giant cell glioblastoma
  • Gliosarcoma
  • Epithelioid glioblastoma

Imaging modalities

Computed tomography (CT) scanning can demonstrate the tumor and associated findings; however, in making the glioblastoma 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. 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.[6]  CT can provide additional information regarding calcification or hemorrhage and can be useful for patients who are unable to undergo MR imaging.[7]

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.[8, 9, 10, 11, 12, 13, 14, 15] 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.

Although a formal diagnosis of glioblastoma relies on histopathology and genetic markers for grading, structural MRIs are routinely performed and can be used to help guide surgery.[16]

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.[17, 18, 19]  FDG-PET can provide functional imaging of glucose metabolism, which is helpful and important information for most cancers.[16]

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, the following generalizations can be made (although some exceptions apply):

  • The incidence of calcification decreases in the spectrum from low-grade astrocytoma to glioblastoma.

  • The incidence of enhancement increases in the spectrum from low-grade astrocytoma (preserved blood-brain barrier [BBB], low enhancement frequency) to glioblastoma (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 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.

NCCN guidelines

The National Comprehensive Cancer Network (NCCN) guidelines consider magnetic resonance imaging (MRI) of the brain to be the gold standard imaging study for glioblastoma.  Although computed tomography is often the first imaging study performed in patients with possible central nervous system lesions, it lacks the resolution of MRI, but it should be used in patients who cannot have an MRI.  Positron emission tomography scanning may be helpful in differentiating tumors from radiation necrosis. It may also be useful in identifying the optimal biopsy area. No laboratory studies are helpful in making the diagnosis of glioblastoma.[20]

 

Computed Tomography

CT scan results offer a relatively high degree of confidence for the diagnosis of glioblastoma. However, some lesions may mimic glioblastoma, such as space-occupying lesions, including brain abscess, infarct with hemorrhagic transformation, and neoplasms of a lower grade than that of glioblastoma. In addition, some types of demyelinating lesions (eg, giant multiple sclerosis plaques) may mimic glioblastoma, 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; and possible little enhancement in diffuse forms.

 

Magnetic Resonance Imaging

MRI has a high degree of confidence in the diagnosis of glioblastoma and is widely used for identifying location and size of brain tumors.[14]  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 on MRIs. These include abscesses and infarcts.[9, 10, 11, 12]

Conventional MRI is limited in its ability to determine type and grade of  brain tumors, but more advanced MRI techniques, such as perfusion weighted imaging, may provide  potentially more physiologic information.[9, 10, 11, 12, 13, 14, 3]

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.)

Research with ultra-high field MR imaging at field strengths of 7 T or higher has been reported for visualization of glioblastoma infiltration to improve target volume delineation.[21, 22, 23, 24, 25, 26]

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).

Gliosarcomas are usually well-circumscribed, sarcomatous or infiltrative gliomatous elements that possibly resemble meningiomas. Other imaging findings are similar to those of glioblastoma multiforme.

Gadolinium-based contrast agents have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). 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.

 

Nuclear Imaging

Positron emission tomography (PET) scanning is a useful adjunct to the evaluation of glioblastoma, 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.

Hatakeyama et al found that combining FDG-PET with arterial spin labeling (ASL) may help differentiate primary central nervous system lymphoma (PCNSL) from glioblastoma.[27]

 

Angiography

Angiographic findings associated with glioblastoma 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. 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 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.