MRI GLIOBLASTOMA MULTIFORM (GBM MRI)

GBM MRI

This is a well known medical truth that Glioblastoma is the most malignant tumor of the brain. It has different terms, it may be called Grade IV astrocytoma or malignant astrocytoma or glioblastoma multiforme (GBM), Here we will discuss MRI Glioblastoma.

Glioblastoma In another word is a fast growing malignant astrocytic tumor which has special characters of having necrosis and neovascularity. considering 1ry malignant intracranial neoplasm, GBM is the most common tumor.

Glioblastoma has 2 types: the first type is Primary or could be named de novo. The second type is secondary, as degeneration
from astrocytoma that has a lower grade, and characterized by necrosis and microvascular proliferation.

According to WHO classifications. According to WHO grading, GBM is grade IV (1).

GBM is which is the most malignant astrocytic tumor, makes about 15% to 20% of all intracranial tumors. In adults, GBM is considered the most wide-spreading primary brain neoplasm (2).

It is believed that most glioblastomas arise from an existent astrocytoma or anaplastic astrocytoma, but few could grow as the primary tumor. According to a clinicopathologic study of 241 gliomas with necropsy data, about 7.5% of glioblastomas appear to have a multicentric origin(3).

Age incidence of GBM is markedly increased after the age of 50. its peak incidence appears more prominent in the sixth decade. GBM is very rare to occur in young age especially less than 30 years.Male to Female ratio is 3:2, it has male prominence as all type of glioma.

The same occurs in clinical presentation, a symptom of rapid increase intracranial pressure, after a short period of one month from its beginning. These forms of tumors have the worst prognosis with the median survival of 12 months.

Good prognosis cause includes young age, GBM occurring as a secondary to another lesion, not as a primary tumor, the third one is surgical debulking (4).

 

Pathological Process and clinical presentation of  GBM 


          GBM pathological malignant characters are a reflection in the MR imaging, and unfortunately, MR imaging suffers from som

e of the limitations seen on pathologic examination.

At the MR, we could see the heterogenicity inside the tumors which is the image of the necrosis and hemorrhage and hypercellularity (5). T2-WI would be very helpful to detect these changes, in this sequence cystic necrosis foci and hemorrhage is shown with debris–fluid levels and lower-intensity regions in areas of hypercellularity.

on spin echo, MR imaging, within the tumors linear regions of the signal void are seen, which reflect the effect of angiogenesis that characterizes glioblastomas. it’s very rare to find calcification in these lesions except they arise in lesions which have a low grade.

The bleeding tumor is a character of GBM, but unfortunately not alone, other tumors as oligodendroglioma and ependymoma have this character, so In MR we should be aware to the good differentiation between Intratumoral hemorrhage and Benign hemorrhage this is well described in the table below (Table 1).

The extensive edema (appear more prominent on WM) associated with this tumor makes a significant mass effect. So it’s very important to define tumor margins and differentiate it from surrounding edema.In the real world, what we call edema is very precise to be described as “tumor plus edema“(6).

The is appears on MR imaging more clear than CT, especially with the improvement of the MR contrast resolution imaging. So every radiologist and physician should know that tumor extends beyond the appeared abnormality regions MRI (7).

Patient with glioblastoma Symptoms usually varies with location. They may present with Seizures, focal neurologic deficits which are common to affect a motor area or limb function. Age Peak of glioblastoma range from 45 to 75 years, although it’s rare in young patients it may occur at any age.gliobasltoma has Relentless progression, its survival rate often < 1 year (8).

Intratumoral hemorrhage Benign hemorrhage
Markedly heterogeneous, related to
Mixed stages of blood
Debris–fluid (intracellular–extracellular blood) levels
Edema + tumor + necrosis with blood
Shows expected signal intensities of acute, subacute, or chronic blood, depending on stage of hematoma
Identification of nonhemorrhagic tumor component No abnormal nonhemorrhagic mass
Delayed evolution of blood-breakdown products Follows expected orderly progression
Absent, diminished, or irregular ferritin/hemosiderin Regular complete ferritin/hemosiderin rim
Persistent surrounding high intensity on long–repetition time images (i.e., tumor/edema) and mass effect, even in late stages Complete resolution of edema and mass effect in chronic stages

Table (1): Difference between Mlaginent intratumoral Hge Vs Bening intracranial Hematoma.(9) (Table 11.8)

Figure (1): Glioblastoma multiforme, gross specimen. A brain section from an autopsy specimen shows a nonhomogeneous cut surface with hemorrhage and necrosis. (Courtesy of Dr. N. K. Gonatas, Pennsylvania University Hospital, Philadelphia, Pennsylvania. (10)

MRI sequences of Localize and characterizations of GBM.

MRI is the best imaging choice for localization and characterization of Glioblastoma. Contrast-enhanced MR is most sensitive, Newer techniques help improve diagnosis/biopsy accuracy like MRS, perfusion, hypoxia imaging, DTI.

Glioblastoma appears as thick, irregularly enhancing tumor, has a  necrotic core.The mass could be seen as heterogeneous, hyperintense mass associated with adjacent infiltration of the tumor and vasogenic edema. (11)

With GBM we could expect to see necrosis, hemorrhage, cysts, fluid levels, neovascularity. GBM may appear diffuse infiltrative mass, and appear necrotic and have poor margins, GBM could cross WM and affect the other side of the cerebral hemisphere, If it occurs and affects corpus callosum, it’s so called butterfly tumor.it may include also anterior and posterior commissures. It’s rare to invade meninges and rarely to be multifocal (~5%).(12)

Most common Location of GBM is supratentorial white matter (WM), the frontal, temporal, parietal which are more likely to be invaded by GBM more than occipital lobes.Cerebral hemispheres are more likely than brainstem, which is more probable location than cerebellum.

Basal ganglia and thalamus are less common(13). In children, brain stem and cerebellum are more common. (14)

So, let’s talk a look at MRI sequences used to help localization and characterization of glioblastoma multiform, and how it appears in each sequence.

T1 Weighted Image: GBM appears as irregular isointense, hypointense WM mass. It’s common to see irregular margins and cyst and of course, necrosis is the main sign. Also, GBM could cause subacute hemorrhage.(15)

T2 Weighted Image: GBM appears as heterogeneous, hyper intense mass with adjacent tumor infiltration or vasogenic edema. We expect to see expect to see hemorrhage,  necrosis, cysts, fluid levels, neovascularity. Viable tumor extends far beyond signal changes. (16)

FLAIR: GBM appears as heterogeneous, hyper intense tumor, associated with infiltration and vasogenic edema. (17)

GRE T2-Weighted MRI: there is the probability of artifact that related to products of the blood. (18)

PWI: in this sequence elevated maximum relative cerebral blood volume in comparison with low-grade tumors, also it has elevated permeability in comparison to low-grade tumors. (19)

T1WI C+: on the sequence, the tumor appears as an irregular enhanced tumor with central necrosis .the tumor enhancement could be patchy or nodular or ring shape. (20)

Figure (2): T1-WI GBM appears as hypo intense lesion affecting corpus callosum genu  forming what is called a butterfly tumor (21)

 

 

Figure (3): T2-WI, GBM appears as hyper intense lesion affecting corpus callosum genu  forming what is called a butterfly tumor (22)

 

Figure (4): (GBM MRI) Axial T1WI C+ FS MR in a 60-year-old man with acute onset of seizures shows a heterogeneously enhancing occipital lobe mass with central necrosis and extension across the splenium of the corpus callosum , characteristic of GBM. The frontal and temporal lobes are the most common locations for GBM.(23)

 

 

Figure (5): (GBM MRI)Axial T1 C+ FS MR in the same patient shows a thick enhancing rind of tumor that surrounds the necrotic tumor core, characteristic of GBM. Other lesions including lymphoma and demyelination may also involve the corpus callosum.(24)

Figure (6):(GBM MRI) Axial FLAIR MR in a patient with GBM shows a heterogeneous mass and the typical extensive surrounding signal abnormality that represents a combination of tumor cells and vasogenic edema. Pathologically, tumor cells are found beyond the regions of signal abnormality.(25)

Figure (7):(GBM MRI) MRS in a patient with recurrent GBM shows a classic malignant tumor spectrum with a markedly elevated choline (Cho) , a low NAA at 2.02 ppm, and an inverted lactate peak  at 1.33. (26)

Sequences are used to plan treatment, assess the completeness of treatment and detect a change in the lesion.

DWI is the best MRI used to accurate pre-operative diagnosis, and also to monitor treatment effects on lesion and differentiation between true and pseudo progression. As Glioblastoma has Lower measured ADC than low-grade gliomas, and there is variable diffusion restriction in solid portions of the tumor.(27)

Figure (8): Axial MR perfusion in the same patient shows an increased rCBV . in the solid parts of the tumor and a low rCBV in the necrotic center .Perfusion MR is helpful to provide an accurate preoperative diagnosis. In addition, it is often used to help guide a biopsy if the location of the tumor prevents the patient from undergoing a complete resection.(28)

 

 

As ADC maps present a very good service to assess tumor grading and effect of treatment. Histogram analysis based on ADC  maps of contrast enhanced Tumor provide a great assessment True from pseudo progression.

Yet we should also assess biomarkers values, e.x percentile values of cumulative ADC histogram . to the good differentiation between true and pseudo progression of the tumor, we should know that at Histogram, the underlying hypothesis indicates the viable tumor components while the higher one indicates the edema and necrotic tissue. this sequence is very useful with heterogeneous nature of glioblastomas that include mixed parts of the active tumor and necrotic parts.(29)

DWI is useful not just in that, it’s also very helpful to differentiate between radiation affection and tumor recurrence and progression by assessment of ADC value differentiate of the GBM during after therapy examinations. (30)

Figure (9): This sequences of MR images of the patient on therapy. These represent the phenomenon of pseudoprogression. Note the upper images were obtained just after initiation of treatment show restriction of enhancement which indicates regression of tumor while the tumor is still growing as illustrated in lower images. Lower images were obtained 1 month later show the enlarged tumor.(31)

 

Diffusion tensor imaging (DTI): can also be used to improve surgical planning.(32)

Perfusion Weighted Imaging (PWI): this sequence is more accurate in illustration tumor outlines, so is very helpful in radiation and surgical planning.also, it’s helpful in the assessment of patients response to radiotherapy by measuring of rCBV. (33)

Functional MRI:  it’s the sequence used to the good planning of the neurological risks and treatment of the tumors. As fMRI helps in localization of the invasion of the cortical center that is responsible for the vital functions like memory, motor, and language .it can alter a neurosurgical decision to approach the GBM either by surgery or not.(34)

MRI Sequences used to grade GBM condition.

In addition to previously described routine anatomical sequences ( T1W C+ and T2W, etc). theses sequence are helpful in the grading of Glioblastoma.

MR perfusion very clever in assessment of tumor components that have a higher grade especially in guiding stereotactic biopsy and provide a good estimation of grading of tumors.(35)

Figure (10): An Example of MR perfusion of (GBM) (36)

Spectroscopy:
it’s used in combination with MRI, MRS to evaluate Glioblastoma type and grade, as the high-grade GBM has higher Cho/Cr and Cho/NAA ratios and also have lipid and lactate as result of necrosis
(Figure 6). it’s  used to differentiate the tumor when it enhances from other enhancement cause (e.g necrosis ), also it’s used to  differentiating the tumor when it does not enhance from edema and other T2 prolongation causes.(37)

Figure (11): An Example of Spectroscopy of (GBM) (38)

 

Functional MRI
Functional MRI is very helpful in grading the condition of glioblastoma patient condition . as it used to map language function. Language paradigms vary with  Tumor location. Yet till now  no a dependable way to measure memory tasks for neurosurgical planning.  fMRI used also for Motor mapping depending on the location of the tumor.(39)

Figure (12): Example of fMRI image of Glioblastoma (40)

Generally speaking, the integration of several techniques of advanced imaging (such as spectroscopy, perfusion imaging, and functional MRI) is very helpful in grading good assessment of the pathological process of glioblastoma.

 

 

 

Treatment options and outcomes for the patient

The usual course of treatment of glioblastoma include Biopsy, then tumor debulking followed by XRT, chemotherapy (temozolomide). Newer anti-angiogenesis agents, particularly bevacizumab (vascular endothelial growth factor blocker) for recurrent disease, let’s talk about it :

 

Radiation therapy: Studies show that radiation therapy, when combined with surgery, give prolonged survival rate if we compared it to the choice of surgery alone. It increases survival from three to four months to seven to twelve months.(41)

 

Chemotherapy – Antineoplastic agents:  No optimal chemotherapeutic regimen could be defined till now, however many studies say that about more than 25% of patient receive adjuvant chemotherapy have a more prolonged survival benefits.(42)

 

Surgery: Many studies say that surgery (biopsy vs resection) have a very important effect on survival length . in a study proves that high-grade GBM who underwent total resection, get two years survival incidence up to 19%.(43) .

in another patient, when we do a subtotal resection, he only had two-year survival incidence of 0%. When we made an analysis of 28 studies, we found survival advantage of the total over subtotal resection. (14 vs 11 ).(44)

GBM MRI Recurrence Monitoring sequences.

Glioblastoma Recurrence is not uncommon, so monitoring of recurrence is important, several sequences we have discussed in this article can be used to monitor GBM recurrence, as beside usual MRI sequences that show a well appeared classic lesion, there are sequences can see beyond standard images, here we are to discuss some of these.

MRI Perfusion:  it’s very helpful in detection of GBM recurrence and differentiation between it and effects of radiation.  this is done by monitoring  ADC values differences. by capturing fluid-volume changes in intracellular and extracellular parts of enhanced parts after post-therapy imaging. (45)

Proton MRS: it gives important biochemical details about metabolites of the brain, this help in the diagnosis of the disease and help neurologist to understand the disease. 1.5 T brain MRS currently has a number of clinical applications, one of its most important application is the early diagnosis of GBM recurrence.(46)

DWI: on its images, the necrosis appears heterogeneous spotty and marked hypointense, so that in tumor recurrence, the maximal ADC is lower than in necrosis. (47)

 

 

 

 

 

 

 

 

 

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Here we are finish GBM MRI topic.

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