|ECR 2018 / C-0245|
|Follow-up of brain tumors: utility of Fluorine 18-Fluorocholine PET|
Findings and procedure details
CT allows initial diagnosis and assessment of the impact of the lesion on the other brain structures: displacement of the midline, existence of herniations, obstruction of the ventricular system and development of hydrocephalus ...
However, MRI allows better characterization of the lesion. Traditional sequences provide additional information about the nature of the tumor: exact information on the location of the tumor, determining their origin on intra or extra axial space, presence of solids or cystic components, existence of intralesional hemorrhage, homogeneous or heterogeneous nature of the lesion ...
There are advanced MRI techniques that allow to go one step further in the characterization of the tumor. These techniques include diffusion, perfusion and magnetic resonance spectroscopy.
● Diffusion obtains information about the facility of water molecules to diffuse in a medium, in this case brain tissue and tumor. A lower diffusion of water molecules, ie, greater diffusion restriction, imply increased cellularity, which is characteristic of some tumors, such as lymphomas, or is associated with higher tumor grade, as in the case of gliomas. Diffusion obtained in DWI images cannot be quantified. However, it is possible to obtain maps of apparent diffusion coefficient (ADC) in which quantification is possible.
● Perfusion allows assessing vascular tumor behavior using dynamic sequences. There are different perfusion techniques. The most used, and which are currently validated for the study of tumors, involve the administration of contrast. They can be performed both by CT and MRI. MRI has better spatial resolution in the study of the brain and so is the technique of choice.
In the case of MRI, it can be performed on T1 weighted sequences using the shortening of the T1 time produced by Gadolinium contrast (DCE) or use magnetic susceptibility sequences showing heterogeneities on the magnetic field produced by the pass of a paramagnetic substance (again the gadolinium) (DSC).
There are new techniques that allow brain perfusion without contrast administration. However, currently they are only available in reference hospitals and are not validated for the study of brain tumors. This is the case of arterial spin labeling sequence (ASL).
● Magnetic resonance spectroscopy allows to know the chemical composition of the tumor. By positioning a region of interest in the lesion, it is possible to know the chemical composition of that structure. There are specific patterns of some diseases on spectroscopy. For gliomas, spectroscopy is different depending on tumor grade.
There are other imaging techniques, belonging to nuclear medicine, which are also used in the assessment of brain lesions and provide valuable information about their physiology. In this paper we will focus on positron emission tomography (PET), specifically on the utility of two radiotracers:
● 18 fluorodeoxyglucose (FDG-PET). This metabolite can measure glucose uptake by different tissues. Tumors, because of their intense mitotic activity, have an increased glucose metabolism. This is manifested in the PET images as an increase on the release of the fluorine atom bonded to the glucose molecule.
● Choline (Cho-PET). Physiologically, choline is present on cell membranes. Choline is replenished by tissues at a rate determined by regeneration needs. In the case of tumors, since they are cells with high mitotic activity, they need to synthesize cell membranes faster than healthy tissue, leading to an increased choline metabolism. Cho-PET can detect areas that have an increased choline metabolism, ie, areas having high mitotic rate, which may correspond to tumor.
Figure 2 summarizes the characteristics in advanced imaging and FDG-PET of high and low grade tumors. In the case of the Choline, behavior of this metabolite is the same in magnetic resonance spectroscopy and in Cho-PET.
In this study the utility of Cho-PET for the diagnosis of brain lesions with high mitotic activity, as high grade gliomas and metastases, is presented. Special emphasis will be made on practical utility and four clinical cases in which the Cho-PET was useful will be developed.
Case 1: Metastatic lung adenocarcinoma
74 years-old male goes to emergency room brought by his relatives because of gait disturbances, specifically mobility problems of his left leg. His family reports a change in his behavior in recent weeks. From the emergency department, it is requested to perform a CT scan (Fig 3).
In the image, a hypodense lesion is observed on right frontal lobe. It is hyperdense on its periphery and it produces significant mass effect. Perilesional edema is observed. Given the suspicion of tumor, it is decided to perform an MRI for better characterization.
Conventional MRI sequences (Fig 4) confirm the suspected diagnosis. The frontal lesion is suggestive of malignancy. It has a center of cystic degeneration (low signal on T1 and high signal on T2) and a solid peripheral portion that avidly enhancing after contrast administration and restricts diffusion. Around the lesion, there is an important perilesional edema that involves the knee of corpus callosum and does not restrict diffusion (vasogenic edema).
Subsequently, taking into account the clinical suspicion, a chest CT scan is performed. It shows a lung adenocarcinomas (Fig 5).So, the most probable diagnosis for brain lesión is metástasis.
In addition to pulmonary surgery, brain tumor surgery was performed. After surgery, a brain MRI was performed (Fig 6). Complete resection of the lesion was observed.
Small areas of hyperintensity on the image T1 after gadolinium administration correspond to areas of bleeding related to surgery (hyperintense on T1 sequence without contrast injection) or areas of contrast uptake caused by reactive changes related to recent surgery.
There are areas of restricted diffusion.
After surgery, radiation therapy is performed and new MRI control is performed five months after surgery (Fig 6).
In periventricular location, adjacent the frontal horn of the right lateral ventricle and knee of corpus callosum, it is observed an area of contrast enhancement that is accompanied by diffusion restriction.
Given these findings, tumor progression or radiation necrosis changes were thought as differential diagnosis. Although the diffusion restriction suggests malignancy, it is necessary to confirm this diagnosis since it determines the realization of a new surgical intervention.
To confirm the diagnosis, perfusion study is performed, particularly by the technique of Dynamic Susceptibility Contrast (DSC) (Fig 7). ROIs were positioned in the region affected and contralateral healthy parenchyma: a symmetrical ROI and a ROI in white matter. In both cases, a significant increase in relative cerebral blood volume is observed in the lesion.
Tumor was also studied by FDG-PET (Fig 7). However, tumor does not present a significant increase in glucose metabolism, which is against a tumor residue or recurrence.
Subsequently, 11 months after surgery, a new MRI was made (Fig 8), showing a progressive increase in size of the lesion. This suggests that lesion is a tumor rest.
At that time, Cho-PET (Fig 8) showed high metabolism of choline. The findings on imaging and patient history led to conclusion that it was a tumor rest and surgery was performed.
Therefore, in this case, techniques that proved to be more useful to determine the diagnosis of the lesion were perfusion study and Cho-PET.
Case 2: Low grade glial tumor
58 year old male presented to emergency room because of dysgeusia and dizziness. It was performed a CT scan (Fig 9) in which a hypodense lesion in right hippocampus which extends above the temporal lobe was observed. It produced a discrete mass effect on adjacent structures.
Given the findings, the MRI study was made (Fig 10). In the images, a homogeneous lesion in all sequences is observed.
● It is hypoattenuating on T1,
● It does not enhance after contrast administration.
● It is hyperintense on T2. No perilesional edema is observed.
● No bleeding remains are seen on the T2 * sequence.
● It does not restrict the diffusion of water molecules.
Perfusion study was performed (Fig 11). ROIs were positioned in the region affected and contralateral healthy parenchyma: a symmetrical ROI and ROI in white matter. A significant increase in relative cerebral blood volume was observed.
FDG-PET (Fig 11) was made. This evidence that the lesion does not have an increased glucose metabolism.
Cho-PET study was performed (Fig 12). In the location of the lesion it was not found an increased metabolism of choline.
All the described findings correspond to a lesion of benign etiology.
Surgery was performed. Intraoperative biopsy suggested diagnosis of low grade glial lesion. The study of the surgical specimen confirmed the diagnosis of gangliocytoma. It is a rare low grade glial tumor (WHO I). Typically, it presents as a solid cortical lesion. The rest of its features are common to other low grade glial tumors.
Case 3: Glioblastoma multiforme
A 68 year old man came to emergency room for tenderness in the area of the mastoid process, without alteration in the soft tissues. Pain increases with cervical hyperflexion.
A CT scan was performed (Fig 13). It shows a hypodense lesion in left cerebellar hemisphere extending to middle cerebellar peduncle. Around the injury, it is observed an hypodense area that corresponds to perilesional edema. The lesion has a significant mass effect that produces occupation of the fourth ventricle. However, ventricular size is normal.
MRI study was made (Fig 14). Images allow best characterization of the lesion discovered in tomography. It is a lesion in left cerebellar hemisphere. It has a necrotic-cystic center that shows low signal intensity on T1 and high signal intensity on T2. Around it, there is a solid portion having an intense contrast ring enhancement with thickened nodular áreas. There is also a solid portion in the anteromedial pole. In DWI, no significant restriction is observed.
Radiological diagnosis of glioblastoma multiforme (WHO IV) was suggested. Intraoperative biopsy established the diagnosis of high grade glioma, glioblastoma multiforme (WHO IV). However, the study of the surgical specimen allowed the definitive diagnosis of pilomyxoid astrocytoma (WHO II), although it showed some anaplastic features.
The pilomyxoid glial astrocytoma is a low grade tumor typically occurring in the diencephalon and affecting young subjects. It usually arises from hypothalamus or optic chiasm. However, they can occur anywhere in the brain, even in the spinal cord.
In addition to surgery, radiotherapy was performed. In the first control after radiotherapy (Fig 15), a central area of necrotic-cystic changes is seen. There is also a peripheral zone that enhances significantly after contrast administration and also presents diffusion restriction.
With these findings, the differential diagnosis was established between tumor recurrence and radionecrosis. It was recommended to monitor closely.
The second post-radiotherapy control (Fig 15) showed clear radiological worsening, with enlargement of the solid portion, more enhancement after contrast administration and perilesional edema. Growth of the lesion growth, and specifically of its solid portion, with increased perilesional edema, strongly suggested tumor recurrence. It was decided to complete the study with Cho-PET (Fig 16).
In this study we observed that the lesion had a significant metabolism of choline, which is also consistent with tumor recurrence.
Case 4: Anaplastic oligodendroglioma
A 70 year old man had continuous headache that had progressively increased in recent months. He provided printed photographs of a radiological study performed in another center and the radiology report. A left frontal lesion is described. It was decided to perform an MRI study.
On MRI (Fig 17), a lesión showing low signal on T1, with presence of some areas of necrotic-cystic degeneration is observed. In its solid portion, it presents a significant contrast enhancement and slightly restricts the diffusion of water molecules.
Given the findings on MRI, a differential diagnosis between oligodendroglioma and low grade astrocytoma was established.
Intraoperative biopsy suggested diagnosis of low grade astrocytoma. Surgical specimen study allowed definitive diagnosis of anaplastic oligodendroglioma.
After surgery, radiation therapy was performed. MRI images of controls made 3 and 15 months after treatment are shown (Fig 18).
In the first control, a left frontal and a subcutaneous cystic area of postsurgical changes was observed. There was also a thin line of contrast enhancement that was accompanied by signal hyperintensity in the diffusion sequence. The findings can be explained as changes in relation to recent surgery.
In the second control, a new onset hyperintense lesion was observed. It presents a significant perilesional edema and diffusion restriction. These findings suggested that there was a tumor recurrence.
It was decided to complete the study with a cerebral perfusion (Fig 19). Increased relative cerebral blood volume in comparison to symmetric region in healthy contralateral brain parenchyma was observed, suggesting tumor recurrence.
Cho-PET also showed a significant increase in metabolism, indicating that there was an active tumor (Fig 20).
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