ORIGINAL ARTICLE

Delayed Development of Radiation Vasculopathy of the
Brain Stem Confirmed by F-18 FDG PET in a Case of
Anaplastic Astrocytoma
Ashok Muthukrishnan, MD, MS, Mehran Bajoghli, MD, and James M. Mountz, MD, PhD

Received for publication August 18, 2006; revision accepted March 27,
2007.
From the Division of Nuclear Medicine, Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA.
Reprints: James M. Mountz, MD, PhD, Division of Nuclear Medicine,
University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsubrgh,
PA 15213. E-mail: mountzjm@upmc.edu.
Copyright © 2007 by Lippincott Williams & Wilkins
ISSN: 0363-9762/07/3207-0527

an average survival of 2 years.2 The peak incidence is in the
fifth and sixth decades of life. On magnetic resonance imaging (MRI), anaplastic astrocytomas typically show inhomogeneous, mixed attenuation intensity with rim enhancement,
and usually with surrounding edema.5,6 While these tumors
can occur anywhere in the cerebral hemispheres, they are
most common in the frontal and temporal lobes. The treatment of astrocytomas can involve surgical resection, radiation therapy, and chemotherapy.7,8 Long-term complications
of radiation therapy include radiation vasculopathy and secondary malignancy. Secondary malignancy development after radiation therapy for the central nervous system has a risk
of approximately 1%–3%.9 –14
The latency from radiation therapy treatment to the
development of vasculopathy ranges from 2 to 25 years with
peak incidence at approximately 3 years.15,16 Cases of delayed radiation injury that developed as late as 27 years after
radiotherapy are extremely rare.17 To date, there have been
very few cases of radiation-induced neoplasm reported after
radiosurgery.18 In another case report radiation vasculopathy
of intracranial major arteries in children has also been described.19 It has been hypothesized that deterioration in prostaglandin I-2 synthesis plays a key role in the genesis of
radiation-induced vasculopathy.20
In addition, it has been suggested that accelerated
atherosclerosis develops in large arteries leading to repeated
small strokes. The histopathology of radiation vasculopathy
is thought to be the result of cerebral capillary destruction
leading to abnormal permeability of the blood brain barrier.21
The brain stem has many vital functions, including
consciousness, controlling heart rate, and respiratory rate.
Brain stem lesions typically present as gait disturbance,
headache, and weakness of the limbs, diplopia, and/or dysphagia. Other symptoms include weakness of one or more
limbs, signifying involvement of the corticospinal, and corticobulbar pathways.22 The brain stem accounts for less than
2% of gliomas and are more common in children than
adults.23,24 On MRI, brain stem tumors are typically isointense or hypointense on T1-weighted images, hyperintense on
T2-weighted images, and enhance uniformly after administration of intravenous gadolinium contrast.25,26 The close
proximity of these tumors to the surrounding critical normal
structures limits invasive procedures such as biopsy or surgical resection.

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Abstract: We present the imaging findings of a 38-year-old female
patient who underwent resection and radiation therapy for an anaplastic astrocytoma in her left temporal lobe 12 years ago. She was
symptom-free until 1 month before admission at which time she
presented with symptoms of right hemiparesis, right facial droop,
and slurred speech. Magnetic resonance imaging (MRI) of the brain
showed a new mass lesion in the left pontine region of the brain
stem. Magnetic resonance spectroscopy imaging of the lesion demonstrated an increase in choline (Ch)/N-acetyl aspartate (NAA)
metabolite values which were nondiagnostic. Since viable tumor
recurrence was strongly suspected, a biopsy was planned, although
this posed significant risk. Therefore, an F-18 FDG brain PET scan
was performed, which demonstrated no metabolic activity in the
pontine lesion leading to the less common diagnosis of long-term
postradiation vasculopathy. Over the next 6 months, the patient’s
symptoms slowly improved and a follow-up MRI scan showed a
decrease in the size of the lesion, consistent with postradiation
vasculopathy and infarction. This case illustrates the importance of
considering the rare diagnosis of radiation-induced vasculopathy in
the differential diagnosis when symptoms of recurrent brain tumor
occur.
Key Words: F-18 FDG, brain stem mass, radiation vasculopathy,
anaplastic astrocytoma
(Clin Nucl Med 2007;32: 527–531)

T

he incidence of primary intracranial malignancy is approximately 7 cases per 100, 000 persons per year.1
Anaplastic astrocytoma is classified as grade 3 by the World
Health Organization (WHO), a category that falls between
low (1 and 2) and high-grade2 astrocytomas.3,4 Common
presenting symptoms are seizures, focal neurologic symptoms, headache, and vomiting among others depending on the
location of the tumor. Overall, there is a poor prognosis with

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Muthukrishnan et al

In terms of imaging for tumor recurrence, CT and MRI
cannot reliably differentiate tumor recurrence from radiation
related changes. MR spectroscopy is particularly helpful for
the differentiation of locally infiltrative tumor from other
types of well-circumscribed intracranial lesions.27 Measurement of choline (Ch) and N-acetyl aspartate (NAA), and their
ratio (Ch/NAA) has shown promise in distinguishing high
grade from low-grade lesions.28,29 Magnetic resonance spectroscopy imaging (MRSI) may be helpful in guiding biopsy
location within lesions that are heterogeneous in nature or
with necrotic or cystic components. F-18 FDG PET scanning
has been widely employed in assessment of brain tumors. It
has shown tremendous utility in the evaluation and management of patients with brain tumors including grading of such
tumors and determination of prognosis.30 –32

CASE REPORT
The patient is a 38-year-old female patient who underwent a left temporal craniotomy for resection of an anaplastic
astrocytoma 12 years ago for which she received whole brain
radiation therapy. Subsequently she underwent periodical
clinical and MR follow-ups. The patient was in her usual
good state of health, until she suffered progressive right facial
droop, dysarthria, and slurred speech as well as right hemiparesis, 12 years after resection. Brain MRI and MRSI were
performed, followed by F-18 FDG PET.

METHODS
The patient was imaged with GE LX Echospeed (General Electric Medical Systems, Milwaukee, WI) high-field
strength 1.5 Tesla (T) MRI scanner, Sagittal T2-weighted,
axial FLAIR, proton density, axial T1 weighted, without and
with IV Gadolinium-DPTA (Gd) enhancement. 1H MR spectroscopic Imaging (PRESS 2D CSI, TR: 1000 –1500 milliseconds, TE: 35,144,288 milliseconds) was performed at 1.5
T over the lesion. Volumes of interest (1.6 ⫻ 1.6 cm3)
selected from the lesion center were analyzed for Ch and
NAA in each zone. F-18 FDG PET scan was obtained on a
Siemens ECAT EXACT HR⫹ in 3D mode, with an in-plane
resolution of 6 mm, full width half maximum, matrix size of
128 ⫻ 128, 25 cm field-of-view. In a quiet and dimly lit
room, with minimal ambient noise to decrease any stimulation of the brain, 406 MBq (10.97 mCi) of F-18 FDG was
injected intravenously. Following a 30-minute uptake period,
transmission images were obtained for the initial 10 minutes
followed by a 30-minute emission acquisition. The images
were reoriented in the transverse, sagittal, coronal, and canthomeatal planes. The PET data was coregistered with the
MR images using the Siemens Syngo software suite.

RESULTS
Interval postsurgery imaging and follow-up MRI of the
brain showed a thin rim of T2 prolongation within the parenchyma adjacent to the resection bed in the inferotemporal fossa,

FIGURE 1. Axial T1 with gadolinium
contrast, and axial T2 flair images
show abnormal signal throughout
the uncus and into the pons, concerning for tumor spread.

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Radiation Vasculopathy of the Brain Stem

frontal and parietal lobes with no evidence of enhancing tumor.
The findings have been consistent with radiation-induced leukomalacia. When the patient presented with progressive neurologic symptoms, MRI of the brain revealed a new focus of
enhancement in the left pons with surrounding edema suggestive
of possible tumor recurrence (Fig. 1). Again there was evidence
of leukomalacia in the surgical bed. MRSI of the lesion showed
diminished NAA/Ch peak and an increase in Ch/NAA metabolite values which were nondiagnostic (Fig. 2). Because of
worsening symptoms, consideration was made to perform a
biopsy. However, because of the critical location of the mass in
the pons that was close to other vital structures noninvasive
evaluation with F-18 FDG PET was recommended to confirm
suspected tumor. The F-18 FDG PET scan showed diminished
F-18 FDG uptake in the left pons (Fig. 3). The PET findings
were consistent with long-term radiation vasculopathy resulting
in brain stem infarction. The most recent follow-up MRI of the
brain after the PET scan showed a decrease in enhancement in
the area of abnormal signal in the left pons (Fig. 4).

On F-18 FDG PET, recurrence of the tumor in brain
stem typically appears as an area of increased uptake more
than the white matter. This case highlights the importance of
considering radiation vasculopathy in the differential diagnosis of recurrence of symptoms in patients with brain stem
tumor status postradiation. In this illustrated example, radiation vasculopathy occurred as a long-term complication extremely late and had symptoms similar to recurrent disease
and in a different location other than the original site of the
tumor. MR imaging to confirm the diagnosis is usually
sufficient, however, as depicted here, the MRI and even MRS
were inconclusive. The findings on the follow-up MR scan,
12 years after resection of the primary tumor, along with the
clinical presentation, prompted high suspicion for recurrent
disease, or for a primary brain stem glioma, albeit less likely.
The evaluation of F-18 FDG PET in this case demonstrated
hypometabolism of the mass in the pons, with intensity of
FDG uptake less than normal white matter activity, consistent
with a benign entity. Stereotactic biopsy of cerebral tumors
can provide a pathologic diagnosis but this can be invasive
with a complication rate lower than that of craniotomy.
Diagnostic yield depends on safe sampling of the most
representative region of the mass.32 The fact that the lesion in
question was ametabolic spared the patient from having a
biopsy of the mass located in a strategically dangerous area.

DISCUSSION
Diffuse leukodystrophy with confluent regions of subcortical gliosis and demyelination can occur secondary to chronic
radiation injury.33,34 Cerebral capillaries may be destroyed leading to abnormal permeability of the blood brain barrier. This
leads to enhancement on cerebral MRI in regions of radiation
changes, which frequently renders delineation between radiation-induced necrosis and tumor recurrence very obscure. The
confounding medical problem is that these patients often present
with clinical symptoms similar to those of tumor recurrence. On
radiologic imaging, diffuse white matter injury appears hypoattenuating on CT and hyperintense on MR imaging.18,19,35

CONCLUSIONS
Patients who present with clinical symptoms akin to
tumor recurrence long after radiation pose a complex diagnostic
problem. Routine anatomic imaging modalities like MR may
reveal new mass lesions that obligate the clinician to take the
biopsy route. F-18 FDG PET imaging should be performed in

FIGURE 2. MR Spectroscopy centered over the left rim enhancing pontine lesion and over a normal appearing region in the
right posterior temporal lobe is shown. The spectrum centered over the left pontine lesion reveals a diminished NAA/choline
ratio. The relative choline peak is increased relative to NAA, the pattern is nonspecific and not typical for tumor. The control
spectrum over the normal right temporal lobe region is within normal limits.
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FIGURE 3. FDG PET shows decreased F-18 FDG uptake in the location of the enhancing lesion seen
on the MRI in the pons region with
no evidence of viable tumor.

FIGURE 4. The most recent follow-up MRI with gadolinium shows
marked diminution of the size and
the intensity of the signal in the previously noted abnormal area of enhancement in the brain stem (arrow), further supporting radiationinduced infarction rather than tumor
recurrence.

such circumstances before an invasive procedure is contemplated and could often circumvent a risky course of action. In the
case presented, a new lesion appeared farther away from the
original tumor site more than a decade after the initial radiation.
The lack of uptake on F-18 FDG PET corresponding to the area
of abnormal signal on MRI confirmed that the brain stem lesion
was long-term radiation-induced vasculopathy and not tumor

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recurrence, which correctly precluded the patient from having a
preventable invasive procedure.
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