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EBI
Soonmee Cha, MD
I.
Imaging of Brain Cancer
II.
Authors
Soonmee Cha, MD
Department of Radiology and Neurological Surgery
University of California, San Francisco
505 Parnassus Avenue
Box 0628, Rm. L358
San Francisco, CA 94143
KEY POINTS
Issues
1. Who should undergo imaging to exclude brain cancer?
Applicability to Children
2. What is the appropriate imaging in subjects at risk for brain cancer?
Applicability to Children
Special Case: Can imaging be used to differentiate post-treatment necrosis from residual
tumor?
Special Case: Neuroimaging modality in patients with suspected brain metastatic disease.
Special Case: How can tumor be differentiated from tumor-mimicking lesions?
Issue 3: What is the role of Proton Magnetic Resonance Spectroscopy (1H MRS) in the
diagnosis and follow-up of brain neoplasms?
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Issue 4: What is the cost-effectiveness of imaging in patients with suspected primary
brain neoplasms or brain metastatic disease?
IV.
Key points:
•
Brain imaging is necessary for optimal localization, characterization and
management of brain cancer prior to surgery in patients with suspected or
confirmed brain tumors. (STRONG EVIDENCE)
•
Due to its superior soft tissue contrast, multi-planar capability and bio-safety,
magnetic resonance imaging with and without gadolinium-based intravenous
contrast material is the preferred method for brain cancer imaging when
compared to computed tomography. (MODERATE EVIDENCE)
•
No adequate data exists on the role of imaging in monitoring brain cancer
response to therapy and differentiating between tumor recurrence and therapy
related changes. (INSUFFICIENT EVIDENCE)
•
No adequate data exists on the role of non-anatomic, physiology-based
imaging, such as proton MR spectroscopy, perfusion and diffusion MR
imaging, and nuclear medicine imaging (SPECT and PET) in monitoring
treatment response or in predicting prognosis and outcome in patients with
brain cancer (INSUFFICIENT EVIDENCE)
•
Human studies conducted on the use of MRS for brain tumors demonstrate
that this non-invasive method is technically feasible and suggest potential
benefits for some of the proposed indications. However, there is a paucity of
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high quality direct evidence demonstrating the impact on diagnostic thinking
and therapeutic decision making.
III.
Discussion of Issues
Issue 1: Who should undergo imaging to exclude brain cancer?
Summary of the Evidence
The scientific evidence on this topic is limited. No strong evidence studies are available.
Most of the available literature is classified as limited and moderate evidence. First, the
three most common clinical symptoms of brain cancer are headache, seizure, and focal
weakness—all of which are neither unique nor specific for the presence of brain cancer
(see Headache and Seizure Chapters). Second, the clinical manifestation of brain cancer
is heavily dependent on the topography of the lesion. For example, lesions in the motor
cortex may have more acute presentation whereas more insidious onset of cognitive or
personality changes are commonly associated with prefrontal cortex tumors.
Despite the aforementioned nonspecific clinical presentation of subjects with brain cancer,
a summary of the guidelines is shown in Table 1. A relatively acute onset of any one of
these symptoms that progresses over time should strongly warrant a brain imaging.
Newton et al cite a consensus among neurologists that the most specific clinical feature of
a brain cancer versus other brain mass lesions is not one particular individual symptom or
sign but, rather, progression over time.
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Issue 2: What is the appropriate imaging in subjects at risk for brain cancer?
Summary
The sensitivity and specificity of MRI is higher than CT for brain neoplasms (moderate
evidence). Therefore, in high-risk subjects suspected of having brain cancer MRI with
and without gadolinium-based contrast agent is the imaging modality of choice to further
characterize the lesion. Table 2 lists advantages and limitations of CT and MRI in the
evaluation of subjects with suspected brain cancer.
There is no strong evidence to suggest that the addition of other diagnostic tests,
such as MR spectroscopy, perfusion MR, PET or SPECT improves either the cost
effectiveness or the outcome in the high-risk group at initial presentation.
Special Case: Neuroimaging differentiation of post-treatment necrosis from residual
tumor.
Imaging differentiation of treatment necrosis and residual/recurrent tumor is
challenging because they both can appear similar and also can co-exist in a single given
lesion. Hence the traditional anatomy based imaging methods have a limited role in the
accurate differentiation between the two entities. Nuclear medicine imaging techniques
such as SPECT and PET provide functional information on tissue metabolism and
oxygen consumption and thus offer theoretical advantage over anatomic imaging in
differentiation tissue necrosis and active tumor. Multiple studies demonstrate that
SPECT is more sensitive and specific than is PET in differentiating tumor recurrence
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from radiation necrosis. There is also insufficient evidence of the role of MR
spectroscopy in this topic (see Issue 3).
Special Case: Neuroimaging modality in patients with suspected brain metastatic
disease
Brain metastases are far more common than primary brain cancer in
adults owing to higher prevalence of systemic cancers and their propensity to
metastasize. Focal neurologic symptoms in a patient with history of systemic
cancer should raise a high suspicion for intracranial metastasis and prompt
imaging. The preferred neuroimaging modality in patients with suspected brain
metastatic disease is MRI with single dose (0.1mmole/kg body weight) of
gadolinium-based contrast agent. Most studies described in the literature suggest
that contrast-enhanced MR imaging is superior to contrast-enhanced CT in the
detection of brain metastatic disease, especially if the lesions are less than 2 cm
(moderate evidence).
Davis and colleagues (moderate evidence) studied comparative imaging
studies in 23 patients comparing contrast-enhanced MR with double dose-delayed
CT. Contrast-enhanced MR imaging demonstrated more than 67 definite or typical
brain metastases. The double dose-delayed CT revealed only 37 metastatic lesions.
The authors concluded that MR imaging with enhancement is superior to double
dose-delayed CT scan for detecting brain metastasis, anatomic localization, and
number of lesions. Golfieri and colleagues reported similar findings (moderate
evidence). They studied 44 patients with small cell carcinoma to detect cerebral
metastases. All patients were studied with contrast-enhanced CT scan and
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gadolinium-enhanced MR imaging. Of all patients, 43% had cerebral metastases.
Both contrast-enhanced CT and gadolinium-enhanced MR imaging detected lesions
greater than 2 cm. For lesions less than 2 cm, 9% were detected only by
gadolinium-enhanced T1-weighted images. The authors concluded that
gadolinium-enhanced T1-weighted images remain the most accurate technique in
the assessment of cerebral metastases. Sze and colleagues performed prospective
and retrospective studies in 75 patients (moderate evidence). In 49 patients, MR
imaging and contrast-enhanced CT were equivalent. In 26 patients, however,
results were discordant, with neither CT nor MR imaging being consistently
superior. MR imaging demonstrated more metastases in 9 of these 26 patients.
Contrast-enhanced CT, however, better depicted lesions in 8 of 26 patients.
There are several reports on using triple dose of contrast agent to increase
sensitivity of lesion detection. In another study by Sze et al, however, have found that
routine triple-dose contrast agent administration in all cases of suspected brain metastasis
was not helpful, could lead to increasing number of false-positive results, and concluded
that the use of triple-dose contrast material is beneficial in selected cases with equivocal
findings or solitary metastasis. Their study was based on 92 consecutive patients with
negative or equivocal findings or a solitary metastasis on single-dose contrast-enhanced
MR images underwent triple-dose studies.
Special Case: How can tumor be differentiated from tumor-mimicking lesions?
There are several intracranial disease processes that can mimic brain cancer and
pose a diagnostic dilemma on both clinical presentation and conventional magnetic
resonance (MR) imaging, such as infarcts, radiation necrosis, demyelinating plaques,
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abscesses, hematomas, and encephalitis. On imaging, any one of these lesions and brain
cancer can both demonstrate contrast enhancement, peri-lesional edema, varying degrees
of mass effect, and central necrosis.
There are numerous reports in the literature of misdiagnosis and mismanagement
of these subjects who were erroneously thought to have brain cancer and, in some cases,
went on to surgical resection for histopathologic confirmation. Surgery is clearly
contraindicated in these subjects and can lead to unnecessary increase in morbidity and
mortality. A large acute demyelinating plaque, in particular, is notorious for mimicking
an aggressive brain cancer. Due to presence of mitotic figures and atypical astrocytes,
this uncertainty occurs not only on clinical presentation and imaging but also on
histopathological examination. The consequence of unnecessary surgery in subjects with
tumor-mimicking lesions can be quite grave and hence every effort should be made to
differentiate them from brain cancer. Anatomic imaging of the brain suffers from
nonspecificity and its inability to differentiate tumor from tumor-mimicking lesions.
Recent developments in non-anatomic, physiology based MR imaging methods, such as
diffusion/perfusion MRI and proton spectroscopic imaging, promise to provide
information not readily available from structural MRI and improve diagnostic accuracy.
Diffusion-weighted MR imaging has been shown to be particularly helpful in
differentiating cystic/necrotic neoplasm from brain abscess by demonstrating marked
reduced diffusion within an abscess. Chang et al compared diffusion-weighted imaging
(DWI) and conventional anatomic MR imaging to distinguish brain abscesses from cystic
or necrotic brain tumors 11 patients with brain abscesses and 15 with cystic or necrotic
brain gliomas or metastases. They found that postcontrast T1WIs yielded a sensitivity of
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60%, a specificity of 27%, a positive predictive value (PPV) of 53%, and a negative
predictive value (NPV) of 33% in the diagnosis of necrotic tumors. DWI yielded a
sensitivity of 93%, a specificity of 91%, a PPV of 93%, and a NPV of 91%. Based on the
analysis of receiver operating characteristic (ROC) curves, they found clear advantage of
DWI as a diagnostic tool in detecting abscess when compared to postcontrast T1WI.
Table 5 lists neurological diseases that can mimic brain cancer both on clinical
grounds and on imaging. By using diffusion-weighted imaging, acute infarct and abscess
could readily be distinguished from brain cancer since reduced diffusion seen with the
first two entities. Highly cellular brain cancer can have reduced diffusion but not to the
same degree as acute infarct or abscess.
Issue 3: What is the role of Proton Magnetic Resonance Spectroscopy (MRS) in the
diagnosis and follow-up of brain neoplasms?
Summary
The Blue Cross Blue Shield Association (BCBSA) Medical Advisory Panel concluded
that the MRS in the evaluation of suspected brain cancer did not meet the Technology
Evaluation Center (TEC) criteria as a diagnostic test, hence further studies in a
prospectively defined population is needed.
Issue 4: What is the cost-effectiveness of imaging in patients with suspected primary
brain neoplasms or brain metastatic disease?
Summary
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Routine brain CT in all patients with lung cancer has a cost-effectiveness ratio of $69,815
per QALY. However, the cost per QALY is highly sensitive to variations in the negative
predictive value of a clinical evaluation, as well as to the cost of CT. CEA of patients
with headache suspected of having a brain neoplasm are presented in the headache
chapter.
Table 1.
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Clinical symptoms suggestive of a brain cancer
Non-migraine, non-chronic headache of moderate to severe degree (see
Headache Chapter)
Partial complex seizure (see Seizure Chapter)
Focal neurological deficit
Speech disturbance
Cognitive or personality change
Visual disturbance
Altered consciousness
Sensory abnormalities
Gait problem or ataxia
Nausea and vomiting without other gastrointestinal illness
Papilledema
Cranial nerve palsy
Table 5.
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Brain cancer mimicking lesions
Infarct
Radiation necrosis
Abscess
Demyelinating plaque
Subacute hematoma
Encephalitis
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