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More about ... Nuclear medicine
Brain imaging with SPECT and PET
Division of Nuclear Medicine, Tygerberg Academic Hospital and Stellenbosch University, Cape Town, South Africa
Corresponding author: J Warwick (jw@sun.ac.za)
Brain single photon emission computed tomography (SPECT) and
positron emission tomography (PET) are well validated and
relatively widely available modalities for the imaging of
brain function or receptor densities. Although structural
magnetic resonance imaging (MRI) and computed tomography (CT)
provide exquisite anatomical detail, SPECT and PET provide
complementary functional information. Frequently, brain
pathology will manifest as functional changes before
anatomical changes are detectable.
The imaging of cerebral metabolism indirectly via perfusion SPECT using Tc-99m hexamethylpropylene amine oxine (HMPAO) or ethylene cystinate dimer (ECD), or directly with PET using [F-18] fluorodeoxyglucose (FDG), is clinically well established. Perfusion SPECT is well tolerated by patients and widely available at relatively low cost. The performance of SPECT and how it reflects brain function are described elsewhere.1 The imaging of neurotransmitter systems is increasingly being used clinically, with increasing numbers of radiopharmaceuticals becoming available commercially, e.g. [I-123] ioflupane to image striatal dopamine transporter (DAT) density. This article briefly discusses the most important clinical applications of brain SPECT and PET.
Dementias
In patients with dementia, anatomical imaging frequently
shows little or no change. Characteristic patterns of
functional involvement using SPECT and PET can, however,
enable more accurate differentiation of these forms of
dementia (Fig. 1). Early detection and accurate determination
of the underlying cause of dementia provide information that
is useful for patient management, and has prognostic
implications.2
Alzheimer’s dementia (AD) classically shows decreased function
in the tempero-parietal regions bilaterally, although this may
be unilateral during the early stages of the disease. Posterior
cingulate gyrus and precuneus involvement are recognised as
early hallmarks. As cases advance, the frontal cortex also
becomes affected. Typically, the primary sensori-motor cortex,
visual cortex, subcortical structures, e.g. the basal ganglia
and thalami, and cerebellar lobes are spared. Currently,
diagnosis of AD is based on clinical criteria, but there is a
move towards complementing diagnostic criteria with molecular
and neuro-imaging markers. Early detection of AD is likely to
become increasingly important in genetically high-risk
individuals.
Vascular dementias can result in lesions involving the cortex, subcortical structures or cerebellum. These types of dementias are normally asymmetric, and classically involve border-zone areas of cerebral arteries. Fronto-temporal dementias are characterised by frontal and/or temporal cortex hypometabolism, with relative sparing of the parietal cortices and precuneus. Lewy body dementia (LBD) can be distinguished from AD based on occipital hypometabolism, and/or abnormal striatal DAT binding.3
Epilepsy
Patients with refractory focal epilepsy, who are candidates for surgical resection of the epileptogenic focus, frequently benefit from SPECT and/or PET imaging.4 The planning of surgery in epileptic patients requires close collaboration between the disciplines of neurology, neurosurgery, radiology, and nuclear medicine. MRI is essential in the management of these patients, although not all epileptogenic foci can be accurately localised using this modality and, conversely, not all anatomical foci are the cause of a patient’s seizures.
The ability of perfusion brain SPECT to capture a snapshot of
brain perfusion in a relatively short time frame enables ictal
SPECT to localise epileptogenic foci. Injection of a
radiopharmaceutical as soon as possible after seizure onset
demonstrates a focal area of increased activity at the site of
the epileptogenic area. In comparison, an interictal scan
(obtained between seizures) shows no abnormalities or even an
area of decreased activity at this site. The detection of the
epileptogenic focus is further enhanced using Subtraction Ictal
SPECT Co-registered with MRI (SISCOM), which requires
subtraction of the interictal SPECT from the ictal SPECT, and
superimposing the images onto anatomical MRI for accurate
anatomical localisation of the lesion (Fig. 2).
Fig. 2. Scans in a patient with refractory focal epilepsy with an epileptogenic focus, showing increased perfusion on ictal SPECT localised to the posterior aspect of the right frontal lobe on SISCOM.
Focal interictal hypometabolism on FDG-PET has also been shown
to correlate with seizure foci (Fig. 3). Hypometabolic areas on
PET often extend well beyond the true epileptogenic zone. PET
can therefore not be used to refine surgical borders, but is
useful for guiding intracranial electrode placement.
Fig. 3. An FDG-PET study in a patient with an epileptogenic focus in the left temporal lobe. The scan shows widespread hypometabolism in this lobe, more extensive than that in the epileptogenic focus alone.
Mild traumatic brain injury
Mild traumatic brain injury (mTBI) typically involves loss of
consciousness, loss of memory, alteration in mental state, or
focal neurological deficit. Commonly, it is associated with
headache, impaired thought processes, memory problems, attention
deficit, mood swings and frustration. Abnormalities are more
frequently found in mTBI patients when SPECT is performed than
with MRI and CT scans.5 Hypoperfusion in the frontal
and parietal lobes is common (Fig. 4), although the basal
ganglia, as well as the occipital, parietal and cerebellar
areas, can also be affected. SPECT has a high sensitivity and
negative predictive value for mTBI, and a normal study is
predictive of good recovery.5 However, given its limited
specificity, SPECT alone is not enough to diagnose mTBI.
Fig. 4. Scans in a patient with a head injury sustained in a motor vehicle accident 4 years previously, who subsequently developed altered personality, cognitive fallout, and depression. The MRI scan (left) is normal, while SPECT shows anterior frontal hypoperfusion consistent with mTBI.
Neurolupus
Brain SPECT and PET have a well-established role in
facilitating the diagnosis of neuropsychiatric involvement in
systemic lupus erythematosus (SLE). Varied and often subtle
clinical manifestations make this a challenging diagnosis.
Anatomical MRI is frequently normal or does not provide an
explanation for the signs and symptoms, in which case SPECT or
PET imaging is appropriate.6 These typically reveal
a pattern of multifocal perfusion deficits, and are useful,
objective tools to assist clinicians in selected cases (Fig.
5). These modalities have a good sensitivity, but a modest
specificity.
Fig. 5. A patient with SLE presented with clinical features suggestive of neurolupus. SPECT shows multiple areas of hypoperfusion in the left frontal and bilateral parietal cortex consistent with neuropsychiatric SLE.
Parkinsonism
The clinical evaluation of patients with parkinsonism can be extremely challenging, even in expert hands. The distinction between Parkinson’s disease (PD), other parkinsonian syndromes such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration and LBD, and other conditions such as essential tremor, has important implications for treatment and prognosis.
SPECT and PET imaging of DAT, dopamine receptors, brain
glucose metabolism, and myocardial autonomic function are
increasingly used to assist with these difficult distinctions.3
Most of these modalities are already available in South
Africa. DAT imaging reveals reduced presynaptic neuronal
degeneration in PD and other parkinsonian syndromes, even when
clinical features are subtle, while conditions such as
essential tremor have normal striatal DAT density (Fig. 6).
Conclusion
In this brief overview the main indications for brain SPECT and PET are discussed. These imaging modalities are available in most major centres in South Africa and are frequently required for the optimal management of a diverse group of neuropsychiatric conditions.
References
1. Warwick JM. Imaging of brain function using SPECT. Metab Brain Dis 2004;19(1-2):113-123.
2. Henderson TA. The diagnosis and evaluation of dementia and mild cognitive impairment with emphasis on SPECT perfusion neuroimaging. CNS Spectrums 2012;17(4):176-206. [http://dx.doi.org/10.1017/s1092852912000636]
3. Booij J, Teune LK, Verberne HJ. The role of molecular imaging in the differential diagnosis of parkinsonism. Q J Nucl Med Mol Imaging 2012;56(1):17-26.
4. Tamber MS, Mountz JM. Advances in the diagnosis and treatment of epilepsy. Semin Nucl Med 2012;42:371-386. [http://dx.doi.org/10.1053/j.semnuclmed.2012.06.005]
5. Lin AP, Liao HJ, Merugumala SK, et al. Metabolic imaging of mild traumatic brain injury. Brain Imaging and Behavior 2012;6:208-223. [http://dx.doi.org/10.1007/s11682-012-9181-4]
6. Bertsias GK, Ioannidis JPA, Aringer M, et al. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: Report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis 2010;69:2074-2082. [http://dx.doi.org/10.1136/ard.2010.130476]
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