Brain Perfusion SPECT

Brain perfusion SPECT shows the distribution of cerebral blood flow, which follows neuronal activity. A lipophilic tracer crosses the blood brain barrier, is trapped in brain cells in proportion to blood flow at the time of injection, and stays fixed, so the images taken later reflect the state at injection.

Technetium-99m HMPAO (exametazime) or technetium-99m ECD (bicisate) is used at 555 to 925 MBq intravenously. The patient lies in a quiet, dimly lit room with eyes open and ears unplugged for 5 to 10 minutes before and after injection, to limit sensory stimulation.

SPECT images are taken 30 to 90 minutes later over 20 to 30 minutes, with attenuation and scatter correction.

The effective dose is about 7 to 10 mSv. The study is cheap and widely available compared with PET. The resolution (8 to 12 mm) is lower than for PET.

Dementia affects about 5 to 7% of people over 60, and Alzheimer disease causes 60 to 70% of cases.

Perfusion SPECT has a sensitivity of about 80 to 85% and a specificity of about 80 to 85% for separating Alzheimer disease from normal ageing and from other dementias.

In epilepsy, ictal SPECT locates the seizure focus in 70 to 90% of patients when the injection is early.

Indications.

• Dementia: differential diagnosis of Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies and vascular dementia.
• Focal epilepsy before surgery: ictal and interictal SPECT with MRI co-registration.
• Cerebrovascular disease: perfusion reserve with acetazolamide in carotid or intracranial stenosis and before bypass surgery.
• Acute stroke or transient ischaemic attack when other imaging is not available.
• Brain death: confirmation of absent cerebral perfusion when clinical tests are not possible.
• Traumatic brain injury, encephalitis and vasculitis (persistent deficits with normal MRI).
• Movement disorders, psychiatric disorders and chronic fatigue are research or limited uses.
• Tumour recurrence against radiation necrosis, using thallium or sestamibi tracers instead.

Contraindications and precautions.

• Pregnancy: avoid unless essential. Breast feeding: interrupt for about 12 hours.
• Sedative, hypnotic and anti-epileptic drugs reduce flow and may be stopped for dementia studies, if safe. For epilepsy studies they are continued.
• Caffeine, alcohol and nicotine alter flow. They are avoided for 12 to 24 hours.
• The tracer must be injected at rest in a quiet room, and the patient must not speak or move.
• HMPAO is unstable and is used within 30 minutes of preparation (stabilised preparations last longer).
• Acetazolamide (1 g intravenously, or 14 mg for each kg in children) is avoided in sulphonamide allergy, severe renal impairment, low potassium or sodium, and uncontrolled glaucoma.
• Ictal injection needs trained staff, monitoring, and a ready tracer, with safe handling of the injection during a seizure.
• Images need a still patient. Sedation is given after the injection in children and agitated patients.

Preparation and technique.

A venous line is placed 10 to 20 minutes before injection, and the patient rests with eyes open. For dementia the tracer is given at rest. For acetazolamide studies, a baseline scan and a scan after the drug (given 15 to 20 minutes before the second injection) are compared.

Ictal studies require the tracer to be injected within seconds of seizure onset, in a video-EEG unit, by trained staff. Interictal scans are done at least 24 hours away from seizures. For brain death the tracer is injected, and images are taken immediately and at 1 hour.

The SPECT acquisition uses a multi-head gamma camera and a high resolution collimator, with a 360 degree orbit. Images are reconstructed and compared with a normal database. In epilepsy, ictal and interictal scans are subtracted and co-registered to MRI.

Normal appearances.

Uptake is symmetrical and highest in the grey matter of the cortex, basal ganglia, thalami and cerebellum, with lower white matter uptake. The visual and sensorimotor cortices and cerebellum show intense uptake. Uptake in the frontal lobes is slightly lower in elderly people.

Interpretation.

• Alzheimer disease: bilateral reduced perfusion in the posterior temporoparietal cortex and posterior cingulate, with sparing of the primary sensorimotor and visual cortex and basal ganglia. Frontal reduction occurs later.
• Frontotemporal dementia: reduced frontal and anterior temporal perfusion, often asymmetric.
• Dementia with Lewy bodies: reduced occipital perfusion in addition to the temporoparietal reduction.
• Vascular dementia: patchy, multifocal defects that follow vascular territories.
• Epilepsy: the seizure focus is hyperperfused on the ictal scan and hypoperfused on the interictal scan. Subtraction of the two images with MRI co-registration locates the focus.
• Stroke: reduced perfusion in the arterial territory, with a crossed reduction in the opposite cerebellar hemisphere (crossed cerebellar diaschisis). Subacute stroke may show luxury perfusion.
• Perfusion reserve: a fall in perfusion after acetazolamide in an area of stenosis shows exhausted reserve and a higher stroke risk. A normal increase of 20 to 30% indicates preserved reserve.
• Brain death: no uptake in the cerebral and cerebellar hemispheres (hollow appearance), with tracer in the scalp and extracranial vessels only.
• Encephalitis and vasculitis: patchy increased or reduced perfusion.
• Traumatic brain injury: focal or diffuse perfusion defects, often larger than the MRI lesion.
• Tumours: reduced perfusion in necrosis, and raised perfusion in active high grade tumours with some tracers.

Critical values and findings needing immediate action.

• Absent cerebral perfusion: supports the diagnosis of brain death, and the clinical team follows the local procedure for confirmation.
• Ictal hyperperfusion with ongoing seizures: treat the seizure (benzodiazepine, anti-epileptic drugs).
• Large perfusion defect with acute neurological deficit: urgent stroke team review.
• Severe hyperperfusion in encephalitis or after a seizure: antimicrobial and anti-epileptic treatment as indicated.
• Acetazolamide reaction (rare): paraesthesia and nausea are usual, and anaphylaxis needs resuscitation.

Limitations and artefacts.

• The spatial resolution is lower than with PET, and small cortical lesions are missed.
• Patient state at injection changes the pattern. Noise, speaking, anxiety and eye closure change flow.
• Drugs (benzodiazepines, barbiturates, antipsychotics, antidepressants), caffeine and alcohol change the pattern.
• Poor radiochemical purity and late injection of unstable HMPAO give poor images.
• Normal ageing, atrophy and partial volume effects reduce measured flow. Comparison with an age matched normal database is needed.
• Head motion and poor attenuation correction cause false defects.
• Ictal SPECT depends on the timing of injection, and late injection shows postictal change instead.
• Subacute stroke shows luxury perfusion that masks the damage.
• The test does not show the cause of a perfusion defect. MRI is needed.
• In dementia, the diagnosis rests on clinical, MRI, and cerebrospinal fluid or PET biomarkers, and SPECT adds supportive information.

Special groups.

• Children: weight based dose, sedation for imaging, and epilepsy surgery planning as the main use.
• Older patients: atrophy and white matter disease complicate the reading.
• Patients with epilepsy: video-EEG unit, and anti-epileptic drugs continued.
• Patients with stroke: perfusion reserve testing before revascularisation.
• Pregnant patients: avoid.
• Regions: dementia, epilepsy (including neurocysticercosis and cerebral malaria sequelae) and stroke are common and under diagnosed. Perfusion SPECT is available in few centres, so CT, MRI, EEG and clinical diagnosis are used.

Follow up tests.

• MRI of the brain, with volumetric and vascular sequences.
• Fluorodeoxyglucose PET for dementia and epilepsy.
• Amyloid or tau PET, cerebrospinal fluid and blood biomarkers for dementia.
• Video-EEG, magnetoencephalography and invasive EEG for epilepsy surgery.
• CT or MR angiography and Doppler ultrasound for cerebrovascular disease.
• Neuropsychological tests.
• Referral to neurology, neurosurgery, geriatrics or psychiatry.