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Applications of cerebral SPECT
Clinical Radiology 66 (2011) 651e661
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.elsevierhealth.com/journals/crad
Pictorial Review
Applications of cerebral SPECT C. McArthur*, R. Jampana, J. Patterson, D. Hadley Department of Neuroradiology, Institute of Neurological Sciences, Glasgow, UK
art icl e i nformat ion Article history: Received 30 September 2010 Received in revised form 21 December 2010 Accepted 29 December 2010
Single-photon emission computed tomography (SPECT) can provide three-dimensional functional images of the brain following the injection of one of a series of radiopharmaceuticals that crosses the bloodebrain barrier and distributes according to cerebral perfusion, neurotransmitter, or cell density. Applications include differentiating between the dementias, evaluating cerebrovascular disease, preoperative localization of epileptogenic foci, diagnosing movement disorders, and evaluation of intracerebral tumours, while also proving a useful research tool. Unlike positronemission tomography (PET), SPECT imaging is widely available and can be performed in any department that has access to a rotating gamma camera. The purpose of this review is to demonstrate the utility of cerebral SPECT and increase awareness of its role in the investigation of neurological and psychiatric disorders. Ó 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Single-photon emission computed tomography (SPECT) is a functional technique introduced in the early 1980s for the investigation of regional cerebral blood flow and receptor density studies.1 It is complementary to computed tomography (CT) and magnetic resonance imaging (MRI), with co-registration possible, and can be more sensitive as many cerebral disease entities show functional changes before structural abnormality. The National institute for Health and Clinical Excellence now recognizes the role of SPECT in the investigation of dementia, Parkinson’s disease (PD), and brain tumours.2e4 A ligand that traces cerebral perfusion, binds to a specific brain receptor/transporter or is taken up by cells is tagged with a radionuclide prior to intravenous injection. Using a rotating gamma camera and the techniques of filtering, back projection, and attenuation correction, a three-dimensional
* Guarantor and correspondent: C. McArthur, Department of Neuroradiology, Institute of Neurological Sciences, Southern General Hospital Campus, 1345 Govan Road, Glasgow G51 4TF. Tel.: þ44 (0) 7973386217. E-mail address: [email protected] (C. McArthur).
image of the distribution of the radionuclide in the brain is obtained. Meticulous acquisition technique is very important to maintain image quality. Patient co-operation is essential with attention to patient comfort, optimal positioning, and use of a head-holder device. Scanning time depends on the radiopharmaceutical, imaging system, and required resolution, with high-quality images of the whole brain obtained in 20e30 min.5 Images are assessed visually and with semiquantitative analysis using voxel-based statistics, such as statistical parametric mapping.
Cerebral perfusion Neuronal tissue that is metabolically more active consumes more oxygen and nutrients and, therefore, has a higher blood flow than less active tissue. Cerebral perfusion and metabolism are coupled in nearly all physiological and pathological situations.6 Perfusion imaging is commonly undertaken with two 99mTc labelled compounds: hexamethylpropylene-amide oxime (HMPAO) and L, L-ethyl cysteinate dimer (ECD). Their differences are related to in vitro stability, uptake, and dosimetry with 99mTc-ECD reflecting cellular metabolic uptake and HMPAO more closely reflecting blood flow.6 Following intravenous
0009-9260/$ e see front matter Ó 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2010.12.015
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Figure 1 Axial images demonstrating a normal averaged HMPAO perfusion scan. This scan is averaged over 32 normal volunteers (i.e., images summed together and then counts per pixel divided by 32) to allow for natural variation in anatomical positioning and gyral/sulcal patterns. The colour scale is shown d dark blue representing lower activity and yellow higher activity. (This colour scale applies to all other SPECT images in the review other than Fig 9) a, right temporal lobe; b, left cerebellar hemisphere; c, right occipital lobe; d, right and left cingulate gyri; e, right thalamus; f, right head of caudate; g, left lentiform nucleus; h, left parietal lobe; i, left frontal lobe.
Figure 2 (a) HMPAO perfusion image in a patient with mild dementia demonstrating reduced perfusion in the parietal and posterior temporal lobes typical of AD (arrows). (b) The HMPAO perfusion image performed on the same patient 3 years later when symptoms had progressed. There is now significantly more reduced temporoparietal perfusion (arrows) and also hypoperfusion in the frontal lobes bilaterally.
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administration of 99mTc-HMPAO it rapidly crosses the bloodebrain barrier (BBB) in proportion to regional cerebral blood flow at the time of delivery. Once in the neuronal and glial cells, it interacts with glutathione and within 1e2 min undergoes stereoisomeric alteration from lipophilic to hydrophilic, becoming trapped within the neuronal tissue providing a snapshot of brain perfusion, hence function, at that time. Maximum uptake is reached in under a minute7 and distribution remains static for many hours.6 To perform a perfusion study, intravenous access is established in advance and injection takes place in a quiet dimly lit room to avoid external stimuli. The patient remains basal for a further 5e10 min and image acquisition delayed for no more than 30 min to allow background clearance from the vascular pool.8 The effective dose for a routine HMPAO perfusion or dopamine transporter (DAT) scan is 4e5 mSv and for a thallium scan up to 18 mSv. The normal adult brain shows symmetrical increased uptake in the temporal, parietal and occipital cortices and basal ganglia, thalami and cingulate gyrus.9 Grey matter is differentiated from white matter due to its increased blood flow (Fig 1). Focal or regional areas of pathologically increased or decreased uptake may be identified.
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SPECT, of 84% with positive SPECT and of 52% with a negative SPECT.14 SPECT studies also provide a higher specificity against other types of dementia than clinical criteria alone (91 versus 70%).13 Correlation should be performed with CT or MRI, which will exclude other diseases, while a normal structural examination will further support the characteristic SPECT findings.
Vascular dementia Symptoms of vascular dementia have a step-wise temporal profile. Multiple small emboli are caused by atherosclerosis of the carotid and middle cerebral arteries (MCAs). Multiple randomly distributed foci of hypoperfusion are seen and there may be involvement of the motor and sensory cortices9 and subcortical structures10
Dementia SPECT shows characteristic patterns of hypoperfusion in each of the dementias.10 The type of dementia has important implications for the patient due to the development of more specific therapies.6 In many cases CT or MRI may only show non-specific or late findings, such as focal or regional atrophy. A clearly normal study is clinically also useful.
Alzheimer’s disease (AD) AD is characterized pathologically by plaques, amyloid deposition, and neurofibrillary tangles. It is no longer a diagnosis of exclusion11 and SPECT is now an established technique used to support the clinical diagnosis.1 It demonstrates bilateral hypoperfusion of the parietal and posterior temporal lobes with sparing of the sensory and motor cortices, visual cortex, basal ganglia, thalami and cerebellar hemispheres (Fig 2) with the temporoparietal hypoperfusion more severe in early-onset disease.9 These perfusion changes may be linked to the well-documented late structural brain changes in AD of temporal lobe and hippocampal atrophy.12 As the disease progresses the frontal lobes also become involved.10 Sensitivity and specificity of SPECT for AD have been shown to be 86 and 96%, respectively,9 and even in mild AD 80% of patients have abnormal SPECT examinations.1 While pathological verification studies suggest that clinical criteria may be more sensitive than SPECT (81 versus 74%)13 the two should be considered complementary. In a group of 70 patients with dementia and 14 controls, all with autopsy, SPECT was most useful when there was a clinical diagnosis of “possible AD” with a probability of AD of 67% without
Figure 3 (a) Selected axial T2-weighted (T2W) fluid-attenuated inversion recovery (FLAIR) MRI images in an elderly man presenting with confusion and difficulty walking demonstrate extensive abnormal white matter signal changes affecting the subcortical and periventricular regions and an old right thalamic infarct (DWI showed no restricted diffusion). (b) HMPAO SPECT demonstrates patchy decreased perfusion in keeping with ischaemic damage and no evidence of the pattern associated with AD or frontotemporal dementia.
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presumably reflecting the variable anatomic localization of the underlying vascular disease. Correlation with structural information from CT or MRI is helpful (Fig 3). Underlying vascular causes resulting in decreased cerebrovascular reserve can be demonstrated by giving a vasodilator, such as acetazolamide, prior to the
radiopharmaceutical.10 Acetazolamide causes an increase in regional cerebral perfusion by 30e50% in areas with intact vascular reserve but not in areas where the arterioles are already fully dilated, such as with ischaemia or small vessel disease. Perfusion will increase in the originally hypoperfused areas of AD patients but remains the
Figure 4 (a) Axial T2W FLAIR MRI in an elderly woman who presented with dementia demonstrates early atrophy with evidence of small vessel disease. (b) HMPAO SPECT shows grossly decreased perfusion in the frontal and anterior temporal lobes and cingulate gyri (arrows) with sparing of the posterior temporal and occipital lobes consistent with frontotemporal dementia. This demonstrates the obvious advantage of SPECT over MRI in this case.
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same or disease.14
decreases
in
those
with
cerebrovascular
Frontotemporal dementia (Pick’s disease) Clinical diagnosis in this condition can be difficult. Symptoms include gradual-onset confusion and changes in personality and behaviour.9 SPECT shows symmetric hypoperfusion of the frontal lobes extending to the anterior cingulate gyri (Fig 4). Behavioural changes are seen when the right temporal lobe is involved and aphasia if the dominant temporal lobe is involved.
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Lewy body dementia Lewy body dementia is now widely recognized as the second commonest form of late-life degenerative dementia after AD and presents with dementia, visual hallucinations, and parkinsonism. Accurate diagnosis of Lewy body dementia is important, not only because such patients respond with serious adverse reactions (increasing confusion, parkinsonism, increased mortality) to antipsychotics, but also because they may be particularly responsive to cholinesterase inhibitors.12 Previously HMPAO was used but the differentiation with AD was poor and this has now been superseded by DAT scanning with the recognition that it is part of the PD spectrum.
Figure 5 Temporal sequence of HMPAO axial images from the same level performed on the same patient who presented with symptoms of a left MCA territory acute infarct. (a) Within 2 h of onset of symptoms there is a large perfusion defect in the left MCA territory representing all underperfused neuronal tissue including the ischaemic penumbra. This is a larger area of abnormality than would be seen on CT at this time, which may still appear normal. (b) Within 3 days of symptoms the hypoperfused area has reduced to a smaller wedge-shaped area in the left frontal lobe. (c) Within 2 weeks, loss of autoregulation has led to the luxury perfusion phenomenon and hyperaemia in the affected region. (d) At 4 months there is an established infarct.
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Cerebrovascular disease Stroke Perfusion SPECT can detect a reduction in blood flow immediately after an acute event and the involved area will be larger on SPECT than on subsequent CT or MRI.9 SPECT
can be used to localize ischaemic stroke with sensitivity and specificity of 61e85.5% and 88e98%, respectively,1,15 and several studies have shown good correlation with the volume of the perfusion deficit and neurological outcome.1,16 Sensitivity decreases in the days/weeks following infarct when inflammatory tissue causes arteriolar dilatation d the luxury perfusion phenomenon. As the
Figure 6 (a) Sagittal CT angiogram maximum intensity projection (MIP) reformat in an elderly patient with a right hemispheric TIA shows severe narrowing of the right internal carotid artery from the carotid bifurcation, which reconstitutes around the level of C2 filling via collaterals (arrows). (b) HMPAO SPECT in the same patient demonstrates mildly decreased cortical perfusion in the right perisylvian region with the basal ganglia still reasonably well perfused. (c) Acetazolamide-enhanced HMPAO SPECT reveals severe haemodynamic compromise with significantly decreased perfusion in the right anterior circulation distribution with the difference in perfusion of each hemisphere becoming much more conspicuous.
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inflammation subsides the necrosed tissue is resorbed and between the hyperaemic phase and the delayed hypoperfusion the scan may be relatively normal. This metabolism/perfusion uncoupling mainly occurs with HMPAO as ECD is poorly retained by necrotic areas.17 The evolution of an ischaemic stroke in the left MCA territory is depicted in Fig 5. With the increasing availability of diffusion MRI and the development of perfusion CT, SPECT may have little role in the diagnosis of acute stroke due to the time delay to image generation.
hypoperfusion will be found. The sensitivity for detecting TIA is 60% in the first 24 h, reducing to 40% in the first week, and a persistent perfusion defect in the first few days is associated with a higher risk of early stroke.9 Conversely, patients scanned within 6 h of onset of symptoms using 99m Tc-ECD with no visualized perfusion deficit and with a count density of >70% compared to the contralateral side were symptom free at 7 days.18
Transient ischaemic attack (TIA)
SPECT with acetazolamide challenge is helpful in evaluation of patients with carotid artery stenosis/occlusion (Fig 6). By assessing vascular reactivity, this test can identify patients at risk of stroke should perfusion further diminish.
SPECT does have prognostic value in the evaluation of TIA. If tracer is injected at the time of symptoms an area of
Carotid stenosis/occlusion
Figure 7 (a) Coronal T2W MRI in a 23-year-old man with intractable complex partial seizures reveals asymmetry of the hippocampi, that on the left being smaller with loss of internal structure, consistent with mesial temporal sclerosis (arrow). (b) Ictal HMPAO SPECT in the same patient was performed <30 s after seizure onset and hyperperfusion is seen in the left anteromedial temporal lobe (asterisks) with decreased perfusion otherwise in the left hemisphere and decreased perfusion in the right temporal lobe. (c) Interictal HMPAO SPECT performed with a 1 week interval since the last seizure shows slight reduction in perfusion of the left temporal lobe (arrows).
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Therefore, this provides objective evidence for the selection of patients with a high-grade asymptomatic carotid stenosis for carotid endarterectomy.19
Epilepsy SPECT has an important role in the evaluation of medically intractable complex partial seizures for lateralization and localization of the seizure focus prior to surgery. Although MRI remains the first-line investigation in focal epilepsy, it cannot always localize the focus and not all anatomical foci are the cause of the seizures.10 Under video surveillance and with electroencephalogram (EEG) monitoring, the patient, who has had their antiepileptic medication tapered off to increase the likelihood of a seizure, is injected with the radiopharmaceutical (through a previously established intravenous line) at seizure onset. The scan is performed several hours later. The delay between seizure onset and tracer injection should be minimized and certainly no more than 30 s otherwise radiopharmaceutical will be picked up in areas of seizure propagation.5 99mTc-HMPAO and ECD are both stable for 6 h and can be kept on the ward for injection. Ictal SPECT
(Fig 7b) typically shows hyperperfusion of the affected area, which may also affect the ipsilateral basal ganglia and thalamus and, possibly, the ipsilateral motor cortex and contralateral cerebellum.9 An inter-ictal scan is performed for comparison (Fig 7c), which may be normal or demonstrate hypoperfusion in the epileptogenic area (occasionally hyperperfusion). The sensitivity of SPECT compared to EEG and surgery for localization in temporal lobe epilepsy is 44 and 43%, respectively, in inter-ictal studies and 97 and 100% in ictal studies.20 The combination of ictal hyperperfusion and interictal hypoperfusion has absolute specificity as no other disease entity can produce this pattern. SPECT may also be useful in differentiating epileptic seizures from pseudoseizures.5 SPECT can be used to map the area of brain perfused with sodium amytal, and hence anaesthetized, during the course of a Wada test21 performed prior to ablative surgery for epilepsy to lateralize speech and memory function and assess the risk of memory impairment following anterior temporal lobectomy. Following catheter angiography, 99m Tc-HMPAO is injected intravenously approximately 40 s after paresis has been induced by the sodium amytal infused into the internal carotid artery, which anaesthetizes
Figure 8 HMPAO perfusion image in a patient who presented with fever and psychiatric symptoms with subsequently confirmed herpes simplex encephalitis. There is marked relative hyperperfusion of the right temporal lobe and limbic structures. (These images have been “windowed” to allow this distribution to be visualized, which makes the remaining brain parenchyma appear relatively underperfused in comparison).
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the ipsilateral cerebral hemisphere with resulting SPECT hypoperfusion.
Herpes simplex encephalitis Diagnosis can be difficult in these patients due to the often atypical and non-specific presentation. Initial CT or MRI may be negative, as may the cerebrospinal fluid (CSF) sample. Hyperperfusion in the affected temporal lobe may be present at an early stage when MRI is normal (Fig 8).5
PD PD is caused by loss of the dopaminergic neurons whose cell bodies originate in the substantia nigra and project to the ipsilateral striatum. Early in the disease it may be difficult to classify some patients with parkinsonism with clinicopathological studies in the early nineties showing that only 65 to 75% of patients with a clinical diagnosis of idiopathic PD present the characteristic neuropathological features, i.e., brainstem Lewy body inclusions.22 The DAT is located in the presynaptic neuron and the dopamine D2 receptor (D2R) in the post-synaptic
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neuron.23 123I beta-carbomethoxy-3 beta-(4-iodophenyl) tropane ([123I]b -CIT) and 123I-ioflupane ([123I]FP-CIT), are two of the most widely used DAT-selective radioligands. The main advantage of [123I]FP-CIT is that the steady state is reached 3 h after a single bolus injection compared with the 18e24 hours required for [123I]b-CIT.22 Unlike the process involved for perfusion imaging the patient is simply injected and then imaged 3 h later. In typical PD there is reduced uptake in the putamen and head of caudate with severity of the reduction graded 1e3 (Fig 9). Using FP-CIT a sensitivity of 97% for a clinical diagnosis of parkinsonism and specificity of 100% for essential tremor has been reported.24 The technique can differentiate between essential tremor and parkinsonian symptoms but not between PD and multisystem atrophy (MSA) or progressive supranuclear palsy (PSP) as degeneration of the presynaptic dopaminergic neurons is common to all of these diseases.23 However, MSA and PSP may also present degeneration of the post-synaptic neurons, and therefore, may show decreased D2R density on SPECT, whereas D2R are preserved or increased in PD25 due to upregulation induced by denervation. Several SPECT tracers that bind to D2 receptors are available, such as 123I-iodobenzamine
Figure 9 FP-CIT (DAT scan) performed in four different patients with worsening degrees of clinical PD. The colour scale is showndblack representing lowest activity and white highest activity. (a) Normal symmetrical uptake in the head of caudate and putamen. (bed) Sequential progressive reduction in uptake in the putamen and head of caudate as the disease worsens (arrows).
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(IBZM), epidepride, and iodolisuride, differing one from another in binding affinity and potentially in sensitivity/ specificity in differentiating PD from other parkinsonian syndromes.22
Cerebral neoplasm 201
TI (thallium 201 chloride), a potassium analogue, is selectively taken up by viable malignant cells in brain tumours with minimal uptake in normal brain. Its uptake depends on increased Naþ/KþeATPase activity in the membranes of malignant cells (potentiated by increased malignant cell density)26 and is related to increased local blood flow, BBB breakdown and cellular retention.27 201 TI has been used to predict histological grade and discriminate between residual tumour and radiation necrosis28,29 as well as to differentiate tumours from other ring-enhancing lesions seen on structural imaging.30 Iodine-123-alpha-methyl-tyrosine is a radiolabelled amino acid taken up by glial cells using an active transport mechanism. This uptake is by the ‘L’ and ‘A’ systems with differential selectivity for each amino acid and the A transporter is more highly expressed in malignant or transformed cells.26 It does not require BBB breakdown and so can demonstrate uptake in low-grade tumours. Its relationship with tumour grade is less clear than with 201thallium. Despite this, tyrosine has been shown to be useful in detection of recurrent glioma31 and has
been used to differentiate radiation necrosis from recurrence of malignant astrocytomas, brain metastases, and other primary brain tumours.5 Fig 10 demonstrates varying degrees of thallium/tyrosine uptake in a malignant glioma found at MRI, which had low and high-grade histological components.
SPECT/CT Many gamma cameras now have hybrid technology allowing sequential acquisition of anatomical and functional images d SPECT/CT d providing accurate image coregistration and an attenuation-correction map. Several studies involving small patient numbers demonstrated that fused images could provide additional information in specific situations in brain imaging: using 99mTc-tetrofosmin, tumours close to areas of increased physiological uptake, tumour recurrence postoperatively,32 and small, deeply located neoplasms following radiotherapy;33 using 111 In-DTPA, location of CSF leakage source.34 However, an earlier study showed no additional benefit of SPECT/CT in patients being investigated for AD (99mTc-ECD), PD (123IFPCIT) or brain tumour recurrence (201Tl).35 Generally for the clinical indications outlined in this review, SPECT/CT is rarely considered essential; however, having a structural examination available when interpreting the SPECT can often refine the report.
Figure 10 (a) Selected axial gadolinium-enhanced MRI images show a large astrocytoma, which demonstrates variable contrast enhancement consistent with varying tumour grade. Greater enhancement, i.e., higher grade, is seen in the more caudal section. (b) 201Thallium uptake is increased in the higher-grade component of the lesion (asterisk). (c) Tyrosine is taken up throughout the tumour as its uptake does not depend on BBB breakdown.
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Research Cerebral SPECT provides non-invasive assessment of brain function in vivo6 and is, therefore, a valuable research tool. Using perfusion tracers, activation paradigms can be used to assess aspects of brain function with administration of the radioligand taking place as the patient performs a cognitive task.10 Serotonin, cholinergic, opioid, benzodiazepine, and nicotinic receptors are further potential targets for SPECT imaging useful in various psychiatric disorders.
Conclusion Cerebral SPECT is a powerful imaging tool with a wide range of clinical applications in evaluation of neurological disorders while providing objective assessment of therapy and intervention. A rapidly expanding range of radiopharmaceuticals will allow this enable to develop further in the future.
References 1. Assessment of brain SPECT. Report of the therapeutics and technology assessment subcommittee of the American academy of neurology. Neurology 1996;46:278e85. 2. Health NCCfM. A NICEeSCIE guideline on supporting people with dementia and their carers in health and social care. National Clinical Practice Guideline Number 42. London: The British psychological society and the Royal College of Psychiatrists; 2007. 3. Conditions TNCCfC. Parkinson’s disease: national clinical guideline for diagnosis and management in primary and secondary care. London: RoyalCollege of Physicians; 2006. 4. Cancer TNCCf. Improving outcomes for people with brain and other CNS tumours. London: National Institute for Health and Clinical Excellence; 2006. 5. Masdeu JC, Arbizu J. Brain single photon emission computed tomography: technological aspects and clinical applications. Semin Neurol 2008;28:423e34. 6. Catafau AM. Brain SPECT in clinical practice. Part I: perfusion. J Nucl Med 2001;42:259e71. 7. Sharp PF, Smith FW, Gemmell HG, et al. Technetium-99m HM-PAO stereoisomers as potential agents for imaging regional cerebral blood flow: human volunteer studies. J Nucl Med 1986;27:171e7. 8. Thomsen G, de Nijs R, Hogh-Rasmussen E, et al. Required time delay from 99m Tc-HMPAO injection to SPECT data acquisition: healthy subjects and patients with rCBF pattern. Eur J Nucl Med Mol Imaging 2008;35:2212e9. 9. Camargo EE. Brain SPECT in neurology and psychiatry. J Nucl Med 2001;42:611e23. 10. Warwick JM. Imaging of brain function using SPECT. Metab Brain Dis 2004;19:113e23. 11. Reisberg B, Burns A, Brodaty H, et al. Diagnosis of Alzheimer’s disease. Report of an international psychogeriatric association special meeting work group under the cosponsorship of Alzheimer’s disease international, the European Federation of Neurological Societies, the World Health Organization, and the World Psychiatric Association. Int Psychogeriatr 1997;9(Suppl. 1):11e38. 12. Lobotesis K, Fenwick JD, Phipps A, et al. Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD. Neurology 2001;56:643e9. 13. Dougall NJ, Bruggink S, Ebmeier KP. Systematic review of the diagnostic accuracy of 99mTc-HMPAO-SPECT in dementia. Am J Geriatr Psychiatry 2004;12:554e70.
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14. Jagust W, Thisted R, Devous Sr MD, et al. SPECT perfusion imaging in the diagnosis of Alzheimer’s disease: a clinicalepathologic study. Neurology 2001;56:950e6. 15. Baird AE, Austin MC, McKay WJ, et al. Sensitivity and specificity of 99mTcHMPAO SPECT cerebral perfusion measurements during the first 48 hours for the localization of cerebral infarction. Stroke 1997;28:976e80. 16. Giubilei F, Lenzi GL, Di Piero V, et al. Predictive value of brain perfusion single-photon emission computed tomography in acute ischemic stroke. Stroke 1990;21:895e900. 17. Mahagne MH, Darcourt J, Migneco O, et al. Early (99m)Tc-ethylcysteinate dimer brain SPECT patterns in the acute phase of stroke as predictors of neurological recovery. Cerebrovasc Dis 2000;10:364e73. 18. Berrouschot J, Barthel H, Hesse S, et al. Differentiation between transient ischemic attack and ischemic stroke within the first six hours after onset of symptoms by using 99mTc-ECD-SPECT. J Cereb Blood Flow Metab 1998;18:921e9. 19. Cikrit DF, Dalsing MC, Harting PS, et al. Cerebral vascular reactivity assessed with acetazolamide single photon emission computer tomography scans before and after carotid endarterectomy. Am J Surg 1997;174:193e7. 20. Devous Sr MD, Thisted RA, Morgan GF, et al. SPECT brain imaging in epilepsy: a meta-analysis. J Nucl Med 1998;39:285e93. 21. de Silva R, Duncan R, Patterson J, et al. Regional cerebral perfusion and amytal distribution during the Wada test. J Nucl Med 1999;40:747e52. 22. Cilia R, Marotta G, Benti R, et al. Brain SPECT imaging in multiple system atrophy. J Neural Transm 2005;112:1635e45. 23. Catafau AM. Brain SPECT of dopaminergic neurotransmission: a new tool with proved clinical impact. Nucl Med Commun 2001;22:1059e60. 24. Benamer TS, Patterson J, Grosset DG, et al. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov Disord 2000;15:503e10. 25. Hierholzer J, Cordes M, Venz S, et al. Loss of dopamine-D2 receptor binding sites in parkinsonian plus syndromes. J Nucl Med 1998;39:954e60. 26. Cruickshank GS. Chapter 6, The use of SPECT in the analysis of brain tumours. In: Duncan R, editor. SPECT imaging of the brain. Glasgow: Kluwer Academic; 1997. pp. 161e78. 27. Martinez del Valle MD, Gomez-Rio M, Horcajadas A, et al. False positive thallium-201 SPECT imaging in brain abscess. Br J Radiol 2000;73:160e4. 28. Oriuchi N, Tamura M, Shibazaki T, et al. Clinical evaluation of thallium201 SPECT in supratentorial gliomas: relationship to histologic grade, prognosis and proliferative activities. J Nucl Med 1993;34:2085e9. 29. Yoshii Y, Satou M, Yamamoto T, et al. The role of thallium-201 single photon emission tomography in the investigation and characterisation of brain tumours in man and their response to treatment. Eur J Nucl Med 1993;20:39e45. 30. Kita T, Hayashi K, Yamamoto M, et al. Does supplementation of contrast MR imaging with thallium-201 brain SPECT improve differentiation between benign and malignant ring-like contrast-enhanced cerebral lesions? Ann Nucl Med 2007;21:251e6. 31. Kuwert T, Woesler B, Morgenroth C, et al. Diagnosis of recurrent glioma with SPECT and iodine-123-alpha-methyl tyrosine. J Nucl Med 1998;39:23e7. 32. Filippi L, Schillaci O, Santoni R, et al. Usefulness of SPECT/CT with a hybrid camera for the functional anatomical mapping of primary brain tumors by [Tc99m] tetrofosmin. Cancer Biother Radiopharm 2006;21:41e8. 33. Filippi L, Santoni R, Nicoli P, et al. Intracranial tumors after radiation therapy: role of 99mTc-tetrofosmin SPECT/CT with a hybrid camera. Cancer Biother Radiopharm 2009;24:229e35. 34. Novotny C, Potzi C, Asenbaum S, et al. SPECT/CT fusion imaging in radionuclide cisternography for localization of liquor leakage sites. J Neuroimaging 2009;19:227e34. 35. Schillaci O, Danieli R, Manni C, et al. Is SPECT/CT with a hybrid camera useful to improve scintigraphic imaging interpretation? Nucl Med Commun 2004;25:705e10.
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.elsevierhealth.com/journals/crad
Pictorial Review
Applications of cerebral SPECT C. McArthur*, R. Jampana, J. Patterson, D. Hadley Department of Neuroradiology, Institute of Neurological Sciences, Glasgow, UK
art icl e i nformat ion Article history: Received 30 September 2010 Received in revised form 21 December 2010 Accepted 29 December 2010
Single-photon emission computed tomography (SPECT) can provide three-dimensional functional images of the brain following the injection of one of a series of radiopharmaceuticals that crosses the bloodebrain barrier and distributes according to cerebral perfusion, neurotransmitter, or cell density. Applications include differentiating between the dementias, evaluating cerebrovascular disease, preoperative localization of epileptogenic foci, diagnosing movement disorders, and evaluation of intracerebral tumours, while also proving a useful research tool. Unlike positronemission tomography (PET), SPECT imaging is widely available and can be performed in any department that has access to a rotating gamma camera. The purpose of this review is to demonstrate the utility of cerebral SPECT and increase awareness of its role in the investigation of neurological and psychiatric disorders. Ó 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Single-photon emission computed tomography (SPECT) is a functional technique introduced in the early 1980s for the investigation of regional cerebral blood flow and receptor density studies.1 It is complementary to computed tomography (CT) and magnetic resonance imaging (MRI), with co-registration possible, and can be more sensitive as many cerebral disease entities show functional changes before structural abnormality. The National institute for Health and Clinical Excellence now recognizes the role of SPECT in the investigation of dementia, Parkinson’s disease (PD), and brain tumours.2e4 A ligand that traces cerebral perfusion, binds to a specific brain receptor/transporter or is taken up by cells is tagged with a radionuclide prior to intravenous injection. Using a rotating gamma camera and the techniques of filtering, back projection, and attenuation correction, a three-dimensional
* Guarantor and correspondent: C. McArthur, Department of Neuroradiology, Institute of Neurological Sciences, Southern General Hospital Campus, 1345 Govan Road, Glasgow G51 4TF. Tel.: þ44 (0) 7973386217. E-mail address: [email protected] (C. McArthur).
image of the distribution of the radionuclide in the brain is obtained. Meticulous acquisition technique is very important to maintain image quality. Patient co-operation is essential with attention to patient comfort, optimal positioning, and use of a head-holder device. Scanning time depends on the radiopharmaceutical, imaging system, and required resolution, with high-quality images of the whole brain obtained in 20e30 min.5 Images are assessed visually and with semiquantitative analysis using voxel-based statistics, such as statistical parametric mapping.
Cerebral perfusion Neuronal tissue that is metabolically more active consumes more oxygen and nutrients and, therefore, has a higher blood flow than less active tissue. Cerebral perfusion and metabolism are coupled in nearly all physiological and pathological situations.6 Perfusion imaging is commonly undertaken with two 99mTc labelled compounds: hexamethylpropylene-amide oxime (HMPAO) and L, L-ethyl cysteinate dimer (ECD). Their differences are related to in vitro stability, uptake, and dosimetry with 99mTc-ECD reflecting cellular metabolic uptake and HMPAO more closely reflecting blood flow.6 Following intravenous
0009-9260/$ e see front matter Ó 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2010.12.015
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Figure 1 Axial images demonstrating a normal averaged HMPAO perfusion scan. This scan is averaged over 32 normal volunteers (i.e., images summed together and then counts per pixel divided by 32) to allow for natural variation in anatomical positioning and gyral/sulcal patterns. The colour scale is shown d dark blue representing lower activity and yellow higher activity. (This colour scale applies to all other SPECT images in the review other than Fig 9) a, right temporal lobe; b, left cerebellar hemisphere; c, right occipital lobe; d, right and left cingulate gyri; e, right thalamus; f, right head of caudate; g, left lentiform nucleus; h, left parietal lobe; i, left frontal lobe.
Figure 2 (a) HMPAO perfusion image in a patient with mild dementia demonstrating reduced perfusion in the parietal and posterior temporal lobes typical of AD (arrows). (b) The HMPAO perfusion image performed on the same patient 3 years later when symptoms had progressed. There is now significantly more reduced temporoparietal perfusion (arrows) and also hypoperfusion in the frontal lobes bilaterally.
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administration of 99mTc-HMPAO it rapidly crosses the bloodebrain barrier (BBB) in proportion to regional cerebral blood flow at the time of delivery. Once in the neuronal and glial cells, it interacts with glutathione and within 1e2 min undergoes stereoisomeric alteration from lipophilic to hydrophilic, becoming trapped within the neuronal tissue providing a snapshot of brain perfusion, hence function, at that time. Maximum uptake is reached in under a minute7 and distribution remains static for many hours.6 To perform a perfusion study, intravenous access is established in advance and injection takes place in a quiet dimly lit room to avoid external stimuli. The patient remains basal for a further 5e10 min and image acquisition delayed for no more than 30 min to allow background clearance from the vascular pool.8 The effective dose for a routine HMPAO perfusion or dopamine transporter (DAT) scan is 4e5 mSv and for a thallium scan up to 18 mSv. The normal adult brain shows symmetrical increased uptake in the temporal, parietal and occipital cortices and basal ganglia, thalami and cingulate gyrus.9 Grey matter is differentiated from white matter due to its increased blood flow (Fig 1). Focal or regional areas of pathologically increased or decreased uptake may be identified.
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SPECT, of 84% with positive SPECT and of 52% with a negative SPECT.14 SPECT studies also provide a higher specificity against other types of dementia than clinical criteria alone (91 versus 70%).13 Correlation should be performed with CT or MRI, which will exclude other diseases, while a normal structural examination will further support the characteristic SPECT findings.
Vascular dementia Symptoms of vascular dementia have a step-wise temporal profile. Multiple small emboli are caused by atherosclerosis of the carotid and middle cerebral arteries (MCAs). Multiple randomly distributed foci of hypoperfusion are seen and there may be involvement of the motor and sensory cortices9 and subcortical structures10
Dementia SPECT shows characteristic patterns of hypoperfusion in each of the dementias.10 The type of dementia has important implications for the patient due to the development of more specific therapies.6 In many cases CT or MRI may only show non-specific or late findings, such as focal or regional atrophy. A clearly normal study is clinically also useful.
Alzheimer’s disease (AD) AD is characterized pathologically by plaques, amyloid deposition, and neurofibrillary tangles. It is no longer a diagnosis of exclusion11 and SPECT is now an established technique used to support the clinical diagnosis.1 It demonstrates bilateral hypoperfusion of the parietal and posterior temporal lobes with sparing of the sensory and motor cortices, visual cortex, basal ganglia, thalami and cerebellar hemispheres (Fig 2) with the temporoparietal hypoperfusion more severe in early-onset disease.9 These perfusion changes may be linked to the well-documented late structural brain changes in AD of temporal lobe and hippocampal atrophy.12 As the disease progresses the frontal lobes also become involved.10 Sensitivity and specificity of SPECT for AD have been shown to be 86 and 96%, respectively,9 and even in mild AD 80% of patients have abnormal SPECT examinations.1 While pathological verification studies suggest that clinical criteria may be more sensitive than SPECT (81 versus 74%)13 the two should be considered complementary. In a group of 70 patients with dementia and 14 controls, all with autopsy, SPECT was most useful when there was a clinical diagnosis of “possible AD” with a probability of AD of 67% without
Figure 3 (a) Selected axial T2-weighted (T2W) fluid-attenuated inversion recovery (FLAIR) MRI images in an elderly man presenting with confusion and difficulty walking demonstrate extensive abnormal white matter signal changes affecting the subcortical and periventricular regions and an old right thalamic infarct (DWI showed no restricted diffusion). (b) HMPAO SPECT demonstrates patchy decreased perfusion in keeping with ischaemic damage and no evidence of the pattern associated with AD or frontotemporal dementia.
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presumably reflecting the variable anatomic localization of the underlying vascular disease. Correlation with structural information from CT or MRI is helpful (Fig 3). Underlying vascular causes resulting in decreased cerebrovascular reserve can be demonstrated by giving a vasodilator, such as acetazolamide, prior to the
radiopharmaceutical.10 Acetazolamide causes an increase in regional cerebral perfusion by 30e50% in areas with intact vascular reserve but not in areas where the arterioles are already fully dilated, such as with ischaemia or small vessel disease. Perfusion will increase in the originally hypoperfused areas of AD patients but remains the
Figure 4 (a) Axial T2W FLAIR MRI in an elderly woman who presented with dementia demonstrates early atrophy with evidence of small vessel disease. (b) HMPAO SPECT shows grossly decreased perfusion in the frontal and anterior temporal lobes and cingulate gyri (arrows) with sparing of the posterior temporal and occipital lobes consistent with frontotemporal dementia. This demonstrates the obvious advantage of SPECT over MRI in this case.
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same or disease.14
decreases
in
those
with
cerebrovascular
Frontotemporal dementia (Pick’s disease) Clinical diagnosis in this condition can be difficult. Symptoms include gradual-onset confusion and changes in personality and behaviour.9 SPECT shows symmetric hypoperfusion of the frontal lobes extending to the anterior cingulate gyri (Fig 4). Behavioural changes are seen when the right temporal lobe is involved and aphasia if the dominant temporal lobe is involved.
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Lewy body dementia Lewy body dementia is now widely recognized as the second commonest form of late-life degenerative dementia after AD and presents with dementia, visual hallucinations, and parkinsonism. Accurate diagnosis of Lewy body dementia is important, not only because such patients respond with serious adverse reactions (increasing confusion, parkinsonism, increased mortality) to antipsychotics, but also because they may be particularly responsive to cholinesterase inhibitors.12 Previously HMPAO was used but the differentiation with AD was poor and this has now been superseded by DAT scanning with the recognition that it is part of the PD spectrum.
Figure 5 Temporal sequence of HMPAO axial images from the same level performed on the same patient who presented with symptoms of a left MCA territory acute infarct. (a) Within 2 h of onset of symptoms there is a large perfusion defect in the left MCA territory representing all underperfused neuronal tissue including the ischaemic penumbra. This is a larger area of abnormality than would be seen on CT at this time, which may still appear normal. (b) Within 3 days of symptoms the hypoperfused area has reduced to a smaller wedge-shaped area in the left frontal lobe. (c) Within 2 weeks, loss of autoregulation has led to the luxury perfusion phenomenon and hyperaemia in the affected region. (d) At 4 months there is an established infarct.
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Cerebrovascular disease Stroke Perfusion SPECT can detect a reduction in blood flow immediately after an acute event and the involved area will be larger on SPECT than on subsequent CT or MRI.9 SPECT
can be used to localize ischaemic stroke with sensitivity and specificity of 61e85.5% and 88e98%, respectively,1,15 and several studies have shown good correlation with the volume of the perfusion deficit and neurological outcome.1,16 Sensitivity decreases in the days/weeks following infarct when inflammatory tissue causes arteriolar dilatation d the luxury perfusion phenomenon. As the
Figure 6 (a) Sagittal CT angiogram maximum intensity projection (MIP) reformat in an elderly patient with a right hemispheric TIA shows severe narrowing of the right internal carotid artery from the carotid bifurcation, which reconstitutes around the level of C2 filling via collaterals (arrows). (b) HMPAO SPECT in the same patient demonstrates mildly decreased cortical perfusion in the right perisylvian region with the basal ganglia still reasonably well perfused. (c) Acetazolamide-enhanced HMPAO SPECT reveals severe haemodynamic compromise with significantly decreased perfusion in the right anterior circulation distribution with the difference in perfusion of each hemisphere becoming much more conspicuous.
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inflammation subsides the necrosed tissue is resorbed and between the hyperaemic phase and the delayed hypoperfusion the scan may be relatively normal. This metabolism/perfusion uncoupling mainly occurs with HMPAO as ECD is poorly retained by necrotic areas.17 The evolution of an ischaemic stroke in the left MCA territory is depicted in Fig 5. With the increasing availability of diffusion MRI and the development of perfusion CT, SPECT may have little role in the diagnosis of acute stroke due to the time delay to image generation.
hypoperfusion will be found. The sensitivity for detecting TIA is 60% in the first 24 h, reducing to 40% in the first week, and a persistent perfusion defect in the first few days is associated with a higher risk of early stroke.9 Conversely, patients scanned within 6 h of onset of symptoms using 99m Tc-ECD with no visualized perfusion deficit and with a count density of >70% compared to the contralateral side were symptom free at 7 days.18
Transient ischaemic attack (TIA)
SPECT with acetazolamide challenge is helpful in evaluation of patients with carotid artery stenosis/occlusion (Fig 6). By assessing vascular reactivity, this test can identify patients at risk of stroke should perfusion further diminish.
SPECT does have prognostic value in the evaluation of TIA. If tracer is injected at the time of symptoms an area of
Carotid stenosis/occlusion
Figure 7 (a) Coronal T2W MRI in a 23-year-old man with intractable complex partial seizures reveals asymmetry of the hippocampi, that on the left being smaller with loss of internal structure, consistent with mesial temporal sclerosis (arrow). (b) Ictal HMPAO SPECT in the same patient was performed <30 s after seizure onset and hyperperfusion is seen in the left anteromedial temporal lobe (asterisks) with decreased perfusion otherwise in the left hemisphere and decreased perfusion in the right temporal lobe. (c) Interictal HMPAO SPECT performed with a 1 week interval since the last seizure shows slight reduction in perfusion of the left temporal lobe (arrows).
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Therefore, this provides objective evidence for the selection of patients with a high-grade asymptomatic carotid stenosis for carotid endarterectomy.19
Epilepsy SPECT has an important role in the evaluation of medically intractable complex partial seizures for lateralization and localization of the seizure focus prior to surgery. Although MRI remains the first-line investigation in focal epilepsy, it cannot always localize the focus and not all anatomical foci are the cause of the seizures.10 Under video surveillance and with electroencephalogram (EEG) monitoring, the patient, who has had their antiepileptic medication tapered off to increase the likelihood of a seizure, is injected with the radiopharmaceutical (through a previously established intravenous line) at seizure onset. The scan is performed several hours later. The delay between seizure onset and tracer injection should be minimized and certainly no more than 30 s otherwise radiopharmaceutical will be picked up in areas of seizure propagation.5 99mTc-HMPAO and ECD are both stable for 6 h and can be kept on the ward for injection. Ictal SPECT
(Fig 7b) typically shows hyperperfusion of the affected area, which may also affect the ipsilateral basal ganglia and thalamus and, possibly, the ipsilateral motor cortex and contralateral cerebellum.9 An inter-ictal scan is performed for comparison (Fig 7c), which may be normal or demonstrate hypoperfusion in the epileptogenic area (occasionally hyperperfusion). The sensitivity of SPECT compared to EEG and surgery for localization in temporal lobe epilepsy is 44 and 43%, respectively, in inter-ictal studies and 97 and 100% in ictal studies.20 The combination of ictal hyperperfusion and interictal hypoperfusion has absolute specificity as no other disease entity can produce this pattern. SPECT may also be useful in differentiating epileptic seizures from pseudoseizures.5 SPECT can be used to map the area of brain perfused with sodium amytal, and hence anaesthetized, during the course of a Wada test21 performed prior to ablative surgery for epilepsy to lateralize speech and memory function and assess the risk of memory impairment following anterior temporal lobectomy. Following catheter angiography, 99m Tc-HMPAO is injected intravenously approximately 40 s after paresis has been induced by the sodium amytal infused into the internal carotid artery, which anaesthetizes
Figure 8 HMPAO perfusion image in a patient who presented with fever and psychiatric symptoms with subsequently confirmed herpes simplex encephalitis. There is marked relative hyperperfusion of the right temporal lobe and limbic structures. (These images have been “windowed” to allow this distribution to be visualized, which makes the remaining brain parenchyma appear relatively underperfused in comparison).
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the ipsilateral cerebral hemisphere with resulting SPECT hypoperfusion.
Herpes simplex encephalitis Diagnosis can be difficult in these patients due to the often atypical and non-specific presentation. Initial CT or MRI may be negative, as may the cerebrospinal fluid (CSF) sample. Hyperperfusion in the affected temporal lobe may be present at an early stage when MRI is normal (Fig 8).5
PD PD is caused by loss of the dopaminergic neurons whose cell bodies originate in the substantia nigra and project to the ipsilateral striatum. Early in the disease it may be difficult to classify some patients with parkinsonism with clinicopathological studies in the early nineties showing that only 65 to 75% of patients with a clinical diagnosis of idiopathic PD present the characteristic neuropathological features, i.e., brainstem Lewy body inclusions.22 The DAT is located in the presynaptic neuron and the dopamine D2 receptor (D2R) in the post-synaptic
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neuron.23 123I beta-carbomethoxy-3 beta-(4-iodophenyl) tropane ([123I]b -CIT) and 123I-ioflupane ([123I]FP-CIT), are two of the most widely used DAT-selective radioligands. The main advantage of [123I]FP-CIT is that the steady state is reached 3 h after a single bolus injection compared with the 18e24 hours required for [123I]b-CIT.22 Unlike the process involved for perfusion imaging the patient is simply injected and then imaged 3 h later. In typical PD there is reduced uptake in the putamen and head of caudate with severity of the reduction graded 1e3 (Fig 9). Using FP-CIT a sensitivity of 97% for a clinical diagnosis of parkinsonism and specificity of 100% for essential tremor has been reported.24 The technique can differentiate between essential tremor and parkinsonian symptoms but not between PD and multisystem atrophy (MSA) or progressive supranuclear palsy (PSP) as degeneration of the presynaptic dopaminergic neurons is common to all of these diseases.23 However, MSA and PSP may also present degeneration of the post-synaptic neurons, and therefore, may show decreased D2R density on SPECT, whereas D2R are preserved or increased in PD25 due to upregulation induced by denervation. Several SPECT tracers that bind to D2 receptors are available, such as 123I-iodobenzamine
Figure 9 FP-CIT (DAT scan) performed in four different patients with worsening degrees of clinical PD. The colour scale is showndblack representing lowest activity and white highest activity. (a) Normal symmetrical uptake in the head of caudate and putamen. (bed) Sequential progressive reduction in uptake in the putamen and head of caudate as the disease worsens (arrows).
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(IBZM), epidepride, and iodolisuride, differing one from another in binding affinity and potentially in sensitivity/ specificity in differentiating PD from other parkinsonian syndromes.22
Cerebral neoplasm 201
TI (thallium 201 chloride), a potassium analogue, is selectively taken up by viable malignant cells in brain tumours with minimal uptake in normal brain. Its uptake depends on increased Naþ/KþeATPase activity in the membranes of malignant cells (potentiated by increased malignant cell density)26 and is related to increased local blood flow, BBB breakdown and cellular retention.27 201 TI has been used to predict histological grade and discriminate between residual tumour and radiation necrosis28,29 as well as to differentiate tumours from other ring-enhancing lesions seen on structural imaging.30 Iodine-123-alpha-methyl-tyrosine is a radiolabelled amino acid taken up by glial cells using an active transport mechanism. This uptake is by the ‘L’ and ‘A’ systems with differential selectivity for each amino acid and the A transporter is more highly expressed in malignant or transformed cells.26 It does not require BBB breakdown and so can demonstrate uptake in low-grade tumours. Its relationship with tumour grade is less clear than with 201thallium. Despite this, tyrosine has been shown to be useful in detection of recurrent glioma31 and has
been used to differentiate radiation necrosis from recurrence of malignant astrocytomas, brain metastases, and other primary brain tumours.5 Fig 10 demonstrates varying degrees of thallium/tyrosine uptake in a malignant glioma found at MRI, which had low and high-grade histological components.
SPECT/CT Many gamma cameras now have hybrid technology allowing sequential acquisition of anatomical and functional images d SPECT/CT d providing accurate image coregistration and an attenuation-correction map. Several studies involving small patient numbers demonstrated that fused images could provide additional information in specific situations in brain imaging: using 99mTc-tetrofosmin, tumours close to areas of increased physiological uptake, tumour recurrence postoperatively,32 and small, deeply located neoplasms following radiotherapy;33 using 111 In-DTPA, location of CSF leakage source.34 However, an earlier study showed no additional benefit of SPECT/CT in patients being investigated for AD (99mTc-ECD), PD (123IFPCIT) or brain tumour recurrence (201Tl).35 Generally for the clinical indications outlined in this review, SPECT/CT is rarely considered essential; however, having a structural examination available when interpreting the SPECT can often refine the report.
Figure 10 (a) Selected axial gadolinium-enhanced MRI images show a large astrocytoma, which demonstrates variable contrast enhancement consistent with varying tumour grade. Greater enhancement, i.e., higher grade, is seen in the more caudal section. (b) 201Thallium uptake is increased in the higher-grade component of the lesion (asterisk). (c) Tyrosine is taken up throughout the tumour as its uptake does not depend on BBB breakdown.
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Research Cerebral SPECT provides non-invasive assessment of brain function in vivo6 and is, therefore, a valuable research tool. Using perfusion tracers, activation paradigms can be used to assess aspects of brain function with administration of the radioligand taking place as the patient performs a cognitive task.10 Serotonin, cholinergic, opioid, benzodiazepine, and nicotinic receptors are further potential targets for SPECT imaging useful in various psychiatric disorders.
Conclusion Cerebral SPECT is a powerful imaging tool with a wide range of clinical applications in evaluation of neurological disorders while providing objective assessment of therapy and intervention. A rapidly expanding range of radiopharmaceuticals will allow this enable to develop further in the future.
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