applications of spect in cognitive neuroscience, neurology...

Guest-editorial

Applications of SPECT in cognitiveneuroscience, neurology and psychiatry

Single photon emission computed tomography hastwo common acronyms – SPECT and SPET. This isinconvenient when performing literature searches andshould be resolved. A search for 1999 captured 105SPET references and 1285 SPECT references so pop-ular opinion is with this option which has been usedconsistently in the articles in this issue. SPET [or“S”PET as it is sometimes called] is a deliberate pref-erence in some cases to emphasise the strong associa-tion with PET. It is, of course, appropriate to compareand contrast such similar technologies and the paperby Montaldi and Mayes has highlighted the strengthsand weaknesses of PET, SPECT and fMRI for mappingneuroactivation patterns. As fMRI operates at a lowerenergy band within the electromagnetic spectrum thanthe emission tomography techniques and does not havethe potential to produce ionisation in tissue it is a theo-retically safer method and will always be the method ofchoice for the study of activation if suitable paradigmscan work effectively within the high field environmentof a magnetic resonance scanner. The risks associatedwith PET and SPECT are, however, based on conserva-tive extrapolation of known effects at higher exposurelevels, are tightly regulated, and are small, being com-parable to many every day activities (for a more com-plete description see Patterson and Wyper [1]). Theproblem from the scientific perspective is that as longas there is a theoretical risk, PET and SPECT expo-sure has to be regulated and so the number of repeatconditions is constrained, whereas fMRI measurementscan be repeated and are limited more by cost and fa-tigue. Even with this limitation, however, SPECT andPET can be used very successfully to investigate acti-vation. Of these two techniques, PET, with15O wa-ter CBF measurement, has better signal to noise ratioalthough the gap is narrowing and current work beingundertaken by the NeuroPhysics Corporation offers theprospect of neuro-SPECT with reconstructed transax-ial resolution of 4.8 mm at 30 kc/s/uCi/ml or 2.9 mmat 11 kc/s/uCi/ml. The main difference for activation

work is that 15O water PET has faster washout andparadigms with up to 12 different or repeat conditionscan be used, whereas SPECT, with the trapped99mTclabelled compounds HMPAO or ECD, is ideal for cap-turing activations which can be sustained for around60 seconds and which are difficult to capture with realtime imaging in PET or fMRI. Each technique has itsplace.

Where emission tomography comes into its own isin the direct measurement of synaptic function by useof tracers with high selectivity and affinity for spe-cific synaptic binding sites. With PET,18F [T1/2 =110 mins] is the most commonly used radioisotopewhereas with SPECT most studies to date have usedthe 159 Kev gamma emitter123I [T 1/2 = 13.2 hrs].Fluorine chemistry is reckoned to be more straight-forward than iodine chemistry and the challenges pre-sented to radio-chemists by SPECT are therefore some-what greater, but as highlighted in papers in this issueby Acton and Mozley and by Shaw et al., there area growing number of clinically useful SPECT ligandsavailable. Most of these have to be synthesised in alocal radiopharmacy and so studies are restricted to thelarger University based centres of excellence, but therecent achievement by Nycomed-Amersham in obtain-ing a European product licence for the dopamine trans-porter ligand FP-CIT [DaTSCAN©R] indicates a desireby companies to bring the unique power of emissiontomography for imaging synaptic function to the mar-ketplace. SPECT rather than PET, being available in allspecialist hospitals and with the capacity for delayedimaging several hours after tracer administration to al-low for non-selectivewashout, may well be the imagingmodality of choice for this work.

This issue of Behavioural Neurology highlights boththe routine and the research roles of SPECT but mostemphasis is on pushing forwards the frontiers ratherthan appraising clinical practice. The paper by Duncandemonstrates the ability of the trapping mechanism ofthe routine SPECT perfusion tracers to capture the lo-

2 Applications of SPECT in cognitive neuroscience, neurology and psychiatry

cation of seizure activity. This is a critical investigationprior to surgery for intractable epilepsy. There are twopapers on imaging specific neurochemical systems,per-haps not surprisingly focusing on the neurotransmitterpathway which has received most attention from PETand SPECT investigators, the dopamine system. Actonand Mozley describe studies in patients with Parkin-sonian symptoms showing the role of SPECT in boththe diagnosis of movement disorders and in the ob-jective monitoring of neuroprotective therapies. Theyintroduce one of the few99mTc labelled compoundsbeing developed for neurotransmitter studies [99mTc-TRODAT-1]. Technetium labelling offers the potentialfor more cost effective imaging, a critical factor if thesetechniques are to survive health economic appraisal.Shaw et al. show how the development of new SPECTtracers has led to an improved understanding of theaction of anti-psychotic drugs in schizophrenia. Newtracers may well hold the key to the changing role ofSPECT, both in research and in clinical practice, but thetechnical complexity and development costs involvedin developing these should not be underestimated.

Several papers in this issue demonstrate how thepower of basic perfusion SPECT can be enhanced byrobust image analysis. The development by Friston etal. [2] of statistical parametric mapping (SPM) and itssubsequent modification for use with SPECT has beenpivotal in the development of SPECT as a technique tostudy the association between regional perfusion andclinical function. Both Ashton et al. and Ebmeierre-analysed old data using SPM and uncovered latentinformation, the former finding that perfusion in thecingulate is associated with negative symptoms in agroup of neuroleptic naive schizophrenic patients andthe latter finding that morning regression slopes weresteeper than evening regression slopes when compar-ing posterior cingulate perfusion with depression rat-ing in patients with major depression. Tooth et al. in-vestigated cognitive deficits after surgery for aneurys-mal subarachnoid haemorrhage [SAH] and,using SPM,found a large common area of subcortical hypoperfu-sion in the patient group compared to controls. Studieslike this, linking SPECT and cognitive testing, couldplay an increasing role in the comparison of SAH treat-ments. The paper by Stamatakis et al. focuses on theapplication of SPM in head injury. It is shown that,

although care is needed in the application of SPM, thetechnique can add robustness to the classification of in-dividual lesions and can also be used for group analysesdespite gross abnormalities in individual scans. Theother paper on SPM, by Barnes et al., explores the useof SPM to help in the classification of abnormalities inscans of patients with dementia. Use of SPM for indi-vidual scan classification is fraught with problems, notleast in the establishment of an appropriate control dataset, but they were able to demonstrate that the methodworks from a technical perspective and produces SPMpatterns consistent with scan appearance. They found,however, that at present there is no evidence to supportthe routine use of SPM for classification. The mainproblem appears to be in interpreting rather than identi-fying equivocal perfusion patterns. More longitudinalstudies with histology are required to compare imagingpatterns with proven pathology.

The clinical areas covered in this special issue onSPECT include epilepsy, movement disorders, demen-tia, stroke, schizophrenia, depression and head injury.In the first three of these SPECT has an establishedroutine role in clinical practice. In all other areas wherethe investigation of brain function is critical SPECThas contributed in research studies. Time will tell towhat extent today’s research evolves into routine prac-tice. The papers selected for this issue have been cho-sen to be representative of developments in these clin-ical areas. They are of value in their own right and,importantly, point to other neuroimaging work in eachparticular specialist field.

References

[1] Patterson, J. and Wyper, D.J., Basics of SPECT; in:SPECTImaging of the Brain, Duncan, ed., Kluwer Academic Publisher,1997, pp. 1–42.

[2] Friston, K.J., Frith, C.D., Liddle, P.F. and Frackowiak, R.S.J.,Comparing functional (PET) images. The assessment of signif-icant change,Journal of Cerebral Blood Flow and Metabolism11 (1991), 690–699.

David J. WyperDaniela Montaldi

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