Validation of the cerebellum as a reference region for SPECT quantification in patients suffering from dementia of the Alzheimer type
Introduction
The authors previously validated a simple quantification method to convert single photon emission computed tomography (SPECT) brain counts into absolute values of regional brain uptake (rBU) of technetium-99m-d,l-hexamethylpropyleneamine oxime (HMPAO), using calibrated point sources as an external standard (Dobbeleir and Dierckx, 1993). Reproducibility studies of cerebellar uptake in a group of 15 subjects, comprising 10 healthy volunteers and five patients, showed a mean deviation of 12.6%. On the other hand, expected large interindividual variability was noted, with cerebellar uptake varying between 31.9 and 72.2×10−6 of the injected lipophilic dose of 740 MBq (20 mCi) of HMPAO per cm3 of brain tissue (Dobbeleir and Dierckx, 1993). A study assessing parameters influencing rBU in 33 healthy volunteers demonstrated that the most important factor underlying interindividual variability was body surface, followed by brain volume. In addition, the previous study stressed the need for registration of basal (`rest') heart rate and also suggested the absence of a significant influence of minor stress on rBU (Dierckx et al., 1994).
As demonstrated by neuropathologial validation, perfusion SPECT has been confirmed to increase the accuracy of diagnoses of Alzheimer's disease (Jobst et al., 1992, Jobst et al., 1997). Although already qualitatively useful as shown by Jobst et al., regional quantitative analysis with a reference region is expected to offer more accurate information. In this context, for longitudinal studies in patients with dementia of the Alzheimer type (DAT), the cerebellum is presently often used as a reference region for SPECT semi-quantification, which assumes the absence of any significant regional influence of physiological fluctuations or pathology (Syed et al., 1992). The rBU quantification method allows testing of the validity of these assumptions by direct assessment of the methodology, i.e. the regional brain uptake of the tracer Tc-99m HMPAO rather than extrapolated regional cerebral blood flow.
Hence, in 13 DAT patients, repeated SPECT studies were performed to assess the reproducibility of cerebellar rBU. Also, mean cerebellar rBU in patients suffering from DAT was calculated, respectively, at resting heart rate, after correction for body surface and after cumulative corrections for body surface and brain volume. This allowed determination of the mean cerebellar rBU for the whole DAT group and comparison with a previously established database obtained in healthy volunteers. It should be stressed that the aim of the SPECT analysis in the DAT patients presented was to address methodological questions, rather than to explore correlations between functional and clinical parameters.
Section snippets
Subjects
Thirteen DAT patients underwent repeated SPECT studies separated by an interval of approximately 2 weeks. It is well known that DAT patients show decreased habituation to novel situations. An effort was made to control variance by keeping the patients in as stable as possible life conditions between scans. Patients were either hospitalized (n=7) or living at home (n=6) during both acquisitions. Inclusion criteria for DAT patients consisted of the diagnosis of probable DAT, according to
Results
As the first clinical population in which to test the rBU quantification method, a group of 13 patients suffering from probable DAT was examined. In addition to the validation of the proposed absolute quantification method in a clinical setting, the results obtained allowed evaluation of the aforementioned hypotheses using perfusion SPECT in patients suffering from DAT. Since only cerebellar and no global cerebral regional analyses were performed, a heterogeneous series of patients with
Discussion
In the study presented, the implementation in clinical neurology and psychiatry of the absolute Tc-99m HMPAO uptake quantification method, using calibrated point sources as an external standard, was explored. The reproducibility and methodological simplicity of the rBU quantification was previously validated on phantoms and in a reference population (Dobbeleir and Dierckx, 1993; Dierckx et al., 1994).
Repeated studies of cerebellar rBU in 13 patients suffering from DAT showed a mean deviation of
Acknowledgements
The authors are grateful to Dr J. Vandevivere for logistical support, and to Mrs D. Welvaert and Ms S. Van den Broeck for secretarial assistance.
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