Can we improve the early diagnosis of Lewy body disease with more accurate quantification of nuclear medicine scans.

Abstract

This thesis investigates the quantification of two scintigraphic biomarkers used for the diagnosis of dementia with Lewy bodies (DLB): 123I-FP-CIT (123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane), commonly known as DaTSCAN™,and cardiac 123I-MIBG(123I-metaiodobenzylguanidine). Accurate quantification is critical as we increasingly move towards diagnosis at the earlier mild cognitive impairment (MCI) stage, where more subtle changes from normality are expected. A range of novel approaches have been examined to overcome technical limitations that have previously been barriers to accurate quantification. Uniquely, this has been studied in cohorts of highly characterised dementia and MCI subjects as well as older adults with normal cognition recruited as age matched controls. The subject studies have been complemented by work using advanced anthropomorphic phantoms. Throughout, the innovative methods have been compared with the established ones. Results are presented in detail and clinical and research relevance is discussed together with proposals for optimal usage. Briefly, the key findings are:FP-CIT key findings•Specific binding ratio values (SBR) for FP-CIT images calculated by different software packages are systematically different, although give similar diagnostic accuracy. •Striatal uptake does not decrease with age in healthy older adults, as previously reported, indicating potential misdiagnosis if age correction is applied. •Absolute quantification separates normal and abnormal subjects less well than relative-quantification with SBR.•Advanced FP-CIT reconstruction methods using SPECT-CT and collimator modelling improve the accuracy of activity concentration measurements in a phantom.•Advanced FP-CIT reconstruction methods affect relative quantification with SBR, but not clinical interpretation. Cardiac MIBG key findings•Different methods of planar MIBG analysis are operator dependent and give systematically different results – recommendations are provided for an optimal method.•Establishing a normal threshold is critical. This thesis shows that previously published values may not be valid in a UK population and proposes a suitable alternative. •Images obtained soon after injection give similar accuracy as those obtained at 3.5 hours (the standard delayed method), and the latter scans could be omitted in the majority of cases. •Planar cardiac MIBG semi-quantification is significantly dependent on subject size. Using SPECT-CT gives greater separation between normal and abnormal scans than planar. II In summary, an in-depth and comprehensive study of technical aspects of Nuclear Medicine biomarker quantification using 123I labelled radiopharmaceuticals for the diagnosis of Lewy body disease is presented in this thesis. This provides a solid foundation for clinical and research application of these techniques in both early and established disease