S.M.A. Hoffmann

Alzheimer’s disease: differences in technetium-99m HMPAO SPECT scan findings between early onset and late onset dementia

Objective: To compare the HMPAO SPECT cerebral perfusion patterns in early and late onset Alzheimer’s disease. Methods: Twenty patients with early onset disease (<65 years) and 44 patients with late onset disease (>65 years) were studied. All patients fulfilled NINCDS-ADRDA clinical criteria and had details of disease severity and length of history at the time of imaging. Technetium-99m HMPAO SPECT brain scans were acquired on a multi-detector gammacamera and analysed visually and with statistical parametric mapping (SPM99). Results: Patients with early onset disease had significantly greater posterior cortical association area involvement whereas those with late onset disease had significantly greater medial temporal hypoperfusion. These findings were unchanged after controlling for disease severity and length of illness. Discussion: These functional imaging findings of the differences between early and late onset Alzheimer’s disease are supported by published findings that include histopathological and clinical evidence; namely late onset patients tend to present with the characteristic involvement of the medial temporal lobes producing marked memory loss whereas early onset patients present with predominant posterior cortical association area involvement. These age related findings should be borne in mind when clinically diagnosing, and interpreting functional brain imaging studies in, patients with suspected Alzheimer’s disease.

A randomised placebo controlled study to assess the effects of cholinergic treatment on muscarinic receptors in Alzheimer's disease.

Objective:To determine the effects of cholinergic treatment on the muscarinic receptor in patients with Alzheimer’s disease. Methods:12 patients with mild to moderate Alzheimer’s disease and six controls were studied. The patients underwent ADAS-COG psychometric assessment and SPECT brain imaging with 123I quinuclidinyl benzilate (QNB), to demonstrate the postsynaptic muscarinic M1 receptor, before being randomised in a double blind study to receive either an acetylcholinesterase inhibitor (donepezil) or placebo for four months. Following this, the ADAS-COG and the 123I-QNB receptor scan were repeated. The controls were imaged on one occasion only. All image analyses were undertaken using SPM99. Results:123I-QNB imaging showed a significant relation between baseline psychometric impairment and deficits on scanning. Both placebo and actively treated groups had reductions in 123I-QNB uptake. Greater reductions in receptor binding were demonstrated in the placebo group than in those receiving active treatment. Intraindividual reproducibility of the 123I-QNB imaging technique appeared highly robust. Conclusions:The results suggest that 123I-QNB uptake is better preserved in Alzheimer’s disease patients on cholinergic treatment than on placebo. Cholinergic treatment may play a neuroprotective role. Sequential 123I-QNB imaging seems to be a powerful tool in monitoring the response of these receptors to disease modifying treatments.

Limitations of the HMPAO SPECT appearances of occipital lobe perfusion in the differential diagnosis of dementia with Lewy bodies

ObjectiveTo assess the utility of the appearances of occipital lobe perfusion on HMPAO SPECT in the diagnosis of dementia with Lewy bodies (DLB) using the 123I-FP-CIT findings as the diagnostic ‘gold standard’. MethodsEighty-four consecutive patients underwent both HMPAO SPECT and 123I-FP-CIT as part of their routine investigations for suspected DLB. ResultsThirty-nine of the 84 FP-CIT scans were abnormal indicating a prevalence of 44% of patients with DLB in this series. In those patients classified as DLB, 28% of HMPAO SPECT scans demonstrated occipital hypoperfusion. In those patients with a dementia other than DLB 31% of patients demonstrated occipital hypoperfusion (P=0.8). ConclusionOccipital lobe hypoperfusion as demonstrated by HMPAO SPECT in patients with suspected Lewy body dementia does not appear to be able to either rule in, or rule out, the diagnosis of DLB.

The contribution of statistical parametric mapping in the assessment of precuneal and medial temporal lobe perfusion by 99mTc-HMPAO SPECT in mild Alzheimer's and Lewy body dementia

AimTo assess the role of 99mTc-hexamethylpropyleneamine oxime single-photon emission computed tomography (99mTc-HMPAO SPECT) imaging of the precuneus and medial temporal lobe in the individual patient with mild Alzheimers disease and dementia with Lewy bodies (DLB) using statistical parametric mapping and visual image interpretation. MethodsThirty-four patients with mild late-onset Alzheimers disease, 20 patients with early-onset Alzheimers disease, 15 patients with DLB and 31 healthy controls were studied. All patients fulfilled appropriate clinical criteria; the DLB patients also had evidence of dopaminergic presynaptic terminal loss on 123I-N-ω-fluoropropyl-2&bgr;-carbomethoxy-3&bgr;-(4-iodophenyl)-tropane imaging. 99mTc-HMPAO SPECT brain scans were acquired on a multidetector gamma camera and images were assessed separately by visual interpretation and with SPM99. ResultsStatistical parametric maps were significantly more accurate than visual image interpretation in all disease categories. In patients with mild late-onset Alzheimers disease, statistical parametric mapping demonstrated significant hypoperfusion to the precuneus in 59% and to the medial temporal lobe in 53%. Seventy-six per cent of these patients had a defect in either location. No controls had precuneal or medial temporal lobe hypoperfusion (specificity, 100%). Statistical parametric mapping also demonstrated 73% of patients with DLB to have precuneal abnormalities, but only 6% had medial temporal lobe involvement. ConclusionThese findings illustrate the capability of statistical parametric mapping to demonstrate reliable abnormalities in the majority, but not all, patients with either mild Alzheimers disease or DLB. Precuneal hypoperfusion is not specific to Alzheimers disease and is equally likely to be found in DLB. In this study, medial temporal hypoperfusion was significantly more common in Alzheimers disease than in DLB. Statistical parametric maps appear to be considerably more reliable than simple visual interpretation of 99mTc-HMPAO images for these regions.

Activity concentration measurements using a conjugate gradient (Siemens xSPECT) reconstruction algorithm in SPECT/CT.

The interest in quantitative single photon emission computer tomography (SPECT) shows potential in a number of clinical applications and now several vendors are providing software and hardware solutions to allow ‘SUV-SPECT’ to mirror metrics used in PET imaging. This brief technical report assesses the accuracy of activity concentration measurements using a new algorithm ‘xSPECT’ from Siemens Healthcare. SPECT/CT data were acquired from a uniform cylinder with 5, 10, 15 and 20 s/projection and NEMA image quality phantom with 25 s/projection. The NEMA phantom had hot spheres filled with an 8 : 1 activity concentration relative to the background compartment. Reconstructions were performed using parameters defined by manufacturer presets available with the algorithm. The accuracy of activity concentration measurements was assessed. A dose calibrator–camera cross-calibration factor (CCF) was derived from the uniform phantom data. In uniform phantom images, a positive bias was observed, ranging from ∼6% in the lower count images to ∼4% in the higher-count images. On the basis of the higher-count data, a CCF of 0.96 was derived. As expected, considerable negative bias was measured in the NEMA spheres using region mean values whereas positive bias was measured in the four largest NEMA spheres. Nonmonotonically increasing recovery curves for the hot spheres suggested the presence of Gibbs edge enhancement from resolution modelling. Sufficiently accurate activity concentration measurements can easily be measured on images reconstructed with the xSPECT algorithm without a CCF. However, the use of a CCF is likely to improve accuracy further. A manual conversion of voxel values into SUV should be possible, provided that the patient weight, injected activity and time between injection and imaging are all known accurately.

Simulation of realistic abnormal SPECT brain perfusion images: application in semi-quantitative analysis.

Simulation is useful in the validation of functional image analysis methods, particularly when considering the number of analysis techniques currently available lacking thorough validation. Problems exist with current simulation methods due to long run times or unrealistic results making it problematic to generate complete datasets. A method is presented for simulating known abnormalities within normal brain SPECT images using a measured point spread function (PSF), and incorporating a stereotactic atlas of the brain for anatomical positioning. This allows for the simulation of realistic images through the use of prior information regarding disease progression. SPECT images of cerebral perfusion have been generated consisting of a control database and a group of simulated abnormal subjects that are to be used in a UK audit of analysis methods. The abnormality is defined in the stereotactic space, then transformed to the individual subject space, convolved with a measured PSF and removed from the normal subject image. The dataset was analysed using SPM99 (Wellcome Department of Imaging Neuroscience, University College, London) and the MarsBaR volume of interest (VOI) analysis toolbox. The results were evaluated by comparison with the known ground truth. The analysis showed improvement when using a smoothing kernel equal to system resolution over the slightly larger kernel used routinely. Significant correlation was found between effective volume of a simulated abnormality and the detected size using SPM99. Improvements in VOI analysis sensitivity were found when using the region median over the region mean. The method and dataset provide an efficient methodology for use in the comparison and cross validation of semi-quantitative analysis methods in brain SPECT, and allow the optimization of analysis parameters.

Optimization of the parameters of a method for computer-aided detection of perfusion deficiencies in brain images.

ObjectiveSimulated data from the recent Institute of Physics and Engineering in Medicine audit of quantitative cerebral perfusion were used to optimize the parameters of eigenimage analysis, a method for computer-aided detection. MethodsTwenty normal images provided by the audit were registered to the International Consortium for Brain Mapping 452 template using HERMES multimodality software and normalized to total counts. Six normal atlases were formed using the mean image and from zero to five eigenimages. Eight patient images, with computer-simulated lesions at known positions, were similarly registered and normalized. For each atlas, z-score images were formed for each patient. Thresholds of z0 = 2–5 in intervals of 0.5 were applied to the z-score images to form binary images of normal and abnormal voxels. A lesion was defined as a connected group of abnormal voxels with a minimum size of 1 ml. Lesions were assigned to one of 12 regions defined by the template. For eight patients, this gave 96 regions, 19 of which were known to contain an abnormality. Receiver-operating characteristic analysis was performed for the regions using z0 as a variable threshold. ResultsFor the receiver-operating characteristic analysis, an optimal area under the curve of approximately 0.90 was found using either one or three eigenimages, whereas good results (sensitivity = 0.75%; specificity = 90%) were obtained for a threshold of z0 approximately equal to 3. When the number of images in the normal dataset was considered, a meta-analysis showed consistency with other studies. ConclusionEigenimage analysis was shown to give good diagnostic accuracy for cerebral perfusion images based on objective evaluation using simulated images.

A simulation method for realistic abnormal SPECT brain perfusion images

Background:Quantitative analysis is widely applied to SPECT perfusion imaging of the brain. Simulation offers a useful system for validating and comparing these methods. A method for simulating realistic abnormal brain SPECT images is presented.Methods: Twenty-nine normal control studies were available. Perfusion abnormalities were introduced in a subset of these subjects to simulate the four most common forms of dementia and varying levels of impairment. The abnormalities were defined in Talairach space, as voxels with percentage perfusion reduction in known anatomical positions. They were spatially transformed to the control subject space, convolved with a measured PSF, and introduced into the normal image. This allowed simulation of abnormal perfusion distribution in a variety of anatomical shapes. Validation of simulation was performed by viewing by an experienced observer. Analysis was performed using SPM99 comparing with the remainder of the controls. Results:The simulated image set was considered visually realistic. SPM99 analysis detected the abnormalities with a sensitivity of 95% and a specificity of 88%. Conclusion:A method has been developed for simulating abnormal SPECT brain images in a variety of realistic anatomical shapes. The data should be suitable for audit of HMPAO SPECT brain perfusion imaging.