P.M. Kemp

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.

The specific uptake size index for quantifying radiopharmaceutical uptake

Quantitative indices of radionuclide uptake in an object of interest provide a useful adjunct to qualitative interpretation in the diagnostic application of radionuclide imaging. This note describes a new measure of total uptake of an organ, the specific uptake size index (SUSI). It can either be related in absolute terms to the total activity injected or to the specific activity in a reference region. As it depends on the total activity in the object, the value obtained will not depend on the resolution of the imaging process, as is the case with some other similar quantitative indices. This has been demonstrated in an experiment using simulated images. The application of the index to quantification of dopamine receptor SPECT imaging and parathyroid-thyroid subtraction planar scintigraphy is described. The index is considered to be of potential value in reducing variation in quantitative assessment of uptake in objects with applications in all areas of radionuclide imaging.

Imaging in dementia with Lewy bodies: a review.

This review discusses the role of functional and structural imaging in patients with suspected dementia with Lewy bodies, with particular emphasis on SPECT and PET dopaminergic and cerebral perfusion/metabolic techniques. It is envisaged that this information may be useful to nuclear medicine physicians, radiologists, psychiatrists, neurologists, geriatricians and physicians.

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.

Imaging the dopaminergic system in suspected parkinsonism, drug induced movement disorders, and Lewy body dementia

This review discusses the role of pre- and post-synaptic dopaminergic imaging in suspected Parkinsons disease, vascular parkinsonism, the parkinsonian syndromes, drug induced movement disorder, and Lewy body dementia. It is envisaged that this information may be useful to neurologists, psychiatrists, physicians/geriatricians, radiologists and nuclear medicine physicians.

Impact of 123I-FP-CIT (DaTSCAN) SPECT on the diagnosis and management of patients with dementia with Lewy bodies: a retrospective study.

ObjectiveTo assess the impact of imaging the presynaptic dopaminergic terminal using DaTSCAN single-photon emission computed tomography (SPECT) on the clinical diagnosis and subsequent management of patients with possible dementia with Lewy bodies (DLB), who were referred for imaging. MethodsA retrospective case note study was undertaken, involving a series of consecutive patients who had undergone DaTSCAN SPECT 12–24 months earlier. ResultsCase notes of 80 patients were reviewed. DaTSCAN imaging results were abnormal (indicating DLB) in 20 (25%) and normal (suggesting an alternative diagnosis or absence of disease) in 60 (75%) patients. Of the 20 patients with an abnormal scan, 18 had a postscan working clinical diagnosis of DLB (90%), one had diagnosis of vascular dementia (5%) and another had no recorded outcome (5%). Fifty-eight out of the 60 patients with a normal DaTSCAN image result had an alternative clinical diagnosis of DLB (95%). Consequently, DaTSCAN findings were concordant with the outcome clinical diagnosis in 76 out of the 80 (95%) cases. Subsequent to DaTSCAN SPECT, scan findings and diagnoses were discussed with patients and/or their carers in 94% of cases and subsequent treatment options discussed in 93% of cases. ConclusionIt would seem that DaTSCAN imaging has a marked influence on the working clinical diagnosis and subsequent management of patients with suspected DLB.

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.

Generation of realistic HMPAO SPECT images using a subresolution sandwich phantom

UNLABELLED Traditional interpretation of rCBF SPECT data is of a qualitative nature and is dependent on the observers understanding of the normal distribution of the tracer. The use of a normal database in quantitative regional analysis facilitates the detection of functional abnormality in individual and group studies by accounting for inter-subject variability. The ability to simulate realistic images would allow various important areas related to the use of normal databases to be studied. These include the optimisation of the detection of abnormal blood flow and the portability of normal databases between gamma camera systems. To investigate this further we have constructed a hardware phantom and scanned various configurations of radioactive brain patterns and simulated skull configurations. METHODS A subresolution sandwich phantom was constructed with a simulated skull which was assembled using a high-resolution segmented MR scan printed with a (99m)TcO₄ - mixture and scanned using a double-headed gamma camera with parallel-hole collimators. Various different grey-to-white matter (GM:WM) ratios and aluminium simulated skull configurations were used. A single difference measure between the phantom data and a control database mean image was used for optimisation. The realism of phantom data was assessed using statistical parametric mapping (SPM) and ROI analysis. RESULTS Optimisation was achieved with a range of WM:GM ratios from 1.9 to 2.4:1 with various simulated skull configurations. CONCLUSION The ability to simulate realistic HMPAO SPECT scans has been demonstrated using a subresolution sandwich phantom. Further work, involving scanning the optimised phantom on different gamma camera systems and comparison with camera-specific normal databases should further refine the phantom configuration.