Howard G. Gemmell

Differential diagnosis in dementia using the cerebral blood flow agent 99mTc HM-PAO: a SPECT study.

One of the potential clinical uses of the new cerebral blood flow agent 99mTc-hexamethylpropyleneamineoxime (HM-PAO) is the investigation of dementia, in particular to differentiate between dementia of the Alzheimer type (DAT) and multiinfarct dementia (MID). In this study 27 patients, 17 with DAT and 10 with MID, and three normal volunteers were imaged both with single photon emission CT and magnetic resonance. The HM-PAO perfusion deficits were much more common in the DAT group than in the MID group, especially in the temporoparietooccipital (TPO) regions. The two groups of patients were found to be significantly different (p less than 0.02), as regards the frequency of occurrence of bilateral TPO perfusion deficits. Four of the 17 DAT patients did not have bilateral TPO deficits but these included the three least impaired patients as assessed by psychometric testing.

Cerebral blood flow and cognitive responses to rivastigmine treatment in Alzheimer's disease.

Twenty seven patients with mild AD were enrolled in a prospective open label controlled study of rivastigmine. Assessments included a range of neuropsychiatric and behavioural measures and rCBF using HMPAO SPECT at baseline, three and six months. Significant enhancement of frontal, parietal and temporal brain blood flow with related psychometric improvement was observed in twelve of the treated patients. A pattern of reduced rCBF and cognitive performance was observed in four unresponsive and eleven untreated patients. The results suggest that alterations in the clinical and cognitive status of patients receiving a cholinesterase inhibitor are paralleled by changes in rCBF. Longitudinal assessment with repeated imaging offers a method of better understanding the effects of cholinesterase inhibition on the AD brain.

Delusions in Alzheimer's disease: spet evidence of right hemispheric dysfunction.

Delusional thinking and related behaviours are common symptoms in Alzheimers disease (AD). The aim of the study was to determine if any consistent cerebral image pattern can be identified using Tc99m-hexamethylpropyleneamine (HMPAO) SPET in AD patients with and without delusions. 18 AD patients with delusion and 15 AD patients without delusion underwent neuropsychological testing and regional cerebral blood flow imaging using Tc99m-HMPAO SPET. The reconstructed data was compared using regions of interest drawn over each cerebral lobe and a statistical parametric mapping (SPM) approach. The neuropsychological testing showed that there was no difference in the profiles of the deluded and non deluded AD patients. The imaging results showed a significant degree of image asymmetry. This took the form of a right hemisphere hypoperfusion mainly in the right frontal and limbic regions. The results do not indicate a specific focal site of hypoperfusion in the patients with delusion. They do, however, indicate that delusions in AD may be associated with areas of hypoperfusion in the right anterior hemisphere.

Changes in the rCBF images of patients with Alzheimer's disease receiving Donepezil therapy

Alzheimers disease is associated with a loss in presynaptic cholinergic function. It has been suggested that cholinergic inhibitors such as donepezil hydrochloride (Donepezil) could restore this function and improve some of the symptoms of Alzheimers disease. Previous work has shown that Donepezil improves cognitive and global function in patients with mild to moderate Alzheimers disease. This study reviewed retrospectively 12 patients who had previously had a 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) single photon emission tomography (SPET) regional cerebral blood flow (rCBF) examination and had gone on to receive Donepezil therapy. These patients were recalled for a further 99Tcm-HMPAO SPET rCBF examination and the image data sets were compared. The results showed an overall increase in global cerebral blood flow (P = 0.04) averaged over the group with a percentage change in blood flow ranging from −1.8% to 6.4%. However, some patients showed a slight decrease in blood flow. When the data were analysed in terms of regional cerebral blood flow, we found that the most significant increase in blood flow occurred in the frontal lobes (P = 0.02).

The use of technetium-99m-HM-PAO in the assessment of patients with dementia and other neuropsychiatric conditions.

One hundred fourteen patients suffering from neuropsychiatric conditions have been studied using 99mTc-labeled hexamethylpropyleneamine oxime (HM-PAO) and single photon emission computed tomography (SPECT). Ninety-one patients had a firm clinical diagnosis while 23 were examined without knowledge of the clinical diagnosis. Of the 91 patients, 51 were suffering from dementia, 25 multi-infarct type and 26 Alzheimers disease. In 19 of the Alzheimers patients, a characteristic pattern of decreased perfusion in the parieto-occipital regions was demonstrated while those with multi-infarct type showed varying degrees of irregular uptake in the cerebral cortex. These appearances are similar to those shown with positron emission tomography (PET) and we believe that HM-PAO will provide a widely available method for identifying patients with Alzheimers disease. Twenty-nine patients were suffering from diseases involving the basal ganglia. Fifteen patients with Parkinsons disease showed no significant abnormality in basal ganglia uptake, while 7 or 8 patients with Huntingtons disease who had full examinations showed decreased uptake in the caudate nuclei. Similarly, four of six patients with other basal ganglia diseases showed impaired uptake by basal ganglia, and it is concluded that HM-PAO may be useful for the diagnosis and management of this type of patient. Twenty-three patients received HM-PAO imaging as part of their diagnostic work-up; in 19 of them, detailed follow-up was obtained, which indicated that in 7 cases the result of the HM-PAO scan altered the clinical diagnosis and in 9 cases resulted in a change in management. In the remaining 13 cases, the study was found to be helpful in confirming the diagnosis.

Single Photon Emission Computed Tomography (SPECT)

Although the principles of single photon emission computed tomography (SPECT) have been well understood for many years and several centers were using SPECT clinically in the late 1960s and early 1970s, there has been a dramatic increase in the number of SPECT installations in recent years. It is now unusual to purchase a gamma camera without SPECT capability and most new cameras are dual-headed, which can offer additional advantages in SPECT. A state-of-the-art gammacamera that iswellmaintainedshouldproduce high-quality SPECT images consistently, and evenolder cameras canproduce acceptable images if care is taken. SPECT is essential for imaging the brain with either cerebral blood flow agents, such as 99mTc-HMPAO, or brain receptors, such as 123I-FP-CIT, and for imaging myocardial perfusion with either 201Tl or the technetium-labeled agents MIBI and tetrofosmin. SPECT is also now widely used in some aspects of skeletal imaging and can be helpful in tumor imaging with, for example, 123I-MIBG, 111In octreotide, or 99mTc NeoSPECT. What is the purpose of SPECT and what is its advantage over planar imaging? Planar imaging portrays a three-dimensional (3-D) distribution of radioactivity as a 2-D image with no depth information and structures at different depths are superimposed. The result is a loss of contrast in the plane of interest due to the presence of activity in overlying and underlying structures, as shown in Figure 2.1.Multiple planar views are an attempt to overcome this problem but SPECT has been developed to tackle the problem directly. SPECT also involves collecting conventional plane views of the patient from different directions but many more views are necessary, typically 64 or 128, although each view usually has fewer counts than would be acceptable in a conventional static image. From these images a set of sections through the patient can then be reconstructed mathematically. Conventionally SPECT images are viewed in three orthogonal planes – transaxial, sagittal, and coronal – as shown in Figure 2.2. Usually the transaxial images are directly obtained from SPECT data; a particular row of pixels in each image obtained with a rotating gamma camera corresponds to a particular transaxial section. The other planes are derived from a stack of transaxial sections.

A comparison of Tc-99m HM-PAO and I-123 IMP cerebral SPECT images in Alzheimer's disease and multi-infarct dementia

SPECT images of the brain can be obtained using either 123I labelled amines or 99mTc-hexamethylpropyleneamineoxime (HM-PAO). Both materials produce images which are blood flow dominated and so appear similar in normal subjects, although the respective mechanisms of uptake are not yet finally established. It seems likely, however, that the different mechanisms of uptake are responsible for recent reports of some differences seen in images obtained with the two types of agent in patients with cerebral pathology, mainly cerebrovascular disease. In this study, 12 demented patients, 6 with dementia of the Alzheimer type (DAT) and 6 with multi infarct dementia (MID), were imaged with 123I-isopropylamphetamine (IMP) and 99mTc-HM-PAO and the images compared. Significantly more lesions were seen with IMP than HM-PAO (P<0.02); out of a possible 120 sites, 41 lesions were seen with IMP compared to 28 with HM-PAO, 23 being seen with both agents. However, it is concluded that either agent can be used for the differential diagnosis of dementia, a task for which the new cerebral blood flow agents seem well suited.

Systematic review of the prognostic effectiveness of SPECT myocardial perfusion scintigraphy in patients with suspected or known coronary artery disease and following myocardial infarction.

ObjectivesIn patients with suspected or known coronary artery disease (CAD), or following myocardial infarction (MI), assessing the degree of ischaemia is important from a prognostic and therapeutic point of view. Single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy (MPS) is a non-invasive technique that allows the presence, location and extent of ischaemia to be determined. The aim of this systematic review was to assess the prognostic effectiveness of SPECT MPS. MethodsWe sought prognostic studies involving SPECT, exercise tolerance testing (ETT) and/or coronary angiography (CA) in people with suspected or known CAD, or following MI. Outcomes included cardiac death, non-fatal MI and revascularization. We searched the following databases: MEDLINE, PREMEDLINE, EMBASE, BIOSIS, Science Citation Index, the Cochrane Library, the Health Management Information Consortium and the Health Technology Assessment Database. ResultsTwenty-one observational studies enrolling 53,762 people reported the general prognostic value of SPECT MPS. In multivariate analysis, SPECT MPS variables yielded both independent and incremental value to combinations of clinical, ETT and angiographic variables in predicting cardiac death or non-fatal MI. Three comparative studies reported lower revascularization rates following a SPECT MPS-CA strategy (6–21%) compared with direct CA (16–44%). Four observational studies enrolling 2106 people reported the prognostic value of SPECT for patients following MI. In multivariate analysis including clinical history, ETT, SPECT MPS and angiographic variables, strategies involving SPECT MPS provided independent and incremental prognostic performance in predicting future cardiac events. ConclusionsSPECT MPS provides important additional information to that from ETT and/or CA that helps to risk-stratify patients with suspected or known CAD or following MI, enabling them to be managed more appropriately. Increasing the use of strategies involving SPECT MPS may identify lower risk patients for whom invasive CA might be avoided.

Alzheimer's disease in adults with Down's syndrome: the relationship between regional cerebral blood flow equivalents and dementia

Twenty adult patients suffering from Downs syndrome (DS) were recruited from hospitals and the community, together with 14 age‐ and sex‐matched controls of normal intelligence. Dementia was diagnosed in patients using a structured psychiatric and physical examination as well as a carer interview and case notes. All patients and controls were imaged using single photon emission computerized tomography with 99mTc‐exametazime. Four patients were clinically demented and all of them showed regional cerebral blood flow (rCBF) changes commonly found in patients with Alzheimers disease, namely bilateral temporo‐parietal deficits. These changes were also observed in about half of the patients without clinical evidence of dementia, but in none of the healthy controls. Across the group of patients, temporo‐parietal rCBF deficits were associated with evidence of deterioration, but not with advancing age.

Cerebral blood flow measured by SPECT as a diagnostic tool in the study of dementia

The aims of this work have been three-fold: 1) to look for common features in the HMPAO distributions of patients of know pathology; 2) to carry out longitudinal studies in these patients; and 3) to consider the role of HMPAO imaging in the management of these patients and in psychiatry generally