H. J. Testa

Single photon emission tomography using 99mTc-HM-PAO in the investigation of dementia.

Single photon emission tomographic imaging of the brain using 99mTc HM-PAO was carried out in patients with a clinical diagnosis of Alzheimers disease, non-Alzheimer frontal-lobe dementia, and progressive supranuclear palsy. Independent assessment of reductions in uptake revealed posterior hemisphere abnormalities in the majority of the Alzheimer group, and selective anterior hemisphere abnormalities in both other groups. The findings were consistent with observed patterns of mental impairment. The imaging technique has potential value in the differential diagnosis of primary cerebral atrophy.

A clinical role for 99mTc-HMPAO SPECT in the investigation of dementia?

OBJECTIVES To provide the clinician with a guide to the clinical utility of 99mTc-HMPAO single photon emission computed tomography (SPECT) and to the interpretation of specific test results in the differential diagnosis of dementia. METHODS Three hundred and sixty three patients with dementia were studied prospectively for a median three (range 1–6) years and classified into disease groups on the basis of established clinical criteria. The degree to which different patterns of cerebral blood flow (CBF) abnormality found on99mTc-HMPAO SPECT imaging at the time of initial patient presentation modified clinical diagnoses was determined by calculating the likelihood ratios for pairwise disease group comparisons. The optimal clinical usage of 99mTc-HMPAO SPECT was determined by calculating the percentage of significant test results for each pairwise disease group comparison. RESULTS Bilateral posterior CBF abnormality was found to significantly increase the odds of a patient having Alzheimer’s disease as opposed to vascular dementia or frontotemporal dementia. Bilateral anterior CBF abnormality significantly increased the odds of a patient having frontotemporal dementia as opposed to Alzheimer’s disease, vascular dementia, or Lewy body disease. “Patchy” CBF changes significantly increased the odds of a patient having vascular dementia as opposed to Alzheimer’s disease. Unilateral anterior, unilateral anterior plus unilateral posterior, and generalised CBF abnormality failed to contribute to the differentiation of any of these forms of dementia. CONCLUSIONS 99mTc-HMPAO SPECT was found to be most useful in distinguishing Alzheimer’s disease from vascular dementia and fronto temporal dementia, and least useful in differentiating between Alzheimer’s disease and Lewy body disease, and between vascular dementia, frontotemporal dementia, and progressive aphasia. It is suggested that CBF SPECT should be used selectively and as an adjunct to clinical evaluation and CT.

Diagnostic patterns of regional atrophy on MRI and regional cerebral blood flow change on SPECT in young onset patients with Alzheimer's disease, frontotemporal dementia and vascular dementia.

Objectives– Alzheimers disease (AD), frontotemporal dementia (FTD) and vascular dementia (VaD) are the three most common causes of young onset dementias. Most neuroimaging studies of these disorders have involved comparisons with normal controls. The aims of this study were to examine the clinical diagnostic value of magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) (in combination and in isolation) in the differentiation of one form of dementia from another from amongst a␣group of AD, FTD and VaD. Methods– T1 weighted MRI images and 99mTc‐HMPAO SPECT images were obtained from consecutive patients with FTD (n=21), AD (n=23) and VaD (n=20) and rated visually by experienced neuroradiologists and nuclear medicine physicians. Results– Asymmetrical atrophy was seen only in FTD. Frontotemporal dementia patients were the most atrophic whereas severe atrophy was rarely observed in VaD. Severe frontal atrophy (unilaterally or bilaterally) and/or asymmetrical atrophy on MRI is highly diagnostic (sensitivity 0.71, specificity 0.93, LR 10.24) of FTD from within a group of FTD and non‐FTD (AD, VaD) patients. Mild or severe parietal atrophy with severe reduction in parietal regional cerebral blood flow on SPECT is diagnostic (sensitivity 0.71, specificity 0.76, LR 3.02) of AD from within a group of AD and non‐AD (VaD, FTD) patients. Conclusion– Anatomical (MRI) and functional (SPECT) imaging provide different information and a combination of these modalities improves diagnostic specificity.

Accuracy of single-photon emission computed tomography in differentiating frontotemporal dementia from Alzheimer's disease.

Background: Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are the commonest causes of presenile dementia. In the absence of a biological marker, diagnosis is reliant on clinical evaluation. Confirmation is often sought from neuroimaging, including single-photon emission computed tomography (SPECT). Most previous SPECT studies lack pathological validation. Aim: To examine the accuracy of SPECT in differentiating FTD from AD in patients with subsequent pathological confirmation. Methods: Technetium-99-labelled hexamethyl propylene amine oxime SPECT images obtained at initial evaluation in 25 pathologically confirmed cases of FTD were examined. These images were visually rated by an experienced blinded nuclear medicine consultant and compared with those of 31 patients with AD, also with pathological validation. Results: A reduction in frontal cerebral blood flow (CBF) was more common in FTD and was of diagnostic value (sensitivity 0.8, specificity 0.65 and likelihood ratio (LR) 2.25; 95% CI 1.35 to 3.77). A pattern of bilateral frontal CBF reduction without the presence of associated bilateral parietal CBF change is diagnostically more accurate (sensitivity 0.80, specificity 0.81 and +LR 4.13, 95% CI 1.96 to 8.71). Diagnostic categorisation (FTD or AD) on the basis of SPECT alone was less accurate than clinical diagnosis (based on neurology and detailed neuropsychological evaluation). One patient with FTD was initially clinically misdiagnosed as AD, owing to the lack of availability of full neuropsychological assessment. However, SPECT correctly diagnosed this patient, providing a diagnostic gain of 4%. Conclusion: Technetium-99-labelled hexamethyl propylene amine oxime SPECT CBF patterns provide valuable information in the diagnosis of FTD and AD. These data can be better used as an adjunct to clinical diagnosis if pathology is to be correctly predicted in life.

A 99mTc-HMPAO single-photon emission computed tomography study of Lewy body disease

Abstract The purpose of this study was to investigate patterns of 99mTc-HMPAO single-photon emission computed tomography (SPECT) abnormality in Lewy body disease (LBD) and to compare findings with those encountered in Alzheimer’s disease (AD). The study group comprised 20 consecutive patient referrals fulfilling clinical criteria for LBD. All patients had fluctuating cognitive impairment and ‘subcortical’ dysfunction with or without perceptuospatial and/or linguistic impairment. Six patients had asymmetrical signs of parkinsonism (three left-sided and three right-sided), and 14 patients had symmetrical features of extrapyramidal involvement. 99mTc-HMPAO SPECT imaging was performed on LBD patients and findings compared with those of 57 patients with ‘probable’ AD and 11 normal age-matched controls. Within the LBD and AD groups, patterns of cortical and subcortical blood-flow abnormality were compared with patterns of cognitive and neurological breakdown. LBD was associated with bilateral posterior cortical blood flow abnormality, a pattern strikingly similar to that found in AD. Within the LBD group, cortical blood-flow abnormality was found to reflect patterns of neurological dysfunction (parkinsonism) indicative of subcortical involvement. In contrast, cortical blood-flow changes did not reflect patterns of neuropsychological impairment suggestive of cortical dysfunction. Within the AD group, cortical blood-flow changes were mirrored by the pattern of neuropsychological impairment. Findings support the notion that cortical blood-flow abnormality in LBD might reflect a combination of direct cortical pathology and cortical deafferentation secondary to subcortical Lewy body pathology. It would appear that 99mTc-HMPAO SPECT imaging is of limited value in the clinical differentiation of LBD and AD.

Choice of reference region in the quantification of single-photon emission tomography in primary degenerative dementia

This study evaluated the effect of using two different reference regions in the quantification of single-photon emission tomography (SPET). SPET scans of 30 patients with Alzheimers disease (AD) and 30 patients with frontotemporal dementia were compared with the scans of ten age-matched controls. Regions of interest (RO1s) were defined on transaxial slices by a semi-automatic method. Regional cerebral blood flow indices (rCBFi) in each R01 were determined by normalizing the count densities to both cerebellar and occipital cortex reference regions. Mean rCBFi for each ROI were calculated for the patient and control groups and significant group differences determined. The number and topographical distribution of ROIs with significant group differences varied depending upon the choice of reference region. The magnitude of these differences was greatest when the cerebellum was used as the reference region. The disparity between results obtained with the two reference regions was most apparent in the AD group. The reasons for these differences are discussed and we conclude that the cerebellum is the more appropriate choice of reference region in the quantification of SPET in primary degenerative dementia.

The contribution of single photon emission tomography to the clinical differentiation of degenerative cortical brain disorders

The accurate clinical diagnosis of degenerative cortical brain disorders is a necessary prerequisite for patient management and the critical evaluation of new treatments. This study has evaluated the ability of single photon emission tomography (SPET) to differentiate between Alzheimers disease (AD) and different forms of non-Alzheimer lobar atrophy (LA), using a multi-purpose system in widespread routine clinical use.99mTc-HMPAO SPET was carried out in patients with AD and three clinical syndromes associated with LA: frontotemporal dementia (FTD), progressive non-fluent aphasia (PA) and semantic dementia (SD). Principal component (PC) analysis was performed on regional cerebral blood flow (rCBF) data and inter-group comparisons were performed for PC scores using multiplet-tests. Three PCs explained 86.5% of the variation in rCBF values between individual patients and normal controls. The first PC reflected the average rCBF value and separated patient groups from normal controls but failed to distinguish between patient groups. The second PC reflected anterior-posterior asymmetry and separated AD from all three forms of LA. This PC also separated FTD and SD from controls but failed to distinguish between FTD, PA and SD. The third PC reflected left-right asymmetry and separated PA from all other groups.99mTc-HMPAO SPET is able to differentiate between degenerative cortical brain disorders in a simple and physiological meaningful way, thereby showing considerable potential as a routine tool in the clinical evaluation and differentiation of AD and LA.

The importance of using anterior and posterior views in the calculation of differential renal function using 99Tcm-DMSA

Radionuclide techniques for determining relative renal function are well established. One simple method uses the count rate from static images obtained using 99Tcm-dimercaptosuccinic acid (DMSA). We have reviewed 277 DMSA scans and shown that it is important to obtain the geometric mean of counts from the anterior and posterior views in order to correct for the different amounts of attenuation for each kidney. If counts were obtained from the posterior view only, erroneous results would be obtained in 8% of children under 13 years, in 28% of patients aged between 13 and 20 years and in 32% of patients over 20 years of age.

The Use of [99mTc]-HM-PAO in the Diagnosis of Primary Degenerative Dementia

The clinical value of single photon emission computed tomography (SPECT) in the differential diagnosis of dementia due to cerebral atrophy was evaluated by comparing the pattern of distribution [99mTc]–HM-PAO in three dementing conditions. Imaging was carried out in 26 patients with suspected Alzheimers disease, 14 with dementia of the frontal-lobe type, and 13 with progressive supranuclear palsy. Images were evaluated and reported without knowledge of clinical diagnosis with respect to regions of reduced uptake of tracer. Reduced uptake in the posterior cerebral hemispheres was characteristic of Alzheimers disease, while selective anterior hemisphere abnormalities characterized both dementia of the frontal-lobe type and progressive supranuclear palsy. The latter conditions could be distinguished on the basis of the appearance of integrity of the rim of the frontal cortex. The technique has an important role in the differentiation of degenerative dementias.

Thallium-201 myocardial imaging in patients with angina pectoris and anomalous aortic origin of the circumflex coronary artery

Anomalous aortic origin of the circumflex coronary artery is the commonest coronary artery anomaly. In this study, the significance of anomalous aortic origin of the circumflex coronary artery was investigated in seven patients with exertional chest pain using exercise thallium scintigraphy. Five patients with circumflex coronary arterial disease served as controls. Myocardial perfusion was normal in the five patients with a nonstenosed anomalous artery. In these patients, exercise heart rate and blood pressure response were normal. Two patients with a stenosed anomalous circumflex coronary artery and four of the five control patients had posterolateral myocardial perfusion defects. It is concluded that anomalous aortic origin of the circumflex coronary artery does not cause impairment of myocardial perfusion unless it is the site of significant coronary arterial stenosis.