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Table of Contents    
Year : 2010  |  Volume : 58  |  Issue : 6  |  Page : 857-862

Tc-99m ethylcysteinate dimer SPECT in the differential diagnosis of dementias

1 Department of Nuclear Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India
2 Department of Neurology, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Date of Acceptance12-Oct-2010
Date of Web Publication10-Dec-2010

Correspondence Address:
Madhavi Tripathi
Division of PET Imaging, MIRC, INMAS, Delhi - 54
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.73745

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 » Abstract 

Background: Dementias produce deficits in perfusion, in part, reflecting decreased metabolic needs. Single photon emission computed tomography (SPECT) studies have reported characteristic anterior-to-posterior perfusion gradients that permit distinction between the various forms of dementia. Aim: We undertook this study to evaluate the role of visual analysis of SPECT perfusion patterns for the differential diagnosis of types of degenerative dementia. Materials and Methods: Tc-99m ethylcysteinate dimer (ECD) was used with a dual-head scanner to generate perfusion images of the brain in 136 patients referred from the dementia clinic. Diagnosis was made by the nuclear physician unaware of clinical diagnosis. Results: Sensitivity, specificity, positive predictive value and negative predictive value of perfusion studies for Alzheimer's dementia were 93.42%, 95.12%, 97.26%, and 88.63%, respectively, and for frontotemporal dementia were 96.29%, 98%, 96.29%, and 98.88%, respectively. Conclusions: Tc-99m ECD brain perfusion SPECT is useful in the differential diagnosis of dementia with particular reference to AD as well as FTD.

Keywords: Alzheimer′s dementia, frontotemporal dementia, SPECT, Tc-99m ECD

How to cite this article:
Tripathi M, Tripathi M, Vibha D, Gowda N, Bal C, Malhotra A. Tc-99m ethylcysteinate dimer SPECT in the differential diagnosis of dementias. Neurol India 2010;58:857-62

How to cite this URL:
Tripathi M, Tripathi M, Vibha D, Gowda N, Bal C, Malhotra A. Tc-99m ethylcysteinate dimer SPECT in the differential diagnosis of dementias. Neurol India [serial online] 2010 [cited 2022 Jan 20];58:857-62. Available from:

 » Introduction Top

Single photon emission computed tomography (SPECT) imaging of regional cerebral blood flow has been used in patients with dementia diseases to determine the effectiveness of this method in identifying the principle cause of dementia in the elderly, Alzheimer's disease (AD) and several other entities that cause dementia, such as diffuse Lewy body disease (DLBD), frontotemporal dementia (FTD), and vascular dementia (VD). We undertook this study to evaluate the role of visual analysis of Technetium (Tc)-99m ethylcysteinate dimer (ECD) SPECT perfusion patterns for the differential diagnosis of degenerative dementia.

 » Materials and Methods Top

A total of 136 patients referred from the combined dementia clinic of the institute, for a SPECT perfusion study, were included. Each patient underwent a detailed neurological and neuropsychological evaluation along with mini-mental state examination (MMSE) score estimation. Vitamin B 12 , T3, T4, and TSH levels were estimated in all patients, followed by computed tomography (CT) or magnetic resonance imaging (MRI) correlation. The clinical diagnosis was based on diagnostic systems reported in literature, the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria were used for diagnosis of possible AD. [1] National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherchι et l'Enseignement en Neurosciences (NINDS-AIREN) criteria were used for VD, [2] and Lund-Manchester criteria were used for the diagnosis of FTD. [3] DLBD was diagnosed using the consensus criteria for DLBD. [4] The SPECT study was done within 64 ± 24 days of the clinical diagnosis. The average time interval between the onset of disease and the performance of SPECT was 2.7 ± 0.52 years.

SPECT protocol

Tc-99m ECD was prepared using the two-vial kit from Board of Radiation and Isotope technology, Department of Atomic energy, Government of India. Patients were injected with 555-740 MBq of Tc-99m ECD in a silent, dimly lit room; with eyes open. The SPECT study was acquired on a dual-head gamma camera (Varicam, Elscint) using a high-resolution low-energy or fan beam collimator. The patients lied supine, with head positioned in the headrest. Acquisition parameters were 25 seconds per stop, 128Χ128 matrix, circular orbit of 180° each head, step, and shoot mode. Data were reconstructed using a Butterworth filter order 10, cut-off 0.5 cycles/pixel. These were corrected for gamma ray attenuation using Chang attenuation coefficient of 0.11/cm. Transaxial, coronal, and sagittal sections were reconstructed with 2 pixel slice thickness.

SPECT images were reported by a Consultant in Nuclear Medicine (CSB) experienced in perfusion image reporting, unaware of the clinical diagnosis. Images were viewed on a monitor with standardised display settings and reported blind to clinical and CT findings apart from the suspicion of dementia. A coloured display (brain-fit or brain-french, Xpertpro/Entegra workstation-GE) was used, ranging from blue as the lowest through magenta and orange to white as the highest. Perfusion was considered abnormal if the area of deficit was below the halfway point of this scale on more than two sections.

The classical patterns of hypoperfusion on SPECT as described in literature so far were considered for the diagnosis of various types of dementia. [5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19] Patterns of cerebral blood flow (CBF) abnormality, which were considered diagnostic for each group are as follows:

  • Alzheimer's disease: Unilateral or bilateral parieto-temporal (symmetric or asymmetric) hypoperfusion with or without unilateral (U/L) or bilateral (B/L) frontal hypoperfusion [5],[6],[7],[8],[9],[10],[11],[12],[13]
  • Vascular dementia: Focal asymmetric perfusion abnormalities or patchy CBF abnormality or hypoperfusion corresponding to vascular territories.[14],[15]
  • Frontotemporal dementia: U/L or B/L frontal (dorsolateral or orbital) along with associated temporal hypoperfusion. [16],[17]
  • Diffuse Lewy body disease: Occipital hypoperfusion was taken as a characteristic of DLBD. This may be associated with cortical or subcortical perfusion defects. [18],[19]
  • Normal CBF pattern.

Statistical analysis

A 2*2 matrix was used to tabulate the test results for the two main disease groups: AD and FTD. Sensitivity and specificity, positive predictive value (PPV) and negative predictive value (NPV) of SPECT perfusion patterns for the two dementia groups were then calculated.

 » Results Top

A total of 19 patients were lost to follow-up and excluded from analysis. Final diagnosis (total = 117 patients) was AD in 76 cases, VD in 10, FTD in 27, and DLBD in 4 cases. [Table 1] shows the patient characteristics for the major dementia groups, significant P was seen for age between the AD and VD groups as well as the AD and FTD groups. This is probably because VD and FTD may have an earlier onset as compared to AD. There was no significant difference between the groups with regard to sex distribution (Chi-square = 0.91), length of history, and MMSE scores [Table 2]. [Table 3] shows sensitivity, specificity, PPV, NPV, and accuracy for positive test results for the two major disease groups comprising AD and FTD. For each of these groups, non-AD and non-FTD were regarded as negative results.
Table 1: Patient characteristics for the major dementia groups

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Table 2: Significance of demographic and clinical features between groups

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Table 3: Sensitivity and specificity, positive and negative predictive value for the diagnosis of AD and FTD

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Sensitivity and specificity of perfusion SPECT for the detection of AD were 93.42% and 95.12%, respectively. The PPV and NPV were 97% and 88%, respectively. Sensitivity and specificity of perfusion SPECT for the detection of FTD were 96.30% and 98.88%, respectively. The PPV and NPV were 96.29% and 98.88%, respectively. Nine cases of vascular dementia were correctly identified on the scan showing multifocal perfusion defects or perfusion defects in vascular territories corresponding to the history of stroke. One case of bihemispheric perfusion abnormality was classified into the AD group on SPECT, while one case of an asymmetric FTD was labelled as VD on SPECT. Two cases of DLBD were correctly identified on the SPECT study, showing occipital hypoperfusion, while one case each was labelled as AD and VD on SPECT.

 » Discussion Top

Functional brain imaging techniques like SPECT can provide substantial assistance in the initial diagnosis of dementia and in the differential diagnosis of specific dementing disorders. [1],[2] This analysis proves the role of perfusion SPECT with Tc-99m ECD for the diagnosis of not only AD but also FTD, with excellent sensitivity and specificity.This study aimed to evaluate the diagnostic utility of Tc-99m ECD perfusion SPECT in supporting specific dementia diagnosis. For this, the diagnosis of the dementias with this procedure has been assessed against the clinical diagnosis. The two major lacunae of this study were that we relied on clinical diagnosis with no histopathological (HP) correlation and only visual inspection of the perfusion images was used for interpretation of SPECT results. In the day-to-day clinical practice, it is difficult to obtain HP confirmation and, often, the patient is treated on the basis of clinical diagnosis. In the group with AD, the most common perfusion abnormality was symmetric or asymmetric hypoperfusion in temporoparietal cortices with or without frontal hypoperfusion [Figure 1], which was consistent with the findings of other studies. [5],[6],[7],[8],[9],[10],[11] The actual contribution of SPECT to the diagnosis of dementias is difficult to establish, primarily because of the limited number of population-based longitudinal studies comparing SPECT with histopathological findings. In the largest published study till date, the Oxford Project to Investigate Memory and Aging (OPTIMA) the sensitivity, specificity, PPV and NPV for the diagnosis of AD with the help of a visual rating of SPECT perfusion patterns were 89%, 60%, 81%, and 74%, respectively. [12] Jagust et al. showed that a clinical diagnosis of possible AD combined with a SPECT scan positive for temporoparietal hypoperfusion was as likely to be associated with AD at death as a clinical diagnosis of a probable AD alone. [13] These studies demonstrate reasonably good prediction of AD pathology from functional brain imaging. The high sensitivity and specificity of our study is probably because we directly recruited patients from the dementia clinic itself.
Figure 1: Tc-99m ECD SPECT in transaxial, sagittal, and coronal planes showing bilateral temporal, parietal, and frontal hypoperfusion (left > right), triangulated for the left parietal perfusion deficit, in a 65-year-old man with a clinical diagnosis of probable Alzheimer's dementia

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Miller et al. initially reported frontal and anterior temporal hypoperfusion as well as relative sparing of parietal and occipital blood flow in patients with FTD as compared to normal controls. [16] McNeill et al.[17] reported that frontal blood flow changes have a sensitivity of 80% and specificity of 65% in distinguishing AD from FTD. In our study, sensitivity and specificity of perfusion SPECT for the detection of FTD was 96% and 98%, respectively. Again, this high sensitivity and specificity might be because patients were referred directly from the dementia clinic. We, however, found that symmetrical or asymmetrical frontotemporal perfusion deficits with sparing of the parietal cortices [Figure 2] was useful in differentiating FTD from AD. Most of the perfusion studies [3],[4],[5],[6],[7] have discussed the role of SPECT in identifying Alzheimer's type dementia pattern; however, in this study, we were able to demonstrate that SPECT is equally useful in identifying a FTD pattern.
Figure 2: Tc-99m ECD SPECT in transaxial, sagittal, and coronal planes showing bilateral frontal and temporal hypoperfusion, triangulated for the frontal perfusion deficit, in a 65-year-old woman with a clinical diagnosis of frontotemporal dementia

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The diagnosis of VD may be difficult to establish because of its features overlapping with other forms of dementia. [14] In our study, 10 patients with VD diagnosed on the basis of clinical history and CT/MRI were found to have focal perfusion abnormalities. This included four patients with vascular deficits in main vessel territories and two patients with associated subcortical perfusion deficits. VD may present with a global hypoperfusion and one such case was wrongly classified as AD on SPECT. One case of FTD with marked asymmetric reduction in frontotemporal perfusion was labelled as VD on SPECT. The diagnosis of VD is confounded by the entity of mixed dementia (AD and VD) and SPECT has a role in identifying an Alzheimer's type of perfusion pattern in patients with vascular deficits on CT or MRI and suspected to have mixed dementia. [15] The role of SPECT in this entity would thus require further evaluation in a larger patient population.

Abnormalities in occipital CBF have been reported in DLBD patients. Two studies with relatively larger number of DLBD patients confirmed occipital hypoperfusion in these patients in comparison with AD patients. [18],[19] A larger number of patients would need to be evaluated to assess the value of Tc-99m ECD SPECT as an adjunct to diagnosis based on clinical criteria in this subgroup of patients.

The findings of this study are largely consistent with the results of previous CBF SPECT studies that have shown posterior CBF abnormality in AD, patchy CBF changes in VD, posterior CBF abnormality in DLBD, and anterior CBF abnormality in FTD. [7-9] Sensitivity and specificity of the Tc-99m ECD SPECT study was best for FTD. This study has shown that Tc-99m SPECT can strengthen a tentative clinical diagnosis at the time of initial patient presentation, not only in AD but also in FTD patients. The procedure appears relatively unstressful, making few demands on the demented patient; also, for the majority of patients, this is a viable clinical procedure. Moreover, the technique is relatively inexpensive and widely available.

An important limitation of the study was the inclusion of only consecutive cases of diagnosed AD, VD, FTD, and DLBD subgroups from the dementia clinic, which did not allow us to evaluate the role of perfusion SPECT in atypical and mixed cases of dementia. As a result of this referral/selection bias, the sensitivities and specificities obtained in this study were high. Inclusion of all consecutive cases of dementia, independent of subtype, would be required to independently evaluate the role of SPECT in dementia without a referral bias.

In conclusion the present study indicates the value of SPECT, using Tc-99m ECD in the investigation of dementing illnesses, particularly AD and FTD. Moreover, this technique may ultimately help refine the clinical distinction between these heterogeneous groups of conditions and increase the understanding of dementia.

 » References Top

1.McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimers disease: Report of the NINCDSADRDA work group under the auspices of the department of health and Human Services task force on Alzheimers Disease. Neurology 1984;34:939-44.  Back to cited text no. 1
2.Miller BL, Ikonte C, Ponton M, Levy M, Boone K, Darby A, et al. A study of Lund-Manchester research criteria for frontotemporal dementia: Clinical and single-photon emission CT correlations. Neurology 1997;48:937-42.  Back to cited text no. 2
3.Roman GC, Tatemichi TK, Erkinjuntti T. Vascular dementia: Diagnostic criteria for research studies-a report on the NINDS-AIREN international workshop. Neurology 1993;43:250-60.  Back to cited text no. 3
4.McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, et al. Consensus guidelines for the clinical and pathological diagnosis of dementia with Lewy bodies: Report of the consortium on DLB international workshop. Neurology 1996;47:1113-24.  Back to cited text no. 4
5.Dougall NJ, Bruggink S, Ebmeier KP. Systematic review of the diagnostic accuracy of 99mTc-HMPAO-SPECT in dementia. Am J Geriatr Psychiatry 2004;12:554-70.  Back to cited text no. 5
6.Bonte FJ, Weiner MF, Bigio EH, White CL 3 rd . Brain blood flow in the dementias: SPECT with histopathologic correlation in 54 patients. Radiology 1997;202:793-7.  Back to cited text no. 6
7.Holman BL, Johnson KA, Gerada B, Carvalho PA, Satlin A. The scintigraphic appearance of Alzheimer's disease: A prospective study using technetium-99m-HMPAO SPECT. J Nucl Med 1992;33:181-5.  Back to cited text no. 7
8.Masterman DL, Mendez MF, Fairbanks LA, Cummings JL. Sensitivity, specificity, and positive predictive value of technetium 99-HMPAO SPECT in discriminating Alzheimer's disease from other dementias. J Geriatr Psychiatry Neurol 1997;10:15-21.  Back to cited text no. 8
9.Waragai M, Mizumura S, Yamada T, Matsuda H. Differentiation of early-stage Alzheimer's disease from other types of dementia using brain perfusion single photon emission computed tomography with easy Z-score imaging system analysis. Dement Geriatr Cogn Disord 2008;26:547-55.   Back to cited text no. 9
10.Derouesne C, Rancurel G, Le Poncin Lafitte M, Rapin JR, Lassen MA. Variability of cerebral blood flow defects in Alzheimer's disease on 123-iodo-isopropyl-amphetamine and single photon emission tomography. Lancet 1985;1:1282.  Back to cited text no. 10
11.Bonte FJ, Harris SH, Hynan LS, Bigio EH, White CL. Tc-99m HMPAO SPECT in the differential diagnosis of the dementias with histopathologic confirmation. Clin Nucl Med 2006;31:376-8.   Back to cited text no. 11
12.Jobst KA, Barnetson LP, Shepstone BJ. Accurate prediction of histologically confirmed Alzheimer's disease and the differential diagnosis of dementia: The use of NINCDS-ADRDA and DSM-III-R criteria, SPECT, X-ray CT, and Apo E4 in medial temporal lobe dementias. Oxford Project to Investigate Memory and Aging. Int Psychogeriatr 1998;10:271-302.  Back to cited text no. 12
13.Jagust W, Thisted R, Devous MD Sr, Van Heertum R, Mayberg H, Jobst K, et al. SPECT perfusion imaging in the diagnosis of Alzheimer's disease: A clinical-pathologic study. Neurology 2001;56:950-6.  Back to cited text no. 13
14.Weinstein HC, Haan J, Van Royen EO, Derix MM, Lancer JB, Van der Zant F, et al. SPECT in the diagnosis of Alzheimers disease and multiinfarct dementia. Clin Neurol Neurosurg 1991;93:39-43.   Back to cited text no. 14
15.Toghi H, Chiba K, Sasaki K, Hiroi S, Ishibashi Y. Cerebral perfusion patterns in vascular dementia of Binswanger type compared with senile dementia of the Alzheimer type: A SPECT study. J Neurol 1991;238:365-70.   Back to cited text no. 15
16.Miller BL, Cummings JL, Villanueva-Meyer J, Boone K, Mehringer CM, Lesser IM, et al. Frontal lobe degeneration: Clinical, neuropsychological, and SPECT characteristics. Neurology 1991;41:1374-82.  Back to cited text no. 16
17.McNeill R, Sare GM, Manoharan M, Testa HJ, Mann DM, Neary D, et al. Accuracy of single-photon emission computed tomography in differentiating frontotemporal dementia from Alzheimer's disease. J Neurol Neurosurg Psychiatry 2007;78:350-5.  Back to cited text no. 17
18.Lobotesis K, Fenwick JD, Phipps A, Ryman A, Swann A, Ballard C, et al. Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD. Neurology 2001;56:643-9.  Back to cited text no. 18
19.Pasquier J, Michel BF, Brenot-Rossi I, Hassan-Sebbag N, Sauvan R, Gastaut JL. Value of (99m)Tc-ECD SPET for the diagnosis of dementia with Lewy bodies. Eur J Nucl Med Mol Imaging 2002;29:1342-8.  Back to cited text no. 19


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3]

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