Neurology India Medknow Publications on behalf of the Neurological Society of India ISSN: 0028-3886 EISSN: 1998-4022 Vol. 58, Num. 6, 2010, pp. 857-862

Neurology India, Vol. 58, No. 6, November-December, 2010, pp. 857-862

Original Article

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

Madhavi Tripathi¹, Manjari Tripathi², Deepti Vibha², Naveen Gowda¹, Chandrashekhar Bal¹, Arun Malhotra¹

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
Correspondence Address: Madhavi Tripathi, Division of PET Imaging, MIRC, INMAS, Delhi - 54, India, madhu_deven@yahoo.com

Date of Acceptance: 12-Oct-2010

Code Number: ni10247

PMID: 21150049
DOI: 10.4103/0028-3886.73745

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

Introduction

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

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

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.

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

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.

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.

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],[8],[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

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