A. Vervaet

Validation of the cerebellum as a reference region for SPECT quantification in patients suffering from dementia of the Alzheimer type

In longitudinal brain studies of dementia of the Alzheimer type (DAT), the cerebellum is often used as a reference region for single photon emission computed tomography (SPECT) quantification, which assumes no significant regional influence of physiological fluctuations or pathology. With the use of absolute quantification in DAT patients, reproducibility of cerebellar uptake of technetium-99m-d,l-hexamethylpropyleneamine oxime (HMPAO) was tested and compared with the mean absolute cerebellar tracer uptake value in DAT patients and healthy control subjects. In 13 DAT patients SPECT studies were repeated within 2 weeks to assess reproducibility of cerebellar regional brain uptake (rBU). With calibrated point sources as scaling factors, cerebellar activity was expressed as rBU of HMPAO per cm3 brain tissue in percent of the injected lipophilic dose of 740 MBq (20 mCi). Also, mean cerebellar rBU in patients suffering from DAT was calculated and compared with a previously established database obtained in healthy volunteers. Repeated SPECT studies within a 2-week interval in clinically stable patients resulted in a mean rBU increase of 6.8 +/- 10.3% in the second SPECT study as compared with the first. A similar shift was previously reported in healthy volunteers. Mean cortical cerebellar rBU values in DAT patients and in the healthy reference population concurred, after cumulative corrections for body surface and for a mean brain volume of 1350 ml (obtained in healthy control subjects), showing respective mean values of 53.9 +/- 7.4 and of 52.0 +/- 7.3 x 10(-6) of the injected lipophilic dose 740 MBq (20 mCi) of HMPAO per cm3 of brain tissue. A unidirectional shift in mean absolute cerebellar uptake values occurs between repeat SPECT examinations in DAT patients similar to previous findings in a group of healthy volunteers. The origin of this phenomenon remains elusive but deserves further study with regard to SPECT (semi)quantification in DAT patients. Most interestingly, the presented findings suggest that with the use of HMPAO SPECT in DAT patients the cerebellum remains scintigraphically uninvolved.

Prevalence and incidence of dementia among 75–80-year-old community-dwelling elderly in different districts of Antwerp, Belgium: The Antwerp Cognition (ANCOG) Study

OBJECTIVE To analyse the prevalence and incidence of dementia in a population of community-dwelling elderly (aged 75-80), living in socio-economically differing districts of Antwerp (Belgium), taking into account possible gender and educational differences. METHODS A longitudinal cohort study (N=825) with a 3-year follow-up period (N=363). The Mini Mental State Examination (MMSE) was used as a primary screen of cognitive functioning. Scoring 21 or below led to a second phase examination by a neurologist, including the CAMDEX-R-N and a neurological examination, to provide a tentative aetiological diagnosis of dementia. These procedures were conducted annually during a 3-year follow-up period. RESULTS In accordance with international literature, the overall prevalence rate of dementia was 8.7%. The cumulative incidence rate (IR) of dementia was 36.60 per 1000Py with annual IRs ranging from 34.39 over 35.16 to 49.04 per 1000Py. Dementia of the Alzheimer type (DAT) was the most occurring prevalent and incident cause. Women appeared to be at higher risk and the occurrence of cognitive deterioration was more prominent in districts with lower socio-economic status, possibly related to a lower education level. CONCLUSION We demonstrate dementia is a considerable health problem in an urban Belgian population of community-dwelling elderly aged between 75 and 80 years old. In order to prepare health care and social security systems for the future management of dementia, proper epidemiological insight into the current and future magnitude of the burden of dementia, taking into account socio-economic differences, to which this study contributes, are required.

Failure to label red blood cells adequately in daily practice using an in vivo method: methodological and clinical considerations

This study was conducted to evaluate the frequency and possible causes of poor red blood cell (RBC) labelling when performing equilibrium gated blood pool (GBP) radionuclide angiography at rest with an in vivo method. The influence of the mode of administration on tagging efficiency was studied by investigating the image quality in 160 patients referred for evaluation of left ventricular (LV) function prior to or after coronary angiography, while using a roughly standardized administration protocol. The patients were subclassified into four groups according to the way both molecules involved in the tagging procedure were administered. When poor image quality was found (in 9.4% of the patients), the labelling efficiency was quantified and the frequency of failed tagging in each group was calculated. A significant association was found between poor labelling and the use of a Teflon catheter or butterfly needle for the injection of the stannous agent. In another 737 patients, in order to avoid the problems observed in the first group, a strict administration protocol was applied to analyse the frequency of poor tagging and its possible causes. Suboptimal image quality was present in 88 patients (11.9%). Quantitatively confirmed poor tagging was present in 36 of the 88 (40.9%, or 4.9% of the whole group); the remaining 52 patients showed borderline normal labelling (>80% bound fraction). Drug interference was studied by comparing the medications used by the 36 patients showing poor binding with those used by 44 control patients. A significant relationship was found between the use of heparin or chemotherapy and the tagging. The influence of several clinical factors on the labelling was also investigated. A significant correlation was found between advanced age, particularly when associated with acute severe disease, and poor labelling efficiency. Finally, in 36 patients with poor labelling, a second GBP test was performed, using either the modified in vivo method or a new commercially available kit for in vitro tagging. This allowed us to evaluate the accuracy of the obtained ejection fraction value when a suboptimal image set is used, and to assess the feasibility of using the new kit in daily practice.

Can we rely on 99Tcm-sestamibi gated tomographic myocardial perfusion imaging to quantify left ventricular function? A comparative study with classical isotopic techniques for the measurement of ejection fraction.

The assessment of left ventricular ejection fraction is an important element in the evaluation of cardiac performance, and one of the most commonly performed tests in nuclear cardiology. The aim of this study was to evaluate the accuracy and reliability of ejection fraction values calculated from ECG-gated myocardial perfusion single photon emission tomography (GSPET) in comparison with standard scintigraphic methods. Eight-frame gated SPET was recorded 60-90 min after the injection of 99Tcm-sestamibi at rest. The ejection fraction was calculated using a semi-automatic edge-detection technique based upon a threshold-searching method and compared with values obtained from first-pass (FPRNA) or equilibrium radionuclide angiography (ERNA) in 60 and 40 patients respectively with a broad range of ejection fraction values. Very good reproducibility was noted, with an inter- and intra-observer variability of -0.2 +/- 3.5% (range -7.6 to 6.9%, r = 0.97) and -0.2 +/- 2.2% (range -5.9 to 3.5%, r = 0.99) respectively. Similarly, a high concordance was found between GSPET and FPRNA and between GSPET and ERNA over the range of ejection fraction values (13 to 77%), the mean (+/-S.D.) difference being 0.8 +/- 3.8% (r = 0.97, P = N.S.) and 0.03 +/- 5.3% (r = 0.94, P = N.S.) respectively. Applying the Bland-Altman plot, no systematic bias of one method related to the other was observed, even at extreme ejection fraction values. Gated myocardial perfusion SPET with a 99Tcm tracer thus offers a unique opportunity to quantify cardiac performance and perfusion simultaneously and non-invasively.

Sensitivity and specificity of 99Tcm-HMPAO single-headed SPECT in dementia.

The sensitivity and specificity of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) single-headed single photon emission computed tomography (SPECT) in dementia were evaluated in elderly patients with a mean age of 84 years suffering from dementia (n = 59) and compared to an age- and sex-matched control group with normal cognitive function (n = 14). The demented patients were classified as suffering from primary degenerative dementia (PDD, n = 51) based on DSM-III-R criteria. Moreover, PDD patients were divided into three subgroups of severity of cognitive impairment, according to their Folstein score. Multi-infarct dementia (MID, n = 8) was diagnosed based on clinical features, computed tomographic findings and Hachinski ischaemic score. Images were assessed qualitatively by visual interpretation of shades of colour in cortical regions. A SPECT defect confined to the frontal, parietal, temporal or (parieto) occipital lobe was defined as one lesion. The mean number of SPECT lesions was 1.4 (range 0-4) in the control group, 2.4 (range 0-8) in the PDD group and 2.9 (range 2-5) in the MID group and showed a significant difference (P < 0.02) between groups. To obtain an acceptable level of specificity of 64.3%, a cut-off value of three lesions had to be chosen. In the PDD group, sensitivity was then 25% for the mildly, 43.8% for the moderately and 46.7% for the severely affected PDD subgroup. In the MID group sensitivity was then 75%. Interestingly, in this elderly patient population the location of lesions was homogenously distributed in all groups, including the control group.

Technetium-99m HMPAO SPET in acute supratentorial ischaemic infarction, expressing deficits as millilitre of zero perfusion.

A comparative interim analysis was performed of clinical parameters, computed tomographic (CT) scan results and technetium-99m hexamethylpropylene amine oxime single-photon emission tomography (SPET) findings obtained within 12 h of acute supratentorial ischaemic infarction. First, the applicability for SPET semiquantification in this study of the “method of Mountz”, simultaneously accounting for extent and degrees of hypoperfusion by expressing deficits as millilitre of zero perfusion, was considered. Next, the relative contributions of perfusion SPET and CT scan in the acute stage of ischaemic infarction were compared in 27 patients (mean age 68.8 years). Finally, the correlation of SPET lesions with clinical parameters at onset was evaluated. The method of Mountz represents a workable, accurate virtual parameter, with the assumption that the contralateral brain region remains uninvolved. Interobserver reproducibility in 12 SPET studies, with lesions varying between 6 and 369 cc, showed a correlation coefficentr of 0.99. In practice, because of inconstant distribution of activities in the brain, the method can only be applied slice by slice and not on the total global volume. While the mean delay since the onset of symptomatology was approximately 7 h for both SPET and CT scan, SPET showed lesions concordant with the clinical neurological findings in 100% and CT scan in only 48%. One could hypothesize that SPET examinations performed later would show larger functional defects, because of the development of additional functional changes secondary to biochemical alterations. However, in this regard no statistically significant differences were found between two subproups, taking the median of delay before SPET examination as cut-off. Finally, when comparing the volumes of SPET lesions during the acute stage with clinical parameters, a statistically significant correlation (P<0.01) was found with the Orgogozo Scale scores describing the neurological deficit, but not with the Glasgow Coma Scale or Frenchay Aphasia Screening Test scores obtained on admittance.

Parameters influencing SPET regional brain uptake of technetium-99m hexamethylpropylene amine oxime measured by calibrated point sources as an external standard

Using calibrated point sources as an external standard to convert single-photon emission tomography (SPET) brain counts into absolute values of regional brain uptake (rBU) of technetium-99m hexamethylpropylene amine oxime (HMPAO), the relative contribution of different parameters to interindividual variability of cerebellar rBU was examined in 33 healthy volunteers. Stepwise regression analysis identified body surface as the most important factor underlying interindividual variability (P<0.001), when compared with brain volume. In the normal volunteer population presented, age decrement of rBU corrected for body surface and brain volume equalled 60.5–0.20×age. Based on the data of eight normal volunteers, including four test-retest studies with heart rate (HR) differences greater than 5 units and four test-stress studies with doubling of heart rate after bicycle exercise, influence of heart rate may be expressed by the equation ΔrBU=0.35 ΔHR. Clinically, estimation of the relative influence of different factors allows normalization and extension of the applicability of the rBU quantification method used from longitudinal studies to group comparisons. Interestingly, results of the Daily Stress Inventory Scale and a subjective rating scale suggest the absence of a significant influence of minor stress on rBU. When using one vial per patient, chromatography may be omitted in clinical routine practice and lipophilicity may be estimated as 90% of the injected dose, if administered within 10 min after preparation. Finally, sensitivity of the quantification method was tested in eight volunteers using acetazolamide brain activation and showed a mean increase in cerebellar rBU of 30.2%, varying between 14.1% and 75.9%.

Quantification of 99Tcm-sestamibi and 123I-BMIPP uptake for predicting functional outcome in chronically ischaemic dysfunctional myocardium.

Little is known about the usefulness of free fatty acid scintigraphy for assessing viability in chronic ischaemic heart disease. To investigate this, we quantified the uptake of 99Tcm-sestamibi and 123I-BMIPP at rest twice within 6 months in 20 patients with chronic ischaemic left ventricular dysfunction and infarction. Four patterns of the relative distribution of both tracers were observed and classified as normal, mismatched, matched and scar. The proportion of the left ventricular surface corresponding to each pattern was expressed as the percentage of the total surface using a polar map. Between the two studies, the patients either underwent revascularization or were treated conservatively. The quantitative results were compared with those of dobutamine stress echocardiography (DSE) in arterial territories with resting contractile dysfunction and correlated with the evolution of regional and global function at follow-up. At baseline, 25 arterial territories were analysed. Using sestamibi, on average one-third of their surface was considered to be normally perfused. No clear association was found between the percent normally perfused surface and the DSE findings. Adding BMIPP and using a value of > 7% of the arterial surface with BMIPP lower than sestamibi (mismatch) as the cut-off for the significance of viability, 14 of 18 mismatched regions were considered viable by DSE, and six of seven with < 7% mismatched surface or matching were not. Fifteen patients were viable, of whom 13 were revascularized (16 territories). At follow-up, global function improved in 11 of the 15 viable patients, all in the revascularized group. Regional improvement was noted in 11 of 16 revascularized territories, and was associated with a significant increase in sestamibi and BMIPP uptake and in the percent normally perfused myocardial surface. In the five patients without significant viability, no functional deterioration or changes in the quantitative parameters were observed during treatment. The results suggest that quantitative analysis of the uptake of sestamibi and BMIPP is a reliable method to objectively assess the presence of myocardial viability in chronic ischaemic heart disease and to predict functional improvement after revascularization.

Head-to-head comparison of uncorrected and scatter corrected, summed and end diastolic myocardial perfusion SPECT in coronary artery disease.

ObjectivesCompared with other non-invasive methods for diagnosing coronary artery disease (CAD), myocardial perfusion imaging (MPI) suffers from some lack of specificity, especially in patients with a small heart. Allowing the assessment of perfusion on end diastolic images instead of summed images, gated single photon emission computed tomography (SPECT) constitutes an attractive method for increasing the accuracy of MPI. Scatter correction, known to improve image contrast, might also be interesting. The present study aimed at comparing scatter corrected to uncorrected gated MPI for CAD diagnosis. MethodsThe results for 100 patients referred for gated 99mTc sestamibi SPECT were analysed. They were divided into two subgroups according to their end systolic volume (ESV) measured by QGS analysis (group A, ESV ≥30 ml, n=65; group B, ESV <30 ml, n=35). For each patient, a total defect score (TDS) was quantified on four polar maps (uncorrected and scatter corrected, summed, and uncorrected and scatter corrected, end diastolic). The optimal TDS separating non-CAD from CAD patients was calculated by analysis of the receiver operating characteristic (ROC) curve for the four data sets, using the coronary angiogram as a ‘gold standard’. ResultsIn the whole patient population, the accuracy of the uncorrected data was 67% for the end diastolic images and 71% for the summed images (sensitivity, 66% and 70%; specificity, 71% and 79%, respectively). After scatter correction, the accuracy did not change for the end diastolic data (accuracy, 67%; sensitivity, 63%; specificity, 93%) and increased to 74% for the summed data (sensitivity, 73%; specificity, 79%). In group A, the uncorrected data were 72% accurate for the end diastolic images and 78% for the summed images (sensitivity, 72% and 79%; specificity, 75% and 75%, respectively). After correction, the accuracy of end diastolic images increased to 77% (sensitivity, 77%; specificity, 75%), and did not change for the summed images (accuracy, 78%; sensitivity, 79%; specificity, 75%). In group B, the accuracy of uncorrected images amounted to 51% for both end diastolic and summed data (sensitivity, 48% and 40%; specificity, 60% and 80%, respectively). After correction, it increased to 57% for the end diastolic images and to 63% for the summed images (sensitivity, 48% and 64%; specificity, 80% and 60%, respectively). ConclusionsDespite lower blurring on end diastolic compared with summed images, non-scatter corrected end diastolic data were least accurate for the diagnosis of coronary artery disease in patients with a high prevalence of disease. Scatter correction, by improving the delineation of perfusion defects, increased the accuracy of quantitative MPI for the diagnosis of CAD in a large number of patients, more particularly in those with a small heart.

240 degrees: why not?

SummarySingle photon emission tomographic imaging of myocardial perfusion with 99Tcm-labelled agents is usually performed with single-detector gamma camera systems and 180° anterior data collection. With multi-detector systems, reconstruction over 180° and 360° has been reported. We used a data set of normal subjects to compare both reconstruction methods. In addition, we tested an alternative approach, reconstructing data from 240° acquisitions, excluding the right posterior views, which provide little myocardial information and which are responsible for a reduced signal-to-noise ratio. On the transverse slices, the known apical distortion with the 180° reconstruction was not noted with the 360° or 240° reconstructions. Using semi-quantitative analysis of apical, mid-ventricular and basal short-axis slices, almost complete overlap was observed between the 240° and 360° circumferential profiles of our 20 normal volunteers, except in the inferior wall where a reduction in activity was noted. However, this rinding was less pronounced with the 240° than with the 180° reconstruction. The frequent reduction in activity in the anterior wall was more prominent with the 180° than with the 240° and 360° reconstructions. A 240° acquisition represents a useful compromise between 180° and 360° imaging protocols when a single-detector device is used, allowing more homogeneous tracer distribution and a reduction in the apical distortion without material change of contrast or doubling of the acquisition time.