Quantitative evaluation of myocardial single-photon emission tomographic imaging: application to the measurement of perfusion defect size and severity

A new method is described for precise quantitative analysis of the relative three-dimensional distribution of myocardial tracers. The system uses a 360° elliptical sampling of radial slices to create activity profiles. These are then positioned onto a common centre at the same angular coordinates as the corresponding radial slice reconstruction planes to generate a two-dimensional polar summary display. Abnormal distribution is then identified by automatic comparison of the patient polar map with the threshold of a normal database defined on a pixel by pixel basis as the normal mean –2.5 SD. Our stress and rest databases currently comprise 34 and 24 studies for sestamibi and tetrofosmin respectively. The present method differs from currently available software in two major respects. First, radial slices are used rather than short-axis slices to minimize operator intervention and to allow quantitative evaluation of the left ventricle volume independent of the heart size and without truncation, in particular near the apex and at the base. This sampling scheme also results in a more homogeneous and sampling-independent partial volume effect. Secondly, quantitative analysis is improved by calculating perfusion defect severity, extent and size in a precise manner. Severity is evaluated relative to a standardized background measurement and to the mean normal value rather than to the threshold value. This parameter was underestimated up to a defect extent of 32 cm² in our phantom studies. Calculation of defect extent takes into account the surface distortion resulting from planar projection by using pixel by pixel weighted factors but it is otherwise overestimated as a result of the limited resolution of the imaging system. Integrating defect severity and extent, our hypoperfusion index appeared to accurately estimate the true defect size in our phantom model (r=0.993). The reproducibility of analysis was 6.24% in phantom studies and 3.10% in patient studies including repeated acquisitions. Applied to a well-documented population of 80 patients, this method resulted in an 86% sensitivity and a 78% specificity for overall coronary artery disease detection with reference to the angiographic data.     

Parieto-occipital hypoperfusion in late whiplash syndrome: first quantitative SPET study using technetium-99m bicisate (ECD)

Brain single-photon emission tomography (SPET) withN,N-1,2-ethylene-diylbis-l-cysteine diethyl ester dihydrochloride (ECD) was performed on ten patients with a clinically high grade late whiplash syndrome and on 11 controls. Two independent readers blinded to the clinical diagnosis were able to separate the ten patients from normal controls. All these patients had qualitative bilateral parieto-occipital hypoperfusion. To confirm this, the perfusion rate of parieto-occipital over global (perfusion index) was calculated after drawing elliptical regions of interest in transversal-oblique slices. The perfusion indices in patients were significantly lower than in controls as tested by the Mann-WhitneyU test. This quantitative study proves our recent qualitatively analysed observation (Lancet 1995; 345: 1513–1514).     

Quality of myocardial perfusion single-photon emission tomography imaging: multicentre evaluation with a cardiac phantom

The aim of the study was to evaluate quality of myocardial perfusion single-photon emission tomography (SPET) imaging in Finnish hospitals. Nineteen nuclear medicine departments participated in the study. A myocardial phantom simulating clinical stress and rest conditions was filled with routinely used isotope solution (technetium-99m or thallium-201). The cardiac insert included three reversible defects (simulating ischaemia): 30×30×14 mm³ septal (90% recovery at rest), 30×20×14 mm³ posterobasal (full recovery) and 20×20×14 mm³ lateral (full recovery). There were two fixed defects (simulating infarct): 30×20×14 mm³ postero-apical and 10×10×6 mm³ apical. The phantom was imaged and interpreted as a myocardial perfusion patient. Reconstruction, printout and reporting were performed according to the clinical routine of each centre. Three nuclear medicine specialists anonymously evaluated the quality of the image sets. The visual scores of the experts were ranked from 1 to 5. Additionally, points from 0 to 8 were given to research reports according to how well perfusion defects were detected. Quantitative points were calculated by comparing background-subtracted and -normalized counts from 12 regions of interest between stress and rest images. Results for technetium studies (12 departments) were better than those for thallium (7 departments). The average visual scores of the experts were 3.7±0.9 for all image sets, 3.2±0.5 for thallium users and 3.9±0.6 for technetium users (P=0.003). Five laboratories received a low score which, according to the specialists, is barely sufficient for limited clinical use. Average points for the reports were 5.6±2.1, 4.9±1.5 and 6.5±1.7 (P=0.051), and for the quantitation 8.2±1.0, 7.9±0.4 and 8.4±1.1 (P=0.185), respectively. Seven out of 22 interpreters did not detect the lateral 20×20×14 mm³ defect; five of them used thallium. This study demonstrated the heterogeneity of myocardial perfusion SPET in Finland. The participating laboratories used a wide scale of methods and, sometimes, inappropriate imaging protocols. The need for quality assurance in nuclear cardiology, correct use of SPET instrumentation and objective comparison of clinical studies is evident. The method described is suitable for external quality assurance and quality improvement of myocardial SPET imaging, and is recommended for regular use in nuclear medicine. Reiceived 15 March and in revised form 9 May 1999     

Coronary vasomotion in patients with syndrome X: evaluation with positron emission tomography and parametric myocardial perfusion imaging

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [¹³N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127±31 ml·min^–1·100 g^–1; group B, 124±30 ml·min^–1·100 g^–1 normal subjects, 105±21 ml·min^–1·100 g^–1 (groups A and B vs normals,P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20±0.23; group B, 1.24±0.22; normal subjects, 1.23±0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71±0.67; group B, 2.77±1.29; normal subjects, 2.91±1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1±4.5 vs 17.0±3.0,P<0.05). In group B (coefficient of variation 19.4±3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.     

A comparison of99mTc-MIBI myocardial SPET with electron beam computed tomography in the assessment of coronary artery disease

We compared technetium-99m methoxyisobutylisonitrile (MIBI) myocardial perfusion single-photon emission tomography (SPET) (MPS) and electron beam computed tomography (EBCT) in order to assess their respective value in the detection of coronary artery disease (CAD).^99mTc-MIBI SPET (stress-resting) and EBCT studies were performed in 51 patients with suspected CAD who underwent coronary angiography (CAG). CAG showed that of the 51 patients, 36 had coronary stenosis 50% while 15 had normal results. A moderate positive rank correlation was found between coronary calcification detected by EBCT and MPS score (r _s=0.5283,P<0.01). The concordance between EBCT and MPS for the evaluation of CAD was 72.5% (37/51). The sensitivity of EBCT in detecting CAD in 51 patients was comparable to that of MPS (81% vs 94%, NS). However, the accuracy of EBCT was lower than that of MPS (78% vs 94%,P<0.025). As regards the detection of individual coronary artery disease, there was no significant difference in sensitivity between EBCT and MPS (65% vs 75%, NS); however, the specificity and accuracy of EBCT were lower than those of MPS (specificity: 77% vs 95%,P<0.005; accuracy 71% vs 85%,P<0.005). The sensitivity, specificity and accuracy of MPS in detecting single-vessel disease were higher than those of EBCT (sensitivity: 86% vs 42%,P<0.025; specificity: 96% vs 70%,P<0.025; accuracy: 93% vs 61%,P<0.005). However, no significant differences in the sensitivity, specificity and accuracy of MPS and EBCT were found in respect of multivessel disease. In conclusion:^99mTc-MIBI myocardial perfusion SPET and EBCT provide different information in the assessment of CAD. The sensitivity of EBCT for the detection of CAD is comparable with that of MPS; however, the specificity and accuracy of EBCT are lower than those of MPS. More reliable results will be obtained if both myocardial perfusion SPET and EBCT are performed.     

Similar effect of revascularization on technetium-99msestamibi and 15-(p-iodophenyl)pentadecanoic acid uptake in myocardial infarction patients

To study its usefulness as a tracer for assessment of the perfusion and viability of myocardium, 15-(p-iodophenyl)pentadecanoic acid (IPPA) was compared with technetium-99m sestamibi (MIBI). Dual-tracer single-photon emission tomography rest imaging was performed no more than 2 months before and 3 months after coronary artery bypass grafting in 28 patients with previous anterior (n=13) or inferior (n=15) infarction. The size of MIBI and IPPA defects decreased from 14%±12% and 13%±9% to 10%±11% and 9%±7%, respectively (P<0.001 for both). The MIBI uptake increased in the infarct zones from 35%±11% to 43%±8% (P<0.001), and in the peri-infarct zones from 50%±11% to 55%±10% (P<0.05). The IPPA uptake increased in the infarct zones from 37%±11% to 44%±13% (P<0.001), and in the peri-infarct zones from 51%±11% to 57%±12% (P<0.05). In nine patients with improved regional echocardiographic wall motion score after bypass surgery, the pre-operative uptake values of both MIBI and IPPA in the infarct and peri-infarct zones were on average slightly but not significantly higher than in 19 patients with no observed improvement in regional wall motion score. In patients with improved regional wall motion, the MIBI scans and the IPPA scans showed (non-significant) decreases in defect size and increases in infarct and peri-infarct zone uptake after bypass surgery. Similar (in some cases significant) changes were observed in the patients without improvement in wall motion. Thus IPPA and MIBI provided similar information about perfusion and viability in pre- and postoperative evaluation of patients with clinically evident myocardial infarction and with normal global ejection fraction. Regardless of the tracer used, the resolution capability of the dual-tracer method with a rest imaging protocol was not sufficient to differentiate viable from non-viable infarction defects in unselected individual patients with a normal ejection fraction. Received 5 March and in revised form 5 May 1999     

A multi-institutional study of interobserver agreement in the evaluation of dementia with rCBF/SPET technetium-99m exametazime (HMPAO)

Although specific patterns of technetium-99m exametazime [^99mTc-hexamethylpropylene amine oxime (HMPAO)] brain single-photon emission tomography (SPET) uptake have been described for patients with dementia, no multi-institutional study has evaluated interobserver agreement. Interobserver agreement for ^99mTc-HMPAO brain SPET uptake patterns in 50 clinically diagnosed demented subjects from four institutions were studied. Neurologists classified these subjects as presumed Alzheimer's disease (n=21), confirmed Alzheimers's disease (n=10), multi-infarct dementia (n=9), HIV-related dementia (n=7), or mixed (n=3). In addition 20 normal (five per institution) ^99mTc-HMPAO studies were included in a randomized blinded evaluation by three readers each from a different institution. Readers classified the general appearance of the images in one of four categories: normal, globally decreased uptake, focal areas of decreased uptake, and patchy changes in uptake. Consensus results show a sensitivity of 72% and specificity of 79% for identifying abnormalities in scans of demented subjects. Readers also rated ^99mTc-HMPAO uptake in eight designated regions in each hemisphere. Significant reader agreement (P < 0.01) for the classification by general appearance and the ratings of regional uptake was obtained. This study demonstrates that interpretation of regional cerebral blood flow/SPET images is concordant across multiple institutions and readers.Subject studies performed at St. Vincent's Hospital, New York     

Role of cardiac computed tomography in patients with suspected coronary artery disease: interaction with nuclear cardiology

Coronary computed tomography (CT) angiography (CTA) and myocardial perfusion single photon emission CT (SPECT, or MPS) provide complementary information on vascular structure and myocardial perfusion. In patients with coronary artery disease (CAD), the combination of both methods is helpful for disease detection and therapeutic strategy planning. This article addresses the utility of coronary CTA with current 64-row multidetector CT instruments, MPS, and the combination of these methods in the evaluation of CAD.     

The significance of a dipyridamole induced 99mTc-MIBI perfusion abnormality on single photon emission tomography: a quantitative validation with labelled water and positron emission tomography

To relate technetium-99m 2-methoxy-isobutylisonitrile (^99mTc-MIBI) uptake to regional myocardial blood flow (rMBF), ^99mTc-MIBI single photon emission tomography (SPET) and H₂ ¹⁵O positron emission tomography (PET) scans were obtained at rest and after dipyridamole infusion in six patients with single vessel coronary artery disease. ^99mTc-MIBI and H₂ ¹⁵O data sets were created for each segment perfused by the stenotic vessel and for a normal reference area, assigning regions on the SPET tomograms to comparable regions on the PET by similar transaxial image reconstructions. All patients demonstrated post-dipyridamole ^99mTc-MIBI perfusion defects in the territories supplied by the stenotic arteries. Resting rMBF in these regions was slightly lower than that in the normal areas (0.82±0.05 vs 0.90±0.09 ml/g/min, P=NS). A 43%±14% reduction in ^99mTc-MIBI activity in the area at risk was coupled with on average a 60%±9% reduction in post-dipyridamole rMBF compared with control regions (0.98±0.08 vs 2.52±0.51 ml/g/min, P<0.001). Thus, SPET assessment of ^99mTc-MIBI uptake tends to underestimate the perfusion contrast between areas with normal and areas with low coronary vasodilatory reserve when compared to PET. However, these findings may still not affect the clinical usefulness of ^99mTc-MIBI and more extensive studies are required to confirm these results in the clinical environment.     

Development of a practical image-based scatter correction method for brain perfusion SPECT: comparison with the TEW method

Purpose An image-based scatter correction (IBSC) method was developed to convert scatter-uncorrected into scatter-corrected SPECT images. The purpose of this study was to validate this method by means of phantom simulations and human studies with ^99mTc-labeled tracers, based on comparison with the conventional triple energy window (TEW) method.Methods The IBSC method corrects scatter on the reconstructed image with Changs attenuation correction factor. The scatter component image is estimated by convolving with a scatter function followed by multiplication with an image-based scatter fraction function. The IBSC method was evaluated with Monte Carlo simulations and ^99mTc-ethyl cysteinate dimer SPECT human brain perfusion studies obtained from five volunteers. The image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were compared.Results Using data obtained from the simulations, the image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were found to be nearly identical for both gray and white matter. In human brain images, no significant differences in image contrast were observed between the IBSC and TEW methods.Conclusion The IBSC method is a simple scatter correction technique feasible for use in clinical routine.     

123I-5-I-R91150, a new single-photon emission tomography ligand for 5-HT2A receptors: influence of age and gender in healthy subjects

5-HT_2A receptors have been implicated in the pathophysiology of mood disorders and in the therapeutic effect of the so-called atypical antipsychotics. Recently, a new radioiodinated ligand with high affinity and selectivity for serotonin 5-HT_2A receptors, ¹²³iodinated 4-amino-N-1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl] 5-iodo-2-methoxybenzamide (¹²³I-5-I-R91150), has been developed and has been shown to be suitable for single-photon emission tomography (SPET) imaging. In this study the influence of age and gender on the ligand binding was investigated in normal volunteers. One hundred and fifty MBq of ¹²³I-5-I-R91150 was administered to 26 normal volunteers (13 females and 13 males) with an age range of 23–60 years. SPET imaging was performed with a triple-headed gamma camera. For semi-quantitative analysis, ratios of ligand binding in different regions of interest to the binding in the cerebellum were calculated. Mean ratios of 1.7 were obtained. No gender difference was demonstrated. 5-HT_2A binding was shown to decline with age. Over an age range of 40 years a reduction in ligand binding of 42%±7% was found. These results are in agreement with in vitro and positron emission tomography findings of a decline in 5-HT_2A receptor binding with age. The findings confirm the suitability of ¹²³I-5-I-R91150 for SPET imaging of 5-HT_2A receptors, and highlight the necessity for age-matched controls in clinical studies. Received 21 March and in revised form 18 August 1998     

A simple method for the quantification of benzodiazepine receptors using iodine-123 iomazenil and single-photon emission tomography

Iodine-123 iomazenil (Iomazenil) is a ligand for central type benzodiazepine receptors that is suitable for single-photon emission tomography (SPET). The purpose of this study was to develop a simple method for the quantification of its binding potential (BP). The method is based on a two-compartment model (K ₁, influx rate constant;k ₂, efflux rate constant;V _T (=K ₁/k ₂), the total distribution volumes relative to the total arterial tracer concentration), and requires two SPET scans and one blood sampling. For a given input function, the radioactivity ratio of the early to delayed scans can be considered to tabulate as a function ofk ₂, and a table lookup procedure provides the correspondingk ₂ value, from whichK ₁ andV _T values are then calculated. The arterial input function is obtained by calibration of the standard input function by the single blood sampling. SPET studies were performed on 14 patients with cerebrovascular diseases, dementia or brain tumours (mean age±SD, 56.0±12.2). None of the patients had any heart, renal or liver disease. A dynamic SPET scan was performed following intravenous bolus injection of Iomazenil. A static SPET scan was performed at 180 min after injection. Frequent blood sampling from the brachial artery was performed on all subjects for determination of the arterial input function. Two-compartment model analysis was validated for calculation of theV _T value of Iomazenil. Good correlations were observed betweenV _T values calculated by three-compartment model analysis and those calculated by the present method, in which the scan time combinations (early scan/delayed scan) used were 15/180 min, 30/180 min or 45/180 min (all combinations:r=0.92), supporting the validity of this method. The present method is simple and applicable for clinical use.     

Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism

Parkinsonism is a feature of a number of neurodegenerative diseases, including Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy. The results of post-mortem studies point to dysfunction of the dopaminergic neurotransmitter system in patients with parkinsonism. Nowadays, by using single-photon emission tomography (SPET) and positron emission tomography (PET) it is possible to visualise both the nigrostriatal dopaminergic neurons and the striatal dopamine D₂ receptors in vivo. Consequently, SPET and PET imaging of elements of the dopaminergic system can play an important role in the diagnosis of several parkinsonian syndromes. This review concentrates on findings of SPET and PET studies of the dopaminergic neurotransmitter system in various parkinsonian syndromes.     

The use of perfusion CT for the evaluation of therapy combining AZD2171 with gefitinib in cancer patients

The purpose of this study was to determine the feasibility of dynamic contrast–enhanced perfusion CT (CTP) in evaluating the hemodynamic response of tumors in the chest and abdomen treated with a combination of AZD2171 and gefitinib. Thirteen patients were examined just before and every 4-6 weeks after starting therapy. Following intravenous injection of a contrast agent, dynamic image acquisition was obtained at the level of a selected tumor location. To calculate perfusion, the maximum-slope method was used. Pre-treatment average perfusion for extra-hepatic masses was 84 ml/min/100 g, for liver masses arterial perfusion was 25 ml/min/100 g, and a portal perfusion of 30 ml/min/100 g was found. After the administration of AZD2171 and gefitinib, in extra-hepatic masses an initial decrease in perfusion of 18% was followed by a plateau and in liver masses an initial decrease of 39% within the lesions and of 36% within a rim region surrounding the lesions was followed by a tendency to recovery of hepatic artery flow. In conclusion, CTP is feasible in showing changes of perfusion induced by anti-angiogenic therapy.     

Relative preservation of peripheral lung function in smoking-related pulmonary emphysema: assessment with 99mTc-MAA perfusion and dynamic 133Xe SPET

In this study the cross-sectional functional differences between the central and peripheral lung in smokers with pulmonary emphysema were evaluated by lung perfusion and dynamic xenon-133 single-photon emission tomography (SPET). The subjects were 81 patients with a long-term smoking history and relatively advanced emphysema, 17 non-smoker patients with non-obstructive lung diseases and six healthy non-smokers. Regional lung functional difference between the peripheral and central lung was assessed in the upper, middle and lower lung zones by technetium-99m macroaggregated albumin SPET and dynamic ¹³³Xe SPET. The distribution of emphysematous changes was assessed by density-mask computed tomography (CT) images which depicted abnormally low attenuation areas (LAAs) of less than –960 Hounsfield units. Two hundred and eighty-eight (59.2%) lung zones of 63 (77.7%) patients with pulmonary emphysema showed relative preservation of lung function in the peripheral lung, with a curvilinear band of normal perfusion (a stripe sign) and a significantly faster ¹³³Xe half-clearance time (T _1/2) than in central lung (P<0.0001). Of these lung zones, 256 (88.8%) showed central-dominant LAA distributions on density-mask CT images, but the remaining 32 zones did not show any regional preference in LAA distribution. Conversely, 117 (24.0%) lung zones of 19 (23.4%) patients showed periphery-dominant perfusion defects and LAA distributions, with significantly prolonged T _1/2 in the peripheral lung area (P<0.0001). The remaining 81 lung zones of the patients with pulmonary emphysema and all the lung zones of the healthy subjects and patients with non-obstructive lung diseases did not show a stripe sign, and no differences were observed in T _1/2 values and LAA distributions between the central and peripheral lung. Relative preservation of peripheral lung function seems to be a characteristic feature in smoking-related pulmonary emphysema, and may indicate a lower susceptibility of peripheral parenchyma to the development of this disease. Received 8 January and in revised form 13 March 2000     

Application of SPET using technetium-99m sestamibi in brain tumours and comparison with expression of the MDR-1 gene: is it possible to predict the response to chemotherapy in patients with gliomas by means of 99mTc-sestamibi SPET?

Technetium-99m sestamibi (MIBI) is thought to be passively taken up by metabolically active tumour cells and effluxed from them by P-glycoprotein (Pgp). This 170-kDa membrane-bound protein, encoded by the MDR-1 gene, acts as an energy-dependent efflux pump for several antineoplastic agents, resulting in multidrug resistance. For this reason, it is of interest whether the tumour’s response to chemotherapy can be predicted by MIBI single-photon emission tomography (SPET). In this study, MIBI SPET was compared with thallium-201 (Tl) SPET using magnetic resonance imaging as a guide in 16 patients with untreated brain tumours [ten glioblastomas (GBs), two anaplastic astrocytomas (AAs), two low-grade gliomas (LGASs) and two metastatic brain tumours) and in four patients who had received treatment for with brain tumours (two GBs, two AAs). In addition, we investigated the expression of the MDR-1 gene and its product Pgp in the same patients, and compared the results with MIBI SPET findings. MIBI, as well as Tl, was highly accumulated and retained in the enhanced region of malignant gliomas. In addition, MIBI SPET yielded sharp and well-contrasted images, and the margin of the tumour was more clearly defined than with Tl SPET due to a good signal-to-noise ratio. Follow-up MIBI SPET in patients who had received therapy showed marked uptake in a patient with malignant transformation, who deteriorated clinically. Patients with no uptake on MIBI SPET showed no sign of recurrence. Semiquantitative analysis of untreated patients showed a relationship between the early uptake index (UI, ratio of average count/pixel in the lesion to that in the contralateral area on early images) and the degree of malignancy (early UI = 1.08±0.06 in LGASs, 4.10±0.84 in AAs, 5.71±3.47 in GBs, and 7.52±1.52 in metastatic brain tumours). The retention index (RI, ratio of delayed to early UI) of MIBI was significantly lower than that of Tl in metastatic brain tumours (P<0.05), but not in malignant gliomas. Histological and biological investigation of gliomas showed that the MDR-1 gene and its product Pgp were expressed only in normal endothelial cells and not in tumour cells or proliferating endothelial cells; Pgp tended to decrease as the degree of malignancy rose. Hence, the presence of Pgp and the grade of malignancy were inversely related in gliomas. By contrast, immunohistochemical study showed strong accumulation of Pgp in metastatic brain tumour cells. These histopathological findings and MIBI SPET findings are compatible with experimental data; MIBI was washed out by Pgp. The main cause of chemoresistance is probably not an increasing drug efflux by Pgp in gliomas. Thus, MIBI SPET is useful for detecting the active lesions, but may not be useful for predicting the response to chemotherapy in gliomas. Received 23 October and in revised form 18 December 1997     

Quantitation of myocardial iodine-123 MIBG uptake in SPET studies: a new approach using the left ventricular cavity and a blood sample as a reference

In patients with chronic heart failure increased sympathetic activity is related to unfavourable prognosis. Since myocardial iodine-123 metaiodobenzylguanidine ([¹²³I]MIBG) uptake is related to myocardial noradrenaline content, i.e. cardiac sympathetic activity, measurement of myocardial [¹²³I]MIBG uptake may be of clinical use in determining prognosis or the effect of pharmacological intervention in these patients. The aim of the present study was to evaluate a new method to quantitate myocardial [¹²³I]MIBG uptake with respect to reproducibility and accuracy. Eighteen [¹²³I]MIBG planar and single-photon emission tomography (SPET) studies of patients with chronic heart failure were evaluated. Myocardial uptake was calculated from the myocardial (MYO) to left ventricular cavity (C) count density ratio and the¹²³I activity in a blood sample. This was performed employing planar LAO images, a single-slice SPET method using the midventricular myocardial short-axis slice, and finally a multi-slice SPET method analysing semi-automatically drawn volumes of interest (VOIs). The accuracy of the multi-slice SPET method was verified using a cardiac phantom. The planar method was found to be reproducible [intra- and interobserver coefficients of variation (IACV and IRCV) were 0.025 and 0.012 respectively] but the mean MYO/C count density ratio was only 1.31±0.16 as a consequence of overprojection. For the single-slice SPET method IACV was 0.2 and IRCV was 0.13, representing poor reproducibility. For the multi-slice SPET method IACV was 0.051, IRCV was 0.047 and the mean MYO/C count density ratio was 5.4±2.42. Accuracy was 81% at a true MYO/C count density ratio of 6 in the phantom. It is concluded that the multi-slice SPET method using the left ventricular cavity VOI and a blood sample as a reference is a reproducible and accurate method for assessing myocardial [¹²³I]MIBG uptake.     

Attenuation correction improves the detection of viable myocardium by thallium-201 cardiac tomography in patients with previous myocardial infarction and left ventricular dysfunction

The aim of this study was to determine the influence of attenuation-corrected thallium-201 stress/redistribution/reinjection single-photon emission tomography (SPET) on the number of viable segments in patients with previous myocardial infarction and dysfunctional myocardium. Fifty-one patients with previous myocardial infarction and left ventricular dysfunction were included in the study. In all patients, ²⁰¹Tl non-corrected (NC) and attenuation-corrected (AC) SPET was performed using a stress/redistribution/reinjection protocol followed by coronary angiography. A semiquantitative analysis was performed using polar maps for NC and AC stress, redistribution and reinjection short-axis and vertical long-axis (apex) slices. Severe (perfusion defect below 50%/maximal count rate: PD_<50), mild and moderate persistent defects for redistribution and reinjection were evaluated for both NC and AC studies. A total of 1581 segments were evaluated by semiquantitative segmental analysis for both NC and AC studies for each redistribution and reinjection map. In the redistribution maps, NC revealed a total of 352 segments and AC a total of 222 segments with impaired perfusion below 50% of the maximal count rate (PD_<50). The mean number of affected segments was 6.9±5.5 in the case of NC and 4.4±4.8 in the case of AC (P<0.001). In the reinjection maps, NC revealed a total of 263 non-viable segments (PD_<50) and AC a total of 169 non-viable segments. The mean number of affected segments was 5.2±5.3 in the case of NC and 3.3±4.2 in the case of AC (P<0.001). Recovery of function was better predicted by AC than by NC in 20% of patients in the follow-up group. Therefore, the use of attenuation correction influences the extent of viable segments by showing more viable segments in either redistribution or reinjection maps. ²⁰¹Tl imaging without attenuation correction may underestimate the extent of tissue viability, which may contribute to the lower sensitivity compared to fluorine-18-fluorodeoxyglucose positron emission tomography, where attenuation correction is a routinely performed procedure. Received 26 October and in revised form 23 December 1998     

Indium-111 pentetreotide single-photon emission tomography in patients with TSH-secreting pituitary adenomas: Correlation with the effect of a single administration of octreotide on serum TSH levels

Few data are available on the visualization of somatostatin receptors in vivo in patients with thyrotropin (TSH)-secreting adenoma. We studied five patients with TSH-secreting adenomas using single-photon emission tomography (SPET) after administration of indium-111 pentetreotide. The intensity of¹¹¹In-pentetreotide uptake by the tumours was correlated with the degree of TSH suppression after a single administration of 100 g octreotide s.c. Five patients (three women and two men) aged 27–46 years were investigated. Except for one patient with acromegaly, all had pure TSH-secreting inmours. One patient was previously untreated, while two had received octreotide, one antithyroid drugs, and one radioiodine. In all patients SPET demonstrated increased uptake of¹¹¹In-pentetreotide by the pituitary adenoma. The target to non-target ratio (T/nT) of¹¹¹In-pentetreotide uptake was higher than 10 in three patients. Administration of 100 g octreotide s.c. caused a significant reduction in TSH levels from 4.8±1.4 mU/l to a nadir of 3.1±1.1 mU/l after 6 h (P<0.001 by ANOVA). Suppression of TSH secretion ranged from 30% to 60% of the baseline value. The T/nT ratio showed a trend toward a direct relationship with the degree of TSH inhibition after acute octreotide administration (r=0.67;P=NS). Our study showed that¹¹¹In-pentetreotide scan visualized somatostatin receptors in all five of the patients with TSH-secreting pituitary adenomas, confirming the frequent presence of somatostatin receptors in these rare tumours, even though the correlation with the TSH inhibition after a single administration of octreotide did not reach significance.     

In vivo metabolic studies of thetrans-(R,R) isomer of radioiodinated IQNP: A new ligand with high affinity for the M1 muscarinic-cholinergic receptor

E-(R,R)-IQNP is a new ligand analogue of IQNB, which has high affinity for the cholinergic-muscarinic receptor. Earlier studies have demonstrated high cerebral uptake of activity with selective localization in M₁ receptor subtype areas of the brain. In this paper we describe the results of metabolic studies of E-(R,R)-IQNP directed at determining the metabolic fate of this ligand and the identification of the radioactive species observed in the brain and heart tissue. Tissue Folch extracts demonstrated that the lipid-soluble extracts from brain contained 87.0%±1.65% of the activity up to 24 h. In the heart, 61.9%±7.50% of the activity was extracted in the lipid-soluble extract after 30 min, decreasing to 51.4%± 0.65% by 4 h. In contrast, data from other tissues studied demonstrated large amounts of either aqueous soluble activity or activity which was not extracted from the tissue pellet material; analysis of lipid organic extracts revealed the following results: liver (4 h), 7.43%± 0.96%; serum (4 h), 3.73%±0.87%; urine (24 h), 9.4%; feces (24 h), 16.5%. Thin-layer chromatographic (TLC) and high-performance liquid chromatographic (HPLC) analyses of lipid-soluble brain extracts indicated that only unmetabolized E-(R,R)-IQNP was detected (99.4%± 1.25%). Activity which was extracted into the organic phase from heart tissue was also determined by TLC and HPLC analysis to contain large amounts of unmetabolized ligand after 4 h (88.5%± 0.57%). In addition, however, low levels of two additional radioactive components were detected which increased with time. TLC analysis of the plasma lipid extracts indicated only a small amount of unmetabolized E-(R,R)-IQNP. In comparison, the liver, feces, and urine lipid extracts contained only metabolites. These initial studies clearly indicate that radioactivity present in the brain after intravenous administration of radioiodinated E-(R,R)-IQNP represents only the unmetabolized ligand and that this new ligand shows promise for single-photon emission tomographic imaging of muscarinic receptors in humans.