Automatic segmentation of dynamic neuroreceptor single-photon emission tomography images using fuzzy clustering

The segmentation of medical images is one of the most important steps in the analysis and quantification of imaging data. However, partial volume artefacts make accurate tissue boundary definition difficult, particularly for images with lower resolution commonly used in nuclear medicine. In single-photon emission tomography (SPET) neuroreceptor studies, areas of specific binding are usually delineated by manually drawing regions of interest (ROIs), a time-consuming and subjective process. This paper applies the technique of fuzzy c-means clustering (FCM) to automatically segment dynamic neuroreceptor SPET images. Fuzzy clustering was tested using a realistic, computer-generated, dynamic SPET phantom derived from segmenting an MR image of an anthropomorphic brain phantom. Also, the utility of applying FCM to real clinical data was assessed by comparison against conventional ROI analysis of iodine-123 iodobenzamide (IBZM) binding to dopamine D₂/D₃ receptors in the brains of humans. In addition, a further test of the methodology was assessed by applying FCM segmentation to [¹²³I]IDAM images (5-iodo-2-[[2-2-[(dimethylamino)methyl]phenyl]thio] benzyl alcohol) of serotonin transporters in non-human primates. In the simulated dynamic SPET phantom, over a wide range of counts and ratios of specific binding to background, FCM correlated very strongly with the true counts (correlation coefficient r ²>0.99, P<0.0001). Similarly, FCM gave segmentation of the [¹²³I]IBZM data comparable with manual ROI analysis, with the binding ratios derived from both methods significantly correlated (r ²=0.83, P<0.0001). Fuzzy clustering is a powerful tool for the automatic, unsupervised segmentation of dynamic neuroreceptor SPET images. Where other automated techniques fail completely, and manual ROI definition would be highly subjective, FCM is capable of segmenting noisy images in a robust and repeatable manner. Received 16 November 1998 and in revised form 20 January 1999     

Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPECT study using 123I-beta-CIT and 123I-IBZM

Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [123I]2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) and [123I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (+/-SD) at the time of head trauma was 5.8+/-4.2. SPET was performed on average 141 days (SD +/-92) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar beta-CIT and IBZM binding ratios (P< or =0.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.     

Assessment of endogenous dopamine release by methylphenidate challenge using iodine-123 iodobenzamide single-photon emission tomography

This double-blind, placebo-controlled study assessed pharmacologically induced endogenous dopamine (DA) release in healthy male volunteers (n=12). Changes in endogenous DA release after injection of the psychostimulant drug methylphenidate were evaluated by single-photon emission tomography (SPET) and constant infusion of iodine-123 iodobenzamide ([¹²³I]IBZM), a D₂ receptor radioligand that is sensitive to endogenous DA release. Methylphenidate induced displacement of striatal [¹²³I]IBZM binding, resulting in a significantly decrease in the specific to non-specific [¹²³I]IBZM uptake ratio (average: 8.6%) in comparison with placebo (average: –1.9%). Moreover, injection of methylphenidate induced significant behavioural responses on the following items: excitement, anxiety, tension, and mannerisms and posturing. The results of this study demonstrate the feasibility of using constant infusion of [¹²³I]IBZM and SPET imaging to measure endogenous DA release after methylphenidate challenge and to investigate neurochemical aspects of behaviour.     

Effects of scatter and attenuation correction on quantitative analysis of beta-CIT brain SPET

The aim of this study was to evaluate the effects of scatter correction (SC) and attenuation correction (AC) on the quantification of dopamine transporters using 123I-beta-CIT brain SPET images. Quantitative analysis was carried out using static SPET images obtained 23 h after injection. We calculated V3" [(striatal-occipital)/occipital ratio] values from images without correction, with AC, and with SC and AC. Two types of regions of interest (ROI) were placed on the striatum: a small square ROI and a larger ROI containing most of the striatum. After validating the correction method in a phantom experiment, a human study was carried out involving eight normal volunteers and 15 patients. The larger ROI yielded smaller V3" values. The effect of attenuation correction was modest, whereas that of scatter correction was marked. It was shown that beta-CIT SPET quantification was affected by the size of the ROI, photon scattering and attenuation, and that scatter and attenuation correction improved the accuracy of the quantification. Methodological standardization in image processing and the type of ROI should be considered when a multi-centre trial is planned.     

Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPET study using 123I-β-CIT and 123I-IBZM

Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [¹²³I]2-#-carbomethoxy-3-#-(4-iodophenyl)tropane (#-CIT) and [¹²³I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (-SD) at the time of head trauma was 5.8dž.2. SPET was performed on average 141 days (SD ᇰ) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar #-CIT and IBZM binding ratios (PА.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.     

In vitro and in vivo evaluation of [123I]IBZM: a potential CNS D-2 dopamine receptor imaging agent

In vitro binding characteristics of a CNS dopamine D-2 receptor imaging agent, (S)-N-[(1-ethyl-2-pyrrolidinyl)] methyl-2-hydroxy-3-iodo-6-methoxybenzamide [( 125I]IBZM), was carried out in rats. Also brain images, as well as organ biodistribution were determined in a monkey following the administration of 123I-labeled compound. The S-(-)-I[125I]IBZM showed high specific dopamine D-2 receptor binding in rat striatum (Kd = 0.426 +/- 0.082 nM, Bmax = 480 +/- 22 fmol/mg of protein). Competition of various ligands for the IBZM binding displayed the following rank order of potency: spiperone greater than S(-)IBZM much greater than R(+)IBZM greater than or equal to S(-)BZM greater than dopamine greater than ketanserin greater than SCH-23390 much greater than propranolol, norepinephrine, serotonin. In vivo planar images of a monkey injected with [123I]IBZM demonstrated a high concentration in basal ganglia of brain. The ratios of activity in the basal ganglia to cerebellum and the cortex to cerebellum in monkey brain were 4.93 and 1.44, respectively, at 120 min postinjection. These preliminary results indicate that [123I]IBZM is a potentially promising imaging agent for the investigation of dopamine D-2 receptors in humans.     

SPECT imaging of D<Subscript>2</Subscript> dopamine receptors and endogenous dopamine release in mice

PURPOSE: The dopamine D(2) receptor (D2R) is important in the mediation of addiction. [(123)I]iodobenzamide (IBZM), a SPECT ligand for the D2R, has been used for in vivo studies of D2R availability in humans, monkeys, and rats. Although mouse models are important in the study of addiction, [(123)I]IBZM has not been used in mice SPECT studies. This study evaluates the use of [(123)I]IBZM for measuring D2R availability in mice. METHODS: Pharmacokinetics of [(123)I]IBZM in mice were studied with pinhole SPECT imaging after intravenous (i.v.) injection of [(123)I]IBZM (20, 40, and 70 MBq). In addition, the ability to measure the release of endogenous dopamine after amphetamine administration with [(123)I]IBZM SPECT was investigated. Thirdly, i.v. administration, the standard route of administration, and intraperitoneal (i.p.) administration of [(123)I]IBZM were compared. RESULTS: Specific binding of [(123)I]IBZM within the mouse striatum could be clearly visualized with SPECT. Peak specific striatal binding ratios were reached around 90 min post-injection. After amphetamine administration, the specific binding ratios of [(123)I]IBZM decreased significantly (-27.2%; n = 6; p = 0.046). Intravenous administration of [(123)I]IBZM led to significantly higher specific binding than i.p. administration of the same dose. However, we found that i.v. administration of a dose of 70 MBq [(123)I]IBZM might result in acute ethanol intoxication because ethanol is used as a preparative aid for the routine production of [(123)I]IBZM. CONCLUSIONS: Imaging of D2R availability and endogenous dopamine release in mice is feasible using [(123)I]IBZM single pinhole SPECT. Using commercially produced [(123)I]IBZM, a dose of 40 MBq injected i.v. can be recommended.     

Determination of arterial input function using fuzzy clustering for quantification of cerebral blood flow with dynamic susceptibility contrast-enhanced MR imaging

An accurate determination of the arterial input function (AIF) is necessary for quantification of cerebral blood flow (CBF) using dynamic susceptibility contrast-enhanced magnetic resonance imaging. In this study, we developed a method for obtaining the AIF automatically using fuzzy c-means (FCM) clustering. The validity of this approach was investigated with computer simulations. We found that this method can automatically extract the AIF, even under very noisy conditions, e.g., when the signal-to-noise ratio is 2. The simulation results also indicated that when using a manual drawing of a region of interest (ROI) (manual ROI method), the contamination of surrounding pixels (background) into ROI caused considerable overestimation of CBF. We applied this method to six subjects and compared it with the manual ROI method. The CBF values, calculated using the AIF obtained using the manual ROI method [CBF(manual)], were significantly higher than those obtained with FCM clustering [CBF(fuzzy)]. This may have been due to the contamination of non-arterial pixels into the manually drawn ROI, as suggested by simulation results. The ratio of CBF(manual) to CBF(fuzzy) ranged from 0.99-1.83 [1.31 +/- 0.26 (mean +/- SD)]. In conclusion, our FCM clustering method appears promising for determination of AIF because it allows automatic, rapid and accurate extraction of arterial pixels. J. Magn. Reson. Imaging 2001;13:797-806.     

In vivo effects of olanzapine on striatal dopamine D(2)/D(3) receptor binding in schizophrenic patients: an iodine-123 iodobenzamide single-photon emission tomography study.

Olanzapine is a new atypical antipsychotic agent that belongs to the same chemical class as clozapine. The pharmacological efficacy of olanzapine (in contrast to that of risperidone) has been shown to be comparable to that of clozapine, but olanzapine has the advantage of producing a less pronounced bone marrow depressing effect than clozapine. The specific aims of this study were (a) to assess dopamine D(2)/D(3) receptor availability in patients treated with olanzapine by means of iodine-123 iodobenzamide [(123)I]IBZM single-photon emission tomography (SPET), (b) to compare the results with findings of [(123)I]IBZM SPET in patients under treatment with risperidone and (c) to correlate the results with the occurrence of extrapyramidal side-effects (EPMS). Brain SPET scans were performed in 20 schizophrenic patients (DSM III R) at 2 h after i.v. administration of 185 MBq [(123)I]IBZM. Images were acquired using a triple-head gamma camera (Picker Prism 3000 XP). For semiquantitative evaluation of D(2)/D(3) receptor binding, transverse slices corrected for attenuation were used to calculate specific uptake values [STR-BKG]/BKG (STR=striatum; BKG=background). The mean daily dose of olanzapine ranged from 0.05 to 0.6 mg/kg body weight. The dopamine D(2)/D(3) receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding [STR-BKG]/BKG ranged from 0.13 to 0.61 (normal controls >0.95). The decreased D(2)/D(3) receptor availability revealed an exponential dose-response relationship (r=-0.85, P<0.001). The slope of the curve was similar to that of risperidone and considerably higher than that of clozapine as compared with the results of a previously published study. EPMS were observed in only one patient, presenting with the lowest D(2)/D(3) availability. The frequency of EPMS induced by olanzapine (5%) was considerably lower than the frequency under risperidone treatment (40%). Our findings suggest an exponential relationship between the daily dose of olanzapine striatal and decreased D(2)/D(3) striatal binding availability. The results are consistent with the findings of in vitro experiments reporting a higher D(2)/D(3) receptor affinity and a similar 5HT(2) receptor affinity of olanzapine as compared with clozapine. Thus, the decreased tendency to induce EPMS at therapeutic doses is not due to the limited occupancy of striatal D(2)/D(3) receptors in vivo. Patients are protected from EPMS by other intrinsic effects of the drug, i.e. the combination of both D(2)/D(3) and 5HT(2) receptor antagonism.     

Demonstration of a reduction in muscarinic receptor binding in early Alzheimer's disease using iodine-123 dexetimide single-photon emission tomography

Decreased muscarinic receptor binding has been suggested in single-photon emission tomography (SPET) studies of Alzheimer's disease. However, it remains unclear whether these changes are present in mildly demented patients, and the role of cortical atrophy in receptor binding assessment has not been investigated. We studied muscarinic receptor binding normalized to neostriatum with SPET using [¹²³I]4-iododexetimide in five mildly affected patients with probable Alzheimer's disease and in five age-matched control subjects. Region of interest (ROI) analysis was performed in a consensus procedure blind to clinical diagnosis using matched magnetic resonance (MRI) images. Cortical atrophy was assessed by calculating percentages of cerebrospinal fluid in each ROI. An observer study with three observers was conducted to validate this method. Alzheimer patients showed statistically significantly less [¹²³I]4-iododexetimide binding in left temporal and right temporo-parietal cortex compared with controls, independent of age, sex and cortical atrophy. Mean intea-observer variability was 3.6% and inter-observer results showed consistent differences in [¹²³I]4-iododexetimide binding between observers. However, differences between patients and controls were comparable among observers and statistically significant in the same regions as in the consensus procedure. Using an MRI-SPET matching technique, we conclude that [¹²³I]4-iododexetimide binding is reduced in patients with mild probable. Alzheimer's disease in areas of temporal and temporoparietal cortex.     

Extraction of arterial input function for measurement of brain perfusion index with 99mTc compounds using fuzzy clustering

Cerebral blood flow (CBF) can be quantified non-invasively using the brain perfusion index (BPI) determined from radionuclide angiographic data generated with 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO). When measuring the BPI, manual drawing of regions of interest (ROIs) (manual ROI method) for the extraction of the arterial input function (AIF) can lead to serious individual differences. The purpose of this study was to apply the fuzzy c-means (FCM) clustering method to determine AIF, and to investigate its usefulness in comparison with the manual ROI method. Radionuclide angiography was performed using a bolus injection of about 555 MBq of 99mTc-HMPAO, followed by sequential imaging (1 sec/frame x 120 s) using a solid-state gamma camera, and the BPI values were calculated using spectral analysis. To investigate the dependence of BPI on the ROI size, we drew five ROIs with different sizes over the aortic arch, and calculated the BPI using the manual ROI method [BPI(manual)] and the FCM clustering method [BPI(FCM)]. Furthermore, we asked 10 individuals to draw ROIs to investigate the inter-operator variability of the two methods. The mean and standard deviation (SD) of BPI(manual) increased with increasing ROI size, whereas the mean of BPI(FCM) was almost constant regardless of the ROI size; the SD of BPI(FCM) was smaller than that of BPI(manual). The inter-operator variability of the FCM clustering method was smaller than that of the manual ROI method. These results suggest that the FCM clustering method appears to be useful for the measurement of BPI, because it allows a reliable and objective determination of AIF.     

Multivariate cluster analysis of dynamic iodine-123 iodobenzamide SPET dopamine D2 receptor images in schizophrenia

This paper describes the application of a multivariate statistical technique to investigate striatal dopamine D₂ receptor concentrations measured by iodine-123 iodobenzamide (¹²³I-IBZM) single-photon emission tomography (SPET). This technique enables the automatic segmentation of dynamic nuclear medicine images based on the underlying time-activity curves present in the data. Once the time-activity curves have been extracted, each pixel can be mapped back on to the underlying distribution, considerably reducing image noise. Cluster analysis has been verified using computer simulations and phantom studies. The technique has been applied to SPET images of dopamine D₂ receptors in a total of 20 healthy and 20 schizophrenic volunteers (22 male, 18 female), using the ligand¹²³I-IBZM. Following automatic image segmentation, the concentration of striatal dopamine D₂ receptors shows a significant left-sided asymmetry in male schizophrenics compared with male controls. The mean left-minus-right laterality index for controls is −1.52 (95% CI −3.72−0.66) and for patients 4.04 (95% CI 1.07−7.01). Analysis of variance shows a caseby-sex-by-side interaction, withF=10.01,P=0.005. We can now demonstrate that the previously observed male sex-specific D₂ receptor asymmetry in schizophrenia, which had failed to attain statistical significance, is valid. Cluster analysis of dynamic nuclear medicine studies provides a powerful tool for automatic segmentation and noise reduction of the images, removing much of the subjectivity inherent in region-of-interest analysis. The observed striatal D₂ asymmetry could reflect long hypothesized disruptions in dopamine-rich cortico-striatallimbic circuits in schizophrenic males.     

A fuzzy c-means (FCM)-based approach for computerized segmentation of breast lesions in dynamic contrast-enhanced MR images

RATIONALE AND OBJECTIVES: Accurate quantification of the shape and extent of breast tumors has a vital role in nearly all applications of breast magnetic resonance (MR) imaging (MRI). Specifically, tumor segmentation is a key component in the computerized assessment of likelihood of malignancy. However, manual delineation of lesions in four-dimensional MR images is labor intensive and subject to interobserver and intraobserver variations. We developed a computerized lesion segmentation method that has the advantage of being automatic, efficient, and objective. MATERIALS AND METHODS: We present a fuzzy c-means (FCM) clustering-based method for the segmentation of breast lesions in three dimensions from contrast-enhanced MR images. The proposed lesion segmentation algorithm consists of six consecutive stages: region of interest (ROI) selection by a human operator, lesion enhancement within the selected ROI, application of FCM on the enhanced ROI, binarization of the lesion membership map, connected-component labeling and object selection, and hole-filling on the selected object. We applied the algorithm to a clinical MR database consisting of 121 primary mass lesions. Manual segmentation of the lesions by an expert MR radiologist served as a reference in the evaluation of the computerized segmentation method. We also compared the proposed algorithm with a previously developed volume-growing (VG) method. RESULTS: For the 121 mass lesions in our database, 97% of lesions were segmented correctly by means of the proposed FCM-based method at an overlap threshold of 0.4, whereas 84% of lesions were correctly segmented by means of the VG method. CONCLUSION: Our proposed algorithm for breast-lesion segmentation in dynamic contrast-enhanced MRI was shown to be effective and efficient.     

Dual SPECT of dopamine system using [99mTc]TRODAT-1 and [123I]IBZM in normal and 6-OHDA-lesioned formosan rock monkeys

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by a severe loss of the dopaminergic neurons in the substantia nigra pars compacta. In this study, we evaluated pre- and post-synaptic binding sites of the dopamine system in three normal and one parkinsonian monkeys using simultaneous [99mTc]TRODAT-1 and [123I]IBZM imaging. The parkinsonian monkey was induced by injecting 6-hydroxydopamine (6-OHDA) bilaterally into the medial forebrain bundle under MRI guidance. [99mTc]TRODAT-1 (targeting dopamine transporters) and [123I]IBZM (targeting D(2)/D(3) receptors) were administered almost simultaneously and the SPECT images were acquired over 4 h using a dual-headed gamma camera equipped with ultra-high resolution fan-beam collimators. Data were obtained using energy window of 15% centered on 140 keV for 99mTc in conjunction with 10% asymmetric energy window in a lower bound at 159 keV for 123I. Single SPECT studies of [99mTc]TRODAT-1 and [123I]IBZM were also performed. We found a comparable image quality and uptake ratios between single- and dual-isotope studies. There are higher TRODAT-1 uptakes in the control monkeys than the 6-OHDA-lesioned monkey. The uptake of [123I] IBZM showed no significant difference between controls and 6-OHDA-lesioned monkey. Our results suggest that dual isotope imaging using [99mTc]TRODAT-1 and [123I]IBZM may be a useful means in evaluating the changes of both pre- and post-synaptic dopamine system in a primate model of parkinsonism.     

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.     

Registration of dynamic dopamine D2 receptor images using principal component analysis

This paper describes a novel technique for registering a dynamic sequence of single-photon emission tomography (SPET) dopamine D₂ receptor images, using principal component analysis (PCA). Conventional methods for registering images, such as count difference and correlation coefficient algorithms, fail to take into account the dynamic nature of the data, resulting in large systematic errors when registering time-varying images. However, by using principal component analysis to extract the temporal structure of the image sequence, misregistration can be quantified by examining the distribution of eigenvalues. The registration procedures were tested using a computer-generated dynamic phantom derived from a high-resolution magnetic resonance image of a realistic brain phantom. Each method was also applied to clinical SPET images of dopamine D₂ receptors, using the ligands iodine-123 iodobenzamide and iodine-123 epidepride, to investigate the influence of misregistration on kinetic modelling parameters and the binding potential. The PCA technique gave highly significant (P<0.001) improvements in image registration, leading to alignment errors in x and y of about 25% of the alternative methods, with reductions in autocorrelations over time. It could also be applied to align image sequences which the other methods failed completely to register, particularly ¹²³I-epidepride scans. The PCA method produced data of much greater quality for subsequent kinetic modelling, with an improvement of nearly 50% in the χ ² of the fit to the compartmental model, and provided superior quality registration of particularly difficult dynamic sequences. Received 1 August and in revised form 21 August 1997     

A new method for measuring dynamic change of tracer distribution using dynamic single photon emission tomography with a slip-ring rotational gamma camera

The clinical applicability of dynamic single photon emission tomograpy (SPET) using a dual-head gamma camera equipped with a slip-ring rotational mechanism, referred to as serial SPET, was examined in the present investigation. Serial SPET enables the production of tomographic images for any arbitrary time frame from an arbitrary range of data to 360 degrees. In a pre-clinical evaluation, a correlation between radioactivity concentration and serial SPET counts was evaluated in a phantom with continuous changes in 99mTc concentration. A differential value was obtained from each pair of SPET images; moreover, moving average approximation processing was investigated with respect to the elimination of noise in the data. In 11 and one patient presenting with cerebrovascular disease and meningioma, respectively, changes in SPET counts were evaluated when 99mTc ethyl cysteinate dimer (99mTc-ECD) was continuously administered at a constant rate in the resting state. Furthermore, in six of 11 subjects with cerebrovascular disease, changes occurring in SPET counts were examined by using acetazolamide loading while continuously administering 99mTc-ECD at a constant rate. Consequently, serial SPET enabled the evaluation of changes in radioactivity concentration over time in both the phantom and preliminary clinical studies. Data analysis by differential processing utilizing moving average approximation processing enabled the detection of minor changes in radioactivity concentration. An increase of 15.1+/-5.4% was observed in SPET counts of the unaffected cerebral hemisphere with acetazolamide loading. The response of the affected hemisphere was less prominent. These findings suggest that serial SPET would be an effective technique for the pharmacokinetic analysis of radiopharmaceuticals.     

Validation of quantitative brain dopamine D2 receptor imaging with a conventional single-head SPET camera

Phantom measurements were performed with a conventional single-head single-photon emission tomography (SPET) camera in order to validate the relevance of the basal ganglia/frontal cortex iodine-123 iodobenzamide (IBZM) uptake ratios measured in patients. Inside a cylindrical phantom (diameter 22 cm), two cylinders with a diameter of 3.3 cm were inserted. The activity concentrations of the cylinders ranged from 6.0 to 22.6 kBq/ml and the cylinder/background activity ratios varied from 1.4 to 3.8. From reconstructed SPET images the cylinder/ background activity ratios were calculated using three different regions of interest (ROIs). A linear relationship between the measured activity ratio and the true activity ratio was obtained. In patient studies, basal ganglia/frontal cortex IBZM uptake ratios determined from the reconstructed slices using attenuation correction prior to reconstruction were 1.30±0.03 in idiopathic Parkinson's disease (n=9), 1.33±0.09 in infantile and juvenile neuronal ceroid lipofuscinosis (n=7) and 1.34±0.05 in narcolepsy (n=8). Patients with Huntington's disease had significantly lower ratios (1.09±0.04, n=5). The corrected basal ganglia/frontal cortex ratios, determined using linear regression, were about 80% higher. The use of dual-window scatter correction increased the measured ratios by about 10%. Although comprehensive correction methods can further improve the resolution in SPET images, the resolution of the SPET system used by us (1.52 cm) will determine what is achievable in basal ganglia D2 receptor imaging.Paper presented in part at the European Association of Nuclear Medicine Congress, 22–26 August 1992, Lisbon, Portugal Correspondence to: P. Nikkinen, Division of Nuclear Medicine, Meilahti Hospital, SF-00290 Helsinki, Finland     

Initial experience with SPECT examinations using [123I]IBZM as a D2-dopamine receptor antagonist in Parkinson's disease.

[123I]IBZM is a new radioactive labelled ligand which has a high affinity and specificity to D2-dopamine receptors. The in vivo kinetics of [123I]IBZM were studied in patients with unilateral and bilateral accentuated idiopathic Parkinson's disease. The uptake in the basal ganglias and the imaging properties of this D2 receptor antagonist as a radiopharmaceutical for SPECT examinations had to be investigated. 5 patients, aged 42-66 years, (2 m/3 f) were examined. Each patient received 185 MBq [123I]IBZM intravenously. Blood samples were taken 0-120 min post injection (p.i.) and time activity curves were plotted. Three SPECT examinations were performed (I: 30-50 min; II: 50-70 min; and III: 70-90 min p.i.). The count rates (counts/pixel) in the basal ganglias and the cerebellum were measured for each SPECT series on transverse slices using the region-of-interest technique. The time-activity curve of [123I]IBZM shows a rapid decline in plasma during the first 10 min followed by a plateau until 120 min after injection. The SPECT examinations demonstrate the highest count rate in the basal ganglia during SPECT series III (i.e., 70-90 min p.i.). The side-to-side difference of the count rates were in the range of 3% in four patients, and 10% in one patient. The biokinetic data of [123I]IBZM make this substance capable as a radiopharmaceutical for SPECT examinations. The basal ganglia are best visualized 70-90 min p.i., thus [123I]IBZM seems to be a promising imaging agent for diseases of the D2-dopaminergic receptor system.     

Whole-body biodistribution, radiation absorbed dose, and brain SPET imaging with [123I]5-I-A-85380 in healthy human subjects

The biodistribution of radioactivity after the administration of a new tracer for alpha4beta2 nicotinic acetylcholine receptors (nAChRs), [123I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), was studied in ten healthy human subjects. Following administration of 98+/-6 MBq [123I]5-I-A-85380, serial whole-body images were acquired over 24 h and corrected for attenuation. One to four brain single-photon emission tomography (SPET) images were also acquired between 2.5 and 24 h. Estimates of radiation absorbed dose were calculated using MIRDOSE 3.1 with a dynamic bladder model and a dynamic gastrointestinal tract model. The estimates of the highest absorbed dose (microGy/MBq) were for the urinary bladder wall (71 and 140), lower large intestine wall (70 and 72), and upper large intestine wall (63 and 64), with 2.4-h and 4.8-h urine voiding intervals, respectively. The whole brain activity at the time of the initial whole-body imaging at 14 min was 5.0% of the injected dose. Consistent with the known distribution of alpha4beta2 nAChRs, SPET images showed the highest activity in the thalamus. These results suggest that [123I]5-I-A-85380 is a promising SPET agent to image alpha4beta2 nAChRs in humans, with acceptable dosimetry and high brain uptake.