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     

Pharmacokinetics and dosimetry of iodine-123 labelled PE2I in humans, a radioligand for dopamine transporter imaging

The iodine-123 labelled selective ligand N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl)nortropane ([¹²³I]PE2I) was evaluated as a probe for in vivo dopamine transporter imaging in the human brain. Six healthy subjects were imaged with a high-resolution single-photon emission tomography scanner. Striatal radioactivity peaked at 1 h after injection. The background radioactivity was low. The volume of distribution in the striatum was 94±24 ml/ml. The results were compared with those of [¹²³I]β-CIT imaging. There was no significant uptake of [¹²³I]PE2I in serotonin-rich regions such as the midbrain, hypothalamus and anterior gingulus, suggesting that in vivo binding is specific for the dopamine transporter. One main polar metabolite of [¹²³I]PE2I was found in plasma, and the parent plasma concentration decayed rapidly. Radiation exposure to the study subject is 0.022±0.004 mSv/MBq (effective dose). The preliminary results suggest that [¹²³I]PE2I is a selective SPET ligand for imaging striatal dopamine transporter density. Received 9 December 1997 and in revised form 20 February 1998     

[99mTc]TRODAT-1: A novel technetium-99m complex as a dopamine transporter imaging agent

Technetium-99m is the most commonly used radionuclide in routine nuclear medicine imaging procedures. Development of^99mTc-labeled receptor-specific imaging agents for studying the central nervous system is potentially useful for evaluation of brain function in normal and disease states. A novel^99mTc-labeled tropane derivative, [^99mTc]TRODAT 1, which is useful as a potential CNS dopamine transporter imaging agent, was evaluated and characterized. After i.v. injection into rats, [^99mTc]TRODAT-1 displayed specific brain uptake in the rat striatal region (striatum-cerebellum/cerebellum ratio 1.8 at 60 min), where dopamine neurons are concentrated. The specific striatal uptake could be blocked by pretreating rats with a dose of competing dopamine transporter ligand, ß-CIT (or RTI-55, i.v., 1 mg/kg). However, the specific striatal uptake of [^99mTc]TRODAT-] was not affected by co-injection of excess free ligand (TRODAT-1, up to 200 g per rat) or by pretreating the rats with haloperidol (i.v., 1 mg/kg). The specific uptake in striatal regions of rats that had prior 6-hydroxydopamine lesion in the substantia nigra area showed a dramatic reduction. The radioactive material recovered from the rat striatal homogenates at 60 min after i.v. injection of [^99mTc]TRODAT-1 showed primarily the original compound (>95%), a good indication of in vivo stability in brain tissue. Similar and comparable organ distribution patterns and brain regional uptakes of [^99mTc]TRODAT-1 were obtained for male and female rats. Ex vivo autoradiography results of rat brain sections further confirmed the high uptake and retention of [^99mTc]TRODAT-1 in the striatal region. In vitro binding studies measuring the affinity to dopamine transporters for the free ligand, TRODAT-1, and a nonradioactive rhenium derivative, Re-TRODAT-1, showed K _i values of 9.7 nM and 14.1 nM, respectively. Behavioral studies in rats using the free ligand, TRODAT-1 and Re-TRODAT-1 indicated that, unlike other tropane derivatives, they displayed no effect on locomotor activity, suggesting low toxicity. These results strongly support the conclusions that this novel^99mTc radioligand binds selectively to dopamine transporters in the brain and that is is potentially useful for in vivo assessment of the loss of dopamine neurons in Parkinson's and other neurodegeneralive diseases.     

Imaging of dopamine D2 and somatostatin receptors in vivo using single-photon emission tomography in a patient with a TSH/PRL-producing pituitary macroadenoma

A 28-year-old man with a thyroid stimulating hormone/prolactin (TSH/PRL)-secreting pituitary macroadenoma is discussed in relation to dopamine D₂ and somatostatin receptor single-photon emission tomography (SPET). The patient presented with decreased vision in the left eye as a result of a temporal visual field defect and with mild hyperthyroidism. Medical therapy was tried. A test dose of both octreotide and bromocriptine resulted in an acute reduction in serum levels of TSH, -subunits and PRL, whereas there was no response to TRIAC. Somatostatin and dopamine D₂ receptors were present on the tumour as visualised by SPET with the ligands indium-111 diethylene triamine penta-acetic acid (DTPA)-octreotide (¹¹¹In-SMS) and iodine-123 iodobenzamide (¹²³I-IBZM), respectively. Therefore, treatment with octreotide 150 g t.i.d. subcutaneously and bromocriptine 10 mg b.i.d. orally was given for > 12 and > 6 weeks, respectively. Following this treatment the visual defects disappeared, although tumour size, as measured by CT scanning, and serum TSH levels did not decrease. SPET with ¹¹¹In-SMS and ¹²³I-IBZM after therapy revealed no change or a possible increase in somatostatin receptor binding potential and a possible decrease in dopamine D₂ receptor binding potential. The lack of long-term effects of the medical treatment is discussed. It is concluded that a high somatostatin and dopamine D₂ receptor binding potential in vivo in a TSH/PRL-producing adenoma does not necessarily predict a successful outcome of medical treatment. Correspondence to: N.P.L.G. Verhoeff     

Iodine-123 labelled PE2I for dopamine transporter imaging: influence of age in healthy subjects

The iodine-123 labelled selective ligand N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane ([¹²³I]PE2I) has been developed and has been shown to be suitable for single-photon emission tomography imaging of the dopamine transporter. In this study the influence of age on ligand binding was investigated in 16 healthy males with an age range of 23– 75 years. Single-photon emission tomography (SPET) imaging was performed with a triple-headed gamma camera. A simplified reference region model, in which the input function was derived from the non-displaceable cerebellar compartment, was used to calculate the volume of distribution in the striatum. The volume of distribution was shown to decline with age (–0.4%/year; P<0.005). The results were in agreement with in vivo and in vitro findings of a decline in dopamine transporter binding with age. The findings confirm the suitability of [¹²³I]PE2I for SPET imaging in clinical routine but emphasize the necessity of using age-matched controls in patient studies. Received 1 June and in revised form 12 June 1999     

高压氧对缺氧缺血性脑损伤新生大鼠细胞凋亡及Caspase-3 mRNA表达的影响

目的　探讨高压氧 (HBO)对缺氧缺血性脑损伤 (HIBD)新生大鼠细胞凋亡及半胱天冬酶 -3m RNA(Caspase- 3m RNA)表达的影响 ,并探讨其可能的机制。方法　健康新生 7d龄 SD大鼠随机分为正常对照组 (CON组 ,n=8) ,左颈总动脉结扎 HIBD组 (n=8)及 HIBD+HBO治疗组 (简称 HBO组 ,n=8)。用免疫组化及原位杂交方法检测各组细胞凋亡及 Caspase- 3m RNA的表达情况。结果　TU NEL 免疫组化结果显示 :CON组的左脑及 HIBD组的右脑未见或偶见阳性细胞 ,HIBD组大鼠左脑组织各个部位均可见到阳性凋亡细胞 ,经 HBO治疗者左脑阳性细胞比未治疗者减少 [(2 5 2 .96± 6 8.5 9)vs(342 .2 4± 74 .16 ) ],差异有显著性意义 (P<0 .0 5 )。Caspase- 3m RNA原位杂交检测结果显示 :CON组无或仅少量阳性细胞出现 ,HIBD组和 HBO组脑皮质、纹状体及海马均可见 Caspase- 3m RNA阳性细胞表达 ,但 HBO组信号明显减少。结论　与 CON组比较 ,HIBD组病变侧脑组织阳性凋亡细胞数增多及Caspase- 3m RNA的表达增强 ;经 HBO治疗后 ,与不经 HBO治疗的 HIBD组比较 ,病变侧脑组织阳性凋亡细胞明显减少 ,Caspase- 3m RNA的表达明显减弱 ,提示 HBO可能通过抑制 Caspase- 3m RNA的表达 ,起到减少细胞凋亡、保护神经元的作用。     

Striatal and extrastriatal imaging of dopamine D2 receptors in the living human brain with [123I]epidepride single-photon emission tomography

The iodine-123 labelled ligand benzamide epidepride was evaluated as a probe for in vivo imaging of striatal and extrastriatal dopamine D₂ receptor sites in the human brain. Four healthy males were imaged with a high-resolution single-photon emission tomography scanner. Striatal radioactivity peaked at 3 h after injection. The specific binding in the striatum was 0.91±0.03 at 3 h and this ratio steadily increased with time. Extrastriatal radioactivity was highest in the thalamus, in the midbrain and in the temporal cortex, and peaked at 45–60 min after injection of tracer. A smaller amount of radioactivity was found in the parietal, frontal and occipital cortices. Two radioactive metabolites were observed, of which one was more lipophilic than the parent compound. The radiation burden to the patient was 0.035 mSv/MBq (effective dose equivalent). The preliminary results showed that [¹²³I]epidepride can be used for imaging striatal and extrastriatal dopamine D₂ receptor sites in the living human brain.     

Comparison of iodine-123 epidepride and iodine-123 IBZM for dopamine D2 receptor imaging in clinically non-functioning pituitary macroadenomas and macroprolactinomas

We compared pituitary iodine-123 epide- pride single-photon emission tomography (SPET) and ¹²³I-IBZM SPET for the in vivo imaging of dopamine D₂ receptors in 15 patients with clinically non-functioning pituitary adenomas. Four patients with dopamine agonist-sensitive macroprolactinomas were studied as positive controls. The uptake of radioactivity in the pituitary was established using a visual scoring system and an uptake index calculated by dividing the average count rates in the pituitary area by the average count rates in the cerebellum. All four macroprolactinomas showed specific binding of ¹²³I-epidepride, but only one showed specific binding of ¹²³I-IBZM. Specific binding of ¹²³I-epidepride was demonstrated in 9 of the 15 clinically non-functioning pituitary adenomas (60%), but specific binding of ¹²³I-IBZM was shown in only 6 of these 15 cases (40%). The uptake of ¹²³I-epidepride in the pituitary region was consistently higher than that of ¹²³I-IBZM. None of the patients who showed absence of uptake of ¹²³I-epidepride in the pituitary area showed uptake of ¹²³I-IBZM in this area. In conclusion: ¹²³I-epidepride SPET is superior to ¹²³I-IBZM SPET for the visualization of dopamine receptor-positive pituitary adenomas. Therefore, ¹²³I-epidepride should replace ¹²³I-IBZM for future D₂ receptor SPET studies of pituitary adenomas. ¹²³I-epidepride SPET potentially might serve to predict the response of clinically non-functioning pituitary adenomas to dopamine agonist therapy. Received 11 July and in revised form 25 September 1998     

11C-雷氯必利的自动化制备及其在新生猪脑PET/CT显像的应用

目的自动化制备D2受体显像剂11 C-雷氯必利(11 C-raclopride),并应用于正常新生猪脑D2受体PET/CT显像。方法气相循环法合成11 C-碘甲烷(CH3I)为中间体制备11 C-raclopride,应用于正常新生猪脑PET/CT动态显像,绘制双侧基底节时间—活性动态曲线。结果制备11 C-raclopride最终产物14.6±3.6(8.8～15.0)mci,比活度68.8±20.9(39.0～86.8)GBq/μmol,放化纯度>99%。PET/CT显像示:3～5min基底节区放射性达高峰,双基底节显示清晰,放射性分布明显高于脑内其它部位;随后,基底节区放射性缓慢降低,30min达稳定水平。结论自动化制备11 C-raclopride的方法简便,过程容易控制,可应用于新生猪D2受体PET/CT显像,为缺氧缺血脑损伤D2受体功能状态的研究奠定基础。     

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.     

Radioiodinated SB 207710 as a radioligand in vivo: imaging of brain 5-HT4 receptors with SPET

Single-photon emission tomography (SPET) and positron emission tomography (PET), when coupled to suitable radioligands, are uniquely powerful for investigating the status of neurotransmitter receptors in vivo. The serotonin subtype-4 (5-HT₄) receptor has discrete and very similar distributions in rodent and primate brain. This receptor population may play a role in normal cognition and memory and is perhaps perturbed in some neuropsychiatric disorders. SB 207710 [(1-butyl-4-piperidinylmethyl)-8-amino-7-iodo-1,4-benzodioxan-5-carboxylate] is a selective high-affinity antagonist at 5-HT₄ receptors. We explored radioiodinated SB 207710 as a possible radioligand for imaging 5-HT₄ receptors in vivo. Rats were injected intravenously with iodine-125 labelled SB 207710, euthanised at known times and dissected to establish radioactivity content in brain tissues. Radioactivity entered brain but cleared rapidly and to a high extent from blood and plasma. Between 45 and 75 min after injection, the ratios of radioactivity concentration in each of 12 selected brain tissues to that in receptor-poor cerebellum correlated with previous measures of 5-HT₄ receptor density distribution in vitro. The highest ratio was about 3.4 in striatum. SB 207710 was labelled with iodine-123 by an iododestannylation procedure. A cynomolgus monkey was injected intravenously with [¹²³I]SB 207710 and examined by SPET. Maximal whole brain uptake of radioactivity was 2.3% of the injected dose at 18 min after radioligand injection. Brain images acquired between 9 and 90 min showed high radioactivity uptake in 5-HT₄ receptor-rich regions, such as striatum, and low uptake in receptor-poor cerebellum. At 169 min the ratio of radioactivity concentration in striatum to that in cerebellum was 4.0. In a second SPET experiment, the cynomolgus monkey was pretreated with a selective 5-HT₄ receptor antagonist, SB 204070, at 20 min before [¹²³I]SB 207710 injection. Radioactivity in all brain regions was reduced almost to the level in cerebellum by 176 min after radioligand injection. These findings show that [¹²³I]SB 207710 is an effective radioligand for imaging brain 5-HT₄ receptors in vivo.For preliminary accounts of this work, see Pike VW et al., J Nucl Med 1998; 39 (Suppl):185; Eur J Nucl Med 1999; 26:991.     

Simplified reference region model for the kinetic analysis of [99mTc]TRODAT-1 binding to dopamine transporters in nonhuman primates using single-photon emission tomography

Accurate quantification of neuroreceptors requires full kinetic modeling of the dynamic single-photon emission tomography (SPET) or positron emission tomography (PET) images, with highly invasive arterial blood sampling. This study investigated the application of a reference region kinetic model to the dynamics of [^99mTc]TRODAT-1 in nonhuman primates, obviating the need for blood sampling. A series of dynamic SPET scans were performed on two baboons following the injection of approximately 700 MBq of [^99mTc]TRODAT-1. Rapid arterial blood samples were taken automatically during scanning. Reconstructed SPET images were co-registered with magnetic resonance imaging (MRI) scans of the baboons, and regions of interest (ROIs) placed on the striatum, cerebellum and cerebral hemispheres. The ROI data were combined with metabolite-corrected blood data, and fitted to a three-compartment kinetic model using nonlinear least squares techniques. The same data were also used in a simplified reference region model, in which the input function was derived from the nondisplaceable tissue compartment. In addition, semiquantitative blinded analysis was performed by three raters to determine the point of transient equilibrium in the specific binding curves. All methods generated values for the ratio of the kinetic rate constants k ₃ /k ₄, which gives an estimate of the binding potential, BP. These were compared with the full kinetic model. The mean values of k ₃ /k ₄ for the three different analysis techniques for each baboon were: 1.17±0.21 and 1.12±0.13 (full kinetic model), 0.93±0.13 and 0.90±0.07 (reference region model), and 0.97±0.18 and 0.92±0.08 (equilibrium method). The reference region method gave significantly lower results than the full kinetic model (P = 0.01), but it also produced a much smaller spread and better quality fits to the kinetic data. The reference region model results for k ₃ /k ₄ correlated very strongly with the full kinetic analysis (r ² = 0.992, P<0.001), and with the equilibrium model (r ² = 0.88, P = 0.002). The subjectivity inherent in the equilibrium method produces inferior results compared with both kinetic analyses. It is suggested that the self-consistency of the reference region model, which requires no arterial blood sampling, provides a more precise and reliable estimate of the binding of [^99mTc]TRODAT-1 to dopamine transporters than full kinetic modeling. The reference region method is also better suited to a routine clinical environment, and would be able to distinguish smaller differences in dopaminergic function between patient groups. Received 26 October 1998 and in revised form 11 January 1999     

External reference markers for the correction of head rotation in brain single-photon emission tomography

Accurate reorientation of brain single-photon emission tomography (SPET) is required for quantitative procedures and for correlation with other imaging modalities. Traditionally, brain SPET has utilized reoriented slices parallel to the orbitomeatal line (OML). Reorientation using internal landmarks would be more convenient but has not been systematically compared with the use of external landmarks. We compared the interobserver reproducibility for defining the sagittal and coronal angular deviations using internal landmarks, a visual method based upon external reference markers, and an automated method based upon external reference markers. Internal landmarks were inaccurate for defining the OML whether this was based upon the frontal-occipital or frontal-cerebellar plane. External reference markers resulted in significantly lower interobserver differences for both sagittal and coronal reorientation. An operator-independent implementation proved to be feasible and provided an objective measure of marker coplanarity. In summary, external reference markers should be used when reproducible reorientation and ROI placement are required.     

Relationship between clinical features of Parkinson's disease and presynaptic dopamine transporter binding assessed with [123I]IPT and single-photon emission tomography

IPT [N-(3-iodopropen-2-yl)-2-carbome-thoxy-3-(4-chlorophenyl) tropane] is a new cocain analogue which allows the presynaptic dopamine transporters to be imaged with single-photon emission tomography (SPET) as early as 1–2 h post injection. In the present study [¹²³I]IPT SPET was performed in patients with Parkinson's disease (PD) to analyse the relationship between specific dopamine tansporter binding and clinical features of the disease. Twenty-six PD patients (Hoehn and Yahr stages I-IV, age range 40–79 years) and eight age-matched controls were studied. SPET imaging was performed 90–120 min after injection of 160–185 MBq [¹²³I]IPT using a triple-head camera. For semiquantitative evaluation of specific [¹²³I]IPT binding, ratios between caudate, putamen and background regions were calculated. Specific [¹²³I]IPT uptake was significantly reduced in PD patients compared to controls. Most patients showed a marked asymmetry with a more pronounced decrease in [¹²³I]IPT binding on the side contralateral to the predominant clinical findings. The putamen was always more affected than the caudate. [¹²³I]IPT binding was significantly correlated with disease duration (r=–0.7,P<0.0001) but not with the age of PD patients (r=–0.10,P=0.61). Specific [¹²³I]IPT uptake in the caudate and putamen, and putamen to caudate ratios, decreased with increasing Hoehn and Yahr stage. Our findings indicate that [¹²³I]IPT SPET may be a useful technique to estimate the extent of nigrostriatal degeneration in PD patients. Close relationships between striatal [¹²³I]IPT binding and clinical features of the disease suggest that this method can be used to objectively follow the course and progression of PD. The reduced putamen to caudate ratios observed even in patients with mild, newly recognized symptoms indicate that particularly this parameter may help to establish the correct diagnosis in the early course of PD.     

Diffusion-weighted imaging in the evaluation of watershed hypoxic-ischemic brain injury in pediatric patients

The purpose of our study was to determine the usefulness of echo-planar diffusion-weighted imaging (EPDI) in the evaluation of watershed hypoxic-ischemic brain injury in pediatric patients. Eighteen patients ranging in age from 3 weeks to 12 years were evaluated for evidence of ischemic/infarction changes on conventional MR and EPDI. Included in the study group were five patients with sickle cell disease, four with congenital heart disease, four with hypotensive episodes with various etiologies, three with sepsis, and two with encephalitis or meningitis. Patients were examined 2 h to 6 days after the initial insult, with follow-up studies in four patients at 1 to 62 days after the initial examination. After conventional MR imaging (T1, FSE T2, and FLAIR), diffusion-weighted MR imaging was performed using high-speed, single-shot EP techniques with TR 6000, TE 144, matrix 96 × 128, FOV 23.3 × 31 and five b values of 0, 160, 360, 640, and 1,000 s/mm². EPDI demonstrated abnormally increased signal in watershed ischemic/infarction zones in all initial cases. Apparent diffusion coefficients (ADC) were obtained in 59 lesions. When compared with radiographically normal (on EPDI) contralateral brain parenchyma, 45 demonstrated a relatively decreased ADC, while eight had normal ( ± 10 %) and six had increased ADC. In four cases, signal abnormalities on EPDI were not seen or exceeded that seen with conventional MR imaging. In the remaining cases, signal abnormalities were obvious on EPDI and more subtle on conventional MR imaging. Follow-up studies demonstrated resolution of abnormal EPDI signal with persistent abnormalities on conventional imaging in some cases, while others revealed an increase in size or number of EPDI signal abnormalities, suggesting ongoing acute ischemic/infarctive changes. EPDI is a rapid, sensitive technique for detecting watershed ischemic/infarction changes in pediatric patients with hypoperfusion episodes, at times before such changes are apparent on conventional MR images and/or are clinically apparent. Received: 5 January 2001/Accepted: 1 February 2001     

IBZM tool: a fully automated expert system for the evaluation of IBZM SPECT studies

Purpose Visual reading of [¹²³I]IBZM SPECT scans depends on the experience of the interpreter. Therefore, semi-quantification of striatal IBZM uptake is commonly considered mandatory. However, semi-quantification is time consuming and prone to error, particularly if the volumes of interest (VOIs) are positioned manually. Therefore, the present paper proposes a new software tool (“IBZM tool”) for fully automated and standardised processing, evaluation and documentation of [¹²³I]IBZM SPECT scans. Methods The IBZM tool is an easy-to-use SPM toolbox. It includes automated procedures for realignment and summation of multiple frames (motion correction), stereotactic normalisation, scaling, VOI analysis of striatum-to-reference ratio R, classification of R and standardised display. In order to evaluate the tool, which was developed at the University of Hamburg, the tool was transferred to the University of Hannover. There it was applied to 27 well-documented subjects: eight patients with multi-system atrophy (MSA), 12 patients with Parkinson’s disease (PD) and seven controls. The IBZM tool was compared with manual VOI analysis. Results The sensitivity and specificity of the IBZM tool for the differentiation of the MSA subjects from the controls were 100% and 86%, respectively. The IBZM tool provided improved statistical power compared with manual VOI analysis. Conclusion The IBZM tool is an expert system for the detection of reduced striatal D₂ availability on [¹²³I]IBZM SPECT scans. The standardised documentation supports visual and semi-quantitative evaluation, and it is useful for presenting the findings to the referring physician. The IBZM tool has the potential for widespread use, since it appears to be fairly independent of the performance characteristics of the particular SPECT system used. The tool is available free of charge.     

Clinical deficits in Huntington disease correlate with reduced striatal uptake on iodine-123 epidepride single-photon emission tomography

Huntington disease (HD) is characterized by severe abnormalities in neurotransmitter concentrations and neuroreceptor density. Quantitative changes in dopamine D₂ receptors occur in the early stages of HD and may be detectable with functional neuroimaging techniques. The aim of this study was to determine whether dopamine D₂ receptor imaging with single-photon emission tomography (SPET) identifies preclinical abnormalities in HD.The study population comprised 32 subjects from families affected by HD: 11 were genetically normal while 21 were genetically positive for HD (seven asymptomatic, six early, three moderate and five advanced findings). Disease severity was determined using a standardized quantitative neurological examination (QNE) and the mini-mental status examination (MMSE). Subjects underwent brain SPET imaging 120 min following intravenous injection of iodine-123 epidepride. Ratios of target (striatal) to nontarget (occipital or whole-brain) uptake were calculated from the reconstructed image data. Striatum to occiput and striatum to whole-brain count ratios correlated negatively with disease stage (P=0.002 and P=0.0002) and QNE (P<0.002 and P=0.0002), and positively with the MMSE (P=0.001 and P<0.001). Uptake was significantly reduced in the moderate-advanced subjects but was still normal for the asymptomatic and early symptomatic stages. It is concluded that reductions in striatal dopamine D₂ receptor density can be detected with ¹²³I epidepride at moderate or advanced stages of HD. In contrast to other reports, we could not identify abnormalities in clinically unaffected or early stages of HD. Received 1 May and in revised form 29 June 1999     

成年大鼠弥漫性脑损伤后海马齿状回神经前体细胞增殖的Glu - iGlURs通路机制研究

 目的观察选择性iGluRs拮抗剂MK-801对弥漫性脑损伤后齿状回神经发生的调控作用,探讨Glu-iGluRs通路在神经发生中的角色.方法选用成年弥漫性脑损伤大鼠模型,采用BrdU标记分裂细胞及免疫组织化学方法,比较弥漫性脑损伤后2、4、6、8、12 d时MK-801干预弥漫性脑损伤组大鼠与相应对照组大鼠之间海马齿状回神经前体细胞的增殖速度.结果MK-801 1 mg/kg腹腔注射后,明显抑制了成年大鼠弥漫性脑损伤后4、6、8、12 d时齿状回神经前体细胞增殖,BrdU免疫阳性细胞数目较相应对照组明显减少(P＜0.01).结论弥漫性脑损伤后脑组织Glu-iGluRs通路的激活促进了海马齿状回神经发生,在这一过程中,NMDA受体介导的级联生物学事件可能发挥了重要作用.     

A simplified method for quantitation of iodine-123 iodobenzamide in human plasma: a technical note

To establish a quantitative single-photon emission tomography (SPET) procedure for imaging CNS D₂ dopamine receptors, measurement of unchanged iodine-123 iodobenzamide (¹²³I-IBZM) (a selective D₂ ligand) in human plasma was investigated. There are three possible radioactive components in human plasma: hydrophilic compounds (iodide ion, etc.), lipophilic metabolites, and unchanged IBZM. Based on the difference in lipophilicity of IBZM and its lipophilic metabolites (LM), a new quantitative method of analysis of ¹²³I-IBZM using a simple solvent extraction was developed. The selective extraction was achieved with n-octane/phosphate buffer (0.1 M, pH 7.4). Extraction efficiency was 93.2% ± 0.3% (n=15) for IBZM from plasma, while 99.3% ± 0.2% (n =12) of LM remained in the aqueous plasma fraction. Twenty-one confirmation tests with plasma containing known ratios of IBZM/LM, ranging between 0.39 and 7.60, were performed. The experimental results were very close to the values of the true ratios over the wide range (accuracy 99%, relative standard error 6.6%). The data from this simplified method are comparable to those obtained by the high-performance liquid chromatography method. This improved method provides an easy and accurate way to quantify unchanged IBZM in human plasma. With appropriate kinetic modeling and in conjunction with a dedicated SPET imaging device for measuring quantitative information, it may be possible to develop a practical method for measuring D₂ receptor density in vivo. Correspondence to: Mei-Ping T. Kung     

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