PET定位伽玛刀治疗癫痫性精神障碍的临床研究

目的 探讨PET定位伽玛刀放射外科治疗癫痫性精神障碍(EPP)的方法及疗效.方法 45例EPP患者依据18F-2-氟-2-脱氧葡萄糖(FDG)PET显像及癫痫发作特点、脑电图、MRI等检查定位致痫灶,依据定位明确情况及患者EPP类型将病例分为2组:(1)发作性精神障碍组(PEP组),共25例,均行癫痫灶伽玛刀治疗.(2)非发作性精神障碍组(NEP),共20例,其中完成致痫灶定位的共16例(NEPc组),行癫痫灶联合胼胝体和双侧扣带回前部伽玛刀治疗;未明确定位的4例(NEPs组)仅行脑深部核团伽玛刀毁损. 结果 精神症状临床疗效总评量表(CGI)疗效指数总体良好率达到62.2％,其中PEP组和NEPs组良好率分别为72.0％和75.0％,明显高于NEPc组的43.8％.62.2％(28/45)癫痫预后达到Wieser Ⅰ～Ⅱ级,20.0％(9/45)达到Ⅲ～Ⅳ级,有效率为82.2％,其中NEPs组有效率为25.0％ (1/4),明显低于PEP和NEPc组的88.0％和87.5％. 结论 药物难治的癫痫性精神障碍患者通过伽玛刀治疗可以达到良好的效果,PEP患者可以行单纯癫痫灶伽玛射线照射,NEP患者应当联合癫痫灶伽玛射线照射及脑深部核团伽玛刀毁损的方法治疗.     

Temporal lobe epilepsy with bilateral seizure origin studied by [18F]FDG-positron emission tomography

Nine patients who underwent presurgical evaluation because of medically refractory temporal lobe epilepsy (TLE) showed either unilateral, although alternating in side, or bilateral simultaneous seizure onsets in both temporal lobes (TL). EEG recordings with semi-invasive foramen ovale electrodes revealed in seven patients a predominance of seizure onset in one TL of between 50% and 88%. In two patients the majority of seizures originated simultaneously in both TL. In four patients a unilateral selective amygdalohippocampectomy resulted in a good to excellent seizure outcome without noteworthy memory deficits and confirmed the preoperative lateralization of the primary epileptogenic focus by interictal ¹⁸F-fluorodeoxyglucose positron emission tomography (PET). Five patients were rejected from surgery due to strong bilaterality of their epilepsy and/or divergent presurgical findings. PET contributed to the decision of whether surgery should be performed: all patients who underwent surgery had a unilateral TL hypometabolism which was concordant with the findings of other tests. Patients in whom surgery was denied had either bilateral temporal hypometabolism or the PET findings were discordant with other results obtained during the presurgical evaluation.     

Striatal dopamine metabolism in living monkeys examined by positron emission tomography

Positron emission tomography, using the dopa analogue [18F]6-fluoro-L-dopa, has been used to depict the neostriatum in living monkeys. The amount of 18F that accumulated preferentially in the striatum could be augmented by a peripheral decarboxylase inhibitor. Striatal 18F could also be discharged with reserpine. This is the first time that the regional distribution of a neurotransmitter has been demonstrated in monkeys.     

Parametric mapping of [18F]fluoromisonidazole positron emission tomography using basis functions

In this study, we show a basis function method (BAFPIC) for voxelwise calculation of kinetic parameters (K₁, k₂, k₃, K_i) and blood volume using an irreversible two-tissue compartment model. BAFPIC was applied to rat ischaemic stroke micro-positron emission tomography data acquired with the hypoxia tracer [¹⁸F]fluoromisonidazole because irreversible two-tissue compartmental modelling provided good fits to data from both hypoxic and normoxic tissues. Simulated data show that BAFPIC produces kinetic parameters with significantly lower variability and bias than nonlinear least squares (NLLS) modelling in hypoxic tissue. The advantage of BAFPIC over NLLS is less pronounced in normoxic tissue. K_i determined from BAFPIC has lower variability than that from the Patlak–Gjedde graphical analysis (PGA) by up to 40% and lower bias, except for normoxic tissue at mid-high noise levels. Consistent with the simulation results, BAFPIC parametric maps of real data suffer less noise-induced variability than do NLLS and PGA. Delineation of hypoxia on BAFPIC k₃ maps is aided by low variability in normoxic tissue, which matches that in K_i maps. BAFPIC produces K_i values that correlate well with those from PGA (r²=0.93 to 0.97; slope 0.99 to 1.05, absolute intercept <0.00002 mL/g per min). BAFPIC is a computationally efficient method of determining parametric maps with low bias and variance.     

Usefulness of positron emission tomography in diagnosis and treatment follow-up of brain tumors

Clinical and experimental use of positron emission tomography (PET) is expanding and allows quantitative assessment of brain tumor's pathophysiology and biochemistry. PET therefore provides different biochemical and molecular information about primary brain tumors when compared to histological methods or neuroradiological studies. Common clinical indications for PET contain primary brain tumor diagnosis and identification of the metabolically most active brain tumor reactions (differentiation of viable tumor tissue from necrosis), prediction of treatment response by measurement of tumor perfusion, or ischemia. The interesting key question remains not only whether the magnitude of biochemical alterations demonstrated by PET reveals prognostic value with respect to survival, but also whether it identifies early disease and differentiates benign from malignant lesions. Moreover, an early identification of treatment success or failure by PET could significantly influence patient management by providing more objective decision criteria for evaluation of specific therapeutic strategies. Specially, as PET represents a novel technology for molecular imaging assays of metabolism and signal transduction to gene expression, reporter gene assays are used to trace the location and temporal level of expression of therapeutic and endogenous genes. PET probes and drugs are being developed together as molecular probes to image the function of targets without disturbing them and in mass amounts to modify the target's function as a drug. Molecular imaging by PET helps to close the gap between in vitro to in vivo integrative biology of disease.     

Relative sparing of the parietal cortex in cerebellar ataxia documented by positron emission tomography

With the intention to assess remote effects of cerebellar dysfunction, 23 patients with inherited or idiopathic cerebellar ataxia were studied with positron emission tomography (PET) and 2[18F]fluoro-2-deoxy-D-glucose (FDG). Eight patients (group 1) suffered from early onset cerebellar ataxia (EOCA, age of symptom onset <20 years), nine patients (group 2) from late onset cerebellar ataxia (LOCA, symptom onset between the ages of 20 and 50), and six patients (group 3) experienced symptom onset beyond the age of 50 years. The pattern of cerebral glucose metabolism in cerebellar ataxia was compared to the results in a control group of 16 healthy subjects. In all patients, a reduction in relative (EOCA, group 1) or absolute (LOCA, groups 2 and 3) values of regional cerebral glucose metabolism (rCMR(glu)) occurred in both cerebellar hemispheres as well as the vermis and both dentate nuclei. In patients from all groups presenting with a clinical syndrome of pure cerebellar ataxia, impairment of regional glucose metabolism also extended to the pontine and brainstem regions. In contrast to this infratentorial reduction of rCMR(glu) in all patients, in those with LOCA, a significant relative increase in rCMR(glu) was present in distinct supratentorial cortical regions, namely the cuneus, the pre-cuneus and the gyrus supramarginalis in the patients of group 2. In group 3, this significant relative increase in rCMR(glu) was restricted to the cuneus. Thus, FDG-PET in patients suffering from cerebellar ataxia shows distinct patterns of altered glucose metabolism which exceed pure cerebellar impairment. Most importantly, FDG-PET yields insight into the influence of cerebellar disease on supratentorial glucose metabolism and documents impairment of supratentorial neuronal function with relative sparing of the parietal cortex.     

PET/CT定位伽玛刀治疗顽固性癫痫的临床研究

目的评价PET/CT定位伽玛刀治疗难治性癫痫的疗效。方法对2007年1月至2010年12月来我院就诊的难治性癫痫患者进行PET/CT检查,30例患者接受了伽玛刀治疗,均以50%等剂量曲线包绕病灶,周边剂量为9～13Gy。根据PET/CT显示的致痫灶的代谢分为低代谢组(A组)和高代谢组(B组,包括高低病灶并存);低代谢组根据PET/CT显示的致痫灶的数量分为单病灶组(A1)和多病灶组(A2)。结果随访12～48个月,30例患者PET显像均表现异常,低代谢灶20例,高代谢灶8例,低代谢灶和高代谢灶共存2例。低代谢组中单病灶14例,多病灶6例。A和B组癫痫发作频率较治疗前明显降低,且B组疗效明显高于A组。A1组和A2组癫痫发作频率较治疗前明显降低,且A1组疗效明显高于A2组。所有治疗病例均未发生明显并发症。结论 PET/CT定位伽玛刀治疗难治性癫痫具有较高的有效率。高代谢组疗、单一病灶组疗效优于低代谢组、多病灶组。     

Effects of ketamine/xylazine and isoflurane on rat brain glucose metabolism measured by 18F‐fluorodeoxyglucose‐positron emission tomography

The aim of the present study was to investigate changes in glucose metabolism in male Wistar rats induced by the anesthetics isoflurane and ketamine combined with xylazine via ¹⁸F‐fluorodeoxyglucose‐positron emission tomography. We analyzed the differential effects of the anesthetics on ¹⁸F‐fluorodeoxyglucose uptake and pharmacokinetics in 33 rats using quantification methods: (a) the standardized uptake value, (b) voxel‐based analyses, and (c) kinetic analysis. Both anesthetics reduced glucose uptake in the entire brain. The voxel‐based analyses detected smaller uptake reductions in the bilateral primary somatosensory system cortex and part of the limbic system in the ketamine‐xylazine (KX) group and in the vestibular nucleus in the isoflurane group. Through kinetic analysis, we found that the volume of distribution and the membrane transport rate K₁ were reduced in the KX group. Through various methods of ¹⁸F‐fluorodeoxyglucose‐positron emission tomography quantification, the present study found that anesthesia with the ketamine‐xylazine combination induced a global reduction of glucose metabolism compared with isoflurane; this reduction of metabolism was relatively lower in the primary somatosensory cortex and part of the limbic system. The volume of distribution of ¹⁸F‐fluorodeoxyglucose and its Glut1‐mediated transport across the brain membranes (K₁) were decreased in the KX group.     

Comparison of cerebral blood flow acquired by simultaneous [15O]water positron emission tomography and arterial spin labeling magnetic resonance imaging

Until recently, no direct comparison between [¹⁵O]water positron emission tomography (PET) and arterial spin labeling (ASL) for measuring cerebral blood flow (CBF) was possible. With the introduction of integrated, hybrid magnetic resonance (MR)-PET scanners, such a comparison becomes feasible. This study presents results of CBF measurements recorded simultaneously with [¹⁵O]water and ASL. A 3T MR-BrainPET scanner was used for the simultaneous acquisition of pseudo-continuous ASL (pCASL) magnetic resonance imaging (MRI) and [¹⁵O]water PET. Quantitative CBF values were compared in 10 young healthy male volunteers at baseline conditions. A statistically significant (P<0.05) correlation was observed between the two modalities; the whole-brain CBF values determined with PET and pCASL were 43.3±6.1 mL and 51.9±7.1 mL per 100 g per minute, respectively. The gray/white matter (GM/WM) ratio of CBF was 3.0 for PET and 3.4 for pCASL. A paired t-test revealed differences in regional CBF between ASL and PET with higher ASL-CBF than PET-CBF values in cortical areas. Using an integrated, hybrid MR-PET a direct simultaneous comparison between ASL and [¹⁵O]water PET became possible for the first time so that temporal, physiologic, and functional variations were avoided. Regional and individual differences were found despite the overall similarity between ASL and PET, requiring further detailed investigations.     

Tryptophan depletion and serotonin loss in selective serotonin reuptake inhibitor-treated depression: an [(18)F] MPPF positron emission tomography study.

BACKGROUND: Recurrence of depressive symptoms after tryptophan depletion (TD) in selective serotonin reuptake inhibitor (SSRI)-treated depression is an important, unexplained phenomenon. With [(18)F] MPPF positron emission tomography (PET), serotonin (5-hydroxytryptamine, 5-HT) 1A receptor binding potential (5-HT(1A)BP) was measured after TD in various brain regions in citalopram-treated depression. This 5-HT(1A)BP measurement is sensitive to changes in extracellular 5-HT in animal models. METHODS: Eight remitted patients with major depressive disorder received [(18)F] MPPF PET scans twice: once after TD and once after sham depletion. Behavioral measures were evaluated with the Hamilton Depression Rating Scale and visual analog scales. RESULTS: No effect on regional 5-HT(1A)BP was observed after TD, despite an 86% decrease in total plasma tryptophan and transient depressive relapse in six of eight patients. CONCLUSIONS: Large-magnitude changes in extracellular 5-HT are not crucial for the mood effects observed in SSRI-treated subjects after TD. Therefore, greater consideration must be given to other mechanisms that involve vulnerability to small perturbations in extracellular 5-HT, such as impairment of signal transduction.     

Measurement of density and affinity for dopamine D2 receptors by a single positron emission tomography scan with multiple injections of [11C]raclopride

Positron emission tomography (PET) with [¹¹C]raclopride has been used to investigate the density (B_max) and affinity (K_d) of dopamine D₂ receptors related to several neurological and psychiatric disorders. However, in assessing the B_max and K_d, multiple PET scans are necessary under variable specific activities of administered [¹¹C]raclopride, resulting in a long study period and unexpected physiological variations. In this paper, we have developed a method of multiple-injection graphical analysis (MI-GA) that provides the B_max and K_d values from a single PET scan with three sequential injections of [¹¹C]raclopride, and we validated the proposed method by performing numerous simulations and PET studies on monkeys. In the simulations, the three-injection protocol was designed according to prior knowledge of the receptor kinetics, and the errors of B_max and K_d estimated by MI-GA were analyzed. Simulations showed that our method could support the calculation of B_max and K_d, despite a slight overestimation compared with the true magnitudes. In monkey studies, we could calculate the B_max and K_d of diseased or normal striatum in a 150 mins scan with the three-injection protocol of [¹¹C]raclopride. Estimated B_max and K_d values of D₂ receptors in normal or partially dopamine-depleted striatum were comparable to the previously reported values.     

Serotonin transporter availability in patients with schizophrenia: a positron emission tomography imaging study with [11C]DASB.

BACKGROUND: Postmortem studies have reported several alterations in serotonin transporter (SERT) binding parameters in patients with schizophrenia. The aim of this study was to compare SERT availability in vivo in patients with schizophrenia and matched control subjects. METHODS: Ten medication-free patients with schizophrenia and 10 healthy subjects underwent positron emission tomography (PET) scans for 90 min after 11C-3-amino-4-(2-dimethylaminomethylphenylthio)benzonitrile ([11C]DASB) injection. Metabolite-corrected arterial input function was measured. Regional distribution volumes (mL/g) were derived with a two tissue compartment kinetic model. Outcome measures for SERT availability included binding potential (BP) and the specific-to-nonspecific equilibrium partition coefficient (V3'). Ten brain regions with high density of SERT and where SERT availability can be reliably quantified with [11C]DASB were included in the analysis. RESULTS: No significant differences were observed in regional BP or V3' between patients and control subjects. No significant relationships were observed between regional SERT availability and severity of positive, negative, and depressive symptoms. CONCLUSIONS: This study failed to detect alterations of SERT availability in patients with schizophrenia; however, this study does not rule out the possibility that schizophrenia might be associated with alterations of SERT density in the cortical regions, where the [11C]DASB-specific binding signal is too low for reliable quantification of SERT.     

Detection of unknown primary tumours in patients with cerebral metastases using whole-body 18F-flouorodeoxyglucose positron emission tomography

Identification of the unknown primary tumours in patients presenting with cerebral metastasis is a continued diagnostic challenge. Despite extensive and lengthy diagnostic work-up, the primary tumours will remain obscure in a significant proportion of the patients. The aim of this study was to evaluate the use of whole-body 18-F-fluorodeoxyglucose positron emission tomography (18FDG PET) scanning in this pursuit. Sixteen patients aged 34-74 years, with histologically confirmed metastatic brain tumours, were included in the study. Whole-body 18FDG PET identified pulmonary foci of probable primary tumours in all patients. Subsequent confirmation of tumour tissue was determined either by direct histological verification or indirectly by the observation of lesion appearance or lesion growth on structural imaging. This could only be obtained in eight of 16 patients, all defined as true positive. Of the remaining eight, a biopsy could not be sampled from seven patients, because of death or limited follow-up investigations, and one patient had pulmonary malignant melanoma metastases. Whole-body 18FDG PET scanning is a sensitive tool in the search for unknown primary tumours of patients with confirmed cerebral metastases allowing early and focused histological confirmation from suspicious lesions.     

Comparison of velocity- and acceleration-selective arterial spin labeling with [15O]H2O positron emission tomography

In the last decade spatially nonselective arterial spin labeling (SNS-ASL) methods such as velocity-selective ASL (VS-ASL) and acceleration-selective ASL have been introduced, which label spins based on their flow velocity or acceleration rather than spatial localization. Since labeling also occurs within the imaging plane, these methods suffer less from transit delay effects than traditional ASL methods. However, there is a need for validation of these techniques. In this study, a comparison was made between these SNS-ASL techniques with [¹⁵O]H₂O positron emission tomography (PET), which is regarded as gold standard to measure quantitatively cerebral blood flow (CBF) in humans. In addition, the question of whether these techniques suffered from sensitivity to arterial cerebral blood volume (aCBV), as opposed to producing pure CBF contrast, was investigated. The results show high voxelwise intracranial correlation (0.72 to 0.89) between the spatial distribution of the perfusion signal from the SNS-ASL methods and the PET CBF maps. A similar gray matter (GM) CBF was measured by dual VS-ASL compared with PET (46.7±4.1 versus 47.1±6.5 mL/100 g/min, respectively). Finally, only minor contribution of aCBV patterns in GM to all SNS-ASL methods was found compared with pseudo-continuous ASL. In conclusion, VS-ASL provides a similar quantitative CBF, and all SNS-ASL methods provide qualitatively similar CBF maps as [¹⁵O]H₂O PET.     

Increased dopamine D2/D3 receptor binding after recovery from anorexia nervosa measured by positron emission tomography and [11c]raclopride.

BACKGROUND: Several lines of evidence support the possibility that disturbances of dopamine (DA) function could contribute to alterations of weight, feeding, motor activity, and reward in anorexia nervosa (AN). METHODS: To assess possibly trait-related disturbances but avoid confounding effects of malnutrition, 10 women who were recovered from AN (REC AN) were compared with 12 healthy control women (CW). Positron emission tomography with [(11)C]raclopride was used to assess DA D2/D3 receptor binding. RESULTS: The women who were recovered from AN had significantly higher [(11)C]raclopride binding potential in the antero-ventral striatum than CW. For REC AN, [(11)C]raclopride binding potential was positively related to harm avoidance in the dorsal caudate and dorsal putamen. CONCLUSIONS: These data lend support for the possibility that decreased intrasynaptic DA concentration or increased D2/D3 receptor density or affinity is associated with AN and might contribute to the characteristic harm avoidance or increased physical activity found in AN. Most intriguing is the possibility that individuals with AN might have a DA related disturbance of reward mechanisms contributing to altered hedonics of feeding behavior and their ascetic, anhedonic temperament.     

Atypical basal ganglia germinoma presenting as cerebral hemiatrophy: diagnosis and follow-up with 11C-methionine positron emission tomography

Objects  Some basal ganglia germinomas are difficult to diagnose in early stage of disease due to vague initial presentation without discernable mass lesion on brain imaging. We performed this study to determine the usefulness of ¹¹C-methionine positron emission tomography (MET PET) for the diagnosis and monitoring of disease activity. Materials and methods  MET PET was performed in three consecutive patients; they presented with cerebral hemiatrophy without definite mass lesions on brain image. The maximum standard tracer uptake values (max SUVs) were calculated and used for the quantitative evaluation of the abnormal MET uptake. A pathological diagnosis was made after stereotactic biopsy using MET PET/computed tomography. The max SUVs significantly decreased after treatment. Conclusion  Basal ganglia germinoma should be considered in the differential diagnosis of patients with progressive hemiparesis and hemiatrophy on magnetic resonance imaging. The MET PET was useful for diagnosis, and it can be valuable in evaluation of treatment effects and monitoring for tumor recurrence.