Cutting-edge brain imaging with positron emission tomography

A review of recent advances in brain imaging using positron emission tomography (PET) is presented in this article. Some properties of the high-resolution research tomograph are described as examples of state-of-the-art PET instrumentation. A summary of current research topics in image reconstruction and quantification is given, with emphasis on the requirements of brain dynamic imaging. A brief overview of image analysis methods is presented, together with some examples of the contributions of quantitative PET imaging to the current understanding of brain function and disease. PET findings must be evaluated in the context of clinical observations and complemented by other imaging modalities whenever possible to ensure a proper interpretation of the data.     

Imaging the pathology of Alzheimer's disease: amyloid-imaging with positron emission tomography

The steep rise in the incidence of Alzheimer's disease (AD) has further added to the considerable public health burden caused by aging of the United States population. Among the most characteristic pathologic hallmarks of AD are neuritic plaques and neurofibrillary tangles. The capability to use positron emission tomography and selective markers for amyloid protein deposition promises to substantially alter the way we diagnosis and manage patients who have AD.     

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.     

Imaging opiate receptors in the human brain with positron emission tomography. Potential applications for drug addiction research.

Positron emission tomography (PET) has been used mostly for the study of brain blood flow and metabolism in normal controls and in a variety of neurological and psychiatric conditions. With the appropriate radiotracers, PET also allows non-invasive imaging and quantification of a growing list of neuroreceptors. 11C-carfentanil and 11C-diprenorphine, 2 potent opiate ligands, have been used to label opiate receptors in vivo in man. Some advantages and limitations of this technique are discussed. PET is a unique tool that could help us understand, at the receptor level, some biochemical aspects of addiction to opiate drugs. Specific questions can be answered, but carefully designed protocols are required.     

Dopaminergic receptor sites in human brain: positron emission tomography

Positron emission tomography (PET) and 11C-labeled pimozide were used to study the dopaminergic (DA) receptor sites in the human striatum by comparing the latter with the cerebellum, which lacks DA receptors. Although 11C-pimozide concentration was not different in these two brain structures up to 53 minutes after IV injection (thus implying large nonspecific binding), a significant retention of radioactivity in striatum relative to cerebellum was found in controls but not in subjects pretreated with the unlabeled competitor haloperidol. This suggests that the striatal retention seen in controls was due to specific binding of 11C-pimozide to DA receptor sites, whereas prior occupation of the receptor sites by the unlabeled competitor was achieved in pretreated subjects.     

Imaging brain cholinergic activity with positron emission tomography: its role in the evaluation of cholinergic treatments in Alzheimer's dementia.

One of the strategies in the treatment of Alzheimer's disease is the use of drugs that enhance cholinergic brain function, since it is believed that cholinergic dysfunction is one of the factors that contributes to cognitive deterioration. Positron emission tomography is a medical imaging method that can be used to measure the concentration, kinetics, and distribution of cholinergic-enhancing drugs directly in the human brain and assess the effects of the drugs at markers of cholinergic cell viability (vesicular transporters, acetylcholinesterase), at muscarininc and nicotinic receptors, at extracellular acetylcholine, at markers of brain function (glucose metabolism and blood flow), and on amyloid plaque burden in vivo in the brains of patients with Alzheimer's disease. In addition, these measures can be applied to assess the drugs' pharmacokinetic and pharmacodynamic properties in the human brain. Since the studies are done in living human subjects, positron emission tomography can evaluate the relationship between the drugs' biological, behavioral, and cognitive effects; monitor changes in brain function in response to chronic treatment; and determine if pharmacologic interventions are neuroprotective. Moreover, because positron emission tomography has the potential to identify Alzheimer's disease during early disease, it can be used to establish whether early interventions can prevent or delay further development.     

Imaging amyloid in Parkinson's disease dementia and dementia with Lewy bodies with positron emission tomography

Although Parkinson's disease with later dementia (PDD) and dementia with Lewy bodies (DLB) are pathologically characterized by the presence of intraneuronal Lewy inclusion bodies, amyloid deposition is also associated to varying degrees with both these disorders. Fibrillar amyloid load can now be quantitated in vivo with positron emission tomography (PET) using imaging biomarkers. Here the reported findings of ¹¹C‐PIB PET studies concerning the amyloid load associated with PD and its influence on dementia are reviewed. It is concluded that the presence of amyloid acts to accelerate the dementia process in Lewy body disorders, though has little influence on its nature. Anti‐amyloid strategies could be a relevant approach for slowing dementia in a number of DLB and PDD cases. © 2009 Movement Disorder Society     

Instrumentation in positron emission tomography

The past 40 years have seen PET scanning evolve from a tool that was used predominantly for research to a valued clinical, imaging modality. Current PET scanners must perform high quality, whole-body, as well as brain, PET. There are several levels of PET devices that range from the dedicated, high-end scanners down to the hybrid PET-SPECT systems that offer varying levels of performance. The incorporation of PET into single, hybrid, multi-modality units that can provide functional and anatomic information is becoming extremely popular. Several manufacturers now provide hybrid PET-CT scanners. There is also a growing interest in dedicated devices for specific applications, such as high-resolution scanners for imaging small animals.     

Tracers for imaging melanin with positron emission tomography

The melanin binding properties of six radioligands were determined in vivo in the eyes of pigmented mice. Binding in the eyes of nonpigmented mice was used to assess nonmelanin binding characteristics. Of these radioligands, 3H-N-methylspiperone showed the best uptake and gave the best signal-to-noise ratio at all time points examined. Its binding appeared essentially irreversible. A PET study with 11C-N-methylspiperone was therefore carried out in a patient with a small ocular melanoma. Increased uptake of 11C-N-methylspiperone was observed in the melanoma. Our studies indicate that PET and radiolabeled NMSP might be used for imaging melanin and for the detection of pigmented melanoma. These results suggest that with a high resolution PET camera it may be feasible to image the melanin-containing cells (dopaminergic neurons) of the substantia nigra in the central nervous system, which could be of interest for the study of Parkinson's disease.     

Cobalt-55 positron emission tomography in late-onset epileptic seizures after thrombo-embolic middle cerebral artery infarction

The pathogenesis of late-onset epileptic seizures after thrombo-embolic cerebral infarction is poorly understood. Our previous positron emission tomographic (PET) studies with 15O have demonstrated that post-apoplectic epilepsy is associated with more severe brain ischemia, but we were unable to determine if this was the cause or the consequence of the seizures. Using cobalt-55 (55Co) as PET tracer we can now distinguish recurrent, recent infarction in patients with a previous old infarct in the same vascular territory. In seven out of twelve patients with post-apoplectic seizures an increased uptake of 55Co was observed in the border area and in two of them also within the old infarct core. In the control group, composed of eight seizure-free patients with also an old infarct involving the cortical territory of the middle cerebral artery, no increase in 55Co uptake was observed on PET examination. The present study indicates that in a significant number of patients late-onset epilepsy is the clinical expression of recurrent strokes, occurring in the same vascular territory.     

Regional brain function in schizophrenia. II. Repeated evaluation with positron emission tomography

Cerebral glucose metabolism was measured twice in a sample of 15 schizophrenics and eight controls, using positron emission tomography (PET) with 18-F-fluorodeoxyglucose. Studies were separated by three to 33 weeks. Patients were unmedicated during the first study, and the majority were receiving neuroleptics during the second study. There were no changes from study 1 to study 2 in average whole-brain metabolic rates, regional cortical activity, or the gradient of subcortical to cortical activity. The steeper subcortical to cortical gradient in schizophrenics, present in the first study, persisted in the second. Changes in this gradient were uncorrelated with changes in clinical status. Laterality (right-left) was stable across studies, and changes toward higher right relative to left hemispheric metabolism were correlated with clinical improvement. The results support the hypothesis of abnormal hemispheric activity in schizophrenia and implicate the subcortical-cortical gradient as another dimension that merits further exploration.     

Dementia with Lewy bodies studied with positron emission tomography

OBJECTIVE: To report a case initially fulfilling the clinical criteria for probable Alzheimer disease, although later clinical features suggested dementia with Lewy bodies. Oxygen 15-labeled positron emission tomograms revealed a pattern of hypometabolism characteristic of Alzheimer disease. At post mortem, there was no evidence of the pathological features of Alzheimer disease, but diffuse cortical Lewy bodies were seen in the pigmented brainstem nuclei and cerebral cortex. DESIGN: A case report. SETTING: Tertiary referral center. PATIENT: A 65-year-old white man presented with a 3-year history of memory loss and language difficulties. RESULTS: Oxygen 15-labeled positron emission tomograms revealed hypometabolism in the frontal, temporal, and parietal lobes, more severe on the left than right. Metabolism in the left caudate was just outside the 95% reference range. Occipital metabolism was normal. CONCLUSIONS: Positron emission tomographic studies have been reported to show occipital hypometabolism in dementia with Lewy bodies, in addition to the characteristic posterior bitemporal biparietal pattern of Alzheimer disease. We suggest that although this finding may favor a diagnosis of dementia with Lewy bodies, it is not necessary for diagnosis.     

Pyridoxine effect on synthesis rate of serotonin in the monkey brain measured with positron emission tomography

Summary The influence of the co-factor pyridoxine, vitamin B6, on the activity of aromatic amino acid decarboxylase enzyme was studied by positron emission tomography, PET in the brain of the Rhesus monkey using the precursor for serotonin synthesis 5-hydroxy-L-tryptophan (5-HTP) radiola-belled with¹¹C in the -position. The rate constant for the formation of serotonin in the corpus striatum was calculated using a two tissue compartment model with reference area in the brain.In baseline investigations, the mean rate constants (±S.D:) for selective utilization of [¹¹C]5-HTP to form [¹¹C]serotonin in the corpus striatum was 0.0080 ± 0.0011 min^–1. Pretreatment with intravenous pyridoxine hydrochloride 10 mg/kg bodyweight before doing a second PET study resulted in an enhanced rate constant by a mean of 20%. The rate increase was statistically significant. The increase varied considerably in different monkeys from no effect to more than 60%. The effect of pyridoxine on aromatic amino acid decarboxylase activity supported a regulatory role of pyridoxine on the synthesis of neurotransmitter in vivo, and may be of importance in diseases with deficiencies in neurotransmitter function.