| مستخلص: |
Dynamic molecular imaging methods now allow detection of acute changes in neurotransmission in the live human brain (neurotransmitter imaging) during task performance. These methods have extended the scope of neuroimaging by allowing study of neurochemical changes associated with cognitive and behavior processing. The neurotransmitter imaging methods however are at the initial stages of development. There is a need to develop novel receptor kinetic models and novel ligands so of development that multiple neurochemicals can be simultaneously detected. Even at the current stage, the technique allows better understanding of human cognition and cognitive disorders. This special issue introduces different aspects of neurotransmitter imaging and provides a flavor of the challenges ahead. Neurochemical control of human cognition has not been adequately studied because of the lack of a reliable method that can detect task induced changes in chemical concentration of the live human brain [1]. Neuroimaging studies are therefore focused the brain mostly on understanding of spatial and temporal aspects of processing. Since neurochemicals, particularly neurotransmitters are important for regulation of brain functions, investigators have explored the possibility of using dynamic molecular imaging to develop methods for detection of neurotransmitters released in the brain in response to pharmacological [2, 3] and cognitive [4-8] challenges. Most of the techniques developed for detection of neurotransmission are based on the principles of molecular imaging which has been traditionally used to study chronic changes in neurotransmission [9]. In recent years these techniques have been increasingly used to study acute changes. This was possible because of development of simplified reference tissue model [10], which allows detection and measurement of time dependent changes in receptor kinetic parameters. This model however, has a significant limitation. It requires maintenance of steady physiological state during the entire scan session. This requirement limits the scope of cognitive studies that can be performed using neurotransmitter imaging because most cognitive paradigms require volunteers to perform control and test task in the same scan session. Since a change of task violates the assumption region of steady state, we developed another model - the linear extension of simplified reference model [11] to eliminate the assumption of steady state. This model allows detection and measurement of dopamine released during transition from the control to test condition in a cognitive experiment. Development of this model allowed cognitive studies in the live human brain but there are a number of other issues that need to be addressed before full potential of neurotransmitter imaging can be exploited to study neurochemical control of the human brain. Issues that need immediate attention include improved sensitivity and specificity of detection; development of methods that allow simultaneous detection of multiple neurochemicals; development of algorithms to allow estimation of temporal sequence of activation. These developments would require efforts at multiple levels and involve formulation of better receptor kinetic models, development of newer ligands and innovative experimental designs. We hope this special issue will stimulate cross talk between experts involved in these areas. The introductory paper by Badgaiyan provides an overview of neurotransmitter imaging method. It highlights some of the basic concepts and problems associated with neurotransmitter imaging. The paper primarily focuses on imaging of dopamine neurotransmission and underscores the importance of receptor-ligand interaction at local and global levels. Dopamine imaging is further discussed by Yodar and colleagues. This paper underscores modeling and design challenges associated with dopamine imaging. It provides a good review of different approaches investigators have used to extract relevant information in neurotransmitter imaging experiments. Imaging of cholinergic receptors is reviewed by Lotfipour and colleagues. The review focuses on detection, mapping and quantification of nicotinic receptors in the context of smoking. It provides an insight into the current state of cholinergic imaging. This insight may be useful in designing studies aimed at understanding neurocognitive conditions in which the cholinergic system is dysregulated. Issues associated with receptor kinetic modeling are discussed by Wack and Badgaiyan. This paper demonstrates that in neurotransmitter imaging experiments noise can be significantly reduced by using complex singular value decomposition approach. This approach could become an integral part of image processing routine in these experiments. Finally, Liu and colleagues discuss how neurotransmitter imaging could be used to evaluate pathophysiological bases of traditional Chinese therapeutic techniques. This approach can be applied to other traditional systems of medicine. Since this is the first special issue on neurotransmitter imaging published in any journal, we hope it will allow development of novel ideas and help advance neurotransmitter imaging technique to a higher level of sensitivity and reliability.... |
