The potential clinical applications of tractographic techniques are numerous [48,49], first and foremost in physiological studies of human CNS, where they enable in vivo identification of the topographic distribution of circuits shown by anatomical primate research and surmised in man.
In neurophysiology, tractography has fostered the development of a new strategy to study brain activity patterns: anatomical connectivity. This technique is
Fig. 8.9. Axial FLAIR image (upper left) compared with fractional anisotropy maps. DTI-based colour orientation map: red = x direction; green = y direction; blue = z direction. A tumour shown in the FLAIR image alters the course of surrounding fibres in several slices, as shown by the DTI data based on the possibility of visualizing directly the connections among the brain areas activated during a given task and conceptually complements two other strategies that explore connectivity, i.e. functional connectivity (the study of how two cerebral areas tend to work in a correlated manner) and effective connectivity (the study of the information flow within an active pattern by identifying its direction and orientation). Anatomi cal connectivity is essential, because it provides evidence for the existence of anatomical connections, which are indispensable elements to confirm and validate the results of functional and effective connectivity studies. An example is the study of the connectivity of the dopaminergic system, which originates in substan-tia nigra neurons in the pars compacta of the mesen-cephalon. Tractography has recently made it possible to identify the course of human dopaminergic fibres as far as the corpus striatum (nigro-striatal circuit) and their subsequent cortical distribution (cortico-striatal circuit)  (Fig. 8.8).
The utilization of this method in neurological investigations is obvious, especially in degenerative CNS disease. In Parkinson's disease, MR has a limited role except in the differential diagnosis from other diseases, since its diagnosis is essentially clinical and thus cannot be made early. By identifying the dopaminergic fibres at their origin, tractography can quantify the axo-nal depletion and thus provide an index of disease severity. Another common degenerative disease, Alzheimer's, is characterized already in its early phase by a depletion of temporo-mesial neurons, which can be identified with tractography [50-58].
In neurophysiology, electrophysiological data - indirect indicators of fibre integrity - could be better interpreted using tractography, which is capable of displaying fibre tracts directly. For instance, corticospinal fibres can be identified and reconstructed with tracto-graphy from their origin through the centrum semiovale, corona radiata, internal capsule and cerebral peduncle. Identification of this bundle is important in neurological diseases like multiple sclerosis, where de-myelination and the consequent axon damage even at a distance from the lesion site can be documented and quantified using these techniques [59-74].
In neurosurgery, knowledge of the course of nerve fibre bundles (Fig. 8.9) and their relationships to the expanding lesion can preserve them from resection [75-85].
Finally, tractography should be applied to identify and describe the brain plasticity phenomena secondary to CNS lesions. Identification of the axonal loss and consequent impairment of further adjacent or distant circuits, normally not involved in a given function, can offer insights into the complex phenomena underpinning clinical recovery and enable better targeted pharmacological and rehabilitation therapy [86-98].
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