The stereotyped process of degenerative events that occurs in distal axon after injury of the proximal parts of a neuron is known as Wallerian degeneration (WD) 
. This pathological process begins with a rapid axonal disintegration and breakdown of myelin sheath, then activation of microglia, with subsequent clearance of tissue debris and gliosis 
. WD occurs in many diseases of the central nervous system (CNS), such as trauma 
, stroke 
, multiple sclerosis 
and Alzheimer's disease 
, etc. Numerous pieces of evidence suggest that WD is one of the major causes for the nonreversible functional deficiency in these diseases 
. Consequently, using a non-invasive approach to early detect and characterize WD in CNS is clinically important, which may help to monitor the progress of axonal degeneration 
, to early predict the prognosis of functional deficiency 
and to assess the outcomes of therapeutic strategies on axonal degeneration 
Diffusion tensor imaging (DTI) measures the random motion of water molecules and has the potential to in vivo
detect changes in microscopic architectures in brain white matter (WM) 
. The DTI-derived indices include mean diffusivity (MD) and fractional anisotropy (FA), which are commonly used to quantify the average amplitude and the directionality of molecular motion, respectively 
. Besides, the primary (λ1) and transverse eigenvalues (λ23) are also popularly used to reflect the diffusivities along the maximal and perpendicular directions, respectively 
The dynamic evolution of diffusion indices in degenerated WM fiber tracts has been delineated previously. In a one-year follow-up study of stroke patients, Yu et al reported that: (1) WD can be detected at the second week with sharply decreased FA and λ1, and increased λ23; (2) from 2 week to 3 month, MD slightly increased accompanied by decreased FA, increased λ23 and unchanged λ1; and (3) all diffusion indices maintained a relatively stable level after 3 months 
. Their findings were consistent with previous studies, using either a single or a multiple time-point data 
. However, these studies cannot answer the exact relationship between the evolution of diffusion indices and its underlying pathologic processes in WD since pathological data cannot be obtained from clinical observations of living patients.
In order to answer the question, a research group had studied the degenerated visual pathway of mice, and found that the detectable decrease of λ1 (3 days after injury) was earlier than the rise of λ23 (5 or 9 days), which were consistent with the time course of decreased phosphorylated neurofilament and myelin basic protein, respectively. Then they proposed that the λ1 represented axonal degeneration whereas the λ23 denoted the myelin clearance 
. However, a recent study had reported an inconsistent results that both the reduced λ1 and the increased λ23 could be found in degenerated fibers at day 3 after unilateral dorsal root axotomy of the spinal cord 
. The authors ascribed the alterations of λ1 and λ23 at the initial stage of WD to axon degeneration. Thus a further study is needed to elucidate the exact relationship between the evolution of diffusion indices and its underlying pathologic processes in WD.
In the present study, we made substantial improvements based on previous studies. Firstly, the observation time (60 days) is much longer and the time points (12 for DTI and 8 for pathology) are much denser than previous studies 
. Secondly, much more pathological processes were observed in the present study, such as the axonal degeneration, microglia activation, debris clearance, and astrocytosis. Finally, we focused on the segment of the degenerated CST within the brain, one of the most important brain WM fiber tracts, which is commonly attacked by a variety of brain disorders. With these improvements, we aimed to elucidate the relationship between the evolution of diffusion indices and its underlying pathological processes in degenerated CST.