it was described for pathophysiological changes in neurological diseases such as alzheimer 's disease   and brain trauma .
more recent studies have suggested that this damage also occurs in the development of glaucoma [ 35 ] .
loss of retinal ganglion cells in the retina and their axons that represent the optic nerve ( 3rd neuron )   and a loss of astrocytes   is the predominant finding in primary open - angle glaucoma .
the axons of various retinal ganglion cell subtypes , differing in specific morphology and function , exit the eye ball and finally converge to anatomically distinguishable layers of the lateral geniculate nucleus ( lgn )   where a loss of neural cells has also been described in glaucoma .
the lgn serves as a  relay station  that transmits the information via the 4th neuron to the primary visual cortex ( v1 ) . even in v1 neurons
the loss of axons of the 3rd neuron and astrocytes , which are placed between the optic nerve fibers becomes visible by a 
functionally , glaucoma results in a loss of visual function , which is detectable by determination of the visual field ( white - white perimetry ) and of the spatial - temporal contrast sensitivity ( frequency doubling test , fdt ) [ 11 , 12 ] .
it is not clear if the loss of axons of the 3rd neuron causes directly an injury of the 4th neuron in humans .
however , animal experiments recently have shown that glaucomatous loss of axons of the 3rd neuron is followed by a loss of the lgn volume which indicates a reduced number of 4th neurons . furthermore , with increasing loss of retinal ganglion cells an increasing loss in lgn neurons was described . in vivo detection of glaucomatous changes along the visual pathway and
we report a new approach for in vivo visualization of pathological changes of the optic radiation ( 4th neuron ) in glaucoma by use of diffusion tensor imaging ( dti ) .
dti is based on the random motion of water molecules , which is associated with their thermal energy at body temperature ( brownian motion ) and which is known as 
diffusion  . in the presence of a strong magnetic gradient a loss of the magnetic resonance signal results as a consequence of the dephasing of spin coherence . in each voxel
the eigenvectors can be characterized from the generated diffusion - weighted magnetic resonance images . in white matter consisting of axons in all directions of a three - dimensional space the diffusion of free water molecules is different ( anisotropy ) [ 15 , 16 ] .
predominantly the orientation of fiber tracts and their micro- and macrostructural features influences the diffusion anisotropy   and provides the direction of the largest eigenvector .
macroscopically the degree of anisotropy assigned to a definite voxel is affected by the variability in the orientation of all white matter tracts in this imaging voxel .
even reconstructions of fiber crossing and branching within the optic chiasm and the lgn are possible by dti . thus , the entire visual pathway from the optic nerve to the visual cortex may be reconstructed . in our work
we intended to introduce the dti as a suitable examination method to detect changes of the optic radiation in glaucoma patients .
a case report in comparison to a healthy age - matched control subject is shown .
subjects received a questionnaire requesting age , gender , known cardiovascular risk factors ( i.e. , arterial hypertension , diabetes , smoking history ) , and cardiovascular events ( i.e. , myocardial infarction , peripheral arterial disease , transient ischemic attack , and stroke ) .
eyes were assessed by a full ophthalmological examination with dilated pupils and judgement of automated perimetry ( octo 101 dg2 , interzeag , schlieren , switzerland ) , of spatial - temporal contrast sensitivity ( fdt , frequency doubling test , carl zeiss meditec ag , jena , germany ) , and nonmydriatic fundus images ( kowa , nonmyd - alpha 45 , japan ) . mri was performed on a 3 t high - field scanner ( magnetom tim trio , siemens , erlangen , germany ) with a gradient field strength up to 45  mt / m ( 72  mt / m effective ) .
the anatomical data were obtained in a t1-weighted 3d - mprage sequence ( tr = 900  ms , te = 3  ms , fov = 23  23  cm , acquisition matrix size = 512  256 reconstructed to 512  512 , reconstructed axial plans with 1.2  mm slice thickness ) . for detection of microangiopathy , a heavily t2-weighted fluid - attenuated inversion recovery ( flair ) sequence covering the whole brain was acquired ( tr = 10000  ms , te = 115  ms , matrix size = 512  512 ) .
dti was performed in the axial plane with 4  mm slice thickness and a 1  mm interslice separation using a single - shot , spin echo , echo planar imaging ( epi ) diffusion tensor sequence thus covering the whole visual pathway ( tr = 3400  ms , te = 93  ms , fov = 23  23  cm , acquisition matrix size = 128  128 reconstructed to 256  256 , number of signal averages = 7 , partial fourier acquisition = 60% ) .
diffusion weighting with a maximal b - factor of 1000  s / mm was carried out along 15 icosahedral directions complemented by one scan with b = 0 .
datasets were automatically corrected for imaging distortions and coregistered in reference to t1-weighted mprage images .
these and further calculations such as determining the independent elements of the diffusion tensor , deriving the corresponding eigenvalues and eigenvectors , were performed with a dedicated software package ( neuro 3d , siemens , erlangen , germany ) . the study was conducted in accordance with the declaration of helsinki on biomedical research involving human subjects . written informed consent
the images of 14 patients were tested for the reliability of the corrected optic radiation segmentation .
two observers postprocessed manually the automatically provided segmentation to exclude cerebral structures that are not a part of the optic radiation and the fractional anisotropy was calculated .
cronbach- at the 95% confidence interval for fa was 0.990 ( right optic radiation , f = 2.340 , p = 0.150 ) and 0.886 ( left optic radiation , f = 1.086 , p = 0.316 ) with df1 = 1 and df2 = 13 .
thus , the intraclass correlation coefficients of reliability of the semiautomated segmentation were within a very good range of reliability . compared to the optic radiation of a healthy volunteer the dti of a patient with primary open - angle glaucoma appears rarefied ( figures 1 and 2 ) .
the number of voxels in the optic radiation of the poag patient is on average a third smaller than in the control subject ( table 1 ) .
calculations of the number of voxels in the manually segmented optic radiation have confirmed the rarefied optic radiation in glaucoma patients .
the underlying pathophysiology of the glaucoma disease is based on a damage of the 3rd neuron with loss of function .
most studies examined primate models of experimentally induced glaucoma . it was reported that in unilateral experimental glaucoma in addition to the damage of retinal ganglion cells also the post - retinal magno- and parvocellular layers of the lgn of the thalamus   and the primary visual cortex may be impaired .
transneuronal degeneration was also found in a postmortem human study of the optic nerve , lgn , and visual cortex . in a primate model of glaucoma
the neuronal degeneration was shown to proceed from the lgn to the visual cortex [ 20 , 21 ] .
a loss of 5060% of the ganglion cells may be already present if visual field defects are detectable by perimetry .
it was also shown in experimental glaucoma that some of the 4th neurons in the lgn have died and surviving neurons were atrophic [ 35 ] . because impairment of the visual field is associated with optic nerve degeneration a certain probability for neurodegeneration of the 4th neuron of the visual pathway may be adopted and even was confirmed .
this case report demonstrates that the dti allows an in vivo visualization of the posterior part of the visual pathway .
this new technique in ophthalmology may be applicable for earlier diagnosis of glaucomatous changes and for noninvasive therapy monitoring in the future .
additionally , the impact for the different entities of optic nerve atrophy should be clearly validated prior to implementation into routine diagnostic .
 glaucomatous optic nerve atrophy may continue to the linked optic radiation by transneuronal degeneration , as described in animal models of glaucoma 
 . in vivo visualization of the visual pathway represents a new challenge in the field of ophthalmology . 
 we present a new approach for illustration of the optic radiation by diffusion tensor imaging ( dti ) based on magnetic resonance imaging ( mri ) . 
 the dti was established by use of a 3 t high - field scanner . 
 the case of a patient with primary open - angle glaucoma is opposed to this one of a healthy subject to demonstrate the visible rarefication of the optic radiation . 
 the goal was to introduce the technique of the dti also in ophthalmology and to demonstrate that it may be useful to judge glaucoma - related differences . 
1. Introduction
2. Materials and Methods
3. Results and Discussion
4. Conclusions