The Relevance of Short-Range Fibers to Cognitive Efficiency and Brain Activation in Aging and Dementia

The integrity of structural connectivity in a functional brain network supports the efficiency of neural processing within relevant brain regions. This study aimed to quantitatively investigate the short- and long-range fibers, and their differential roles in the lower cognitive efficiency in aging and dementia. Three groups of healthy young, healthy older adults and patients with Alzheimer''s disease (AD) participated in this combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) study on prospective memory (PM). Short- and long-range fiber tracts within the PM task engaged brain networks were generated. The correlation between the fMRI signal change, PM performance and the DTI characters were calculated. FMRI results showed that the PM-specific frontal activations in three groups were distributed hierarchically along the rostrocaudal axis in the frontal lobe. In an overall PM condition generally activated brain network among the three groups, tractography was used to generate the short-range fibers, and they were found impaired in both healthy older adults and AD patients. However, the long-range fiber tracts were only impaired in AD. Additionally, the mean diffusivity (MD) of short-range but not long-range fibers was positively correlated with fMRI signal change and negatively correlated with the efficiency of PM performance. This study suggests that the disintegrity of short-range fibers may contribute more to the lower cognitive efficiency and higher compensatory brain activation in healthy older adults and more in AD patients.     

Optimization of in vivo high-resolution DTI of non-human primates on a 3T human scanner

Magnetic resonance (MR) diffusion tensor imaging (DTI) has emerged as a unique technique to reveal small anatomical structures of brain by characterizing the diffusion process of water molecules within an image voxel. Combined with fiber tractography techniques, DTI can be further used to reveal white matter fibers and connectivity in the brain non-invasively. The non-human primate brain study provides important supplemental means for human brain exploration since the two species share close anatomical and functional similarities. There is therefore increasing interest in in vivo non-human primate DTI studies. However, several technical challenges need to be addressed to perform non-human primate brain DTI and fiber tractography. We have established an imaging protocol together with a post-acquisition procedure for high-resolution in vivo non-human primate DTI studies using a 3T human clinical scanner. Data acquired with this procedure is appropriate for accurate diffusion tensor quantification and fiber tractography, and is accessible within an acceptable scan time. We investigated in detail the effects of spatial resolution and SNR on diffusion tensor-derived quantities and fiber tractography. Our results should be of general utility for implementation of in vivo non-human primate DTI studies.     

Advanced diffusion MRI fiber tracking in neurosurgical and neurodegenerative disorders and neuroanatomical studies: A review

Diffusion MRI enabled in vivo microstructural imaging of the fiber tracts in the brain resulting in its application in a wide range of settings, including in neurological and neurosurgical disorders. Conventional approaches such as diffusion tensor imaging (DTI) have been shown to have limited applications due to the crossing fiber problem and the susceptibility of their quantitative indices to partial volume effects. To overcome these limitations, the recent focus has shifted to the advanced acquisition methods and their related analytical approaches. Advanced white matter imaging techniques provide superior qualitative data in terms of demonstration of multiple crossing fibers in their spatial orientation in a three dimensional manner in the brain. In this review paper, we discuss the advancements in diffusion MRI and introduce their roles. Using examples, we demonstrate the role of advanced diffusion MRI-based fiber tracking in neuroanatomical studies. Results from its preliminary application in the evaluation of intracranial space occupying lesions, including with respect to future directions for prognostication, are also presented. Building upon the previous DTI studies assessing white matter disease in Huntington's disease and Amyotrophic lateral sclerosis; we also discuss approaches which have led to encouraging preliminary results towards developing an imaging biomarker for these conditions.     

Estimating the Confidence Level of White Matter Connections Obtained with MRI Tractography

Background

Since the emergence of diffusion tensor imaging, a lot of work has been done to better understand the properties of diffusion MRI tractography. However, the validation of the reconstructed fiber connections remains problematic in many respects. For example, it is difficult to assess whether a connection is the result of the diffusion coherence contrast itself or the simple result of other uncontrolled parameters like for example: noise, brain geometry and algorithmic characteristics.

Methodology/Principal Findings

In this work, we propose a method to estimate the respective contributions of diffusion coherence versus other effects to a tractography result by comparing data sets with and without diffusion coherence contrast. We use this methodology to assign a confidence level to every gray matter to gray matter connection and add this new information directly in the connectivity matrix.

Conclusions/Significance

Our results demonstrate that whereas we can have a strong confidence in mid- and long-range connections obtained by a tractography experiment, it is difficult to distinguish between short connections traced due to diffusion coherence contrast from those produced by chance due to the other uncontrolled factors of the tractography methodology.     

Improved sensitivity to cerebral white matter abnormalities in Alzheimer's disease with spherical deconvolution based tractography

Diffusion tensor imaging (DTI) based fiber tractography (FT) is the most popular approach for investigating white matter tracts in vivo, despite its inability to reconstruct fiber pathways in regions with "crossing fibers." Recently, constrained spherical deconvolution (CSD) has been developed to mitigate the adverse effects of "crossing fibers" on DTI based FT. Notwithstanding the methodological benefit, the clinical relevance of CSD based FT for the assessment of white matter abnormalities remains unclear. In this work, we evaluated the applicability of a hybrid framework, in which CSD based FT is combined with conventional DTI metrics to assess white matter abnormalities in 25 patients with early Alzheimer's disease. Both CSD and DTI based FT were used to reconstruct two white matter tracts: one with regions of "crossing fibers," i.e., the superior longitudinal fasciculus (SLF) and one which contains only one fiber orientation, i.e. the midsagittal section of the corpus callosum (CC). The DTI metrics, fractional anisotropy (FA) and mean diffusivity (MD), obtained from these tracts were related to memory function. Our results show that in the tract with "crossing fibers" the relation between FA/MD and memory was stronger with CSD than with DTI based FT. By contrast, in the fiber bundle where one fiber population predominates, the relation between FA/MD and memory was comparable between both tractography methods. Importantly, these associations were most pronounced after adjustment for the planar diffusion coefficient, a measure reflecting the degree of fiber organization complexity. These findings indicate that compared to conventionally applied DTI based FT, CSD based FT combined with DTI metrics can increase the sensitivity to detect functionally significant white matter abnormalities in tracts with complex white matter architecture.     

Sparse Solution of Fiber Orientation Distribution Function by Diffusion Decomposition

Fiber orientation is the key information in diffusion tractography. Several deconvolution methods have been proposed to obtain fiber orientations by estimating a fiber orientation distribution function (ODF). However, the L ₂ regularization used in deconvolution often leads to false fibers that compromise the specificity of the results. To address this problem, we propose a method called diffusion decomposition, which obtains a sparse solution of fiber ODF by decomposing the diffusion ODF obtained from q-ball imaging (QBI), diffusion spectrum imaging (DSI), or generalized q-sampling imaging (GQI). A simulation study, a phantom study, and an in-vivo study were conducted to examine the performance of diffusion decomposition. The simulation study showed that diffusion decomposition was more accurate than both constrained spherical deconvolution and ball-and-sticks model. The phantom study showed that the angular error of diffusion decomposition was significantly lower than those of constrained spherical deconvolution at 30° crossing and ball-and-sticks model at 60° crossing. The in-vivo study showed that diffusion decomposition can be applied to QBI, DSI, or GQI, and the resolved fiber orientations were consistent regardless of the diffusion sampling schemes and diffusion reconstruction methods. The performance of diffusion decomposition was further demonstrated by resolving crossing fibers on a 30-direction QBI dataset and a 40-direction DSI dataset. In conclusion, diffusion decomposition can improve angular resolution and resolve crossing fibers in datasets with low SNR and substantially reduced number of diffusion encoding directions. These advantages may be valuable for human connectome studies and clinical research.     

Multi-Shell Hybrid Diffusion Imaging (HYDI) at 7 Tesla in TgF344-AD Transgenic Alzheimer Rats

Diffusion weighted imaging (DWI) is widely used to study microstructural characteristics of the brain. Diffusion tensor imaging (DTI) and high-angular resolution imaging (HARDI) are frequently used in radiology and neuroscience research but can be limited in describing the signal behavior in composite nerve fiber structures. Here, we developed and assessed the benefit of a comprehensive diffusion encoding scheme, known as hybrid diffusion imaging (HYDI), composed of 300 DWI volumes acquired at 7-Tesla with diffusion weightings at b = 1000, 3000, 4000, 8000 and 12000 s/mm² and applied it in transgenic Alzheimer rats (line TgF344-AD) that model the full clinico-pathological spectrum of the human disease. We studied and visualized the effects of the multiple concentric “shells” when computing three distinct anisotropy maps–fractional anisotropy (FA), generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA). We tested the added value of the multi-shell q-space sampling scheme, when reconstructing neural pathways using mathematical frameworks from DTI and q-ball imaging (QBI). We show a range of properties of HYDI, including lower apparent anisotropy when using high b-value shells in DTI-based reconstructions, and increases in apparent anisotropy in QBI-based reconstructions. Regardless of the reconstruction scheme, HYDI improves FA-, GFA- and NQA-aided tractography. HYDI may be valuable in human connectome projects and clinical research, as well as magnetic resonance research in experimental animals.     

Optic Radiation Fiber Tractography in Glioma Patients Based on High Angular Resolution Diffusion Imaging with Compressed Sensing Compared with Diffusion Tensor Imaging - Initial Experience

Objective

Up to now, fiber tractography in the clinical routine is mostly based on diffusion tensor imaging (DTI). However, there are known drawbacks in the resolution of crossing or kissing fibers and in the vicinity of a tumor or edema. These restrictions can be overcome by tractography based on High Angular Resolution Diffusion Imaging (HARDI) which in turn requires larger numbers of gradients resulting in longer acquisition times. Using compressed sensing (CS) techniques, HARDI signals can be obtained by using less non-collinear diffusion gradients, thus enabling the use of HARDI-based fiber tractography in the clinical routine.

Methods

Eight patients with gliomas in the temporal lobe, in proximity to the optic radiation (OR), underwent 3T MRI including a diffusion-weighted dataset with 30 gradient directions. Fiber tractography of the OR using a deterministic streamline algorithm based on DTI was compared to tractography based on reconstructed diffusion signals using HARDI+CS.

Results

HARDI+CS based tractography displayed the OR more conclusively compared to the DTI-based results in all eight cases. In particular, the potential of HARDI+CS-based tractography was observed for cases of high grade gliomas with significant peritumoral edema, larger tumor size or closer proximity of tumor and reconstructed fiber tract.

Conclusions

Overcoming the problem of long acquisition times, HARDI+CS seems to be a promising basis for fiber tractography of the OR in regions of disturbed diffusion, areas of high interest in glioma surgery.     

Increased Global and Local Efficiency of Human Brain Anatomical Networks Detected with FLAIR-DTI Compared to Non-FLAIR-DTI

Diffusion-weighted MRI (DW-MRI), the only non-invasive technique for probing human brain white matter structures in vivo, has been widely used in both fundamental studies and clinical applications. Many studies have utilized diffusion tensor imaging (DTI) and tractography approaches to explore the topological properties of human brain anatomical networks by using the single tensor model, the basic model to quantify DTI indices and tractography. However, the conventional DTI technique does not take into account contamination by the cerebrospinal fluid (CSF), which has been known to affect the estimated DTI measures and tractography in the single tensor model. Previous studies have shown that the Fluid-Attenuated Inversion Recovery (FLAIR) technique can suppress the contribution of the CSF to the DW-MRI signal. We acquired DTI datasets from twenty-two subjects using both FLAIR-DTI and conventional DTI (non-FLAIR-DTI) techniques, constructed brain anatomical networks using deterministic tractography, and compared the topological properties of the anatomical networks derived from the two types of DTI techniques. Although the brain anatomical networks derived from both types of DTI datasets showed small-world properties, we found that the brain anatomical networks derived from the FLAIR-DTI showed significantly increased global and local network efficiency compared with those derived from the conventional DTI. The increases in the network regional topological properties derived from the FLAIR-DTI technique were observed in CSF-filled regions, including the postcentral gyrus, periventricular regions, inferior frontal and temporal gyri, and regions in the visual cortex. Because brain anatomical networks derived from conventional DTI datasets with tractography have been widely used in many studies, our findings may have important implications for studying human brain anatomical networks derived from DW-MRI data and tractography.     

Resolving the three-dimensional myoarchitecture of bovine esophageal wall with diffusion spectrum imaging and tractography

In order to determine the three-dimensional (3D) resolved muscular anatomy of the mammalian esophagus, we have examined its myoarchitecture with diffusion spectrum magnetic resonance imaging (DSI) and tractography. DSI measures diffusion displacement as a function of magnetic gradients of varied direction and intensity and displays the displacement profile as a 3D contour per voxel. In tractography, the orientation vectors of maximum diffusion/voxel are identified, and intervoxel associations are constructed by a streamline algorithm based on angular similarity in order to generate mesoscale myofiber tracts. We demonstrate that the proximal body of the esophagus consists of helically aligned crossing fiber populations that overlap between layers in the form of a “zipper” region along the length of the tissue. With increasingly distal position along the length of the tissue, helix angle and skeletal muscle prevalence are reduced such that fibers align themselves in the most distal location into distinct inner circular and outer longitudinal smooth muscle layers. We conclude that esophageal myoanatomy consists of crossing myofibers exhibiting a decreasing degree of helicity as a function of axial position and propose that this unique geometric construct provides a mechanism to resist distension and promote aboral flow. This work was supported by the National Institutes of Health (grants RO1-DC05604 to Richard J. Gilbert and RO1- MH64044 to Van J. Wedeen.     

Bayesian regularization of diffusion tensor images

Diffusion tensor imaging (DTI) is a powerful tool in the study of the course of nerve fiber bundles in the human brain. Using DTI, the local fiber orientation in each image voxel can be described by a diffusion tensor which is constructed from local measurements of diffusion coefficients along several directions. The measured diffusion coefficients and thereby the diffusion tensors are subject to noise, leading to possibly flawed representations of the 3-dimensional (3D) fiber bundles. In this paper, we develop a Bayesian procedure for regularizing the diffusion tensor field, fully utilizing the available 3D information of fiber orientation. The use of the procedure is exemplified on synthetic and in vivo data.     

Associating the mesoscale fiber organization of the tongue with local strain rate during swallowing

The tongue is an intricately configured muscular organ that undergoes a stereotypical set of deformations during the course of normal human swallowing. In order to demonstrate quantitatively the relationship between 3D aligned lingual fiber organization and mechanics during swallowing, the tissue's myoarchitecture and strain rate were imaged before and during the propulsive phase of a 3.0ml water bolus swallow. Mesoscale fiber organization was imaged with high-resolution diffusion tensor imaging (DTI) and multi-voxel myofiber tracts generated along maximum diffusion vectors. Tissue compression/expansion was obtained via lingual pressure-gated phase-contrast (PC) MRI, a method which determines local strain rate as a function of the phase shift occurring along an applied gradient vector. The co-alignment of myofiber tract direction and the localized principal strain rate vectors was obtained by translating the strain rate tensor into the reference frame with the primary axis parallel to the maximum diffusion vector using Mohr's circle, resulting in the generation of fiber-aligned strain rate (FASR). DTI tractography displayed the complete fiber anatomy of the tongue, consisting of a core region of orthogonally aligned fibers encased within a longitudinal sheath, which merge with the externally connected styloglossus, hyoglossus, and genioglossus fibers. FASR images obtained in the mid-sagittal plane demonstrated that bolus propulsion was associated with prominent compressive strain aligned with the genioglossus muscle combined with expansive strain aligned with the verticalis and geniohyoid muscles. These data demonstrate that lingual deformation during swallowing involves complex interactions involving intrinsic and extrinsic muscles, whose contractility is directed by the alignment of mesoscale fiber tracts.     

Diffusion MRI of complex neural architecture

While functional brain imaging methods can locate the cortical regions subserving particular cognitive functions, the connectivity between the functional areas of the human brain remains poorly understood. Recently, investigators have proposed a method to image neural connectivity noninvasively using a magnetic resonance imaging method called diffusion tensor imaging (DTI). DTI measures the molecular diffusion of water along neural pathways. Accurate reconstruction of neural connectivity patterns from DTI has been hindered, however, by the inability of DTI to resolve more than a single axon direction within each imaging voxel. Here, we present a novel magnetic resonance imaging technique that can resolve multiple axon directions within a single voxel. The technique, called q-ball imaging, can resolve intravoxel white matter fiber crossing as well as white matter insertions into cortex. The ability of q-ball imaging to resolve complex intravoxel fiber architecture eliminates a key obstacle to mapping neural connectivity in the human brain noninvasively.     

Dynamic Responses of Selective Brain White Matter Fiber Tracts to Binge Alcohol and Recovery in the Rat

To determine the dynamics of white matter vulnerability to excessive alcohol consumption, diffusion tensor imaging (DTI) was used in an animal model of alcohol exposure. Quantitative, in vivo fiber tracking results are presented from rats with DTI conducted at 3 time points: baseline; after 4 days of intragastric alcohol to blood alcohol levels of ~250mg/dL; and after one week of recovery. Binge alcohol followed by a week of sobriety resulted in rapidly reversible decreases in fractional anisotropy (FA), a measure of the coherence of fiber tracts, in callosal genu and fimbria-fornix but not splenium; and increases in mean diffusivity (MD), an index of freely diffusing water in tissue, selective to the fimbria-fornix. These effects were confirmed with tract-based spatial statistics (TBSS). The directionality of changes in DTI metrics reproduce those observed in human alcoholism. That a single exposure to binge alcohol can cause substantial transient changes detectable in DTI metrics demonstrates the potential for rapid neuroplasticity.     

Improving DTI Tractography by including Diagonal Tract Propagation

Tractography algorithms have been developed to reconstruct likely WM pathways in the brain from diffusion tensor imaging (DTI) data. In this study, an elegant and simple means for improving existing tractography algorithms is proposed by allowing tracts to propagate through diagonal trajectories between voxels, instead of only rectilinearly to their facewise neighbors. A series of tests (using both real and simulated data sets) are utilized to show several benefits of this new approach. First, the inclusion of diagonal tract propagation decreases the dependence of an algorithm on the arbitrary orientation of coordinate axes and therefore reduces numerical errors associated with that bias (which are also demonstrated here). Moreover, both quantitatively and qualitatively, including diagonals decreases overall noise sensitivity of results and leads to significantly greater efficiency in scanning protocols; that is, the obtained tracts converge much more quickly (i.e., in a smaller amount of scanning time) to those of data sets with high SNR and spatial resolution. Importantly, the inclusion of diagonal propagation adds essentially no appreciable time of calculation or computational costs to standard methods. This study focuses on the widely-used streamline tracking method, FACT (fiber assessment by continuous tracking), and the modified method is termed "FACTID" (FACT including diagonals).     

Microstructural White Matter Changes Underlying Cognitive and Behavioural Impairment in ALS – An In Vivo Study Using DTI

Background

A relevant fraction of patients with amyotrophic lateral sclerosis (ALS) exhibit a fronto-temporal pattern of cognitive and behavioural disturbances with pronounced deficits in executive functioning and cognitive control of behaviour. Structural imaging shows a decline in fronto-temporal brain areas, but most brain imaging studies did not evaluate cognitive status. We investigated microstructural white matter changes underlying cognitive impairment using diffusion tensor imaging (DTI) in a large cohort of ALS patients.

Methods

We assessed 72 non-demented ALS patients and 65 matched healthy control subjects using a comprehensive neuropsychological test battery and DTI. We compared DTI measures of fiber tract integrity using tract-based spatial statistics among ALS patients with and without cognitive impairment and healthy controls. Neuropsychological performance and behavioural measures were correlated with DTI measures.

Results

Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts, including the corticospinal tract and the body of corpus callosum. Those with impairments (ca. 30%) additionally presented significant white matter alterations in extra-motor regions, particularly the frontal lobe. Executive and memory performance and behavioural measures were correlated with fiber tract integrity in large association tracts.

Conclusion

In non-demented cognitively impaired ALS patients, white matter changes measured by DTI are related to disturbances of executive and memory functions, including prefrontal and temporal regions. In a group comparison, DTI is able to observe differences between cognitively unimpaired and impaired ALS patients.     

The cerebro-morphological fingerprint of a progeroid syndrome: white matter changes correlate with neurological symptoms in xeroderma pigmentosum

Background

Xeroderma pigmentosum (XP) is a rare autosomal recessive progeroid syndrome. It has recently been shown that the underlying DNA repair defect plays a central role in the aging process. In addition to skin symptoms, various premature neurological abnormalities have been reported.

Methodology/Principal Findings

We present the clinical neurological phenotype in 14 XP patients (seven subtypes), in seven of these patients together with conventional and multiparametric advanced MRI data to assess the macrostructural and microstructural cerebral morphology in comparison to controls, including volumetric measurements, MR spectroscopy (¹H MRS), and diffusion tensor imaging (DTI). Clinical hallmarks were spinocerebellar ataxia, pyramidal tract signs, and mild cognitive deficits. DTI demonstrated significantly reduced WM directionality in all regions investigated, i.e. the thalamus, the corticospinal tracts and the dorsal corpus callosum. Single patients showed a marked relative hippocampal volume reduction, but the patients were not different from controls in the volumetric measurements of hippocampal and whole brain volumes at group level. However, ¹H MRS demonstrated that the hippocampal formation was metabolically altered.

Conclusions

The most prominent feature was the white matter affectation, as assessed by DTI, with volume and directionality reductions of the fiber projections involving both the craniocaudal fibers and the interhemispheric connections. These findings, although heterogeneous among the study sample, could be correlated with the clinico-neurological symptoms. The imaging findings support the position that myelin structures degrade prematurely in the brain of XP patients.     

Autism and Sensory Processing Disorders: Shared White Matter Disruption in Sensory Pathways but Divergent Connectivity in Social-Emotional Pathways

Over 90% of children with Autism Spectrum Disorders (ASD) demonstrate atypical sensory behaviors. In fact, hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment is now included in the DSM-5 diagnostic criteria. However, there are children with sensory processing differences who do not meet an ASD diagnosis but do show atypical sensory behaviors to the same or greater degree as ASD children. We previously demonstrated that children with Sensory Processing Disorders (SPD) have impaired white matter microstructure, and that this white matter microstructural pathology correlates with atypical sensory behavior. In this study, we use diffusion tensor imaging (DTI) fiber tractography to evaluate the structural connectivity of specific white matter tracts in boys with ASD (n = 15) and boys with SPD (n = 16), relative to typically developing children (n = 23). We define white matter tracts using probabilistic streamline tractography and assess the strength of tract connectivity using mean fractional anisotropy. Both the SPD and ASD cohorts demonstrate decreased connectivity relative to controls in parieto-occipital tracts involved in sensory perception and multisensory integration. However, the ASD group alone shows impaired connectivity, relative to controls, in temporal tracts thought to subserve social-emotional processing. In addition to these group difference analyses, we take a dimensional approach to assessing the relationship between white matter connectivity and participant function. These correlational analyses reveal significant associations of white matter connectivity with auditory processing, working memory, social skills, and inattention across our three study groups. These findings help elucidate the roles of specific neural circuits in neurodevelopmental disorders, and begin to explore the dimensional relationship between critical cognitive functions and structural connectivity across affected and unaffected children.     

DTI of the Visual Pathway - White Matter Tracts and Cerebral Lesions

DTI is a technique that identifies white matter tracts (WMT) non-invasively in healthy and non-healthy patients using diffusion measurements. Similar to visual pathways (VP), WMT are not visible with classical MRI or intra-operatively with microscope. DTI will help neurosurgeons to prevent destruction of the VP while removing lesions adjacent to this WMT. We have performed DTI on fifty patients before and after surgery between March 2012 to January 2014. To navigate we used a 3DT1-weighted sequence. Additionally, we performed a T2-weighted and DTI-sequences. The parameters used were, FOV: 200 x 200 mm, slice thickness: 2 mm, and acquisition matrix: 96 x 96 yielding nearly isotropic voxels of 2 x 2 x 2 mm. Axial MRI was carried out using a 32 gradient direction and one b0-image. We used Echo-Planar-Imaging (EPI) and ASSET parallel imaging with an acceleration factor of 2 and b-value of 800 s/mm². The scanning time was less than 9 min.The DTI-data obtained were processed using a FDA approved surgical navigation system program which uses a straightforward fiber-tracking approach known as fiber assignment by continuous tracking (FACT). This is based on the propagation of lines between regions of interest (ROI) which is defined by a physician. A maximum angle of 50, FA start value of 0.10 and ADC stop value of 0.20 mm²/s were the parameters used for tractography.There are some limitations to this technique. The limited acquisition time frame enforces trade-offs in the image quality. Another important point not to be neglected is the brain shift during surgery. As for the latter intra-operative MRI might be helpful. Furthermore the risk of false positive or false negative tracts needs to be taken into account which might compromise the final results.