Kerstin Pannek

Traumatic brain injury, major depression, and diffusion tensor imaging: Making connections ☆

UNLABELLED It is common for depression to develop after traumatic brain injury (TBI), yet despite poorer recovery, there is a lack in our understanding of whether post-TBI brain changes involved in depression are akin to those in people with depression without TBI. Modern neuroimaging has helped recognize degrees of diffuse axonal injury (DAI) as being related to extent of TBI, but its ability to predict long-term functioning is limited and has not been considered in the context of post-TBI depression. A more recent brain imaging technique (diffusion tensor imaging; DTI) can measure the integrity of white matter by measuring the directionality or anisotropy of water molecule diffusion along the axons of nerve fibers. AIM To review DTI results in the TBI and depression literatures to determine whether this can elucidate the etiology of the development of depression after TBI. METHOD We reviewed the TBI/DTI (40 articles) and depression/DTI literatures (17 articles). No articles were found that used DTI to investigate depression post-TBI, although there were some common brain regions identified between the TBI/DTI and depression/DTI studies, including frontotemporal, corpus callosum, and structures contained within the basal ganglia. Specifically, the internal capsule was commonly reported to have significantly reduced fractional anisotropy, which agrees with deep brain stimulation studies. CONCLUSION It is suggested that measuring the degree of DAI by utilizing DTI in those with or without depression post-TBI, will greatly enhance prediction of functional outcome.

MRI Structural Connectivity, Disruption of Primary Sensorimotor Pathways, and Hand Function in Cerebral Palsy

Brain injury and subsequent plasticity of sensory and corticospinal pathways play an integral role in determining paretic hand function in congenital hemiplegia. There is limited knowledge regarding the relationship between the disruption of sensorimotor thalamic pathways projecting into the primary motor cortex and motor control. This study sought to investigate the relationship between the structural connectivity of motor networks that anatomically link the brain stem with the precentral and postcentral gyri with paretic motor sensory function by using an automated analysis strategy. Magnetic resonance imaging structural connectivity was measured by using high-angular-resolution diffusion imaging, probabilistic tractography, and the anatomic parcellation of high-resolution structural images in 16 children with congenital unilateral periventricular white-matter damage. Connectivity of the corticospinal and corticothalamic pathways was determined by using an asymmetry index based on the number of streamlines contained within these projections and compared with measures of paretic hand function and bimanual coordination. For cortical development, the volume of the ipsilesional precentral gyrus was significantly reduced. For connectivity measures, the numbers of streamlines in corticospinal tracts and corticothalamic pathways within the ipsilesional hemisphere were decreased compared with the contralesional side. The sensorimotor thalamic projections were more significantly correlated with paretic hand functions than were the corticospinal tracts. These data support the concept that preservation of sensorimotor thalamic pathways that directly project into the primary motor cortex has more influence on motor function control of the paretic hand than does preservation of corticospinal tracts.

Comparative mouse brain tractography of diffusion magnetic resonance imaging

Diffusion magnetic resonance imaging (dMRI) tractography can be employed to simultaneously analyze three-dimensional white matter tracts in the brain. Numerous methods have been proposed to model diffusion-weighted magnetic resonance data for tractography, and we have explored the functionality of some of these for studying white and grey matter pathways in ex vivo mouse brain. Using various deterministic and probabilistic algorithms across a range of regions of interest we found that probabilistic tractography provides a more robust means of visualizing both white and grey matter pathways than deterministic tractography. Importantly, we demonstrate the sensitivity of probabilistic tractography profiles to streamline number, step size, curvature, fiber orientation distribution threshold, and wholebrain versus region of interest seeding. Using anatomically well-defined corticothalamic pathways, we show how projection maps can permit the topographical assessment of probabilistic tractography. Finally, we show how different tractography approaches can impact on dMRI assessment of tract changes in a mouse deficient for the frontal cortex morphogen, fibroblast growth factor 17. In conclusion, probabilistic tractography can elucidate the phenotypes of mice with neurodegenerative or neurodevelopmental disorders in a quantitative manner.

Direct evidence of intra- and interhemispheric corticomotor network degeneration in amyotrophic lateral sclerosis: An automated MRI structural connectivity study

Although the pathogenesis of amyotrophic lateral sclerosis (ALS) is uncertain, there is mounting neuroimaging evidence to suggest a mechanism involving the degeneration of multiple white matter (WM) motor and extramotor neural networks. This insight has been achieved, in part, by using MRI Diffusion Tensor Imaging (DTI) and the voxelwise analysis of anisotropy indices, along with DTI tractography to determine which specific motor pathways are involved with ALS pathology. Automated MRI structural connectivity analyses, which probe WM connections linking various functionally discrete cortical regions, have the potential to provide novel information about degenerative processes within multiple white matter (WM) pathways. Our hypothesis is that measures of altered intra- and interhemispheric structural connectivity of the primary motor and somatosensory cortex will provide an improved assessment of corticomotor involvement in ALS. To test this hypothesis, we acquired High Angular Resolution Diffusion Imaging (HARDI) scans along with high resolution structural images (sMRI) on 15 patients with clinical evidence of upper and lower motor neuron involvement, and 20 matched control participants. Whole brain probabilistic tractography was applied to define specific WM pathways connecting discrete corticomotor targets generated from anatomical parcellation of sMRI of the brain. The integrity of these connections was interrogated by comparing the mean fractional anisotropy (FA) derived for each WM pathway. To assist in the interpretation of results, we measured the reproducibility of the FA summary measures over time (6months) in control participants. We also incorporated into our analysis pipeline the evaluation and replacement of outlier voxels due to head motion and physiological noise. When assessing corticomotor connectivity, we found a significant reduction in mean FA within a number of intra- and interhemispheric motor pathways in ALS patients. The abnormal intrahemispheric pathways include the corticospinal tracts involving the left and right precentral gyri (lh.preCG, rh.preCG) and brainstem (bs); right postcentral gyrus (rh.postCG) and bs; lh.preCG and left posterior cingulate gyrus (lh.PCG); rh.preCG and right posterior cingulate gyrus (rh.PCG); and the rh.preCG and right paracentral gyrus (rh.paraCG). The abnormal interhemispheric pathways included the lh.preCG and rh.preCG; lh.preCG and rh.paraCG; lh.preCG and right superior frontal gyrus (rh.supFG); lh.preCG and rh.postCG; rh.preCG and left paracentral gyrus (lh.paraCG); rh.preCG and left superior frontal gyrus (lh.supFG); and the rh.preCG and left caudal middle frontal gyrus (lh.caudMF). The reproducibility of the measurement of these pathways was high (variation less than 5%). Maps of the outlier rejection voxels, revealed clusters within the corpus callosum and corticospinal projections. This finding highlights the importance of correcting for motion artefacts and physiological noise when studying clinical populations. Our novel findings, many of which are consistent with known pathology, show extensive involvement and degeneration of multiple corticomotor pathways in patients with upper and lower motor neuron signs and provide support for the use of automated structural connectivity techniques for studying neurodegenerative disease processes.

Distinguishing Recurrent Primary Brain Tumor from Radiation Injury: A Preliminary Study Using a Susceptibility-Weighted MR Imaging−Guided Apparent Diffusion Coefficient Analysis Strategy

BACKGROUND AND PURPOSE: The accurate delineation of tumor recurrence presents a significant problem in neuro-oncology. Our aim was to improve the identification of brain tumor recurrence from chemoradiation injury by using CE-SWI, a technique that provides improved visualization of the heterogeneous patterns of brain tumor pathology, to guide the analysis of ADC measures within the peritumoral territory. MATERIALS AND METHODS: Seventeen patients who were being treated for high-grade glial neoplasms took part in the study. All patients presented with new enhancing lesions on follow-up CE-T1. Recurrence or chemoradiation injury was confirmed from either histologic analysis or extensive clinical follow-up. Regions of enhancement on registered CE-SWI and CE-T1 images were extracted in a semiautomated fashion and transferred to coregistered ADC maps. Significant differences in ADC measures defined within the enhancement volumes on serial MR images were analyzed by using a nonparametric Kolmogorov-Smirnov approach and correlated with clinical follow-up diagnoses. RESULTS: Analysis of the serial data revealed that patients with a diagnosis of tumor recurrence had significantly reduced ADC measures within the enhancement volume delineated on CE-SWI. In contrast, patients with SD had significantly elevated ADC within the CE-SWI enhancement volume. CONCLUSIONS: The findings of an increase in enhancement volume delineated on serial CE-SWI maps, along with a concomitant reduction in ADC within this volume for patients with recurrent tumor, provide support for such an approach to be used to assist in follow-up patient management strategies.

The average pathlength map: A diffusion MRI tractography-derived index for studying brain pathology

Magnetic resonance diffusion tractography provides a powerful tool for the assessment of white matter architecture in vivo. Quantitative tractography metrics, such as streamline length, have successfully been used in the study of brain pathology. To date, these studies have relied on a priori knowledge of which tracts are affected by injury or pathology and manual delineation of regions of interest (ROIs) for use as waypoints in tractography. This limits the analyses to specific tracts under investigation and relies on the accurate and consistent placement of ROIs. We present a fully automated technique for the voxel-wise analysis of streamline length within the entire brain, the Average Pathlength Map (APM). We highlight the precision and reproducibility of voxel-wise average streamline length over time, and assess normal variability of pathlength values in a cohort of 43 healthy participants. Additionally, we demonstrate the utility of this approach by performing voxel-wise comparison between pathlength values obtained from a patient with a severe traumatic brain injury (TBI, Glasgow Coma Scale Score=7) and those from control participants. Our analysis shows that voxel-wise average pathlength values are comparable to fractional anisotropy (FA) in terms of reproducibility and variability. For the TBI patient, we observed a significant reduction in streamline pathlength in the genu of the corpus callosum and its projections into the frontal lobe. This study demonstrates that the average pathlength map can be used for voxel-based analysis of a quantitative tractography metric within the whole brain, removing both the dependence on a priori knowledge of affected pathways and time-consuming manual delineation of ROIs.

An automated strategy for the delineation and parcellation of commissural pathways suitable for clinical populations utilising high angular resolution diffusion imaging tractography

There is a growing interest in understanding alterations to the interhemispheric transfer of information as a result of brain injury and neurological disease. To facilitate research, we have developed a fully automated method for the accurate extraction of commissural pathways (corpus callosum (CC) and anterior commissure (AC)) and functional parcellation of the CC using a high angular resolution diffusion imaging (HARDI) based probabilistic tractography approach that is applicable to clinical populations. The CC was divided into 33 functional divisions based on its connections to cortical parcellations derived from individual structural images in 8 healthy participants. Probabilistic CC population maps acquired at two different b-values (1000 s mm(-2) and 3000 s mm(-2)) are presented. Topography of the CC was consistent with histology reports. We show that HARDI data acquired at a higher b-value reveals more callosal-temporal connections than low b-value data. With respect to intra-subject precision, data acquired using a higher b-value show superior reproducibility of the delineated CC area on the midsagittal plane (MSP), as well as the total number of callosal streamlines and the number of clustered callosal streamlines. The AC was delineated in all 8 participants using high b-value HARDI tractography. Cortical projections of the AC were analysed and are in agreement with known anatomy. We conclude that, while data acquired at a lower b-value may be used, this is associated with a loss in quality, both in the delineation of commissural pathways and, potentially, the reproducibility of results over time.

Diffusion MRI of the neonate brain: acquisition, processing and analysis techniques

Diffusion MRI (dMRI) is a popular noninvasive imaging modality for the investigation of the neonate brain. It enables the assessment of white matter integrity, and is particularly suited for studying white matter maturation in the preterm and term neonate brain. Diffusion tractography allows the delineation of white matter pathways and assessment of connectivity in vivo. In this review, we address the challenges of performing and analysing neonate dMRI. Of particular importance in dMRI analysis is adequate data preprocessing to reduce image distortions inherent to the acquisition technique, as well as artefacts caused by head movement. We present a summary of techniques that should be used in the preprocessing of neonate dMRI data, and demonstrate the effect of these important correction steps. Furthermore, we give an overview of available analysis techniques, ranging from voxel-based analysis of anisotropy metrics including tract-based spatial statistics (TBSS) to recently developed methods of statistical analysis addressing issues of resolving complex white matter architecture. We highlight the importance of resolving crossing fibres for tractography and outline several tractography-based techniques, including connectivity-based segmentation, the connectome and tractography mapping. These techniques provide powerful tools for the investigation of brain development and maturation.

HOMOR: higher order model outlier rejection for high b-value MR diffusion data.

Diffusion MR images are prone to artefacts caused by head movement and cardiac pulsation. Previous techniques for the automated voxel-wise detection of signal intensity outliers have relied on the fit of the diffusion tensor to the data (RESTORE). However, the diffusion tensor cannot appropriately model more than a single fibre population, which may lead to inaccuracies when identifying outlier voxels in crossing fibre regions, particularly when high b-values are used to obtain increased angular contrast. HOMOR (higher order model outlier rejection) was developed to overcome this limitation and is introduced in this study. HOMOR is closely related to RESTORE, but employs a higher order model capable of resolving multiple fibre populations within a voxel. Using high b-value (b=3000 s/mm2) diffusion data from a population of 90 healthy participants, as well as simulations, HOMOR was found to identify a decreased number of outlier voxels compared to RESTORE primarily within areas of crossing, bending and fanning fibres. At lower b-values, however, RESTORE and HOMOR give similar results, which is demonstrated using diffusion data acquired at b=1000 s/mm2 in a mixed cohort. This study demonstrates that, although RESTORE is suitable for low b-value data, HOMOR is better suited for high b-value data.

Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions

Background Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. Aim The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Methods Data of 50 children with unilateral CP caused by periventricular white matter lesions (5–17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7–16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm2) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment—AHA) was assessed in connections that showed significant differences in FA compared to CTD. Results FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r2 = 0.16–0.44; p < 0.05). Conclusion This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention.