Flavio Dell'Acqua

Atlasing location, asymmetry and inter-subject variability of white matter tracts in the human brain with MR diffusion tractography

The purpose of this study is to create a white matter atlas of the human brain using diffusion tensor imaging (DTI) tractography and to describe the constant and variable features of the major pathways. DTI was acquired from 40 healthy right-handed adults and reconstructed tracts mapped within a common reference space (MNI). Group effect maps of each tract defined constant anatomical features while overlap maps were generated to study inter-subject variability and to compare DTI derived anatomy with a histological atlas. Two patients were studied to assess the localizing validity of the atlas. The DTI-derived maps are overall consistent with a previously published histological atlas. A statistically significant leftward asymmetry was found for the volume and number of streamlines of the cortico-spinal tract and the direct connections between Brocas and Wernickes territories (long segment). A statistically significant rightward asymmetry was found for the inferior fronto-occipital fasciculus and the fronto-parietal connections (anterior segment) of the arcuate fasciculus. Furthermore, males showed a left lateralization of the fronto-temporal segment of the arcuate fasciculus (long segment), while females had a more bilateral distribution. In two patients with brain lesions, DTI was acquired and tractography used to show that the tracts affected by the lesions were correctly identified by the atlas. This study suggests that DTI-derived maps can be used together with a previous histological atlas to establish the relationship of focal lesions with nearby tracts and improve clinico-anatomical correlation.

A modified damped Richardson-Lucy algorithm to reduce isotropic background effects in spherical deconvolution

Spherical deconvolution methods have been applied to diffusion MRI to improve diffusion tensor tractography results in brain regions with multiple fibre crossing. Recent developments, such as the introduction of non-negative constraints on the solution, allow a more accurate estimation of fibre orientations by reducing instability effects due to noise robustness. Standard convolution methods do not, however, adequately model the effects of partial volume from isotropic tissue, such as gray matter, or cerebrospinal fluid, which may degrade spherical deconvolution results. Here we use a newly developed spherical deconvolution algorithm based on an adaptive regularization (damped version of the Richardson-Lucy algorithm) to reduce isotropic partial volume effects. Results from both simulated and in vivo datasets show that, compared to a standard non-negative constrained algorithm, the damped Richardson-Lucy algorithm reduces spurious fibre orientations and preserves angular resolution of the main fibre orientations. These findings suggest that, in some brain regions, non-negative constraints alone may not be sufficient to reduce spurious fibre orientations. Considering both the speed of processing and the scan time required, this new method has the potential for better characterizing white matter anatomy and the integrity of pathological tissue.

Can spherical deconvolution provide more information than fiber orientations? Hindrance modulated orientational anisotropy, a true-tract specific index to characterize white matter diffusion

Diffusion tensor imaging (DTI) methods are widely used to reconstruct white matter trajectories and to quantify tissue changes using the average diffusion properties of each brain voxel. Spherical deconvolution (SD) methods have been developed to overcome the limitations of the diffusion tensor model in resolving crossing fibers and to improve tractography reconstructions. However, the use of SD methods to obtain quantitative indices of white matter integrity has not been extensively explored. In this study, we show that the hindrance modulated orientational anisotropy (HMOA) index, defined as the absolute amplitude of each lobe of the fiber orientation distribution, can be used as a compact measure to characterize the diffusion properties along each fiber orientation in white matter regions with complex organization. We demonstrate that the HMOA is highly sensitive to changes in fiber diffusivity (e.g., myelination processes or axonal loss) and to differences in the microstructural organization of white matter like axonal diameter and fiber dispersion. Using simulations to describe diffusivity changes observed in normal brain development and disorders, we observed that the HMOA is able to identify white matter changes that are not detectable with conventional DTI indices. We also show that the HMOA index can be used as an effective threshold for in vivo data to improve tractography reconstructions and to better map white matter complexity inside the brain. In conclusion, the HMOA represents a true tract‐specific and sensitive index and provides a compact characterization of white matter diffusion properties with potential for widespread application in normal and clinical populations. Hum Brain Mapp 34:2464–2483, 2013.

The anatomy of extended limbic pathways in Asperger syndrome: a preliminary diffusion tensor imaging tractography study

It has been suggested that people with autistic spectrum disorder (ASD) have altered development (and connectivity) of limbic circuits. However, direct evidence of anatomical differences specific to white matter pathways underlying social behaviour and emotions in ASD is lacking. We used Diffusion Tensor Imaging Tractography to compare, in vivo, the microstructural integrity and age-related differences in the extended limbic pathways between subjects with Asperger syndrome and healthy controls. Twenty-four males with Asperger syndrome (mean age 23+/-12 years, age range: 9-54 years) and 42 age-matched male controls (mean age 25+/-10 years, age range: 9-54 years) were studied. We quantified tract-specific diffusivity measurements as indirect indexes of microstructural integrity (e.g. fractional anisotropy, FA; mean diffusivity, MD) and tract volume (e.g. number of streamlines) of the main limbic tracts. The dissected limbic pathways included the inferior longitudinal fasciculus, inferior frontal occipital fasciculus, uncinate, cingulum and fornix. There were no significant between-group differences in FA and MD. However, compared to healthy controls, individuals with Asperger syndrome had a significantly higher number of streamlines in the right (p=.003) and left (p=.03) cingulum, and in the right (p=.03) and left (p=.04) inferior longitudinal fasciculus. In contrast, people with Asperger syndrome had a significantly lower number of streamlines in the right uncinate (p=.02). Within each group there were significant age-related differences in MD and number of streamlines, but not FA. However, the only significant age-related between-group difference was in mean diffusivity of the left uncinate fasciculus (Z(obs)=2.05) (p=.02). Our preliminary findings suggest that people with Asperger syndrome have significant differences in the anatomy, and maturation, of some (but not all) limbic tracts.

Beyond cortical localization in clinico-anatomical correlation

Last year was the 150th anniversary of Paul Brocas landmark case report on speech disorder that paved the way for subsequent studies of cortical localization of higher cognitive functions. However, many complex functions rely on the activity of distributed networks rather than single cortical areas. Hence, it is important to understand how brain regions are linked within large-scale networks and to map lesions onto connecting white matter tracts. To facilitate this network approach we provide a synopsis of classical neurological syndromes associated with frontal, parietal, occipital, temporal and limbic lesions. A review of tractography studies in a variety of neuropsychiatric disorders is also included. The synopsis is accompanied by a new atlas of the human white matter connections based on diffusion tensor tractography freely downloadable on http://www.natbrainlab.com. Clinicians can use the maps to accurately identify the tract affected by lesions visible on conventional CT or MRI. The atlas will also assist researchers to interpret their group analysis results. We hope that the synopsis and the atlas by allowing a precise localization of white matter lesions and associated symptoms will facilitate future work on the functional correlates of human neural networks as derived from the study of clinical populations. Our goal is to stimulate clinicians to develop a critical approach to clinico-anatomical correlative studies and broaden their view of clinical anatomy beyond the cortical surface in order to encompass the dysfunction related to connecting pathways.

White matter connections of the supplementary motor area in humans

Introduction The supplementary motor area (SMA) is frequently involved by brain tumours (particularly WHO grade II gliomas). Surgery in this area can be followed by the ‘SMA syndrome’, characterised by contralateral akinesia and mutism. Knowledge of the connections of the SMA can provide new insights on the genesis of the SMA syndrome, and a better understanding of the challenges related to operating in this region. Methods White matter connections of the SMA were studied with both postmortem dissection and advance diffusion imaging tractography. Postmortem dissections were performed according to the Klingler technique. 12 specimens were fixed in 10% formalin and frozen at −15°C for 2 weeks. After thawing, dissection was performed with blunt dissectors. For diffusion tractography, high-resolution diffusion imaging datasets from 10 adult healthy controls from the Human Connectome Project database were used. Whole brain tractography was performed using a spherical deconvolution approach. Results Five main connections were identified in both postmortem dissections and tractography reconstructions: (1) U-fibres running in the precentral sulcus, connecting the precentral gyrus and the SMA; (2) U-fibres running in the cingulate sulcus, connecting the SMA with the cingulate gyrus; (3) frontal ‘aslant’ fascicle, directly connecting the SMA with the pars opercularis of the inferior frontal gyrus; (4) medial fibres connecting the SMA with the striatum; and (5) SMA callosal fibres. Good concordance was observed between postmortem dissections and diffusion tractography. Conclusions The SMA shows a wide range of white matter connections with motor, language and lymbic areas. Features of the SMA syndrome (akinesia and mutism) can be better understood on the basis of these findings.

From Phineas Gage and Monsieur Leborgne to H.M.: Revisiting Disconnection Syndromes

On the 50th anniversary of Norman Geschwinds seminal paper entitled ‘Disconnexion syndrome in animal and man’, we pay tribute to his ideas by applying contemporary tractography methods to understand white matter disconnection in 3 classic cases that made history in behavioral neurology. We first documented the locus and extent of the brain lesion from the computerized tomography of Phineas Gages skull and the magnetic resonance images of Louis Victor Leborgnes brain, Brocas first patient, and Henry Gustave Molaison. We then applied the reconstructed lesions to an atlas of white matter connections obtained from diffusion tractography of 129 healthy adults. Our results showed that in all 3 patients, disruption extended to connections projecting to areas distant from the lesion. We confirmed that the damaged tracts link areas that in contemporary neuroscience are considered functionally engaged for tasks related to emotion and decision-making (Gage), language production (Leborgne), and declarative memory (Molaison). Our findings suggest that even historic cases should be reappraised within a disconnection framework whose principles were plainly established by the associationist schools in the last 2 centuries.

Frontal networks in adults with autism spectrum disorder

Autism spectrum disorder (ASD) is proposed to reflect atypical connectivity between higher-order association areas. Using diffusion imaging, Catani et al. reveal associations between ASD and white matter abnormalities of the frontal lobe, and suggest that the condition is linked to aberrant developmental trajectories of frontal networks that persist in adulthood.

Tractography-based connectomes are dominated by false-positive connections

Fiber tractography based on non-invasive diffusion imaging is at the heart of connectivity studies of the human brain. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain dataset with ground truth white matter tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. While most state-of-the-art algorithms reconstructed 90% of ground truth bundles to at least some extent, on average they produced four times more invalid than valid bundles. About half of the invalid bundles occurred systematically in the majority of submissions. Our results demonstrate fundamental ambiguities inherent to tract reconstruction methods based on diffusion orientation information, with critical consequences for the approach of diffusion tractography in particular and human connectivity studies in general.

Reinforcement of the Brain's Rich-Club Architecture Following Early Neurodevelopmental Disruption Caused by Very Preterm Birth

The second half of pregnancy is a crucial period for the development of structural brain connectivity, and an abrupt interruption of the typical processes of development during this phase caused by the very preterm birth (<33 weeks of gestation) is likely to result in long-lasting consequences. We used structural and diffusion imaging data to reconstruct the brain structural connectome in very preterm-born adults. We assessed its rich-club organization and modularity as 2 characteristics reflecting the capacity to support global and local information exchange, respectively. Our results suggest that the establishment of global connectivity patterns is prioritized over peripheral connectivity following early neurodevelopmental disruption. The very preterm brain exhibited a stronger rich-club architecture than the control brain, despite possessing a relative paucity of white matter resources. Using a simulated lesion approach, we also investigated whether putative structural reorganization takes place in the very preterm brain in order to compensate for its anatomical constraints. We found that connections between the basal ganglia and (pre-) motor regions, as well as connections between subcortical regions, assumed an altered role in the structural connectivity of the very preterm brain, and that such alterations had functional implications for information flow, rule learning, and verbal IQ.