Carmelo Milazzo

Cortical and Subcortical Connections of the Human Claustrum Revealed In Vivo by Constrained Spherical Deconvolution Tractography

The claustrum is a thin layer of gray matter that is at the center of an active scientific debate. Recently, Constrained Spherical Deconvolution (CSD) tractography has proved to be an extraordinary tool allowing to track white matter fibers from cortex to cortical and subcortical targets with subvoxel resolution. The aim of this study was to evaluate claustral connectivity in the human brain. Ten normal brains were analyzed by using the High Angular Resolution Diffusion Imaging CSD-based technique. Tractography revealed 4 groups of white matter fibers connecting the claustrum with the brain cortex: Anterior, posterior, superior, and lateral. The anterior and posterior cortico-claustral tracts connected the claustrum to prefrontal cortex and visual areas. The superior tract linked the claustrum with sensory-motor areas, while the lateral pathway connected the claustrum to the auditory cortex. In addition, we demonstrated a claustral medial pathway connecting the claustrum with the basal ganglia, specifically with caudate nucleus, putamen, and globus pallidus. An interesting and exciting new finding was the demonstration of a bilateral connection between claustrum and contralateral cortical areas and a well-represented interclaustral communication with interconnection bundles interspersed within the bulk of the trunk of the corpus callosum. The physiological and pathophysiological relevance of these findings are discussed.

Basal ganglia network by constrained spherical deconvolution: a possible cortico-pallidal pathway?

In the recent past, basal ganglia circuitry was simplified as represented by the direct and indirect pathways and by hyperdirect pathways. Based on data from animal studies, we hypothesized a fourth pathway, the cortico‐pallidal, pathway, that complements the hyperdirect pathway to the subthalamus. Ten normal brains were analyzed by using the high angular resolution diffusion imaging—constrained spherical deconvolution (CSD)‐based technique. The study was performed with a 3T magnetic resonance imaging (MRI) scanner (Achieva, Philips Healthcare, Best, Netherlands); by using a 32‐channel SENSE head coil. We showed that CSD is a powerful technique that allows a fine evaluation of both the long and small tracts between cortex and basal ganglia, including direct, indirect, and hyperdirect pathways. In addition, a pathway directly connecting the cortex to the globus pallidus was seen. Our results confirm that the CSD tractography is a valuable technique allowing a reliable reconstruction of small‐ and long‐fiber pathways in brain regions with multiple fiber orientations, such as basal ganglia. This could open a future scenario in which CSD could be used to focally target with deep brain stimulation (DBS) the small bundles within the basal ganglia loops.

On the R2 relaxometry in complex multi-peak multi-Echo chemical shift-based water-fat quantification: Applications to the neuromuscular diseases

PURPOSE Investigation of the feasibility of the R2⁎ mapping techniques by using latest theoretical models corrected for confounding factors and optimized for signal to noise ratio. THEORY AND METHODS The improvement of the performance of state of the art magnetic resonance imaging (MRI) relaxometry algorithms is challenging because of a non-negligible bias and still unresolved numerical instabilities. Here, R2⁎ mapping reconstructions, including complex fitting with multi-spectral fat-correction by using single-decay and double-decay formulation, are deeply studied in order to investigate and identify optimal configuration parameters and minimize the occurrence of numerical artifacts. The effects of echo number, echo spacing, and fat/water relaxation model type are evaluated through both simulated and in-vivo data. We also explore the stability and feasibility of the fat/water relaxation model by analyzing the impact of high percentage of fat infiltrations and local transverse relaxation differences among biological species. RESULTS The main limits of the MRI relaxometry are the presence of bias and the occurrence of artifacts, which significantly affect its accuracy. Chemical-shift complex R2⁎-correct single-decay reconstructions exhibit a large bias in presence of a significant difference in the relaxation rates of fat and water and with fat concentration larger than 30%. We find that for fat-dominated tissues or in patients affected by extensive iron deposition, MRI reconstructions accounting for multi-exponential relaxation time provide accurate R2⁎ measurements and are less prone to numerical artifacts. CONCLUSIONS Complex fitting and fat-correction with multi-exponential decay formulation outperforms the conventional single-decay approximation in various diagnostic scenarios. Although it still lacks of numerical stability, which requires model enhancement and support from spectroscopy, it offers promising perspectives for the development of relaxometry as a reliable tool to improve tissue characterization and monitoring of neuromuscular disorders.

Does Pelvic Incidence Influence the Morphology of the Sacroiliac Joint

Pelvic Incidence is defined as the angle between the perpendicular line to the upper plate of S1 at its midpoint and the line between this point and the center of bicoxofemoral line, it describes the position of femural heads in relation to sacrum. Recently some authors described a direct correlation between high values of PI and large AP pelvic axis (horizontal pelvis) and a wide pelvic ring [1]. Also the acetabular orientation is influenced by PI ; high values of PI means a more vertical acetabulum. Having regard to the relationship between PI and the main structures involved in the load transfer, to date no studies that correlate the morphology of the Sacroiliac Joint (SiJ) and PI were performed. The aim of this study is to evaluate the different morphology of the auricular surface of the sacrum comparing two groups of healthy young people with low ( 40°) PI. We retrospectively analysed 51 consecutive young (between 20 and 35 y.o.) people. After the evaluation of PI the sample was divided into two groups: 31 people belong to the group A (PI 40°). The following morphological parameters of the SiJ were analysed: length of long axis (LLA), length of short axis (LSA), length of oblique axis (LOA), ratio between long and short axis (RLSA), angle between axis (ABA) and surface; global shape of the joint was evaluated; two new parameters were introduced, SiJ Tilt (SiJT), defined as the angle between the vertical line and the long axis of the SiJ and SiJ Slope (SiJS), defined as the angle between the horizontal line and the short axis of the SiJ. We found a strong statistically significant correlations (p-value 0.05) between PI and RLSA, shape, ABA, SiJT and SiJS; a weaker correlations (p-value 0.10) between PI and LLA, LSA were observed; no statistically significant correlation between PI and LOA and surface were observed. The results underline that there is a strong correlation between pelvic morphology and SiJ anatomy. Further studies, about the different pattern of forces distribution among SiJ, will need to be performed to have a better knowledge that could help to understand the biomechanics and pathophysiology of normal and pathological SiJ.

Constrained Spherical Deconvolution Tractography reveals a direct cerebello-ventro tegmental pathway in humans

Introduction. In addition to its role in motor control, reflex adaption and motor learning in the past years numerous studies demonstrated the role of the cerebellum in non-motor functions. Furthermore, lesional animal and neuroimaging in vivo human studies demonstrated connections of the cerebellum with brain regions involved in cognitive, emotional, motivation linguistic processing [1, 2]. Although, studies suggest the role of the cerebellum in neuropsychiatric disorders of the mesocorticolimbic structure (i.e. schizophrenia), at the present time the existence cerebello-ventro tegmental pathway has been demonstrated in only in rodents and only hypothesized in humans. Aim. The goal of this in vivo constrained spherical deconvolution (CSD) tractography study is the investigation on the presence of a direct cerebello-ventro tegmental pathway in the human brain. Material and Methods. We recruited 15 human subjects with no previous history of neurological or psychiatric disorders. The entire study was performed using a 3T Achieva Philips scanner; a SENSE 8 channels head coil, acquiring T1 weighted 3D TFE, DTI sequence; data were analyzed by using constrained spherical deconvolution techniques (CDS). Results. We demonstrated with CSD dentate-ventral midbrain connections. In particular, we found a direct route linking between the dentate nucleus and the ventro tegmental area. Conclusions. This study provides for the first time the existence of a human dentate nucleus connections with the ventro tegmental area, moreover the existence of this cerebello-midbrain pathway suggest that the cerebellum may be involved in the modulation of the mesocorticolimbic system and in related neuropsychiatric disorders such as the schizophrenia.

Limbic-motor areas interactions as revealed by Constrained Spherical Deconvolution tractography: a mechanism to shape complex motor behaviors?

Although there are several evidences in animal research on the emotional motor-limbic subcortical system including amygdala, hyppocampus, parahyppocampal cortex and nucleus accumbens, little is known about its connections to cortical motor-related areas. All these structures are in a position to influence behavior via cortical motor-related areas, which in turn have access, both directly and indirectly, to descending motor pathways. If on the one hand, many animal studies have investigated the neural connectivity of the motor-limbic system using electrophysiological and tracing techniques, on the other hand the use of these methods in the live human brain is limited and elusive due to their invasive nature [1]. By contrast, recent developments in diffusion magnetic resonance imaging and tractography have allowed for non-invasive and in vivo investigation of the human brain. Diffusion-based tractography is a method analyzing the preferential water diffusivity directionality along white matter bundles, thus calculating the highest mathematical probability that water diffuses in a given direction [2]. Using diffusion-weighted magnetic resonance imaging and Constrained Spherical Deconvolution tractography on a population of 15 healthy subjects, we provided tractographic evidence of a structural connection between the amygdala and motor-related areas in humans. These direct limbic-motor pathways may allow for the regulation and modulation of complex motor behaviors and subtle behaviors such as social interactions. The demonstration of these interactions might be fundamental for the comprehension of the pathophysiology of several limbic-sensorimotor diseases, such autism spectrum disorders and motor conversion disorders.

Morphometric evaluation of the pedicles of the lumbar spine according to L5 lateral tilt classification

A classification of the lumbar spine according to the pedicle lateral tilt (PLT) of L5 pedicle was recently proposed [1]. In this work the sample was divided into three categories, the first or Wing Type (WT) includes people with a PLT >36° (41,8%), the second or V Type (VT) includes people with a PLT between 30° and 36° (48%) and the third or U Type (UT) includes people with a PLT <30 (10,2%). The aim of the study is to evaluate the bone morphometric values and the distance between the pedicles and the nervous structures. Similar works are present in literature [2], but some are lack or for the size of the sample or for the parameters analysed. In our work seven parameters were considered: Pedicle Width (PW), Pedicle Height, Interpedicular Distance (IPD), Pedicle-Inferior Root Distance (PIRD), Pedicle-Superior Root Distance (PSRD), Root Exit Angle (REA), Nerve Root Diameter (NRD). In this study 325 patients were evaluated, a CT and MRI scan were taken to analyse respectively bone morphometry (CT) and distance between nervous structures (MRI). Statistically significant results were observed in five out seven categories, at L5: PW has a mean value of 18,5 mm in WT, 17,2 mm in VT and 15,8 mm for UT; PH has a mean value of 13,4 mm in WT, 12,8 mm (VT) and 11,2 mm in UT; IPD has a mean value of 29,2 mm in WT, 27,3 mm in VT and 25,8 mm in UT; PSRD has a mean value of 4,9 mm in WT, 4,6 mm in VT and 4,4 mm in UT; PDSD has a mean value of 1,9 mm in WT, 1,5 mm in VT and 1,3 mm in UT; REA has a mean value of 43° in WT, 40,2° in VT and 37,8° in UT. No differences were observed for PIRD (with a mean value of 1,5 mm) and NRD (with a mean value of 4 mm). Similar results were also observed for the pedicles of L4, whereas for the proximal pedicles (L3, L2 and L1) were not observed statistically significant differences into the three categories. In conclusion, the results obtained in this paper confirms the need to adopt our proposed classification according to the anatomic differences observed into our sample; in particular VT pedicle of L5 and L4 could be considered as “complicated” in a pedicle screw fixation surgery, based on the reduced bone volume and the close distance to nervous structures.

Advances from probabilistic tractography in connections of the limbic system with the cerebellum

The limbic system is a complex set of brain structures located on both sides of the thalamus, right under the cerebrum. It is not a separate system but a collection of structures from the telencephalon, diencephalon, and mesencephalon, including the hippocampus, amygdala, anterior thalamic nuclei, fornix, columns of fornix, mammillary body, septum pellucidum, habenular commissure, cingulate gyrus, parahippocampal gyrus, limbic cortex, pars of olfactory system and limbic midbrain areas. Nevertheless, recent studies showed that the definition of anatomical structures considered part of the limbic system is a controversial subject. Although the role of the cerebellum was traditionally considered mainly associated to motion control, it has been recently suggested a cerebellar involvement in emotions control, cognitive processes and social behavior. In this regard, we have previously demonstrated that the cerebellum is interconnected with the hippocampus [1]. In this work, a wider sample of normal subjects was examined by using probabilistic Constrained Spherical Deconvolution (CSD) tractography, which represents a method able to overcome many limitations of other Diffusion Tensor Imaging (DTI) techniques, providing more accurate data [2]. We found evidences in the human brain that the cerebellum is widely linked with limbic-related structures and provided a more reliable demonstration of direct cerebello-limbic pathways. In addition, we further extendend our analysis to the other limbic connections including uncinated fasciculus, cingulate fasciculus, inferior longitudinal fasciculus, anterior thalamic connections and fornix. Although these pathways have been already described in the tractographic literature we provided reconstruction and quantitative analysis, which could be potentially useful to explore pathological conditions damaging this system. Finally, the demonstration of the existence of cerebello-limbic connections could constitute an important step in the knowledge of the anatomic substrate of non-motor cerebellar functions.

Neural correlates of fatigue in multiple sclerosis: a diffusion tensor imaging and transcranial magnetic stimulation study

Fatigue is a common and specific symptom in neurological diseases described as an overwhelming feeling of extreme exhaustion, and it concerns the inability to sustain a force or work rate during exercise, often defined as “objective fatigue”. Many patients displaying symptoms of physical and mental fatigue have no profound weakness, persistent or progressive cognitive decline or failure of peripheral neuromuscular function. This particular type of fatigue has been termed neurasthenia, frequently reported by patients suffering from multiple sclerosis (MS). The pathological substrate of behavioral deficit in MS is not entirely understood and may reside both in grey matter involvement and white matter injury, with derangement of white matter tracts architecture [1]. In order to investigate the role of connectivity alterations in the development of fatigue and behavioral impairment in MS patients, we examined 19 MS patients combining neurophysiological paradigm by means of Transcranial Magnetic Stimulation (TMS), cognitive assessment and Magnetic Resonance Imagining (MRI) with Diffusion Tensor Imaging (DTI) based tools. DTI is a noninvasive MRI technique [2] that can be used to probe the structural integrity of white matter through quantitative parameters, such as Fractional Anysotropy (FA). We were able to reconstruct the anterior thalamic projections and the caudate-cortical loop tracts, finding lower FA values in the right hemispheres, which results in weaker connectivity in patients compared with controls. In addition, we analysed the thalamic and basal ganglia volume, showing a significant atrophy of striatum and thalamus in fatigued patients, correlated to the neurodegenerative process of the striatum-thalamus loop. We assume that fatigue and cognitive impairment could be related to micro-structural impairment of white matter tracts of the cortical-subcortical-cortical loop.

Study of“Shaken Baby Syndrome”: Morphological and Diffusion MRI Data

Shaken baby syndrome (SBS) is the most common cause of death related to child abuse; nonfatal consequences of SBS include varying degrees of visual, motor and cognitive impairment due to severe brain damage in almost 30% of infants with SBS. Brain damage occurs from the biomechanical forces, swelling, ischemia and altered vascular autoregulation and from additionally axonal damage[1].In the present study we want to examine a cohort of 7 patient affected by SBS and compare their data with controls choosen by same range of age, 19 months till 60. Using MRI techniques we define a new paradigm for demonstrating, through voxel based morphometry, deficiencies, connected to white and grey matter regions, in the prefrontal cortex and also in the hippocampus, amygdala, corpus callosum and optical radiation. Adding diffusion tensor imaging technique by constrained spherical deconvolution[2] our study put in evidence connectivity between investigated areas, suggesting neural network abnormalities. With this “state of art” studies we can show a correlation between childhood abuse and brain structures modification. Our aim is to make a longitudinal study on the anatomical data of these patients following their clinical evolution.