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The Val d'Agri Basin is a Quaternary sedimentary basin topping multiple tectonic units of the southern Apennines fold-and-thrust belt and a giant oilfield within deeper Apulian Platform carbonates. This basin is bounded by the seismically active East Agri (EAFS) and Monti della Maddalena (MMFS) extensional fault systems. The reservoir rocks are sealed and separated from shallower thrust sheets by a clay-rich and overpressured mélange. The role of this mélange during fault evolution at shallow crustal levels is widely debated and perhaps underestimated. Here, through multi-scale structural analyses and U–Pb dating of syn-tectonic calcite mineralizations, we gain new insights into the Val d'Agri fault system architecture, their structural maturity, and their relations with both natural and induced seismicity. Consistent with present-day NE-SW crustal stretching, the macro-scale structural architecture of both EAFS and MMFS is controlled by NW-SE and NE-SW fault sets, which displaced and in part re-sheared inherited pre- and syn-orogenic structures. The lack of evident clustering of meso-scale faults and the radial pattern of related slickenlines suggest that polygonal-like faulting occurred, particularly along the EAFS, due to lateral spreading of the Irpinia mélange in the subsurface. Structural data show that the MMFS is characterized by a higher structural maturity (slip longevity), with calcite U–Pb ages indicating the onset of long-lasting extensional tectonics in Early-Middle Miocene time. The original results are discussed in terms of seismotectonic setting of the study area, emphasizing the role played by both the thickness and spatial distribution of plastic mélange in modulating fluid pressure and seismic faulting. • High-angle fault systems bounding the Val d'Agri Basin (Southern Italy). • Polygonal-like style of faulting linked to the occurrence of a tectonic mélange. • Pre- and post- orogenic tectonic activity dated by calcite U–Pb geochronology. • Fault architecture and seismotectonic implications. [ABSTRACT FROM AUTHOR]

The complex fluid saturation distribution and influence of microscale and mesoscale fractures on the fluid accumulation and flow properties of carbonates are still interesting challenges for petroleum geologists. For this reason, in order to know the relative role played by the aforementioned features on the storage and migration properties of tight limestones, the present work focuses on a surface analogue cropping out in southern Italy. By first applying a deterministic Discrete Fracture Network (DFN) modelling to a 1 m3 geocellular volume, an amount of 0.3% of fracture porosity and a fracture connectivity configuration above the percolation threshold are computed. In addition to mesoscale fracture porosity, in order to gather information on matrix porosity and microscale fractures, we investigate the pore type, geometry, and textural anisotropy of selected rock plugs by mean of integrated petrophysical, ultrasonic, and optical microscopy analyses experiments. Results show values of connected porosity ranging between 1% and 6%, presence of vugs localized along pre-existing structural heterogeneities, and the predominance of stiff pores within the carbonate matrix. The rare microfractures are mainly oriented orthogonal to bedding. The estimated crack density (0.19) shows that the contribution of fracture porosity at microscale (ɸ = 0.078%) is very low if compared to that of matrix porosity and also a structural configuration above the percolation. The present study therefore documents that the carbonate matrix forms an isotropic medium, which profoundly affects the storage capability of the study limestones. In fact, the amount of storage provided by carbonate matrix and microscale fractures is greater than that due to mesoscale fractures. Moreover, we document that the matrix contribution on porosity is much more significant than the contribution provided by microfractures. Finally, the present work shows the importance of integrating different methodologies on the assessment of fracture porosity at different scales of observation. In fact, a great benefit for development and production operations can be obtained by performing studies of surface analogs, which allow the detailed investigation of rock masses below seismic resolution. • The work focuses on the role played by micro and mesoscale fractures on the storage and migration properties of limestones. • The mesoscale fracture porosity and connectivity are computed by using a deterministic DFN. • The pore type, geometry, and textural anisotropy are investigated by mean of petrophysical and ultrasonic analyses. • Results show the predominance of microscale matrix porosity over mesoscale fracture porosity. [ABSTRACT FROM AUTHOR]

The work tackles the control exerted by a sub-seismic fracture network on both secondary porosity and correspondent permeability of outcropping tight carbonates. Taking advantage of excellent 3D exposures, located in the Murge Plateau of southern Italy, the fracture network is investigated at different scales of observation. The rock multi-layer is made up of 10's of cm-thick, sub-horizontal, laterally continuous limestone beds crosscut by stratabound fractures, non-stratabound fractures, and small faults named as persistent fracture zones with low amounts of offset. Stratabound fractures consist of bed-perpendicular joints and sheared joints, non-stratabound fractures of incipient, cm-offset, sub-vertical faults, whereas the 10's of cm-offset persistent fracture zones are made up of 10's of m-high, m-thick fractured damage zones. The aforementioned structural elements localize within discrete carbonate units bounded by primary features such as bed surfaces, prominent surfaces and sedimentary breccia horizons. Such interfaces therefore affected the fracture stratigraphy of the limestone rock, and thus impact the fluid flow properties of the carbonate multilayer by compartmentalizing deformation. In the field, the fracture network is investigated by means of scanline and scan area methodologies to document the orientation, intensity, height distribution, mechanical aperture and roughness of individual fractures exposed along vertical outcrops and pavements of abandoned quarries. Then, Discrete Fracture Network (DFN) models of representative geocellular volumes are built, according to the different scales of analysis, to compute both fracture porosity and correspondent permeability (K xx , K yy , K zz ). Results of such a work show that the most prominent non-stratabound fracture set forms the major control on fluid storage and migration at the scales of single beds and bed-packages. At a larger scale, we document that fluid migration mainly occurs along the persistent fracture zones, which enhance the fault-parallel flow. As a whole, the persistent fracture zones form localized fluid conduits embedded within carbonate matrices that show isotropic fluid flow properties. [ABSTRACT FROM AUTHOR]

Abstract: This contribution focuses on the controls exerted by sedimentological, petrographic and mechanical rock properties on the distribution of bed-perpendicular joints throughout layered carbonates. The study was conducted on Tortonian, shallow-marine skeletal grainstones and rudstones cropping out in the Granada Basin, southern Spain. The results of combined field and laboratory analyses are consistent with the rock grain size of the studied carbonates exerting a key control on distribution of the bed-perpendicular joints. A positive correlation between joint spacing and mechanical unit thickness is computed for the grainstones, whereas joints are almost absent in rudstones. The rock grain size affected the diagenetic processes, such as cementation and dissolution, and therefore the resulting porosity and uniaxial compressive strength (UCS) values. Quantitative data show that higher UCS values are commonly associated with greater calcite amounts, lower values of porosity and finer grain sizes and, hence, denser bed-perpendicular joint sets. In conclusion, this study documents that it is possible to infer the density of bed-perpendicular joints in layered carbonates based on the sedimentological, petrographic and mechanical parameters. Considering the impact that this type of joints has on subsurface fluid flow, the acquired knowledge can help the management of geofluids as well as the overall prediction of carbonate reservoir quality. [Copyright &y& Elsevier]

Abstract: Fractures can play an important role in the fluid storage–migration properties of fault damage zones. In this present contribution, we document the role exerted by fractures on fluid flow in carbonate damage zones of hydrocarbon-bearing, km-long, oblique-slip normal faults with 10''s of m-throw. The carbonate fault damage zones were analysed by mean of scan line surveys conducted in both tar-free and tar-rich outcrops. In this way, the relationships among the individual fracture characteristics (length, spacing, aperture, orientation, connectivity and distance from slip surfaces pertaining to small faults of the fault damage zones) and hydrocarbons have been established. Data obtained by scan line surveys were also used to compute the amount of fracture porosity, the degree of fracture connectivity and, based upon simple assumptions, the orientation of the local σ hmax at times of faulting. Additionally, scan line surveys were also carried out along outcrops exposing unfaulted carbonate host rocks. The results of our computation are consistent with a carbonate host rock made up of a quite isotropic fracture array comprised of isolated and coupled fractures, in which individual fracture sets have negative exponential spacing distributions. In terms of fluid flow, the fracture array of the carbonate host rock enhances the fluid storage. Conversely, the fracture array of the fault damage zones is characterized by a pronounced anisotropy due to interconnected fractures, which enhance the fluid migration. Fractures in the fault damage zones include those inherited from background deformation and others related to the faulting processes. The latter fracture sets are characterized by power law spacing distributions. In conclusion, counter-intuitively, both fracture length and fracture spacing do not have any correlation with hydrocarbons in the fault damage zones. On the contrary, fracture anisotropy, fracture spread and fracture orientation are positively correlated with hydrocarbons. [Copyright &y& Elsevier]

Faults are characterized by a complex internal architecture. In carbonates, the geometry, attitude, and distribution of fault-related fractures and subsidiary faults can largely affect the petrophysical properties and hydraulic behavior of the fault zone. This work investigates the footwall damage zone of a seismic-scale normal fault (throw ∼ 300 m) from a structural, petrophysical and seismic point of view. The studied Venere Fault (VF) bounds the intra-mountain Fucino Basin (central Italy) and crosscuts Lower Cretaceous platform carbonates. A significant portion of the footwall VF damage zone (VF-DZ) is well exposed in the 400 × 200 m Santilli Quarry. There, we assess the amount of outcrop-scale fracture porosity and permeability by in-situ fracture analyses and permeability measurements. The results show a composite power-law decay of fracture intensity away from the main slip surfaces, strongly influenced by subsidiary faults. An outcrop-based, digital 2D model of the VF-DZ is constructed and populated with acoustic properties (Vp, Vs and density) derived from both the matrix and fracture porosities. This model is enlarged five times and used for seismic modelling to investigate the seismic signature of the VF-DZ under different but realistic geological and geophysical conditions. Seismic modelling suggests that within the modelled damage zone and for wave frequencies of 20–40 Hz, seismic impedance contrasts associated with subsidiary faults may be imaged, depending on the degree of fracture porosity, fracture aperture, and the illumination angle (a measure of the maximum dip that can be imaged), the last two parameters being controlled by overburden depth. These results have implications for the seismic interpretation and characterization of fault zones in carbonates, and hence for the evaluation of fluid migration through these structures. • Detailed field measurements of fault damage zone in tight carbonates. • Power-law decay of fracture intensity away from main slip surfaces. • Subsidiary faults largely affect the petrophysical properties of the damage zone. • Subsurface imaging of the damage zone is investigated via seismic modelling. • Fault seismic response depends on geological and geophysical parameters. [ABSTRACT FROM AUTHOR]

Abstract: A dramatic paradigm shift is taking place in our understanding of the pathophysiology of multiple sclerosis (MS). An important contribution to such a shift has been made possible by the advances in magnetic resonance imaging (MRI) technology, which allows structural damage to be quantified in the brains of patients with MS and to be followed over the course of the disease. Modern quantitative MR techniques have reshaped the picture of MS, leading to the definition of the so- called “axonal hypothesis” (i.e., changes in axonal metabolism, morphology, or density are important determinants of functional impairment in MS). Metrics derived from magnetization transfer and diffusion-weighted MRI enable us to quantify the extent of structural changes occurring within T2-visible lesions and normal-appearing tissues (including gray matter), with increased pathological specificity over conventional MRI to irreversible tissue damage; proton MR spectroscopy adds valuable pieces of information on the biochemical nature of such changes. Finally, functional MRI can provide new insights into the role of cortical adaptive changes in limiting the clinical consequences of MS-related irreversible structural damage. Our current understanding of the pathophysiology of MS is that this is not only a disease of the white matter, characterized by focal inflammatory lesions, but also a disease involving more subtle and diffuse damage throughout the white and gray matter. The inflammatory and neurodegenerative components of the disease process are present from the earliest observable phases of the disease, but appear to be, at least partially, dissociated. In addition, recovery and repair play an important role in the genesis of the clinical manifestations of the disease, involving both structural changes and plastic reorganization of the cortex. This new picture of MS has important implications in the context of treatment options, since it suggests that agents that protect against neurodegeneration or promote tissue repair may have an important role to play alongside agents acting on the inflammatory component of the disease [Copyright &y& Elsevier]

This study aims at evaluating the control exerted by fracture stratigraphy and diagenetic processes on oil first migration through an outcropping, mixed carbonate-siliciclastic succession. The present work included results of sedimentological, paleontological, mineralogical, petrographic, structural, and microstructural analyses carried out on organic-rich shales exposed at the Favignana Island of Sicily, Italy. The analyses focus on Upper Triassic yellowish siltstones and greyish laminated dolomitic limestones, which form a 10's of m-thick succession exposed along the westernmost portion of the Sicilian fold-and-thrust belt. The studied succession deposited in a coastal lagoon associated to a wide carbonate platform, in which anoxic bottom conditions allowed the preservation of the organic matter forming catagenetic patches and veins/fractures infill. In fact, two orthogonal fracture sets perpendicular to bedding are pervaded by organic matter. They are hence interpreted as structural elements that affected the paleofluid circulation and oil migration within the Triassic source rock. These two orthogonal sets form the background fracture network predating the formation of three other sets infilled mainly with calcite cements. The latest fracture set also includes barite cements implying a hydrothermal origin (<200 °C), as supported by the R1 and R3 mixed-layer Illite-Smectite (I–S) stacking. Data are consistent with a burial depth of the sedimentary succession of about 3 ± 0.5 km. In light of these considerations, the study area might represent an outcropping stratigraphic and structural analogue of the source rocks buried in the offshore of western Sicily and northern Tunisia. • Triassic source rocks of western Sicily, Italy. • Outcrop analogue study of Triassic subsurface carbonate plays. • Anoxic coastal lagoons as depositional settings for Upper Triassic organic matter. • Background fractures acted as conduits for oil first migration. • Three main diagenetic phases recorded in the mixed carbonate-siliciclastic source rock. [ABSTRACT FROM AUTHOR]

This work focuses on the structural setting of a small area of the Murge Plateau, southern Italy, exposing Turonian bauxites and encompassing Upper Cretaceous carbonates of the Apulian Platform. By combining field geological and structural mapping with mineralogical and petrographic investigations of representative rock samples, we document the control exerted by Late Cretaceous, syn-sedimentary, high-angle faults and dilational fissures striking ca. N105E, N135E, N170E, and N45E. Altogether, these structural elements formed a few km-long, transtensional fault system along which karst-related shafts, dissolution caves, and sinkholes developed. Karst processes first affected the topmost limestone beds of the Valanginian-Cenomanian Bari Fm. Then, during Turonian, in a continental setting, cycles of terrigenous sediment deposition and weathering localized in the karst-related cavities, dilational fissures, and at the top of down-dropped fault blocks. Weathering of the Al–Si rich sediments formed bauxites made up of kaolinite, boehmite, goethite, hematite, and anatase mineral phases. The relative enrichment in kaolinite with respect to boehmite documented for the breccia and conglomerate matrix topping the bauxites is interpreted as due to lower degrees of weathering. Differently, the individual bauxite beds do not show any internal significant variation in terms of their mineral assemblages, but form angular unconformities due to syn-sedimentary faulting. The subsequent marine transgression also occurred under the influence of active tectonics, as displayed by growth folds at the bottom of the Conacian-Early Campanian Altamura Fm. The overall results of this study are in agreement with those previously reported for nearby areas of the Murge Plateau exposing Santonian limestone rocks of the Altamura Fm. Accordingly, we infer that Late Cretaceous transtensional faulting of the Apulian Platform was due to a far field stress state, likely associated to the orogenic processes that involved the northern edge of the Adriatic micro-plate. • Significant variations of the mineral phases characterize the karst bauxites. • Karst bauxites closely associated to syn-sedimentary faults and dilational fissures. • Bauxite beds forming a ca. 20° angular unconformity. • Cycles of sediment deposition and weathering affected by trastensional faulting. • Syn-sedimentary, transtensional faulting due to a far field stress state. [ABSTRACT FROM AUTHOR]

The Upper Cretaceous carbonates cropping out in the Murge Plateau are good analogues of the fractured and faulted carbonate oil reservoirs of southern Italy. For this reason, a detailed field analysis focused on structural architecture of fault and fracture networks has been carried out in the Murge Plateau. The well-bedded carbonates exposed there are crosscut by a set of bed-parallel stylolites and two sets of bed-perpendicular cross-orthogonal joints/veins. These structural elements were likely formed under vertical loading during burial diagenesis and flexure of the Apulian foreland of the Southern Apennines fold-and-thrust belt. Bed-parallel stylolites and bed-perpendicular cross-orthogonal joints/veins represent the background deformation that was overprinted by the fault-related localized deformation. The fault sets documented in the study area are arranged in two kinematically-compatible fault networks. The first one is made up of WNW-ESE and NNW-SSE oriented strike-slip faults, right- and left-lateral, respectively, and NW–SE oriented normal faults. The second fault network consists of WNW-ESE oriented left-lateral strike-slip faults, and NE–SW oriented normal faults. First, both architecture and dimensional parameters of the fault and fracture networks have been characterized and computed by means of statistical analysis. Then, the permeability structures associated to the aforementioned networks have been assessed in order to determine the role exerted by fault architecture and dissolution/cementation processes on the fluid storage and migration pathways within the studied platform carbonates. Network 1 faults show a quite variable fluid behavior, in which the fluid flow is strongly affected by inherited structural elements and karst dissolution, whereas network 2 faults show a more uniform, fluid conduit behavior. [ABSTRACT FROM AUTHOR]

Abstract: Three main sets of deformation bands are identified in the Lower Pleistocene carbonate grainstones of Favignana Island (Italy). A bedding-parallel set is interpreted to contain compaction bands, based on the lack of evidence for shear. The other two sets are oriented at a high-angle to bedding, forming a conjugate pair comprised of compactive strike-slip shear bands. In this study, we focus on the compactive shear bands documenting their development, as well as analyzing their dimensional parameters and scaling relationships. Single compactive shear bands are thin, tabular zones with porosity less than the surrounding host rocks, and have thicknesses and displacements on the order of a few mm. The growth process for these structures involves localizing further deformation within zones of closely-spaced compactive shear bands and, possibly, along continuous slip surfaces within fault rocks overprinting older zones of bands. During growth, single bands, zones of bands and faults can interact and link, producing larger structures. The transitions from one growth step to another, which are controlled by changes in the deformation behavior (i.e. banding vs. faulting), are recorded by different values of the dimensional parameters for the structures (i.e. length, thickness and displacement). These transitions are also reflected by the ratios and distributions of the dimensional parameters. Considering the lesser porosity values of the structures with respect to the host rock, the results of this contribution could be helpful for mapping, assessing, and simulating carbonate grainstone reservoirs with similar structures. [Copyright &y& Elsevier]

The high-angle faults bounding the High Agri Valley Basin eastwards are well-exposed at the Viggiano Mt., southern Italy. There, these faults crosscut Mesozoic shallow-water carbonates and permit the multiscale analyses of fault and fracture geometry and distribution. Aiming at assessing the control exerted by carbonate lithofacies and scales of observation, we combine field and digital structural analyses to compute the values of 1D and 2D fracture density and intensity, and the dimensional properties of single fault and fracture sets. As a result, from outcrop to reservoir scales we document a scale-variant geometry of faults and fractures, and the great variation of both fracture density and intensity among the studied carbonate lithofacies. Furthermore, we compute a P21 dimensional scaling factor of ca. 20 for over 3 order magnitude, whereas inconsistent results are achieved for the P20 values. Not considering the control exerted by the single carbonate lithofacies, at a reservoir scale we document that the small-scale faults greatly impact the computed P21 values. • Scale-variant geometry of fractures and fault arrays from the outcrop to reservoir scale. • Truncation effects are associated with digital structural analysis. • A scaling factor of 20 is computed for outcrop-to-reservoir scale P21 computations. [ABSTRACT FROM AUTHOR]

Depositional and diagenetic processes profoundly control the structural evolution of shallow-water carbonates through time. We focus on the Lower Jurassic platform carbonates pertaining to the southern Apennines fold-and-thrusts belt, Italy, by performing 3D digital outcrop modeling, field structural analysis, and microstructural investigation. Results show that pressure solution of the platform carbonates was affected by the grain size of single beds. Since early diagenesis, pressure solution localized within the coarser-grained carbonate beds, forming wave-like solution surfaces. Crosscutting relations among blocky cements, bed-parallel solution surfaces and high-angle veins show that pressure solution occurred during burial diagenesis with formation of wave-like solution surfaces, and during Late Miocene tectonic burial with formation of seismogram-like solution surfaces. The tectonic burial postdated the thrusting-related flexural slip folding and small-scale thrusting of the platform carbonates. Small scale thrusting took place by means of shearing of the bed-parallel heterogeneities, and formation of bed-oblique slickolites resulting in the development of back thrusts characterized by flat-ramp-flat geometries. The main results of this work are synthesized in a six-stage synoptic scheme reporting the structural evolution of the platform carbonates. Outcomes are helpful for the better assessment of geofluid production/storage from/in fractured platform carbonates pertaining to fold-and-thrust belts. • Pressure solution processes affected the primary bed-parallel interfaces. • Pressure solution processes were more pronounced in grain-supported carbonates. • Pressure solution processes affected the fracture stratigraphy of the carbonates. • Fracture stratigraphy of the platform carbonates evolved during diagenesis. • Fracture stratigraphy of the platform carbonates evolved during thrusting tectonics. [ABSTRACT FROM AUTHOR]

Active faults within the southern Apennines fold-and-thrust belt modulate the present-day upwelling of hydrothermal fluids at surface. In the Monte Alpi area, we investigated the structural and geo-morphological settings of a ~10 km2-wide area, and texture and stable isotope composition of Quaternary travertine deposits to identify the present day fault-controlled pathways of low-T hydrothermal fluids at shallow crustal depths. Results of 1:10,000 geological mapping and microstructural analyses show that the Monte Alpi travertines were deposited in a paleo-fluvial environment consisting of cascades and pool/barrage systems, including shallow caves. Travertines precipitated from CO 2 -rich meteoric-derived paleo-fluids that yielded δ 18O compositions from −7.7‰ to −10.1‰. Values in this range overlap the δ 18O values of water from active hydrothermal springs in the study area. Accordingly, we assess that travertines precipitated from fluids similar to those currently emerging from low-T (~22 °C) hydrothermal springs active in the study area. In particular, the SO 4 chemical signature of hydrothermal springs indicates a complex circulation implying: (1) the infiltration at depth of original meteoric fluid into the Monte Alpi carbonate massif; (2) fluid warming by the geothermal gradient, CO 2 enrichment, and interaction with the local stratigraphy (Messinian sulphate-rich deposits); and (3) fluid upwelling through highly permeable fault zone compartments that correspond to fault intersections. Structural analysis and aerial photo interpretation show that sub-parallel fault scarps and landslide escarpments controlled the depositional setting of the travertines. Moreover, travertines only occur above carbonates rocks, whereas travertines are virtually absent along fault scarps and landslide escarpments in shales and metapelites. We conclude that, at fault intersections, high-permability fluid conduits localize along fault zones that sub-parallel the current σh max of the southern Apennines. In contrast, we infer that clay smearing along fault segment that cut shales and metapelites resulted in low-permeability fault zones, which hampered fluid upwelling. • Low-T (22 °C) hydrothermal fluids originate from meteoric waters warmed at depth. • Hydrothermal fluids feed springs with constant flow rates and temperatures. • Hydrothermal fluid precipitate travertines in cascades, pools, barrages, and caves. • Fluids channelled at depth within a fault zone oriented sub-parallels to σh max. • Clay smearing along faults in marls and shales hindered hydrothermal fluids upwelling. [ABSTRACT FROM AUTHOR]

Progressive supranuclear palsy (PSP) can occur with two main clinical presentations, classified as classical Richardson’s syndrome (PSP-RS) and as PSP-parkinsonism (PSP-P), the most common atypical PSP variant. The differential diagnosis between them is challenging, as well as from idiopathic Parkinson’s disease (PD). Therefore, we studied different neuroimaging markers, using both conventional and unconventional MRI methods to test their value in the diagnostic work up of PSP and PD patients. Ten PSP-RS, 10 PSP-P, 25 PD patients, and 24 healthy controls were studied. Neuroimiging investigations included MRI brainstem region of interest measurements, as well as voxel-based morphometry (VBM) analysis. The pons/midbrain and the MR parkinsonism index allowed to differentiate PSP-RS from PD with high sensitivity (90%, 100%), specificity (96%, 92%), and accuracy (94%, 97%). Only the pons/midbrain was found to distinguish PSP-P from PD, but with a lower diagnostic accuracy (sensitivity = 60%, specificity = 96%, accuracy = 86%). Compared to PSP-RS, PSP-P experienced a different pattern of both gray matter and white matter atrophy on VBM. Compared to PSP-RS, PSP-P experience a relatively less severe atrophy of infratentorial brain. The pons/midbrain looks as a promising measure in the differentiation of individual PSP-P from PD patients. [ABSTRACT FROM AUTHOR]

Introduction Diffusion tensor imaging (DTI)-based metrics are increasingly used for analyzing ALS-associated whitematter alteration patterns and were included inthe Neuroimaging Society in Amyotrophic Lateral Sclerosis (NiSALS) concept ( Turner et al., 2011 ). The objective of this multicenter study was to assess structural connectivity in ALS at a large sample size to address the challenges of DTI data analysis from multiple study sites. Methods Four-hundred and ninety DTI data sets from patients with ALS ( N = 268) and controls ( N = 222) were collected from 8 study centers (Dublin, Ireland; Edinborough, UK; Jena, Germany; Miami, US; Milan, Italy; Oxford, UK; Rostock, Germany, Ulm, Germany). Data were obtained by different MRI-systems and by use of different DTI-protocols. In a first step, comparability of data with the aim of pooling was tested by a statistical analysis of fractional anisotropy (FA) in controls’ data. All analyses were performed by use of the Tensor Imaging and Fiber Tracking (TIFT) software. Statistical comparisons in terms of average FA-values ( Müller et al., 2013 ) were performed for the controls’ groups of the different centers. In a consecutive step, the calculated 3D correction matrices were then applied to the corresponding ALS patient subgroups of the different centers. Results Data collection and data quality control resulted in 442 DTI data sets (253 ALS patients and 189 controls) useful for this study, i.e. 48 data sets had to be excluded. All data samples of all centers showed a characteristic pattern (FA decrease along the corticospinal tracts) for comparison at the group level. Inter-center pooling of data showed ALS affectations in the CST (“horseshoe” configuration) as well as affectations in regions that have recently been reported to be relevant in ALS (frontocortical whitematter regions, hippocampal regions, as well as midbrain and brainstem) ( Kassubek et al., 2014 ). Conclusion This large scale multicenter NiSALS study investigated solutions to challenges in the process of pooling MRI data recorded at various study centers in ALS. This approach is of utmost importance in order to establish MRI-based techniques as read-outs both fornatural history assessment and for potential upcoming disease-modifying multicenter studies in ALS ( Roßkopf et al., in press ). [ABSTRACT FROM AUTHOR]