Scattered Light Imaging: Resolving the substructure of nerve fiber crossings in whole brain sections with micrometer resolution.

For developing a detailed network model of the brain based on image reconstructions, it is necessary to spatially resolve crossing nerve fibers. The accuracy hereby depends on many factors, including the spatial resolution of the imaging technique. 3D Polarized Light Imaging (3D-PLI) allows the three-dimensional reconstruction of nerve fiber tracts in whole brain sections with micrometer in-plane resolution, but leaves uncertainties in pixels containing crossing fibers. Here we introduce Scattered Light Imaging (SLI) to resolve the substructure of nerve fiber crossings. The measurement is performed on the same unstained histological brain sections as in 3D-PLI. By illuminating the brain sections from different angles and measuring the transmitted (scattered) light under normal incidence, light intensity profiles are obtained that are characteristic for the underlying brain tissue structure. We have developed a fully automated evaluation of the intensity profiles, allowing the user to extract various characteristics, like the individual directions of in-plane crossing nerve fibers, for each image pixel at once. We validate the reconstructed nerve fiber directions against results from previous simulation studies, scatterometry measurements, and fiber directions obtained from 3D-PLI. We demonstrate in different brain samples (human optic tracts, vervet monkey brain, rat brain) that the 2D fiber directions can be reliably reconstructed for up to three crossing nerve fiber bundles in each image pixel with an in-plane resolution of up to 6.5 µm. We show that SLI also yields reliable fiber directions in brain regions with low 3D-PLI signals coming from regions with a low density of myelinated nerve fibers or out-of-plane fibers. This makes Scattered Light Imaging a promising new imaging technique, providing crucial information about the organization of crossing nerve fibers in the brain.

Minimally invasive cerclage at the tibia using a modified Goetze technique: An anatomical study.

INTRODUCTION: The use of minimally invasive cerclages at the tibia is not very common. First, clinical results of a new operative technique published recently showed no increased complication rate. The aim of this anatomical study was to determine, if it is possible to introduce a minimally invasive cerclage at different levels of the tibia without encasing relevant nerves, vessels or tendons into the cerclage using this technique. HYPOTHESIS: The minimally invasive introduction of a cerclage at the tibia is possible without encasing relevant anatomical structures. MATERIAL AND METHODS: Using the minimally invasive operative technique in 10 human cadaveric lower legs, cerclages were inserted at 4 different levels of each tibia. They were defined from proximal to distal as level 1-4. The legs were severed at the levels of the cerclages and examined for any relevant encased anatomical structures. Afterwards, the shortest distance between each relevant anatomical structure and the cerclage was measured. RESULTS: There was no encasing of any relevant anatomical structures in any specimen at any level. In the proximal half of the lower leg, the closest anatomical structures to the inserted cerclage were arteria et vena tibialis posterior (at level 1: 5.2 resp. 4.3mm, at level 2: 4.0 resp. 5.5mm). In the distal half of the lower leg arteria et vena tibialis anterior (level 3: 1.8 and 2.0mm, level 4: 1.6 and 1.5mm), nervus fibularis profundus (level 3: 2.2mm, level 4: 1.2mm) and the tendon of musculus tibialis posterior (level 3: 0.8mm, level 4: 1.1mm) were in closest proximity of the cerclage. DISCUSSION: The results of this anatomical study suggest that the minimally invasive insertion of cerclages at the tibia without encasing relevant anatomical structures is possible but requires a correct operative technique. The structures at highest risk are arteria et vena tibialis posterior in the proximal half of the tibia and arteria et vena tibialis anterior, nervus fibularis profundus and the tendon of musculus tibialis posterior in the distal half. LEVEL OF EVIDENCE: Not applicable; experimental anatomical study.

Common structural correlates of trait impulsiveness and perceptual reasoning in adolescence.

BACKGROUND: Trait impulsiveness is a potential factor that predicts both substance use and certain psychiatric disorders. This study investigates whether there are common structural cerebral correlates of trait impulsiveness and cognitive functioning in a large sample of healthy adolescents from the IMAGEN project. METHODS: Clusters of gray matter (GM) volume associated with trait impulsiveness, Cloningers' revised temperament, and character inventory impulsiveness (TCI-R-I) were identified in a whole brain analysis using optimized voxel-based morphometry in 115 healthy 14-year-olds. The clusters were tested for correlations with performance on the nonverbal tests (Block Design, BD; Matrix Reasoning, MT) of the Wechsler Scale of Intelligence for Children IV reflecting perceptual reasoning. RESULTS: Cloningers' impulsiveness (TCI-R-I) score was significantly inversely associated with GM volume in left orbitofrontal cortex (OFC). Frontal clusters found were positively correlated with performance in perceptual reasoning tasks (Bonferroni corrected). No significant correlations between TCI-R-I and perceptual reasoning were observed. CONCLUSIONS: The neural correlate of trait impulsiveness in the OFC matches an area where brain function has previously been related to inhibitory control. Additionally, orbitofrontal GM volume was associated with scores for perceptual reasoning. The data show for the first time structural correlates of both cognitive functioning and impulsiveness in healthy adolescent subjects.

Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering.

Myelinated axons (nerve fibers) efficiently transmit signals throughout the brain via action potentials. Multiple methods that are sensitive to axon orientations, from microscopy to magnetic resonance imaging, aim to reconstruct the brain's structural connectome. As billions of nerve fibers traverse the brain with various possible geometries at each point, resolving fiber crossings is necessary to generate accurate structural connectivity maps. However, doing so with specificity is a challenging task because signals originating from oriented fibers can be influenced by brain (micro)structures unrelated to myelinated axons. X-ray scattering can specifically probe myelinated axons due to the periodicity of the myelin sheath, which yields distinct peaks in the scattering pattern. Here, we show that small-angle X-ray scattering (SAXS) can be used to detect myelinated, axon-specific fiber crossings. We first demonstrate the capability using strips of human corpus callosum to create artificial double- and triple-crossing fiber geometries, and we then apply the method in mouse, pig, vervet monkey, and human brains. We compare results to polarized light imaging (3D-PLI), tracer experiments, and to outputs from diffusion MRI that sometimes fails to detect crossings. Given its specificity, capability of 3-dimensional sampling and high resolution, SAXS could serve as a ground truth for validating fiber orientations derived using diffusion MRI as well as microscopy-based methods. STATEMENT OF SIGNIFICANCE: To study how the nerve fibers in our brain are interconnected, scientists need to visualize their trajectories, which often cross one another. Here, we show the unique capacity of small-angle X-ray scattering (SAXS) to study these fiber crossings without use of labeling, taking advantage of SAXS's specificity to myelin - the insulating sheath that is wrapped around nerve fibers. We use SAXS to detect double and triple crossing fibers and unveil intricate crossings in mouse, pig, vervet monkey, and human brains. This non-destructive method can uncover complex fiber trajectories and validate other less specific imaging methods (e.g., MRI or microscopy), towards accurate mapping of neuronal connectivity in the animal and human brain.

Manual dexterity correlating with right lobule VI volume in right-handed 14-year-olds.

BACKGROUND: Dexterity is a fundamental skill in our everyday life. Particularly, the fine-tuning of reaching for objects is of high relevance and crucially coordinated by the cerebellum. Although neuronal cerebellar structures mediate dexterity, classical whole brain voxel-based morphometry (VBM) has not identified structural correlates of dexterity in the cerebellum. METHODS: Clusters of gray matter (GM) volume associated with the Purdue Pegboard Dexterity Test, a test of fine motor skills and complex upper limb movements, were identified in a cerebellum-optimized VBM analysis using the Spatially Unbiased Infratentorial (SUIT) toolbox in 65 healthy, right-handed 14-year-olds. For comparison, classical whole brain VBM was performed. RESULTS: The cerebellum-optimized VBM indicated a significant positive correlation between manual dexterity and GM volume in the right cerebellum Lobule VI, corrected for multiple comparisons and non-stationary smoothness. The classical whole brain VBM revealed positive associations (uncorrected) between dexterity performance and GM volume in the left SMA (BA 6), right fusiform gyrus (BA 20) and left cuneus (BA 18), but not cerebellar structures. CONCLUSIONS: The results indicate that cerebellar GM volumes in the right Lobule VI predict manual dexterity in healthy untrained humans when cerebellum-optimized VBM is employed. Although conventional VBM identified brain motor network areas it failed to detect cerebellar structures. Thus, previous studies might have underestimated the importance of cerebellum in manual dexterity.

Accompanying injuries in tibial shaft fractures: how often is there an additional violation of the posterior malleolus and which factors are predictive? A retrospective cohort study.

INTRODUCTION: An undislocated fracture of the posterior malleolus is a common concomitant injury in tibial shaft spiral fractures. Nevertheless, these accompanying injuries cannot always be reliably assessed using conventional X-rays. Thus, the aim of the study is to evaluate how often a fracture of the posterior malleolus occurs with tibial shaft fractures (AO:42A/B/C and AO:43A) and which factors-identifiable in conventional X-rays-are predictive. METHODS: Retrospective evaluation of X-ray and CT images revealed a total of 103 patients with low-energy tibial shaft fractures without direct joint involvement. Proximal fractures and fractures involving the knee were excluded. Basic data on injury, the trauma mechanism, the path of the fracture, bony avulsions of the posterior syndesmosis and the procedures performed were evaluated. RESULTS: Thirty-nine fractures were located in the middle third of the tibia, 64 in the distal third. In 65 cases, a spiral fracture (simple or wedge fracture) was found. In 31/103 fractures, an additional osseous avulsion of the posterior syndesmosis could be detected, 5 (16.1%) of them were not recognized preoperatively due to an absence of CT imaging. In three of these patients, a fracture of the posterior malleolus was only recognized postoperatively, and an additional surgery was necessary. The spiral fractures were classified in the a.p. X-ray according to their path from lateral proximal to medial distal (Type A) or from medial proximal to lateral distal (Type B). A Pearson chi-square test and Fisher's exact test showed a highly significant accumulation of accompanying posterior malleolus fractures for type A fractures (p = 0.001), regardless of the location of the fracture. In addition, the fractures with involvement of the posterior malleolus had a significantly higher proportion in the fractures of the distal third (p = 0.003). There was no statistically significant relationship between the height of the fracture and the path of the fracture (type A or B). These two factors seem to be independent factors for participation of the posterior malleolus. CONCLUSION: In 40.6% of the tibial shaft fractures in the distal third, in 56.9% of the type A spiral fractures and in 67.6% of the type A fractures in the distal third, the ankle joint is involved with bony avulsion of the posterior syndesmosis, which is not always recognized in conventional X-rays. To avoid complications such as additional operations, instability and post-traumatic arthrosis, we recommend preoperative imaging of the ankle using CT for these fractures. LEVEL OF EVIDENCE: III, retrospective cohort study. TRAIL REGISTRATION NUMBER: DRKS00024536.

New ways of treatment of fractures of the humeral shaft: does the combination of intramedullary nail osteosynthesis and cerclage improve the healing process?

INTRODUCTION: The humeral shaft fracture is a rare fracture of the long bones with various treatment options. Dreaded complications such as lesions of the radial nerve or non-unions make the decision for what kind of therapy option more difficult. Biomechanically the upper arm is mostly exposed to rotational forces, which affect intramedullary nail osteosynthesis. Additive cerclage may compensate for these in spiral fractures. The aim of this study is to investigate what effect a combination of intramedullary nail osteosynthesis and limited invasive cerclage has on the rate of healing. In addition, this study addresses the question if complications arise as a result of cerclage. METHODS: In this retrospective study, 109 patients were evaluated, who, during a period of 6 years, underwent operative treatment of a humerus shaft fracture with a combination of intramedullary nail osteosynthesis and additive cerclage. The primary end point was to establish the rate of healing. A secondary end point was to evaluate complications such as infections and damage to the nerve. This was followed by an examination of patient files and X-ray images and a statistical analysis with SPSS. RESULTS AND CONCLUSION: The healing process shows a non-union rate of 2.6%, and complications such as secondary radial nerve lesions of 4.6%. The antegrade intramedullary nail osteosynthesis with limited invasive, additive cerclage reduces the risk of non-union and does not lead to an increased risk of iatrogenic damage to the radial nerve. Wound healing was not impaired and there were no infections through the cerclage in our patient cohort.

Automated computation of nerve fibre inclinations from 3D polarised light imaging measurements of brain tissue.

The method 3D polarised light imaging (3D-PLI) measures the birefringence of histological brain sections to determine the spatial course of nerve fibres (myelinated axons). While the in-plane fibre directions can be determined with high accuracy, the computation of the out-of-plane fibre inclinations is more challenging because they are derived from the amplitude of the birefringence signals, which depends e.g. on the amount of nerve fibres. One possibility to improve the accuracy is to consider the average transmitted light intensity (transmittance weighting). The current procedure requires effortful manual adjustment of parameters and anatomical knowledge. Here, we introduce an automated, optimised computation of the fibre inclinations, allowing for a much faster, reproducible determination of fibre orientations in 3D-PLI. Depending on the degree of myelination, the algorithm uses different models (transmittance-weighted, unweighted, or a linear combination), allowing to account for regionally specific behaviour. As the algorithm is parallelised and GPU optimised, it can be applied to large data sets. Moreover, it only uses images from standard 3D-PLI measurements without tilting, and can therefore be applied to existing data sets from previous measurements. The functionality is demonstrated on unstained coronal and sagittal histological sections of vervet monkey and rat brains.

A minimally invasive cerclage of the tibia in a modified Goetze technique: operative technique and first clinical results.

INTRODUCTION: In spiral fractures of the tibia, the stability of an osteosynthesis may be significantly increased by additive cerclages and, according to biomechanical studies, be brought into a state that allows immediate full weight bearing. As early as 1933, Goetze described a minimally invasive technique for classic steel cerclages. This technique was modified, so that it can be used for modern cable cerclages in a soft part saving way. METHOD: After closed reduction, an 8 Fr redon drain is first inserted in a minimally invasive manner, strictly along the bone and placed around the tibia via 1 cm incisions on the anterolateral and dorsomedial tibial edges using a curette and a tissue protection sleeve. Via this drain, a 1.7 mm cable cerclage can be inserted. The fracture is then anatomically reduced while simultaneously tightening the cerclage. Subsequently, a nail or a minimally invasive plate osteosynthesis is executed using the standard technique. Using the hospital documentation system, data of patients that were treated with additional cerclages for tibial fractures between 01/01/2014 and 06/30/2020 were subjected to a retrospective analysis for postoperative complications (wound-healing problems, infections and neurovascular injury). Inclusion criteria were: operatively treated tibial fractures, at least one minimally invasive additive cerclage, and age of 18 years or older. Exclusion criteria were: periprosthetic or pathological fractures and the primary need of reconstructive plastic surgery. SPSS was used for statistical analysis. RESULTS: 96 tibial shaft spiral fractures were treated with a total of 113 additive cerclages. The foregoing resulted in 10 (10.4%) postoperative wound infections, 7 of which did not involve the cerclage. One lesion of the profundal peroneal nerve was detected, which largely declined after cerclage removal. In 3 cases, local irritation from the cerclage occurred and required removal of material. CONCLUSION: In the described technique, cerclages may be inserted additively at the tibia in a minimally invasive manner and with a few complications, thus significantly increasing the stability of an osteosynthesis. How this ultimately affects fracture healing is the subject of an ongoing study.

Scatterometry Measurements With Scattered Light Imaging Enable New Insights Into the Nerve Fiber Architecture of the Brain.

The correct reconstruction of individual (crossing) nerve fibers is a prerequisite when constructing a detailed network model of the brain. The recently developed technique Scattered Light Imaging (SLI) allows the reconstruction of crossing nerve fiber pathways in whole brain tissue samples with micrometer resolution: the individual fiber orientations are determined by illuminating unstained histological brain sections from different directions, measuring the transmitted scattered light under normal incidence, and studying the light intensity profiles of each pixel in the resulting image series. So far, SLI measurements were performed with a fixed polar angle of illumination and a small number of illumination directions, providing only an estimate of the nerve fiber directions and limited information about the underlying tissue structure. Here, we use a display with individually controllable light-emitting diodes to measure the full distribution of scattered light behind the sample (scattering pattern) for each image pixel at once, enabling scatterometry measurements of whole brain tissue samples. We compare our results to coherent Fourier scatterometry (raster-scanning the sample with a non-focused laser beam) and previous SLI measurements with fixed polar angle of illumination, using sections from a vervet monkey brain and human optic tracts. Finally, we present SLI scatterometry measurements of a human brain section with 3 µm in-plane resolution, demonstrating that the technique is a powerful approach to gain new insights into the nerve fiber architecture of the human brain.

Pathological gambling is linked to reduced activation of the mesolimbic reward system.

By analogy to drug dependence, it has been speculated that the underlying pathology in pathological gambling is a reduction in the sensitivity of the reward system. Studying pathological gamblers and controls during a guessing game using functional magnetic resonance imaging, we observed a reduction of ventral striatal and ventromedial prefrontal activation in the pathological gamblers that was negatively correlated with gambling severity, linking hypoactivation of these areas to disease severity.

FAConstructor: an interactive tool for geometric modeling of nerve fiber architectures in the brain.

PURPOSE: The technique 3D polarized light imaging (3D-PLI) allows to reconstruct nerve fiber orientations of postmortem brains with ultra-high resolution. To better understand the physical principles behind 3D-PLI and improve the accuracy and reliability of the reconstructed fiber orientations, numerical simulations are employed which use synthetic nerve fiber models as input. As the generation of fiber models can be challenging and very time-consuming, we have developed the open source FAConstructor tool which enables a fast and efficient generation of synthetic fiber models for 3D-PLI simulations. METHODS: The program was developed as an interactive tool, allowing the user to define fiber pathways with interpolation methods or parametric functions and providing visual feedback. RESULTS: Performance tests showed that most processes scale almost linearly with the amount of fiber points in FAConstructor. Fiber models consisting of < 1.6 million data points retain a frame rate of more than 30 frames per second, which guarantees a stable and fluent workflow. The applicability of FAConstructor was demonstrated on a well-defined fiber model (Fiber Cup phantom) for two different simulation approaches, reproducing effects known from 3D-PLI measurements. CONCLUSION: We have implemented a user-friendly and efficient tool that enables an interactive and fast generation of synthetic nerve fiber configurations for 3D-PLI simulations. Already existing fiber models can easily be modified, allowing to simulate many different fiber models in a reasonable amount of time.