Sensory processing sensitivity and axonal microarchitecture: identifying brain structural characteristics for behavior.

Previous research using functional MRI identified brain regions associated with sensory processing sensitivity (SPS), a proposed normal phenotype trait. To further validate SPS, to characterize it anatomically, and to test the usefulness in psychology of methodologies that assess axonal properties, the present study correlated SPS proxy questionnaire scores (adjusted for neuroticism) with diffusion tensor imaging (DTI) measures. Participants (n = 408) from the Human Connectome Project were studied. Voxelwise analysis showed that mean- and radial diffusivity correlated positively with SPS scores in the right and left subcallosal and anterior-ventral cingulum bundle, and the right forceps minor of the corpus callosum, all frontal cortex areas generally underlying emotion, motivation, and cognition. Further analyses showed correlations throughout medial frontal cortical regions in the right and left ventromedial prefrontal cortex, including the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate, and arcuate fasciculus. Fractional anisotropy was negatively correlated with SPS scores in white matter (WM) of the right premotor/motor/somatosensory/supramarginal gyrus regions. Region of interest (ROI) analysis showed small effect sizes (- 0.165 to 0.148) in WM of the precuneus and inferior frontal gyrus. Other ROI effects were found in the dorsal-, ventral visual pathways and primary auditory cortex. The results reveal that in a large group of participants, axonal microarchitectural differences can be identified with SPS traits that are subtle and in the range of typical behavior. The results suggest that the heightened sensory processing in people who show that SPS may be influenced by the microstructure of WM in specific cortical regions. Although previous fMRI studies had identified most of these areas, the DTI results put a new focus on brain areas related to attention and cognitive flexibility, empathy, emotion, and first levels of sensory processing, as in primary auditory cortex. Psychological trait characterization may benefit from DTI methodology by identifying influential brain systems for traits.

Author Correction: The challenge of mapping the human connectome based on diffusion tractography.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Superoanterior Fasciculus (SAF): A Novel White Matter Pathway in the Human Brain?

Fiber tractography (FT) using diffusion magnetic resonance imaging (dMRI) is widely used for investigating microstructural properties of white matter (WM) fiber-bundles and for mapping structural connections of the human brain. While studying the architectural configuration of the brain's circuitry with FT is not without controversy, recent progress in acquisition, processing, modeling, analysis, and visualization of dMRI data pushes forward the reliability in reconstructing WM pathways. Despite being aware of the well-known pitfalls in analyzing dMRI data and several other limitations of FT discussed in recent literature, we present the superoanterior fasciculus (SAF), a novel bilateral fiber tract in the frontal region of the human brain that-to the best of our knowledge-has not been documented. The SAF has a similar shape to the anterior part of the cingulum bundle, but it is located more frontally. To minimize the possibility that these FT findings are based on acquisition or processing artifacts, different dMRI data sets and processing pipelines have been used to describe the SAF. Furthermore, we evaluated the configuration of the SAF with complementary methods, such as polarized light imaging (PLI) and human brain dissections. The FT results of the SAF demonstrate a long pathway, consistent across individuals, while the human dissections indicate fiber pathways connecting the postero-dorsal with the antero-dorsal cortices of the frontal lobe.

The challenge of mapping the human connectome based on diffusion tractography.

Tractography based on non-invasive diffusion imaging is central to the study of human brain connectivity. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain data set with ground truth tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. Here, we report the encouraging finding that most state-of-the-art algorithms produce tractograms containing 90% of the ground truth bundles (to at least some extent). However, the same tractograms contain many more invalid than valid bundles, and half of these invalid bundles occur systematically across research groups. Taken together, our results demonstrate and confirm fundamental ambiguities inherent in tract reconstruction based on orientation information alone, which need to be considered when interpreting tractography and connectivity results. Our approach provides a novel framework for estimating reliability of tractography and encourages innovation to address its current limitations.

Quantitative effects of inclusion of fat on muscle diffusion tensor MRI measurements.

PURPOSE: To determine the minimum water percentage in a muscle region of interest that would allow diffusion tensor (DT-) MRI data to reflect the diffusion properties of pure muscle accurately. MATERIALS AND METHODS: Proton density-weighted images with and without fat saturation were obtained at the mid-thigh in four subjects. Co-registered DT-MR images were used to calculate the diffusion tensor's eigenvalues and fractional anisotropy. RESULTS: The eigenvalues transitioned monotonically as a function of water signal percentage from values near to those expected for pure fat to those for pure muscle. Also, the fractional anisotropy transitioned monotonically from 0.50 (fat) to 0.20 (muscle). For water signal percentages >55%, none of the diffusion indices differed significantly from those for regions of >90% muscle. CONCLUSION: Accounting for the T1 and T2 values of muscle and fat and the pulse sequence properties, it is concluded that, as a conservative estimate, regions must contain at least 76% muscle tissue to reflect the diffusion properties of pure muscle accurately.

Safety of routine early MRI in preterm infants.

BACKGROUND: Cerebral MRI performed on preterm infants at term-equivalent 30 weeks' gestational age (GA) is increasingly performed as part of standard clinical care. OBJECTIVE: We evaluated safety of these early MRI procedures. MATERIALS AND METHODS: We retrospectively collected data on patient safety of preterm infants who underwent early MRI scans. Data were collected at fixed times before and after the MRI scan. MRI procedures were carried out according to a comprehensive guideline. RESULTS: A total of 52 infants underwent an MRI scan at 30 weeks' GA. Although no serious adverse events occurred and vital parameters remained stable during the procedure, minor adverse events were encountered in 26 infants (50%). The MRI was terminated in three infants (5.8%) because of respiratory instability. Increased respiratory support within 24 h after the MRI was necessary for 12 infants (23.1%) and was significantly associated with GA, birth weight and the mode of respiratory support. Hypothermia (core temperature < 36°C) occurred in nine infants (17.3%). Temperature dropped significantly after the MRI scan. CONCLUSION: Minor adverse events after MRI procedures at 30 weeks GA were common and should not be underestimated. A dedicated and comprehensive guideline for MRI procedures in preterm infants is essential.

Polynomial fitting of DT-MRI fiber tracts allows accurate estimation of muscle architectural parameters.

Fiber curvature is a functionally significant muscle structural property, but its estimation from diffusion-tensor magnetic resonance imaging fiber tracking data may be confounded by noise. The purpose of this study was to investigate the use of polynomial fitting of fiber tracts for improving the accuracy and precision of fiber curvature (κ) measurements. Simulated image data sets were created in order to provide data with known values for κ and pennation angle (θ). Simulations were designed to test the effects of increasing inherent fiber curvature (3.8, 7.9, 11.8 and 15.3 m(-1)), signal-to-noise ratio (50, 75, 100 and 150) and voxel geometry (13.8- and 27.0-mm(3) voxel volume with isotropic resolution; 13.5-mm(3) volume with an aspect ratio of 4.0) on κ and θ measurements. In the originally reconstructed tracts, θ was estimated accurately under most curvature and all imaging conditions studied; however, the estimates of κ were imprecise and inaccurate. Fitting the tracts to second-order polynomial functions provided accurate and precise estimates of κ for all conditions except very high curvature (κ=15.3 m(-1)), while preserving the accuracy of the θ estimates. Similarly, polynomial fitting of in vivo fiber tracking data reduced the κ values of fitted tracts from those of unfitted tracts and did not change the θ values. Polynomial fitting of fiber tracts allows accurate estimation of physiologically reasonable values of κ, while preserving the accuracy of θ estimation.

Repeatability of DTI-based skeletal muscle fiber tracking.

Diffusion tensor imaging (DTI)-based muscle fiber tracking enables the measurement of muscle architectural parameters, such as pennation angle (theta) and fiber tract length (L(ft)), throughout the entire muscle. Little is known, however, about the repeatability of either the muscle architectural measures or the underlying diffusion measures. Therefore, the goal of this study was to investigate the repeatability of DTI fiber tracking-based measurements and theta and L(ft). Four DTI acquisitions were performed on two days that allowed for between acquisition, within day, and between day analyses. The eigenvalues and fractional anisotropy were calculated at the maximum cross-sectional area of, and fiber tracking was performed in, the tibialis anterior muscle of nine healthy subjects. The between acquisitions condition had the highest repeatability for the DTI indices and the architectural parameters. The overall inter class correlation coefficients (ICC's) were greater than 0.6 for both theta and L(ft) and the repeatability coefficients were theta < 10.2 degrees and L(ft) < 50 mm. In conclusion, under the experimental and data analysis conditions used, the repeatability of the diffusion measures is very good and repeatability of the architectural measurements is acceptable. Therefore, this study demonstrates the feasibility for longitudinal studies of alterations in muscle architecture using DTI-based fiber tracking, under similar noise conditions and with similar diffusion characteristics.

DTI-based muscle fiber tracking of the quadriceps mechanism in lateral patellar dislocation.

PURPOSE: To determine the feasibility of using diffusion tensor MRI (DT-MRI) -based muscle fiber tracking to create biomechanical models of the quadriceps mechanism in healthy subjects and those with chronic lateral patellar dislocation (LPD). MATERIALS AND METHODS: Four healthy (average 14.5 years old; BMI 21.8) and four chronic LPD (average 17.3 years old; BMI 22.4) females underwent DT and axial T1W MRI of the thighs. The anatomical and physiologic cross-sectional areas (ACSA and PCSA, respectively) and pennation angle were calculated of the vastus lateralis oblique (VLO) and vastus medialis oblique (VMO) muscles. The predicted resultant force vector on the patella was calculated. RESULTS: The VLO pennation angles in healthy and LPD subjects were 18.7 and 14.5 degrees, respectively (P=0.141). The VMO pennation angles in healthy and LPD subjects were 11.4 and 14.8 degrees, respectively (P=0.02). The ACSA and PCSA VLO:VMO ratios in healthy and LPD subjects were 1.9:1.6 and 2.1:1.6, respectively (P=0.025 and 0.202, respectively). Regardless of whether ACSA or PCSA was used to predict resultant lateral force vectors, the values differed between healthy and LPD subjects (approximately 2 and approximately 5.3 degrees, respectively; P<0.05). CONCLUSION: Chronic LPD patients had more laterally directed predicted resultant force vectors than healthy subjects. Our preliminary results suggest that biomechanical models of the quadriceps mechanism in patients with chronic LPD and healthy subjects can be created in healthy subjects and patients with chronic LPD using DT-MRI.

Quantitative assessment of DTI-based muscle fiber tracking and optimal tracking parameters.

Diffusion tensor imaging-based fiber tracking in skeletal muscle has been used to reconstruct and quantify muscle architecture. In addition, the consistent pattern of muscle fiber geometry enables a quantitative assessment of the fiber tracking. This work describes a method to determine the accuracy of individual muscle fiber tracts based on the location at which the fibers terminate, the fiber path, and similarity to the neighboring fibers. In addition, the effect of different stop criteria settings on this quantitative assessment was investigated. Fiber tracking was performed on the tibialis anterior muscle of nine healthy subjects. Complete fiber tracts covered 89.4 +/- 9.6% and 75.0 +/- 15.2% of the aponeurosis area in the superficial and deep compartments, respectively. Applications of the method include the exclusion of erroneous fiber-tracking results, quantitative assessment of data set quality, and the assessment of fiber-tracking stop criteria.

Skeletal muscle degeneration and regeneration after femoral artery ligation in mice: monitoring with diffusion MR imaging.

PURPOSE: To prospectively evaluate quantitative diffusion magnetic resonance (MR) imaging for monitoring skeletal muscle injury and repair after femoral artery ligation in mice. MATERIALS AND METHODS: All experimental procedures were approved by the local institutional animal care and use committee. Muscle degeneration and regeneration were induced in 16 mice by using unilateral ligation of the femoral artery. Diffusion-tensor and T2-weighted MR imaging examinations were performed before, immediately after, and 3, 10, and 21 days after ligation. Histologic analysis was also performed at these time points. The dynamic changes in T2 and in five diffusion-tensor imaging indexes were studied by using histogram analysis. Differences between the ligated and nonligated limbs were assessed with paired t tests, and analysis of variance was used to determine temporal evolutions. Parametric maps were clustered to depict regional differences in the responses of the different MR imaging indexes. RESULTS: MR indexes in the ligated limb changed over time (P < .007), and temporal evolutions in the ligated and nonligated limbs differed significantly (P < .001). When ischemia was induced, diffusivity and T2 increased, with a maximum change at 3 days, when most muscle damage was observed at histologic analysis. At 10 days, diffusion values were reduced overall, whereas T2 was still increased. At 21 days, parameter values had largely returned to normal. Changes on the diffusion-tensor and T2 maps had spatial differences, which corresponded to the different phases of tissue regeneration observed at histologic analysis. An additional finding was the transient change in direction of the principal eigenvector during the period of maximal muscle damage. CONCLUSION: After femoral artery ligation, the diffusion-tensor indexes changed dynamically in association with the severity and location of muscle damage.

Diffusion Tensor MRI Assessment of Skeletal Muscle Architecture.

Diffusion-tensor magnetic resonance imaging (DTI) offers great potential for understanding structure-function relationships in skeletal muscle. The basis for these studies is that water diffuses more readily along the long axes of muscle fibers than along their transverse axes. This diffusion anisotropy can be characterized using a tensor, with the orientation of the principal eigenvalue corresponding to the long axis of the muscle fiber. These local, voxel-based directions can be combined by a fiber tracking algorithm to reconstruct the whole-muscle architecture. The fiber tracking data can be used to characterize important muscle architectural parameters, such as pennation angle, fiber length, and physiological cross-sectional area. The second and third eigenvalues convey information about muscle structural properties along the fibers' transverse axes. A comprehensive description of the sources of transverse diffusion restriction in muscle and how their relative importance may vary with the image acquisition conditions does not yet exist, but may ultimately make DTI a useful tool in studies of skeletal muscle microstructure as well. Ultimately, DTI-based longitudinal studies of changes in muscle architecture may provide insight into the relationships between structure and function in muscle, the time frames of muscle wasting, and in studying adaptations that maintain muscle functionality.

DTI-based assessment of ischemia-reperfusion in mouse skeletal muscle.

Diffusion tensor imaging (DTI) is frequently applied to characterize the microscopic geometrical properties of tissue. To establish whether and how diffusion MRI responds to transient ischemia of skeletal muscle, we studied the effects of ischemia and reperfusion using DTI and T2-weighted MRI before and during ischemia and up to 24 hr after reperfusion. Ischemia was induced by 50 min of hindlimb occlusion with or without dorsal flexor stimulation. During ischemia the apparent diffusion coefficient (ADC) tended to decrease (up to 15%), whereas the fractional anisotropy (FA) and T2 showed a varied response depending on the protocol and muscle type. During reperfusion the ADC and T2 initially increased and subsequently renormalized for the occlusion protocol. For the occlusion plus stimulation (OS) protocol, the FA was decreased by 13% and the ADC and T2 were increased by 20% and 57%, respectively, after 24 hr in the stimulated muscle complex. In the latter tissue the three DTI eigenvalues gradually increased upon reperfusion. The smallest eigenvalue (lambda3) showed the largest relative increase. Changes in DTI indices in the reperfusion phases followed a similar time course as the changes in T2. The changes in MR indices after 24 hr correlated with the tissue damage quantified with histology. The highest correlation was observed for lambda3 (R2 = 0.81). This study shows that DTI can be used to assess ischemia-induced damage to skeletal muscle.

Determination of mouse skeletal muscle architecture using three-dimensional diffusion tensor imaging.

Muscle architecture is the main determinant of the mechanical behavior of skeletal muscles. This study explored the feasibility of diffusion tensor imaging (DTI) and fiber tracking to noninvasively determine the in vivo three-dimensional (3D) architecture of skeletal muscle in mouse hind leg. In six mice, the hindlimb was imaged with a diffusion-weighted (DW) 3D fast spin-echo (FSE) sequence followed by the acquisition of an exercise-induced, T(2)-enhanced data set. The data showed the expected fiber organization, from which the physiological cross-sectional area (PCSA), fiber length, and pennation angle for the tibialis anterior (TA) were obtained. The values of these parameters ranged from 5.4-9.1 mm(2), 5.8-7.8 mm, and 21-24 degrees , respectively, which is in agreement with values obtained previously with the use of invasive methods. This study shows that 3D DT acquisition and fiber tracking is feasible for the skeletal muscle of mice, and thus enables the quantitative determination of muscle architecture.

An MR-compatible device for the in situ assessment of isometric contractile performance of mouse hind-limb ankle flexors.

The goal of the present study was to develop and evaluate an isometric dynamometer for measuring mouse ankle flexor torque after electric stimulation of the nerve. The dynamometer was to be used within an magnetic resonance (MR) apparatus and should require minimal surgical intervention. To quantify the effect of the magnetic field on contractile parameters, measurements were performed both outside and inside the MR apparatus. The effect of magnetic field gradient switching that accompanies rapid MR scanning was tested also. The set-up required no surgical intervention except for chronic implantation of an electrode. The dynamometer has a high mechanical frequency response (270 Hz). Measured muscle strengths were identical outside and inside the MR scanner. However, during fast magnetic field gradient switching, the variability increased and the measured strength decreased slightly (7%). The noise level of the dynamometer (0.02-0.03 N.mm) was low compared with the strength of the dorsal flexors (2 N.mm). Fast gradient switching increased the noise level (0.07 N.mm). The dynamometer had no observable adverse effects on the quality of the MR images of the mouse hind limb. We conclude that the dynamometer enables accurate measurements of mechanical muscle performance during exercise protocols within an MR apparatus under physiological conditions.