Martijn Froeling

Diffusion‐tensor MRI reveals the complex muscle architecture of the human forearm

To design a time‐efficient patient‐friendly clinical diffusion tensor MRI protocol and postprocessing tool to study the complex muscle architecture of the human forearm.

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.Though tractography is widely used, it has not been systematically validated. Here, authors report results from 20 groups showing that many tractography algorithms produce both valid and invalid bundles.

DTI of human skeletal muscle: the effects of diffusion encoding parameters, signal‐to‐noise ratio and T2 on tensor indices and fiber tracts

In this study, we have performed simulations to address the effects of diffusion encoding parameters, signal‐to‐noise ratio (SNR) and T2 on skeletal muscle diffusion tensor indices and fiber tracts. Where appropriate, simulations were corroborated and validated by in vivo diffusion tensor imaging (DTI) of human skeletal muscle. Specifically, we have addressed: (i) the accuracy and precision of the diffusion parameters and eigenvectors at different SNR levels; (ii) the effects of the diffusion gradient direction encoding scheme; (iii) the optimal b value for diffusion tensor estimation; (iv) the effects of changes in skeletal muscle T2; and, finally, the influence of SNR on fiber tractography and derived (v) fiber lengths, (vi) pennation angles and (vii) fiber curvatures. We conclude that accurate DTI of skeletal muscle requires an SNR of at least 25, a b value of between 400 and 500 s/mm2, and data acquired with at least 12 diffusion gradient directions homogeneously distributed on half a sphere. Furthermore, for DTI studies focusing on skeletal muscle injury or pathology, apparent changes in the diffusion parameters need to be interpreted with great care in view of the confounding effects of T2, particularly for moderate to low SNR values. Copyright

Muscle changes detected with diffusion-tensor imaging after long-distance running

PURPOSE To develop a protocol for diffusion-tensor imaging (DTI) of the complete upper legs and to demonstrate feasibility of detection of subclinical sports-related muscle changes in athletes after strenuous exercise, which remain undetected by using conventional T2-weighted magnetic resonance (MR) imaging with fat suppression. MATERIALS AND METHODS The research was approved by the institutional ethics committee review board, and the volunteers provided written consent before the study. Five male amateur long-distance runners underwent an MR examination (DTI, T1-weighted MR imaging, and T2-weighted MR imaging with fat suppression) of both upper legs 1 week before, 2 days after, and 3 weeks after they participated in a marathon. The tensor eigenvalues (λ1, λ2, and λ3), the mean diffusivity, and the fractional anisotropy (FA) were derived from the DTI data. Data per muscle from the three time-points were compared by using a two-way mixed-design analysis of variance with a Bonferroni posthoc test. RESULTS The DTI protocol allowed imaging of both complete upper legs with adequate signal-to-noise ratio and within a 20-minute imaging time. After the marathon, T2-weighted MR imaging revealed grade 1 muscle strains in nine of the 180 investigated muscles. The three eigenvalues, mean diffusivity, and FA were significantly increased (P < .05) in the biceps femoris muscle 2 days after running. Mean diffusivity and eigenvalues λ1 and λ2 were significantly (P < .05) increased in the semitendinosus and gracilis muscles 2 days after the marathon. CONCLUSION A feasible method for DTI measurements of the upper legs was developed that fully included frequently injured muscles, such as hamstrings, in one single imaging session. This study also revealed changes in DTI parameters that over time were not revealed by qualitative T2-weighted MR imaging with fat suppression.

Architectural configuration and microstructural properties of the sacral plexus: A diffusion tensor MRI and fiber tractography study

The ability to investigate microstructural properties of the central nervous system with diffusion tensor imaging (DTI) has been shown in many studies. More recently, DTI is being applied outside the brain showing promising results, for instance, for investigating muscle tissue. In this work, we demonstrate the feasibility of diffusion tensor imaging (DTI) and fiber tractography to study the nerves of the sacral plexus in humans in vivo and to assess the architectural configuration and microstructural properties of these peripheral nerves. For this research goal we optimized the acquisition parameters of a DTI sequence and acquired data from 10 healthy adults and one 12-year patient having spina bifida and neurogenic bladder dysfunction. For the healthy volunteers, we estimated the fractional anisotropy (FA) and mean (MD), axial (AD), and radial diffusivities (RD) of the sacral plexus nerves which may serve as a baseline for future studies. We demonstrated that tractography of the sacral plexus on a 3 Tesla MR scanner is feasible, giving 3D insight in the general anatomy and organization of the nerves L4 to S3. In addition, branches to the pudendal nerve were also found in 4 volunteers. There were no significant differences in any of the estimated diffusion measures between the right and left sided nerves or between the nerves L4 to S3 on an intra-subject basis. Furthermore, clinical feasibility of DTI and tractography in a child having spina bifida and neurogenic bladder dysfunction is demonstrated. The architectural configuration of the childs sacral plexus was comparable with the healthy volunteers and no significant disrupted nerve fibers were observed. However, there are strong indications that abnormal diffusion characteristics are present at the level of the neural tube defect due to incomplete segments of the nerves that are close to the vertebrae. These findings are encouraging for using DTI as a means to investigate changes in microstructural properties of the nerves of the sacral plexus. Moreover, this new methodology may provide a new avenue to a better analysis and diagnosis of neurogenic bladder dysfunctions.

Feasibility of diffusion tensor imaging (DTI) with fibre tractography of the normal female pelvic floor

ObjectivesTo prospectively determine the feasibility of diffusion tensor imaging (DTI) with fibre tractography as a tool for the three-dimensional (3D) visualisation of normal pelvic floor anatomy.MethodsFive young female nulliparous subjects (mean age 28 ± 3 years) underwent DTI at 3.0T. Two-dimensional diffusion-weighted axial spin-echo echo-planar (SP-EPI) pulse sequence of the pelvic floor was performed, with additional T2-TSE multiplanar sequences for anatomical reference. Fibre tractography for visualisation of predefined pelvic floor and pelvic wall muscles was performed offline by two observers, applying a consensus method. Three eigenvalues (λ1, λ2, λ3), fractional anisotropy (FA) and mean diffusivity (MD) were calculated from the fibre trajectories.ResultsIn all subjects fibre tractography resulted in a satisfactory anatomical representation of the pubovisceral muscle, perineal body, anal - and urethral sphincter complex and internal obturator muscle. Mean FA values ranged from 0.23 ± 0.02 to 0.30 ± 0.04, MD values from 1.30 ± 0.08 to 1.73 ± 0.12 × 10−³ mm²/s. Muscular structures in the superficial layer of the pelvic floor could not be satisfactorily identified.ConclusionsThis study demonstrates the feasibility of visualising the complex three-dimensional pelvic floor architecture using 3T-DTI with fibre tractography. DTI of the deep female pelvic floor may provide new insights into pelvic floor disorders.

Reproducibility of diffusion tensor imaging in human forearm muscles at 3.0 T in a clinical setting

The aim of the present study was to evaluate a fast clinical protocol to enable diffusion tensor imaging of the human forearm and assess the reproducibility of six diffusion tensor imaging parameters, i.e., the tensor eigenvalues (λ1, λ2, and λ3), mean diffusivity, fractional anisotropy, and ellipsoid eccentricity. The right forearms of 10 healthy volunteers were scanned twice, with a 1‐week interval. Reproducibility of the diffusion tensor imaging parameters was interpreted using Bland‐Altman plots, coefficient of repeatability, repeatability index, and the intraclass correlation coefficient. Analysis was done for three regions of interest: the whole muscle volume, flexor digitorum profundus, and extensor digitorum. The Bland‐Altman analysis showed that there is good agreement between the two measurements. Based on the intraclass correlation coefficients, agreement was substantial (0.59 < intraclass correlation coefficient < 0.92) for all six parameters of the whole muscle volume and flexor digitorum profundus but only fair (0.18 < intraclass correlation coefficient < 0.64) for the extensor digitorum. Using a 7 min 40 sec scan protocol, which was well tolerated by the volunteers, the reproducibility of diffusion tensor imaging parameters was demonstrated. However, repeatability varies, depending on the region of interest and diffusion tensor imaging parameters. This should be taken into account when a longitudinal study is designed. Magn Reson Med, 2010.

Tractography-based connectomes are dominated by false-positive connections

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

Investigating the non-linearity of the BOLD cerebrovascular reactivity response to targeted hypo/hypercapnia at 7 T

Cerebrovascular reactivity (CVR) is a mechanism responsible for maintaining stable perfusion pressure within the brain via smooth muscle mediated modulations of vascular tone. The amplitude of cerebral blood flow (CBF) change in response to a stimulus has been evaluated using Blood Oxygen Level Dependent (BOLD) MRI, however the relationship between the stimulus and the measured signal remains unclear. CVR measured invasively in animal models and using blood-velocity based measurements in humans has demonstrated a sigmoidal relationship between cerebral blood flow and CO2 partial pressure. Using an ultra-high magnetic field strength (7T) MRI scanner and a computer controlled gas delivery system, we examined the regional and voxel-wise CVR response in relation to a targeted progressively increasing hypo- to hypercapnic stimulus. The aim of this study was to assess the non-linearity/sigmoidal behavior of the CVR response at varying arterial CO2 (PaCO2) levels. We find that a sigmoidal model provides a better description of the BOLD signal response to increasing PaCO2 than a linear model. A distinct whole-brain and gray matter BOLD-CVR signal plateau was observed in both voxel-wise and regional analysis. Furthermore, we demonstrate that a progressively increasing stimulus in combination with a sigmoidal response model can be used to obtain CVR values and provides additional physiologically relevant information (such as linear and non-linear response domains, and maximum response amplitudes) that may be more difficult to obtain from blocked CVR experiments. Considering these results, we propose an alternative way in which to define CVR based on the derivative of the BOLD-CVR response curve, which can potentially be used to differentiate between healthy and diseased vascular states.

Techniques and applications of skeletal muscle diffusion tensor imaging: A review

Diffusion tensor imaging (DTI) is increasingly applied to study skeletal muscle physiology, anatomy, and pathology. The reason for this growing interest is that DTI offers unique, noninvasive, and potentially diagnostically relevant imaging readouts of skeletal muscle structure that are difficult or impossible to obtain otherwise. DTI has been shown to be feasible within most skeletal muscles. DTI parameters are highly sensitive to patient‐specific properties such as age, body mass index (BMI), and gender, but also to more transient factors such as exercise, rest, pressure, temperature, and relative joint position. However, when designing a DTI study one should not only be aware of sensitivity to the above‐mentioned factors but also the fact that the DTI parameters are dependent on several acquisition parameters such as echo time, b‐value, and diffusion mixing time. The purpose of this review is to provide an overview of DTI studies covering the technical, demographic, and clinical aspects of DTI in skeletal muscles. First we will focus on the critical aspects of the acquisition protocol. Second, we will cover the reported normal variance in skeletal muscle diffusion parameters, and finally we provide an overview of clinical studies and reported parameter changes due to several (patho‐)physiological conditions. J. Magn. Reson. Imaging 2016;43:773–788