Periodic Reporting for period 1 - I-MUSCLE (Imaging of MUscle Shape Changes during eLEctrically-stimulated contractions)
Okres sprawozdawczy: 2022-09-01 do 2024-08-31
To move our body, we need skeletal muscles to contract and produce force. While doing so, the muscles change shape in a complex pattern. Additionally, there is a large variability between the shapes of different muscles, and between the same muscle in different individuals. Despite the obvious presence of such astounding variation in muscle shape, we know little about its functional role in force production.
While different factors contribute to muscle force production, these factors also affect the muscle’s shape during contraction, resulting in a theoretical close relation between the muscle’s shape and force production.
In I-MUSCLE, we aimed to take an innovative experimental approach in investigating the link between 3D whole muscle shape changes and muscle force production, which would simultaneously advance the current state-of-the-art in medical imaging for measuring muscle shapes during contraction. To achieve the overall aim, we aimed to focus on 3 specific objectives: (1) to determine the best approach for measuring dynamic muscle shape changes in situ, (2) to assess the relation between muscle shape and force during different modes of contraction, and (3) to assess the effect of local stimulation on muscle shape changes.
The next steps to be taken with I-MUSCLE were to use ultrafast CT for testing and optimising the use of stereo X-ray video for measurements of muscle shape during dynamic contractions (Objective (Obj.) 1; Fig. 1). By taking an in situ (on domestic chickens (gallus gallus domesticus)) approach, and by using electrical stimulations, we could control the activation and directly measure the forces produced by the stimulated muscle. These approaches would allow us to perform, for the first time ever, a series of experiments in which the whole muscle shape is imaged during electrical stimulation to answer key questions about the functional role of muscle shape changes in force production. We aimed to assess the muscle shape changes under different conditions (different muscle-tendon unit lengths and different contraction modes) (i) when activating the muscle globally through electrical stimulation of the nerve (Obj. 2; Fig. 1), and (ii) when only specific parts of the muscle (i.e. proximally or distally) are activated (Obj. 3; Fig. 1). While the proposed measurements for IMUSCLE cannot be performed in humans, it is a necessary first step to advance the methodology and to validate the close link between 3D whole muscle shape changes and muscle force production.
The above described measurements however, are not possible with the current state-of-the-art. To tackle this challenge, we therefore aimed, with I-MUSCLE, to advance the current state-of-the-art in 3D whole muscle imaging. By advancing the current state-of-the-art and answering key questions, I-MUSCLE therefore has the potential to accelerate application in vivo in humans, in healthy and clinical populations. We therefore expected the project to have impact in the field of biomechanics, in the medical imaging industry, and in clinical settings. The project was therefore expected to result in two main contributions: (i) a step-wise increase in our fundamental understanding of muscle shape changes during contraction and its relation to muscle force, and (ii) a significant advancement in the state-of-the-art of medical imaging for muscle shape measurements. Scientific impact. By advancing the state-of-the-art technology, this project may lead to the transitioning towards less-invasive measurements that can eventually be applied to humans and would for example allow the study of muscle contraction under certain constraints, following training or injury, or allowing further clinical research, e.g. in conditions that impair muscle contraction (and likely shape changes) such as post-stroke or in children with cerebral palsy. The importance of I-MUSCLE is therefore to take the first step in a step-wise advancement in our ability to measure 3D whole muscle shapes during movement, as this can currently only be done at rest (e.g. with MRI).
The knowledge contribution of I-MUSCLE was expected to also reach beyond the field of muscle mechanics as it would increase our fundamental understanding on how muscles change shape and how these shape changes are functionally linked to muscle force. This new knowledge would impact other disciplines such as rehabilitation and engineering by highlighting the importance of unrestricted muscle shape changes in relation to muscle force production. This is relevant in many cases such as when using restrictive casks or braces post-injury or post-surgery. The findings would further inform on how local muscle stimulations, as often used in rehabilitation, affect muscle shape changes and ultimately muscle forces, which could lead to better treatment plans. The fundamental nature of this project and the resulting knowledge on how natural muscles change shape would further benefit the design of bio-engineered muscles. While future projects will be required to measure 3D whole muscle shape changes during contraction in humans, I-MUSCLE is a key stepping stone towards: 1. improved (post-surgery) rehabilitation, whether due to neurological conditions or injury. Local stimulations that were to be evaluated are also functionally relevant as there is evidence of task-dependent local muscle activation in healthy humans and in clinical scenarios, (e.g. electrical muscle stimulations in rehabilitation or Botox injection for treatment of cerebral palsy to reduce activation of specific parts of the muscle) (benefit for patients); 2. the transition from ex vivo to in situ and ultimately in vivo measurements of muscle shape changes during contraction (knowledge benefit), and 3. by doing so, reducing and ultimately replacing the need for animal experiments (ethical benefit).
While different factors contribute to muscle force production, these factors also affect the muscle’s shape during contraction, resulting in a theoretical close relation between the muscle’s shape and force production.
In I-MUSCLE, we aimed to take an innovative experimental approach in investigating the link between 3D whole muscle shape changes and muscle force production, which would simultaneously advance the current state-of-the-art in medical imaging for measuring muscle shapes during contraction. To achieve the overall aim, we aimed to focus on 3 specific objectives: (1) to determine the best approach for measuring dynamic muscle shape changes in situ, (2) to assess the relation between muscle shape and force during different modes of contraction, and (3) to assess the effect of local stimulation on muscle shape changes.
The next steps to be taken with I-MUSCLE were to use ultrafast CT for testing and optimising the use of stereo X-ray video for measurements of muscle shape during dynamic contractions (Objective (Obj.) 1; Fig. 1). By taking an in situ (on domestic chickens (gallus gallus domesticus)) approach, and by using electrical stimulations, we could control the activation and directly measure the forces produced by the stimulated muscle. These approaches would allow us to perform, for the first time ever, a series of experiments in which the whole muscle shape is imaged during electrical stimulation to answer key questions about the functional role of muscle shape changes in force production. We aimed to assess the muscle shape changes under different conditions (different muscle-tendon unit lengths and different contraction modes) (i) when activating the muscle globally through electrical stimulation of the nerve (Obj. 2; Fig. 1), and (ii) when only specific parts of the muscle (i.e. proximally or distally) are activated (Obj. 3; Fig. 1). While the proposed measurements for IMUSCLE cannot be performed in humans, it is a necessary first step to advance the methodology and to validate the close link between 3D whole muscle shape changes and muscle force production.
The above described measurements however, are not possible with the current state-of-the-art. To tackle this challenge, we therefore aimed, with I-MUSCLE, to advance the current state-of-the-art in 3D whole muscle imaging. By advancing the current state-of-the-art and answering key questions, I-MUSCLE therefore has the potential to accelerate application in vivo in humans, in healthy and clinical populations. We therefore expected the project to have impact in the field of biomechanics, in the medical imaging industry, and in clinical settings. The project was therefore expected to result in two main contributions: (i) a step-wise increase in our fundamental understanding of muscle shape changes during contraction and its relation to muscle force, and (ii) a significant advancement in the state-of-the-art of medical imaging for muscle shape measurements. Scientific impact. By advancing the state-of-the-art technology, this project may lead to the transitioning towards less-invasive measurements that can eventually be applied to humans and would for example allow the study of muscle contraction under certain constraints, following training or injury, or allowing further clinical research, e.g. in conditions that impair muscle contraction (and likely shape changes) such as post-stroke or in children with cerebral palsy. The importance of I-MUSCLE is therefore to take the first step in a step-wise advancement in our ability to measure 3D whole muscle shapes during movement, as this can currently only be done at rest (e.g. with MRI).
The knowledge contribution of I-MUSCLE was expected to also reach beyond the field of muscle mechanics as it would increase our fundamental understanding on how muscles change shape and how these shape changes are functionally linked to muscle force. This new knowledge would impact other disciplines such as rehabilitation and engineering by highlighting the importance of unrestricted muscle shape changes in relation to muscle force production. This is relevant in many cases such as when using restrictive casks or braces post-injury or post-surgery. The findings would further inform on how local muscle stimulations, as often used in rehabilitation, affect muscle shape changes and ultimately muscle forces, which could lead to better treatment plans. The fundamental nature of this project and the resulting knowledge on how natural muscles change shape would further benefit the design of bio-engineered muscles. While future projects will be required to measure 3D whole muscle shape changes during contraction in humans, I-MUSCLE is a key stepping stone towards: 1. improved (post-surgery) rehabilitation, whether due to neurological conditions or injury. Local stimulations that were to be evaluated are also functionally relevant as there is evidence of task-dependent local muscle activation in healthy humans and in clinical scenarios, (e.g. electrical muscle stimulations in rehabilitation or Botox injection for treatment of cerebral palsy to reduce activation of specific parts of the muscle) (benefit for patients); 2. the transition from ex vivo to in situ and ultimately in vivo measurements of muscle shape changes during contraction (knowledge benefit), and 3. by doing so, reducing and ultimately replacing the need for animal experiments (ethical benefit).
Three specific objectives were formulated towards the main aim described in under header 1.:
i) to determine the best approach for measuring dynamic muscle shape changes in situ
ii) to assess the relation between muscle shape and force during different modes of contraction
iii) to assess the effect of local stimulation on muscle shape changes
Significant progress was made towards the first objective, which focussed on the methodological aspect of the project and an advancement of the current state-of-the-art. In short, we experimented with the different surgical aspects and techniques related to the project (i.e. inserting opaque metal markers and applying a powder to the muscle with as minimal disruptive surgical handling as possible). We collected data under static as well as simulated dynamic conditions and found initial proof that the proposed advancement of the current-state-of-the-art is feasible.
The Fellow also obtained a FELASA Function B certificate following a 168-hour (study time included, 6 ECTS) course, which was a requirement for performing the technical surgeries in the project.
No progress was made towards the other objectives given the early termination of the grant agreement (after 4 months).
i) to determine the best approach for measuring dynamic muscle shape changes in situ
ii) to assess the relation between muscle shape and force during different modes of contraction
iii) to assess the effect of local stimulation on muscle shape changes
Significant progress was made towards the first objective, which focussed on the methodological aspect of the project and an advancement of the current state-of-the-art. In short, we experimented with the different surgical aspects and techniques related to the project (i.e. inserting opaque metal markers and applying a powder to the muscle with as minimal disruptive surgical handling as possible). We collected data under static as well as simulated dynamic conditions and found initial proof that the proposed advancement of the current-state-of-the-art is feasible.
The Fellow also obtained a FELASA Function B certificate following a 168-hour (study time included, 6 ECTS) course, which was a requirement for performing the technical surgeries in the project.
No progress was made towards the other objectives given the early termination of the grant agreement (after 4 months).
Preliminary results provided initial proof that the proposed advancement of the current-state-of-the-art is feasible, more specifically that the proposed technique can be used to track 3D whole muscle shape changes dynamically, at least during muscle stretching. This confirmed already early that the anticipated impact of advancing the current state-of-the-art in muscle imaging techniques and answering key questions on muscle contraction is achievable.
Given the early termination of the grant agreement, further results and advancement are pending and new funding is required to continue this exciting project and achieve the expected impact.
Given the early termination of the grant agreement, further results and advancement are pending and new funding is required to continue this exciting project and achieve the expected impact.