Individually Customisable, Non-Invasive Head Immobilisation for Primates with the Option for Voluntary Engagement
Lead Research Organisation:
Newcastle University
Department Name: Institute of Neuroscience
Abstract
Many neuroscientific laboratories that require head immobilisation in animal procedures use surgically implanted head posts. By contrast, nearly all head immobilisation procedures with humans rely on non-invasive head restraint techniques. Some attempts have been made over the years to develop non-invasive head restraints for, in particular, work with awake and behaving nonhuman primates, but these systems have had little impact in replacing the surgically implanted head posts.
We have identified several reasons why the previous systems may not have been broadly accepted. Some of the issues are that the current systems, 1) are of the 'one size fits all' approach and thus will not work with animals of different sizes or those of different species, 2) often prevent access for eye tracking and sound or visual stimulation that many laboratories require during head immobilisation, 3) cause distress when being used, 4) create pressure points that can become infected or do not sufficiently immobilise the head, and 5) to our knowledge, there do not seem to be options where the animals can be trained to voluntarily engage a head immobilisation system for shorter period of restraint. Thus many laboratories continue to rely on what they are used to: surgically implanted head post options.
We propose a customised head immobilisation system and an approach in this proposal that aims to address all of these issues. Our approach is based on non-invasive head restraints that are being used daily in hospitals across the U.K. for adult and child cancer patients. For instance if a person is diagnosed with head or neck cancer this might require urgent radiotherapy treatment. This treatment depends on a precise, customised head immobilisation system so that head movement can be minimised during high-energy radiotherapy that targets cancerous cells while minimising neighbouring tissue damage. Thereby, cancer radiotherapy units have become experts at providing individually customised, non-invasive head immobilisation options for patients of many sizes.
For this project we have established a collaboration with the Cancer Radiotherapy Unit at the Freeman Hospital in Newcastle. Out of the approaches that they routinely use with humans we have identified one that has the potential to overcome the limitations of previous head restrain approaches in nonhuman primates. We aim to develop and test this system in several primates of different sizes (and in two different species). We will evaluate the effectiveness of the system and the quality of the data that can be obtained using common neuroscientific procedures and will engage a commercial partner to help us to broadly market and distribute the systems.
In particular, we aim to develop highly customisable helmets and a novel approach where the animals will be trained to engage a face mask system for shorter periods of immobilisation. In these ways, the project provides considerable opportunity for innovation to help to reduce the reliance on invasive approaches. In particular for animals participating in non-invasive procedures, such as brain imaging or infra-red eye tracking techniques that are commonly in use with humans, a non-invasive head immobilisation system has the opportunity to make these approaches 100% non-invasive.
We have identified several reasons why the previous systems may not have been broadly accepted. Some of the issues are that the current systems, 1) are of the 'one size fits all' approach and thus will not work with animals of different sizes or those of different species, 2) often prevent access for eye tracking and sound or visual stimulation that many laboratories require during head immobilisation, 3) cause distress when being used, 4) create pressure points that can become infected or do not sufficiently immobilise the head, and 5) to our knowledge, there do not seem to be options where the animals can be trained to voluntarily engage a head immobilisation system for shorter period of restraint. Thus many laboratories continue to rely on what they are used to: surgically implanted head post options.
We propose a customised head immobilisation system and an approach in this proposal that aims to address all of these issues. Our approach is based on non-invasive head restraints that are being used daily in hospitals across the U.K. for adult and child cancer patients. For instance if a person is diagnosed with head or neck cancer this might require urgent radiotherapy treatment. This treatment depends on a precise, customised head immobilisation system so that head movement can be minimised during high-energy radiotherapy that targets cancerous cells while minimising neighbouring tissue damage. Thereby, cancer radiotherapy units have become experts at providing individually customised, non-invasive head immobilisation options for patients of many sizes.
For this project we have established a collaboration with the Cancer Radiotherapy Unit at the Freeman Hospital in Newcastle. Out of the approaches that they routinely use with humans we have identified one that has the potential to overcome the limitations of previous head restrain approaches in nonhuman primates. We aim to develop and test this system in several primates of different sizes (and in two different species). We will evaluate the effectiveness of the system and the quality of the data that can be obtained using common neuroscientific procedures and will engage a commercial partner to help us to broadly market and distribute the systems.
In particular, we aim to develop highly customisable helmets and a novel approach where the animals will be trained to engage a face mask system for shorter periods of immobilisation. In these ways, the project provides considerable opportunity for innovation to help to reduce the reliance on invasive approaches. In particular for animals participating in non-invasive procedures, such as brain imaging or infra-red eye tracking techniques that are commonly in use with humans, a non-invasive head immobilisation system has the opportunity to make these approaches 100% non-invasive.
Technical Summary
We aim to develop two customised head immobilisation systems. Each has distinct advantages.
Helmet System: We have developed a prototype of this system for a macaque based on a similar approach for human non-invasive head immobilisation. The helmet is obtained by making a model of the primate's head which can be used to create the helmet and face moulds without further work on the animal. This head model can be obtained in one of several ways to provide flexibility to the user. Once the head model is available it is cut in half so that the back piece and the front piece of the helmet can be created. Then a translucent thermoplastic sheet a few millimetres thick is heated so that it can be moulded around the head pieces. The helmet system aims to provide head immobilisation for a longer period of time, and greater stability for electrophysiological recordings from a recording chamber, which can be incorporated into the helmet design by cutting away a region for the chamber implant. The helmet will have the user specific head post piece attached as needed to flexibly integrate into the laboratory-specific system.
Temporary Head Immobilisation System (T.H.I.S.): The customised face mask will be attached to the front of the animal's chair. Then the animal will have the option to engage the face mask for shorter periods of time (<30 secs) of "self" immobilisation after which it can move its head and obtain a juice or food reward. When the animal is ready, the computer will start the testing trial if the eye tracker detects the presence of the eye in a particular position, or we can incorporate pressure sensors into the mask.
The efficacy of both systems will be tested with fMRI, eye tracking, and, time permitting, electrophysiological recording. In animals that have a head post implant we can compare the results when they are immobilised using their implant or when we use the helmet system or T.H.I.S. (whereby a cut out will be made around the implant).
Helmet System: We have developed a prototype of this system for a macaque based on a similar approach for human non-invasive head immobilisation. The helmet is obtained by making a model of the primate's head which can be used to create the helmet and face moulds without further work on the animal. This head model can be obtained in one of several ways to provide flexibility to the user. Once the head model is available it is cut in half so that the back piece and the front piece of the helmet can be created. Then a translucent thermoplastic sheet a few millimetres thick is heated so that it can be moulded around the head pieces. The helmet system aims to provide head immobilisation for a longer period of time, and greater stability for electrophysiological recordings from a recording chamber, which can be incorporated into the helmet design by cutting away a region for the chamber implant. The helmet will have the user specific head post piece attached as needed to flexibly integrate into the laboratory-specific system.
Temporary Head Immobilisation System (T.H.I.S.): The customised face mask will be attached to the front of the animal's chair. Then the animal will have the option to engage the face mask for shorter periods of time (<30 secs) of "self" immobilisation after which it can move its head and obtain a juice or food reward. When the animal is ready, the computer will start the testing trial if the eye tracker detects the presence of the eye in a particular position, or we can incorporate pressure sensors into the mask.
The efficacy of both systems will be tested with fMRI, eye tracking, and, time permitting, electrophysiological recording. In animals that have a head post implant we can compare the results when they are immobilised using their implant or when we use the helmet system or T.H.I.S. (whereby a cut out will be made around the implant).
Planned Impact
Primates participating in research procedures: This project is likely to have a direct positive impact on the welfare of nonhuman primates participating in neuroscientific procedures that require head immobilisation. The approach to develop non-invasive head restraint options will benefit at least the animals participating in otherwise non-invasive approaches, such as those in use with humans, e.g., MRI, EEG, eye tracking. Surgical procedures will still be needed for projects that require chambers for neurophysiological recordings or neuropharamacological study. However, even here we could refine these procedures because the implants could be minimized by not having to include a head post since our helmet systems could accommodate space for a chamber, resulting in smaller implants and less chance of infection in comparison to current procedures. To quantify this impact, we aim to establish a website where the scientific community can be polled on whether they have implemented or plant to implement more non-invasive procedures and whether these have reduced invasive procedures or animal numbers.
NC3Rs: Our project will directly impact upon the refinement of head immobilisation procedures with primates. Since our procedures will develop techniques for smaller primates like marmosets, they might also in the long run be useful for restraint procedures with other animals such as mice, rodents and birds. During our project duration we aim to address Refinement but could also have an impact on Reduction. The reason for this is that surgically implanted head posts sometimes cause delays due to infection or need to be removed with months to years of recovery of the animal. In these cases another animal is brought in to move advance the project. Such animal numbers will be documented and fed back to the NC3Rs after project completion.
Veterinary staff: The veterinary might benefit from a reduction in their workload to maintain animals with surgical implants and in conducting surgical procedures. Fewer implants could also reduce the possibility of animals developing antibiotic resistant bacteria. The impact on the veterinary staff will be polled after project completion.
Public: Any effort to improve animal welfare will improve the public perception of animal use in research. Pictures of animals with implants tend to be viewed more negatively even by lay people wishing to develop an informed opinion of medically related research in nonhuman primates. This project can help research institutions to be more transparent about the work that is conducted and to reduce the sensationalism created by pictures of animals with implants. Our planned web page could have an opportunity for a discussion form on the impression of scientific and animal welfare improvements, or links to these elsewhere.
Home Office. The project is also likely to result in the Home Office downgrading the severity bands of a number of projects if it is seen that efforts are being made to use non-invasive approaches, wherever possible.
Human Procedures in NHS Hospitals. Our developments could also indirectly improve NHS procedures for cancer radiotherapy patients. For instance, our accommodation techniques for helping animals to adjust to longer periods of restraint or the voluntary engagement system might, by way of our collaborators, be used to improve procedures with cancer patients, especially children.
Industry impact: A number of research projects that require head immobilisation are also conducted in the industrial sector. If the academic sector advances effective non-invasive head restraints, it is likely that the industrial sector will take note and implement these procedures, especially if they would reduce cost, as anticipated. Our goals to broadly communicate and distribute potential products are likely to help this potential impact to materialise.
NC3Rs: Our project will directly impact upon the refinement of head immobilisation procedures with primates. Since our procedures will develop techniques for smaller primates like marmosets, they might also in the long run be useful for restraint procedures with other animals such as mice, rodents and birds. During our project duration we aim to address Refinement but could also have an impact on Reduction. The reason for this is that surgically implanted head posts sometimes cause delays due to infection or need to be removed with months to years of recovery of the animal. In these cases another animal is brought in to move advance the project. Such animal numbers will be documented and fed back to the NC3Rs after project completion.
Veterinary staff: The veterinary might benefit from a reduction in their workload to maintain animals with surgical implants and in conducting surgical procedures. Fewer implants could also reduce the possibility of animals developing antibiotic resistant bacteria. The impact on the veterinary staff will be polled after project completion.
Public: Any effort to improve animal welfare will improve the public perception of animal use in research. Pictures of animals with implants tend to be viewed more negatively even by lay people wishing to develop an informed opinion of medically related research in nonhuman primates. This project can help research institutions to be more transparent about the work that is conducted and to reduce the sensationalism created by pictures of animals with implants. Our planned web page could have an opportunity for a discussion form on the impression of scientific and animal welfare improvements, or links to these elsewhere.
Home Office. The project is also likely to result in the Home Office downgrading the severity bands of a number of projects if it is seen that efforts are being made to use non-invasive approaches, wherever possible.
Human Procedures in NHS Hospitals. Our developments could also indirectly improve NHS procedures for cancer radiotherapy patients. For instance, our accommodation techniques for helping animals to adjust to longer periods of restraint or the voluntary engagement system might, by way of our collaborators, be used to improve procedures with cancer patients, especially children.
Industry impact: A number of research projects that require head immobilisation are also conducted in the industrial sector. If the academic sector advances effective non-invasive head restraints, it is likely that the industrial sector will take note and implement these procedures, especially if they would reduce cost, as anticipated. Our goals to broadly communicate and distribute potential products are likely to help this potential impact to materialise.