Detecting bladder volume and pressure from sacral nerve signals: the key to future artificial control
Lead Research Organisation:
University College London
Department Name: Medical Physics and Biomedical Eng
Abstract
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People |
ORCID iD |
| Nicholas Donaldson (Principal Investigator) |
Publications
Metcalfe B
(2020)
Selective Recording of Urinary Bladder Fullness from the Extradural Sacral Roots.
in Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
Metcalfe BW
(2017)
A New Method for Neural Spike Alignment: The Centroid Filter.
in IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society
Metcalfe BW
(2018)
First demonstration of velocity selective recording from the pig vagus using a nerve cuff shows respiration afferents.
in Biomedical engineering letters
Taylor J
(2020)
The Effects of the Presence of Multiple Conduction Velocities in the Analysis of Electrically-Evoked Compound Action Potentials (eCAPs).
in Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
| Description | The essence of this project is to investigate if bladder pressure and volume can be estimated using electrodes implanted at an extradural site acutely and chronically. The conduction velocities of the sensory (myelinated) afferent fibres from mechanoreceptors of the genital region in sheep are similar to those of fibres conveying bladder pressure and volume information in man (approximately 38 and 41 m/s respectively). In order to discriminate between these signals, we propose to use a method that we have been developing called velocity selective recording (VSR) that may make this possible without using nerve interfaces that are difficult to implant or that endanger these important nerves. The principle of VSR is based on the fact that action potentials (APs) propagate at specific velocities and that these velocities are closely related to the nerve fibre diameter (for myelinated nerves). If, therefore, a recording of neural traffic can be characterised in terms of its velocity spectrum, it will provide a signature relating the recorded signals to their function (VSR can also discriminate between afferent and efferent traffic on a mixed nerve, such as extradural bladder nerves). The method requires multi-electrode cuffs (MECs) and we have used such devices with as many as 11 electrodes along the length of a nerve cuff. Since the signals appearing at the electrodes of an MEC in response to naturally-occurring (physiological) ENG are very small (order of 1 µV) a very low noise environment is required. This requires not only specially-designed recording instrumentation but also an electrically quiet environment with well-characterised and understood background interference sources. This latter requirement is particularly hard to achieve in a modern operating room (OR), which tends to contain many electrically-based devices. Most of our effort to date has therefore been directed towards preparing and characterising the experimental set-up in a designated OR at the Royal Veterinary College (RVC) so that successful neural recordings can be made that make maximum use of our various resources and that do not require expensive additional interference reduction equipment. To date, four acute implantations have been carried out on sheep (15 June 2018, 30 October 2018, 13 December 2018 and 1 March 2019). The first three experiments were significantly compromised by the presence of electrical interference and only compound action potentials (CAPs), evoked by electrical stimulation were recordable. In response to this, two extra days were spent in the OR (3 January and 1 February 2019) with the instrumentation alone, in an attempt to understand these sources. These efforts were successful and in the most recent critical experiment (1 March 2019) we were able to record physiological ENG in response to touch stimulation of the skin in the region of the animal's tail. These recordings were clear above the noise and repeatable. So far, we have used two methods for detecting bladder afferent signals: (i) monitoring the running RMS amplitude of the wide-band amplifier output, and (ii) listening to this raw recording during the experiment. Despite filling the bladder to very large volume (1 litre) and the consequent high pressure (50cm water), there was no apparent neural signal. This might be due to the long period of anaesthesia but it shows that signal processing is essential. The challenge now is, therefore, to see whether the bladder afferent signals can be extracted using VSR. In summary, our findings to date have been; 1. A custom 5-channel integrated amplifier system (CMOS asic) has been constructed (configurable for 10 channels as needed) and its performance verified; 2. A new multi-electrode cuff (MEC) has been designed and built (4 electrodes initially but with a capability to increase to 10 or more); 3. A special tool has been designed to aid the implantation of the MECs on extradural roots of sheep; 4. The OR has been characterised for electrical interference and counter measures taken so that the recording instrumentation is not compromised by the environment; 5. The cuff impedances (2-and 4-wire configurations) have been extensively characterised in vitro and in vivo; 6. Repeatable 4-electrode (configured as 3 dipole channels) in vivo measurements have been made of naturally-occurring (physiological) ENG evoked by (a) stroking and (b) pricking with needles the tissue close to the animal's tail; |
| Exploitation Route | We intend to publish several papers about this difficult technique (nerve signal recording) to assist other researchers and clinicians. |
| Sectors | Electronics,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | We are doing this research to find out whether it is possible to detect the volume and pressure in the urinary bladder from the natural nerve activity in the corresponding nerve roots. Finetech Medical Ltd is the UK company that makes bladder-control neuroprostheses for spinal cord injured patients. So far, our findings suggest that this idea is unlikely to be feasible because although neural signals are detectable, they are very small indeed, close to the noise floor, and prone to interference. I keep the company up to date with our results and we continue to explore alternative approaches, especially more biological approaches encouraging neuroplasticity. |
| First Year Of Impact | 2020 |
| Sector | Healthcare |
| Impact Types | Societal,Economic |
| Title | Nerve cuffs for sacral nerve roots |
| Description | Multiple electrode cuff designed for use in particular surgical space yet convenient to implant. The cuff has been shown to fit into the space provided by the laminectomy. A prototype implantaion tool has be made and tested. The cuff can be closed round the nerve root and sealed. Impedances have been measured after implantation. The recording environment has been characterised and recording set-up improved so that now microvolt level differential recording possible on multiple channels without significant interference. Cutaneous afferent nerve signals have been recorded when rubbing the sheep's rump (S3 dermatome). March 2020. We have improved the recording set-up in the operating theatre so that usually there is no apparent interference and the RMS input voltage (random) is about 1uV. We started with a 4-electrode cuff and progressed to 10 electrodes on two 5-wire implant-grade cables. The method of fabricating the cuffs has been improved. We changed the method of closing the cuff during implantation and that has meant that we now get higher impedances within the cuff which will have increase the signal amplitudes and reduced the interference. Special tools are needed to implant the cuffs and three designs have been made and tested during the operations. Having done 9 non-recovery sheep, in which the animal is euthanized and the end of the experiment, we did 2 in which the animal was allowed to recover and further measurements were made a week later under anaesthesia before death. We designed and made a special 'head connector' around a military grade hermetic socket with a hydroxy-apatite-coated titanium flange which should bod to the skin. These sockets have 13 pins, 10 for the cuff electrodes and one for the internal reference electrode. Two sheep have now been implanted with cuffs joined o these head connectors. Special trocars were made to enable the cables to be tunnelled from the sacrum and head to implantable Craggs Connectors in the middle of the sheep's back. The first of these connectors looks good after a month. We have not yet managed to detect bladder signals in the awake animals: a major difficulty is the proximity of the powerful Medium Wave transmitter at Brookman's Park (only 3km away) so we hear too much of Radio 5 Live. Many of these methods will be relevant to the development of Bioelectronic Medicines, even if not for artificial control of the bladder. |
| Type Of Material | Physiological assessment or outcome measure |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | none yet |
| Description | Finetech Medical Ltd |
| Organisation | Finetech Medical |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | If the method we are investigating is successful (i.e. feasible), this company will be the obvious benefactors be cause they manufacture medical implants to control the urinary bladder after spinal cord injury. I am in close contact with the company. We keep them informed |
| Collaborator Contribution | They supply us with implant components (mostly paid for from our grant) |
| Impact | Our experimental implanted devices have been prepared for experiments as planned |
| Description | Research with large mammals |
| Organisation | Royal Veterinary College (RVC) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Making the implants for animal experiments |
| Collaborator Contribution | RVC: providing animals and animal-care team. Bath: electronic desig, electronic apparatus, bench testing, data analysis |
| Impact | Post mortem anatomical study in sheep |
| Start Year | 2017 |
| Description | Research with large mammals |
| Organisation | University of Bath |
| Department | Department of Electronic and Electrical Engineering |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Making the implants for animal experiments |
| Collaborator Contribution | RVC: providing animals and animal-care team. Bath: electronic desig, electronic apparatus, bench testing, data analysis |
| Impact | Post mortem anatomical study in sheep |
| Start Year | 2017 |