Clinical applications of peripheral neurostimulation are sprouting, since the capability of modulating neural activity has been thoroughly exposed, micro-electrodes' technology has vastly improved, and new minimally invasive surgical approaches are being proposed. A large population is affected by sexual dysfunctions, and the interest for new treatments is high, so it appeared as good candidate for a novel electroceutical. Genital arousal is known to be controlled by parasympathetic (promoting), sympathetic (inhibiting), and somatic activity. A research over the neuroanatomy showed that most of the fibers of interest origin from the second to fourth sacral nerve, namely the efferent parasympathetic fibers (mainly from S3), and the afferent sensory fibers carrying the stimuli responsible of triggering reflex arousal, later forming the pudendal nerve. The third sacral nerve and the pudendal nerve follow a clear course, and surgical approaches are well known, so they were chosen as targets. It was of primary interest to benchmark existing electrodes, the Interstim quadripolar lead and a multipolar cuff, regarding selectivity, supposed as a first requirement to deliver effective stimulation without inducing pain, spasms, or other collateral phenomena. For this purpose, a hybrid modeling approach was employed: the two target nerves were 3D modeled (for the pudendal nerve histological cross-sections were used; for the third sacral nerve they were not available, for which a randomly-generated section was used, swept along a realistic trajectory); FEM electrical modeling was performed to simulate the potential field generated by current injection from each active site; the nerves were populated with compartmentalized axons; the extracellular potential obtained by interpolation of the FEM results; neurophysiological simulations, using the model of axon by McIntyre et al., were performed to estimate whether, and at which injected charge level, each axon fired along its length; and finally parameters such as fascicular recruitment thresholds and selectivity were computed, the results interpreted to obtain hints to guide the development of a novel solution. The work was performed during a permanence at the Neuroengineering Lab of ETH Zürich.
Le applicazioni cliniche della neurostimolazione periferica si stanno moltiplicando, grazie all'attuale ampia comprensione della possibilità di modulare l'attività neurale, al miglioramento sostanziale della tecnologia dei micro-elettrodi, ed allo sviluppo di nuove tecniche chirurgiche ad invasività minima. Una larga parte della popolazione è affetta da disfunzioni sessuali, e l'interesse per nuove terapie è alto, appare quindi un buon candidato per un nuovo extit{electroceutical}. L'arousal genitale è controllato dall'attività parasimpatica (promotrice), simpatica (inibitrice), e somatica. Una ricerca sulla neuroanatomia ha mostrato che la maggior parte delle fibre di interesse ha origine tra il secondo e il quarto nervo sacrale, nello specifico, le fibre parasimpatiche efferenti (principalmente da S3), e le fibre sensoriali, afferenti, che trasmettono gli stimoli responsabili dell'attivazione dell'arousal di riflesso, che si raccolgono poi nel nervo pudendo. Il terzo nervo sacrale e il nervo pudendo seguono un percorso ben definito, ed approcci chirurgici sono ben noti, sono stati perciò selezionati come obiettivi per la stimolazione. Di interesse primario è stata la valutazione di elettrodi preesistenti, il lead quadripolare Interstim ed un cuff multipolare, riguardo alla selettività, supposta come primo requisito per somminitrare una stimolazione effettiva evitando di indurre dolore, spasmi, od altri effetti collaterali. A questo proposito è stato impiegato un approcio di modellazione ibrida: i due nervi target sono stati modellati in 3D (per il nervo pudendo utilizzando cross-sezioni istologiche; per il nervo sacrale, per cui le stesse non erano disponibili, è stata utilizzata una cross-sezione generata casualmente, estrusa lungo una traiettoria realistica); è stata eseguita modellazione elettrica FEM per simulare il potenziale generato da iniezione di corrente da ogni sito attivo; i nervi sono stati popolati da assoni compartimentalizzati; il potenziale extracellulare è stato estratto per interpolazione dai risultati FEM; sono state eseguite simulazioni neurofisiologiche, utilizzando il modello di assone di McIntyre et al., per stimare se, ed a quale livello di carica iniettata, si fosse verificato il firing per ogni assone; ed infine sono stati calcolati parametri quali soglie di reclutamento del fascicolo e selettività, i risultati interpretati per ottenere indicazioni per guidare lo sviluppo di una soluzione innovativa. Il lavoro è stato effettuato durante una permanenza presso il Neuroengineering Lab dell'ETH Zürich.
Development of a computational model of the human sacral and pudendal nerves to design a neural interface for a bioelectronic device treating sexual dysfunctions
Ciotti, Federico
2019/2020
Abstract
Clinical applications of peripheral neurostimulation are sprouting, since the capability of modulating neural activity has been thoroughly exposed, micro-electrodes' technology has vastly improved, and new minimally invasive surgical approaches are being proposed. A large population is affected by sexual dysfunctions, and the interest for new treatments is high, so it appeared as good candidate for a novel electroceutical. Genital arousal is known to be controlled by parasympathetic (promoting), sympathetic (inhibiting), and somatic activity. A research over the neuroanatomy showed that most of the fibers of interest origin from the second to fourth sacral nerve, namely the efferent parasympathetic fibers (mainly from S3), and the afferent sensory fibers carrying the stimuli responsible of triggering reflex arousal, later forming the pudendal nerve. The third sacral nerve and the pudendal nerve follow a clear course, and surgical approaches are well known, so they were chosen as targets. It was of primary interest to benchmark existing electrodes, the Interstim quadripolar lead and a multipolar cuff, regarding selectivity, supposed as a first requirement to deliver effective stimulation without inducing pain, spasms, or other collateral phenomena. For this purpose, a hybrid modeling approach was employed: the two target nerves were 3D modeled (for the pudendal nerve histological cross-sections were used; for the third sacral nerve they were not available, for which a randomly-generated section was used, swept along a realistic trajectory); FEM electrical modeling was performed to simulate the potential field generated by current injection from each active site; the nerves were populated with compartmentalized axons; the extracellular potential obtained by interpolation of the FEM results; neurophysiological simulations, using the model of axon by McIntyre et al., were performed to estimate whether, and at which injected charge level, each axon fired along its length; and finally parameters such as fascicular recruitment thresholds and selectivity were computed, the results interpreted to obtain hints to guide the development of a novel solution. The work was performed during a permanence at the Neuroengineering Lab of ETH Zürich.| File | Dimensione | Formato | |
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https://hdl.handle.net/10589/166698