Ultrasound localization microscopy and functional ultrasound imaging reveal atypical features of the trigeminal ganglion vasculature

Abstract

The functional imaging within the trigeminal ganglion (TG) is highly challenging due to its small size and deep localization. This study combined a methodological framework able to dive into the rat trigeminal nociceptive system by jointly providing 1) imaging of the TG blood vasculature at microscopic resolution, and 2) the measurement of hemodynamic responses evoked by orofacial stimulations in anesthetized rats. Despite the small number of sensory neurons within the TG, functional ultrasound imaging was able to image and quantify a strong and highly localized hemodynamic response in the ipsilateral TG, evoked not only by mechanical or chemical stimulations of corneal nociceptive fibers, but also by cutaneous mechanical stimulations of the ophthalmic and maxillary orofacial regions using a von Frey hair. The in vivo quantitative imaging of the TG’s vasculature using ultrasound localization microscopy combined with in toto labelling reveals particular features of the vascularization of the area containing the sensory neurons, that are likely the origin of this strong vaso-trigeminal response. This innovative imaging approach opens the path for future studies on the mechanisms underlying changes in trigeminal local blood flow and evoked hemodynamic responses, key mechanisms for the understanding and treatment of debilitating trigeminal pain conditions.

A scoping review of current and emerging techniques for evaluation of peripheral nerve health, degeneration and regeneration: part 2, non-invasive imaging

“…High-frequency contrast-enhanced US using microbubbles of inert gas has also successfully quantified peripheral nerve perfusion [196], which may turn out to be relevant in detecting vascular growth associated with regenerating nerve or even correlate with axon density. In a study into neurovascular coupling, the trigeminal ganglion was examined using microbubble tracking and a 15 MHz US probe with an ultrafast neuroimager, showing a significant hemodynamic response following afferent activation (corneal nociceptive) [202]. This is interesting because the number of neurons that needed to be activated for a hemodynamic response to be detected was low (about 300 neurons) and suggests the neurovascular coupling of distal peripheral nerve might be able to be assessed similarly to sensory ganglia at such a detailed level.…”

Neuro-imagerie fonctionnelle ultrasonore : vers une meilleure compréhension de la physiologie et de la physiopathologie des douleurs aiguës et chroniques

“…L'imagerie fonctionnelle des TG constitue un défi important du fait de leur petite taille et de leur localisation profonde. Nous avons récemment mis en évidence la possibilité d'imager par ifUS avec une grande résolution les TG et d'étudier la réponse hémodynamique fonctionnelle évoquée par l'activation des nocicepteurs trigéminés en réponse à des stimuli nociceptifs chez le rat [27]. Pour la première fois chez le rongeur, nous avons mis en évidence des réponses hémodynamiques dans le TG en réponse à des stimulations cornéennes nociceptives ou allodyniques, mais également des stimulations mécaniques hyperalgiques des régions ophtalmique et périorbitaire (Figure 4).…”

“…Pour la première fois chez le rongeur, nous avons mis en évidence des réponses hémodynamiques dans le TG en réponse à des stimulations cornéennes nociceptives ou allodyniques, mais également des stimulations mécaniques hyperalgiques des régions ophtalmique et périorbitaire (Figure 4). Nous avons démontré la présence d'une somatotopie fonctionnelle précise à l'intérieur du TG chez le rat [27].…”

Retinal functional ultrasound imaging (rfUS) for assessing neurovascular alterations: a pilot study on a rat model of dementia

“…Functional ultrasound (fUS) is a relatively recent functional neuroimaging technique analog to functional MRI that uses ultrafast plane waves ultrasound imaging to acquire images of the brain microvasculature at high spatiotemporal resolution 18 , 19 . It is highly sensitive and can detect tiny changes in blood volumes associated with local functional hyperemia, even in deep cerebral structures 20 . The technique has been applied successfully to image brain activity in different species and humans intra-operatively 21 or neonates through the transfontanellar window 22 as in adults, the skull bone acts as a partial barrier to ultrasonic propagation.…”