Assessment of White Matter Loss Using Bond-Selective Photoacoustic Imaging in a Rat Model of Contusive Spinal Cord Injury

Abstract

White matter (WM) loss is a critical event after spinal cord injury (SCI). Conventionally, such loss has been measured with histological and histochemical approaches, although the procedures are complex and may cause artifact. Recently, coherent Raman microscopy has been proven to be an emerging technology to study de-and remyelination of the injured spinal cord; however, limited penetration depth and small imaging field prevent it from comprehensive assessments of large areas of damaged tissues. Here, we report the use of bond-selective photoacoustic (PA) imaging with 1730-nm excitation, where the first overtone vibration of CH 2 bond is located, to assess WM loss after a contusive SCI in adult rats. By employing the first overtone vibration of CH 2 bond as the contrast, the mapping of the WM in an intact spinal cord was achieved in a label-free three-dimensional manner, and the physiological change of the spinal cord before and after injury was observed. Moreover, the recovery of the spinal cord from contusive injury with the treatment of a neuroprotective nanomedicine ferulic-acid-conjugated glycol chitosan (FA-GC) was also observed. Our study suggests that bond-selective PA imaging is a valuable tool to assess the progression of WM pathology after SCI as well as neuroprotective therapeutics in a label-free manner.

Bond-selective photoacoustic imaging by converting molecular vibration into acoustic waves

“…Through conversion of molecular vibration into acoustic waves, vibration-based PA imaging enables the visualization of different molecules and chemical components in biological tissue. Thus far, CH 2 -rich lipids [31] , [32] , [33] , [34] , [35] , [36] , CH 3 -rich collagen [33] , O—H bond-rich water [37] , nerve [38] , [39] , intramuscular fat [34] , [40] , and neural white matter [41] have all been investigated. Particularly, the detection of overtone absorption of C—H bonds has recently drawn attention [42] , [43] , [44] , [45] , [46] , [47] , [48] , since C—H bonds are highly concentrated in certain types of biological components, such as lipid and collagen.…”

“…However, real-time imaging is not feasible and artifacts are often introduced during histological processing. Wu et al used PAM with 1730 nm excitation to assess white matter loss after a contusive spinal cord injury in adult rats [41] . Owing to the abundance of CH 2 groups in the myelin sheath, white matter in the spinal cord can be easily visualized ( Fig.…”

Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats

“…In general, the one-time intraperitoneal application of the stable gastric pentadecapeptide BPC 157 is much like the engraftment of neural stem cells [16] or bone marrow stromal cells [17] into the lesion site. One should consider the primary phase lesion and hemorrhaging that results from mechanical damage during SCI as well as the secondary phase lesion that lasts several hours or even several months and is accompanied by edema, hemorrhage, inflammation, and cytotoxic edema [44][45][46][47] and may extend to the white matter area and lead to white matter degeneration and damage [48,49]. This substantiates the evidence that the spared white matter holds the key to the functional motor recovery of the hind limbs after SCI and is closely correlated with the functional restoration of the paralyzed hind limbs [50][51][52].…”

Label‐free in vivo imaging of peripheral nerve by multispectral photoacoustic tomography

“…Myelin sheaths surrounding axons are abundant in lipids, thus providing an opportunity to apply photoacoustic imaging for visualization of nerves with specific contrast. More recently, photoacoustic microscopy (PAM) has been successfully employed to image peripheral nerves in mice and white matter in rats . However, translation of this technique to the clinical setting is hindered by millimeter‐scale imaging depth and slow imaging speed of this microscopy technique.…”