In vivo contrast‐enhanced microCT for the monitoring of mouse thoracic, lumbar, and coccygeal intervertebral discs

Abstract

Mouse models are often used for studies of intervertebral disc (IVD) homeostasis and degeneration, yet the relatively small size of the IVD poses challenges for noninvasive, longitudinal imaging modalities. The recently developed contrast‐enhanced microCT (CEμCT) using Ioversol has been successful in detecting degenerative changes in the murine IVD ex vivo at the micrometer scale. Further leveraging the superior biocompatibility of Ioversol as a contrast agent, we demonstrate the in vivo use of this CEμCT technique to examine IVDs at multiple spinal sites. Ioversol was administered via tail vein injection (TVI) in growing and adult male FVB/NJ mice (n = 5 /group). The animals were anesthetized and underwent in vivo micro‐computed tomographic (microCT) at the coccygeal (CC5/CC6), lumbar (L5/6), and thoracic (T12/T13) IVDs. TVI of Ioversol was well‐tolerated by all animals. As Ioversol filtered through the kidneys and accumulated in the bladder, the attenuations of the mouse bladder and kidneys increased due to the high molecular weight of Ioversol, confirming that the Ioversol is biological available. Average IVD attenuations increased 3%‐15% following TVI (ANOVA; P < .01). The presence of Ioversol in the IVD combined with high‐resolution microCT allow for nondestructive visualization of structural features of the IVD. These results demonstrate CEμCT with Ioversol as a viable strategy for the in vivo monitoring of multiple mouse IVDs during degeneration, disease, and injury.

The degenerative impact of hyperglycemia on the structure and mechanics of developing murine intervertebral discs

“…Whole tails were harvested from 3‐ to 4‐month‐old female db/db (n = 8) and db/+ (n = 9) mice postmortem as described previously. 45 Caudal spines were then collected from the tails per existing protocol. 39 , 40 …”

Spine biomechanical testing methodologies: The controversy of consensus vs scientific evidence

“…Sagittal plain X‐rays of intact spines are commonly used in the clinical assessment of spine and disc health, where osteophytes and disc height narrowing can be viewed. CT provides a three‐dimensional reconstruction but is not as commonly used for characterizing motion segments for in vitro testing, due to challenges in imaging soft tissues 105 . CT imaging is more commonly applied in bone research to provide bone mineral density as an assessment of bone quality and strength 106 …”

“…CT provides a three-dimensional reconstruction but is not as commonly used for characterizing motion segments for in vitro testing, due to challenges in imaging soft tissues. 105 CT imaging is more commonly applied in bone research to provide bone mineral density as an assessment of bone quality and strength. 106 Soft tissues are easier to visualize through MR imaging, with relative disc health being assessed with the Pfirrmann scale.…”

Controversies in spine research: Organ culture versus in vivo models for studies of the intervertebral disc

“…The improvement in resolution and imaging quality enables more sophisticated biochemical and detailed structural analyses of the IVD and enables more mechanistic studies to be conducted. Likewise, parallel, clinically relevant imaging parameters, such as IVD hydration, IVD height index, and bone parameters, can also be obtained from the higher‐resolution ex vivo imaging 97,163–165 . Another advantage in terms of imaging organ culture models is the application of molecular imaging to track changes in the biological activity of cells in organ culture over time (e.g., cell metabolism).…”