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Non-invasive imaging demonstrates clinical features of ankylosing spondylitis in a rat adjuvant model: a case study
N Accart1, J Dawson, F Kolbinger
1Novartis Institute for Biomedical Research. nathalie.accart_gris@novartis.com.
Abstract:
Ankylosing spondylitis is a common rheumatic disease involving both inflammatory erosive osteopenia and bony overgrowth. Main disease features are recapitulated in small rodents challenged with complete Freund's adjuvant. MRI was used to follow longitudinally in vivo changes induced in the rat spine and micro-CT as terminal assessment of bone damage. Histochemistry methods were used to validate these imaging modalities in view of preclinical drug testing and translational applications of spine imaging. Animals were examined using a 3D fat-suppressed gradient-echo sequence, following the injection of gadolinium. At the end of the study, spines were excised for micro-CT and histological examination. Signals reflecting inflammation were detected at levels L5-L6 of the lumbar spine throughout the experimental period, peaking at day 27 after adjuvant. At day 14 the inflammatory response occurred along ligaments but it expanded to nearby soft tissues at later time points. From day 27 onwards inflammation was also detected within the bone, in areas where erosion occurred, and bone-like structures were formed. Micro-CT showed bone remodeling. Histology of isolated spines confirmed the inflammation and bone remodeling observed in vivo. The present study including three complementary approaches clearly demonstrates the potential of imaging for longitudinal assessments of changes in the spine in this animal model in view of preclinical pharmacological studies. The excellent correlation seen between the in vivo images and the histology underlines its fundamental role in the validation of non-invasive imaging readouts.
Insights
This study demonstrates how advanced imaging techniques like MRI and micro-CT can track spinal changes in an animal model of ankylosing spondylitis. These methods validate non-invasive imaging for preclinical drug testing in rheumatic diseases.
Area of Science:
- Rheumatology
- Medical Imaging
- Preclinical Research
Background:
- Ankylosing spondylitis is a rheumatic disease characterized by inflammation, bone erosion, and overgrowth.
- Complete Freund's adjuvant in rodents mimics key features of ankylosing spondylitis.
- Longitudinal in vivo imaging is crucial for assessing disease progression and therapeutic efficacy.
Purpose of the Study:
- To longitudinally assess spinal changes in a rat model of ankylosing spondylitis using in vivo imaging.
- To validate MRI and micro-CT as tools for preclinical drug testing in spinal imaging.
- To correlate imaging findings with histological data for enhanced accuracy.
Main Methods:
- Longitudinal in vivo MRI (3D fat-suppressed gradient-echo sequence with gadolinium) of rat spines.
- Terminal assessment using micro-CT for bone damage evaluation.
- Histochemistry methods for validation of imaging modalities.
Main Results:
- Inflammation signals were detected in the lumbar spine (L5-L6), peaking at day 27.
- Inflammatory response progressed from ligaments to soft tissues and bone.
- Micro-CT revealed bone remodeling, with histological examination confirming inflammation and bone changes.
- Excellent correlation was observed between in vivo imaging and histology.
Conclusions:
- Imaging modalities, including MRI and micro-CT, are valuable for longitudinal assessment of spinal changes in this ankylosing spondylitis model.
- These imaging techniques support preclinical pharmacological studies by providing validated non-invasive readouts.
- The study highlights the potential of imaging for advancing translational research in rheumatic diseases.
