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Page 1: Computed Tomography and In Vivo 9.4 Tesla Magnetic Resonance Imaging … · 2017-01-30 · Computed Tomography and In Vivo 9.4 Tesla Magnetic Resonance Imaging as a Comprehensive

Computed Tomography and In Vivo 9.4 Tesla Magnetic Resonance Imaging as a Comprehensive Tool to Assess Variably Healed 6 and 52 Week Osteochondral Knee Defects

+1 Menendez, M I; 1Powell, K A; 1 Carlton, M; 1 Bertone, A L

+1 The Ohio State University, Columbus, Ohio [email protected]

INTRODUCTION: Experimentally-created full-thickness osteochondral defects are commonly used to study healing of bone and cartilage in vivo. Frequently used animal models include small animals such as rabbits1, guinea pigs and rats. Quantifying bone and cartilage, particularly serially in live small animals, is a challenge to obtain high resolution within a reasonable acquisition time and to have confidence in the location of the defect once healed. The goal of our study was to use high resolution imaging modalities individually, and in combination, to assess bone, cartilage and meniscus in healing rabbit knee defects. METHODS: The study protocol was approved by The Ohio State University IACUC. Osteochondral defects had been drilled (3mm diameter, 5 mm depth) bilaterally on the medial and lateral condyles of the distal femur of each rabbit and assigned a variety of protocols, including injection with viral vectors encoding for bone morphogenetic proteins (BMP-2 and BMP-6). These treatments resulted in a range of bone and cartilage healing within the core of the drill hole, permitting imaging development and validation over a diversity of extent and type of repair tissue. Under general anesthesia at 52 weeks of healing, 10 rabbit distal femurs (n=20) were scanned in a Bruker BioSpec 94/30 (Bruker BioSpin, Germany) scanner using a 40 mm rat brain surface coil in a 154 mm quadrature volume resonator. Parameters and coils were adjusted to maximize the resolution of the soft tissues (cartilage and meniscus) or bone in the images. Immediately after euthanasia and harvest of distal femurs, µCT was performed at 6 weeks (n=10) and 52 weeks (n=10) of healing using an InveonTM system (Siemens, Erlangen Germany). Outcome µCT measurements included Bone Mineral Density (BMD; mg/cm3), Bone Mineral Content (BMC; mg), Bone Volume (BV; cm3) and Tissue Volume (TV; cm3). In addition, a subjective visual core for extent and severity of surface irregularity of defects in the µCT 3D reconstructions and the gross specimens was performed (Fig 1). For 52 weeks data, isotropic data sets at a spatial resolution of 0.02 mm were obtained and down sampled to a resolution of 0.08 mm for automated spatial registration and comparison to the MSME MRI data sets.

RESULTS: Micro-computed Tomography: On µCT, bone cores had greater amount and density of bone at 52 weeks than 6 weeks. (Figure 2) At 6 weeks, there were no significant differences in BMD, BMC, BV and TV among the defects. As expected, at 52 weeks, the µCT confirmed a greater BMD, BMC and BV (p<0.05) in BMP2-treated defects. On the 3D reconstructions, the BMP-6 had greater scores for extent of surface irregularities (p<0.05) than other groups.

Magnetic Resonance Imaging: MRI in vivo at 52 weeks was best obtained with coronal FLASH (TR=500

ms, TE=4.9 ms, FA=40o) images at a resolution of 0.16 x 0.16 x 1.0 mm3 to

evaluate articular cartilage and menisci. (Figure 3) Coronal MSME (TR=1000 ms, TE=14 ms) at a resolution of 0.09 x 0.09x 1 mm3 were best to evaluate bone trabeculae and marrow in vivo. (Figure 4B) The µCT and the MRI data were specially registered such that the cartilage and subchondral bone healing of the lesions could be assessed using both modalities simultaneously. Accurate superimposition of these imaging modalities identified the area of the healing bone core (Figure 4). In mostly healed or healed lesions (BMP-2 treated lesions), MRI bone acquisition was necessary to visualize the defects at 52 weeks as defect cores were not identified on µCT. This permitted confidence that the evaluation of the bone core lesion was performed at the correct location on uCT. Soft tissue MRI acquisition failed in many instances to identify the bone defects, particularly in well heal defects (Figure 3). The combination of both modalities was helpful to evaluate, via MRI, the healed cartilage and adjacent meniscus at the surface of the bone defect (Figure 4). Quantitative evaluation was accomplished by analyses of variance using a two-way ANOVA. Differences with a p-value < 0.05 were considered statistically significant. Comparisons were performed between the treatment groups. (GraphPad Prism Software Inc.,San Diego, Ca, 2003).

DISCUSSION: In well healed defects, µCT or MRI alone could not accurately identify the original core, leading to potentially inaccurate measurements. A combination of both modalities using superimposition of MRI and uCT images, permitted the anatomy and the location of healed core defects. These imaging modalities in combination provide the most comprehensive and accurate assessment of bone, cartilage and meniscus on healed 52 weeks osteochondral defects on a rabbit model. REFERENCES 1. Liu S, Shen S, Zhu T, Liang W, Huang L, Chen H, Wu H. Skeletal Radiol. 2009 Apr 9 ACKNOWLEDGEMENT: We would like to thank the Wiseman Hall ULAR surgical facilities and the Wright Center of Innovation in Biomedical Imaging.

Figure 3 : MRI image evaluating cartilage and meniscus. The image shows irregularity (arrow) in the cartilage surface and the meniscus at the core identified by superimposition with bone MRI and µCT.

B A

Figure 1: Representative µCT 3D reconstruction images of the rabbit distal femurs at 6 weeks (left) and 52 weeks (right). Surfaces were scored for extent and severity of irregularities.

Figure 2: µCT of defect core at 6wks (left) and 52 wks (right) at 300mg/cc3 mineral threshold showing greater amount and density of bone in the core by 52 wks.

Figure 4: 52 week 3D reconstruction distal femurs; µCT (left) and superimposed MR (right) with the same registration. Soft tissue can be evaluated directly over the defect with confidence of the lesion location.

Poster No. 1001 • 56th Annual Meeting of the Orthopaedic Research Society

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