Assessment of the efficacy of MRI for detection of changes in bone morphology in a mouse model of bone injury

Taha, May; Manske, Sarah L.; Kristensen, Erika; Taiani, Jaymi T.; Krawetz, Roman; Wu, Ying; Ponjevic, Dragana; Matyas, John R.; Boyd, Steven K.; Rancourt, Derrick E.; Dunn, Jeff F.

doi:10.1002/jmri.23876

Cited by 13 publications

(19 citation statements)

References 21 publications

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“…Moreover, MRI provides more information on the tissues surrounding the fractured area, including bone marrow, muscles, periosteum and fat [8–10]. …”

Section: Introductionmentioning

confidence: 99%

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Time-Dependent Changes in T1 during Fracture Healing in Juvenile Rats: A Quantitative MR Approach

et al. 2016

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Quantitative magnetic resonance imaging (qMRI) offers several advantages in imaging and determination of soft tissue alterations when compared to qualitative imaging techniques. Although applications in brain and muscle tissues are well studied, its suitability to quantify relaxation times of intact and injured bone tissue, especially in children, is widely unknown. The objective observation of a fracture including its age determination can become of legal interest in cases of child abuse or maltreatment. Therefore, the aim of this study is the determination of time dependent changes in intact and corresponding injured bones in immature rats via qMRI, to provide the basis for an objective and radiation-free approach for fracture dating. Thirty-five MR scans of 7 Sprague-Dawley rats (male, 4 weeks old, 100 ± 5 g) were acquired on a 3T MRI scanner (TimTrio, Siemens AG, Erlangen, Germany) after the surgical infliction of an epiphyseal fracture in the tibia. The images were taken at days 1, 3, 7, 14, 28, 42 and 82 post-surgery. A proton density-weighted and a T1-weighted 3D FLASH sequence were acquired to calculate the longitudinal relaxation time T1 of the fractured region and the surrounding tissues. The calculation of T1 in intact and injured bone resulted in a quantitative observation of bone development in intact juvenile tibiae as well as the bone healing process in the injured tibiae. In both areas, T1 decreased over time. To evaluate the differences in T1 behaviour between the intact and injured bone, the relative T1 values (bone-fracture) were calculated, showing clear detectable alterations of T1 after fracture occurrence. These results indicate that qMRI has a high potential not only for clinically relevant applications to detect growth defects or developmental alterations in juvenile bones, but also for forensically relevant applications such as the dating of fractures in cases of child abuse or maltreatment.

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“…Moreover, MRI provides more information on the tissues surrounding the fractured area, including bone marrow, muscles, periosteum and fat [8–10]. …”

Section: Introductionmentioning

confidence: 99%

“…Additionally, Baron et al described time dependent changes in quantitative MRI (qMRI) measurements of fractures in adult subjects as a precursor for a quantitative fracture dating approach. Therefore, MRI could become the more adequate method for the diagnosis and dating of a fracture [8,10]. …”

Section: Introductionmentioning

confidence: 99%

Time-Dependent Changes in T1 during Fracture Healing in Juvenile Rats: A Quantitative MR Approach

et al. 2016

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“…However, the limitations of that study are firstly, that the mice were sacrificed before the MRI examination and therefore the tissue contrast may have differed from the in vivo situation, and secondly, the limited spatial resolution possible with the 4.7-Tesla system used in this study. Taha et al [10] investigated different MR imaging techniques at 9.4-T field strength and showed that a proton density weighted TSE sequence performed best for the evaluation of bone healing. This method was able to discriminate between bone and soft tissue, including the medullary space and granulation tissue at the injury site at a higher contrast than μCT imaging.…”

Section: Discussionmentioning

confidence: 99%

“…However, there are no studies reported testing in vivo MRI during endochondral fracture healing in mice. Previous work includes post mortem MRI in mice with articular fractures [9] and in vivo MRI to monitor intramembranous bone-defect healing [10]. Both studies showed promising results, despite limited spatial resolution and tissue contrast.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of high-resolution In Vivo MRI for longitudinal analysis of endochondral fracture healing in mice

Haffner‐Luntzer¹,

Müller‐Graf²,

Matthys³

et al. 2017

PLoS ONE

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Mice are extensively used for experimental bone-healing studies. However, there are few established nondestructive in vivo techniques for longitudinal fracture-healing analysis in mice, including in vivo micro-computed tomography (μCT) and radiography. Importantly, none of the established methods can discriminate between non-mineralized fibrous tissue and cartilage in the soft fracture callus. Therefore, the objective was to establish high-resolution in vivo magnetic resonance imaging (MRI) for the longitudinal assessment of soft callus formation during bone healing in mice. C57BL/6J mice received a femur osteotomy stabilized using an external fixator and were randomly assigned to five groups. Group 1 mice were scanned three times longitudinally during fracture healing using an optimized MRI scanning protocol to establish an algorithm to characterize the different fracture-callus tissues. Mice of groups 2–4 were scanned once on day 10, 14 or 21, respectively, euthanized after scanning and their femurs subjected to ex vivo μCT and histomorphometric analysis to compare the data assessed by MRI with μCT and histology. Control group 5 mice were not scanned. After 28 days, mice of groups 1 and 5 were euthanized and the fracture-healing outcome was evaluated by bending-test, μCT and histology to determine whether the repeated anesthesia, handling and the MRI measurements themselves influenced fracture healing. The callus-tissue values determined by MRI were mostly comparable to those obtained by μCT and histomorphometric analysis. However, at time points characterized by small relative bone or cartilage areas, MRI measurements were weakly comparable to histomorphometric data, possibly due to the inferior spatial resolution. Importantly, at the early and intermediate phases of healing, cartilage and fibrous-tissue values obtained by MRI were highly accurate. Furthermore, repeated anesthesia, handling and MRI scans did not impact bone healing. Therefore, we demonstrated the feasibility of high-resolution in vivo MRI for longitudinal assessment of soft callus formation during murine endochondral fracture healing.

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“…In fact, MRI is used in the clinical setting to identify cartilage defects and may be used to identify HO, a lesion that forms through endochondral ossification, prior to ossification[ 3 , 21 , 22 ]. MRI may also have potential in detecting changes regular bone morphology induced by HO[ 23 , 24 ]. Similarly, positron emission tomography (PET) scans allow for identification of foci with high metabolic activity[ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Heterotopic Ossification Using Radiographic Imaging: Evidence for a Paradigm Shift

et al. 2015

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Heterotopic ossification (HO) is the growth of extra-skeletal bone which occurs following trauma, burns, and in patients with genetic bone morphogenetic protein (BMP) receptor mutations. The clinical and laboratory evaluation of HO is dependent on radiographic imaging to identify and characterize these lesions. Here we show that despite its inadequacies, plain film radiography and single modality microCT continue to serve as a primary method of HO imaging in nearly 30% of published in vivo literature. Furthermore, we demonstrate that detailed microCT analysis is superior to plain film and single modality microCT radiography specifically in the evaluation of HO formed through three representative models due to its ability to 1) define structural relationships between growing extra-skeletal bone and normal, anatomic bone, 2) provide accurate quantification and growth rate based on volume of the space-occupying lesion, thereby facilitating assessments of therapeutic intervention, 3) identify HO at earlier times allowing for evaluation of early intervention, and 4) characterization of metrics of bone physiology including porosity, tissue mineral density, and cortical and trabecular volume. Examination of our trauma model using microCT demonstrated two separate areas of HO based on anatomic location and relationship with surrounding, normal bone structures. Additionally, microCT allows HO growth rate to be evaluated to characterize HO progression. Taken together, these data demonstrate the need for a paradigm shift in the evaluation of HO towards microCT as a standard tool for imaging.

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Assessment of the efficacy of MRI for detection of changes in bone morphology in a mouse model of bone injury

Abstract: The RARE sequence was the most suitable for MRI bone imaging. It enabled the detection of hard and even soft tissue changes. These findings suggest that MRI could be an effective imaging modality for assessing changes in bone morphology and pathobiology.

Cited by 13 publications

References 21 publications

Time-Dependent Changes in T1 during Fracture Healing in Juvenile Rats: A Quantitative MR Approach

Time-Dependent Changes in T1 during Fracture Healing in Juvenile Rats: A Quantitative MR Approach

Evaluation of high-resolution In Vivo MRI for longitudinal analysis of endochondral fracture healing in mice

Characterization of Heterotopic Ossification Using Radiographic Imaging: Evidence for a Paradigm Shift

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