Let’s talk about the imaging diagnostic research of heterotopic ossification?
Heterotopic ossification (HO) refers to the occurrence of osteoblasts in non-bone tissues such as muscles or connective tissues, and in soft tissues. The pathological manifestations of mature lamellar bone. Although CT examination is significantly better than X-ray examination in terms of localization and quantification of HO, and is of great significance in guiding surgical treatment, when HO is diagnosed by CT examination, mature plate-shaped bone has already formed, so it is not helpful for early preventive treatment of HO. big.
Abstract
The early diagnosis of heterotopic ossification (HO) is very important. Currently, clinical practice mainly relies on X-ray, CT, MRI, ultrasound and nuclear surgery. Medical and other imaging examinations can be used for early diagnosis of HO. Compared with traditional X-ray and CT examination, MRI examination has certain advantages in the early diagnosis of HO, but the cost is higher. Nuclear medicine examination is currently recognized as the most sensitive method for HO examination. However, the harmfulness of injected radioactive drugs seriously limits its use. Application in diagnosing HO; Raman spectroscopy and near-infrared optical imaging technology are not yet mature and have not been used clinically. Ultrasound examination has the advantages of non-invasive, convenient and cheap, and is widely used in clinical practice. This article reviews the research progress in early diagnosis of HO imaging.
Keywords
Heterotopic ossification; imaging; early diagnosis
Heterotopic ossification (HO) refers to non-bone tissue such as muscle or connective tissue The pathological manifestation of osteoblasts appearing and forming mature lamellar bone in soft tissue [1]. At present, the pathogenesis of HO is not yet clear, and it may be related to factors such as signal transduction pathways induced by stimulation and injury sites, and the environment [2]. Once ectopic bone forms, it will severely restrict joint movement and cause the joint to lose its mobility. Therefore, early diagnosis of HO is particularly important. At present, clinical diagnosis of HO mainly relies on imaging examinations such as X-ray, CT, MRI, ultrasound, and nuclear medicine. In recent years, the diagnostic value of near-infrared optical imaging, Raman spectroscopy and other technologies for HO has gradually attracted attention. This article reviews the imaging early diagnosis of HO.
1X-ray inspection
X-ray inspection is the most common inspection method for HO. However, the density resolution of X-ray images is low, and early HO mostly manifests only as soft tissue lesions, which are similar to the clinical manifestations of chondrosarcoma, local infection, hematoma, etc., so its specificity is poor. Ectopic bone can only be discovered 3 to 6 weeks after injury through ordinary X-ray examination [3]. As HO matures, point-like calcifications gradually appear on X-ray images. After the soft tissue swelling disappears, the density of calcifications gradually increases and becomes clearer. The calcification site moves from the periphery to the center, eventually forming mature lamellar bone [4] , which is a typical early HOX line performance. Li Wenqin et al. [5] conducted X-ray examinations on 64 HO patients after spinal cord injury and found that early X-rays showed increased density of soft tissues around joints caused by edema and flocculent shadows caused by calcium deposition, and then gradually increased density. The bone cortex and trabeculae were in the shape of clouds, lumps, and cords, and trabeculae were clearly visible in the lesions in 20 cases. Observation of continuous X-rays of HO shows that the density of the ossification area gradually increases and the edges gradually become clearer. The clear edges of the ossification area indicate that the ectopic bone tissue tends to mature [6]. However, immature bone and mature bone often overlap on X-rays. , so it is difficult to judge whether the ectopic bone is mature. In short, HO discovered by X-ray examination is mostly in the third stage of pathological bone formation, and has missed the best opportunity for preventive treatment. It can only be surgically removed after the ectopic bone matures. Therefore, X-ray examination is of little value in early diagnosis of HO.
2CT examination
CT examination can display ectopic bone tissue more clearly than Determine the location and shape of early HO [7-8].
Fujimori et al. [9] found that the detection rate of HO by CT examination was significantly higher than that by X-ray examination. Fukutake et al. [10] found that CT images can show a HO structure of >0.1mm2. Anthonissen et al.[11] further studied and found that micro-CT examination could clearly display small granular to flaky ectopic bones around the hip joint of the rat model. All the above indicate that CT examination has higher density resolution. Brownley et al. [12] found that multi-modal micro-CT examination is better than X-ray examination and single-modality micro-CT examination in assessing the formation of HO. Clinical studies [13-14] have confirmed that three-dimensional CT examination can intuitively and comprehensively locate HO and correctly guide resection through different approaches. CT three-dimensional reconstruction technology can accurately locate the positional relationship between hyperplastic ectopic bone and normal blood vessels and muscles, which also has important guiding significance for the formulation of surgical plans [15]. Some scholars [16] believe that CT examination can show inconspicuous damage in early stage myositis ossificans muscle tissue with or without slight calcification of surrounding tissue. When bone mineralization is band-like and shows signs similar to mature bone cortex, the diagnosis of HO is basically established [4]. Three-dimensional radiotherapy based on CT examination is more effective than ordinary empirical localized radiotherapy [17]. Although CT examination is significantly better than X-ray examination in terms of localization and quantification of HO, and is of great significance in guiding surgical treatment, when CT examination diagnoses HO, mature plate-shaped bone has already formed, so it is not helpful for early preventive treatment of HO. big.
3MRI examination
MRI examination is not as good at displaying bone tissue as X-ray and CT examination, but it has strong resolution of soft tissue. Some scholars [18-19] have found that combined MRI and CT examination can better diagnose HO. Research [20] found that MRI imaging changes in HO lesions can be found approximately 20.2 days after injury. MRI examination can also show changes in the joint synovium and surrounding soft tissues in the early stages of HO, as well as edema and liquefaction around the joints. Compared with X-ray and CT examinations, it has advantages in judging the maturity of ectopic bones [5]. Govindarajan et al. [16] performed MRI examination on a patient with early-stage paravertebral right-sided myositis ossificans and found that the T2-weighted axial image showed an uneven high signal in the center of the injury site, surrounded by a narrow ring of low signal. Signal ring, low signal ring adjacent to soft tissue edema. The T1-weighted axial image before enhancement shows equal intensity of signals at the injury site and surrounding muscles. The post-enhancement T1-weighted image shows strong signal intensity in surrounding muscles, which increases as the signal in the center of the injury increases. Sullivan et al. [4] also found in MRI examinations of patients with early HO of the hip joint that uneven high T2-weighted signals and low-signal rings representing calcification frequently appeared in the center of the injury. It can be seen that although MRI examination is helpful for the early diagnosis of HO, its specificity is low, it is difficult to distinguish it from infection, the misdiagnosis rate is high, and the cost of MRI examination is high, which limits its clinical promotion and application.
4 Ultrasound examination and Doppler technology
At present, the diagnosis of HO by ultrasonic examination abroad is still in the exploratory stage. In recent years, there are literatures [11-12] on the use of high-frequency ultrasonic examination for HO. The diagnostic value of ultrasonography was discussed and it was found that ultrasonography is more sensitive to local soft tissue damage and calcification. Falsetti et al. [21] studied that the ultrasound manifestations of HO are related to the course of the disease and the degree of calcification of the lesions. It is a dynamic process. With the development of calcifications, the degree of mineralization at the outer edge of the middle zone gradually deepens, which appears as strong on ultrasound examination. Echo; when clinical symptoms appear 3 to 4 weeks after the injury, the ultrasound examination performance of HO is basically consistent with the bone cortex, the ultrasound beam is completely reflected, the ossification area shows a strong echo shadow and the sound shadow is visible behind it, which is summarized in the diagnosis of HO by ultrasound examination. The typical image is in the shape of a ring, that is, the center is hypoechoic, the periphery is hyperechoic, and the surrounding soft tissue is hypoechoic. This typical manifestation is most obvious in the hip.
Some scholars [22] used high-frequency ultrasound to examine patients with neurogenic HO. Patients with hip joint HO showed typical internal hypoechoic performance. Combined with color Doppler examination of hemodynamic changes in the internal hypoechoic area, HO can be diagnosed early. Moses et al. [23] applied high-frequency ultrasonic examination to early diagnose patients with ligament ossification and found that the missed diagnosis rate was only 6. They believed that high-frequency ultrasonic examination has early diagnostic value for ligament ossification and has high sensitivity. Some studies [24] believe that bedside ultrasonography is easy to use in clinical diagnosis and treatment because of its portability, non-radioactivity, and low cost. Ultrasound examination can well distinguish HO from pathological changes such as thrombus and hematoma. Ultrasound examination can be performed about 2 weeks after injury. Typical cloud-like changes can be seen in the examination, which can detect HO earlier than X-ray examination, which facilitates clinical targeted preventive treatment and observation of patient treatment and prognosis. Yochum et al. [25] studied that ultrasound examination can diagnose post-traumatic myositis ossificans 2 weeks earlier than X-ray examination, and at the same time, the progression of myositis ossificans can be monitored based on changes in ultrasound images. A clinical study [26] found that ultrasonography has reliable value in the early diagnosis of HO after spinal cord injury. It can be seen that ultrasonography is the best choice for early clinical diagnosis of HO, with the advantages of being non-invasive, convenient and cheap.
5 Nuclear medicine examination
5.1 Three-phase nuclide bone scan
Three-phase nuclide bone scan is the most sensitive method to detect HO[27], which can Positive findings are shown 4 to 6 weeks earlier than X-ray examination, and continuous three-phase radionuclide bone scans can be used to monitor the metabolic activity of ectopic bone tissue and predict the incidence of postoperative HO. Schurch et al. [28] studied that radioactivity in the blood flow phase and blood pool phase of three-phase nuclide bone scan increased after injury, and radioactivity accumulation occurred in the delayed phase about 1 week after injury in the blood flow phase and blood pool phase. Three-phase nuclide bone scanning can also determine the maturity and osteogenic activity of bone tissue by quantitatively monitoring the dynamic changes in tracer uptake rate, so as to select the best time for surgery. Surgery can minimize the recurrence rate only after the bone tissue has matured. Khoury et al. [29] found that when the uptake of 99m technetium (Tc)-methylene diphosphonate (MDP) increased in HO patients, 99mTc-methoxyisobutylnitrile (MIBI) did not aggregate abnormally, and it was believed that the combination of 99mTc -The three-phase radionuclide bone scan method of MDP and 99mTc-MIBI can effectively identify early myositis ossificans and malignant tumors and avoid invasive examinations. Studies [28] have shown that three-phase radionuclide bone scan can show early signs of HO as early as 2 weeks after injury, which has important guiding significance for clinical preventive treatment. Although three-phase nuclide bone scanning has the highest sensitivity, it requires the injection of radioactive drugs, which greatly limits its clinical application.
5.2 Single-photon emission tomography/CT examination
Compared with three-phase nuclide bone scan, single-photon emission tomography (SPECT)/CT examination can accurately locate lesions The location, nature and extent can show early subtle non-specific abnormal signals in three-phase radionuclide bone scans [30-31]. Using 99mTc-MDP as a radioactive drug for SPECT/CT examination can accurately locate the active areas of osteoblasts. Yin et al. [32] performed a SPECT/CT examination on a rectal cancer patient with lower limb paralysis and difficulty in mobility who showed bone damage on radionuclide bone imaging. The results showed that the radioactive tracer accumulated in large amounts between T7 and T8. The patient was confirmed to have HO in the posterior longitudinal ligament and ligamentum flavum. Lin et al. [33] performed SPECT/CT examination on a patient with brain injury and found that a large amount of 99mTc-MDP accumulated in the soft tissue of the acetabulum, and the presence of HO was finally confirmed. Lima et al. [34] believe that while using SPECT/CT examination to understand the maturity of ectopic bone tissue, it can also conduct preoperative assessment of HO surgical resection patients and predict the prognosis and recurrence rate of patients after ectopic bone resection. Although SPECT/CT examination is more accurate and sensitive than three-phase radionuclide bone scan, it is limited by the same reasons and cannot be popularized in diagnosing HO.
5.3 Positron emission computed tomography/CT examination
Positron emission computed tomography (PET)/CT examination is an organic combination of functional metabolic imaging and CT Together with the new imaging examination method, the metabolism of new ectopic bone can be judged by observing the distribution of positron nuclides in non-bone tissues such as soft tissue, and it can also accurately locate ectopic bone tissue. Glastonbury et al. [35] conducted multiple CT or PET/CT examinations on 6 patients who had ossification after head and neck tumor resection and used fibular free flap for bone reconstruction. The results showed that the ossification tissue gradually thickened and became stable. , 3 patients had imaging changes one month after bone reconstruction, and all of them were subsequently confirmed to have ossification formation by other imaging examinations. No absorption or dissolution of the ossified tissue occurred until 20 months after reconstruction. Deryk et al. [36] performed deoxyglucose (FDG)-PET examination on a patient diagnosed with mesenteric HO through biopsy and histological analysis, and the results showed that the degree of glucose metabolism at the injured site was slightly enhanced. All the above indicate that PET/CT examination can provide important information for the early diagnosis of HO.
6 Raman spectroscopy and near-infrared optical imaging
Raman spectroscopy and near-infrared optical imaging also have certain value in the early diagnosis of HO. Peterson et al. [37] studied the early diagnostic value of Raman spectroscopy detection method in the formation of HO after burns. The mouse model with Achilles tendon resection on one side was divided into a burn group and a control group, and they were divided into a burn group and a control group at the early stage (5d, Raman spectrum imaging and micro-CT examination were performed on the Achilles tendon resection side and the non-resection side at 2 weeks and 3 weeks) and late period (3 months). The results showed that micro-CT examination 5 to 21 days after injury showed bone mineralization in the burn group before HO. The increase in mineralization signal was significantly higher than that in the control group, and as time went by, the difference in mineralization signal intensity between the two groups gradually increased. In vitro Raman spectroscopy imaging showed that the number of ectopic bones in the burn group was significantly greater than that in the control group, and the new ectopic bone was different from that in the control group. Preexisting cortical bone has clear differences in its image in the Raman spectrum. Papour et al. [38] proposed a low-energy and fast (1 frame per second) Raman optical imaging system in 2015. Compared with traditional Raman spectroscopic imaging, it has a larger field of view and can be used without the need for a spectrometer. By distinguishing bone tissue from surrounding soft tissue, this imaging system provides the possibility for bedside diagnosis of HO. Perosky et al. [39] found in subsequent studies that near-infrared optical imaging can also detect the occurrence and development of HO early in animal models, and can detect the formation of micro-mineralization in soft tissues before CT examination. Raman spectroscopy and near-infrared optical imaging have the advantages of sensitivity and non-invasiveness, and have good development prospects in early diagnosis of HO, but they are both immature and have not yet been used clinically.
7Conclusion
Ultrasound examination combined with Doppler technology is relatively mature and can diagnose HO earlier than X-ray and CT examination. Compared with MRI and nuclear medicine examination, it is non-invasive. , economical and other advantages, it can be better popularized in clinical practice, which is the direction of early diagnosis of HO in the future. Various imaging examinations have their advantages and disadvantages. Clinicians should comprehensively evaluate high-risk patients and combine multiple imaging examinations according to the actual situation for early diagnosis of HO to avoid missed diagnosis and misdiagnosis.
References
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