? Heterotopic ossification (HO) refers to the pathological manifestation that osteoblasts appear in non-bone tissues such as muscle or connective tissue, and mature lamellar bone is formed in soft tissue. Although CT examination is obviously superior to X-ray examination in the localization and quantification of HO, and it is of great significance to guide surgical treatment, when CT examination confirms HO, mature plate-like bone has already formed, which is not conducive to early preventive treatment of HO.
abstract
Early diagnosis of heterotopic ossification is very important. At present, the early diagnosis of HO mainly depends on X-ray, CT, MRI, ultrasound and nuclear medicine. Compared with traditional X-ray and CT examination, MRI examination has certain advantages in the early diagnosis of HO, but its cost is higher. Nuclear medicine examination is currently recognized as the most sensitive method for HO examination, but the harmfulness of injecting radioactive drugs seriously limits its application in HO diagnosis. Raman spectroscopy and near infrared optical imaging technology are immature and have not been applied to clinic. Ultrasound examination has the advantages of non-invasive, convenient and cheap, and is widely used in clinic. This article reviews the research progress of early diagnosis of HO imaging.
key word
Ectopic ossification; Imaging; early diagnosis
Heterotopic ossification (HO) refers to the pathological manifestation that osteoblasts appear in non-bone tissues such as muscle or connective tissue, and mature lamellar bone is formed in soft tissues [1]. At present, the pathogenesis of HO is not clear, which may be related to stimulation, signal transduction pathway induced by injury site, environment and other factors [2]. Once heterotopic bone is formed, it will seriously restrict joint activity and make the joint lose its function. Therefore, the early diagnosis of HO is particularly important. At present, the clinical diagnosis of HO mainly depends on X-ray, CT, MRI, ultrasound, nuclear medicine and other imaging examinations, but in recent years, near-infrared optical imaging, Raman spectroscopy and other technologies have gradually attracted attention to the diagnostic value of HO. This article reviews the imaging early diagnosis of HO.
1X line inspection
X-ray examination is the most common examination method for HO. However, the density resolution of X-ray images is low, and early HO only shows soft tissue lesions, which are similar to clinical manifestations such as chondrosarcoma, local infection and hematoma, with poor specificity. Ordinary X-ray examination shows that ectopic bone needs 3 ~ 6 weeks after injury [3]. With the maturity of HO, punctate calcifications gradually appeared on X-ray images. After the swelling of soft tissue was eliminated, the density of calcified shadow gradually increased and the development was clearer. The calcified site moves from the periphery to the center, eventually forming a mature lamellar bone [4], which is a typical early HOX line manifestation. Li et al. [5] examined 64 patients with trabecular bone after spinal cord injury by X-ray, and found that the soft tissue density around the joint increased in the early X-ray film, which caused edema and flocculent shadow due to calcium deposition, and then the density of cortical bone and trabecular bone gradually increased, showing clouds, blocks and cords, of which trabecular bone was clearly visible in 20 cases. According to the continuous X-ray film of HO, the density of ossification area gradually increases and the edge gradually becomes clear, which clearly indicates that ectopic bone tissue tends to mature [6]. However, immature bone and mature bone often overlap on X-ray films, so it is difficult to judge whether ectopic bone is mature or not. In a word, the HO found by X-ray examination is mostly in the third stage of pathological bone formation, and the best opportunity for preventive treatment has been missed, so we can only wait until the ectopic bone is mature before surgical resection. Therefore, X-ray examination is of little value in the early diagnosis of HO.
2CT test
Compared with X-ray examination, CT examination can show ectopic bone tissue more clearly, find tiny lesions of HO that X-ray examination can't find, and judge the position and shape of early HO more accurately [7-8]. Fujimori et al [9] found that the detection rate of HO by CT was significantly higher than that by X-ray. Fukutake et al. [10] found that CT images can display >: HO structure of 0. 1mm2. Anthonissen et al. [1 1] further research found that micro-CT examination can clearly show the heterotopic bone around the hip joint of the rat model. The above shows that CT examination has high density resolution. Brownley et al [12] found that polymorphic micro-CT examination is superior to X-ray examination and monomodal micro-CT examination in evaluating HO formation. Clinical study [13- 14] confirmed that three-dimensional CT examination can locate HO intuitively and comprehensively, and guide the resection correctly through different approaches. CT three-dimensional reconstruction technology can accurately locate the positional relationship between hyperplastic ectopic bone and normal blood vessels and muscles, and it is also of great guiding significance for the formulation of surgical plans [15]. Some scholars [16] think that CT examination can show no obvious damage in the muscle tissue of early myositis ossificans, with or without mild calcification in the surrounding tissues. The diagnosis of HO is basically established when bone mineralization is banded and shows signs similar to mature cortical bone [4]. Three-dimensional radiotherapy based on CT examination is more effective than ordinary empirical localization radiotherapy [17]. Although CT examination is obviously superior to X-ray examination in the localization and quantification of HO, and it is of great significance to guide surgical treatment, when CT examination confirms HO, mature plate-like bone has already formed, which is not conducive to early preventive treatment of HO.
3MRI examination
MRI is not as good as X-ray and CT in displaying bone tissue, but it has strong resolution on soft tissue. Some scholars [18- 19] found that the combination of MRI and CT examination can make the diagnosis of HO more clear. Research [20] found that the MRI changes of HO lesions can be found about 20.2d after injury. MRI can also show the changes of synovium and surrounding soft tissues in the early stage of HO, as well as the edema and liquefaction around joints, which is superior to X-ray and CT in judging the maturity of ectopic bone [5]. Govindarajan et al. [16] performed MRI examination on 1 patients with early lumbar myositis ossificans, and found that T2-weighted axial bitmap showed uneven high signal intensity in the center of the injury site, with 1 narrow low signal rings around it, which were adjacent to soft tissue edema. Before enhancement, ` T 1 weighted axial diagram showed that the strength of the injured site and surrounding muscles was the same. Sullivan et al. [4] also found in the MRI examination of patients with HO in the early stage of hip joint that uneven high T2-weighted signal and low signal ring representing calcification often appeared in the injury center. It can be seen that although MRI 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 is high, which limits its clinical application.
Ultrasonic examination and Doppler technique
At present, the ultrasonic diagnosis of HO abroad is still in the exploratory stage. In recent years, the literature [1 1- 12] has discussed the diagnostic value of high-frequency ultrasound, and found that ultrasound is sensitive to local soft tissue injury and calcification. True TTI et al. [2 1] think that the ultrasonic manifestations of HO are related to the course of disease and the degree of calcification, which is a dynamic process. With the development of calcification, the mineralization degree of the median lateral margin gradually deepened, and the ultrasound showed strong echo; When clinical symptoms appeared 3 ~ 4 weeks after injury, the ultrasonic manifestations of HO were basically the same as those of bone cortex, the ultrasonic beam was completely reflected, and the ossified area showed strong echo shadow, followed by sound shadow. It is concluded that the typical image of ultrasonic diagnosis of HO is annular, that is, the central hypoechoic and the peripheral hyperechoic, while the peripheral soft tissues are hypoechoic, especially the hip joint. Some scholars [22] used high-frequency ultrasound to examine patients with neurogenic HO, and patients with hip joint HO showed typical internal hypoechoic manifestations. Combined with color Doppler, the hemodynamic changes in this internal hypoechoic region can be used for early diagnosis of HO. Moses et al. [23] applied high-frequency ultrasound to early diagnose patients with ligament ossification, and found that the missed diagnosis rate was only 6%. They believe that high-frequency ultrasound has early diagnostic value and high sensitivity for ligament ossification. Some studies [24] think that bedside ultrasound examination has the advantages of portability, no radioactivity, low cost and so on, which is convenient for clinical diagnosis and treatment, and ultrasound examination can well distinguish HO from thrombosis, hematoma and other diseases. About 2 weeks after injury, typical changes in the form of clouds can be found by ultrasound, and HO can be found earlier than X-ray examination, which is convenient for clinical targeted prevention and treatment and observation of patients' treatment and prognosis. Yochum et al. [25] think that ultrasound examination can diagnose myositis ossificans after trauma two weeks earlier than X-ray examination, and can monitor the progress of myositis ossificans according to the changes of ultrasound images. Clinical research [26] found that ultrasound examination has reliable value for early diagnosis of HO after spinal cord injury. It can be seen that ultrasound examination is the best choice for early clinical diagnosis of HO, which has the advantages of non-invasive, convenient and cheap.
5 nuclear medical examination
5. 1 three-phase radionuclide bone scanning
Three-phase radionuclide bone scanning is the most sensitive method to detect HO [27], which can show positive manifestations 4 ~ 6 weeks earlier than X-ray examination. Continuous three-phase radionuclide bone scanning can be used to monitor the metabolic activity of ectopic bone tissue and predict the incidence of HO after operation. Schurch et al. [28] think that the blood flow phase and blood pool phase of three-phase radionuclide bone scanning are radioactive after injury, and the delayed phase appears radioactive aggregation within about 1 week after the blood flow phase and blood pool phase are injured. Three-phase radionuclide bone scanning can also judge the maturity and osteogenic activity of bone tissue by quantitatively monitoring the dynamic change of tracer uptake rate, so as to choose the best operation opportunity. Only after the bone tissue matures can surgery minimize the recurrence rate. Khoury et al. [29] found that when the intake of 99m Tc)- methylene diphosphonate (MDP) increased in HO patients, there was no abnormal aggregation of 99mTc- methoxyisobutyl nitrile (MIBI), and they thought that the three-phase radionuclide bone scanning combined with 99mTc-MDP and 99mTc-MIBI could effectively distinguish early myositis ossificans from malignant tumors. Research [28] shows that three-phase radionuclide bone scanning can show the early signs of HO within 2 weeks after injury at the earliest, which has important guiding significance for clinical prevention and treatment. Three-phase radionuclide bone scanning has the highest sensitivity, but it needs to inject radioactive drugs, which greatly limits its clinical application.
5.2 Single photon emission tomography /CT examination
Compared with three-phase radionuclide bone scanning, single photon emission tomography /CT can accurately locate the location, nature and degree of the lesion, and can display early subtle non-specific abnormal signals in three-phase radionuclide bone scanning [30-3 1]. Using 99mTc-MDP as radiopharmaceutical for SPECT/CT examination can accurately locate the active site of osteoblasts. Yin et al. [32] performed SPECT/CT examination on 1 case of rectal cancer patients with lower limb paralysis and difficulty in movement who showed bone injury by radionuclide bone imaging. The results showed that a large number of radioactive tracers gathered between T7 and T8, and the patient was diagnosed as posterior longitudinal ligament and ligamentum flavum HO. Lin et al. [33] examined 1 patient with brain injury by SPECT/CT, and found a large amount of 99mTc-MDP accumulated in acetabular soft tissue, which finally confirmed the existence of HO. Lima et al [34] think that SPECT/CT can not only know the maturity of ectopic bone tissue, but also evaluate the patients after HO operation 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 scanning, it cannot be popularized in the diagnosis of HO due to the same reason.
5.3 positron emission computed tomography /CT examination
Positron emission computed tomography (PET)/CT examination is a new imaging method which organically combines functional metabolic imaging with CT. It can judge the metabolism of ectopic bone in newborns by observing the distribution of positron nuclides in non-bone tissues such as soft tissues, and can also accurately locate ectopic bone tissues. Glastonbury et al. [35] performed CT or PET/CT examination on 6 patients with ossification after head and neck tumor resection. The results showed that the ossified tissue gradually thickened and stabilized. Three patients showed imaging changes 65,438+0 months after bone reconstruction, and all of them were confirmed as ossification by other imaging examinations. Until 20 months after reconstruction, no ossified tissue was absorbed or dissolved. Deryk et al. [36] examined 1 case of mesenteric HO confirmed by biopsy and histological analysis, and the results showed that the degree of glucose metabolism at the injured site was slightly enhanced. It shows that PET/CT examination can provide important information for the early diagnosis of HO.
Raman spectroscopy and near infrared optical imaging
Raman spectroscopy and near infrared optical imaging are also valuable for the early diagnosis of HO. Peterson et al. [37] studied the early diagnostic value of Raman spectroscopy in the formation of HO after burn, divided the mouse model with one achilles tendon removed into burn group and control group, and performed Raman spectroscopy imaging and microscopic CT examination on the removed achilles tendon and the unresected achilles tendon at early stage (5 days, 2 weeks and 3 weeks) and late stage (3 months) respectively. The results showed that micro-CT examination showed that the bone mineralization signal in burn group was significantly higher than that in control group 5 ~ 2 1 day after injury, and the difference of mineralization signal intensity between the two groups gradually increased with time. In vitro Raman spectroscopic imaging showed that the number of ectopic bones in burn group was significantly higher than that in control group, and the Raman spectroscopic image of new ectopic bone was obviously different from that of original cortical bone. Papour et al. [38] proposed a low-energy fast Raman optical imaging system (per second 1 frame) on 20/5, which has a larger field of view than traditional Raman spectral imaging and can distinguish bone tissue from surrounding soft tissue without spectrometer. This imaging system provides the possibility for bedside diagnosis of HO. Perosky et al. [39] found in the follow-up research that near infrared optical imaging can also detect the occurrence and development of HO in animal models at an early stage, and find 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 a good development prospect in the early diagnosis of HO, but they are not yet mature and have not been applied to clinic.
7 conclusion
Ultrasonic examination combined with Doppler technique is mature, which can diagnose HO earlier than X-ray and CT examination. Compared with MRI and nuclear medicine examination, it is non-invasive and economical, and can be better popularized in clinic, which is the direction of early diagnosis of HO in the future. Various imaging examinations have their own advantages and disadvantages. Clinicians should comprehensively evaluate high-risk patients and make an early diagnosis of HO according to the actual situation combined with various imaging examinations to avoid missed diagnosis and misdiagnosis.
refer to
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