Advances in imaging of ischemic necrosis of the femoral head
Avascular necrosis of the femoral head (ANFH) is a common and difficult disease in orthopedics, with a high disability rate. Early detection, clear diagnosis and rapid adoption of effective measures can prevent further development of femoral head necrosis, thereby preventing femoral head collapse and restoring joint function. In order to improve the early diagnosis rate of this disease, it is crucial to choose the appropriate imaging methods. Now, we are going to evaluate the progress, respective advantages and application limits of several imaging diagnostics such as X-ray, CT, MRI and ECT.
1, the etiology of ANFH
The etiology of ANFH is not yet completely clear, and is generally divided into two categories: traumatic and non-traumatic. Traumatic mainly includes femoral neck fracture, hip dislocation, acetabular fracture and intertrochanteric fracture, among which femoral neck fracture has the highest chance of ANFH. The pathogenesis of traumatic ANFH is well established, mainly due to ischemic and hypoxic necrosis of the femoral head as a result of dissection of the arterial vessels supplying the femoral head [3]. The etiology of non-traumatic ANFH is more complex. According to a large-scale epidemiological survey in Japan, post-corticosteroid treatment and alcohol abuse were found to be the two most risk factors, which were associated with approximately more than 90% of patients [4]. The main mechanisms of non-traumatic ANFH pathogenesis are as follows.
(i) thrombosis and fat embolism in the blood supply arteries ;
② Increased intra-medullary pressure;
(iii) Occlusion of small arteries;
(iv) obstruction of venous return. The pathological process of traumatic and non-traumatic causes of ANFH is basically the same, mainly the response of different tissues of the bone marrow to hypoxia due to insufficient blood supply after femoral head ischemia. Hematopoietic tissues die 6-12 hours after the occurrence of hypoxia, bone cells die 12-48 hours, and adipocytes die 2-5 days later. Chai Benfu et al. demonstrated that after ischemic necrosis of the femoral head, a repair response occurs at the edge of the necrotic bone tissue, close to the normal bone tissue, manifesting as localized revascularization and new bone formation. Jiang et al. divided the pathological process of ANFH into the necrotic phase and the repair phase. The necrotic phase is the necrosis of bone marrow cells and bone marrow adipocytes, and the scaffolding and density of bone trabeculae in bone tissue remain unchanged; the repair phase is the filling of necrotic bone tissue by the resorption of new blood vessels and granulation tissue, along with the formation of new bone.
2. Diagnostic imaging of ANFH
2.1 X-ray plain film
Plain X-ray examination can be widely used in both general and primary hospitals because of its convenience and low cost. Because the X-ray film reflects the amount of mineral content in the bone, it cannot reflect the pathological process of necrosis of bone marrow cells and fat cells in the bone marrow cavity during the ischemic-necrotic phase of ANFH, and it can be shown on the X-ray film only when the mineral content in and around the bone necrotic area has changed significantly during the bone repair phase. According to Xuezhe Zhang et al, the early radiographic changes of ANFH are partial depression or flattening of the articular surface of the femoral head, and the central part of the femoral head and the upper lateral area immediately adjacent to the articular surface show a mild increase in density. In the middle stage, the femoral head is flattened, the joint surface is irregular, and the density is irregularly increased, with mild cystic degeneration and fragmentation in between.
In the late stage, the femoral head was obviously deformed, with bone resorption and dissolution, shortened and deformed femoral neck, narrowed joint space, and combined with osteoarthrosis. Zhao Dewei also proposed a four-stage classification for the X-ray diagnosis of ANFH [1]: Stage I, no positive X-ray findings, occasionally uniform or speckled sparse areas can be seen. In stage II, bone reconstruction is seen on X-ray, showing diffuse osteoporosis and cystic changes of reduced bone density mixed with increased bone density, with occasional crescentic signs (signs of separation or collapse of subchondral bone trabeculae from cartilage). In stage III, there are obvious cystic changes with surrounding sclerosis and flattening of the femoral head in the weight-bearing area. In stage IV, the head of the femur is clearly collapsed and flattened combined with degenerative joint changes. Zhao Dewei’s X-ray staging of ANFH basically follows the diagnostic criteria proposed by Ficat et al [10] in 1980, which is still widely accepted and adopted by the medical community.
2.2 CT
CT has greatly improved the accuracy of early diagnosis of ANFH with its advantages of thin cross-sectional scanning, high-density resolution, and selective determination of CT values for lesion sites. In 1990, Xuezhe Zhang et al [6] first reported the CT manifestations of ANFH in China: early changes were intact femoral head without fragmentation, or with slight scattered fragmentation and deformation of the stellate sign (normal femoral head trabeculae were arranged radially with the femoral head as the center, extending outward from thick to thin); late changes were fragmentation and deformation of the femoral head, with bone resorption areas between fragments and obvious deformation or disappearance of the stellate sign. On the basis of Xuezhe Zhang’s study, there have been new additions and refinements to the CT diagnosis of ANFH in recent years. Hu Jiumin et al. proposed that, in addition to the disappearance of the “star sign” and distortion of bone trabeculae, the presence of patches and strips of high-density sclerotic areas and multiple forms of osteosclerosis in the femoral head, as well as cortical thickening and sclerosis at the edge of the femoral head, are also early CT signs of ANFH.
In addition to the disappearance of the “star sign”, distorted trabeculae, patchy and striped osteosclerotic areas, and small cystic bone resorption areas, the cystic low-density areas are more common in the anterior part of the femoral head, and cortical fracture and collapse in late ANFH occur mostly at the anterior superior edge of the femoral head, as suggested by Xu Shulin [12]. Diagnosis of early changes in ANFH mainly relies on the morphological changes of bone trabeculae, i.e., the change of the stellate sign to determine, and it, like ordinary X-ray, can only be diagnosed when the repair process of osteonecrosis causes changes in the density of bone tissue on the X-ray. However, CT has obvious advantages over X-ray plain film because of its imaging characteristics, that is, it can detect early subtle changes of hyperplasia, sclerosis, fragmentation, cystic changes, etc. Both the detection of early ANFH and the reflection of the extent of lesions are significantly better than X-ray plain film, but the inability to show the necrotic stage of ANFH is its limit.
2.3 MRI
MRI is a biomagnetic spin imaging technique, which has the advantages of CT (cross-sectional scan, high-density resolution), but can also perform multi-angle imaging (cross-sectional, sagittal, coronal) without changing the patient’s position, and has multi-parametric imaging techniques (T1WI, T2WI, STIR, etc.), thus advancing the early diagnosis of ANFH to the stage of osteonecrosis (i.e., bone marrow cell and bone marrow adipocyte necrosis) stage. Chen Qin et al. concluded that the accuracy rate of diagnosing ANFH was 100% for MRI, 73.7% for CT, and 71.9% for X-ray plain film. In China, Wu Zhenhua et al [14] first reported the MRI staging and manifestation of ANFH: the femoral head had normal morphology on T1-weighted images in the early and middle stages, with a curved low-signal band against the edge and a high-signal area within it, and another high-signal band appeared on the inner side of the low-signal band on T2-weighted images. In the late stage, the femoral head was mostly or completely low-signal, interspersed with speckled high-signal, with head flattening and collapse, and a low-signal band around the necrotic area, and a high-signal band also appeared on the medial side of the T2-weighted image.
Zhaoyu Liu et al. demonstrated the reflection of the pathological process of ANFH by MRI through animal experiments: MRI revealed a punctate low signal of 2L diameter in the bone marrow cavity of the femoral head on T1WI and T2WI at 7 days postoperatively in the modeled animals, and pathological sections showed small focal lysis and necrosis of bone marrow cells with inflammatory cell infiltration. At 14 days after surgery, a diffuse distribution of punctate and small lamellar hyposignal areas appeared in the femoral head, and the pathological section showed necrotic fusion of bone marrow cells and osteoblasts into lamellar form.
Yuan Wen suggested that the “double line sign” is an important sign to identify early ANFH, i.e., in the T2WI SE sequence, the low-signal band surrounding the osteonecrosis is surrounded by the inner high-signal band, which represents the reactive interface between living and dead bone, and the low-signal band represents sclerotic bone and the high-signal band represents granulation tissue. In contrast, the study by Chen Qin et al [13] further elucidated the basis for MRI signal changes in the lesion area of ANFH to reflect its pathological changes and MRI staging. They concluded that high signal in T1WI and isosignal in T2WI of the lesion area indicated that fat still existed in the bone marrow, and low signal in T1WI and high signal in T2WI of the lesion area indicated that the fat was necrotic, and after fibrosis occurred in the lesion area, T1WI and T2WI were both low signal.MRI, with its sensitivity to adipocytes and direct multi-level and multi-directional imaging, is the most effective for the diagnosis of early ANFH compared with MRI is the most accurate and sensitive compared with other imaging examinations, but due to the expensive price, the clinical application cannot be popular is its limit.
2.4 ECT (nuclide scan)
ECT is the functional imaging of the human body using nuclear technology (nuclide and nuclide labeling compounds, nuclear instruments). Computer Tomography (ECT) has been used in clinical practice since the invention of CT in 1972. It is a technique for imaging radioisotopes in stereoscopic images in vivo, because its three-time imaging of bone mainly reflects the state of bone blood flow (in the dynamic phase, the radioactivity curve mainly reflects the blood flow of the femoral head vessels. In the blood pool phase, it mainly reflects the venous blood flow condition of the femoral head.
In the static phase, the tracer is deposited in the bone tissue), so it is very sensitive to the early diagnosis of ANFH. According to Li Jinying et al, in the early stage of ANFH, ECT shows a radiographic nuclear defect in the femoral head area without surrounding concentrated reaction due to low local blood supply and metabolism. In the repair period, due to revascularization, dead bone repair and new bone formation, the radioactive uptake increases, and in the late stage, the affected area shows abnormal radioactive concentration. The animal experimental study by Sang Shih-Biao and others showed that the bone imaging of ANFH was hypometabolic in the early stage, and then gradually increased until the peak at the pre-collapse stage. Since ECT mainly reflects the state of bone blood flow and only suggests poor blood perfusion in the femoral head, it is not specific for the diagnosis of ANFH, which is the limit of ECT for ANFH diagnosis.
In summary, X-ray plain film, CT, MRI and ECT can reflect the pathological changes of ANFH, but due to the difference of their respective imaging mechanisms, they reflect the pathological process of ANFH differently. when X-ray plain film and CT are positive, the lesion has already entered the repair phase, so it is difficult to achieve early diagnosis, and although nuclear scan can reflect the early ischemic state, its specificity is poor. MRI, on the other hand, can reflect both early ischemic necrotic phase adipocytes and bone marrow cell death, and is also specific, so it is currently considered the most sensitive and specific among all imaging diagnostic methods for ANFH. We believe that for the high-risk group of ANFH, inexpensive and convenient X-ray plain film should be preferred for screening, and for those with negative X-ray film, MRI qualitative examination is preferred for further examination and diagnosis, so that the examination suffered by patients is economical, easy, fast and accurate, thus achieving the purpose of early diagnosis and early treatment.
Progress in the treatment of ischemic necrosis of the femoral head
Ischemic necrosis of the femoral head is a difficult orthopedic disease with complex etiology and incompletely understood pathological mechanism, and its necrosis and collapse cause serious impairment of hip joint function and high disability rate. At present, the following treatment methods are commonly used clinically.
(1) non-surgical treatment: Chinese and Western medicine, physiotherapy, massage, etc. have certain efficacy, but there is no special effect, and the efficacy is slow.
(2) Medullary decompression: one of the causes of ischemic necrosis of the femoral head is increased intraosseous pressure. Medullary decompression opens the closed state of the medullary cavity of the femoral head, decreases the resistance of the surrounding blood vessels, reduces the intraosseous pressure, increases the blood flow, improves the blood circulation of the femoral head, and relieves the patient’s pain symptoms. It was the main treatment in 1974 to 1980. However, Liu Yujun proposed in the 12th issue of China Orthopaedic Injury in 2001 that the excellent rate of medullary decompression for femoral head necrosis is not high because this procedure only solves the “effect” of the disease, i.e., the intra-articular pressure, but fails to solve the “cause” of the disease, i.e., the blood supply to the head and neck. Therefore, it cannot correct the lack of oxygen in the femoral head due to ischemia, and theoretically cannot terminate the necrotic pathological process.
(3) Osteotomy with vascularized bone flap: The mechanism is to scrape away the necrotic bone in the femoral head and neck and implant the bone with vascularized bone block, which serves to decompress, mechanically support, and reconstruct the blood supply system in the head and neck, solving the head and neck ischemia, while reducing the pressure on the femoral head and creating conditions for the repair of necrotic femoral head tissue. The literature reports (Chen Zhongwei et al, Preliminary report on the treatment of aseptic necrosis of the femoral head in adults with rotating deep iliac vessels iliac bone graft, Chinese Journal of Microsurgery, 1986.9(2): 74) that the excellent rate is above 80%, which is the main treatment method for ischemic necrosis of the femoral head at present, the shortcoming mainly lies in the large trauma, which patients are mostly unwilling to accept.
(4) Artificial femoral head replacement: It is mainly applied to stage III-IV ischemic necrosis of the femoral head. Meanwhile, because artificial femoral head replacement is easy to be complicated by infection, nerve injury, dislocation, splitting of the upper end of the femur, ossifying myositis, sinking and loose displacement of the prosthesis, many scholars believe that artificial femoral head replacement is only suitable for the elderly.
Interventional therapy is a treatment method between non-surgical therapy and surgical therapy, which follows the leading medical idea of the 21st century, both minimally invasive treatment, and its goals and objectives are minimally invasive, quick, less painful and effective. Since 1994, some people have tried to apply interventional treatment for ischemic necrosis of the femoral head and achieved certain efficacy, but the efficacy is not yet ideal, and further discussion is needed on the best combination of perfusion drugs, the choice of dose, the combination of effective interventional treatment and local medication, and the re-treatment cycle of interventional treatment.
1 Anatomy of the local nutrient vessels of the bone: The blood circulation of the head and neck of the femur mainly comes from the 3 arterial bands of the medial and lateral rotor femoral arteries and the occluded artery. The internal and external rotor femoral arteries form the elective femoral artery ring at the base of the starved femoral head and neck beyond the attachment of the joint capsule between the rotors, and the main branches are the anterior supporting band artery, the posterior supporting band artery, the posterior superior supporting band artery, and the posterior inferior supporting band artery in four groups of vascular bundles, accounting for more than 70% of the blood supply to the femoral head. The main branch of the occluding artery is the femoral ligament artery, which anastomoses with the posterior supporting band artery by about 14.8%, accounting for about 5% of the blood supply to the femoral head.
2 The mechanism of interventional treatment: Studies have shown that trauma, hormones and alcoholism are the three main factors causing ANFH, accounting for more than 93% of ANFH cases. Trauma is caused by acute ischemia and ischemic necrosis of the femoral head due to dissection of the internal and external arteries and thromboembolism, or ischemic necrosis of the femoral head due to increased local vascular permeability caused by traumatic arthritis, and chronic ischemia of the femoral head due to slow blood flow, blood stagnation, and obstruction of blood perfusion caused by plasma leakage.
There are many theories on the mechanism of ANFH from hormone and alcohol abuse, among which the lipid metabolism disorder theory and the intravascular coagulation theory are dominant.
(1) Hormone use and alcohol abuse can cause disturbance of lipid metabolism, increase of free fatty acids in the blood, and local formation of fat embolism;
②Hormone use and alcohol abuse can cause endothelial damage of fine blood vessels, collagen exposure of the vessel wall, local aggregation of platelets, release of TXA2, and thrombus formation; on the other hand, due to the damage of vascular endothelium, the release of PGA2 is reduced, leading to local vascular contracture and thrombus formation. As the femoral vasculature is a terminal vessel with little collateral circulation, once the blood supply is blocked, it affects the nutrition of the femoral head and leads to ischemic and hypoxic necrosis of bone cells or bone marrow cells.
The mechanism of ANFH is mainly vasospasm, embolus formation and microcirculation disorder, so antispasm, thrombolysis and improvement of microcirculation are the key to treat ischemic necrosis of the femoral head. Chinese herbal medicine, physical therapy and massage, and external counterpulsation can improve the blood supply of tissues and relieve clinical symptoms to varying degrees, but oral and intravenous drug delivery methods distribute drugs throughout the body, and the concentration and effects of drugs on target organs are very limited, and the femoral head has not yet been found to have a particularly concentrated effect on a certain drug, and the external effects are as ineffective as scratching an itch on the tiny blood vessels.
With the development of medical imaging, the vascular interventional perfusion therapy technique was applied to the treatment of ischemic necrosis of the femoral head in 1994, and the main blood supply vessels of the femoral head and neck, the internal femoral artery, the external femoral artery, and the closed artery, were selected to perfuse antispasmodic thrombolytic drugs, which achieved certain efficacy in the treatment of ANFH due to the directness of drug action, high local drug concentration, and the first-pass effect of drug action, thus providing This has opened up a treatment pathway between surgery and non-surgery for ANFH. However, due to the complexity of the pathological mechanism of ANFH and the lack of specific therapeutic drugs, the selection and synergistic combination of drugs is the key to the effectiveness of treatment, therefore, we have used clinically used antispasmodic, thrombolytic, improve microcirculation of Chinese and Western drugs for the combination of perfusion.
3.Interventional treatment method: We use Seldinger technique to puncture and cannulate the femoral artery through the contralateral femoral artery, and the catheter is selected from 5.0F Cobra tube, and the catheter is super-selected to enter the medial and lateral femoral artery and the closed artery, and then the target artery is angiographed to observe the blood supply to the femoral head, and then the drugs are infused (poppy bases 30-120mg + Chuanxiongzin injection 60-100mL + 654-2 20-60mg). 654-2 20-60mg+danshen injection 30-60mL+low molecular dextrose 60-120mL), 2-3 times for each hip perfusion treatment, the interval is two weeks between the second and the first, and three months between the third and the second, supplemented with functional exercise exercises for functional exercise of the hip joint, and try to avoid weight-bearing for more than three months.
4.Efficacy of interventional treatment: We treated 38 patients with early ANFH in the hip, and all cases were followed up, with a minimum follow-up time of 6 months and a maximum of 2 years. Comparative observations were made using nuclear scan for Ficat stage I ANFH cases and X-ray films for Ficat stage II cases. According to the criteria for evaluating the efficacy of adult ischemic necrosis of the femoral head developed by the Orthopedic Society of the Chinese Medical Association at the first osteonecrosis society in Dandong, Liaoning Province, in 1995, the efficacy of this group of cases was evaluated, mainly by four total scores (25 points for pain, 18 points for function, 17 points for joint mobility, and 40 points for X-ray evaluation) standard scores to comprehensively analyze the function of the hip joint, and the efficacy scores were excellent: >90 points; good: 75 ～The results are shown in the table.
Staging Number of hips (n) Before treatment (points) After treatment (points) Difference
Phase I ( 6) 77.5±0.5 100±0.00 * 22.5±0.5
Phase II ( 32) 54.56±7.27 93.5 ±5.11 * 41.23±8.51
The difference in scores before and after treatment was significant by t-test (p<0.05)
The diagnosis and post-treatment control of stage I cases were determined by nuclear bone scan, and the original nuclear defect was restored to normal after treatment; the pre- and post-treatment control of stage II cases was performed by X-ray film, and the necrotic cystic area disappeared or decreased after treatment, and new bone filled in. From the angiogram before and after treatment, the number of blood vessels in the femoral head area was significantly increased, thickened and lengthened, and staining was enhanced after interventional treatment. The overall treatment excellence rate of 38 cases of early ischemic necrosis of the femoral head in the combined Chinese and Western medicine interventional comprehensive treatment was over 95%.