The relation of vertebral artery occlusion and intravertebral cleft: a prospective magnetic resonance angiography study

Purpose To detect the relationship between the vertebral artery occlusion and the intravertebral cleft (IVC). Methods A prospective evaluation of the vertebral segmental artery condition from the T10 to L4 with the magnetic resonance angiography (MRA) was performed in 44 osteoporosis vertebral compression fracture (OVCF) patients. The artery condition was divided into the patency, narrow, occlusion. The lesion segmental occlusion rate (LSOR) and the total occlusion rate (TOR) was calculated. The relation of the vertebral artery occlusion and the IVC formation was assessed with the univariate analysis. Results


Introduction
Osteoporosis vertebral compression fracture (OVCF) is the commonest osteoporosis fracture. Systemic treatment can always relieve the pain. However, the OVCF with intravertebral cleft (IVC) formation was always indicating a poor prognosis even after the vertebral augmentation surgery. Complications such as cement leakage [1], augmented vertebra recollapse ( Fig.1 f, g) [2], and the adjacent vertebral fracture [3] were more common in IVC patients. IVC was an area of low-intensity on T1-weighted and high-intensity or low-intensity on T2-weighted MRI in fracture vertebra ( Fig.1 b, c, d) [4].
The hypotheses of IVC formation were controversial. They were avascular necrosis (AVN) [5], air formation [6], biomechanics changes [7], and pseudarthrosis formation [8]. Among them, the AVN theory hypothesizes that the IVC is the sign of osteonecrosis resulted from the vascular insult, which received increasing attention from researchers [9,10].
There is growing evidence that the poor blood supply of the vertebrae leads to the IVC. Lin [9] found that the IVC was related to the adjacent vertebrae poor bone marrow perfusion identi ed by the dynamic contrast-enhanced magnetic resonance imaging. Kim found high artery occlusion rate in the IVC patients by magnetic resonance angiography (MRA) [10]. Due to the lack of a control group in Kim's study, the segmental artery occlusion leading to the IVC could not be concluded. Therefore, we performed this study to elucidate the relationship between segmental artery occlusion and IVC formation (Fig.1 e).

Methods
The study was approved by the Ethics Review Committee of Peking University People's Hospital with an approval number of 2019PHB240. All the written informed consents were acquired from the patients.

Patients
We prospectively recruited 44 patients (male: female= 14: 30) with OVCF from the traumatic orthopedic department at a tertiary grade-A hospital. The patients with a long time between traumatic and surgery were tended to be included in this research. Patients with infection or malignancy were excluded from this study. The affected vertebrae were T5 in 1 patient, T9 in 4 patients, T10 in 1 patient, T11 in 3 patients, T12 in 9 patients, L1 in 14 patients, L2 in 8 patients, L3 in 1 patient, L4 in 3 patients, L5 in 2 patients. All the patients underwent the X-ray and MRA for the thoracic or lumbar spine. The subjects were divided into the IVC group and the non-IVC group according to the MRI.

Sample size calculation
For comparing the occlusion rate of compression vertebral artery between the non-IVC group and IVC group. Previous literature revealed that the occlusion rate of vertebral artery in patients with IVC was 57.8% [10]. The incidence of lumbar artery occlusion was 19%-27% [11]. Therefore, we assumed that the incidence of artery occlusion in non-IVC patient was 0.3, which is a little higher than the normal vertebral occlusion rate for the compression fracture. The incidence of artery occlusion in the IVC group was 0.6.
The α was 0.05 and β was 0.2. The number of IVC group and the non-IVC group was 1:1. The calculated sample size was as follows: number of arteries in non-IVC group was 40 and IVC group was 40. [12] Data Collection The characteristics of the patients were age, gender, body mass index (BMI), and fracture levels. The comorbidities affecting the blood supply of the patients were recorded to re ects the blood supply condition. The vertebral avascular risk factors assessment included hypertension, diabetes mellitus, coronary heart disease, cerebral infarction, hormone usage, and smoking [13]. Each factor was regarded as 1 point and the vertebral avascular risk factor was the sum of all scores of the patient.
All data collection including the X-ray or CT, MRI, MRA results were reviewed by the double-blind method. The IVC data and vertebral occlusion condition were separately collected by two experienced surgeons.
There were pairs of segmental arteries of each thoracic and lumbar vertebrae except the L5 [15]. MRA covered T10 to L4 segments and corresponding arteries condition were recorded. Each vertebral artery condition was classi ed into patency, narrow, occlusion and was scored into 1, 0.5, 0, respectively (Fig. 2).
The compression vertebral segmental artery occlusion condition was observed and recorded by an experienced surgeon twice with an interval of more than one month. The intraclass correlation e ciency in the segmental artery occlusion was 0.788 (P < 0.001). The vertebral artery condition from the T10 to the L4 of each patient were all recorded. The compression vertebral segmental arteries were labeled. The occlusion rate was divided into the lesion segmental occlusion rate (LSOR) and the total occlusion rate (TOR). The LSOR was the sum of both two sides of the fractured vertebral artery condition dividing the lesion segmental arteries number. The total occlusion rate was the sum of whole vertebrae (T10-L4) artery condition divided by the total artery number.

Data Analysis
The basic characteristics were compared between the IVC and non-IVC groups, including age, gender, BMI, vertebral avascular risk factors, thoracolumbar levels (T11-L2), fracture severity, preoperative compression ratio, the time before MRI, LSOR, and TOR.

Results
Total 44 patients (male: female= 14: 30) with 46 fractured vertebrae were included in this study. The mean age of the patients was 74.6 years old. Twenty-one (45.6%) of the compression vertebrae had IVC. The mean time from injury to MRI diagnosis was 21 days. There was a total of 588 vertebral arteries and the total occlusion rate was 15.2%. And there were 46 fracture levels with 92 vertebral arteries. The total segmental artery occlusion rate was 15.3% (Table 1). Among the unfractured levels, artery occlusion or narrow rate of T10 was 20.9%, T11 was 23.8%, T12 was 34.3%, L1 was 23.3%, L2 was 8.4%, L3 was 4.6%, and L4 was 8.9% (Fig.3).
There were 42 IVC vertebral fracture levels arteries and 50 non-IVC vertebral fracture levels arteries. The time from injury to MRI diagnosis had a signi cant difference between the IVC group and the non-IVC group (P=0.041). There was no signi cant difference in age, gender, BMI, vertebral avascular risk factors, thoracolumbar levels (T11-L2), fracture severity, preoperative compression ratio (P>0.05). Neither the lesion segmental occlusion rate (LSOR) nor the total occlusion rate (TOR) showed a signi cant difference between the IVC and non-IVC patients (P>0.05) ( Table 2). Discussion IVC formation in the osteoporosis vertebral compression fracture was signi cantly associated with the poor prognosis of the patients [1][2][3]. Therefore, the pathogenesis of the IVC received much attention.
Finding the pathogenesis for IVC could help because there were not satisfying treatment method [16,17].
IVC was considered as the sign of avascular osteonecrosis of the vertebral [18]. Dupuy et al [19] and Libicher et al [5] both revealed the avascular osteonecrosis of the vertebral in the IVC patients by the biopsies. Once vertebral compression fracture happened, the vertebra needed more blood supply in osteocyte growth and vertebral reconstruction [20]. If the artery could not provide su cient blood supply, the osteogenesis might arrest and the vertebral nonunion happened.
The hypothesis of the vertebral ischemic theory was proposed. Nambu et al [21] showed that bilateral segmental artery ligation reduced the vertebral blood ow. Lin et al [9] used dynamic contrast-enhanced magnetic resonance imaging to assess the vertebral bone marrow perfusion of the adjacent vertebrae and found that the IVC formation was associated with the poor marrow perfusion. Kim et al [10] found that there was around 60% segmental artery occlusion in the IVC levels by MRA. All these indicated the occlusion of the segmental arteries might have an association with IVC. However, the lack of a control group made Kim's studies impossible to provide solid evidence for the relation of the arteries occlusion and IVC. Therefore, we performed this study to further elucidate the association between the formation of the IVC and segmental artery occlusion.
The LOSR and TOR had no signi cant difference between the IVC and non-IVC group. LOSR was considered as in uencing the local vertebrae blood supply and the TOR re ected the whole vertebrae blood supply. The result indicated that vertebral segmental artery occlusion was not associated with the formation of the IVC. Once the segmental artery occlusion happened, the vertebral collateral arteries might form to compensate the vertebra blood supply [15] (Fig. 4). Therefore, the MRA detection for the artery occlusion may not absolutely re ect the vertebral ischemia condition. Segmental arteries occlusion could not be used for predicting the IVC formation.
From the T10 to the L4, there were pairs of segmental arteries of the vertebrae. The L5 segmental artery was the median sacral artery, which was not included in the assessment [22]. We assessed the artery condition from T10 to L4 and found that the vertebral arteries were more likely occluded in the thoraciclumbar region. This region is a transition zone from the thoracic to the lumbar which has the maximum motion range and suffered much stress [18]. Both two factors lead the thoracic-lumbar region arteries prone to occlude. No relation was found between the vertebral fracture and the artery occlusion. The occlusion rate of the fracture levels is almost the same with the total segmental artery occlusion rate.
This indicated that the vertebral fracture might not lead to the segmental artery occlusion, which was opposite to the view of Kim [10].
There were several limitations. This is not a large-scale study. However, we calculated the sample size according to previous studies and considered that the sample size was enough to draw a conclusion. The detection of the IVC and artery occlusion was at the same time point. Hence, the in uence of vertebral long-term ischemia could not be detected. Artery occlusion without IVC formation did not mean the IVC would not form after the MRA examination. A repeated MRI evaluation might help to further investigate.

Conclusions
Some previous studies provided clues for the relationship between segmental artery occlusion and IVC. However, we provided opposite evidence that the segmental artery occlusion did not lead to the IVC. And vertebral compression fracture was unrelated to the segmental artery occlusion. The segmental artery occlusion was more likely to happen in the thoracolumbar levels.