Magnetic Resonance Imaging Research of Thoracic Inlet Parameters in the Cervical and Cervicothoracic Spine in Degenerative Cervical Spondylosis

Magnetic Resonance Imaging Research of Thoracic Inlet Parameters in the Cervical and Cervicothoracic Spine in Degenerative Cervical Spondylosis

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Journal Pre-proof The Magnetic Resonance Imaging Research of Thoracic Inlet Parameters at Cervical and Cervicothoracic Spine in Degenerative Cervical Spondylosis Wanli Li, Fangcai Li, Xiaobo Yang, Shunjie Yu, Weishan Chen, Qixin Chen PII:

S1878-8750(20)30097-8

DOI:

https://doi.org/10.1016/j.wneu.2020.01.079

Reference:

WNEU 14109

To appear in:

World Neurosurgery

Received Date: 16 August 2019 Revised Date:

10 January 2020

Accepted Date: 11 January 2020

Please cite this article as: Li W, Li F, Yang X, Yu S, Chen W, Chen Q, The Magnetic Resonance Imaging Research of Thoracic Inlet Parameters at Cervical and Cervicothoracic Spine in Degenerative Cervical Spondylosis, World Neurosurgery (2020), doi: https://doi.org/10.1016/j.wneu.2020.01.079. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc.

Title Page Full Title The Magnetic Resonance Imaging Research of Thoracic Inlet Parameters at Cervical and Cervicothoracic Spine in Degenerative Cervical Spondylosis

Short Title Thoracic Inlet Parameters in Degenerative Cervical Spondylosis

The author/co-authors informations Wanli Li, Fangcai Li, Xiaobo Yang, Shunjie Yu, Weishan Chen, Qixin Chen Department of Orthopedics Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, People’s Republic of China To whom correspondence should be addressed: Wanli Li, M.D. [E-mail: [email protected]]

The Magnetic Resonance Imaging Research of Thoracic Inlet Parameters at Cervical and Cervicothoracic Spine in Degenerative Cervical Spondylosis Abstract Objective The purpose of this study was to examine the thoracic inlet angle (TIA) as well as its related parameters on cervical and cervical-thoracic vertebra in patients with degenerative cervical spondylosis (DCS) and explore the association of TIA, tilt angle of neck (NT), and tilt angle of the first thoracic spine (T1S) with cervical degeneration score. Methods The patients with DCS were included from January, 2014 to December, 2017. The relavant parameters were assessed on T2-weighted MRI. The association of cervical parameters with cervical degeneration score was examined by multiple linear regression model. Results 204 patients were eligible and enrolled, in which the mean age was 55-56 years, 126 of them were males. Male had significantly higher thoracic inlet parameters than females (all P<0.05). Thoracic inlet parameters were positively correlated with age (all P<0.05). After adjustment for age and gender, the significant association between TIA and cervical or cervical-thoracic spine degeneration scores was not observed in all vertebras. Meanwhile, male had higher height of each vertebra (VH) and height of each inter-vertebral disc (IVDH) than females. Only VH of C7, T1, T2 and IVDH of C6/C7, T1/T2, T2/T3 was significantly and positively associated with TIA (all P<0.05). Conclusion Age was positively correlated with thoracic inlet parameters in DCS patients. Males had significantly higher thoracic inlet parameters than females, due to higher VH and IVDH in males. However, TIA was not associated with the level of cervical disc degeneration. But the clinical relevance of these findings has not been established. Keywords

Degenerative cervical spondylosis, Cervical and Cervicothoracic spine, Thoracic inlet angle, Magnetic resonance imaging, Cervical degeneration score

Introduction Sagittal imbalance is the critical promoter in the pathogenesis of spine degeneration and its related symptoms1,2. Thoracic inlet angle (TIA), a morphological parameter, including pelvic incidence (PI), has been validated to be an indicator for the compensation in the cervical vertebra in the previous studies 2,3,4. Its magnitude is correlated with an increased risk of spine degeneration, the previous study found that patients with TIA less than 71° were more likely to suffer cervical kyphosis (CK)3.

Geometrically, tilt angle of neck (NT) is related to TIA and tilt angle of the first thoracic spine (T1S), namely TIA = T1S + NT7. TIA, T1S, and NT are valuable for assessing the sagittal balance of the cervical spine2,5,6. Although recent study has highlighted the significant correlation among TIA, NT, T1S and aging based on X-ray study in asymptomatic population, however, there exist paucity of investigation on the correlation between these parameters and degenerative cervical disease8,14. Moreover, given the vague appearance of TIA in X-ray and its potential harm due to ionization radiation, it is more rational to attempt magnetic resonance imaging (MRI) in clinical practice. 9-13

Hence, in this study, we intended to clarify the following study questions with the utility of MRI: 1. the relationship between TIA as well as its related parameters and the degeneration in cervical or cervical-thoracic vertebra; 2. specifically how the former relationship was affected by age and gender; 3. the association of TIA, NT, and T1S with cervical degeneration score by widely accepted grading systems for degenerative cervical spondylosis.

Patients and Methods Based on the Electronic Medical Record (EMR) established in the Spine Surgery Department, the Second Affiliated Hospital of Zhejiang University, a retrospective analysis was performed on 340 patients diagnosed with degenerative cervical spondylosis (DCS), the patients visited the hospital between January 2014 and

December 2017.

The inclusion criteria were (1) the patients with DCS, and (2) all vertebral bodies and inter-vertebral discs should be distinct in MRI. The exclusion criteria met any one of following conditions: (1) trauma, (2) pathological vertebral fracture, (3) ossification of the posterior longitudinal ligament or the ligamentum flavum, or (4) the history of cervical surgery.

The basic characteristics including patient age and gender were extracted from EMR. The research program has been approved by ethics committee of The Second Affiliated Hospital of Zhejiang University.

Radiologic Measurements The following parameters in sagittal plane were obtained from MRI Scanner (Siemens 1.5 Tesla, USA), T2-weighted imaging with the patients on supine position. The measuring approach of following parameters is presented in Figure 1. (1) Thoracic inlet parameters: NT was defined as the angle between the vertical line through the apex of manubrium and the line connecting the center of cranial endplate of T1 with the apex of manubrium. T1S was defined as the angle between the horizontal line and the cranial endplate of T1. TIA was defined as the angle between the vertical line through the center of the cranial endplate of T1 and the line connecting the center of the cranial endplate of T1 with the apex of manubrium15. (2) Height of vertebra (VH) from the 3rd cervical vertebra (C3) to the 3rd thoracic vertebra (T3) was measured. VH was defined as the distance between upper and bottom cranials of each vertebral body. (3) Height of inter-vertebral disc (IVDH) from the 2nd/3rd cervical vertebra to the 3rd/4th thoracic vertebra (T3/4). IVDH was measured as the distance between the midpoints of the caudal endplate of the lower vertebra to the midpoint of the cranial endplate of the upper vertebra.

Grading system for Disc Degeneration According to Jacobs’s grading system for Disc Degeneration on T2-weighted imaging, cervical disc degeneration was classified into four grades: Grade 0, iso-intensity to hyper-intensity without collapse; Grade 1, hypo-intensity without collapse; Grade 2, hypo-intensity with collapse and modicum osteophytes; Grade 3, hypo-intensity with collapse and evident osteophytes. 16

According to Miyazaki M’s grading system for Disc Degeneration on T2-weighted imaging, cervical disc degeneration was classified into five grades: Grade I, even texture of nucleus pulposus (NP) with hyper-intensity. The boundary between NP and AF is distinct. Disc height is normal; Grade II: Uneven texture of NP with hyper-intensity. The boundary between NP and AF is distinct. Disc height is normal; Grade III: Uneven texture of NP with iso-intensity to hypo-intensity. The boundary between NP and AF is equivocal. Disc height is lost; Grade IV: Uneven texture of NP with hypo-intensity. The boundary between NP and AF is diminished. Disc height is lost; Grade V: Uneven texture of NP with hypo-intensity. The boundary between NP and AF is diminished. Disc is collapsed. 17 Fig 2 showed diagrammatic sketch of two kinds of grading systems.

Statistical Analysis The analysis was conducted with SPSS Version 19.0 (Armonk, NY, IBM Corp,.). The results were presented as the mean ± standard deviation (SD) for continuous variables. Linear regression model was performed to identify the associations of age and gender with TIA, T1S and NT, respectively. After adjustment for age and gender, the association of TIA with cervical degeneration scores, VH, and IVDH was estimated by multiple linear regression models, respectively. P<0.05 was considered as statistical significance.

Results 204 patients with average age 55-56 years were eligible and enrolled, 126 of them

were male.

The associations of gender and age with thoracic inlet parameters Compared with those parameters in males, TIA (β = -6.000, se =1.308, P<0.001), all of T1S (-3.752, 1.090, 0.001), and NT (-2.247, 1.037, 0.031) were smaller in females (Table 1). Overall, age was significantly and positively associated with TIA (β = 0.358, se =0.060, P<0.001), T1S (0.196, 0.050, <0.001), and NT (0.162, 0.048, 0.001), respectively ( Table 2 and Figure 3). However, the association of age with TIA, T1S, and NT was stronger in males than those in female, especially in NT (Figure 3).

The associations of TIA with two kind cervical degeneration scores by multiple linear regression models After adjustment for age and gender, the significant association of TIA with cervical degeneration scores in all cervical vertebras was not observed, despite of Jacobs’s grading system or Miyazaki M’s grading system (Table 3).

The associations of TIA with VH and IVDH multiple linear regression models Male VH and IVDH were longer than females’ in all vertebras (Table 4). While the associations of TIA with VH and IVDH in each vertebra were evaluated by multiple linear regression models, only VH of C7(P=0.001), T1(P<0.001), T2(P=0.014), and IVDH of C6/C7(P=0.001), T1/T2 (P=0.040), T2/T3(P=0.040) were significantly and positively associated with TIA, after adjustment for age and gender (Table 5).

Discussion Rife et al18 have demonstrated the indispensable role of sagittal imbalance especially cervical lordosis in the pathogenesis of spine degenerative disease. TIA, T1S, and NT properly reflect the magnitude of sagittal balance in cervical vertebra2,5,6,13. TIA and T1S showed tremendous values in predicting the occurrence of DCS19,20. In our study, we found that the TIA, NT, and TS were positively correlated with age in patients with DCS, respectively . Nevertheless, the association of TIA and age was stronger

than that of T1S or NT.

Previous studies have verified high T1 slope to be the predisposing pathologica l change and potential risk factor for the development of Modic changes (MC) as well as the ensuing DCS1520. In our study, we adopted two kinds of MRI grading systems to evaluate the relation between TIA and cervical disc degener ation. However, we did not found obvious association between TIA and cervic al disc degeneration.

We also found that C5/C6 disc had higher scores than other spine discs in tw o kinds of grading systems, which indicated C5/6 was the most prone segment to degeneration. Jia et al23 found Modic changes to be more pervasive at C56 and C6-7, the result was similar to our findings.

To our knowledge, this is the first study investigating the relationship between TIA and VH, IVDH of cervical and cervical-thoracic vertebrae. We found that the VH of C7, T1, T2 and IVDH of C6/C7, T1/T2, T2/T3 had significant relevance to TIA. C7/T1 was the watershed of cervical vertebra and thoracic vertebra, thus C7 bears more stress than other cervical vertebra, T1 and T2 share the similar biomechanical property8,17,22. Hence, these sections are more common in cervical lordosis and thoracic kyphosis. A part of VH and IVDH would narrow with aging, which might lead to the increase of TIA, cervical lordosis, and thoracic kyphosis. We speculated that maybe the reason that the decisive factor of the TIA was not all parts of cervical degeneration but only the height reduction of VH and narrowing of IVDH.

Another interesting finding was the discrepancy of TIA, T1S, NT, VH, and IVDH across the gender. All these parameters were significantly higher in males than in females. Higher thoracic inlet parameters in male might be mostly due to higher VH and IVDH, and if the natural degenerative speed of cervical vertebra was similar between male and female, the increase of TIA, T1S and NT were similar.

Nonetheless, this study still had some limitations. Firstly, we did not take spinal function scores into consideration, impairing the clinical extent of our result. Secondly, the parameters determined in our study were primarily based on supine position, rather than prone or standing position, whereas standing position is still the gold standard for deformity measurements. Thirdly, assessing disc degeneration from MRI varies among physicians. Fourthly, based on the studies from Korean, Japanese and European population, TIA, T1S and NT varied across races, but no significant differences.1,4,5,14,21 The discrepancy between races may hinder our findings extrapolate to other populations. Finally, this study did not enroll asymptomatic population as a control group, which can better reveal the relation of TIA and related parameters to the degree of the spine degeneration.

Conclusion In patients with DCS, age was positively correlated with thoracic inlet parameters. Males had significantly higher thoracic inlet parameters than females, due to higher VH and IVDH in males. However, TIA was not associated with the level of cervical disc degeneration. But the clinical relevance of these findings has not been established.

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Table Table 1. General parameters and thoracic inlet parameters between genders Male

Female

β(se)

P

N

126

78

-

-

Age(year)

56.330 ± 10.493

55.540 ± 10.866

-

-

TIA (°)

78.310 ± 9.847

72.030 ± 9.663

-6.000 (1.308)

<0.001

T1sope (°)

25.520 ± 7.406

21.610 ± 8.375

-3.752 (1.090)

0.001

Neck Tilt (°)

52.800 ± 7.245

50.420 ± 7.510

-2.247 (1.037)

0.031

N=Number. The values were represented as the mean ± standard deviation (SD). In the statistical analysis of thoracic inlet parameters with gender, males’ data was as a reference.

Table 2. The association between thoracic inlet parameters with age β(se)

P

TIA

0.358 (0.060)

<0.001

T1sope

0.196 (0.050)

<0.001

Neck Tilt

0.162 (0.048)

0.001

Table 3. The adjusted* association of TIA with two kind cervical degeneration scores in each cervical disc by multiple regression models, respectively. Spine Disc

DD score

N

β(se)

P

Jacobs’s grading system =0

26

Ref

=1

178

0.010(2.083)

=0

16

Ref

=1

157

0.004(2.480)

0.969

=2

27 0.031(3.039)

0.771

=3

4

C2/3 0.879

C3/4

=0

15

Ref

=1

134

-0.031(2.623)

0.796

=2

47 -0.056(2.939)

0.661

=3

8

=0

9

Ref

=1

74

0.261(3.214)

0.085

=2

103

0.086(3.184)

0.580

=3

18

0.043(3.787)

0.681

=0

9

Ref

=1

74

0.155(2.716)

0.212

=2

103

0.025(3.070)

0.840

=3

18

-0.105(4.327)

0.174

=0

60

Ref

=1

136

=2

8

=3

0

C4/5

C5/6

C6/7

C7/T1

0.073(1.637)

0.316

-

-

Miyazaki M’s grading system

C2/3

C3/4

=1

0

-

=2

53

Ref

=3

110

0.085(1.595)

0.276

=4

41

0.100(2.029)

0.210

=5

0

-

-

=1

0

-

-

=2

17

Ref

=3

100

0.004(2.418)

0.973

=4

69

-0.059(2.558)

0.617

=5

18

0.000(3.243)

0.999

=1

0

-

-

=2

11

Ref

C4/5

-

=3

73

0.072(2.96)

0.602

=4

83

0.111(2.969)

0.439

=5

37

0.024(3.227)

0.844

=1

0

-

-

=2

4

=3

51

=4

72

0.013(1.627)

0.861

=5

77

-0.085(1.673)

0.285

=1

0

-

-

=2

15

Ref

=3

85

0.182(2.525)

0.137

=4

70

0.091(2.619)

0.452

=5

34

-0.034(2.943)

0.753

=1

4

=2

70

=3

91

=4

37

=5

2

Ref C5/6

C6/7

Ref C7/T1

0.013(1.604)

0.864

0.071(2.052)

0.366

*adjustment for gender and age. #disc degeneration score (dummy variables, in Jacobs’s grading system, take DD score=0 as a reference; in Miyazaki M’s grading system take DD score=2 as a reference. when the number of DD score less than 9, merge neighboring score) of each cervical disc (from C2/3 to C7/T1).

Table 4. The mean value and statistical dispersion of VH and IVDH in different genders VH Segments

Male N

Mean ± SD

Female N

Mean ± SD

C3

126

10.94±1.182

78

9.59±1.062

C4

126

10.44±1.312

78

9.45±1.124

C5

126

10.03±1.265

78

9.13±1.049

C6

126

9.90±1.046

78

9.01±1.013

C7

126

11.33±1.213

78

10.06±0.931

T1

126

13.60±1.334

78

12.03±1.162

T2

125

14.70±1.404

78

13.17±1.133

T3

92

14.90±1.49

74

13.50±1.208

IVDH C2/3

126

7.17±0.947

78

6.79±0.972

C3/4

126

7.18±1.148

78

6.88±1.259

C4/5

126

7.16±1.162

78

6.49±1.029

C5/6

126

6.75±1.308

78

6.14±1.113

C6/7

126

7.20±1.403

78

7.03±1.173

C7/T1

126

7.25±1.05

78

7.14±0.879

T1/T2

126

6.54±0.918

78

6.45±0.714

T2/T3

126

6.54±0.918

78

6.45±0.714

T3/T4

61

5.75±1.043

65

6.00±0.848

Table 5. The adjusted* association of TIA with VH and IVDH by multiple regression model, respectively Segments

N

β(se)

P

VH C3

203

0.403(0.565)

0.476

C4

203

-0.231(0.514)

0.655

C5

203

-0.071(0.539)

0.896

C6

203

0.342(0.620)

0.582

C7

203

1.849(0.560)

0.001

T1

203

1.768(0.489)

<0.001

T2

202

1.203(0.487)

0.014

T3

165

1.005(0.508)

0.050

IVDH C2/3

203

-0.949 (0.673)

0.160

C3/4

203

0.500(0.536)

0.352

C4/5

203

0.366(0.579)

0.528

C5/6

203

0.922(0.526)

0.081

C6/7

203

1.671(0.491)

0.001

C7/T1

203

-1.036(0.643)

0.109

T1/T2

203

-1.555(0.751)

0.040

T2/T3

203

-1.555(0.751)

0.040

T3/T4

125

0.359(0.873)

0.681

* adjustment for gender, age.

Table Table 1. General parameters and thoracic inlet parameters between genders Male

Female

β(se)

P

N

126

78

-

-

Age(year)

56.330 ± 10.493

55.540 ± 10.866

-

-

TIA (°)

78.310 ± 9.847

72.030 ± 9.663

-6.000 (1.308)

<0.001

T1sope (°)

25.520 ± 7.406

21.610 ± 8.375

-3.752 (1.090)

0.001

Neck Tilt (°)

52.800 ± 7.245

50.420 ± 7.510

-2.247 (1.037)

0.031

N=Number. The values were represented as the mean ± standard deviation (SD). In the statistical analysis of thoracic inlet parameters with gender, males’ data was as a reference.

Table 2. The association between thoracic inlet parameters with age β(se)

P

TIA

0.358 (0.060)

<0.001

T1sope

0.196 (0.050)

<0.001

Neck Tilt

0.162 (0.048)

0.001

Table 3. The adjusted* association of TIA with two kind cervical degeneration scores in each cervical disc by multiple regression models, respectively. Spine Disc

DD score

N

β(se)

P

Jacobs’s grading system =0

26

Ref

=1

178

0.010(2.083)

=0

16

Ref

=1

157

0.004(2.480)

0.969

=2

27 0.031(3.039)

0.771

=3

4

C2/3 0.879

C3/4

=0

15

Ref

=1

134

-0.031(2.623)

0.796

=2

47 -0.056(2.939)

0.661

=3

8

=0

9

Ref

=1

74

0.261(3.214)

0.085

=2

103

0.086(3.184)

0.580

=3

18

0.043(3.787)

0.681

=0

9

Ref

=1

74

0.155(2.716)

0.212

=2

103

0.025(3.070)

0.840

=3

18

-0.105(4.327)

0.174

=0

60

Ref

=1

136

=2

8

=3

0

C4/5

C5/6

C6/7

C7/T1

0.073(1.637)

0.316

-

-

Miyazaki M’s grading system

C2/3

C3/4

=1

0

-

=2

53

Ref

=3

110

0.085(1.595)

0.276

=4

41

0.100(2.029)

0.210

=5

0

-

-

=1

0

-

-

=2

17

Ref

=3

100

0.004(2.418)

0.973

=4

69

-0.059(2.558)

0.617

=5

18

0.000(3.243)

0.999

=1

0

-

-

=2

11

Ref

C4/5

-

=3

73

0.072(2.96)

0.602

=4

83

0.111(2.969)

0.439

=5

37

0.024(3.227)

0.844

=1

0

-

-

=2

4

=3

51

=4

72

0.013(1.627)

0.861

=5

77

-0.085(1.673)

0.285

=1

0

-

-

=2

15

Ref

=3

85

0.182(2.525)

0.137

=4

70

0.091(2.619)

0.452

=5

34

-0.034(2.943)

0.753

=1

4

=2

70

=3

91

=4

37

=5

2

Ref C5/6

C6/7

Ref C7/T1

0.013(1.604)

0.864

0.071(2.052)

0.366

*adjustment for gender and age. #disc degeneration score (dummy variables, in Jacobs’s grading system, take DD score=0 as a reference; in Miyazaki M’s grading system take DD score=2 as a reference. when the number of DD score less than 9, merge neighboring score) of each cervical disc (from C2/3 to C7/T1).

Table 4. The mean value and statistical dispersion of VH and IVDH in different genders VH Segments

Male N

Mean ± SD

Female N

Mean ± SD

C3

126

10.94±1.182

78

9.59±1.062

C4

126

10.44±1.312

78

9.45±1.124

C5

126

10.03±1.265

78

9.13±1.049

C6

126

9.90±1.046

78

9.01±1.013

C7

126

11.33±1.213

78

10.06±0.931

T1

126

13.60±1.334

78

12.03±1.162

T2

125

14.70±1.404

78

13.17±1.133

T3

92

14.90±1.49

74

13.50±1.208

IVDH C2/3

126

7.17±0.947

78

6.79±0.972

C3/4

126

7.18±1.148

78

6.88±1.259

C4/5

126

7.16±1.162

78

6.49±1.029

C5/6

126

6.75±1.308

78

6.14±1.113

C6/7

126

7.20±1.403

78

7.03±1.173

C7/T1

126

7.25±1.05

78

7.14±0.879

T1/T2

126

6.54±0.918

78

6.45±0.714

T2/T3

126

6.54±0.918

78

6.45±0.714

T3/T4

61

5.75±1.043

65

6.00±0.848

Table 5. The adjusted* association of TIA with VH and IVDH by multiple regression model, respectively Segments

N

β(se)

P

VH C3

203

0.403(0.565)

0.476

C4

203

-0.231(0.514)

0.655

C5

203

-0.071(0.539)

0.896

C6

203

0.342(0.620)

0.582

C7

203

1.849(0.560)

0.001

T1

203

1.768(0.489)

<0.001

T2

202

1.203(0.487)

0.014

T3

165

1.005(0.508)

0.050

IVDH C2/3

203

-0.949 (0.673)

0.160

C3/4

203

0.500(0.536)

0.352

C4/5

203

0.366(0.579)

0.528

C5/6

203

0.922(0.526)

0.081

C6/7

203

1.671(0.491)

0.001

C7/T1

203

-1.036(0.643)

0.109

T1/T2

203

-1.555(0.751)

0.040

T2/T3

203

-1.555(0.751)

0.040

T3/T4

125

0.359(0.873)

0.681

* adjustment for gender, age.

Abbreviations and Acronyms DCS: Degenerative cervical spondylosis TIA: Thoracic inlet angle NT: Neck tilt T1S: T1 slope MRI: Magnetic resonance imaging VH: Vertebral height IVDH: Intervertebral disc height

Credit Author Statement Wanli Li generated the idea, origanized the study and modified the manuscript., Fangcai Li collected, managed and analyzed the clinical data; Xiaobo Yang collected the clinical data. Shunjie Yu collected the clinical data and drafted the manuscript; Weishan Chen and Qixin Chen provided the suggestion and comments for study and coordinated the study team.