**4. Discussion**

To the best of our knowledge, this is the first study comparing the characteristics of patients with and without an identifiable T1 slope. This was a pilot study in outpatients as a preliminary step to determine the clinical significance of T1 slope visibility on surgery. In this study, the T1 slope could not be identified in 46.7% of the cases. T1 slope was invisible predominantly in males. In males, the C2-7 SVA was significantly larger, and the C2-7 angle in extension was significantly smaller in cases with an invisible T1 slope. The same trend was observed in females, but the difference was insignificant. Thus, the T1 slope was invisible in the male physique, and cases with anterior cervical shift characterized by larger C2-7 SVA.

The T1 slope was first reported by Knott et al. [1] in 2010 as the T1 sagittal angle. They noted that the T1 slope was positively correlated with the C2 SVA, influencing the global sagittal balance. Additionally, several other recent studies have addressed the relationship between the T1 slope and other parameters of the global sagittal balance of the spine. Patients with a large T1 slope require large cervical lordosis to preserve the sagittal balance of the cervical spine, suggesting that the T1 slope affects cervical sagittal alignment [14]. Furthermore, Lee et al. [3,15] reported a significant relationship between the T1 slope and thoracic kyphosis. A significant weak correlation between the T1 slope and lumbar lordosis was also reported [15]. These findings sugges<sup>t</sup> that the T1 slope is associated with cervical sagittal alignment and thoracic and lumbar sagittal alignment, in addition to the fact that the T1 slope is an important factor for global sagittal alignment. However, it

has been reported that upright cervical radiographs are more accurate than whole spine radiographs for evaluating cervical spine alignment, including T1 slope. This study used upright cervical spine radiographs instead of whole spine radiographs [16].

Despite the importance of the T1 slope, the T1 vertebral body is often unclear on cervical radiographic images due to interference of the shoulder contour, especially in obese or muscular individuals [11,17], resulting in difficulty in identifying the T1 slope. In previous reports, the T1 slope was difficult to identify in approximately one-third of the cases [12,17]. In this study, the T1 slope could not be identified in 46.7% of the cases, almost consistent with the previous observation.

Several alternative methods have been investigated in cases with an invisible T1 slope, including magnetic resonance imaging (MRI) or computed tomography (CT). T1s-CL is important for cervical spine postoperative alignment assessment. In a study examining alternative parameters to T1s-CL, the C2 slope was the parameter that correlated best with pre- and postoperative changes [18]. Supine MRI and CT images cannot be considered an alternative to the T1 slope on lateral radiographs as these images are not captured in the upright position [19]. Jun et al. reported that the T1 slope angle on radiographs was larger than on CT images. However, a significant correlation was noted between the T1 slope angles on radiographs and CT images [10]. Park et al. correlated C7 slope with T1 slope by measuring T1 slope on CT based on C7 slope on X-ray. However, they excluded cases where the T1 slope was not visible on the X-ray [13]. A strong correlation between C7 slope and T1 slope has been found in MRI studies with the patient seated in upright weight-bearing neutral positions. However, no comparison with x-rays has been made [20]. Ideally, the imaging modality enabling clear visualization of the T1 upper endplate in an upright position, such as EOS® (EOS® imaging, Paris, France), is generally desired [21]. EOS® is the EOS imaging system, a novel technique that allows for acquiring images of the body or of body sections in standing position and under normal weight-bearing conditions [22]. However, many facilities do not have access to EOS, and researchers have to exclude cases in which the T1 upper endplate is invisible. As an alternative to the T1 slope on lateral radiographs, the C7 slope reportedly correlated significantly with the T1 slope [12,17].

We showed that cases with invisible T1 slopes had some notable characteristics. First, the T1 slope was invisible in males. This may be affected by differences in body thickness and shoulder position between men and women: the T1 upper endplate could be affected by the shoulder and thoracic trunk, especially in obese and short-necked patients [10]. Furthermore, Reynolds et al. demonstrated that neck circumference influences cervical sagittal alignment [23]. Neck circumference is influenced by muscle or obesity [24]; thus, it can influence T1 slope visibility. Further, we found significant differences in extension (C2-7) angle and C2-7 SVA between patients in the I and V groups. In cases where the cervical vertebrae shift forward and the cervical backward bending angle is small, T1 is hidden under the soft tissue and appears invisible, as shown in Figure 4. The risk of kyphotic deformity after cervical decompression is high in cases with a large C2-7 SVA shift [25]. Many cases require deformity correction, and the T1 slope must be considered to achieve an ideal cervical lordosis. The classification of cervical spine deformity is based on the T1 slope [26]. However, it might be necessary to consider a new classification based on a reliably measurable index such as the C7 slope [12].

There are some limitations to this study. First, the number of patients included in this study was small. Further, this study was conducted on symptomatic patients, which may have affected the global alignments. To overcome this problem, clinicians should consider investigating the radiography of healthy individuals. However, these patients may be evaluated in clinical studies for surgical results. Furthermore, the condition of radiographic imaging was not completely unified; thus, it could affect T1 visibility. It would also have been desirable for the three surgeons to blindly classify the patients into the V and I groups before starting the study. However, since there were no numerical data, the three surgeons discussed the decision from the beginning. As a result, it was necessary to discuss and decide one way or the other, and the result would not have been different even if we had

done it blindly at the beginning. In addition, C2-7 SVA and C2-7 angles were measured by a single person, and the validation is insufficient.

## **5. Conclusions**

In summary, our study analyzed the differences in demographic and radiological characteristics between patients with visible or invisible T1 slopes. Our findings sugges<sup>t</sup> that the T1 slope tends to be invisible in males with greater C2-7 SVA. This was a pilot study. Therefore, based on the results of this study, we would like to accumulate surgical cases in the future and further investigate the clinical significance of this study.

**Author Contributions:** Conceptualization, A.M.; methodology, S.I. (Sadayuki Ito); software, A.M.; validation, A.M.; formal analysis, S.I. (Sadayuki Ito); investigation, S.I. (Sadayuki Ito), H.N., A.M., K.A., M.M., N.S., H.T., H.K. and S.I. (Shiro Imagama); resources, S.I. (Sadayuki Ito), H.N., A.M., K.A., M.M., N.S., H.T., H.K. and S.I. (Shiro Imagama); data curation, A.M.; writing—original draft preparation, S.I. (Sadayuki Ito); writing—review and editing, S.I. (Sadayuki Ito) and H.N.; supervision, S.I. (Shiro Imagama); project administration, H.N. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research did not receive any specific gran<sup>t</sup> from funding agencies in the public, commercial, or not-for-profit sectors.

**Institutional Review Board Statement:** The research protocol was approved by the Human Research Ethics Committee and the University's Institutional Review Board (approval number: 2005-0354-3). All participants gave written informed consent prior to participation. The research procedure was carried out in accordance with the principles of the Declaration of Helsinki.

**Informed Consent Statement:** Informed consent was obtained from all subjects involved in the study.

**Data Availability Statement:** The data of this study are available from the corresponding author upon request.

**Acknowledgments:** We are grateful to the staff of the department of radiology at Nagoya University Hospital.

**Conflicts of Interest:** The authors declare that there is no conflict of interest regarding the publication of this paper.
