Table 1. Three-dimensional anatomical definitions of the 61 osseous/hard tissue 3D CBCT landmarks used this study. Landmarks are listed according to landmarking module and type, which indicates whether they are midline or bilateral landmarks.

Module Type Landmarks Definition Face Midline Nasion Midpoint of the fronto-nasal suture. Prosthion Most anterior point of the maxillary in the midline (Between central incisors). A Point Point of maximum concavity of the maxillary alveolar process in the midline (Between central incisors). ANS Most anterior mid-point of the of . PNS Most posterior mid-point of the posterior nasal spine of the palatine . Bilateral Orbitale Most antero-inferior point on the inferior orbital rim. Supraorbitale Most superior and anterior point of the superior orbital rim (not including the supraorbital notch). Frontozygomatic Antero-lateral point on the Fronto-Zygomatic Suture suture. Zygomatic Most latero-inferior point on the lateral curve of Arch the . Jugale Deepest midpoint of the jugal process of maxilla. Nasal Cavity Point of junction of lateral wall of nose, nasal floor and nasal process of maxilla. Cranial Midline Basion Midpoint of the anterior border of the anterior Base curvature of the foramen magnum. Sella Mid-point of the sella turcica. Sella Inferior Most inferior and mid-point of the floor of the sella turcica. Sella Posterior Most posterior and mid-point of the posterior border of the sella turcica. Clinoidale Most anterior and mid-point of the anterior border of the sella turcica. Most superior point of the crista galli. Opisthion Midpoint of the posterior border of the posterior curvature of the foramen magnum.

1

Bilateral Porion Most superior and mid-point of the external auditory meatus. Glenoid Fossa Most superior point of maximum curvature in glenoid fossa. Foramen Ovale Most antero-medial and superior point of the anterior border of the foramen ovale. Optic Canal Most antero-lateral and superior point of the anterior border of the optic canal. Anterior Most anterior superior point on the anterior Cranial Fossa border of the middle cranial fossa. Internal Acoustic Most posterior lateral point on the posterior Meatus border of the internal acoustic meatus. Hypoglossal Most antero-medial and superior point of the Canal anterior border of the hypoglossal canal (anterior border of the posterior canal in case of 2 canals).

Mandible Midline Infradentale Point where the crown/root of the right mandibular central incisor meets the alveolar projection. B Point Point of maximum concavity of the alveolar process in the midline (Between central incisors). Pogonion Most anterior point on the symphysis of the mandible. Gnathion Most antero-inferior point on the contour of the (between Pogonion and Menton). Menton Most inferior point of the mandibular symphysis. Bilateral Coronoid Most superior point of the tip of the coronoid process. Condylion Most superior and posterior point on the condyle of the mandible. Articulare Most posterior point of the posterior curvature of the head of the condyle. Gonion Highest point of the curvature of the mandibular angle formed by the junction of the ramus and the body of the mandible. Teeth Bilateral Upper Incisor Most superior point on the apex of the root of the Root right maxillary central incisor.

2

Upper Incisor Tip Mid-point of the incisal edge of the right maxillary central incisor. Upper Incisor Most anterior point on the labial curvature of the Labial right maxillary central incisor. Crown Lower Incisor Most inferior point on the apex of the root of the Root right mandibular central incisor. Lower Incisor Mid-point of the incisal edge of the right Tip mandibular central incisor. Lower Incisor Most anterior point on the labial curvature of the Labial Crown right mandibular central incisor. Upper Molar Most superior point of the tip of the mesio-buccal Root root of the first maxillary molar. Upper Molar Most superior point of the mesio-buccal cusp tip Cusp of the first maxillary molar. Lower Most inferior point of the tip of the mesial root of Molar Root the first mandibular molar. Lower Molar Most superior point of the mesio-buccal cusp tip Cusp of the first mandibular molar.

3

Table 2. Intraclass correlation coefficients by X, Y, and Z landmark coordinate for intra-rater consistency (“ICC within raters”) and inter-rater agreement (“ICC between raters”). Landmarks are sorted by module. For bilateral landmarks, estimates are provided for both sides.

ICC within raters ICC between raters

Module Landmark Side X Y Z X Y Z

Face Nasion Midline 1.00 1.00 1.00 1.00 1.00 1.00

Prosthion Midline 0.74 0.91 0.65 0.81 0.97 0.80

A Point Midline 0.74 0.96 0.79 0.76 0.96 0.91

Anterior Nasal Midline 0.70 0.88 0.98 0.87 0.90 0.97 Spine

Posterior Nasal Midline 0.31 0.96 0.93 0.16 0.95 0.97 Spine

Orbitale Right 0.73 0.78 0.95 0.71 0.86 0.96

Left 0.54 0.74 0.94 0.61 0.79 0.92

Supraorbitale Right 0.88 0.89 0.90 0.32 0.79 0.76

Left 0.62 0.83 0.87 0.20 0.51 0.84

Frontozygomatic Right 0.95 0.96 0.95 0.94 0.98 0.94 Suture Left 0.95 0.93 0.91 0.89 0.96 0.94

Zygomatic Arch Right 0.96 0.86 0.94 0.98 0.87 0.96

Left 0.96 0.70 0.95 0.98 0.78 0.96

Jugale Right 0.75 0.88 0.85 0.67 0.93 0.87

Left 0.71 0.87 0.79 0.73 0.89 0.89

Nasal Cavity Right 0.71 0.91 0.91 0.68 0.94 0.96

Left 0.58 0.90 0.85 0.77 0.95 0.92

Basion Midline 1.00 0.99 0.97 1.00 0.98 0.98

4

Cranial Sella Midline 0.40 0.98 0.97 0.63 0.96 0.97 Base Sella Inferior Midline 0.49 0.96 0.98 0.76 0.93 0.99

Sella Posterior Midline 0.43 0.96 0.96 0.67 0.97 0.93

Clinoidale Midline 0.42 0.98 0.96 0.65 0.99 0.98

Cribriform Plate Midline 0.84 0.81 0.88 0.93 0.93 0.88

Opisthion Midline 0.61 0.99 0.94 0.55 0.97 0.97

Porion Right 0.76 0.97 0.95 0.73 0.97 0.96

Left 0.76 0.96 0.95 0.75 0.99 0.96

Glenoid Fossa Right 0.78 0.97 0.96 0.73 0.97 0.96

Left 0.75 0.96 0.96 0.61 0.93 0.95

Foramen Ovale Right 0.81 0.97 0.94 0.77 0.98 0.97

Left 0.66 0.97 0.92 0.77 0.97 0.95

Optic Canal Right 0.73 0.70 0.97 0.89 0.79 0.94

Left 0.81 0.75 0.95 0.76 0.70 0.94

Anterior Cranial Right 0.55 0.97 0.95 0.49 0.93 0.97 Fossa Left 0.61 0.94 0.93 0.54 0.94 0.97

Internal Acoustic Right 0.91 0.99 0.93 0.91 0.99 0.98 Meatus Left 0.84 0.98 0.96 0.91 0.99 0.97

Hypoglossal Canal Right 0.76 0.98 0.93 0.88 0.98 0.96

Left 0.87 0.98 0.95 0.91 0.98 0.94

Mandible Infradentale Midline 0.86 0.99 0.95 0.91 0.99 0.91

B Point Midline 0.88 1.00 0.92 0.92 0.99 0.98

Pogonion Midline 0.84 0.99 0.97 0.94 0.99 0.98

Gnathion Midline 0.93 0.99 0.99 0.94 0.99 0.99

5

Menton Midline 0.91 0.99 0.99 0.93 0.99 0.99

Coronoid Process Right 0.96 0.97 0.98 0.95 0.95 0.98

Left 0.97 0.97 0.97 0.98 0.95 0.98

Condylion Right 0.69 0.97 0.93 0.76 0.97 0.98

Left 0.64 0.93 0.94 0.74 0.97 0.97

Articulare Right 0.82 0.99 0.92 0.66 0.98 0.93

Left 0.62 0.98 0.91 0.76 0.97 0.95

Gonion Right 0.93 0.96 0.91 0.92 0.97 0.98

Left 0.97 0.97 0.95 0.96 0.97 0.97

Teeth Upper Incisor Root 0.74 0.98 0.97 0.94 0.99 0.97

Tip 0.80 0.99 0.97 0.88 0.99 0.97

Labial 0.79 0.92 0.89 0.84 0.95 0.91 Crown

Lower Incisor Root 0.96 1.00 0.97 0.97 1.00 0.98

Tip 0.96 1.00 0.97 0.97 1.00 0.98

Labial 0.96 0.98 0.91 0.98 0.97 0.90 Crown

Upper Molar Cusp 0.88 0.97 0.97 0.94 0.97 0.98

Root 0.74 0.93 0.98 0.60 0.98 0.98

Lower Molar Cusp 0.91 0.96 0.97 0.90 0.99 0.98

Root 0.85 0.95 0.98 0.86 0.99 0.98

6

Table 3. Measurement error estimates. Overall error per landmark was calculated via 3D RMSE around the mean and also calculated separately for each X, Y and Z landmark coordinates based on the standard deviation around the mean. Landmarks are sorted by module. All estimates are presented in mm and for bilateral landmarks, error measures are calculated independently for each side.

Module Landmark Side RMSE SD_X SD_Y SD_Z

Face Nasion Midline 0.00 0.00 0.00 0.00

Prosthion Midline 1.42 0.60 1.14 2.16

A Point Midline 1.21 0.63 0.69 1.39

Anterior Nasal Spine Midline 1.06 0.53 0.94 0.72

Posterior Nasal Spine Midline 1.18 0.78 1.02 1.31

Orbitale Right 1.22 1.26 0.79 0.72

Left 1.31 1.46 1.01 0.74

Supraorbitale Right 1.45 1.98 0.78 1.04

Left 1.57 2.48 1.18 0.94

Frontozygomatic Right 1.00 0.53 0.54 0.88 Suture Left 1.05 0.63 0.57 0.92

Zygomatic Arch Right 1.34 0.53 1.72 0.99

Left 1.36 0.56 2.00 0.86

Jugale Right 1.40 1.28 1.04 1.57

Left 1.36 1.23 1.11 1.47

Nasal Cavity Right 1.29 1.18 0.93 1.08

Left 1.29 1.11 0.79 1.32

Cranial Basion Midline 1.00 0.00 0.70 0.88 Base Sella Midline 1.08 0.68 0.57 0.95

7

Sella Inferior Midline 1.06 0.64 0.71 0.77

Sella Posterior Midline 1.17 0.67 0.58 1.35

Clinoidale Midline 1.05 0.70 0.45 0.91

Cribriform Plate Midline 1.12 0.43 0.83 1.22

Opisthion Midline 1.31 0.98 1.07 1.35

Porion Right 1.29 1.42 1.05 0.72

Left 1.14 0.99 0.81 0.72

Glenoid Fossa Right 1.29 1.28 1.05 0.90

Left 1.30 1.38 1.02 0.89

Foramen Ovale Right 1.17 0.89 0.64 1.07

Left 1.19 0.87 0.70 1.22

Optic Canal Right 1.26 0.86 1.47 0.96

Left 1.35 1.27 1.49 0.98

Anterior Cranial Fossa Right 1.35 1.53 1.02 0.98

Left 1.26 1.28 0.95 0.84

Internal Acoustic Right 1.12 0.84 0.69 0.94 Meatus Left 1.11 0.86 0.58 0.90

Hypoglossal Canal Right 1.09 0.68 0.67 0.96

Left 1.17 0.72 0.78 1.21

Mandible Infradentale Midline 1.31 1.08 1.10 1.34

B Point Midline 1.33 0.98 0.84 1.76

Pogonion Midline 1.28 1.10 0.95 1.21

Gnathion Midline 1.20 0.90 1.03 0.95

Menton Midline 1.23 0.97 1.26 0.75

8

Coronoid Process Right 1.05 0.59 0.81 0.77

Left 0.99 0.49 0.65 0.76

Condylion Right 1.34 1.69 0.88 0.90

Left 1.34 1.68 0.93 1.01

Articulare Right 1.29 1.02 0.69 1.39

Left 1.23 1.12 0.67 1.22

Gonion Right 1.47 0.85 1.70 1.65

Left 1.41 0.85 1.62 1.42

Teeth Upper Incisor Root 1.02 0.63 0.60 0.77

Tip 1.06 0.72 0.69 0.77

Labial 1.37 0.77 1.64 1.41 Crown

Lower Incisor Root 1.04 0.68 0.78 0.74

Tip 1.00 0.65 0.67 0.63

Labial 1.43 0.64 1.93 1.37 Crown

Upper Molar Cusp 1.13 0.74 0.87 0.89

Root 1.36 1.65 1.49 0.76

Lower Molar Cusp 1.27 1.07 1.53 0.88

Root 1.32 1.18 1.66 0.81

9