Example Dogs A–H. Top and third rows – T1-weighted midsagittal MRI images with superimposed framework of lines and angles.

<p>The yellow lines represent the significant variables in the study: F-diameter and Angle 2 and 5. Angle 3, and Lines AE and BC also found to be significant for CM and syringomyelia and are represented in the red (angle) and blue (lines). From left to right (i.e. Dogs A to D and E to H) there is an increase in CM and syringomyelia affectedness. The second and bottom rows detail the corresponding three dimensional images for each dog constructed from the MRI DICOM. For each dog, the age at time of MRI, maximum transverse width of the central canal dilation or syringomyelia is detailed. CCD – central canal dilatation; Yrs – years; CM – Chiari like malformation; SM – syringomyelia.</p

Function values for the SM NO and SM YES groups.

<p>The SM YES dogs have slightly higher values of the function (more positive) and the SM NO dogs have slightly lower values. A few SM YES dogs can be seen to be outliers (*) with unusually high function values.</p

Midline sagittal T1-weighted MRI of hindbrain and craniocervical region of a three year old female Griffon Bruxellois with the framework of measured lines and angles assessing conformational features associated with CM.

<p>The upper image has been “windowed” to create improved contrast and highlight bony landmarks with a magnification of the area of the optic nerve and canal (inset). The lower image demonstrates the same without the windowing effect. All line measurements start from one of 9 points: (A) dorsum of spheno-occipital synchondrosis. (B) basion of basioccipital bone. (C) rostral edge of the dorsal lamina of the atlas. (D) junction between the supraoccipital bone and the occipital crest. (E) most dorsal point of intersection of the cerebellum with the occipital lobe circle. (F) center of occipital lobe circle placed on the cranial baseline (HAI) and extending to encompass the occipital lobes. The centre of the circle is F. (G) point at which the optic nerve deviates into the canal (inset). (H) most caudal point of the olfactory bulb. (I) intersection point with the extended HA baseline. 5 angles measured are (1) ABC, (2) CAF, (3) AID, (4) AGH and (5) AFG.</p

Number of dogs within degrees 0, 1, 2 for Chiari-like malformation (CM) and Syringomyelia (SM).

<p>CM0 - no CM; CM1 - cerebellum indented by supraoccipital bone; CM2 - cerebellum impacted or herniated into foramen magnum; SM0 - normal; SM1 - central canal dilation or a separate syrinx, which has an internal diameter of less than 2 mm or a pre-syrinx alone; SM2 - syringomyelia (central canal dilation which has an internal diameter of 2 mm or greater, a separate syrinx, or pre-syrinx with central canal dilation). Syringomyelia may be late onset condition so SM0 dogs less than 3 years of age were excluded from statistical calculations for syringomyelia as their clear status could not be assured. Conversely SM1 and SM2 dogs less than 3 years old were included as identifying conformational and genetic indicators of this severe phenotype was a paramount goal of the study.</p

Summary of Discriminant Analyses.

<p>The variables that yielded the most statistical power of discriminatory functions have been summarized as ‘success’. The magnitude of contribution from each variable is given (Smaller/Larger), with the level of “success” indicating the unbiased rate of dogs correctly classified. CM – Chiari like malformation; SM – Syringomyelia.</p

Function1 (horizontal) is plotted against Function 2 [vertical].

<p>The group means (centroid; dark crosses) move more to the left as the CM0 to CM1 to CM2 i.e. CM absent to present.</p

Significant variables identified in the statistical analysis for Chiari-like malformation.

<p>F is the Analysis of Variance [ANOVA] test statistic. It assesses the ratio of between group variation to within group variation with higher values indicating the likelihood of a group effect.</p

Grading of Chiari-like malformation and syringomyelia according to the British Veterinary Association/Kennel Club Chiari-like malformation and Syringomyelia Health Scheme.

<p><b>Syringomyelia</b> is defined as a fluid-filled cavity that includes or is distinct from the central canal of the spinal.</p><p><b>Pre-syrinx</b> is defined as spinal cord oedema, and may be a transitional state prior to development of syringomyelia. Pre-syrinx has the appearance of high signal intensity on T2-weighted images consistent with marked increased fluid content within the spinal cord substance but not of free fluid. On T1-weighted images the spinal cord is either normal or has a slightly hypointense signal <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088120#pone.0088120-BVA1" target="_blank">[32]</a>.</p

Diagrammatic illustrations to show the hypothetical effects of compensatory changes in skull dimensions and brain shape when there is craniosynostosis or shortening of certain skull bones.

<p>These figures were created using Adobe Photoshop (<a href="http://www.adobe.com/products/photoshopfamily.html" target="_blank">http://www.adobe.com/products/photoshopfamily.html</a>) which enables manipulation of shapes with fixed points facilitating a simple representation of the distortion. a) Normal; the skull is represented by a black box and brain by a grey circle with reference points w, x, y and z. Asterisk – fixed reference point outside brain. b) Uniform rostrocaudal shortening (black arrows). There is a compensatory increase in height of the brain (white arrow). Lines xy, yz (yellow) and wy (blue) increase and angles wyz and xyz decrease c) Cranial base shortening (black arrow); asymmetrical shortening results in an axial tilting of the brain. There is also a compensatory increase in height (white arrow). Line xy and yz increases (yellow), wy shortens (blue) and angle wyx and xyz decrease. d) Caudal dorsoventral shortening (black arrow). There is a compensatory lengthening of the brain and rostral increase in height (white arrow). Line wy increase (blue), xy and yz shorten (yellow), angle xyz decreases e) cranial base and caudal dorsoventral shortening. When the cranial base and the caudal part of the skull are shortened the circular model brain becomes increasing ellipsoid and there is greater axial tilt with an increase in height rostrally (white arrow). The ventorostral part (olfactory bulbs) is displaced ventrally, the dorsocaudal part (occipital lobes) is displaced caudally and the ventrocaudal part (hindbrain) is displaced rostrally. Line yz shortens and angle xyz decreases. However distance to the external reference point (asterisk) increases (red dotted line). This illustration is offered as an explanation for the increase in line AE and BC in this study and also for the change in brain shape with increasing CM affectedness.</p

Significant variables identified in the statistical analysis for syringomyelia.

<p>F is the Analysis of Variance [ANOVA] test statistic. It assesses the ratio of between group variation to within group variation with higher values indicating the likelihood of a group effect.</p