A Framework for Anemia Differential Diagnosis in Paleopathology Incorporating Metric Methods

Abstract

Objectives: This paper explores metric manifestations of anemia in crania undergoing growth and development using micro-CT imaging. It proposes a framework for assigning a most-likely diagnostic option for anemia, based on evaluating the parameters proposed in this study.

Materials and methods: Sixty-eight orbits/frontal bones of individuals aged birth to 15 years from Quebecois and Dutch archaeological collections dating to the 18th and 19th centuries underwent micro-CT analysis. Individuals were visually assessed for skeletal manifestations of marrow hyperplasia within the internal marrow space using a scoring rubric. Bone microarchitecture measurements were used to calculate T-scores and identify individuals who displayed potential manifestations of marrow hyperplasia. Relative cortical thickness ratios of the frontal bone were calculated for 16 individuals. Error testing was performed for all evaluations.

Results: Using the micro-CT analysis and our diagnostic framework, anemia was inferred in 16% (10/61) of the sample that was preserved well enough for the study. Trabecular separation T-scores were considered the most significant metric for evaluating anemia. Frontal bone ratios were regarded as less insightful due to the imaging technique used. Age had a significant effect on bone measurements, and high repeatability was seen across methods.

Discussion: In this study, recommendations for assigning a diagnostic option prioritize evaluating metric features strongly related to anemia through a biological approach that considers the etiology of marrow hyperplasia. Including a combination of metric and internal visual evaluation criteria provides clearer lines of evidence for the assessment of abnormal bone changes associated with anemia beyond the macroscopic evaluation of porous lesions.

Keywords: cribra orbitalia; marrow hyperplasia; micro‐CT; porotic hyperostosis; porotic lesions.

FIGURE 1

Method of taking measurements for the frontal bone ratio calculation. (a) Arrow indicates location of frontal bone ratio measurement on 3D model. (b) Trabecular space measurement, which is a 2D linear measurement. Arrows indicate the length of the measurement. (c) Ectocranial cortical measurement, indicated by arrows. (d) Endocranial cortical measurement, indicated by arrows. Final ratio is calculated by dividing the measurement from (b) by the sum of the measurements from (c, d).

FIGURE 2

Examples and description of cortical thinning for each scoring category. (a) Cortical thinning score of 0. (b) Cortical thinning score of 1. Arrow indicates a patch of mild thinning, which was present throughout this orbit. (c) Cortical thinning score of 2, where mild thinning is present over more than 50% of the visible cortex. (d) Cortical thinning score of 2, where marked thinning on is present on less than 50% of the visible cortex. (e) Cortical thinning score of 3, where marked thinning on is present on more than 50% of the visible cortex. In this case, the cortex is so thin that it has worn away in patches.

FIGURE 3

Examples of increased trabecular separation for each scoring category, and location of scoring. (a) Location where orbit should be scored (lower third) is highlighted by the box. (b) Increased trabecular separation score of 0. (c) Increased trabecular separation score of 1. (d) Increased trabecular separation score of 2, where mildly abnormally large trabecular separation is seen throughout more than 50% of the marrow space. (e) Increased trabecular separation score of 2, where marked abnormally large trabecular separation (score of 3) is present throughout less than 50% of the marrow space. (f) Increased trabecular separation score of 3.

FIGURE 4

Examples of trabecular thinning for each scoring category. (a) Location where orbit should be scored (lower third) is highlighted by the box. (b) Thinned trabeculae score of 0. (c) Trabecular thinning score of 1. The cortical bone is thin in general, and the trabeculae do not look markedly thin in comparison. (d) Trabecular thinning score of 2 where mild trabecular thinning is seen throughout more than 50% of the trabeculae in the marrow space. (e) Trabecular thinning score of 2 where marked trabecular thinning (score of 3) is present throughout less than 50% of the marrow space. (f) Trabecular thinning score of 3.

FIGURE 5

Placement for the measurement sample box, where microarchitecture measurements were taken. The sample box measures 10 × 10 × 15 mm. The longest edge of the rectangular box was aligned parallel to the orbital lamina, and the lateral edge of the rectangle was aligned with the zygomatic process of the frontal bone, just before where the supraorbital margin begins to curve inferiorly (a, inferior view of right orbital lamina). On the medial‐lateral 2D view, the centre of the box was aligned with the orbital lamina, and oriented such that the most inferior edge was parallel to the centre of the orbital roof (b).

FIGURE 6

Flow diagram showing the various considerations for assigning diagnostic certainty during anemia assessment. D = diagnostic of, HC = highly consistent with, N = not consistent with.

FIGURE 7

Decision tree demonstrating how anemia assessments were done using the available data from this study.

FIGURE 8

Micro‐CT reconstruction of orbit (sagittal view, anterior towards the right) from individual 7A11‐S57 (approximately 1 year old), who displays significant trabecular and cortical thinning, and increased trabecular separation. All observers agreed that skeletal manifestations of marrow hyperplasia were present in this individual.

FIGURE 9

Bone microarchitecture measurements plotted against age estimate midpoints. Trendlines demonstrate the positive relationship between age and increased measurements.