Calcification of Costal Cartilage in the Adult Rib Cage · calcification to be considered when modelling changes in the mechanics of the rib cage with age, and have explored a

Abstract Costal cartilage bridges the sternum and the ribs and plays a key role in the biomechanics of the

chest. Costal cartilage is known to calcify in local regions with age, which can substantially stiffen its overall

response to loading. However, the rate of accumulation of the calcified volume is not well quantified. Current

computational models of the thorax assign a homogeneous soft material to cartilage segments, yet their finite

element meshes are well suited to the specification of interstitial calcification zones, should applicable data

become available.

This study measures volumes and extents of costal cartilage calcification from 205 live subject CT scans.

Significant increases in volume calcification – both in a given cartilage segment and in the lengthwise extent of

those segments that experience calcification – are seen with age (p<0.0001). Age and sex accounted for 35% of

all inter‐individual population variability. Specific recommendations for introducing person‐age via regional

calcification to models of the costal cartilage are that (1) calcification volume within a segment should increase

at the rate of 0.9 mm (for an equivalent cube edge length) per decade, and (2) should involve an increasing

lengthwise extent of the cartilage segment at a rate of at least 7% per decade.

Keywords age, calcification, cartilage, costal cartilage calcification, rib.

I. INTRODUCTION

The chest plays a major role in mitigating the forces that the body experiences during motor vehicle crash

events. Costal cartilage is a key structural component of the chest, contributing to its rigidity and reinforcing the

chest wall by bridging the space between the sternum and the ribs. Simulated stiffening of the costal cartilage

through an added tough outer shell has been shown to increase the overall chest stiffness by 50% [1], and

simulated stiffening of the cartilage material itself has increased subsequent stress levels in the ribs by 63%

during loading of the sternum [2] and increased rib fractures in diagonal belt loading [3].

Costal cartilage is organised in a series of segments connected to the ribs, with typical topology connecting

ribs 1‐4 directly to the sternum, ribs 5‐7 to both the sternum and to superior segments, and ribs 8‐10 to only

superiorly neighbouring segments. Its material structure includes a hyaline cartilage mid‐substance surrounded

by an outer layer of perichondrium. Over time, portions of the costal cartilage can calcify (less commonly but

more precisely termed ossify), producing inhomogeneities of substantially harder and stiffer material properties

within or around a cartilage segment. This calcification can substantially stiffen the mechanical response of the

cartilage, particularly when the calcified tissue forms a bridge across the length of a costal segment [4].

An association between advancing age and presence (or size) of calcification is well documented [5‐9], and

studies have also described differences between the typical patterns of calcification seen between males and

females [8,10]. Results from these studies have been used forensically to help estimate the age and sex of

unknown deceased persons [8,11]. However, with the most common data source being X‐ray images taken from

an anterior aspect, there is limited volumetric information describing the typical amounts and distribution of

calcification that might inform 3D biomechanical models.

Computational human body models are increasingly being used to understand the biomechanics of the

thorax to loading, and recent efforts have included the concept of person‐age by building models specifically

representing elderly individuals [3,12‐14]. Forman and Kent [15] have highlighted the need for costal cartilage

calcification to be considered when modelling changes in the mechanics of the rib cage with age, and have

explored a methodology for the placement of calcified elements within current model meshes. One aspect still

SA. Holcombe, PhD ([email protected], +17346475444) and S. Ejima, PhD are Research Scientists at the University of Michigan in the International Center for Automotive Medicine (ICAM), USA. SC. Wang, PhD, MD, is a University of Michigan Professor of Surgery and director of ICAM, USA.

Calcification of Costal Cartilage in the Adult Rib Cage.

SA. Holcombe, S. Ejima, SC. Wang

IRC-17-106 IRCOBI conference 2017

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lacking, however, is an understanding of how much of a given cartilage segment should be specified as calcified

within a model in order to best represent the costal cartilage of a given demographic.

This study aims to contribute to the body of knowledge required to address that need by quantifying the

volume and extent of cartilage calcification that is seen in adults, and to describe the population variability that

exists for such measures. Specifically, this study aims to quantify the rate of calcification accumulation with age

that is typical within a live adult population, and to quantify the differences in calcification amount that is

expected between males and females. Such information can help build more accurate models of calcified

cartilage in order to better understand the effect that age has on the biomechanics of the chest.

II. METHODS

Scan and Study Population

The study population consisted of 205 individuals (110 female, 95 male) aged 17 to 91 years. All subjects had

received chest CT scans obtained for trauma purposes between 2001 and 2016, collected from the International

Center for Automotive Medicine (ICAM) morphomics database. All scans were taken in a supine position. Scan

axial resolution ranged from 0.56 mm to 0.97 mm, and scan slice spacing ranged from 0.625 mm (53% of scans)

to 5.0 mm (2% of scans) with 93% of scans taken at 1.25 mm spacing or lower. 47 subjects with rib fractures

were retained in the study, however subjects with extreme skeletal abnormalities or fixation devices present in

the scan were excluded.

Costal Cartilage Identification

To identify regions of costal cartilage calcification from within the CT image volumes a set of curved 3D

reformations through those image spaces were developed via custom‐made routines in MATLAB 2016b (The

Mathworks Inc., Natick, MA). These reformations serve to spatially isolate the anterior chest wall (containing

the costal cartilage segments and the sternum) from other parts of the body. Within this space, traditional

histogram‐based segmentation and morphological operations can then extract the volumetric regions of locally

calcified cartilage.

The reformations are based on a grid of landmarks that are placed manually into the 3D space of the CT scan

at (1) the ends of left and right ribs (designating the start of each costal segment), (2) the sternal connection

locations (or ends of each costal segment), and (3) a point approximately mid‐way along each costal segment at

its cross‐sectional centre. A curved 3D surface is then generated that passes smoothly through this grid of

landmarks [16], forming an approximate representation of the mid‐surface of the anterior chest wall as depicted

in Fig. 1 (left). A volumetric region encompassing the costal cartilage is identified as the 3D space within a 10

mm offset from this mid‐surface. Anatomically, costal cartilage segments meet the ribs at a cup‐shaped

depression in the rib cortical bone, and the rib end landmark is placed specifically at the apex of this cup [4].

Similarly, a depression is present at the sternal end of the cartilage segments and the apex of each cup is chosen

for the placement of each sternal connection landmark. To ensure accuracy, custom MATLAB interfaces were

written allowing a user to place an approximate landmark on regular axial CT slices, then adjust that landmark

using multiply resliced oblique views centred on that local region.

Image voxels for the 2nd through 5th rib cartilage segments were resampled through this curved volumetric

region from the original CT data using bilinear interpolation. The zone between each sternal landmark was

excluded, and the remaining space was partitioned into individual segments for each rib level based on

proximity to the central curve from each rib end to sternal connection point. A threshold of 180 Hounsfield

Units (HU) was used to separate calcified regions of cartilage from the other (lower density) surrounding tissues.

Minor morphological operations then removed extremely small calcification regions (less than 1 mm3) and to

remove the internal thoracic arteries which run vertically adjacent to the sternum, producing the isolated

regions of calcification as illustrated in Fig. 1 (right). Note that under this overall segmentation scheme the small

amount of bone contiguous with the rib or the sternum which forms the connecting cup (which is on the order

of 5 mm deep) will also be classified as calcification.


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Fig. 1. Example mid‐surface of the chest wall through cartilage segments built from the grid of manually placed rib end, sternum connection, and mid‐segment landmarks (left). In this view costal cartilage calcification is clearly visible as white regions along segments. Full volumetric regions from the same subject are shown in 3D (right).

Measured Variables and Statistical Analyses

The primary object of measurement was the volumetric amount of calcification identified within each

cartilage segment space, and this volume, V, was recorded for each segment in units of mm3. To improve data

normality for statistical analyses, and to retain conceptual understanding, volumetric results are presented in

this study by a cubed root transformation to the edge length E (mm) of a cube containing the equivalent volume

of calcification as was measured from within the costal segment. A secondary measurement for the extent of

calcification along a segment was characterised by the lengthwise percentage (LenPcnt, %) of each costal

segment that contained any calcified region within its cross section. For example, a segment with calcification

regions emanating from the ribs and from the sternum each involving some portion of 20 % of the segment’s

overall length would be designated with a lengthwise percentage (LenPcnt) of 40 %.

These measurements were taken from eight separate cartilage segments (ribs 2 through 5, left and right

sides of the body), amounting to a total of 1640 observations. Results are reported firstly on a per‐segment

basis and, for statistical analyses, the average E and LenPcnt values are taken across all segments per individual

reducing the data to one observation per individual. Multivariable linear regression is performed to investigate

associations between measured variables and subject age and sex, with statistical significance reported at the

p<0.05 level.

III. RESULTS

Measurements of calcification volume were collected from all costal cartilage segments. Fig. 2 shows the

population distribution of equivalent cube edge length (E, mm) of these volumes for males and females,

stratified by rib segment level. These distributions show that males typically have a higher calcification volume

than females at each segment level (p<0.01). Lower rib levels (4 and 5) are also seen to contain a marginally

greater volume of calcification than levels 2 and 3 (with E increased by 2.1 mm, p<0.01). For reference, the

average segment lengths are given in Fig. 2, showing a clear trend for lower cartilage segments being longer

than upper segments at increments of approximately 8 mm. When considering the percentage length of rib

segments that show calcification involvement (LenPcnt), there are no longer clear sex differences or differences

in extent calcification by rib segment level.


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Fig. 2. Results per segment for the overall calcification volume (given by the equivalent cube edge length, E), the geometric length of each segment (mm), and the percentage length of a cartilage segment with non‐zero calcification involvement (LenPcnt). Boxes show the median and the 25th to 75th quantile ranges and whiskers extend to the ±2.7 sigma range (99.7% coverage).

The measurements of calcification volume (E) were averaged across the eight costal segments for each

individual, and are shown by age and sex in Fig. 3 below. Linear regression trend lines are also shown, with

regression coefficients summarised in Table 1. Regression results showed significant increases (p<0.0001) in the

volume calcification (with equivalent cube edge length, E, increasing at the rate of 0.9 mm per decade) and

extent calcification with age (additional 6.9 % of segment length involvement per decade). Males had higher

overall volumes of calcification (average E across all segments being 1.56 mm larger, p<0.0001) than females,

however no significant difference in extent calcification () was seen between sexes (p>0.1). Results also did not

support any sex‐based differences in the rate of calcification accumulation with age, as subsequent regression

models with an additional age‐sex interaction term found that term to not be significantly different to zero

(p>0.1).


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Fig. 3. Average calcification volume (equivalent cube edge length, E) per segment by age (top left), and average lengthwise extent of calcified cartilage (LenPcnt, top right). Chest wall mid‐surface images for individuals marked A‐C are shown for comparison (bottom row).

TABLE I MULTIVARIABLE REGRESSION RESULTS TO CALCIFICATION MEASUREMENTS

E (mm) r2 = 0.35 LenPcnt (%) r2 = 0.26

Predictor Estimate p Estimate p

Intercept 2.545 < 0.0001 21.805 < 0.0001

Sex (0=M,1=F) ‐1.567 < 0.0001 ‐5.502 0.13

Age (years) 0.089 < 0.0001 0.689 < 0.0001

IV. DISCUSSION

This study reports quantitative measurements of costal cartilage calcification taken from CT images from a

population of live adult subjects. There has been previous in‐depth quantitative analysis of cartilage segments

from 11 PMHSs at the microstructure level using MicroCT [4], and limited quantitative data from analysis of

large populations for the purpose of age and sex determination using X‐ray imaging [9,10]. The measurements

presented here are intended to assist researchers design calcification schemes that can be added to current

human body computational models in order to better model the aging process within the costal cartilage.

In part due to a limited amount of available information, current thoracic computational models assign a

single homogeneous material to the costal cartilage, with material properties representative of the hyaline

cartilage mid‐substance without calcification [17‐19]. Such finite element models, however, have the capacity to

assign specific material properties to individual finite elements within a solidly meshed part. Furthermore, shell

elements can be added to cartilage surface parts to form a separate perichondrium layer, again capable of non‐

uniform material properties.

Forman and Kent [20] implemented an inhomogeneous cartilage material into subject‐specific finite element

component models of the costal cartilage. Their modelling schematic included setting the distinct solid finite

elements corresponding to regions of calcification (as derived from CT images of the cadaveric specimens being

modelled) to a stiffer material property. Forman and Kent [15] further expanded this methodology by

introducing a parametric calcification severity, whereby progressively larger (or smaller) clusters of elements

were assigned the calcification material model compared to a baseline individual. The calcification scoring

system used was based partly on methods developed by McCormick [7] from anterior X‐ray images. The

A B C


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technique used here instead utilises 3D volumetric data from CT images to quantify calcification amounts. This

could advance the modelling methodology (whereby specific finite elements are set to a calcified material

property) by setting volumetric targets explicating the amount that a calcification region should expand in order

to provide a target volume of calcification and consequently represent a chosen increase in age.

Microstructural studies have shown that calcification can occur in multiple different structured morphologies

including, in some cases, dense shells surrounding a core of struts similar to trabeculae [4]. While not possible to

discern under clinical CT scan resolutions, these fine details are also not easily represented in current full body

computational models (which have cartilage element edge lengths in the order of 2‐10 mm). This study has

consequently focused on quantifying the overall volumes of calcification within a segment and understanding a

simplified representation of its spatial distribution. Analytic work has explored microstructural connectivity

variations in cartilage, simulating the elastic modulus of heterogeneous cartilage segments with calcified regions

assigned either in clusters or dispersed throughout a cartilage segment [21]. Results showed that stiffness

increases substantially as calcification connectivity increases, suggesting that FE models would exhibit different

behaviour based both on the amount of calcification imposed, and on its spatial configuration within a cartilage

segment.

The volumes of calcification reported in the current results are consistent with expectations based on

previous literature. Most studies report that calcification typically begins to form in approximately the third

decade of life [9,22], is commonly of moderate severity between ages 50–60 [5,7], and is moderate or severe in

approximately 45% of persons over 75 [7,23]. The current data largely reflects these trends, however it is

notable that the lowest end of the calcification volume distribution does not actually reach zero. This is likely

due to the relatively simplistic delineation between rib bone and costal cartilage that is used here, whereby the

cartilage and rib or sternal bones are separated via an assumption about their connections’ cup‐shaped

morphology. This assumption means that the periphery of this cup‐shaped depression likely contains small

volumes of rib bone which are being considered as calcified volume, making the overall calcification volume

non‐zero.

Observation of the calcification patterns seen from mid‐surface reformations of the chest wall (see Fig. 3

second row, for example) match well with previous descriptions of sex‐based differences in the morphology of

accumulated calcified cartilage. Specifically, males are reported to exhibit a peripheral pattern characterised by

ossification of the inferior and superior costal cartilage margin, whereas females show one or more central

calcification patterns with pyramidal‐shaped central tongues of ossification or centrally‐placed smooth globules

of ossification [6,22]. Such differences are seen clearly in the two highly calcified individuals highlighted in Fig. 3

(lower row), and similar patterns were observed across most other individuals. Cartilage calcification occurs as

calcium uptake into the cartilage tissue increases. The underlying mechanism for this difference between males

and females in costal cartilage calcification patterns has not been fully explored. However, with calcium uptake

into cartilage tissue being the primary cause of calcification in general, early hypotheses have come from finding

similar dimorphisms in cartilage presentation near the thyroid gland suggesting hormonal differences between

males and females may be involved [6,24,25], as well finding high calcium concentrations in sections of the

aorta more frequently in males than females [25].

In terms of its application to computational models, one limitation of the data presented here comes from

the fact that it is based on the segmentation of calcified regions of the costal cartilage, but without an

accompanying segmentation of the overall cartilage segment. The reason for this is that the difference in radio‐

density between costal cartilage and its various surrounding tissues (such as muscle, fat) is relatively small, such

that a simple histogram‐based threshold is unable to clearly separate these body components. Cartilage

calcification, on the other hand, is considerably denser than other local materials and as such it can be easily

segmented after localising the containing region for a given segment of costal cartilage. The consequence of

measuring only the calcified regions within a segment is that no true volumetric percentage of calcification can

be reported. As a surrogate for this more desirable measurement, we have utilised the costal segment length

(which does not require segmentation of a full cartilage segment) and chosen to report a lengthwise percentage

of calcification as a guide for researchers choosing a scheme for calcification growth along the cartilage

segment.


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V. CONCLUSIONS

Measurements of costal cartilage calcification volumes and distribution have shown significant trends with age. Age and sex are seen to account for around 35% of all inter‐individual population variability in the total volume of calcified cartilage. The lengthwise extent of calcified regions of a cartilage segments is also seen to increase significantly with age. Results provide volumetric guidelines for the introduction of regional calcification within the costal cartilage. Specifically, it is recommended when incorporating person‐age into models that the calcified cartilage volume should increase at the rate of 0.9 mm (for an equivalent cube edge length) per decade, and should involve an increasing lengthwise extent of the cartilage segment at a rate of at least 7% per decade.

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Calcification of Costal Cartilage in the Adult Rib Cage · calcification to be considered when modelling changes in the mechanics of the rib cage with age, and have explored a