Background
Quantitative ultrasound (QUS) is currently used to predict fracture risk in
osteoporotic or osteopenic individuals who are typically over 50 years of age. The use
of QUS has shifted in recent years to evaluate bone strength/bone density in children
and adolescents, however, the applicability of using QUS on subadults is questioned
as current clinical devices are designed for adult sized feet and fully skeletally matured
calcanei. Majority of these clinical devices use 1 inch (25 mm) diameter ultrasound
transducers that are fixed in location, and when these devices are performed on
children the region of interest targeted either includes additional soft tissue, cortical
bone edges, or only measures a small portion of bone leading to inaccurate
measurements. Due to these limitations, recommendations are needed to improve
quantitative ultrasound application in a paediatric/subadult population using the
calcaneus to accurately measure bone status/health. Studies have demonstrated that
earlier monitoring and identification of individuals at risk of bone loss related
conditions such as osteoporosis can undergo treatments, medication, and/or exercise
regimes to accrue bone mass and dramatically reduce their likelihood of getting these
conditions, emphasising the importance of monitoring bone health in children and
subadults.
Aims
Our future goal is to monitor and evaluate bone architecture and density in individuals
from early childhood to adulthood to reduce the risk of osteopenia, osteoporosis, or
diminished bone related fractures. Unfortunately, current studies have demonstrated
that current commercial QUS devices are not suitable for subadult use. For our goal to
become a reality three things are needed; (1) an improved understanding of calcaneal
development and anatomical variation that goes beyond current literature, (2)
subadult-specific standards or guidelines for identifying the best location or site for
transducer placement on the calcaneus to avoid unwanted inclusions of surrounding
soft tissue or cortical bone edges, and (3) improved understanding on how surrounding
soft tissue of the heel affects ultrasound measurements and determine if varying
thicknesses in overlying soft tissues such as superficial fascia have any influence on
QUS derived attenuation measurements.
Methods
De-identified, retrospective multi-slice computed tomography (MSCT) scans
and lateral plain radiographs of the tarsus were obtained from individuals aged birth
to 20 years with 568 CT scans (295 females; 274 males) and 266 lateral plain
radiographs (119 females; 147 males). In total 834 scans were collected from the
Queensland Health Enterprise PACS database, representing North-Eastern hospitals
in Australia, with all scans being conducted between 2010 and 2020. All scans were
imported into DICOM viewer software Horos for morphological analyses.
Ossification and fusion of the calcaneal apophysis was assessed using a novel 11 stage
scoring criteria. This method demonstrated almost perfect agreement for inter- and
intra-observer error, demonstrating high reliability. In addition, maximum diameter,
vertical and horizontal distances were measured from three different anatomical
palpable landmarks, to determine which method is most suitable to reliably identify
the centre point of the region of interest. Ethical approval was granted by The
Children’s Health Queensland Hospital and Health Service Human Research Ethics
Committee (LNR/19/QCHQ/51243), ratified by the Queensland University of
Technology Research Ethics Unit (Approval No. 1900000946) and approved by the
Queensland Government under the Public Health Act (Section 284) 2020 (RD008018).
For human donor material, 15 feet were collected from separate fresh-frozen
donor bodies at the Medical Engineering Research Facility (MERF). Frequencydependent attenuation measurements were conducted at a select region of interest
using anatomical landmarks. Quantitative ultrasound measurements were conducted
with the foot intact and at each subsequent tissue layer as each foot went through a
series of soft tissue dissections. In addition to ultrasound measurements, heel and soft
tissue thickness was measured to help inform and identify if any specific tissue layer
influenced ultrasound measurements.
Results
This PhD project provides Queensland specific standards for assessing calcaneal
apophyseal developmental stage using computed tomography analysis, and novel
predictive regression models for developmental stage estimation using known age and
sex. These sex-specific multinomial linear regression models have a predictive
accuracy of 81% and should be used to aid in the diagnosis of heel pain conditions
such as apophysitis or identify developmental delays in subadults. This study
demonstrated significant sexual dimorphism in ossification and fusion with females
developing significantly earlier than males. Additionally, due to the use of computed
tomography, this is the first study to evaluate the ossification and fusion of the medial
and lateral processes of the calcaneus. This study also investigated and reported the
anatomical variation in the timing and spatial formation of the calcaneal apophysis and
its processes which should be used to minimise misdiagnosis of calcaneal fractures or
apophysitis. Understanding calcaneal apophyseal developmental trends has improved
our anatomical knowledge which is essential for better patient care, clinical assessment
and management of subadult patients.
Now that an in-depth investigation on calcaneal apophyseal development and
the anatomical variation present within the Queensland population has been conducted
and reported in this PhD, the maximum anatomical region of interest diameter on the
calcaneus was identified for quantitative ultrasound transducer placement.
Understanding development and variation allows us to avoid unwanted surrounding
soft tissues or apophyseal cartilage in all individuals aged 0 – 20 years. Once the centre
point of the largest anatomical region of interest was identified, novel distance
methods were created to identify this centre point from three anatomical palpable
landmarks. These novel methods were than compared to the existing ‘Jaworski
method’ which uses a fixed ratio to identify the centre point for transducer placement
and quantitative ultrasound measurements. We demonstrated that palpable landmarks
located superior to the subtalar joint such as the medial and lateral malleoli are not
suitable or reliable for the identification of the region of interest centre point due to
large variation for any given chronological age category, with the minimum and
maximum distances leading to the position of the transducer to be located outside of
the maximum anatomical region of interest. In contrast, the calcaneal tendon method
had relatively low measurement variance and should be used to identify the preferred
location for transducer placement. The existing ‘Jaworski method’ led to large
measurement ranges with 10.6% of points being located outside of the region of
interest, which could have the unwanted inclusion of soft tissue or cartilage. Therefore,
the calcaneal tendon method should be used clinically to identify a point to place the
receiver ultrasound transducer for improved quantitative measurements. An additional
goal of this study was to determine if current quantitative ultrasound devices with their
fixed 1 inch (25 mm) diameter transducers are acceptable to use in subadults. In this
study we found that the region of interest increased significantly with age for males
and females, and that a ½ inch (12.7 mm) or ¾ inch (19 mm) diameter receiver
transducer should be used in individuals younger than 7 years of age. A 1 inch (25.4
mm) diameter receiver transducer can be used in all individuals older than 7 years and
therefore current commercial device transducer sizes can be used. However, the
current fixed in place transducers used in commercial devices cannot be used due to
the size and location of the calcaneus in subadults. It is recommended that the
transducers should be mobile and can be manually adjusted so they lie on the identified
region of interest calculated using the calcaneal tendon method for that individual’s
sex and age.
We demonstrated that soft tissue layers overlying the calcaneus including the
skin, superficial fascia and deep fascia had no significant influence over frequencydependent attenuation measurements. These results are similar to previous literature
which found that attenuation values did not change when soft tissue as a whole (skin
to deep fascia) was removed. These results allow us to suggest that frequencydependent attenuation values measured at the calcaneus will not be influenced or
affected in individuals with increased muscle thickness or an increase in adiposity
levels.
Conclusion
This study was the first to report on an in-depth investigation on calcaneal
apophyseal development and anatomical variation using computed tomography. Also,
using a novel medical imaging approach, a novel calcaneal tendon palpable landmark
method was created and identified as being the most reliable method to identify a
centre point of an anatomical region of interest for ultrasound transducer placement
for the estimation and evaluation of bone status in subadults. Soft tissue influences
were investigated using quantitative ultrasound.
The three separate studies within this PhD overall improved the understanding
of: 1) calcaneal apophyseal development and anatomical variation, 2) the influence
soft tissue has on bone status ultrasound measurements, and 3) region of interest centre
point selection used to identify transducer placement in subadults to avoid unwanted
inclusion of soft tissues. All three studies will lead to a better informed location for
ultrasound measurement in subadults for early monitoring and assessment to minimise
the risk of early onset osteopenia, osteoporosis, or bone loss related fractures, as
accruement of bone density and overall strength occurs early in childhood and
adolescent development.
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