In-vitro comparison of volumetric and areal bone mineral density measurements between ultrasound transit time spectroscopy and microcomputed tomography

Abstract

Quantitative ultrasound is a scientifically and clinically accepted diagnostic technique for assessing and predicting osteoporotic fracture risk. However, it does not provide a direct measurement of areal bone mineral density, and hence cannot implement the World Health Organization T score criteria for osteoporosis and osteopenia. In this study, we developed a novel method based on the concept of ultrasound transit time spectroscopy (UTTS) to derive volumetric and areal bone mineral densities. Through-transmission ultrasound signals at 1 MHz were used to measure 12 human femoral head in-vitro bone samples. Volumetric and areal bone mineral densities were calculated from the derived and corrected ultrasound transit time spectra. A linear regression model was used to compare the results obtained by ultrasound with those by microcomputed tomography. This analysis showed coefficients of determination (R²) of 86% and 80% for volumetric and areal bone mineral density, respectively. Given that quantitative ultrasound is nonionizing, low cost, and portable, we propose that directly derived areal bone mineral density obtained using ultrasound transit time spectroscopy, UTTS-aBMD, may be utilized for osteoporosis assessment, implementing the WHO T score criteria.

Introduction

Osteoporosis is defined as “a skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture” [1]. Osteoporosis has become a formidable problem due to its increasing prevalence worldwide and because it often develops without symptoms or pain. There is a need for an accurate diagnostic technique for the early identification of those at risk of osteoporotic fracture.

Clinically, the conventional method to identify osteoporosis involves the measurement of areal bone mineral density (aBMD) using dual energy X-ray absorptiometry (DXA), which is usually performed at the anatomic sites affected by osteoporosis such as the lower spine, hip, and wrist. aBMD provides a measure of bone mineral content (BMC, g) over a projected scan area (cm²), and is expressed as g cm⁻². In 1994, the World Health Organization established new measurement criteria for osteoporosis based on the T score for aBMD, which can be defined numerically as:

$$\text{Tscore}=\left[\left({\text{aBMD}}_{\text{s}}-{\text{aBMD}}_{\text{yn}}\right)/{\text{SD}}_{\text{yn}}\right]$$

where s and yn denote the individual subject and young normal population, respectively, and SD is the standard deviation.

The T score is used to categorize a given individual as having normal (T score ≥ –1), low or osteopenic (–2.5 < T score < –1), or osteoporotic (T score ≤ –2.5) bone density [2]. The term osteoporosis is hence used to describe both the disease process leading to fracture as well as a measurement criterion.

DXA uses two X-ray energies. Their relative transmission intensities along with the known attenuation coefficients of bone and soft tissue are used to derive aBMD. However, DXA is expensive, requires radiation exposure, and has limited availability in rural or less developed communities.

Volumetric bone mineral density (vBMD), often termed “apparent density”, describes the BMC (g) within a measured volume of tissue (cm³), and is expressed as g cm⁻³. vBMD is generally assessed using quantitative computed tomography (QCT). Unlike the two-dimensional DXA, QCT is a three-dimensional (3D) imaging modality that can assess cortical and cancellous bone compartments separately. However, QCT requires a radiation dose 10 times higher than that used for DXA, which generally makes QCT impractical as a routine assessment tool [3].

An alternative modality, quantitative ultrasound (QUS), has been shown to provide a reliable prediction of osteoporotic fracture risk [4], [5], [6], [7], [8]. In contrast to DXA and QCT, QUS is simpler to use, free from ionizing radiation, cheaper, and portable. QUS assessment is generally performed at the calcaneus because of its easy access, high percentage of cancellous bone (90%) and little overlying soft tissue [9]. The predominant measurement parameters are attenuation, which is generally denoted as the broadband ultrasonic attenuation (BUA, dB MHz⁻¹), and speed of sound (SoS, m s⁻¹). A significant impediment to the routine implementation of QUS has been the inability to transpose the measurement parameters of BUA and SoS into bone density, in particular vBMD or aBMD.

In 2011, Langton [9] introduced the novel concept of ultrasound transit time spectroscopy (UTTS), which describes the propagation of ultrasound waves through a bi-material complex composite, such as cancellous bone, as an array of parallel “sonic-rays”. The transit time of each sonic-ray (t_i) is determined as the amount of bone and marrow through which it propagates, having minimum (t_min) and maximum (t_max) values through entire bone and marrow, respectively. The transit time spectrum (TTS) can be described as the proportion of sonic-rays (P(t_i)) over the transit time range, t_min to t_max [10], as shown in Fig. 1.

The TTS is derived through mathematical deconvolution of an ultrasound signal recorded following propagation through the test sample with that recorded through a reference material, generally water [11]. These two signals are referred to as “output” and “input,” respectively.

UTTS has been scientifically validated in both transmission [12], [13], [14], [15], [16] and pulse-echo [12], [17], [18] modes, including estimation of the ratio of bone volume to tissue volume (BV/TV) and various structural parameters of cancellous bone [19].

The primary aim of this study was to examine the feasibility of using UTTS to determine in-vitro derived vBMD and aBMD in 12 human cancellous bone samples.