As a progressive bone disease, osteoporosis, characterized by the loss of bone mass and density, is a major health concern. According to the National Osteoporosis Foundation, 10 million Americans have osteoporosis, and approximately 34 million more have low bone mass, placing them at increased risk for this disease. As a consequence, 50% of patients suffering from hip fracture can never walk again, and 20% of them will die within 1 year. Traditionally, dual energy X-ray absorptiometry (DXA or DEXA) is regarded as the clinical gold standard for the diagnosis of osteoporosis by assessing the bone mineral density (BMD). Quantitative ultrasound (QUS) technology provides an alternative way for bone health assessment by measuring the speed of sound (SOS) and broadband ultrasound attenuation (BUA).These ultrasound properties are highly related to BMD and have been used clinically in the form of a diagnostic device. Both DXA and QUS assess site-specific BMD, but are less reflective of the bone microarchitecture (BMA) and other biological properties, which are considered important for predicting bone fragility.
The emerging biomedical photoacoustic (PA) techniques have shown the unique capability to assess the highly sensitive optical absorption contrast in deep biological tissue. By leveraging the optical contrast, PA technique provides a novel opportunity for assessing additional molecular and biochemical properties of bone beyond bone density and structure alone. In previous studies, the Mandelis lab developed a dual backscattered US and PA radar for the assessment of bone structures and density variations, and demonstrated that PA measurement could discriminate the changes associated with osteoporosis. Recently, our group demonstrated that, by analyzing the PA signal from bone in frequency domain, the changes in BMA in a rat model of estrogen-deficient bone loss and drug-induced preservation can be quantified. More recently, via both computational modeling and a clinical study on a small cohort of 20 subjects including 10 normal volunteers and 10 osteoporosis patients, our group validated the feasibility of PA measurement combined with QUS, that is, PAQUS, for assessment of both chemical properties and microarchitecture of human calcaneus in vivo. Encouraged by the success in this initial clinical study, our group is working on further development and commercialization of the PAQUS technology.
Fig.1 The experimental setup and the system calibration for the in vivo study on human subjects. (a)-(c) The experimental setup for PA measurement of a human calcaneus bone. By measuring the laser-induced PA signal from a 200-μm microbead, as shown in (d), the frequency response of the PA detection system was calibrated, as shown in (e).
Fig.2 Comparison between the 3D simulation results (upper panel) and the in vivo experimental results (lower panel). (a) 3D numerical simulation results of the PA signals from the two digital bone samples with different levels of bone volume/total volume (BV/TV), one representing the condition of healthy bone (i.e. 20-30 years old) and the other representing the condition of osteoporosis bone (i.e. > 50 years old). The signals from the calcaneus bone are marked by ROI. (b) The corresponding power spectrum density (PSD) curves of the PA signals from the two digital bone samples. (c) The calibrated PSD curves of the two digital bone samples. (d) The PA signals acquired from the heels of a healthy volunteer and an osteoporosis patient, respectively. The signals from the calcaneus bone are marked by ROI. (e) The corresponding power spectrum density (PSD) curves of the PA signals from the calcaneus bones of the two subjects. (f) The calibrated PSD curves of the PA signals from the calcaneus bones of the two subjects.
Fig. 3. Consistency comparison between the printed model and the original input model along different 2D perspectives for PAQUS system calibration. Green, red, and blue areas indicate accurate (consistent), over (dense), and under (sparse) printing, respectively. (a-c) and (d-f) show the results from a model without and a model with drainage holes, respectively.