The hallmark of osteoarthritis (OA) is the breakdown of cartilage and it usually affects the hands, feet and weight-bearing joints, such as knees, hips and spine. At worst, the cartilage cushion may completely wear away such that bones rub against each other causing inflammation, swelling and pain. Hyaline cartilage covers the subchondral bone to form the smooth articular surface of joints [1
]. Hyaline cartilage can be further divided into three zones according to its regional organization. During the growth of the bone tissue, mineralization progressively takes place at the junction of hyaline cartilage and subchondral bone resulting in a layer of calcified cartilage with a tidemark separation. To illustrate the general cartilage structure and OA features histology of a femoral condyle with OA symptoms is given in
. The cartilage is thinner and deteriorates in the region with OA. Poole’s study provides further details on composition and structure of articular cartilage [2
(a) Histology of a femoral condyle with pronounced OA symptoms and (b) The dashed blue box indicates the measured region and the cartilage layer thicknesses of interest.
The prevalence of OA increases with age such that 1 in 5 adults aged 50-59 [3
] and 9.6% of men and 18% of women aged over 60 have symptomatic osteoarthritis [4
]. Therefore, it is a contemporary major medical challenge with high socioeconomic impact as early diagnosis and treatment of OA can help to prevent deterioration before irreversible damage is done. Current imaging diagnostic tools for OA are X-ray and MRI (magnetic resonance imaging), however, both of them are not able to detect early deterioration of cartilage. Therefore, there is a pressing need to develop a technique for detecting and monitoring changes in cartilage. This is particularly important in OA research where animal models are used as histology is currently the only technique to confirm the establishment and grade the severity of osteoarthritis [5
] and requires sacrifice of many animals at different time points. A non-invasive imaging technique can help standardize the quantification of osteoarthritic grading and greatly reduce the number of animals sacrificed.
Previously, researchers have demonstrated the use of optical coherence tomography (OCT) for assessment the cartilage thickness and the result is quite promising in both in vitro
] and in vivo
]. Structural changes including surface erosion [8
], hypocellularity [9
], subsurface tears [10
] were observed using OCT. In addition, OCT demonstrates the potential to detect changes at the early reversible stage of OA [11
], through the loss of birefringence or birefringence changes in cartilage [9
]. However, the image data can be difficult to interpret and prevents quantitative mapping of cartilage structure [13
]. This has initiated our investigation to find other techniques to fill this gap. Here we have studied whether Terahertz pulsed imaging (TPI) has the ability to quantify OA or be an auxiliary method to compliment details seen in OCT images.
Several potential applications of THz to medicine have been investigated including skin cancer [15
], breast cancer [16
] and dentistry [17
]. THz radiation possesses numerous characteristics that make it well suited for biomedical applications. For example, it is non-ionizing which means it would be safe to use for screening as well as diagnostic purposes. Through its sensitivity to molecular structures of biomolecules it can distinguish between: tissues [18
], different chemicals within drugs [19
], DNA bases [20
] and polymorphic forms of medicines [21
]. Thus, several research groups are focusing their efforts to developing waveguides to channel the THz beam to the sample [22
]. Recently, a miniaturized THz endoscope system was developed by Ji et al
] and it demonstrates the possibility of performing THz imaging inside the body thus opening up the future possibility of in vivo
monitoring of osteoarthritis.
Cartilage thickness is a crucial measurement when diagnosing OA. Early experiments imaging cartilage with THz radiation were conducted by Knobloch et al
] on excised pig larynx tissue. They demonstrated the absorption difference of THz radiation on the cartilage from the surrounding soft tissue. Subsequently, Jung et al
] measured the THz spectral properties of human articular cartilage and showed differences between osteoarthritic cartilage and normal cartilage. Here we explored the potential of TPI to quantitatively measure cartilage thickness building on a previous study [27
] and extending our findings with additional measurements performed on formalin fixed rabbit femoral condyles with OA. Formalin fixing reduces the absorption of the tissue (by removing water which strongly absorbs THz radiation) [29
]. Considering the effects of absorption independently, to see to the same depth in the fresh tissue the SNR for the measurement would need to be increased: SNRFresh
, where α_fresh and α_fixed represent the absorption coefficients of the fresh and fixed tissue respectively. In this paper we have not made these measurements and they will be the subject of a follow up study. Advancements in terahertz technology are targeting increases in SNR as well as miniaturization to make intra-operative in vivo
measurements possible in the future.