Light on osteoarthritic joint: from bench to bed

Abstract

Osteoarthritis (OA) is one of the rapidly growing disability-associated conditions with population aging worldwide. There is a pressing need for precise diagnosis and timely intervention for OA in the early stage. Current clinical imaging modalities, including pain radiography, magnetic resonance imaging, ultrasound, and optical coherent tomography, are limited to provide structural changes when the damage has been established or advanced. It prompts further endeavors in search of novel functional and molecular imaging, which potentially enables early diagnosis and intervention of OA. A hybrid imaging modality based on photothermal effects, photoacoustic imaging, has drawn wide attention in recent years and has seen a variety of biomedical applications, due to its great performance in yielding high-contrast and high-resolution images from structure to function, from tissue down to molecular levels, from animals to human subjects. Photoacoustic imaging has witnessed gratifying potentials and preliminary effects in OA diagnosis. Regarding the treatment of OA, photothermal-triggered therapy has exhibited its attractions for enhanced therapeutic outcomes. In this narrative review, we will discuss photoacoustic imaging for the diagnosis and monitoring of OA at different stages. Structural, functional, and molecular parameter changes associated with OA joints captured by photoacoustics will be summarized, forming the diagnosis perspective of the review. Photothermal therapy applications related to OA will also be discussed herein. Lastly, relevant clinical applications and its potential solutions to extend photoacoustic imaging to deeper OA situations have been proposed. Although some aspects may not be covered, this mini review provides a better understanding of the diagnosis and treatment of OA with exciting innovations based on tissue photothermal effects. It may also inspire more explorations in the field towards earlier and better theranostics of OA.

Keywords: Osteoarthritis; cartilage; photoacoustic imaging; photothermal therapy; synovium.

Figure 1

(A) A continuum from micro to macro by photoacoustic imaging. (B) An example of micro-scale structural photoacoustic imaging. Photoacoustic microscopy and hematoxylin and eosin-stained figures of normal human breast tissue . (C) An example of macro-scale structural photoacoustic imaging. Photoacoustic computed tomography of human breast cancer . (D) An example of micro-scale functional photoacoustic imaging. Oxygen saturation of mouse brain . Adapted with permission from -. Copyright © 2017, Copyright © 2018, and Copyright © 2015 Springer Nature.

Figure 2

Illustration of structural and microenvironment transformations during OA progression. Compared with normal joints, OA joints will undergo different degrees of changes with the OA progression. In early-stage OA, the surface contour of cartilage is lightly unregulated, the superficial zone of articular cartilage splits slightly, the subchondral bone plate is thinner yet more porous, and a few vessels erode into the avascular cartilage. In late-stage OA, the whole cartilage structure is completely destroyed, which is usually accompanied with subchondral bone sclerosis, joint space narrowing, osteophyte formation, and more vessels erosion into the cartilage.

Figure 3

(A) US, PA and the merged images of knee joints in different stages. (B-C) Quantified PA amplitudes at different stages from cartilage and subchondral bone, respectively. Figures adapted with permission from Ref . Copyright © 2015, Elsevier.

Figure 4

DMM knee joints at different stages being visualized with B mode ultrasound, PD mode ultrasound, and PA imaging, respectively. (A)-(C), B mode ultrasound images of the knee joints at baseline, 1 month, and 4 months, respectively. (D)-(F), PD mode ultrasound images of the knee joints at baseline, 1 month, and 4 months, respectively. (G)-(I), PA images of the knee joints at baseline, 1 month, and 4 months, respectively. Figures adapted with permission from Ref . Copyright © 2018, Elsevier.

Figure 5

(A)-(H) Different functional parameters (Hb, HbO2, water contents, and acoustic velocity) of normal and OA joints, respectively, through multi-wavelength PA imaging. Figures adapted with permission from Ref. . Copyright © 2010, The Optical Society.

Figure 6

(A) In vivo knee OA model establishment process. (B) The cartoon figure (left) of knee OA and the photos (right) of OA and normal knees. (C) SERS spectra. (D) I2228/I1418 SERS intensity change versus time. (E) Ultrasound (US)/PA images of the OA and normal knees. PA signals are marked in red circles. (F) 750 nm, 1250 nm, and the ratiometric PA images. (G) Ratiometric PA750/PA1250 value versus time for OA and normal knees. Scale bar is 1 mm in (F). Figures adapted with permission from Ref. . Copyright © 2020, Wiley-VCH GmbH.

Figure 7

(A) Relaxation time of PA signals at different degrees of cartilage damage. (B)-(C) Histological results of normal porcine cartilage and 12 hours trypsin treated cartilage, respectively. Figures adapted with permission Ref.. Copyright © 2006, Wiley-Liss, Inc.

Figure 8

(A) Schematic diagram of the preparation of PLL-MNPs and the mechanism of diagnosis of OA cartilage degeneration with PAI. (B) PA images of cartilage after immersion in different contrast media for 24 hours. Scale bar: 5 mm. (C) PA images of early and late stages of OA with PLL-MNPs, PA post-treatment monitoring after hyaluronic acid (HA) injection, and its comparison with Mankin scoring system results. Figures adapted with permission from Ref. . Copyright © 2018, Royal Society of Chemistry.

Figure 9

(A) Reaction process of the NHsPP nanoparticles in the OA after light illumination. (B) Spatial distributions of NHsPP nanoparticles in the OA and normal joints at different times. (C) PA signals of the nanoparticles in the OA joints at different time. (D) Nanoparticle-enhanced photothermal images under laser irradiation. (E) The temperatures changes with time under the photothermal effect. (F-K) Semi-quantitative comparisons between different treatment methods as a function of time. Figures adapted with permission from Ref. . Copyright © 2019, Royal Society of Chemistry.

Figure 10

(A) - (B) Schematic diagram of the synthetization and reaction process of the MCD nanoparticles. (C)- (F) Photothermal effect and remaining time duration of the MCD in mouse joints. (G) - (I) Semiquantitative comparisons of inflammatory factors (TNF-α, IL-1β, and IL-8), therapy outcomes (three proteins associated with OA pathology and cartilage reconstruction), composite scores, movement distance, and velocity in OA joints among different treatment methods. Figures adapted with permission from Ref. . Copyright © 2019, American Chemical Society.

Figure 11

(A) Photograph of the PAT system. (B) Photograph of the finger joint through different sections. (C)-(D) PA recovered 3D absorption coefficient image of the corona section for normal and OA joints, respectively. (E)-(F) PA recovered 3D absorption coefficient image of the sagittal section for normal and OA joints, respectively. CL: cartilage; DIP: distal interphalangeal joint; DP: distal phalanx; IP: intermediate phalanx; SF: synovial fluid. Figures adapted with permission from Ref. . Copyright © 2011, American Association of Physicists in Medicine.

Figure 12

(A)-(C) PA spectra of different damaged cartilage (least damaged, medium damaged and most damaged) at 500 nm- 700 nm. (D)-(F) PA spectra of different damaged cartilage (least damaged, medium damaged and most damaged) at 710 nm- 1300 nm. Figures adapted with permission from Ref. . Copyright © 1969, Elsevier (1969).