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Inflammation is a multistep process triggered by a variety of causes and agents. This results in acute and/or chronic inflammation, which leads to host response in terms of cell recruitment, adaptions of the vasculature, and changes of the tissue composition and extracellular matrix. All of these aspects pose possible targets for opto-/photoacoustic imaging. Figure created with BioRender.com.
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Optoacoustic or photoacoustic imaging (OAI/PAI) is a technology which enables non-invasive visualization of laser-illuminated tissue by the detection of acoustic signals. The combination of “light in” and “sound out” offers unprecedented scalability with a high penetration depth and resolution. The wide range of biomedical applications makes this t...
Citations
... 10,11 Uniquely, OAI combines high optical contrast and deep tissue penetration over several centimeters. While two-dimensional OAI has previously been used to assess different inflammatory and degenerative diseases, 12 three-dimensional OAI may further improve visualization and signal quantification. 13,14 In this study, we assessed the imaging capabilities of three-dimensional OAI to resolve muscle degeneration and therapeutic effects in SMA. ...
... 67 An OAI system comprises three primary elements: (1) a light source (usually a pulsed laser) with illumination optics, delivering light energy to the tissue; (2) one or more ultrasound detectors measuring the generated acoustic signals; and (3) a signal processing and reconstruction unit for image creation. 69 In medical applications, OAI 69 70 may be particularly useful in oncology, where it can aid in cancer detection, monitoring treatment response and guiding targeted therapies. [71][72][73] So far, various OAI techniques have been explored in dermatological, 74 75 metabolic, 76 gastrointestinal 77-79 and musculoskeletal diseases. ...
... To distinguish the estimated concentration of the single chromophores, spectral identification (ie, 'unmixing') is applied based on the single absorbance spectra of the chromophores. 69 Thus, MSOT's ability to visualise both anatomical structures and molecular processes makes it a versatile tool that is able to enrich conventional ultrasound images with a spatial representation of metabolic activity. 88 Notably, MSOT is handled similarly to a standard ultrasound device and the examination time does not exceed that of a typical ultrasound examination, making it suitable for bedside use. ...
It is known that metabolic shifts and tissue remodelling precede the development of visible inflammation and structural organ damage in inflammatory rheumatic diseases such as the inflammatory arthritides. As such, visualising and measuring metabolic tissue activity could be useful to identify biomarkers of disease activity already in a very early phase. Recent advances in imaging have led to the development of so-called ‘metabolic imaging’ tools that can detect these changes in metabolism in an increasingly accurate manner and non-invasively.
Nuclear imaging techniques such as ¹⁸ F-D-glucose and fibroblast activation protein inhibitor-labelled positron emission tomography are increasingly used and have yielded impressing results in the visualisation (including whole-body staging) of inflammatory changes in both early and established arthritis. Furthermore, optical imaging-based bedside techniques such as multispectral optoacoustic tomography and fluorescence optical imaging are advancing our understanding of arthritis by identifying intra-articular metabolic changes that correlate with the onset of inflammation with high precision and without the need of ionising radiation.
Metabolic imaging holds great potential for improving the management of patients with inflammatory arthritis by contributing to early disease interception and improving diagnostic accuracy, thereby paving the way for a more personalised approach to therapy strategies including preventive strategies. In this narrative review, we discuss state-of-the-art metabolic imaging methods used in the assessment of arthritis and inflammation, and we advocate for more extensive research endeavours to elucidate their full field of application in rheumatology.
... By applying several wavelengths, specific optoacoustic spectra of different endogenous (oxygenated and deoxygenated hemoglobin, lipids, collagens, and melanin) and exogenous chromophores (dyes like indocyanine green) can be detected and quantified [111][112][113]. Hemoglobin is especially predestined for OAI, as it is one of the main absorbers in the used Near-infrared field of light and a surrogate OAI biomarker for various inflammatory [114] and cardiovascular diseases [115][116][117]. Furthermore, OAI allows scalability of the imaging device and resolution from cells and animal models to humans [110]. ...
Inflammatory bowel disease (IBD) comprises a group of relapsing, chronic diseases of the gastrointestinal tract that, in addition to adults, can affect children and adolescents. To detect relapses of inflammation, these patients require close observation, frequent follow-up, and therapeutic adjustments. While reference standard diagnostics include anamnestic factors, laboratory and stool sample assessment, performing specific imaging in children and adolescents is much more challenging than in adults. Endoscopic and classic cross-sectional imaging modalities may be invasive and often require sedation for younger patients. For this reason, intestinal ultrasound (IUS) is becoming increasingly important for the non-invasive assessment of the intestine and its inflammatory affection. In this review, we would like to shed light on the current state of the art and provide an outlook on developments in this field that could potentially spare these patients more invasive follow-up procedures.
... Photoacoustic imaging (PAI) is an emerging scalable imaging technology that combines the high contrast of optical imaging with the spatiotemporal resolution of ultrasound (Beard, 2011). Using light absorption by endogenous molecules, such as haemoglobin in red blood cells, PAI can reveal the emergence of diseases ranging from inflammation to cancer in both preclinical animal models and in patients (Brown et al., 2019;Regensburger et al., 2021;Steinberg et al., 2019;Wang & Hu, 2012). Extracting accurate photoacoustic imaging biomarkers, such as blood oxygen saturation, from raw data requires a robust image reconstruction and analysis process, which is challenging due to the high dimensionality of the data across spatial, spectral and temporal domains. ...
... 1,5,6 This advantage has established optoacoustic imaging as a powerful modality and supports ensuing clinical trials. 1,[7][8][9][10] Multi-wavelength illumination and processing equipped with optoacoustic tomography, coined as multispectral optoacoustic tomography (MSOT), allows for separation of optoacoustically active chromophores, including oxyhemoglobin and deoxyhemoglobin, with the caveat that absorption spectra are unique. However, with few distinct endogenous contrast agents, 11,12 MSOT clinical trials have largely been limited to conditions involving differential oxygenation, such as breast cancer, [13][14][15] inflammatory bowel diseases, [16][17][18] or dermatologic conditions. ...
Optoacoustic imaging has grown in clinical relevance due to inherent advantages in sensitivity, resolution, and imaging depth, but the development of contrast agents is lacking. This study assesses the influence of structural features of squaraine dyes on optoacoustic activity through computational models, in vitro testing, and in vivo experimentation. The squaraine scaffold was decorated with halogens and side-chain extensions. Extension of side chains and heavy halogenation of squaraines both increased optoacoustic signals individually, although they had a more significant effect in tandem. Density functional theory models suggest that the origin of the increased optoacoustic signal is the increase in transition dipole moment and vibrational entropy, which manifested as increased absorbance in near-infrared region (NIR) wavelengths and decreased fluorescence quantum yield. This study provides insight into the structure-function relationships that will lead guiding principles for optimizing optoacoustic contrast agents. Further developments of squaraines and other agents will further increase the relevance of optoacoustic imaging in a clinical setting.
... In this regard, Multispectral Optoacoustic Tomography (MSOT) enables visualization and quantification of muscle tissue properties, such as hemoglobin of different oxygenation states over a broad range of applications (5)(6)(7)(8). MSOT has already demonstrated feasible to detect differences in terms of hemoglobin saturation of the calf muscle between healthy volunteers (HV) and different stages of PAD (9). However, its diagnostic accuracy to differentiate between healthy and early claudication stage, which would be clinically relevant, is still elusive. ...
Background
Multispectral optoacoustic tomography (MSOT), a molecular sensitive ultrasound, offers a non-invasive diagnostic approach to image the deep-tissue biomarkers.
Objectives
The authors aimed to investigate the diagnostic accuracy of MSOT to distinguish between healthy volunteers (HV) and patients with intermittent claudication (IC) by assessing hemoglobin-related biomarkers in calf muscle tissue.
Methods
In this monocentric, cross-sectional diagnostic trial using derivation (DC) and validation cohorts (VC) yll subjects underwent standardized PAD diagnostics. This included pulse palpation, ankle brachial index (ABI), duplex sonography, 6-minute walk test (6MWT), and assessment of health-related quality of life (VASCUQOL-6). The vascular occlusion profile in IC patients was confirmed by angiography (aggregated TransAtlantic Inter-Society Consensus classification, aTASC). MSOT imaging of calf muscle was performed before and after standardized heel raise provocation.
Participants
Of 123 screened individuals, 102 completed the study. MSOT-derived oxygenation (msO2) after the exercise differentiated IC and HV with an area under curve the receiver operator characteristics curve (AUROC) in DC by 0.99 (95%CI 0.97;1.00, p<0.001, sensitivity: 100%, specificity: 95.8%) and in the VC by 0.95 (95%CI 0.95;1.00, p<0.001, sensitivity: 96.2%, specificity: 96.0%). mSO2 positively correlated with the ABI post-exercise (R=0.83, 95%CI 0.75;0.88, P<0.001), the absolute walking distance in the 6MWT (R=0.77, 95%CI 0.68;0.84, P<0.001), the VASCUQOL-6 (R=0.79, 95%CI 0.70;0.85, P<0.001) and negatively with aTASC classification (R=-0.80, 95%CI -0.86;-0.72, P<0.001).
Conclusions
Post-exercise MSOT-derived saturation in the calf muscle was validated as a new and promising diagnostic biomarker to distinguish between HV and IC patients yielding high sensitivity and specificity. (NCT05373927)
... More importantly, PAI is on the pathway for clinical translation into mainstream medicine [16,17], with a variety of applications demonstrated in patients using the tomographic PAI geometry, with a substantial number of studies applying PAI for cancer visualisation, especially in breast cancer [18][19][20][21]. Recently, a wide range of potential further clinical applications have emerged, such as evaluation of skin microvasculature [22,23], functional and endoscopic assessment of the gastrointestinal tract [24,25], surgical guidance [26], monitoring inflammation [27][28][29] and monitoring lymphadenopathies [30] / lymphedema [31]. These diverse applications demonstrate the future clinical potential for PAI underpinned by the versatile nature of the hardware implementations available. ...
... In addition to molecular imaging, high resolution PAI studies provide access to information on vessel architecture, which is important when assessing vascular function and disease status in a range of conditions [27,69]. Quantification of these higher resolution images is rarely applied, and even more rarely validated, although a recent report shows that validation is possible [70]. ...
Photoacoustic imaging (PAI), also referred to as optoacoustic imaging, has shown promise in early-stage clinical trials in a range of applications from inflammatory diseases to cancer. While the first PAI systems have recently received regulatory approvals, successful adoption of PAI technology into healthcare systems for clinical decision making must still overcome a range of barriers, from education and training to data acquisition and interpretation. The International Photoacoustic Standardisation Consortium (IPASC) undertook an community exercise in 2022 to identify and understand these barriers, then develop a roadmap of strategic plans to address them. Here, we outline the nature and scope of the barriers that were identified, along with short-, medium- and long-term community efforts required to overcome them, both within and beyond the IPASC group.
... Photoacoustic imaging (PAI) is an emerging non-invasive imaging modality with high spatial and temporal resolution. PAI takes advantage of the 'optoacoustic effect' to generate image contrast through ultrasound detection of optical absorption events [15][16][17]. Pulses of near-infrared light are absorbed by tissue chromophores which undergo thermoelastic expansion and produce acoustic signal. This acoustic signal production is then detected by ultrasound transducers. ...
... PAI has been investigated for a range of clinical disease-site applications including breast, skin, peripheral vascular diseases, musculoskeletal, gastrointestinal, and adipose tissue [15]. However clinical translation of PAI technologies has been limited due to fundamental physical limitations in penetration depth of less than ~ 7 -10 cm [15,17]. While methods to increase the penetration depth of PAI and accuracy of PAI measurements in deeper tissues are actively being explored to advance this non-invasive imaging technology, the application of PAI to the developing infant presents an especially promising setting as penetration depths in commercially available PAI systems are capable of imaging throughout the body, especially in premature infants at highest risk for disease. ...
Background: Within the premature infant intestine, oxygenation and motility play key physiological roles in healthy development and disease such as necrotizing enterocolitis. To date, there are limited techniques to reliably assess these physiological functions that are also clinically feasible for critically ill infants. To address this clinical need, we hypothesized that photoacoustic imaging (PAI) can provide non-invasive assessment of intestinal tissue oxygenation and motility to characterize intestinal physiology and health.
Methods: Ultrasound and photoacoustic images were acquired in 2-day and 4-day old neonatal rats. For PAI assessment of intestinal tissue oxygenation, an inspired gas challenge was performed using hypoxic, normoxic, and hyperoxic inspired oxygen (FiO2). For intestinal motility, oral administration of ICG contrast agent was used to compare control animals to an experimental model of loperamide-induced intestinal motility inhibition.
Results: PAI demonstrated progressive increases in oxygen saturation (sO2) as FiO2 increased, while the pattern of oxygen localization remained relatively consistent in both 2-day and 4-day old neonatal rats. Analysis of intraluminal ICG contrast enhanced PAI images yielded a map of the motility index in control and loperamide treated rats. From PAI analysis, loperamide significantly inhibited intestinal motility, with a 32.6% decrease in intestinal motility index scores in 4-day old rats.
Conclusion: These data establish the feasibility and application of PAI to non-invasively and quantitatively measure intestinal tissue oxygenation and motility. This proof-of-concept study is an important first step in developing and optimizing photoacoustic imaging to provide valuable insight into intestinal health and disease to improve the care of premature infants.
... To increase the speci city for detection, externally applied contrast agents with distinct optoacoustic spectra [12,13] can be used for precise optoacoustic visualization [14][15][16]. While contrast-enhanced imaging typically requires intravenous application and in optics, often near surface detection, [17,18], MSOT goes beyond these limitations and enables clinically relevant transabdominal deep tissue penetration [19][20][21]. ...
Real-time imaging and functional assessment of the intestinal tract and its transit poses a significant challenge to traditional clinical diagnostic methods. Multispectral optoacoustic tomography (MSOT), a molecular-sensitive imaging technology, offers the potential to visualize endogenous and exogenous chromophores in tissue. Herein we present a novel approach using the orally administered clinical-approved fluorescent dye indocyanine green (ICG) for bed-side, non-ionizing evaluation of gastrointestinal passage. We were able to show the detectability and stability of ICG in phantom experiments. Furthermore, ten healthy subjects underwent MSOT imaging at multiple timepoints over eight hours after ingestion of a standardized meal with and without ICG. ICG signals could be visualized and quantified in different intestinal segments, while its excretion was confirmed by fluorescent imaging of stool samples. These findings indicate that contrast-enhanced MSOT (CE-MSOT) provides a translatable real-time imaging approach for functional assessment of the gastrointestinal tract.
... This emerging imaging technique has the potential for high-resolution dermatologic imaging, namely, to diagnose skin melanomas [26,36,37], carcinomas [11], psoriasis [11,12,36], atopic dermatitis [36,37], burn injuries [12,36], and bacterial wound infection [11,36]. Thyroid imaging [12,[38][39][40][41], reproductive [12,21,42,43] and urological [7,44] systems imaging, neonatal imaging [7,45,46], gastrointestinal imaging [44,[47][48][49], adipose tissue imaging [41,50], musculoskeletal imaging [44,51], ophthalmologic imaging [52], and even diagnosis of COVID-19 [53] have also been successfully performed by exploring the photoacoustic effect. Furthermore, PAI can also be useful for biopsy guidance [43,49], image-guided therapy [54], drug delivery [54,55], and intraoperative imaging [55][56][57]. ...
... This emerging imaging technique has the potential for high-resolution dermatologic imaging, namely, to diagnose skin melanomas [26,36,37], carcinomas [11], psoriasis [11,12,36], atopic dermatitis [36,37], burn injuries [12,36], and bacterial wound infection [11,36]. Thyroid imaging [12,[38][39][40][41], reproductive [12,21,42,43] and urological [7,44] systems imaging, neonatal imaging [7,45,46], gastrointestinal imaging [44,[47][48][49], adipose tissue imaging [41,50], musculoskeletal imaging [44,51], ophthalmologic imaging [52], and even diagnosis of COVID-19 [53] have also been successfully performed by exploring the photoacoustic effect. Furthermore, PAI can also be useful for biopsy guidance [43,49], image-guided therapy [54], drug delivery [54,55], and intraoperative imaging [55][56][57]. ...
... This emerging imaging technique has the potential for high-resolution dermatologic imaging, namely, to diagnose skin melanomas [26,36,37], carcinomas [11], psoriasis [11,12,36], atopic dermatitis [36,37], burn injuries [12,36], and bacterial wound infection [11,36]. Thyroid imaging [12,[38][39][40][41], reproductive [12,21,42,43] and urological [7,44] systems imaging, neonatal imaging [7,45,46], gastrointestinal imaging [44,[47][48][49], adipose tissue imaging [41,50], musculoskeletal imaging [44,51], ophthalmologic imaging [52], and even diagnosis of COVID-19 [53] have also been successfully performed by exploring the photoacoustic effect. Furthermore, PAI can also be useful for biopsy guidance [43,49], image-guided therapy [54], drug delivery [54,55], and intraoperative imaging [55][56][57]. ...
The photoacoustic effect is an emerging technology that has sparked significant interest in the research field since an acoustic wave can be produced simply by the incidence of light on a material or tissue. This phenomenon has been extensively investigated, not only to perform photoacoustic imaging but also to develop highly miniaturized ultrasound probes that can provide biologically meaningful information. Therefore, this review aims to outline the materials and their fabrication process that can be employed as photoacoustic targets, both biological and non-biological, and report the main components’ features to achieve a certain performance. When designing a device, it is of utmost importance to model it at an early stage for a deeper understanding and to ease the optimization process. As such, throughout this article, the different methods already implemented to model the photoacoustic effect are introduced, as well as the advantages and drawbacks inherent in each approach. However, some remaining challenges are still faced when developing such a system regarding its fabrication, modeling, and characterization, which are also discussed.
