Non-invasive measurements of blood glucose levels by time-gating mid-infrared optoacoustic signals.

Non-invasive glucose monitoring (NIGM) represents an attractive alternative to finger pricking for blood glucose assessment and management of diabetes. Nevertheless, current NIGM techniques do not measure glucose concentrations in blood but rely on indirect bulk measurement of glucose in interstitial fluid, where glucose is diluted and glucose dynamics are different from those in the blood, which impairs NIGM accuracy. Here we introduce a new biosensor, termed depth-gated mid-infrared optoacoustic sensor (DIROS), which allows, for the first time, non-invasive glucose detection in blood-rich volumes in the skin. DIROS minimizes interference caused by the stratum corneum and other superficial skin layers by time-gating mid-infrared optoacoustic signals to enable depth-selective localization of glucose readings in skin. In measurements on the ears of (female) mice, DIROS displays improved accuracy over bulk-tissue glucose measurements. Our work demonstrates how signal localization can improve NIGM accuracy and positions DIROS as a holistic approach, with high translational potential, that addresses a key limitation of current NIGM methods.

Phase-shifting optothermal microscopy enables live-cell mid-infrared hyperspectral imaging of large cell populations at high confluency.

Rapid live-cell hyperspectral imaging at large fields of view (FOVs) and high cell confluency remains challenging for conventional vibrational spectroscopy-based microscopy technologies. At the same time, imaging at high cell confluency and large FOVs is important for proper cell function and statistical significance of measurements, respectively. Here, we introduce phase-shifting mid-infrared optothermal microscopy (PSOM), which interprets molecular-vibrational information as the optical path difference induced by mid-infrared absorption and can take snapshot vibrational images over broad excitation areas at high live-cell confluency. By means of phase-shifting, PSOM suppresses noise to a quarter of current optothermal microscopy modalities to allow capturing live-cell vibrational images at FOVs up to 50 times larger than state of the art. PSOM also reduces illumination power flux density (PFD) down to four orders of magnitude lower than other conventional vibrational microscopy methods, such as coherent anti-Stokes Raman scattering (CARS), thus considerably decreasing the risk of cell photodamage.

Quality control in clinical raster-scan optoacoustic mesoscopy.

Optoacoustic (photoacoustic) mesoscopy bridges the gap between optoacoustic microscopy and macroscopy and enables high-resolution visualization deeper than optical microscopy. Nevertheless, as images may be affected by motion and noise, it is critical to develop methodologies that offer standardization and quality control to ensure that high-quality datasets are reproducibly obtained from patient scans. Such development is particularly important for ensuring reliability in applying machine learning methods or for reliably measuring disease biomarkers. We propose herein a quality control scheme to assess the quality of data collected. A reference scan of a suture phantom is performed to characterize the system noise level before each raster-scan optoacoustic mesoscopy (RSOM) measurement. Using the recorded RSOM data, we develop a method that estimates the amount of motion in the raw data. These motion metrics are employed to classify the quality of raw data collected and derive a quality assessment index (QASIN) for each raw measurement. Using simulations, we propose a selection criterion of images with sufficient QASIN, leading to the compilation of RSOM datasets with consistent quality. Using 160 RSOM measurements from healthy volunteers, we show that RSOM images that were selected using QASIN were of higher quality and fidelity compared to non-selected images. We discuss how this quality control scheme can enable the standardization of RSOM images for clinical and biomedical applications.

PARP1-targeted fluorescence molecular endoscopy as novel tool for early detection of esophageal dysplasia and adenocarcinoma.

BACKGROUND: Esophageal cancer is one of the 10 most common cancers worldwide and its incidence is dramatically increasing. Despite some improvements, the current surveillance protocol with white light endoscopy and random untargeted biopsies collection (Seattle protocol) fails to diagnose dysplastic and cancerous lesions in up to 50% of patients. Therefore, new endoscopic imaging technologies in combination with tumor-specific molecular probes are needed to improve early detection. Herein, we investigated the use of the fluorescent Poly (ADP-ribose) Polymerase 1 (PARP1)-inhibitor PARPi-FL for early detection of dysplastic lesions in patient-derived organoids and transgenic mouse models, which closely mimic the transformation from non-malignant Barrett's Esophagus (BE) to invasive esophageal adenocarcinoma (EAC). METHODS: We determined PARP1 expression via immunohistochemistry (IHC) in human biospecimens and mouse tissues. We also assessed PARPi-FL uptake in patient- and mouse-derived organoids. Following intravenous injection of 75 nmol PARPi-FL/mouse in L2-IL1B (n = 4) and L2-IL1B/IL8Tg mice (n = 12), we conducted fluorescence molecular endoscopy (FME) and/or imaged whole excised stomachs to assess PARPi-FL accumulation in dysplastic lesions. L2-IL1B/IL8Tg mice (n = 3) and wild-type (WT) mice (n = 2) without PARPi-FL injection served as controls. The imaging results were validated by confocal microscopy and IHC of excised tissues. RESULTS: IHC on patient and murine tissue revealed similar patterns of increasing PARP1 expression in presence of dysplasia and cancer. In human and murine organoids, PARPi-FL localized to PARP1-expressing epithelial cell nuclei after 10 min of incubation. Injection of PARPi-FL in transgenic mouse models of BE resulted in the successful detection of lesions via FME, with a mean target-to-background ratio > 2 independently from the disease stage. The localization of PARPi-FL in the lesions was confirmed by imaging of the excised stomachs and confocal microscopy. Without PARPi-FL injection, identification of lesions via FME in transgenic mice was not possible. CONCLUSION: PARPi-FL imaging is a promising approach for clinically needed improved detection of dysplastic and malignant EAC lesions in patients with BE. Since PARPi-FL is currently evaluated in a phase 2 clinical trial for oral cancer detection after topical application, clinical translation for early detection of dysplasia and EAC in BE patients via FME screening appears feasible.

Machine learning analysis of human skin by optoacoustic mesoscopy for automated extraction of psoriasis and aging biomarkers.

Ultra-wideband raster-scan optoacoustic mesoscopy (RSOM) is a novel modality that has demonstrated unprecedented ability to visualize epidermal and dermal structures in-vivo. However, an automatic and quantitative analysis of three-dimensional RSOM datasets remains unexplored. In this work we present our framework: Deep Learning RSOM Analysis Pipeline (DeepRAP), to analyze and quantify morphological skin features recorded by RSOM and extract imaging biomarkers for disease characterization. DeepRAP uses a multi-network segmentation strategy based on convolutional neural networks with transfer learning. This strategy enabled the automatic recognition of skin layers and subsequent segmentation of dermal microvasculature with an accuracy equivalent to human assessment. DeepRAP was validated against manual segmentation on 25 psoriasis patients under treatment and our biomarker extraction was shown to characterize disease severity and progression well with a strong correlation to physician evaluation and histology. In a unique validation experiment, we applied DeepRAP in a time series sequence of occlusion-induced hyperemia from 10 healthy volunteers. We observe how the biomarkers decrease and recover during the occlusion and release process, demonstrating accurate performance and reproducibility of DeepRAP. Furthermore, we analyzed a cohort of 75 volunteers and defined a relationship between aging and microvascular features in-vivo. More precisely, this study revealed that fine microvascular features in the dermal layer have the strongest correlation to age. The ability of our newly developed framework to enable the rapid study of human skin morphology and microvasculature in-vivo promises to replace biopsy studies, increasing the translational potential of RSOM.

AAPM Task Group Report 311: Guidance for performance evaluation of fluorescence-guided surgery systems.

The last decade has seen a large growth in fluorescence-guided surgery (FGS) imaging and interventions. With the increasing number of clinical specialties implementing FGS, the range of systems with radically different physical designs, image processing approaches, and performance requirements is expanding. This variety of systems makes it nearly impossible to specify uniform performance goals, yet at the same time, utilization of different devices in new clinical procedures and trials indicates some need for common knowledge bases and a quality assessment paradigm to ensure that effective translation and use occurs. It is feasible to identify key fundamental image quality characteristics and corresponding objective test methods that should be determined such that there are consistent conventions across a variety of FGS devices. This report outlines test methods, tissue simulating phantoms and suggested guidelines, as well as personnel needs and professional knowledge bases that can be established. This report frames the issues with guidance and feedback from related societies and agencies having vested interest in the outcome, coming from an independent scientific group formed from academics and international federal agencies for the establishment of these professional guidelines.

Dermal features derived from optoacoustic tomograms via machine learning correlate microangiopathy phenotypes with diabetes stage.

Skin microangiopathy has been associated with diabetes. Here we show that skin-microangiopathy phenotypes in humans can be correlated with diabetes stage via morphophysiological cutaneous features extracted from raster-scan optoacoustic mesoscopy (RSOM) images of skin on the leg. We obtained 199 RSOM images from 115 participants (40 healthy and 75 with diabetes), and used machine learning to segment skin layers and microvasculature to identify clinically explainable features pertaining to different depths and scales of detail that provided the highest predictive power. Features in the dermal layer at the scale of detail of 0.1-1 mm (such as the number of junction-to-junction branches) were highly sensitive to diabetes stage. A 'microangiopathy score' compiling the 32 most-relevant features predicted the presence of diabetes with an area under the receiver operating characteristic curve of 0.84. The analysis of morphophysiological cutaneous features via RSOM may allow for the discovery of diabetes biomarkers in the skin and for the monitoring of diabetes status.

Overdriven laser diode optoacoustic microscopy.

Laser diodes are small and inexpensive but don't afford the pulse energy and beam profile required for optoacoustic (photoacoustic) microscopy. Using two novel modulation concepts, i.e. overdriving continuous-wave laser diodes (CWLD) and frequency-wavelength multiplexing (FWM) based on illumination pulse-trains, we demonstrate concurrent multi-wavelength optoacoustic microscopy with signal-to-noise ratios of > 17 dB, < 2 µm resolution at repetition rates of 1 MHz. This unprecedented performance based on an adaptable trigger engine allowed us to contrast FWM to wavelength alternating acquisition using identical optical components. We showcase this concept's superiority over conventional optoacoustic microscopes by visualizing vascular oxygenation dynamics and circulating tumor cells in mice. This work positions laser diodes as a technology allowing affordable, tunable, and miniaturizable optoacoustic microscopy.

Optoacoustic biomarkers of lipids, hemorrhage and inflammation in carotid atherosclerosis.

Imaging plays a critical role in exploring the pathophysiology and enabling the diagnostics and therapy assessment in carotid artery disease. Ultrasonography, computed tomography, magnetic resonance imaging and nuclear medicine techniques have been used to extract of known characteristics of plaque vulnerability, such as inflammation, intraplaque hemorrhage and high lipid content. Despite the plethora of available techniques, there is still a need for new modalities to better characterize the plaque and provide novel biomarkers that might help to detect the vulnerable plaque early enough and before a stroke occurs. Optoacoustics, by providing a multiscale characterization of the morphology and pathophysiology of the plaque could offer such an option. By visualizing endogenous (e.g., hemoglobin, lipids) and exogenous (e.g., injected dyes) chromophores, optoacoustic technologies have shown great capability in imaging lipids, hemoglobin and inflammation in different applications and settings. Herein, we provide an overview of the main optoacoustic systems and scales of detail that enable imaging of carotid plaques in vitro, in small animals and humans. Finally, we discuss the limitations of this novel set of techniques while investigating their potential to enable a deeper understanding of carotid plaque pathophysiology and possibly improve the diagnostics in future patients with carotid artery disease.

Using reflectometry to minimize the dependence of fluorescence intensity on optical absorption and scattering.

The total diffuse reflectance RT and the effective attenuation coefficient µeff of an optically diffuse medium map uniquely onto its absorption and reduced scattering coefficients. Using this premise, we developed a methodology where RT and the slope of the logarithmic spatially resolved reflectance, a quantity related to µeff, are the inputs of a look-up table to correct the dependence of fluorescent signals on the media's optical properties. This methodology does not require an estimation of the medium's optical property, avoiding elaborate simulations and their errors to offer accurate and fast corrections. The experimental demonstration of our method yielded a mean relative error in fluorophore concentrations of less than 4% over a wide range of optical property variations. We discuss how the method developed can be employed to improve image fidelity and fluorochrome quantification in fluorescence molecular imaging clinical applications.

Opening a window to skin biomarkers for diabetes stage with optoacoustic mesoscopy.

Being the largest and most accessible organ of the human body, the skin could offer a window to diabetes-related complications on the microvasculature. However, skin microvasculature is typically assessed by histological analysis, which is not suited for applications to large populations or longitudinal studies. We introduce ultra-wideband raster-scan optoacoustic mesoscopy (RSOM) for precise, non-invasive assessment of diabetes-related changes in the dermal microvasculature and skin micro-anatomy, resolved with unprecedented sensitivity and detail without the need for contrast agents. Providing unique imaging contrast, we explored a possible role for RSOM as an investigational tool in diabetes healthcare and offer the first comprehensive study investigating the relationship between different diabetes complications and microvascular features in vivo. We applied RSOM to scan the pretibial area of 95 participants with diabetes mellitus and 48 age-matched volunteers without diabetes, grouped according to disease complications, and extracted six label-free optoacoustic biomarkers of human skin, including dermal microvasculature density and epidermal parameters, based on a novel image-processing pipeline. We then correlated these biomarkers to disease severity and found statistically significant effects on microvasculature parameters as a function of diabetes complications. We discuss how label-free RSOM biomarkers can lead to a quantitative assessment of the systemic effects of diabetes and its complications, complementing the qualitative assessment allowed by current clinical metrics, possibly leading to a precise scoring system that captures the gradual evolution of the disease.

Clinical and Translational Imaging and Sensing of Diabetic Microangiopathy: A Narrative Review.

Microvascular changes in diabetes affect the function of several critical organs, such as the kidneys, heart, brain, eye, and skin, among others. The possibility of detecting such changes early enough in order to take appropriate actions renders the development of appropriate tools and techniques an imperative need. To this end, several sensing and imaging techniques have been developed or employed in the assessment of microangiopathy in patients with diabetes. Herein, we present such techniques; we provide insights into their principles of operation while discussing the characteristics that make them appropriate for such use. Finally, apart from already established techniques, we present novel ones with great translational potential, such as optoacoustic technologies, which are expected to enter clinical practice in the foreseeable future.

Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS).

BACKGROUND: Remission of type 2 diabetes can occur as a result of weight loss and is characterised by liver fat and pancreas fat reduction and recovered insulin secretion. In this analysis, we aimed to investigate the mechanisms of weight loss- induced remission in people with prediabetes. METHODS: In this prespecified post-hoc analysis, weight loss-induced resolution of prediabetes in the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS) was assessed, and the results were validated against participants from the Diabetes Prevention Program (DPP) study. For PLIS, between March 1, 2012, and Aug 31, 2016, participants were recruited from eight clinical study centres (including seven university hospitals) in Germany and randomly assigned to receive either a control intervention, a standard lifestyle intervention (ie, DPP-based intervention), or an intensified lifestyle intervention for 12 months. For DPP, participants were recruited from 23 clinical study centres in the USA between July 31, 1996, and May 18, 1999, and randomly assigned to receive either a standard lifestyle intervention, metformin, or placebo. In both PLIS and DPP, only participants who were randomly assigned to receive lifestyle intervention or placebo and who lost at least 5% of their bodyweight were included in this analysis. Responders were defined as people who returned to normal fasting plasma glucose (FPG; <5·6 mmol/L), normal glucose tolerance (<7·8 mmol/L), and HbA1c less than 39 mmol/mol after 12 months of lifestyle intervention or placebo or control intervention. Non-responders were defined as people who had FPG, 2 h glucose, or HbA1c more than these thresholds. The main outcomes for this analysis were insulin sensitivity, insulin secretion, visceral adipose tissue (VAT), and intrahepatic lipid content (IHL) and were evaluated via linear mixed models. FINDINGS: Of 1160 participants recruited to PLIS, 298 (25·7%) had weight loss of 5% or more of their bodyweight at baseline. 128 (43%) of 298 participants were responders and 170 (57%) were non-responders. Responders were younger than non-responders (mean age 55·6 years [SD 9·9] vs 60·4 years [8·6]; p<0·0001). The DPP validation cohort included 683 participants who lost at least 5% of their bodyweight at baseline. Of these, 132 (19%) were responders and 551 (81%) were non-responders. In PLIS, BMI reduction was similar between responders and non-responders (responders mean at baseline 32·4 kg/m2 [SD 5·6] to mean at 12 months 29·0 kg/m2 [4·9] vs non-responders 32·1 kg/m2 [5·9] to 29·2 kg/m2 [5·4]; p=0·86). However, whole-body insulin sensitivity increased more in responders than in non-responders (mean at baseline 291 mL/[min × m2], SD 60 to mean at 12 months 378 mL/[min × m2], 56 vs 278 mL/[min × m2], 62, to 323 mL/[min × m2], 66; p<0·0001), whereas insulin secretion did not differ within groups over time or between groups (responders mean at baseline 175 pmol/mmol [SD 64] to mean at 12 months 163·7 pmol/mmol [60·6] vs non-responders 158·0 pmol/mmol [55·6] to 154·1 pmol/mmol [56·2]; p=0·46). IHL decreased in both groups, without a difference between groups (responders mean at baseline 10·1% [SD 8·7] to mean at 12 months 3·5% [3·9] vs non-responders 10·3% [8·1] to 4·2% [4·2]; p=0·34); however, VAT decreased more in responders than in non-responders (mean at baseline 6·2 L [SD 2·9] to mean at 12 months 4·1 L [2·3] vs 5·7 L [2·3] to 4·5 L [2·2]; p=0·0003). Responders had a 73% lower risk of developing type 2 diabetes than non-responders in the 2 years after the intervention ended. INTERPRETATION: By contrast to remission of type 2 diabetes, resolution of prediabetes was characterised by an improvement in insulin sensitivity and reduced VAT. Because return to normal glucose regulation (NGR) prevents development of type 2 diabetes, we propose the concept of remission of prediabetes in analogy to type 2 diabetes. We suggest that remission of prediabetes should be the primary therapeutic aim in individuals with prediabetes. FUNDING: German Federal Ministry for Education and Research via the German Center for Diabetes Research; the Ministry of Science, Research and the Arts Baden-Württemberg; the Helmholtz Association and Helmholtz Munich; the Cluster of Excellence Controlling Microbes to Fight Infections; and the German Research Foundation.

Neurotoxin-Derived Optical Probes for Biological and Medical Imaging.

The superb specificity and potency of biological toxins targeting various ion channels and receptors are of major interest for the delivery of therapeutics to distinct cell types and subcellular compartments. Fused with reporter proteins or labelled with fluorophores and nanocomposites, animal toxins and their detoxified variants also offer expanding opportunities for visualisation of a range of molecular processes and functions in preclinical models, as well as clinical studies. This article presents state-of-the-art optical probes derived from neurotoxins targeting ion channels, with discussions of their applications in basic and translational biomedical research. It describes the design and production of probes and reviews their applications with advantages and limitations, with prospects for future improvements. Given the advances in imaging tools and expanding research areas benefiting from the use of optical probes, described here resources should assist the discovery process and facilitate high-precision interrogation and therapeutic interventions.

Range verification of a clinical proton beam in an abdominal phantom by co-registration of ionoacoustics and ultrasound.

Objective.The range uncertainty in proton radiotherapy is a limiting factor to achieve optimum dose conformity to the tumour volume. Ionoacoustics is a promising approach forin siturange verification, which would allow to reduce the size of the irradiated volume relative to the tumour volume. The energy deposition of a pulsed proton beam leads to an acoustic pressure wave (ionoacoustics), the detection of which allows conclusion about the distance between the Bragg peak and the acoustic detector. This information can be transferred into a co-registered ultrasound image, marking the Bragg peak position relative to the surrounding anatomy.Approach.A CIRS 3D abdominal phantom was irradiated with 126 MeV protons at a clinical proton therapy centre. Acoustic signals were recorded on the beam axis distal to the Bragg peak with a Cetacean C305X hydrophone. The ionoacoustic measurements were processed with a correlation filter using simulated filter templates. The hydrophone was rigidly attached to an ultrasound device (Interson GP-C01) recording ultrasound images of the irradiated region.Main results.The time of flight obtained from ionoacoustic measurements were transferred to an ultrasound image by means of an optoacoustic calibration measurement. The Bragg peak position was marked in the ultrasound image with a statistical uncertainty ofσ= 0.5 mm of 24 individual measurements depositing 1.2 Gy at the Bragg peak. The difference between the evaluated Bragg peak position and the one obtained from irradiation planning (1.0 mm) is smaller than the typical range uncertainty (≈4 mm) at the given penetration depth (10 cm).Significance.The measurements show that it is possible to determine the Bragg peak position of a clinical proton beam with submillimetre precision and transfer the information to an ultrasound image of the irradiated region. The dose required for this is smaller than that used for a typical irradiation fraction.

Towards in vivo characterization of thyroid nodules suspicious for malignancy using multispectral optoacoustic tomography.

PURPOSE: Patient-tailored management of thyroid nodules requires improved risk of malignancy stratification by accurate preoperative nodule assessment, aiming to personalize decisions concerning diagnostics and treatment. Here, we perform an exploratory pilot study to identify possible patterns on multispectral optoacoustic tomography (MSOT) for thyroid malignancy stratification. For the first time, we directly correlate MSOT images with histopathology data on a detailed level. METHODS: We use recently enhanced data processing and image reconstruction methods for MSOT to provide next-level image quality by means of improved spatial resolution and spectral contrast. We examine optoacoustic features in thyroid nodules associated with vascular patterns and correlate these directly with reference histopathology. RESULTS: Our methods show the ability to resolve blood vessels with diameters of 250 µm at depths of up to 2 cm. The vessel diameters derived on MSOT showed an excellent correlation (R2-score of 0.9426) with the vessel diameters on histopathology. Subsequently, we identify features of malignancy observable in MSOT, such as intranodular microvascularity and extrathyroidal extension verified by histopathology. Despite these promising features in selected patients, we could not determine statistically relevant differences between benign and malignant thyroid nodules based on mean oxygen saturation in thyroid nodules. Thus, we illustrate general imaging artifacts of the whole field of optoacoustic imaging that reduce image fidelity and distort spectral contrast, which impedes quantification of chromophore presence based on mean concentrations. CONCLUSION: We recommend examining optoacoustic features in addition to chromophore quantification to rank malignancy risk. We present optoacoustic images of thyroid nodules with the highest spatial resolution and spectral contrast to date, directly correlated to histopathology, pushing the clinical translation of MSOT.

Spotlight on Nerves: Portable Multispectral Optoacoustic Imaging of Peripheral Nerve Vascularization and Morphology.

Various morphological and functional parameters of peripheral nerves and their vascular supply are indicative of pathological changes due to injury or disease. Based on recent improvements in optoacoustic image quality, the ability of multispectral optoacoustic tomography, to investigate the vascular environment and morphology of peripheral nerves is explored in vivo in a pilot study on healthy volunteers in tandem with ultrasound imaging (OPUS). The unique ability of optoacoustic imaging to visualize the vasa nervorum by observing intraneural vessels in healthy nerves is showcased in vivo for the first time. In addition, it is demonstrated that the label-free spectral optoacoustic contrast of the perfused connective tissue of peripheral nerves can be linked to the endogenous contrast of hemoglobin and collagen. Metrics are introduced to analyze the composition of tissue based on its optoacoustic contrast and show that the high-resolution spectral contrast reveals specific differences between nervous tissue and reference tissue in the nerve's surrounding. How this showcased extraction of peripheral nerve characteristics using multispectral optoacoustic and ultrasound imaging could offer new insights into the pathophysiology of nerve damage and neuropathies, for example, in the context of diabetes is discussed.

Accounting for blood attenuation in intravascular near-infrared fluorescence-ultrasound imaging using a fluorophore-coated guidewire.

Significance: Intravascular near-infrared fluorescence (NIRF) imaging aims to improve the inspection of vascular pathology using fluorescent agents with specificity to vascular disease biomarkers. The method has been developed to operate in tandem with an anatomical modality, such as intravascular ultrasound (IVUS), and complements anatomical readings with pathophysiological contrast, enhancing the information obtained from the hybrid examination. Aim: However, attenuation of NIRF signals by blood challenges NIRF quantification. We propose a new method for attenuation correction in NIRF intravascular imaging based on a fluorophore-coated guidewire that is used as a reference for the fluorescence measurement and provides a real-time measurement of blood attenuation during the NIRF examination. Approach: We examine the performance of the method in a porcine coronary artery ex vivo and phantoms using a 3.2F NIRF-IVUS catheter. Results: We demonstrate marked improvement over uncorrected signals of up to 4.5-fold and errors of < 11 % for target signals acquired at distances up to 1 mm from the catheter system employed. Conclusions: The method offers a potential means of improving the accuracy of intravascular NIRF imaging under in vivo conditions.

Skeletal muscle optoacoustics reveals patterns of circulatory function and oxygen metabolism during exercise.

Imaging skeletal muscle function and metabolism, as reported by local hemodynamics and oxygen kinetics, can elucidate muscle performance, severity of an underlying disease or outcome of a treatment. Herein, we used multispectral optoacoustic tomography (MSOT) to image hemodynamics and oxygen kinetics within muscle during exercise. Four healthy volunteers underwent three different hand-grip exercise challenges (60s isometric, 120s intermittent isometric and 60s isotonic). During isometric contraction, MSOT showed a decrease of HbO2, Hb and total blood volume (TBV), followed by a prominent increase after the end of contraction. Corresponding hemodynamic behaviors were recorded during the intermittent isometric and isotonic exercises. A more detailed analysis of MSOT readouts revealed insights into arteriovenous oxygen differences and muscle oxygen consumption during all exercise schemes. These results demonstrate an excellent capability of visualizing both circulatory function and oxygen metabolism within skeletal muscle under exercise, with great potential implications for muscle research, including relevant disease diagnostics.

Non-invasive multispectral optoacoustic tomography resolves intrahepatic lipids in patients with hepatic steatosis.

Hepatic steatosis is characterized by intrahepatic lipid accumulation and may lead to irreversible liver damage if untreated. Here, we investigate whether multispectral optoacoustic tomography (MSOT) can offer label-free detection of liver lipid content to enable non-invasive characterization of hepatic steatosis by analyzing the spectral region around 930 nm, where lipids characteristically absorb. In a pilot study, we apply MSOT to measure liver and surrounding tissues in five patients with liver steatosis and five healthy volunteers, revealing significantly higher absorptions at 930 nm in the patients, while no significant difference was observed in the subcutaneous adipose tissue of the two groups. We further corroborated the human observations with corresponding MSOT measurements in high fat diet (HFD) - and regular chow diet (CD)-fed mice. This study introduces MSOT as a potential non-invasive and portable technique for detecting/monitoring hepatic steatosis in clinical settings, providing justification for larger studies.