Effects of Acute Hyperoxia on Autonomic Function and Coronary Tone in Patients with Peripheral Artery Disease.

Numerous studies have shown that oxidative stress plays an important role in peripheral artery disease (PAD). Prior reports suggested autonomic dysfunction in PAD. We hypothesized that responses of the autonomic nervous system and coronary tone would be impaired in patients with PAD during exposure to acute hyperoxia, an oxidative stressor. In 20 PAD patients and 16 healthy, sex and age-matched controls, beat-by-beat heart rate (HR, from ECG) and blood pressure (BP, with Finometer) were recorded for 10 minutes during room air breathing and 5 minutes of hyperoxia. Cardiovagal baroreflex sensitivity and HR variability (HRV) were evaluated as measures of autonomic function. Transthoracic coronary echocardiography was used to assess peak coronary blood flow velocity (CBV) in the left anterior descending coronary artery. Cardiaovagal baroreflex sensitivity at rest was lower in PAD than in healthy controls. Hyperoxia raised BP solely in the patients with PAD, with no change observed in healthy controls. Hyperoxia induced an increase in cardiac parasympathetic activity assessed by the high-frequency component of HRV in healthy controls but not in PAD. Indices of parasympathetic activity were lower in PAD than in healthy controls throughout the trial as well as during hyperoxia. Hyperoxia induced coronary vasoconstriction in both groups, while the coronary perfusion time fraction was lower in PAD than in healthy controls. These results suggest that the response in parasympathetic activity to hyperoxia (i.e., oxidative stress) is blunted and the coronary perfusion time is shorter in PAD patients.

Three-Dimensional Characterization of Dry Particle Coating Structures Originating from the Mechano-fusion Process.

Dry particle coating processes are of key importance for creating functionalized materials. By a change in surface structure, initiated during coating, a surface property change and thus functionalization can be achieved. This study introduces an innovative approach employing 3D X-ray micro-computed tomography (micro-CT) to characterize coated particles, consisting of spherical alumina particles (d50 = 45.64 µm), called hosts, surrounded by spherical polystyrene particles (d50 = 3.5 µm), called guests. The formed structures, hetero-aggregates, are generated by dry particle coating using mechano-fusion (MF). A deeper understanding of the influence of MF process parameters on the coating structures is a crucial step toward tailoring of coating structure, resulting surface property and functionalization. Therefore, the influence of rotational speed, process time, and total mechanical energy input during MF is explored. Leveraging micro-CT data, acquired of coated particles, enables non-stereologically biased and quantitative coating structure analysis. The guest's coating thickness is analyzed using the maximum inscribed sphere and ray method, two different local thickness measurement approaches. Particle-discrete information of the coating structure are available after a proper image processing workflow is implemented. Coating efficiency and guest's neighboring relations (nearest neighbor distance and number of neighbors inside search radius) are evaluated.

Influence of Hydrolyzed Metal Ions and Surfactants on the Phase Transfer of Al2O3, SiO2, and SnO2.

There are various possibilities for changing the surface properties of particles. In this work, the charge reversal on different metal oxides with different electrolytes is investigated and whether this allows a change in wettability due to a subsequent adsorption of surfactants, e.g., sodium dodecyl sulfate (SDS). It is investigated if the materials of the particles differ only by the isoelectric point or if the surface chemistry of the materials has an influence on the charge reversal as well. Furthermore, the adsorption of SDS as an anionic surfactant is examined, which is also characterized by a second charge reversal and related to a sign change of the electrophoretic mobility µe. Finally, it is examined whether the adsorption of the hydrolyzed metal ions and the subsequent adsorption of SDS are effective enough to hydrophobize the particles and allow phase transfer from the aqueous to second nonaqueous liquid phase. In addition, the influence of pH is investigated because the hydrolyzed metal cations are formed only in a certain pH range, which means that the bridge formed between the particle surface and the surfactant works only in a certain pH range, which would allow pH-selective extraction of the particle system into the second nonaqueous liquid phase.

Introduction to the Theme "Pharmacological Individuality: New Insights and Strategies for Personalized and Precise Drug Treatment".

The reviews in Volume 64 of the Annual Review of Pharmacology and Toxicology cover diverse topics. A common theme in many of the reviews is the interindividual variability in the clinical response to drugs. Highlighted areas include emerging developments in pharmacogenomics that can predict the personal risk for drug inefficacy and/or adverse drug reactions. Other reviews focus on the use of circulating biomarkers to define drug metabolism phenotypes and the effect of circadian regulation on drug response. Another emerging technology, digital twins that model individual patients, is used to generate computational simulations of drug effects and identify optimal personalized treatments. Another variable that may affect clinical outcomes, the nocebo response (an adverse reaction to a placebo), complicates clinical trials. These reviews further document that pharmacological individuality is an essential component of the concepts of personalized medicine and precision medicine and will likely have an important impact on patient care.

Rheuma-VOR study: optimising healthcare of rheumatic diseases by multiprofessional coordinating centres.

OBJECTIVES: Early diagnosis of inflammatory arthritis is critical to prevent joint damage and functional incapacities. However, the discrepancy between recommendations of early diagnosis and reality is remarkable. The Rheuma-VOR study aimed to improve the time to diagnosis of patients with early arthritis by coordinating cooperation between primary care physicians, specialists and patients in Germany. METHODS: This prospective non-randomised multicentre study involved 2340 primary care physicians, 72 rheumatologists, 4 university hospitals and 4 rheumatology centres in 4 German Federal States. The two coprimary endpoints (time to diagnosis and screening performance of primary care physicians) were evaluated for early versus late implementation phase. Additionally, time to diagnosis and secondary endpoints (decrease of disease activity, increase in quality of life and overall well-being, improvement of fatigue, depression, functional ability, and work ability, reduction in drug and medical costs and hospitalisation) were compared with a reference cohort of the German Rheumatism Research Centre (DRFZ) reflecting standard care. RESULTS: A total of 7049 patients were enrolled in the coordination centres and 1537 patients were diagnosed with a rheumatic disease and consented to further participation. A follow-up consultation after 1 year was realised in 592 patients. The time to diagnosis endpoint and the secondary endpoints were met. In addition, the calculation of cost-effectiveness shows that Rheuma-VOR has a dominant cost-benefit ratio compared with standard care. DISCUSSION: Rheuma-VOR has shown an improvement in rheumatological care, patient-reported outcome parameters and cost savings by coordinating the cooperation of primary care physicians, rheumatologists and patients, in a nationwide approach.

Glucose metabolism and autonomic function in healthy individuals and patients with type 2 diabetes mellitus at rest and during exercise.

Autonomic dysfunction is a common complication of type 2 diabetes mellitus (T2DM). However, the character of dysfunction varies in different reports. Differences in measurement methodology and complications might have influenced the inconsistent results. We sought to evaluate comprehensively the relationship between abnormal glucose metabolism and autonomic function at rest and the response to exercise in healthy individuals and T2DM patients. We hypothesized that both sympathetic and parasympathetic indices would decrease with the progression of abnormal glucose metabolism in individuals with few complications related to high sympathetic tone. Twenty healthy individuals and 11 T2DM patients without clinically evident cardiovascular disease other than controlled hypertension were examined. Resting muscle sympathetic nerve activity (MSNA), heart rate variability, spontaneous cardiovagal baroreflex sensitivity (CBRS), sympathetic baroreflex sensitivity and the MSNA response to handgrip exercise were measured. Resting MSNA was lower in patients with T2DM than in healthy control subjects (P = 0.011). Resting MSNA was negatively correlated with haemoglobin A1c in all subjects (R = -0.45, P = 0.024). The parasympathetic components of heart rate variability and CBRS were negatively correlated with glycaemic/insulin indices in all subjects and even in the control group only (all, P < 0.05). In all subjects, the MSNA response to exercise was positively correlated with fasting blood glucose (R = 0.69, P < 0.001). Resting sympathetic activity and parasympathetic modulation of heart rate were decreased in relationship to abnormal glucose metabolism. Meanwhile, the sympathetic responses to handgrip were preserved in diabetics. The responses were correlated with glucose/insulin parameters throughout diabetic and control subjects. These results suggest the importance of a comprehensive assessment of autonomic function in T2DM.

Effects of a Web-Based Lifestyle Intervention on Physical Fitness and Health in Physically Inactive Adults: A Randomized Controlled Trial.

Web-based lifestyle interventions are a new area of health research. This randomized controlled trial evaluated the effectiveness of an interactive web-based health program on physical fitness and health. N = 189 healthy adults participated in a 12-week interactive (intervention) or non-interactive (control) web-based health program. The intervention provided a web-based lifestyle intervention to promote physical activity and fitness through individualized activities as part of a fully automated, multimodal health program. The control intervention included health information. Cardiorespiratory fitness measured as maximum oxygen uptake (VO2max) was the primary outcome, while musculoskeletal fitness, physical activity and dietary behavior, and physiological health outcomes were assessed as secondary outcomes (t0: 0 months, t1: 3 months, t2: 9 months, t3: 15 months). Statistical analysis was performed with robust linear mixed models. There were significant time effects in the primary outcome (VO2max) (t0-t1: p = 0.018) and individual secondary outcomes for the interactive web-based health program, but no significant interaction effects in any of the outcomes between the interactive and non-interactive web-based health program. This study did not demonstrate the effectiveness of an interactive compared with a non-interactive web-based health program in physically inactive adults. Future research should further develop the evidence on web-based lifestyle interventions.

A cross-sectoral approach to utilizing health claims data for quality assurance in medical rehabilitation: study protocol of a combined prospective longitudinal and retrospective cohort study.

BACKGROUND: Measuring the quality of provided healthcare presents many challenges, especially in the context of medical rehabilitation. Rehabilitation is based on a holistic biopsychosocial model of health that includes a person's long-term functioning; hence, outcome domains are very diverse. In Germany, rehabilitation outcomes are currently assessed via patient and physician surveys. Health insurance claims data has the potential to simplify current quality assurance procedures in Germany, since its comprehensive collection is federally mandated from every healthcare provider. By using a cross-sectoral approach, quality assessments in rehabilitation can be adjusted for the quality provided in previous sectors and individual patient risk factors. METHODS: SEQUAR combines two studies: In a prospective longitudinal study, 600 orthopedic rehabilitation patients and their physicians are surveyed at 4 and 2 time points, respectively, throughout rehabilitation and a follow-up period of 6 months. The questionnaires include validated instruments used in the current best-practice quality assurance procedures. In a retrospective cohort study, a nationwide claims database with more than 312,000 orthopedic rehabilitation patients will be used to perform exploratory analysis for the identification of quality indicators. The identified SEQUAR claims data quality indicators will be calculated for our prospective study participants and tested for their ability to approximate or replace the currently used, best-practice quality indicators based on primary data. DISCUSSION: The identified SEQUAR quality indicators will be used to draft a novel, state-of-the-art quality assurance procedure that reduces the administrative burden of current procedures. Further research into the applicability to other indications of rehabilitation is required. TRIAL REGISTRATION: WHO UTN: U1111-1276-7141; DRKS-ID: DRKS00028747 (Date of Registration in DRKS: 2022/08/10).

Rehabilitation facilities' research needs and knowledge transfer in Southwest Germany: Data of the REHA-KNOWS study.

The REHA-KNOWS study was conducted to identify research needs, to explore attitudes and barriers towards health services research as well as to investigate knowledge transfer strategies in rehabilitation facilities in Southwest Germany. We designed a short online survey with 18 questions. From March to May 2023, we surveyed representatives of rehabilitation facilities in two German Federal States (Baden-Wuerttemberg and Saarland) using an online questionnaire provided via UniparkⓇ. The dataset contains all responses from n=88 individuals. We applied a list-based sampling approach and contacted n=206 rehabilitation facilities in total. Data collection started on March 2nd and the last response was received on May 2nd. As this sampling strategy allows multiple answers per facility, we applied an anonymized coding system to identify the affiliation of each respondent. In total, the 88 responses come from 74 centers. The dataset includes information on characteristics of the facility where the respondents work, the perceived benefits and barriers regarding health services research in practice, the need for research on specific topics and the transfer strategies established within the facilities. Analyses of these topics were performed in a descriptive and exploratory manner. This data offers the potential to be linked with data resulting from future research in this field in other Federal States of Germany. Further subgroup analyses can be performed with this dataset for specific research questions.

Particle-Bubble Interactions: an Investigation of the Three-Phase Contact Line by Atomic Force Microscopy.

The dynamics of the three-phase contact line during particle-bubble interactions determine the stability of particle-bubble aggregates in flotation. The interaction of particles and sessile gas bubbles can be studied by colloidal probe atomic force microscopy (CP-AFM). This paper demonstrates a method to obtain the contact angle, the position of the three-phase contact line on the particle, and the bubble profile by utilizing the full information contained in AFM force-distance curves, i.e., force and CP-position information as well as the work done to move the three-phase contact line on the CP-particle. The proposed method does not require any assumption of a constant contact angle or a constant opening angle. This is achieved by the combined solution of the particle force balance and an expression for the work required to move the three-phase contact line over the colloid probe. The applicability to AFM force-distance measurements was demonstrated for the interaction of a hydrophobic SiO2 or a hydrophobic Al2O3 colloidal probe particle with sessile gas bubbles having radii between 45 and 80 µm.

Influence of different discharge levels on the mechanical recycling efficiency of lithium-ion batteries.

Prior to the mechanical processing, discharging is necessary to prevent hazards. While the discharging process, different phenomena can occur changing the characteristics of the functional units of LIB. This study reveals the influence on the mechanical recycling and the obtained material when different discharge levels are used for various cells differing in their cell chemistry. It shows that for different cells, for example, copper deposits happen on the cathode as well as active material deposits on the separator foil. These new properties deteriorate the black mass quality and show contamination of the products with other material streams. It is being tested whether established sub-processes are suitable. However, it becomes clear that further recycling steps (e.g. flotation, hydrometallurgy) can be influenced as well as their product quality and element specific yield.

Aortic blood pressure and pulse wave indices responses to exercise in peripheral artery disease.

Peripheral artery disease (PAD) refers to obstructed blood flow in peripheral arteries typically due to atherosclerotic plaques. How PAD alters aortic blood pressure and pressure wave propagation during exercise is unclear. Thus, this study examined central blood pressure responses to plantar flexion exercise by investigating aortic pulse wave properties in PAD. Thirteen subjects with PAD and 13 healthy [age-, sex-, body mass index (BMI) matched] subjects performed rhythmic plantar flexion for 14 min or until fatigue (20 contractions/min; started at 2 kg with 1 kg/min increment up to 12 kg). Brachial (oscillometric cuff) and radial (SphygmoCor) blood pressure and derived-aortic waveforms were analyzed during supine rest and plantar flexion exercise. At rest, baseline augmentation index (P = 0.0263) and cardiac wasted energy (P = 0.0321) were greater in PAD due to earlier arrival of the reflected wave (P = 0.0289). During exercise, aortic blood pressure (aMAP) and aortic pulse pressure showed significant interaction effects (P = 0.0041 and P = 0.0109, respectively). In particular, PAD had a greater aMAP increase at peak exercise (P = 0.0147). Moreover, the tension time index was greater during exercise in PAD (P = 0.0173), especially at peak exercise (P = 0.0173), whereas the diastolic time index (P = 0.0685) was not different between the two groups. Hence, during exercise, the subendocardial viability ratio was lower in PAD (P = 0.0164), especially at peak exercise (P = 0.0164). The results suggest that in PAD, the aortic blood pressure responses and myocardial oxygen demand during exercise are increased compared with healthy controls.

How do (false) positively screened patients experience a screening programme for liver cirrhosis or fibrosis in Germany? A qualitative study.

OBJECTIVE: This study aimed to explore psychosocial consequences of (false) positive liver screening results and to identify influencing factors for perceived strain within a multistage screening programme for liver cirrhosis and fibrosis in Germany. METHODS: Between June 2018 and May 2019, all positively screened patients were asked to participate in the study (n = 158). N = 11 telephone interviews and n = 4 follow-up interviews were conducted. Semi-structured telephone interviews were carried out. The analysis followed a structuring content analysis approach. Thereby, categories were first defined deductively. Second, the categories were revised inductively based on the data. RESULTS: The main themes found regarding the consequences of the screening were categorised in emotional reactions and behavioural reactions. Few respondents described negative emotional consequences related to screening. Those seem to be mostly driven by suboptimal patient-provider communication and might be worsened when transparent information transfer fails to happen. As a result, patients sought information and support in their social environment. All patients reported positive attitudes towards liver screening. CONCLUSION: To reduce the potential occurrence of psychosocial consequences during the screening process, medical screening should be performed in the context of transparent information. Regular health communication on the side of health professionals and increasing patients' health literacy might contribute to avoiding negative emotions in line with screening. PATIENT OR PUBLIC CONTRIBUTION: This study recognises the wide-ranging patients' perspectives regarding the consequences of liver screening which should be taken into consideration when implementing a new screening programme to ensure a patient-centred approach.

Needs assessment towards research data management at the Medical Faculty of the University of Freiburg - Data of the BE-KONFORM study.

In order to investigate employees' needs of the Medical Faculty of the University of Freiburg regarding research data management, the BE-KONFORM study was performed in a two-step approach. First, guideline-based qualitative video interviews with four researchers were performed to identify key constructs of relevance. Second, a standardized online survey was conducted from 1st to 15th of November 2020 based on e-mail invitation by the dean and a faculty newsletter. The questionnaire was provided bilingual (English and German) using a backward-forward translation method, no reminders and incentives were used to increase the response rate. The online survey was programmed in REDCap and was accessible via online link. The target population were members of the Medical Faculty (listed in the newsletter mailing list) regardless of the type of working contract signed. The final dataset contains 236 complete cases (90% German and 10% English). The study includes a randomised module asking for data publication (group A) or not (group B). 113 cases were randomized into group A and 99% of them consented to the publication of the collected research data in anonymized form (n=112). The dataset comprised questions about work-related characteristics (professional status, working experience, scientific field of work), data management-related items (definition of research data management, type of data used, type of storage used for saving data, use of electronic laboratory notebooks), experience and attitudes towards data publication in data repositories, as well as needs and preferences regarding research data management support. The produced data offers the possibility to connect with other data collected in this field in other contexts (faculties or universities).

Effect of Cyclooxygenase Inhibition on Peripheral Venous Distension Reflex in Healthy Humans.

BACKGROUND: Peripheral venous distension evokes a pressor reflex (venous distension reflex). Afferent group III and IV nerves innervating veins are suggested as the afferent arm of the venous distension reflex. Prostaglandins stimulate/sensitize group III/IV nerves. We hypothesized that inhibition of prostaglandin synthesis by local cyclooxygenase blockade would attenuate the muscle sympathetic nerve activity (MSNA) and blood pressure responses to venous distension. METHODS: Nineteen healthy volunteers (age, 27±5 years) participated in the study with 2 visits. To induce venous distension, a volume of solution (saline alone or 9 mg ketorolac tromethamine in saline) was infused into the vein in the antecubital fossa of an arterially occluded forearm. During the procedure, beat-by-beat heart rate, blood pressure and MSNA were recorded simultaneously. The vein size was measured with ultrasound. RESULTS: In both visits, the venous distension procedure significantly increased blood pressure, heart rate, and MSNA (all, P<0.05). The increase in mean arterial pressure and MSNA in the ketorolac visit was significantly lower than in the control visit (∆ mean arterial pressure, 7.0±6.2 versus 13.8±7.7 mm Hg; ∆MSNA, 6.0±7.1 versus 14.8±7.7 bursts/min; both, P<0.05). The increase in vein size induced by the infusion was not different between visits. CONCLUSIONS: The presented data show that cyclooxygenase blockade attenuates the responses in MSNA and blood pressure to peripheral venous distension reflex. The results suggest that cyclooxygenase products play a key role in evoking afferent activation responsible for the venous distension reflex.

Mapping intertidal macrophytes in fjords in Southwest Greenland using Sentinel-2 imagery.

Changes in the distribution of coastal macrophytes in Greenland, and elsewhere in the Arctic are difficult to quantify as the region remains challenging to access and monitor. Satellite imagery, in particular Sentinel-2 (S2), may enable large-scale monitoring of coastal areas in Greenland but its use is impacted by the optically complex environments and the scarcity of supporting data in the region. Additionally, the canopies of the dominant macrophyte species in Greenland do not extend to the sea surface, limiting the use of indices that exploit the reflection of near-infrared radiation by vegetation due to its absorption by seawater. Three hypotheses are tested: I) 10-m S2 imagery and commonly used detection methods can identify intertidal macrophytes that are exposed at low tide in an optically complex fjord system in Greenland impacted by marine and land terminating glaciers; II) detached and floating macrophytes accumulate in patches that are sufficiently large to be detected by 10-m S2 images; III) iceberg scour and/or turbid meltwater runoff shape the spatial distribution of intertidal macroalgae in fjord systems with marine-terminating glaciers. The NDVI produced the best results in optically complex fjord systems in Greenland. 12 km2 of exposed intertidal macrophytes were identified in the study area at low tide. Floating mats of macrophytes ranged in area from 400 m2 to 326,800 m2 and were most common at the mouth of the fjord. Icebergs and turbidity appear to play a role in structuring the distribution of intertidal macrophytes and the retreat of marine terminating glaciers could allow macrophytes cover to expand. The challenges and solutions presented here apply to most fjords in Greenland and, therefore, the methodology may be extended to produce a Greenland-wide estimate of intertidal macrophytes.

Microbiological profile, preclinical pharmacokinetics and efficacy of CRS0393, a novel antimycobacterial agent targeting MmpL3.

The benzothiazole amide CRS0393 demonstrated excellent in vitro activity against nontuberculous mycobacteria (NTM), including M. abscessus isolates from cystic fibrosis (CF) patients, with minimum inhibitory concentrations (MICs) of ≤0.03-0.5 µg/mL. The essential transport protein MmpL3 was confirmed as the target via analysis of spontaneous resistant mutants and further biological profiling. In mouse pharmacokinetic studies, intratracheal instillation of a single dose of CRS0393 resulted in high concentrations of drug in epithelial lining fluid (ELF) and lung tissue, which remained above the M. abscessus MIC for at least 9 hours post-dose. This exposure resulted in a penetration ratio of 261 for ELF and 54 for lung tissue relative to plasma. CRS0393 showed good oral bioavailability, particularly when formulated in kolliphor oil, with a lung-to-plasma penetration ratio ranging from 0.5 to 4. CRS0393 demonstrated concentration-dependent reduction of intracellular M. abscessus in a THP-1 macrophage infection model. CRS0393 was well tolerated following intranasal administration (8 mg/kg) or oral dosing (25 mg/kg) once daily for 28 days in dexamethasone-treated C3HeB/FeJ mice. Efficacy against M. abscessus strain 103 was achieved via the intranasal route, while oral dosing will need further optimization. CRS0393 holds promise for development as a novel agent with broad antimycobacterial activity.

Introduction to the Theme "Development of New Drugs: Moving from the Bench to Bedside and Improved Patient Care".

Investigations in pharmacology and toxicology range from molecular studies to clinical care. Studies in basic and clinical pharmacology and in preclinical and clinical toxicology are all essential in bringing new knowledge and new drugs into clinical use. The 30 reviews in Volume 63 of the Annual Review of Pharmacology and Toxicology explore topics across this spectrum. Examples include "Zebrafish as a Mainstream Model for In Vivo Systems Pharmacology and Toxicology" and "Artificial Intelligence and Machine Learning for Lead-to-Candidate Decision-Making and Beyond." Other reviews discuss components important for drug discovery and development and the use of pharmaceuticals in a variety of diseases. Air pollution continues to increase globally; accordingly, "Air Pollution-Related Neurotoxicity Across the Life Span" is a timely and forward-thinking review. Volume 63 also explores the use of contemporary technologies such as electronic health records, pharmacogenetics, and new drug delivery systems that help enhance and improve the utility of new therapies.

Depth-Resolved Localization Microangiography in the NIR-II Window.

Detailed characterization of microvascular alterations requires high-resolution 3D imaging methods capable of providing both morphological and functional information. Existing optical microscopy tools are routinely used for microangiography, yet offer suboptimal trade-offs between the achievable field of view and spatial resolution with the intense light scattering in biological tissues further limiting the achievable penetration depth. Herein, a new approach for volumetric deep-tissue microangiography based on stereovision combined with super-resolution localization imaging is introduced that overcomes the spatial resolution limits imposed by light diffusion and optical diffraction in wide-field imaging configurations. The method capitalizes on localization and tracking of flowing fluorescent particles in the second near-infrared window (NIR-II, ≈1000-1700 nm), with the third (depth) dimension added by triangulation and stereo-matching of images acquired with two short-wave infrared cameras operating in a dual-view mode. The 3D imaging capability enabled with the proposed method facilitates a detailed visualization of microvascular networks and an accurate blood flow quantification. Experiments performed in tissue-mimicking phantoms demonstrate that high resolution is preserved up to a depth of 4 mm in a turbid medium. Transcranial microangiography of the entire murine cortex and penetrating vessels is further demonstrated at capillary level resolution.

Enhancing optoacoustic mesoscopy through calibration-based iterative reconstruction.

Optoacoustic mesoscopy combines rich optical absorption contrast with high spatial resolution at tissue depths beyond reach for microscopic techniques employing focused light excitation. The mesoscopic imaging performance is commonly hindered by the use of inaccurate delay-and-sum reconstruction approaches and idealized modeling assumptions. In principle, image reconstruction performance could be enhanced by simulating the optoacoustic signal generation, propagation, and detection path. However, for most realistic experimental scenarios, the underlying total impulse response (TIR) cannot be accurately modelled. Here we propose to capture the TIR by scanning of a sub-resolution sized absorber. Significant improvement of spatial resolution and depth uniformity is demonstrated over 3 mm range, outperforming delay-and-sum and model-based reconstruction implementations. Reconstruction performance is validated by imaging subcutaneous murine vasculature and human skin in vivo. The proposed experimental calibration and reconstruction paradigm facilitates quantitative inversions while averting complex physics-based simulations. It can readily be applied to other imaging modalities employing TIR-based reconstructions.