An Automatic 3-D Ultrasound and Photoacoustic Combined Imaging System for Human Inflammatory Arthritis.

Aiming at a point-of-care device for rheumatology clinics, we developed an automatic 3-D imaging system combining the emerging photoacoustic (PA) imaging with conventional Doppler ultrasound (US) for detecting human inflammatory arthritis. This system is based on a commercial-grade GE HealthCare (GEHC, Chicago, IL, USA) Vivid E95 US machine and a Universal Robot UR3 robotic arm. This system automatically locates the patient's finger joints from a photograph taken by an overhead camera powered by an automatic hand joint identification method, followed by the robotic arm moving the imaging probe to the targeted joint to scan and obtain 3-D PA and Doppler US images. The GEHC US machine was modified to enable high-speed, high-resolution PA imaging while maintaining the features available on the system. The commercial-grade image quality and the high sensitivity in detecting inflammation in peripheral joints via PA technology hold great potential to significantly benefit clinical care of inflammatory arthritis in a novel way.

Longitudinal volumetric assessment of inflammatory arthritis via photoacoustic imaging and Doppler ultrasound imaging.

Aiming at clinical translation, we developed an automatic 3D imaging system combining the emerging photoacoustic imaging with conventional Doppler ultrasound for detecting inflammatory arthritis. This system was built with a GE HealthCare (GEHC) Vivid™ E95 ultrasound system and a Universal Robot UR3 robotic arm. In this work, the performance of this system was examined with a longitudinal study utilizing a clinically relevant adjuvant induced arthritis (AIA) murine model. After adjuvant injection, daily imaging of the rat ankle joints was conducted until joint inflammation was obvious based on visual inspection. Processed imaging results and statistical analyses indicated that both the hyperemia (enhanced blood volume) detected by photoacoustic imaging and the enhanced blood flow detected by Doppler ultrasound reflected the progress of joint inflammation. However, photoacoustic imaging, by leveraging the highly sensitive optical contrast, detected inflammation earlier than Doppler ultrasound, and also showed changes that are more statistically significant. This side-by-side comparison between photoacoustic imaging and Doppler ultrasound using the same commercial grade GEHC ultrasound machine demonstrates the advantage and potential value of the emerging photoacoustic imaging for rheumatology clinical care of arthritis.

Glassfrogs conceal blood in their liver to maintain transparency.

Transparency in animals is a complex form of camouflage involving mechanisms that reduce light scattering and absorption throughout the organism. In vertebrates, attaining transparency is difficult because their circulatory system is full of red blood cells (RBCs) that strongly attenuate light. Here, we document how glassfrogs overcome this challenge by concealing these cells from view. Using photoacoustic imaging to track RBCs in vivo, we show that resting glassfrogs increase transparency two- to threefold by removing ~89% of their RBCs from circulation and packing them within their liver. Vertebrate transparency thus requires both see-through tissues and active mechanisms that "clear" respiratory pigments from these tissues. Furthermore, glassfrogs' ability to regulate the location, density, and packing of RBCs without clotting offers insight in metabolic, hemodynamic, and blood-clot research.

Nomograms for prediction of breast cancer in breast imaging reporting and data system (BI-RADS) ultrasound category 4 or 5 lesions: A single-center retrospective study based on radiomics features.

Purpose: To develop nomograms for predicting breast malignancy in BI-RADS ultrasound (US) category 4 or 5 lesions based on radiomics features. Methods: Between January 2020 and January 2022, we prospectively collected and retrospectively analyzed the medical records of 496 patients pathologically proven breast lesions in our hospital. The data set was divided into model training group and validation testing group with a 75/25 split. Radiomics features were obtained using the PyRadiomics package, and the radiomics score was established by least absolute shrinkage and selection operator regression. A nomogram was developed for BI-RADS US category 4 or 5 lesions according to the results of multivariate regression analysis from the training group. Result: The AUCs of radiomics score consisting of 31 US features was 0.886. The AUC of the model constructed with radiomics score, patient age, lesion diameter identified by US and BI-RADS category involved was 0.956 (95% CI, 0.910-0.972) for the training group and 0.937 (95% CI, 0.893-0.965) for the validation cohort. The calibration curves showed good agreement between the predictions and observations. Conclusions: Both nomogram and radiomics score can be used as methods to assist radiologists and clinicians in predicting breast malignancy in BI-RADS US category 4 or 5 lesions.

Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy.

High-speed high-resolution imaging of the whole-brain hemodynamics is critically important to facilitating neurovascular research. High imaging speed and image quality are crucial to visualizing real-time hemodynamics in complex brain vascular networks, and tracking fast pathophysiological activities at the microvessel level, which will enable advances in current queries in neurovascular and brain metabolism research, including stroke, dementia, and acute brain injury. Further, real-time imaging of oxygen saturation of hemoglobin (sO2) can capture fast-paced oxygen delivery dynamics, which is needed to solve pertinent questions in these fields and beyond. Here, we present a novel ultrafast functional photoacoustic microscopy (UFF-PAM) to image the whole-brain hemodynamics and oxygenation. UFF-PAM takes advantage of several key engineering innovations, including stimulated Raman scattering (SRS) based dual-wavelength laser excitation, water-immersible 12-facet-polygon scanner, high-sensitivity ultrasound transducer, and deep-learning-based image upsampling. A volumetric imaging rate of 2 Hz has been achieved over a field of view (FOV) of 11 × 7.5 × 1.5 mm3 with a high spatial resolution of ~10 µm. Using the UFF-PAM system, we have demonstrated proof-of-concept studies on the mouse brains in response to systemic hypoxia, sodium nitroprusside, and stroke. We observed the mouse brain's fast morphological and functional changes over the entire cortex, including vasoconstriction, vasodilation, and deoxygenation. More interestingly, for the first time, with the whole-brain FOV and micro-vessel resolution, we captured the vasoconstriction and hypoxia simultaneously in the spreading depolarization (SD) wave. We expect the new imaging technology will provide a great potential for fundamental brain research under various pathological and physiological conditions.

Detection of weak optical absorption by optical-resolution photoacoustic microscopy.

Optical-resolution photoacoustic microscopy (OR-PAM) is one of the major implementations of photoacoustic (PA) imaging. With tightly focused optical illumination and high-frequency ultrasound detection, OR-PAM provides micrometer-level resolutions as well as high sensitivity to optical absorption contrast. Traditionally, it is assumed that the detected PA signal in OR-PAM has a linear dependence on the target's optical absorption coefficient, which is the basis for quantitative functional and molecular PA imaging. In this paper, we demonstrate that, due to the limited detection bandwidth and detection view, OR-PAM can have a strong nonlinear dependence on the optical absorption, especially for weak optical absorption (<10 cm-1). We have investigated the nonlinear dependence in OR-PAM using numerical simulations, analyzed the underlining mechanisms, proposed potential solutions, and experimentally confirmed the results on phantoms. This work may correct a traditional misunderstanding of the OR-PAM signals and improve quantitative accuracy for functional and molecular applications.

Characterization of anthocyanin and proanthocyanidin biosynthesis in two strawberry genotypes during fruit development in response to different light qualities.

LED-based light sources that can provide narrowly-centered spectrum have been frequently applied to manipulate the plant growth, development and metabolism in recent years. This study aimed to find out the effect of different light qualities on the production of anthocyanins and proanthocyanidins. The results showed RL (red light), BL (blue light), RBL (red light: blue light = 1:1) induced the strawberry fruit coloration earlier by increasing the content of total anthocyanins as a result of high expression of related genes, which was also concluded from a⁎, C⁎, h° values in 'Tokun' at 28 DAF, and RBL significantly promoted anthocyanin and proanthocyanidin biosynthesis in these two strawberry genotypes during fruit development. Simultaneously, the contents of anthocyanins and proanthocyanidins in 'Toyonaka' were also remarkably upregulated by BL and RL, respectively, indicating different strawberry genotypes to some extent probably had a distinct response to light quality. Hence, genotype factor should be taken into consideration when supplement of light quality was used as practical application in strawberry cultivation. Taken together, this study provided an insight into a further understanding of roles of light quality in the color formation for strawberry and a potential means to increase the health-related values of strawberry through altering the anthocyanin and proanthocyanidin contents of the fruit.

Evaluation of suitable reference genes for qRT-PCR normalization in strawberry (Fragaria × ananassa) under different experimental conditions.

BACKGROUND: Strawberry has received much attention due to its nutritional value, unique flavor, and attractive appearance. The availability of the whole genome sequence and multiple transcriptome databases allows the great possibility to explore gene functions, comprehensively. Gene expression profiles of a target gene can provide clues towards the understanding of its biological function. Quantitative real-time PCR (qRT-PCR) is a preferred method for rapid quantification of gene expression. The accuracy of the results obtained by this method requires the reference genes with consistently stable expression to normalize its data. RESULTS: In present study, the expression stability of seven candidate reference genes in diverse sample subsets of different tissues and fruit developmental stages, and plant subjected to light quality and low temperature treatments was evaluated using three statistical algorithms, geNorm, NormFinder, and BestKeeper. Our data indicated that the expression stability of reference genes varied under different experimental conditions. Overall, DBP, HISTH4, ACTIN1 and GAPDH expressed much more stably. PIRUV, ACTIN2 and 18S were not recommended for normalization in given experimental conditions due to low stability. In addition, the relative expression pattern of HY5 (ELONGATED HYPOCOTYL5) was conducted to further confirm the reliability of the reference genes, which demonstrated the correct adoption of reference genes was of great importance in qRT-PCR analysis. CONCLUSIONS: Expression stability of reference genes from strawberry varied across selected experimental conditions. Systematic validation of reference genes prior to calculation of target gene expression level should be done to improve the accuracy and consistency of qRT-PCR analysis.