Photoacoustic imaging (PAI) enables the visualization of optical contrast with ultrasonic imaging. It is a field of intense research, with great promise for clinical application. Understanding the ...principles of PAI is important for engineering research and image interpretation.
In this tutorial review, we lay out the imaging physics, instrumentation requirements, standardization, and some practical examples for (junior) researchers, who have an interest in developing PAI systems and applications for clinical translation or applying PAI in clinical research.
We discuss PAI principles and implementation in a shared context, emphasizing technical solutions that are amenable to broad clinical deployment, considering factors such as robustness, mobility, and cost in addition to image quality and quantification.
Photoacoustics, capitalizing on endogenous contrast or administered contrast agents that are approved for human use, yields highly informative images in clinical settings, which can support diagnosis and interventions in the future.
PAI offers unique image contrast that has been demonstrated in a broad set of clinical scenarios. The transition of PAI from a "nice-to-have" to a "need-to-have" modality will require dedicated clinical studies that evaluate therapeutic decision-making based on PAI and consideration of the actual value for patients and clinicians, compared with the associated cost.
Breast cancer is one of the most diagnosed types of cancer worldwide. Volumetric ultrasound breast imaging, combined with MRI can improve lesion detection rate, reduce examination time, and improve ...lesion diagnosis. However, to our knowledge, there are no 3D US breast imaging systems available that facilitate 3D US - MRI image fusion. In this paper, a novel Automated Cone-based Breast Ultrasound System (ACBUS) is introduced. The system facilitates volumetric ultrasound acquisition of the breast in a prone position without deforming it by the US transducer. Quality of ACBUS images for reconstructions at different voxel sizes (0.25 and 0.50 mm isotropic) was compared to quality of the Automated Breast Volumetric Scanner (ABVS) (Siemens Ultrasound, Issaquah, WA, USA) in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and resolution using a custom made phantom. The ACBUS image data were registered to MRI image data utilizing surface matching and the registration accuracy was quantified using an internal marker. The technology was also evaluated in vivo. The phantom-based quantitative analysis demonstrated that ACBUS can deliver volumetric breast images with an image quality similar to the images delivered by a currently commercially available Siemens ABVS. We demonstrate on the phantom and in vivo that ACBUS enables adequate MRI-3D US fusion. To our conclusion, ACBUS might be a suitable candidate for a second-look breast US exam, patient follow-up, and US guided biopsy planning.
Normothermic machine perfusion (NMP) provides a platform for pre-transplant kidney quality assessment that is essential for the use of marginal donor kidneys. Laser speckle contrast imaging (LSCI) ...presents distinct advantages as a real-time and noncontact imaging technique for measuring microcirculation. In this study, we aimed to assess the value of LSCI in visualizing renal cortical perfusion and investigate the additional value of dual-side LSCI measurements compared to single aspect measurement during NMP.
Porcine kidneys were obtained from a slaughterhouse and then underwent NMP. LSCI was used to measure one-sided cortical perfusion in the first 100 min of NMP. Thereafter, the inferior renal artery branch was occluded to induce partial ischemia and LSCI measurements on both ventral and dorsal sides were performed.
LSCI fluxes correlated linearly with the renal blood flow (R
= 0.90, p < 0.001). After renal artery branch occlusion, absence of renal cortical perfusion could be visualized and semiquantified by LSCI. The overall ischemic area percentage of the ventral and dorsal sides was comparable (median interquartile range IQR, 38 24-43% vs. 29 17-46%, p = 0.43), but heterogenous patterns between the two aspects were observed. There was a significant difference in oxygen consumption (mean ± standard deviation SD, 2.57 ± 0.63 vs. 1.83 ± 0.49 mLO
/min/100 g, p < 0.001), urine output (median IQR, 1.3 1.1-1.7 vs. 0.8 0.6-1.3 mL/min, p < 0.05), lactate dehydrogenase (mean ± SD, 768 ± 370 vs. 905 ± 401 U/L, p < 0.05) and AST (mean ± SD, 352 ± 285 vs. 462 ± 383 U/L, p < 0.01) before and after renal artery occlusion, while no significant difference was found in creatinine clearance, fractional excretion of sodium, total sodium reabsorption and histological damage.
LSCI fluxes correlated linearly with renal blood flow during NMP. Renal cortical microcirculation and absent perfusion can be visualized and semiquantified by LSCI. It provides a relative understanding of perfusion levels, allowing for a qualitative comparison between regions in the kidney. Dual-side LSCI measurements are of added value compared to single aspect measurement and renal function markers.
Two of the largest protected areas on earth are U.S. National Monuments in the Pacific Ocean. Numerous claims have been made about the impacts of these protected areas on the fishing industry, but ...there has been no ex post empirical evaluation of their effects. We use administrative data documenting individual fishing events to evaluate the economic impact of the expansion of these two monuments on the Hawaii longline fishing fleet. Surprisingly, catch and catch-per-unit-effort are higher since the expansions began. To disentangle the causal effect of the expansions from confounding factors, we use unaffected control fisheries to perform a difference-in-differences analysis. We find that the monument expansions had little, if any, negative impacts on the fishing industry, corroborating ecological models that have predicted minimal impacts from closing large parts of the Pacific Ocean to fishing.
Sensory systems continually adjust the way stimuli are processed. What are the circuit mechanisms underlying this plasticity? We investigated how synapses in the retina of zebrafish adjust to changes ...in the temporal contrast of a visual stimulus by imaging activity in vivo. Following an increase in contrast, bipolar cell synapses with strong initial responses depressed, whereas synapses with weak initial responses facilitated. Depression and facilitation predominated in different strata of the inner retina, where bipolar cell output was anticorrelated with the activity of amacrine cell synapses providing inhibitory feedback. Pharmacological block of GABAergic feedback converted facilitating bipolar cell synapses into depressing ones. These results indicate that depression intrinsic to bipolar cell synapses causes adaptation of the ganglion cell response to contrast, whereas depression in amacrine cell synapses causes sensitization. Distinct microcircuits segregating to different layers of the retina can cause simultaneous increases or decreases in the gain of neural responses.
Due to the shortage of kidneys donated for transplantation, surgeons are forced to use the organs with an elevated risk of poor function or even failure. Although the existing methods for ...pre-transplant quality evaluation have been validated over decades in population cohort studies across the world, new methods are needed as long as delayed graft function or failure in a kidney transplant occurs. In this study, we explored the potential of utilizing photoacoustic (PA) imaging during normothermic machine perfusion (NMP) as a means of evaluating kidney quality. We closely monitored twenty-two porcine kidneys using 3D PA imaging during a two-hour NMP session. Based on biochemical analyses of perfusate and produced urine, the kidneys were categorized into ‘non-functional’ and ‘functional’ groups. Our primary focus was to quantify oxygenation (sO2) within the kidney cortical layer of depths 2 mm, 4 mm, and 6 mm using two-wavelength PA imaging. Next, receiver operating characteristic (ROC) analysis was performed to determine an optimal cortical layer depth and time point for the quantification of sO2 to discriminate between functional and non-functional organs. Finally, for each depth, we assessed the correlation between sO2 and creatinine clearance (CrCl), oxygen consumption (VO2), and renal blood flow (RBF).
We found that hypoxia of the renal cortex is associated with poor renal function. In addition, the determination of sO2 within the 2 mm depth of the renal cortex after 30 min of NMP effectively distinguishes between functional and non-functional kidneys. The non-functional kidneys can be detected with the sensitivity and specificity of 80% and 85% respectively, using the cut-off point of sO2 < 39%. Oxygenation significantly correlates with RBF and VO2 in all kidneys. In functional kidneys, sO2 correlated with CrCl, which is not the case for non-functional kidneys.
We conclude that the presented technique has a high potential for supporting organ selection for kidney transplantation.
Engulfment of extracellular material by phagocytosis or macropinocytosis depends on the ability of cells to generate specialized cup-shaped protrusions. To effectively capture and internalize their ...targets, these cups are organized into a ring or ruffle of actin-driven protrusion encircling a non-protrusive interior domain. These functional domains depend on the combined activities of multiple Ras and Rho family small GTPases, but how their activities are integrated and differentially regulated over space and time is unknown. Here, we show that the amoeba Dictyostelium discoideum coordinates Ras and Rac activity using the multidomain protein RGBARG (RCC1, RhoGEF, BAR, and RasGAP-containing protein). We find RGBARG uses a tripartite mechanism of Ras, Rac, and phospholipid interactions to localize at the protruding edge and interface with the interior of both macropinocytic and phagocytic cups. There, we propose RGBARG shapes the protrusion by expanding Rac activation at the rim while suppressing expansion of the active Ras interior domain. Consequently, cells lacking RGBARG form enlarged, flat interior domains unable to generate large macropinosomes. During phagocytosis, we find that disruption of RGBARG causes a geometry-specific defect in engulfing rod-shaped bacteria and ellipsoidal beads. This demonstrates the importance of coordinating small GTPase activities during engulfment of more complex shapes and thus the full physiological range of microbes, and how this is achieved in a model professional phagocyte.
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•We identify a new regulator that shapes macropinocytic and phagocytic cups•Shaping protrusions into cups requires differential regulation of Ras and Rac•Cups are organized by integrating interactions with phospholipids and multiple GTPases•Defective cup formation causes a target shape-specific defect in phagocytosis
Forming cup-shaped protrusions allows cells to engulf extracellular fluid and particles by macropinocytosis and phagocytosis, respectively. Buckley et al. identify a new regulator that differentially regulates small GTPases to generate the cup shape. They propose a model whereby this coordinates the shape and allows cells to engulf different shapes.
Series of Eu-apatites were synthesized by precipitation from aqueous solutions with the Eu/Ca atomic ratio from 0.5% to 5% at T = 90 °C. Resulting precipitates were studied using different ...experimental techniques including X-ray powder diffraction, infrared and raman spectroscopy, scanning elecrton microscopy, EDX and photoluminescent spectroscopy.
Eu-doped Ca-deficit nanosized non-stoichiometric hydroxyapatite with high water content has been obtained throughout the experiment. Europium content in the synthesized apatites reaches 0.24 apfu (Eu/Ca = 2.5%). Relations between Eu content is the solution and precipitate have been established. It was shown that Eu-monacite starts to precipitate as secondary phase at Eu/Ca ratio in starting solution 1% or higher. Maximum luminescence is observed in apatite with ∼2% Eu/Ca ratio (which equals to ∼0.2 apfu and corresponds to 3% Eu/Ca ratio in the starting solution). As an important and brand-new result, apatite with 2% Eu/Ca ratio can be considered as the most appropriate material for the producing biolabels for luminescent research in medicine and biology.
•Hydroxyapatites with different amount of Eu3+ (Eu/Ca 0.5–5%) have been synthesized.•Precipitates were studied by XRD, IRS, SEM, EDX and photoluminescent spectroscopy.•Eu/Ca ratio in apatite is less than this ratio in the starting solution.•Eu-monacite occurs as secondary phase at Eu/Ca ratio in solution 1% or higher.•Maximum luminescence is observed in apatite with ∼2% Eu/Ca ratio (3% in solution).
Background
Among available breast biopsy techniques, ultrasound (US)‐guided biopsy is preferable because it is relatively inexpensive and provides live imaging feedback. The availability of magnetic ...resonance imaging (MRI)‐3D US image fusion would facilitate US‐guided biopsy even for US occult lesions to reduce the need for expensive and time‐consuming MRI‐guided biopsy. In this paper, we propose a novel Automated Cone‐based Breast Ultrasound Scanning and Biopsy System (ACBUS‐BS) to scan and biopsy breasts of women in prone position. It is based on a previously developed system, called ACBUS, that facilitates MRI‐3D US image fusion imaging of the breast employing a conical container filled with coupling medium.
Purpose
The purpose of this study was to introduce the ABCUS‐BS system and demonstrate its feasibility for biopsy of US occult lesions.
Method
The biopsy procedure with the ACBUS‐BS comprises four steps: target localization, positioning, preparation, and biopsy. The biopsy outcome can be impacted by 5 types of errors: due to lesion segmentation, MRI‐3D US registration, navigation, lesion tracking during repositioning, and US inaccuracy (due to sound speed difference between the sample and the one used for image reconstruction).
For the quantification, we use a soft custom‐made polyvinyl alcohol phantom (PVA) containing eight lesions (three US‐occult and five US‐visible lesions of 10 mm in diameter) and a commercial breast mimicking phantom with a median stiffness of 7.6 and 28 kPa, respectively. Errors of all types were quantified using the custom‐made phantom. The error due to lesion tracking was also quantified with the commercial phantom.
Finally, the technology was validated by biopsying the custom‐made phantom and comparing the size of the biopsied material to the original lesion size. The average size of the 10‐mm‐sized lesions in the biopsy specimen was 7.00 ± 0.92 mm (6.33 ± 1.16 mm for US occult lesions, and 7.40 ± 0.55 mm for US‐visible lesions).
Results
For the PVA phantom, the errors due to registration, navigation, lesion tracking during repositioning, and US inaccuracy were 1.33, 0.30, 2.12, and 0.55 mm. The total error was 4.01 mm. For the commercial phantom, the error due to lesion tracking was estimated at 1.10 mm, and the total error was 4.11 mm. Given these results, the system is expected to successfully biopsy lesions larger than 8.22 mm in diameter. Patient studies will have to be carried out to confirm this in vivo.
Conclusion
The ACBUS‐BS facilitates US‐guided biopsy of lesions detected in pre‐MRI and therefore might offer a low‐cost alternative to MRI‐guided biopsy. We demonstrated the feasibility of the approach by successfully taking biopsies of five US‐visible and three US‐occult lesions embedded in a soft breast‐shaped phantom.
The visual system transmits information about fast and slow changes in light intensity through separate neural pathways. We used in vivo imaging to investigate how bipolar cells transmit these ...signals to the inner retina. We found that the volume of the synaptic terminal is an intrinsic property that contributes to different temporal filters. Individual cells transmit through multiple terminals varying in size, but smaller terminals generate faster and larger calcium transients to trigger vesicle release with higher initial gain, followed by more profound adaptation. Smaller terminals transmitted higher stimulus frequencies more effectively. Modeling global calcium dynamics triggering vesicle release indicated that variations in the volume of presynaptic compartments contribute directly to all these differences in response dynamics. These results indicate how one neuron can transmit different temporal components in the visual signal through synaptic terminals of varying geometries with different adaptational properties.
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