Photoacoustic/ultrasound Research Articles

Machine learning radiomics based on intra and peri tumor PA/US images distinguish between luminal and non-luminal tumors in breast cancers

PurposeThis study aimed to evaluate a radiomics model using Photoacoustic/ultrasound (PA/US) imaging at intra and peri-tumoral area to differentiate Luminal and non-Luminal breast cancer (BC) and to determine the optimal peritumoral area for accurate classification. Materials and methodsFrom February 2022 to April 2024, this study continuously collected 322 patients at Shenzhen People’s Hospital, using standardized conditions for PA/US imaging of BC. Regions of interest were delineated using ITK-SNAP, with peritumoral regions of 2 mm, 4 mm, and 6 mm automatically expanded using code from the Pyradiomic package. Feature extraction was subsequently performed using Pyradiomics. The study employed Z-score normalization, Spearman correlation for feature correlation, and LASSO regression for feature selection, validated through 10-fold cross-validation. The radiomics model integrated intra and peri-tumoral area, evaluated by receiver operating characteristic curve(ROC), Calibration and Decision Curve Analysis(DCA). ResultsWe extracted and selected features from intratumoral and peritumoral PA/US images regions at 2 mm, 4 mm, and 6 mm. The comprehensive radiomics model, integrating these regions, demonstrated enhanced diagnostic performance, especially the 4 mm model which showed the highest area under the curve(AUC):0.898(0.78–1.00) and comparably high accuracy (0.900) and sensitivity (0.937). This model outperformed the standalone clinical model and combined clinical-radiomics model in distinguishing between Luminal and non-Luminal BC, as evidenced in the test set results. ConclusionThis study developed a radiomics model integrating intratumoral and peritumoral at 4 mm region PA/US model, enhancing the differentiation of Luminal from non-Luminal BC. It demonstrated the diagnostic utility of peritumoral characteristics, reducing the need for invasive biopsies and aiding chemotherapy planning, while emphasizing the importance of optimizing tumor surrounding size for improved model accuracy.

Illumination-adjustable photoacoustic and harmonic ultrasound for tracking magnetically driven microrobots.

The development of microrobots for biomedical applications has enabled tasks such as targeted drug delivery, minimally invasive surgeries, and precise diagnostics. However, effective in vivo navigation and control remain challenging due to their small size and complex body environment. Photoacoustic (PA) and ultrasound (US) imaging techniques, which offer high contrast, high resolution, and deep tissue penetration, are integrated to enhance microrobot visualization and tracking. Traditional imaging systems have a narrow effective illumination area, suffer from severe reflection artifacts, and are affected by strong electromagnetic fields. To address this, we present an illumination-adjustable PA and harmonic US imaging system with a customized pushrod mechanism for real-time focus adjustment. Experiments demonstrate high-resolution imaging and accurate microrobot positioning, showcasing the potential for biomedical applications, especially in minimally invasive procedures.

Deep learning combined with attention mechanisms to assist radiologists in enhancing breast cancer diagnosis: a study on photoacoustic imaging.

Accurate prediction of breast cancer (BC) is essential for effective treatment planning and improving patient outcomes. This study proposes a novel deep learning (DL) approach using photoacoustic (PA) imaging to enhance BC prediction accuracy. We enrolled 334 patients with breast lesions from Shenzhen People's Hospital between January 2022 and January 2024. Our method employs a ResNet50-based model combined with attention mechanisms to analyze photoacoustic ultrasound (PA-US) images. Experiments demonstrated that the PAUS-ResAM50 model achieved superior performance, with an AUC of 0.917 (95% CI: 0.884 -0.951), sensitivity of 0.750, accuracy of 0.854, and specificity of 0.920 in the training set. In the testing set, the model maintained high performance with an AUC of 0.870 (95% CI: 0.778-0.962), sensitivity of 0.786, specificity of 0.872, and accuracy of 0.836. Our model significantly outperformed other models, including PAUS-ResNet50, BMUS-ResAM50, and BMUS-ResNet50, as validated by the DeLong test (p < 0.05 for all comparisons). Additionally, the PAUS-ResAM50 model improved radiologists' diagnostic specificity without reducing sensitivity, highlighting its potential for clinical application. In conclusion, the PAUS-ResAM50 model demonstrates substantial promise for optimizing BC diagnosis and aiding radiologists in early detection of BC.

In Vivo Photoacoustic Ultrasound (PAUS) Assay for Monitoring Tendon Collagen Compositional Changes during Injury and Healing.

Tendon injury and healing involve significant changes to tissue biology and composition. Current techniques often require animal sacrifice or tissue destruction, limiting assessment of dynamic changes in tendons, including treatment response, disease development, rupture risk, and healing progression. Changes in tendon composition, such as altered collagen content, can significantly impact tendon mechanics and function. Analyses of compositional changes typically require ex vivo techniques with animal sacrifice or destruction of the tissue. In vivo evaluation of tendons is critical for longitudinal assessment. We hypothesize that photoacoustic ultrasound detects differences in collagen concentration throughout healing. We utilized photoacoustic ultrasound, a hybrid imaging modality that combines ultrasound and laser-induced photoacoustic signals to create detailed and high-resolution images of tendons, to identify its endogenous collagen composition. We correlated the photoacoustic signal to picrosirius red staining. The results show that the photoacoustic ultrasound-estimated collagen content in tendons correlates well with picrosirius red staining. This study demonstrates that photoacoustic ultrasound can assess injury-induced compositional changes within tendons and is the first study to image these targets in rat Achilles tendon in vivo.

Multimodal PA/US imaging in Rheumatoid Arthritis: Enhanced correlation with clinical scores

BackgroundAccurate assessment of Rheumatoid Arthritis (RA) activity remains a challenge. Multimodal photoacoustic/ultrasound (PA/US) joint imaging emerges as a novel imaging modality capable of depicting microvascularization and oxygenation levels in inflamed joints associated with RA. However, the scarcity of large-scale studies limits the exploration of correlating joint oxygenation status with disease activity. ObjectiveThis study aimed to explore the correlation between multimodal PA/US imaging scores and RA disease activity, assessing its clinical applicability in managing RA. MethodsIn this study, we recruited 111 patients diagnosed with RA and conducted examinations of seven small joints on their clinically dominant side using a PA/US imaging system. The PA and power Doppler ultrasound (PDUS) signals were semi-quantitatively assessed using a 0–3 grading system. The cumulative scores for PA and PDUS across these seven joints (PA-sum and PDUS-sum) were calculated. Relative oxygen saturation (So2) values of inflamed joints on the clinically dominant side were measured, and categorized into four distinct PA+So2 patterns. The correlation between PA/US imaging scores and disease activity indices was systematically evaluated. ResultsAnalysis of 777 small joints in 111 patients revealed that the PA-sum scores exhibited a strong positive correlation with standard clinical scores for RA, including DAS28 [ESR] (ρ = 0.682), DAS28 [CRP] (ρ = 0.683), CDAI (ρ = 0.738), and SDAI (ρ = 0.739), all with p < 0.001. These correlations were superior to those of the PDUS-sum scores (DAS28 [ESR] ρ = 0.559, DAS28 [CRP] ρ = 0.555, CDAI ρ = 0.575, SDAI ρ = 0.581, p < 0.001). Significantly, in patients with higher PA-sum scores, notable differences were observed in the erythrocyte sedimentation rate (ESR) (p < 0.01) and swollen joint count 28 (SJC28) (p < 0.01) between hypoxia and intermediate groups. Notably, RA patients in the hypoxia group exhibited higher clinical scores in certain clinical indices. ConclusionMulti-modal PA/US imaging introduces potential advancements in RA assessment, especially regarding So2 evaluations in synovial tissues and associated PA scores. However, further studies are warranted, particularly with more substantial sample sizes and in multi-center settings. SummaryThis study utilized multi-modal PA/US imaging to analyze Rheumatoid Arthritis (RA) patients' synovial tissues and affected joints. When juxtaposed with traditional PDUS imaging, the PA approach demonstrated enhanced sensitivity, especially concerning detecting small vessels in thickened synovium and inflamed tendon sheaths. Furthermore, correlations between the derived PA scores, PA+So2 patterns, and standard clinical RA scores were observed. These findings suggest that multi-modal PA/US imaging could be a valuable tool in the comprehensive assessment of RA, offering insights not only into disease activity but also into the oxygenation status of synovial tissues. However, as promising as these results are, further investigations, especially in larger and diverse patient populations, are imperative. Key points⸸ Multi-modal PA/US Imaging in RA: This novel technique was used to assess the So2 values in synovial tissues and determine PA scores of affected RA joints.⸸ Correlation significantly with Clinical RA Scores: Correlations significantly were noted between PA scores, PA+So2 patterns, and standard clinical RA metrics, hinting at the potential clinical applicability of the technique.

High-frequency photoacoustic and ultrasound imaging for skin evaluation: Pilot study for the assessment of a chemical burn.

Skin architecture and its underlying vascular structure could be used to assess the health status of skin. A non-invasive, high resolution and deep imaging modality able to visualize skin subcutaneous layers and vasculature structures could be useful for determining and characterizing skin disease and trauma. In this study, a multispectral high-frequency, linear array-based photoacoustic/ultrasound (PAUS) probe is developed and implemented for the imaging of rat skin in vivo. The study seeks to demonstrate the probe capabilities for visualizing the skin and its underlying structures, and for monitoring changes in skin structure and composition during a 5-day course of a chemical burn. We analayze composition of lipids, water, oxy-hemoglobin, and deoxy-hemoglobin (for determination of oxygen saturation) in the skin tissue. The study successfully demonstrated the high-frequency PAUS imaging probe was able to provide 3D images of the rat skin architecture, underlying vasculature structures, and oxygen saturation, water, lipids and total hemoglobin.

Video-rate endocavity photoacoustic/harmonic ultrasound imaging with miniaturized light delivery.

Endocavity ultrasound (US) imaging is a frequently employed diagnostic technique in gynecology and urology for the assessment of male and female genital diseases that present challenges for conventional transabdominal imaging. The integration of photoacoustic (PA) imaging with clinical US imaging has displayed promising outcomes in clinical research. Nonetheless, its application has been constrained due to size limitations, restricting it to spatially confined locations such as vaginal or rectal canals. This study presents the development of a video-rate (20Hz) endocavity PA/harmonic US imaging (EPAUSI) system. The approach incorporates a commercially available endocavity US probe with a miniaturized laser delivery unit, comprised of a single large-core fiber and a line beamshaping engineered diffuser. The system facilitates real-time image display and subsequent processing, including angular energy density correction and spectral unmixing, in offline mode. The spatial resolutions of the concurrently acquired PA and harmonic US images were measured at and in the radial direction, respectively, and 1.22deg and 1.50deg in the angular direction, respectively. Furthermore, the system demonstrated its capability in multispectral PA imaging by successfully distinguishing two clinical dyes in a tissue-mimicking phantom. Its rapid temporal resolution enabled the capture of kinetic dye perfusion into an ex vivo porcine ovary through the depth of porcine uterine tissue. EPAUSI proved its clinical viability by detecting pulsating hemodynamics in the male rat's prostate in vivo and accurately classifying human blood vessels into arteries and veins based on measurements. Our proposed EPAUSI system holds the potential to unveil previously overlooked indicators of vascular alterations in genital cancers or endometriosis, addressing pressing requirements in the fields of gynecology and urology.

Correlation between oxygenation status of extra-synovial tissue of wrist and disease activity in rheumatoid arthritis: a photoacoustic imaging study.

Rheumatoid arthritis (RA) is characterized by hypoxia in the synovial tissue. While photoacoustic imaging (PA) offers a method to evaluate tissue oxygenation in RA patients, studies exploring the link between extra-synovial tissue of wrist oxygenation and disease activity remain scarce. We aimed to assess synovial oxygenation in RA patients using a multimodal photoacoustic-ultrasound (PA/US) imaging system and establish its correlation with disease activity. A retrospective study was conducted on 111 patients with RA and 72 healthy controls from 2022 to 2023. Dual-wavelength PA imaging quantified oxygen saturation (So2) levels in the synovial membrane and peri-wrist region. Oxygenation states were categorised as hyperoxia, intermediate oxygenation, and hypoxia based on So2 values. The association between oxygenation levels and the clinical disease activity index was evaluated using a one-way analysis of variance, complemented by the Kruskal-Wallis test with Bonferroni adjustment. Of the patients with RA, 39 exhibited hyperoxia, 24 had intermediate oxygenation, and 48 had hypoxia in the wrist extra-synovial tissue. All of the control participants exhibited the hyperoxia status. Oxygenation levels in patients with RA correlated with clinical metrics. Patients with intermediate oxygenation had a lower disease activity index compared with those with hypoxia and hyperoxia. A significant correlation exists between wrist extra-synovial tissue oxygenation and disease activity in patients with RA.

Assessment of Oxygen Saturation in Breast Lesions Using Photoacoustic Imaging: Correlation With Benign and Malignant Disease

BackgroundHypoxia is a hallmark of breast cancer (BC). Photoacoustic (PA) imaging, based on the use of laser-generated ultrasound (US), can detect oxygen saturation (So2) in the tissues of breast lesion patients. PurposeTo measure the oxygenation status of tissue in and on both sides of the lesion in breast lesion participants using a multimodal Photoacoustic/ultrasound (PA/US) imaging system and to determine the correlation between So2 measured by PA imaging and benign or malignant disease. Materials and MethodsMultimodal PA/US imaging and gray-scale US (GSUS) of breast lesion was performed in consecutive breast lesion participants imaged in the US Outpatient Clinic between 2022 and 2023. Dual-wavelength PA imaging was used to measure the So2 value inside the lesion and on both sides of the tissue, and to distinguish benign from malignant lesions based on the So2 value. The ability of So2 to distinguish benign from malignant breast lesions was evaluated by the receiver operating characteristic curve (ROC) and the De-Long test. ResultsA total of 120 breast lesion participants (median age, 42.5 years) were included in the study. The malignant lesions exhibited lower So2 levels compared to benign lesions (malignant: 71.30%; benign: 83.81%; P < .01). Moreover, PA/US imaging demonstrates superior diagnostic results compared to GSUS, with an area under the curve (AUC) of 0.89 versus 0.70, sensitivity of 89.58% versus 85.42%, and specificity of 86.11% versus 55.56% at the So2 cut-off value of 78.85 (P < .001). The false positive rate in GSUS reduced by 30.75%, and the false negative rate diminished by 4.16% with PA /US diagnosis. Finally, the So2 on both sides tissues of malignant lesions are lower than that of benign lesions (P < .01). ConclusionPA imaging allows for the assessment of So2 within the lesions of breast lesion patients, thereby facilitating a superior distinction between benign and malignant lesions.

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.

Photoacoustic/ultrasonic dual-mode imaging for monitoring angiogenesis and synovial erosion in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the formation of new vessels, synovial proliferation and destruction of articular cartilage. However, characteristic early diagnostic and therapeutic monitoring methods are still lacking. We report a study using a photoacoustic/ultrasound (PA/US) dual-mode imaging for RA disease. By establishing a collagen-induced (CIA) RA mouse model to classify disease states based on a subjective grading system, PA/US imaging allows real-time assessment of synovial erosion and vascular opacification within the knee joint in different disease states at high spatial resolution. The system also quantitatively monitors subcutaneous vascular physiology and morphology in the hind paw of mice, measuring the area and photoacoustic signal intensity of vascular proliferation and showing a positive correlation with disease grading. Compared to traditional subjective scoring of arthritis severity, the PA/US imaging is more sensitive i.e., vascular signals and synovial erosion can be observed early in the course of arthritis.

Validation of photoacoustic/ultrasound dual imaging in evaluating blood oxygen saturation.

Photoacoustic imaging (PAI) was performed to evaluate oxygen saturation (sO2) of blood-mimicking phantoms, femoral arteries in beagles, and radial arteries in humans at various sO2 plateaus. The accuracy (root mean square error, RMSE) of PAI sO2 compared with reference sO2 was calculated. In blood-mimicking phantoms, PAI achieved an accuracy of 1.49% and a mean absolute error (MAE) of 1.09% within 25 mm depth, and good linearity (R = 0.968; p < 0.001) was obtained between PAI sO2 and reference sO2. In canine femoral arteries, PAI achieved an accuracy of 2.16% and an MAE of 1.58% within 8 mm depth (R = 0.965; p < 0.001). In human radial arteries, PAI achieved an accuracy of 3.97% and an MAE of 3.28% in depth from 4 to 14 mm (R = 0.892; p < 0.001). For PAI sO2 evaluation at different depths in healthy volunteers, the RMSE accuracy of PAI sO2 increased from 2.66% to 24.96% with depth increasing from 4 to 14 mm. Through the multiscale method, we confirmed the feasibility of the hand-held photoacoustic/ultrasound (PA/US) in evaluating sO2. These results demonstrate the potential clinical value of PAI in evaluating blood sO2. Consequently, protocols for verifying the feasibility of medical devices based on PAI may be established.

Acoustic-resolution-based spectroscopic photoacoustic endoscopy towards molecular imaging in deep tissues.

Due to many technical difficulties, the study of molecular photoacoustic endoscopic (PAE) imaging in deep tissues is limited. In this work, we have set up a multimodal acoustic-resolution-based PAE (AR-PAE) system to image the rabbit rectum and preliminarily explored the potential of molecular PAE for deep-seated targets in proof-of-concept. We developed an improved back-projection (IBP) algorithm for focused detection over the centimeter-scale imaging depth. We also developed a deep-learning-based algorithm to remove the electrical noise from the step motor to prevent data averaging for reduced scanning time. We injected a dose of indocyanine green (ICG) near the rabbit rectum and compared 2D and 3D photoacoustic/ultrasound (PA/US) images at different wavelengths. We proposed incorporating a small camera to guide the slow PA/US endoscopic scan. Results show that this system has achieved a lateral resolution of about 0.77/0.65 mm for PA/US images with a signal-to-noise ratio (SNR) of 25/38 dB at an imaging depth of 1.4 cm. We found that the rectum wall and the ICG can be well distinguished spectroscopically. Results also show that the PA images at 532 nm have higher signal intensity and reflection artifacts from pelvic tendons and bones than those at longer wavelengths such as 800 nm. The proposed methods and the intuitive findings in this work may guide and promote the development of high-penetration molecular PAE.

A Feasible Multimodal Photoacoustic Imaging Approach for Evaluating the Clinical Symptoms of Inflammatory Arthritis.

Numerous traditional medical imaging methods, including computed tomography with X-rays, positron emission tomography (PET), and magnetic resonance imaging (MRI), are utilized frequently in medical settings to screen for illnesses, diagnose patients, and track the effectiveness of treatments. When examining bone protrusions, CT is preferred over MRI for scanning connective tissue. Although the picture quality of PET is inferior to that of CT and MR, it is outstanding for detecting the molecular markers and metabolic functions of illnesses. To give high-resolution structural pictures and improved ailment sensitivity and specificity within another image, multimodal data and substantial therapeutic influence on advanced diagnostics and therapeutics have been used. The goal was to evaluate the clinical significance of multimodal photoacoustic/ultrasound (PA/US) articular imaging scoring, a cutting-edge image technique that may show the microvessels and oxygen levels of rheumatoid arthritis-related inflamed joints (RA). The PA/US imaging technology analyzed seven tiny joints. The PA and power Doppler (PD) impulses were semiquantified using a 0–3 grading scale, and the averages of the PA and PD scores for the seven joints are computed. Three PA+SO2 types were found determined by the relative oxygen levels (SO2) measurements of the affected joints. Researchers evaluated the relationships between the disease activity ratings and the PA/US imaging ratings. The PA scores and medical ratings that reflect the extent of the pain have strong relationships with each other, as do the PA+SO2 combinations. PA may be clinically useful in assessing RA. Thus, the research evaluated the clinical symptoms of inflammatory arthritis using a multimodal photoacoustic image process.

Handheld volumetric photoacoustic/ultrasound imaging using an internal scanning mechanism

Photoacoustic/ultrasound (PA/US) dual-modality imaging has been evolving rapidly for the last two decades. Handheld PA/US probes with different implementations have attracted particular attention due to their convenience and high applicability. However, developing a volumetric dual-modality PA/US imaging probe with a compact design remains a challenge. Here, we develop a handheld volumetric PA/US imaging probe with a special light-ultrasound coupling design and an internal scanning mechanism. A coaxial design for the excitation and detection paths in a customized 3D-printed housing with a size of 110 × 90 × 64 mm3 is proposed to optimize the signal-to-noise ratio (SNR) of the handheld probe for deep tissue imaging. Two parallel and synchronously rotational acoustic reflectors allow for volumetric imaging with an effective field of view (FOV) of more than 30 mm × 20 mm × 8 mm. In addition to simulation and phantom validations, in vivo human trials are successfully carried out, demonstrating the high imaging quality and stability of the system for potential clinical translations.

Multifunctional liposome for photoacoustic/ultrasound imaging-guided chemo/photothermal retinoblastoma therapy

Retinoblastoma (RB) is a malignant intraocular neoplasm that occurs in children. Diagnosis and therapy are frequently delayed, often leading to metastasis, which necessitates effective imaging and treatment. In recent years, the use of nanoplatforms allowing both imaging and targeted treatment has attracted much attention. Herein, we report a novel nanoplatform folate-receptor (FR) targeted laser-activatable liposome termed FA-DOX-ICG-PFP@Lip, which is loaded with doxorubicin (DOX)/indocyanine green (ICG) and liquid perfluoropentane (PFP) for photoacoustic/ultrasound (PA/US) dual-modal imaging-guided chemo/photothermal RB therapy. The dual-modal imaging capability, photothermal conversion under laser irradiation, biocompatibility, and antitumor ability of these liposomes were appraised. The multifunctional liposome showed a good tumor targeting ability and was efficacious as a dual-modality contrast agent both in vivo and in vitro. When laser-irradiated, the liposome converted light energy to heat. This action caused immediate destruction of tumor cells, while simultaneously initiating PFP phase transformation to release DOX, resulting in both photothermal and chemotherapeutic antitumor effects. Notably, the FA-DOX-ICG-PFP@Lip showed good biocompatibility and no systemic toxicity was observed after laser irradiation in RB tumor-bearing mice. Hence, the FA-DOX-ICG-PFP@Lip shows great promise for dual-modal imaging-guided chemo/photothermal therapy, and may have significant value for diagnosing and treating RB.

Noninvasive Dual-Modality Photoacoustic-Ultrasonic Imaging to Detect Mammalian Embryo Abnormalities after Prenatal Exposure to Methylmercury Chloride (MMC): A Mouse Study.

Background:Severe environmental pollution and contaminants left in the environment due to the abuse of chemicals, such as methylmercury, are associated with an increasing number of embryonic disorders. Ultrasound imaging has been widely used to investigate embryonic development malformation and dysorganoplasia in both research and clinics. However, this technique is limited by its low contrast and lacking functional parameters such as the ability to measure blood oxygen saturation () and hemoglobin content (HbT) in tissues, measures that could be early vital indicators for embryonic development abnormality. Herein, we proposed combining two highly complementary techniques into a photoacoustic-ultrasound (PA-US) dual-modality imaging approach to noninvasively detect early mouse embryo abnormalities caused by methylmercury chloride (MMC) in real time.Objectives:This study aimed to assess the use of PA-US dual-modality imaging for noninvasive detection of embryonic toxicity at different stages of growth following prenatal MMC exposure. Additionally, we compared the PA-US imagining results to traditional histological methods to determine whether this noninvasive method could detect early developmental defects in utero.Methods:Different dosages of MMC were administrated to pregnant mice by gavage to establish models of different levels of embryonic malformation. Ultrasound, photoacoustic signal intensity (PSI), blood oxygen saturation (), and hemoglobin content (HbT) were quantified in all experimental groups. Furthermore, the embryos were sectioned and examined for pathological changes.Results:Using PA-US imaging, we detected differences in PSI, , HbT, and heart volume at embryonic day (E)14.5 and E11.5 for low and high dosages of MMC, respectively. More important, our results showed that differences between control and treated embryos identified by in utero PA-US imaging were consistent with those identified in ex vivo embryos using histological methods.Conclusion:Our results suggest that noninvasive dual-modality PA-US is a promising strategy for detecting developmental toxicology in the uterus. Overall, this study presents a new approach for detecting embryonic toxicities, which could be crucial in clinics when diagnosing aberrant embryonic development. https://doi.org/10.1289/EHP8907

Suite of 3D test objects for performance assessment of hybrid photoacoustic-ultrasound breast imaging systems

.SignificanceDuring the development and early testing phases of new photoacoustic (PA) breast imaging systems, several choices need to be made in aspects of system design and measurement sequences. Decision-making can be complex for state-of-the-art systems such as 3D hybrid photoacoustic-ultrasound (PA-US) breast imagers intended for multispectral quantitative imaging. These systems have a large set of design choices and system settings that affect imaging performance in different ways and often require trade-offs. Decisions have to be made carefully as they can strongly influence the imaging performance.AimA systematic approach to assess the influence of various choices on the imaging performance in carefully controlled laboratory situations is crucial before starting with human studies. Test objects and phantoms are used for first imaging studies, but most reported structures have a 2D geometry and are not suitable to assess all the image quality characteristics (IQCs) of 3D hybrid PA-US systems.ApproachOur work introduces a suite of five test objects designed for hybrid PA-US systems with a 3D detection aperture. We present the test object designs and production protocols and explain how they can be used to study various performance measures. To demonstrate the utility of the developed objects, measurements are made with an existing tomographic PA system.ResultsTwo test objects were developed for measurements of the US detectors’ impulse responses and light distribution on the breast surface. Three others were developed to assess image quality and quantitative accuracy of the PA and US modes. Three of the five objects were imaged to demonstrate their use.ConclusionsThe developed test objects allow one to study influences of various choices in design and system settings. With this, IQCs can be assessed as a function of measurement sequence settings for the PA and US modes in a controlled way. Systematic studies and measurements using these objects will help to optimize various system settings and measurement protocols in laboratory situations before embarking on human studies.

In vivo anatomical imaging of colorectum by tens-of-micron-resolved photoacoustic/ultrasonic endoscope

The existing photoacoustic/ultrasound (PA/US) endoscopes with compromise in lateral resolution were difficult to realize superior anatomical imaging. To obtain comprehensive biological information of the colorectum in a noninvasive manner, a tens-of-micron-resolved PA/US endoscope with a 360° field of view was developed. A coaxial structure, which ensures optical and acoustic foci aligned, was employed, and a PVDF-based focused transducer with a high frequency was applied. The endoscopic system achieved lateral resolutions of 16 μm (PA) and 73 μm (US), and axial resolution of 65 μm. Phantom and ex vivo experiments were performed to estimate the performance of the dual-modality endoscope. In vivo three-dimensional imaging of rabbit colorectum exhibited the intact vascular network at different depths from the mucosa of the colorectal wall to the mesentery, and the structures beneath them. Therefore, in vivo anatomical imaging demonstrates that the tens-of-micron-resolved PA/US endoscope holds great potential in the clinical detection of colorectal diseases.

Motion-compensated noninvasive periodontal health monitoring using handheld and motor-based photoacoustic-ultrasound imaging systems.

Simultaneous visualization of the teeth and periodontium is of significant clinical interest for image-based monitoring of periodontal health. We recently reported the application of a dual-modality photoacoustic-ultrasound (PA-US) imaging system for resolving periodontal anatomy and periodontal pocket depths in humans. This work utilized a linear array transducer attached to a stepper motor to generate 3D images via maximum intensity projection. This prior work also used a medical head immobilizer to reduce artifacts during volume rendering caused by motion from the subject (e.g., breathing, minor head movements). However, this solution does not completely eliminate motion artifacts while also complicating the imaging procedure and causing patient discomfort. To address this issue, we report the implementation of an image registration technique to correctly align B-mode PA-US images and generate artifact-free 2D cross-sections. Application of the deshaking technique to PA phantoms revealed 80% similarity to the ground truth when shaking was intentionally applied during stepper motor scans. Images from handheld sweeps could also be deshaken using an LED PA-US scanner. In ex vivo porcine mandibles, pigmentation of the enamel was well-estimated within 0.1 mm error. The pocket depth measured in a healthy human subject was also in good agreement with our prior study. This report demonstrates that a modality-independent registration technique can be applied to clinically relevant PA-US scans of the periodontium to reduce operator burden of skill and subject discomfort while showing potential for handheld clinical periodontal imaging.