Diffuse optical tomography for mapping cerebral hemodynamics and functional connectivity in delirium.

INTRODUCTION: Delirium is associated with mortality and new onset dementia, yet the underlying pathophysiology remains poorly understood. Development of imaging biomarkers has been difficult given the challenging nature of imaging delirious patients. Diffuse optical tomography (DOT) offers a promising approach for investigating delirium given its portability and three-dimensional capabilities. METHODS: Twenty-five delirious and matched non-delirious patients (n = 50) were examined using DOT, comparing cerebral oxygenation and functional connectivity in the prefrontal cortex during and after an episode of delirium. RESULTS: Total hemoglobin values were significantly decreased in the delirium group, even after delirium resolution. Functional connectivity between the dorsolateral prefrontal cortex and dorsomedial prefrontal cortex was strengthened post-resolution compared to during an episode; however, this relationship was still significantly weaker compared to controls. DISCUSSION: These findings highlight DOT's potential as an imaging biomarker to measure impaired cerebral oxygenation and functional dysconnectivity during and after delirium. Future studies should focus on the role of cerebral oxygenation in delirium pathogenesis and exploring the etiological link between delirium and dementias. HIGHLIGHTS: We developed a portable diffuse optical tomography (DOT) system for bedside three-dimensional functional neuroimaging to study delirium in the hospital. We implemented a novel DOT task-focused seed-based correlation analysis. DOT revealed decreased cerebral oxygenation and functional connectivity strength in the delirium group, even after resolution of delirium.

The effect of tumor vascular remodeling and immune microenvironment activation induced by radiotherapy: quantitative evaluation with magnetic resonance/photoacoustic dual-modality imaging.

Background: Tumor radiotherapy combined with immunotherapy for solid tumors has been proposed, but tumor vascular structure abnormalities and immune microenvironment often affect the therapeutic effect of tumor, and multimodal imaging technology can provide more accurate and comprehensive information in tumor research. The purpose of this study was to evaluate the dynamic monitoring of tumor blood vessels and microenvironment induced by radiotherapy by magnetic resonance/photoacoustic (MR/PA) imaging, and to explore its application value in radiotherapy combined with immunotherapy. Methods: The tumor-bearing mice were randomly allocated into six groups, which received different doses of radiation therapy (2 Gy ×14 or 8 Gy ×3) and anti-programmed death ligand-1 (PD-L1) antibody for two consecutive weeks. MR/PA imaging was used to noninvasively evaluate the response of tumor to different doses of radiotherapy, combined with histopathological techniques to observe the tumor vessels and microenvironment. Results: The inhibitory effect of high-dose radiotherapy on tumors was significantly greater than that of low-dose radiotherapy, with the MR images revealing that the signal intensity decreased significantly (P<0.05). Compared with those in the other groups, the tumor vascular density decreased significantly (P<0.01), and the vascular maturity index increased significantly in the low-dose group (P<0.05). The PA images showed that the deoxyhemoglobin and total hemoglobin levels decreased and the SO2 level increased after radiation treatment (P<0.05). In addition, the high-dose group had an increased number of tumor-infiltrating lymphocytes (CD4+ T and CD8+ T cells) (P<0.01, P<0.05) and natural killer cells (P<0.001) and increased PD-L1 expression in the tumors (P<0.05). The combination of radiotherapy and immunotherapy increased the survival rate of the mice (P<0.05), and a regimen of an 8 Gy dose of radiation combined with immunotherapy inhibited tumor growth and increased the survival rate of the mice to a greater degree than the 2 Gy radiation dose with immunotherapy combination (P=0.002). Conclusions: Differential fractionation radiotherapy doses exert biological effects on tumor vascular and the immune microenvironment, and MR/PA can be used to evaluate tumor vascular remodeling after radiotherapy, which has certain value for the clinical applications of radiotherapy combined with immunotherapy.

High-resolution imaging in studies of alcohol effect on prenatal development.

Fetal alcohol syndrome represents the leading known preventable cause of mental retardation. FAS is on the most severe side of fetal alcohol spectrum disorders that stem from the deleterious effects of prenatal alcohol exposure. Affecting as many as 1 to 5 out of 100 children, FASD most often results in brain abnormalities that extend to structure, function, and cerebral hemodynamics. The present review provides an analysis of high-resolution imaging techniques that are used in animals and human subjects to characterize PAE-driven changes in the developing brain. Variants of magnetic resonance imaging such as magnetic resonance microscopy, magnetic resonance spectroscopy, diffusion tensor imaging, along with positron emission tomography, single-photon emission computed tomography, and photoacoustic imaging, are modalities that are used to study the influence of PAE on brain structure and function. This review briefly describes the aforementioned imaging modalities, the main findings that were obtained using each modality, and touches upon the advantages/disadvantages of each imaging approach.

Microwave-induced thermoacoustic microscopy based on short-pulse microwave and high-frequency point-focused ultrasonic transducer.

BACKGROUND: As an emerging hybrid imaging modality, microwave-induced thermoacoustic imaging (MITAI) provides high contrast and deep tissue penetration, and has been extensively applied in cancer diagnosis, arthritis detection, and brain research. However, the previous studies had a limited spatial resolution of about 0.45-1.5 mm. PURPOSE: Here, we describe a microwave-induced thermoacoustic microscopy (MITAM) system to help overcome the resolution limitation of current MITAI to image more subtle tissue features. On this basis, this paper applies MITAM to the thin skin and to demonstrate the potential of MITAM in detecting scleroderma. METHODS: To achieve high resolution, short pulse width microwave (pulse width: 70 ns) and high-frequency ultrasonic point-focused transducer (center frequency: 25 MHz) were used to build the MITAM system. Two parallel copper wires with a diameter of 90 µm in the X/Y plane and Y/Z plane were imaged to estimate X/Y/Z resolution. Nine Balb/c mice were randomly divided into three groups and injected with different concentrations of bleomycin to induce scleroderma models. Their ex vivo skins were then imaged by our MITAM system. Visual observations were performed on the 3-dimensional skins MITAM images. And the mean value, Standard deviation, quartile distance, and signal-to-noise ratio were calculated to verify the results of the qualitative observations. Hematoxylin-Eosin (HE) and Masson staining were used to validate the findings of the MITAM. RESULTS: The thickness of each imaged skin was measured to be about 450 µm. As an organ composed of multiple layers of tissues, the skin needs to be imaged at high resolution for the detection of related diseases. The results obtained showed that the improved resolution (68 µm in the Z-axis and 135 µm in the X-axis/Y-axis) of MITAM over conventional MITAI allowed us to differentiate scleroderma skins from normal skins and to identify the severity of scleroderma skins, consistent with the pathological findings of these skins. CONCLUSIONS: The preliminary results obtained indicate that the MITAM can relieve the resolution limitation of traditional MITAI and has the potential to detection scleroderma. However, the transmission-type MITAM mentioned in this paper is difficult to image in vivo due to the narrow area between the antenna and the transducer. In the future, a reflective scanning MITAM will be constructed to detect scleroderma in vivo.

Split Ring Resonator Topology Based Microwave Induced Thermoacoustic Imaging (SRR-MTAI).

Microwave-induced thermoacoustic imaging (MTAI) using low-energy and long-wavelength microwave photons has great potential in detecting deep-seated diseases due to its unique ability of visualizing intrinsic electric properties of tissue in high resolution. However, the low contrast in conductivity between a target (e.g., a tumor) and the surroundings sets a fundamental limit for achieving a high imaging sensitivity, which significantly hinders its biomedical applications. To overcome this limit, we develop a split ring resonator (SRR) topology based MTAI (SRR-MTAI) approach to achieve highly sensitive detection by precise manipulation and efficient delivery of microwave energy. The in vitro experiments show that SRR-MTAI demonstrates an ultrahigh sensitivity of distinguishing a 0.4% difference in saline concentrations and a 2.5-fold enhancement of detecting a tissue target which mimicks a tumor embedded at a depth of 2 cm. The in vivo animal experiments conducted indicate that the imaging sensitivity between a tumor and the surrounding tissue is increased by 3.3-fold using SRR-MTAI. The dramatic enhancement in imaging sensitivity suggests that SRR-MTAI has the potential to open new avenues for MTAI to tackle a variety of biomedical problems that were impossible previously.

A one-step method for quantitative microwave-induced thermoacoustic tomography.

BACKGROUND: Electrical conductivity directly correlates with tissue functional information such as blood and water contents, and quantitative extraction of tissue conductivity is of significant importance for disease detection and diagnosis using microwave-induced thermoacoustic tomography (TAT). OBJECTIVE: The existing quantitative TAT (qTAT) approaches capable of extracting tissue conductivity require two steps for the recovery of conductivity. Such two steps approaches depend on an accurate knowledge of the microwave energy loss distribution in tissue and offer a slow computational convergence rate. The purpose of this study is to develop a new algorithm to reconstruct tissue conductivity with higher reconstruction accuracy and greater computational efficiency. METHODS: We propose an improved qTAT method for direct recovery of tissue conductivity from thermoacoustic data measured along the boundary with only one step without the dependence of microwave energy loss information. The feasibility of our one-step qTAT method is validated in both simulated and tissue-mimicking phantom experiments with single-target and multi-target configurations with different contrast levels. RESULTS: Compared with the previous two-step methods, our one-step qTAT method improves the accuracy of conductivity recovery with approximately one-fold reduction in the mean absolute error (MAE) and root mean square error (RMSE) with p-values greater than 0.05. In addition, the convergence rate is improved by more than two folds for the one-step method. CONCLUSIONS: The study demonstrates that new method can quantitatively reconstruct conductivity of tissue more accurately and efficiently over the existing qTAT methods, leading to potentially enhanced accuracy for disease detection and diagnosis.

Monitoring neonatal brain hemorrhage progression by photoacoustic tomography.

Neonatal brain hemorrhage (NBH) is the most common neurological disorder in neonates and its clinical interventions are very limited. Understanding the pathology of NBH by non-invasive in-vivo characterization of standardized animal models is essential for developing potential treatments. Currently, there is no suitable tool to provide non-invasive, non-ionizing dynamic imaging of neonatal mouse models with high resolution, high contrast, and deep imaging depth. In this study, we implemented a fast 3D photoacoustic tomography (PAT) system suitable for imaging neonatal mouse brains with good image quality and demonstrated its feasibility in non-invasive monitoring of the dynamic process of NBH in the whole neonatal mouse brain. The results present a high resolution and sensitivity for NBH detection. Both morphological and hemodynamic changes of the hematoma were accurately obtained. Our results demonstrated the potential of PAT as a powerful tool for the preclinical study of neonatal brain hemorrhage.

Noninvasive optoacoustic imaging of breast tumor microvasculature in response to radiotherapy.

Detailed insight into the radiation-induced changes in tumor microvasculature is crucial to maximize the efficacy of radiotherapy against breast cancer. Recent advances in imaging have enabled precise targeting of solid lesions. However, intratumoral heterogeneity makes treatment planning and monitoring more challenging. Conventional imaging cannot provide high-resolution observation and longitudinal monitoring of large-scale microvascular in response to radiotherapy directly in deep tissues. Herein, we report on an emerging non-invasive imaging assessment method of morphological and functional tumor microvasculature responses with high spatio-temporal resolution by means of optoacoustic imaging (OAI). In vivo imaging of 4T1 breast tumor response to a conventional fractionated radiotherapy at varying dose (14 × 2 Gy and 3 × 8 Gy) has been performed after 2 weeks following treatment. Remarkably, optoacoustic images can generate richful contrast for the tumor microvascular architecture. Besides, the functional status of tumor microvasculature and tumor oxygenation levels were further estimated using OAI. The results revealed the differential (size-dependent) nature of vascular responses to radiation treatments at varying doses. The vessels exhibited an decrease in their density accompanied by a decline in the number of vascular segments following irradiation, compared to the control group. The measurements further revealed an increase of tumor oxygenation levels for 14 × 2 Gy and 3 × 8 Gy irradiations. Our results suggest that OAI could be used to assess the response to radiotherapy based on changes in the functional and morphological status of tumor microvasculature, which are closely linked to the intratumor microenvironment. OAI assessment of the tumor microenvironment such as oxygenation status has the potential to be applied to precise radiotherapy strategy.

Clinical photoacoustic/ultrasound dual-modal imaging: Current status and future trends.

Photoacoustic tomography (PAT) is an emerging biomedical imaging modality that combines optical and ultrasonic imaging, providing overlapping fields of view. This hybrid approach allows for a natural integration of PAT and ultrasound (US) imaging in a single platform. Due to the similarities in signal acquisition and processing, the combination of PAT and US imaging creates a new hybrid imaging for novel clinical applications. Over the recent years, particular attention is paid to the development of PAT/US dual-modal systems highlighting mutual benefits in clinical cases, with an aim of substantially improving the specificity and sensitivity for diagnosis of diseases. The demonstrated feasibility and accuracy in these efforts open an avenue of translating PAT/US imaging to practical clinical applications. In this review, the current PAT/US dual-modal imaging systems are discussed in detail, and their promising clinical applications are presented and compared systematically. Finally, this review describes the potential impacts of these combined systems in the coming future.

Thin ceramic PZT dual- and multi-frequency pMUT arrays for photoacoustic imaging.

Miniaturized ultrasonic transducer arrays with multiple frequencies are key components in endoscopic photoacoustic imaging (PAI) systems to achieve high spatial resolution and large imaging depth for biomedical applications. In this article, we report on the development of ceramic thin-film PZT-based dual- and multi-frequency piezoelectric micromachined ultrasonic transducer (pMUT) arrays and the demonstration of their PAI applications. With chips sized 3.5 mm in length or 10 mm in diameter, square and ring-shaped pMUT arrays incorporating as many as 2520 pMUT elements and multiple frequencies ranging from 1 MHz to 8 MHz were developed for endoscopic PAI applications. Thin ceramic PZT with a thickness of 9 µm was obtained by wafer bonding and chemical mechanical polishing (CMP) techniques and employed as the piezoelectric layer of the pMUT arrays, whose piezoelectric constant d 31 was measured to be as high as 140 pm/V. Benefiting from this high piezoelectric constant, the fabricated pMUT arrays exhibited high electromechanical coupling coefficients and large vibration displacements. In addition to electrical, mechanical, and acoustic characterization, PAI experiments with pencil leads embedded into an agar phantom were conducted with the fabricated dual- and multi-frequency pMUT arrays. Photoacoustic signals were successfully detected by pMUT elements with different frequencies and used to reconstruct single and fused photoacoustic images, which clearly demonstrated the advantages of using dual- and multi-frequency pMUT arrays to provide comprehensive photoacoustic images with high spatial resolution and large signal-to-noise ratio simultaneously.

Flexible Piezoelectric and Pyroelectric Nanogenerators Based on PAN/TMAB Nanocomposite Fiber Mats for Self-Power Multifunctional Sensors.

Self-powered wearable electronics to convert mechanical and thermal energy into electrical energy are important for biomedical monitoring, which highly require good flexibility, comfortability, signal sensitivity, and accuracy. In this work, composite nanofiber mats of polyacrylonitrile (PAN) and trimethylamine borane (TMAB) were prepared by electrospinning, which exhibited excellent piezoelectric and pyroelectric abilities in harvesting mechanical and thermal energy. The PAN/TMAB-4 nanofiber mats not only generated a high voltage of up to 2.56 V and a high power of 0.19 µW upon shape deformation but also exhibited linear voltage response to thermal gradient. The hybrid piezoelectric and pyroelectric output signals were successfully integrated together and have been applied to precisely monitor human vital signs, including elbow bending angles, foot posture, and breathing status, in real time by attaching the flexible sensors to proper human body parts. Overall, good flexibility, bifunctional sensing ability, and self-power make PAN-/TMAB-type sensors very attractive in fabricating high-performance electronics for detecting motion, monitoring health, and making portable microelectronics.

Optical neuroimaging: advancing transcranial magnetic stimulation treatments of psychiatric disorders.

Transcranial magnetic stimulation (TMS) has been established as an important and effective treatment for various psychiatric disorders. However, its effectiveness has likely been limited due to the dearth of neuronavigational tools for targeting purposes, unclear ideal stimulation parameters, and a lack of knowledge regarding the physiological response of the brain to TMS in each psychiatric condition. Modern optical imaging modalities, such as functional near-infrared spectroscopy and diffuse optical tomography, are promising tools for the study of TMS optimization and functional targeting in psychiatric disorders. They possess a unique combination of high spatial and temporal resolutions, portability, real-time capability, and relatively low costs. In this mini-review, we discuss the advent of optical imaging techniques and their innovative use in several psychiatric conditions including depression, panic disorder, phobias, and eating disorders. With further investment and research in the development of these optical imaging approaches, their potential will be paramount for the advancement of TMS treatment protocols in psychiatry.

Evaluation of Tracheal Stenosis in Rabbits Using Multispectral Optoacoustic Tomography.

Objective: Photoacoustic tomography (PAT) and multispectral optoacoustic tomography (MSOT) are evolving technologies that are capable of delivering real-time, high-resolution images of tissues. The purpose of this study was to evaluate the feasibility of using PAT and MSOT for detecting histology in a rabbit tracheal stenosis model. Method: A total of 12 rabbits (9 stenosis and three control) were randomly divided into four groups (A, B, C and D). Each group consisted of three rabbits, which were staged at the first, fourth, and eighth weeks of stenosis progression, respectively. PAT/MSOT images and corresponding histology from these experimental animals were compared, for analyzing the morphologic features and quantitative tracheal measurements in different tracheal stenosis stage. Result: Both the PAT images and corresponding histology indicated the most severe degree of stenosis in group C. MSOT images indicated notable differences in tracheal contents of group B and D. Conclusion: This study suggests that PAT/MSOT are potentially valuable non-invasive modality which are capable of evaluating tracheal structure and function in vivo.

Photoacoustic imaging for in vivo quantification of alcohol-induced structural and functional changes in cerebral vasculature in high alcohol-preferring mice (HAP).

Alcohol-induced structural and functional changes were studied in vivo by photoacoustic tomography (PAT) of the cerebrovascular system in selectively bred alcohol-preferring mice. High (HAP) and low (LAP) alcohol-preferring mice are replicate lines of mice selectively bred to prefer 10% (v/v) ethanol to water and water to ethanol, respectively, in a free-access two-bottle choice scenario. A cohort of 15 singly-housed alcohol-preferring mice (five HAP mice for the experimental group, five LAP mice for the control group, and five other LAP mice set aside) were given free-access two-bottle choice 10% ethanol (v/v) and water in 50-mL graduated drinking bottles mounted on each of their cages for 4 weeks prior to PAT brain scanning. A daily log of the volume of ethanol consumed over a 24-h period was kept. At the end of the fourth week, blood samples were collected from the HAP mice and blood ethanol concentrations (BECs) were measured to ascertain their levels of ethanol intoxication. The mice were then grouped into five weight-matched pairs of HAP and LAP for comparison purposes, and noninvasive in vivo PAT imaging was performed on each weight-matched pair. To mimic a binge drinking paradigm, mice were rearranged into four weight-matched groups of three animals each: an HAP mouse and two LAP mice. For each group, one HAP mouse and one LAP mouse received a 20% ethanol solution via intraperitoneal (i.p.) injection after 24 h of ethanol abstinence, in weight-based doses of 3 g/kg prior to imaging, while the last LAP mouse received a sham i.p. injection. PAT images of the brain were collected for 30 min thereafter. Cerebral vascular diameters for selected vessels of interest were extracted from the PAT images and compared between HAP mice and LAP mice. For the binge scenario, changes in vessel diameter and hemoglobin oxygen saturation were extracted from PAT images and studied over a 30-min duration. Vascular diameter was significantly smaller in HAP mice compared to LAP mice in weight-matched pairs. Hemoglobin-oxygen saturation and vessel diameter dropped more quickly in LAP mice than in HAP mice following a 20% ethanol i.p. injection (3 g/kg), with a 32% reduction in cerebrovascular diameter in a 30-min period. This study demonstrates the effectiveness of PAT in alcohol addiction imaging and diagnosis, and its feasibility in studying alcohol-induced changes in vascular structure and perfusion. It also adds to other bodies of evidence to suggest that the effects of binge drinking are more adverse in occasional drinkers than habitual drinkers.

First assessment of thermoacoustic tomography for in vivo detection of rheumatoid arthritis in the finger joints detection of rheumatoid arthritis in the finger joints.

BACKGROUND: The diagnosis of rheumatoid arthritis (RA) is complicated because of the complexity of symptoms and joint structures. Current clinical imaging techniques for the diagnosis of RA have strengths and weaknesses. Emerging imaging techniques need to be developed for the diagnosis or auxiliary diagnosis of RA. PURPOSE: This study aimed to demonstrate the potential of thermoacoustic tomography (TAT) for in vivo detection of RA in the finger joints. METHODS: Finger joints were imaged by a TAT system using three different microwave illumination methods including pyramidal horn antenna, and parallel in-phase and anti-phase microwave illuminations. Both diseased and healthy joints were imaged and compared when the three microwave illumination methods were used. Magnetic resonance imaging (MRI) of all the joints was performed to validate the TAT findings. In addition, two diseased joints were imaged at two time points by the pyramidal horn antenna-based TAT to track/monitor the progression of RA during a time period of 16 months. Three-dimensional (3-D) TAT images of the joints were also obtained. RESULTS: The TAT images of the diseased joints displayed abnormalities in bone and soft tissues compared to the healthy ones. The TAT images by pyramidal horn antenna and in-phase microwave illumination showed high similarity in image appearance, while the anti-phase-based TAT images provided different information about the disease. We found that the TAT findings matched well with the MRI images. The 3-D TAT images effectively displayed the stereoscopic effect of joint lesions. Finally, it was evident that TAT could detect the development of the lesions in 16 months. CONCLUSION: TAT can noninvasively visualize bone lesions and soft tissue abnormalities in the joints with RA. This first in vivo assessment of TAT provides a foundation for its clinical application to the diagnosis and monitoring of RA in the finger joints.

Three-dimensional optical imaging of brain activation during transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) of the brain is an effective clinical treatment for psychiatric disorders. Noninvasive neuroimaging during rTMS allows visualization of cortical brain activations and responses, and it is a potential tool for investigating the neurophysiological response occurring actively during stimulation. In this paper, we present a fast diffuse optical tomography (DOT) approach for three-dimensional brain mapping of hemodynamics during rTMS. Eight healthy subjects were enrolled in the study. These subjects received 10 Hz stimulation with 80%and 100%of resting motor threshold (rMT), respectively, for 4 seconds for each stimulation. Significant hemodynamic activation was observed in all cases with the strongest response when 100%rMT stimulation was applied. This work demonstrates that fast DOT has the potential to become a powerful tool for noninvasive three-dimensional imaging of the brain during rTMS.

Photoacoustic imaging in evaluating early intestinal ischemia injury and reperfusion injury in rat models.

BACKGROUND: It remains a challenge to distinguish whether the damaged intestine is viable in treating acute mesenteric ischemia. In this study, photoacoustic imaging (PAI) was used to observe intestinal tissue viability after ischemia and reperfusion injury in rats. METHODS: An in vivo study was conducted using forty male SD rats, which were randomly divided into a sham-operated (SO) group, a 1 h ischemia group, a 2 h ischemia group, and an ischemia-reperfusion (I/R) group with 10 rats in each group. In the ischemia group, the superior mesenteric artery (SMA) was isolated and clamped for 1 and 2 h, respectively, and in the I/R group, after ischemia for 1 h, the clamp was removed and reperfused for 1 h. The same time interval was used in the SO group. Immediately after establishing the animal model, a PAI examination was performed, and the small intestine was collected for histopathology. RESULTS: The levels of PAI parameters Hb, HbR, MAP 760, and MAP 840 were increased to different degrees in the ischemia groups, especially in the 2 h ischemia group, compared with the SO group (P<0.05), and with prolongation of the ischemia time, the injury was aggravated. All PAI signal levels except HbO in the I/R group were higher than those in the control group, and the increased range differed, especially in Hb and MAP 840. Using western blot, compared with the SO group, the BAX increased significantly in the 2 h ischemia group (P<0.05), and Caspase-3 in the experimental group was significantly higher than in the SO group (P<0.05). The level of HIF-1α increased in the 2 h ischemia group and I/R group (P<0.05), and TUNEL staining showed that the number of positive apoptotic nuclei in the 2 h ischemia group was significantly higher than in the SO group (P<0.05). Hematoxylin-eosin (HE) staining showed that ischemia for 2 hours was the most serious, with obvious mucosal damage, extensive epithelial injury, and bleeding. CONCLUSIONS: PAI can be used as an effective tool to detect acute intestinal ischemia injury and quantitatively evaluate tissue viability.

Technical Note: Compact thermoacoustic imaging system based on a low-cost and miniaturized microwave generator for in vivo biomedical imaging.

PURPOSE: Most of existing thermoacoustic imaging (TAI) studies generally utilized a linear modulator-based high peak power magnetron generator (MG) for efficient TA signal excitation. However, a linear modulator-based MG is bulky and expensive. Here we present a low-cost and compact thermoacoustic imaging (TAI) system based on a miniaturized MG. METHODS: The MG is based on solid-state modulator and operates at 3.05 ± 0.025 GHz, with a peak power of up to 60 kW and adjustable pulse duration from 70 to 600 ns. The dimensions and weight of this MG are 350 × 210 × 70 mm3 (Width × Length × Height) and 7.5 kg, respectively. RESULTS: The spatial resolution of the miniaturized MG-based TAI system is determined to be from 0.3 to 1.4 mm using controlled phantom experiments. The system is further evaluated using in vivo experiments where the finger joints and vasculature in the forearm and opisthenar of human participants are successfully imaged. CONCLUSIONS: This study suggests that the miniaturized MG based TAI systems can be used for in vivo joint and vascular imaging with multiscale resolutions (0.3-1.4 mm).

Integrated thermoacoustic and ultrasound imaging based on the combination of a hollow concave transducer array and a linear transducer array.

To integrate the high resolution of ultrasound imaging (UI) and the high tissue specificity of thermoacoustic imaging (TAI) and to achieve an easy and precise co-registration of the two different imaging modalities, we present and demonstrate a hybrid thermoacoustic and ultrasound (TA/US) imaging system based on the combination of a novel hollow concave array and a commercial linear array. This TA/US imaging system can provide enhanced imaging of both tissues' mechanical and dielectric properties. We verified the effective imaging performance of the hybrid TA/US system using tissue phantom experiments.In vivoTA/US imaging of the wrist and foot in healthy volunteers was also demonstrated using the hybrid system. This hollow concave array provided enhanced imaging performance for TAI because of its wide angular coverage with an optimal center frequency, showing a large effective imaging field of view (FOV) and improved images with high contrast and superior quality. Compared with stand-alone UI or TAI, the hybrid TA/US imaging presented more complete tissue anatomical structures, like skin, muscles, tendons, blood vessels, and bones for possible human disease diagnosis, although the US image quality using the hybrid system was slightly lower because the distance between the tissue and commercial ultrasound array was not ideal. This study suggests that the hybrid TA/US imaging approach has the potential to become a clinical tool for diagnosis of diseases in the wrist and foot.

Neuroimaging of depression with diffuse optical tomography during repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) is an effective and safe treatment for depression; however, its potential has likely been hindered due to non-optimized targeting, unclear ideal stimulation parameters, and lack of information regarding how the brain is physiologically responding during and after stimulation. While neuroimaging is ideal for obtaining such critical information, existing modalities have been limited due to poor resolutions, along with significant noise interference from the electromagnetic spectrum. In this study, we used a novel diffuse optical tomography (DOT) device in order to advance our understanding of the neurophysiological effects of rTMS in depression. Healthy and depressed subjects aged 18-70 were recruited. Treatment parameters were standardized with targeting of the left dorsolateral prefrontal cortex with a magnetic field intensity of 100% of motor threshold, pulse frequency of 10 per second, a 4 s stimulation time and a 26 s rest time. DOT imaging was simultaneously acquired from the contralateral dorsolateral prefrontal cortex. Six healthy and seven depressed subjects were included for final analysis. Hemoglobin changes and volumetric three-dimensional activation patterns were successfully captured. Depressed subjects were observed to have a delayed and less robust response to rTMS with a decreased volume of activation compared to healthy subjects. In this first-in-human study, we demonstrated the ability of DOT to safely and reliably capture and compare cortical response patterns to rTMS in depressed and healthy subjects. We introduced this emerging optical functional imaging modality as a novel approach to investigating targeting, new treatment parameters, and physiological effects of rTMS in depression.