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Traditional diagnostic techniques including visual examination, ultrasound (US), and magnetic resonance imaging (MRI) have limitations of in-depth information for the detection of nail disorders, resolution, and practicality. This pilot study, for the first time, evaluates a dual-modality imaging system that combines photoacoustic tomography (PAT) with the US for the multiparametric quantitative assessment of human nail. The study involved a small cohort of five healthy volunteers who underwent PAT/US imaging for acquiring the nail unit data. The PAT/US dual-modality imaging successfully revealed the fine anatomical structures and microvascular distribution within the nail and nail bed. Moreover, this system utilized multispectral PAT to analyze functional tissue parameters, including oxygenated hemoglobin, deoxyhemoglobin, oxygen saturation, and collagen under tourniquet and cold stimulus tests to evaluate changes in the microcirculation of the nail bed. The quantitative analysis of multispectral PAT reconstructed images demonstrated heightened sensitivity in detecting alterations in blood oxygenation levels and collagen content within the nail bed, under simulated different physiological conditions. This pilot study highlights the potential of PAT/US dual-modality imaging as a real-time, noninvasive diagnostic modality for evaluating human nail health and for early detection of nail bed pathologies.

Puncture biopsy is an important clinical technique to obtain diseased tissue for pathological diagnosis, where imaging guidance is critical. In this paper, we describe a metal reflector-enhanced microwave-induced thermoacoustic imaging (TAI) approach capable of guiding puncture biopsy for detection of breast cancer and joint diseases. Numerical experimentations simulating puncture guidance in breast cancer and knee gout models were first conducted using (CST STUDIO SUITE) (CST) software, and then ex-vivo experiments were performed followed by qualitative observations and semi-quantitative analysis. The results of both the simulations and ex-vivo experiments showed that our reflector-enhanced TAI could image the puncture needle in high resolution with a large depth of [Formula: see text][Formula: see text]cm.

Sepsis is a life-threatening syndrome consisting of physiological, pathological, and biochemical abnormalities induced by infection which continues to be a major public health burden. It remains one of the most common reasons for intensive care unit (ICU) admission. Delirium precipitated by sepsis in the intensive care setting is one of its most common neuropsychiatric complications that leads to prolonged hospitalization, increased mortality, and an increased risk of incident dementia. Understanding the pathophysiology and neurobiological mechanisms of sepsis-associated delirium is difficult; neuroimaging biomarkers are lacking due to difficulties with imaging critically ill patients. Optical imaging techniques, including near-infrared spectroscopy and diffuse optical tomography are potentially promising approaches for investigating this pathophysiology due to their portability and high spatiotemporal resolution. In this review, we examine the emergence of optical neuroimaging techniques for the study of sepsis-associated delirium in the ICU and how they can further advance our knowledge and lead to the development of improved preventative, predictive, and therapeutic strategies.

Functional neuroimaging studies of neuropsychiatric disorders and cognitive impairment are commonly conducted in the clinic setting but less so in the acutely medically ill while hospitalized. This is largely due to technical and logistical limitations, given the lack of portable devices with high spatial and temporal resolutions. This exploratory study reports on the development and implementation of a novel diffuse optical tomography (DOT) system that can be employed for bedside three-dimensional functional neuroimaging. To test this portable DOT system, our protocol included a task-based sequence involving the Months Backwards Test with imaging centered on the bilateral prefrontal cortex. Fifteen subjects were recruited from intensive care units and the general wards of a single tertiary academic hospital and included in our final analysis. Volumetric hemoglobin analyses of the dorsolateral prefrontal cortex (DLPFC) and dorsomedial prefrontal cortex (DMPFC) were reliably captured in all our subjects. The peak value was calculated to be 3.36 µM and 0.74 µM for oxygenated-hemoglobin (HbO) and total-hemoglobin (HbT) (p < 0.042, [HbT]), respectively. The standard error was calculated to be 4.58 uM and 3.68 uM for (HbO) and (HbT). We additionally developed a seed-based correlation analysis to demonstrate the capability of DOT in studying functional connectivity. The right DLPFC was found to be moderately associated with the left DLPFC in all our subjects (r = 0.656). The DMPFC was observed to be associated with the left DLPFC but less so (r = 0.273) at the group level. Overall, the contribution of left-to-right DLPFC connectivity was significantly higher than left DLPFC to DMPFC in our group (p = 0.012). Future studies should investigate the potential of such a DOT system in the research of neuropsychiatric and neurocognitive disorders within the hospital to study different types of mechanisms, pathophysiology, and interventions that occur acutely and can advance our knowledge of these disorders.

Abstract 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.

Abstract 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.

Photoacoustic imaging (PAI) is an emerging biomedical imaging modality, offering numerous advantages, including high resolution and high contrast. In its application to brain imaging, however, the photoacoustic (PA) signals from brain tissue weaken considerably due to the distortion effects of the skull. This attenuation reduces the resolution and contrast significantly. To address this issue, here we describe a Log-MSR algorithm that combines the logarithmic depth logarithmic enhancement (Log) algorithm and the multi-scale Retinex (MSR) algorithm. In this method, the Log algorithm performs local weighted compensation based on signal attenuation for different depths, while the MSR algorithm improves the contrast of the image. The proposed Log-MSR algorithm was tested and validated using several phantom and in vivo experiments. The enhanced images constructed by the Log-MSR algorithm were qualitatively and quantitatively analyzed in terms of brain structure and function. Our results show that the Log-MSR algorithm may provide a significant enhancement to photoacoustic imaging of deep brain tissue.

This study aims to explore the feasibility of fine-needle aspiration biopsy (FNAB) under dual modal photoacoustic tomography(PAT)/ultrasound (US) imaging. A total of 25 patients who have thyroid nodules with thyroid imaging reporting and data system (TIRADS) 3 and 4 (malignant risk Bethesda system for reporting thyroid cytopathology diagnostic category (DC) I: 4%(1/25); DC II: 12% (3/25); DC III: 20% (5/25); DC IV: 8% (2/25); DC V: 32% (8/25); and DC VI: 24% (6/25). The DC I nodule exhibited inadequate cytology and had structural characteristic of predominant calcifications in PAT/US mapping. The DC V-VI nodules showed lower photoacoustic (PA) signals compared to the DC I-IV nodules. Regions with a high PA signal demonstrated a significant number of erythrocytes in FNAB cytology. Moreover, nodules with microcalcifications did not show a significant difference compared to their surroundings in the PA signal, while nodules with macrocalcifications gave higher PA signals compared to their surroundings. The conclusions are as follows: combining US with PAT can evaluate the structure and function of thyroid nodules in vivo. This study demonstrates that dual modal PAT/US imaging has the potential to be an effective clinical tool to guide FNAB of thyroid nodules.

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.

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.

Abstract 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.

Microwave-induced thermoacoustic imaging (MTAI) has emerged as a potential biomedical imaging modality with over 20-year growth. MTAI typically employs pulsed microwave as the pumping source, and detects the microwave-induced ultrasound wave via acoustic transducers. Therefore, it features high acoustic resolution, rich electromagnetic contrast, and large imaging depth. Benefiting from these unique advantages, MTAI has been extensively applied to various fields including pathology, biology, material and medicine. Till now, MTAI has been deployed for a wide range of biomedical applications, including cancer diagnosis, joint evaluation, brain investigation and endoscopy. This paper provides a comprehensive review on (1) essential physics (endogenous/exogenous contrast mechanisms, penetration depth and resolution), (2) hardware configurations and software implementations (excitation source, antenna, ultrasound detector and image recovery algorithm), (3) animal studies and clinical applications, and (4) future directions.

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.

Abstract We have developed a computer-aided diagnosis system based on a convolutional neural network that aims to classify breast mass lesions in optical tomographic images obtained using a diffuse optical tomography system, which is suitable for repeated measurements in mass screening. Sixty-three optical tomographic images were collected from women with dense breasts, and a dataset of 1260 2D gray scale images sliced from these 3D images was built. After image preprocessing and normalization, we tested the network on this dataset and obtained 0.80 specificity, 0.95 sensitivity, 90.2% accuracy, and 0.94 area under the receiver operating characteristic curve (AUC). Furthermore, a data augmentation method was implemented to alleviate the imbalance between benign and malignant samples in the dataset. The sensitivity, specificity, accuracy, and AUC of the classification on the augmented dataset were 0.88, 0.96, 93.3%, and 0.95, respectively.

In this article, we propose a new approach utilizing diffuse optical tomography (DOT) to monitoring the changes in tissues’ optical properties and temperature in high-intensity focused ultrasound (HIFU) therapy. By correlating the tissue reduced scattering coefficient (μs’) reconstructed by DOT and the temperature measured by a thermocouple, the quantitative relationship between μs’ and temperature in HIFU treatment was explored. The experiments were conducted using porcine and chicken breast muscle tissues during HIFU; the temperature of each tissue sample was recorded using a thermocouple. To incorporate the temperature dependency of tissue optical properties, both polynomial and exponential models were utilized to fit the experimental data. The results show that the change of μs’ during HIFU treatment could be detected in real-time using DOT and that this change of μs’ is quantitatively correlated with tissue temperature. Furthermore, while the tissue-type-dependent relationship between μs’ and temperature is non-linear in nature, it is stable and repeatable. Therefore, our approach has the potential to be used to predict temperature of tissue during HIFU treatment.

We present a systematical study on comparison between water and dry coupling in photoacoustic tomography of the human finger joints. Compared to the direct water immersion of the finger for water coupling, the dry coupling is realized through a transparent PDMS film-based water bag, which ensures water-free contact with the skin. The results obtained suggest that the dry coupling provides image quality comparable to that by water coupling while eliminating the wrinkling of the finger joint caused by the water immersion. In addition, the dry coupling offers more stable hemodynamic images than the water coupling as the water immersion of the finger joint causes reduction in blood vessel size.

Iterative reconstruction algorithm based on finite element (FE) modeling is a powerful approach in photoacoustic tomography (PAT). However, an iterative inverse algorithm using conventional FE meshing of the entire imaging zone is computationally demanding, which hinders this powerful tool in applications where quick image acquisition and/or a large image matrix is needed. To address this challenge, parallel computing techniques are proposed and implemented in the field. Here, we present an alternative approach for 2D PAT, which locoregionally reconstructs the region of interest (ROI) instead of the full imaging zone. Our simulated and phantom experimental results demonstrate that this ROI reconstruction algorithm can produce almost the same image quality as the conventional full zone-based reconstruction algorithm; however, the computation time can be significantly reduced without any additional hardware cost by more than two orders of magnitude (100-fold). This algorithm is further applied and validated in an in vivo study. The major vessel structures in a rat’s brain can be imaged clearly using our ROI-based approach, coupled with a mesh of 11,801 nodes. This novel algorithm can also be parallelized using MPI or GPU acceleration techniques to further enhance the reconstruction performance of FE-based PAT.

Abstract Tunable-aspect ratio gold nanorods have been synthesized by a modified seed-mediated synthesis method. Ascorbic acid was employed as a shape controller to induce anisotropic growth, which made the aspect ratio of the synthesized gold nanorods range from 8.5 to 15.6. These nanorods possess tunable longitudinal surface plasmon resonance absorption band, covering a broad near-infrared (NIR) range, from ~ 680 to 1100 nm. When modified with thiol-polyethylene glycol (SH-PEG), the synthesized Au nanorods showed excellent biocompatibility and stability, which foreshadowed the great potential of their NIR application as photoacoustic contrast agent. Due to their adjustable absorbance in the NIR, the synthesized Au nanorods could offer stronger contrast (3.1 times to the control group without contrast agent used) and higher signal-noise ratio values (SNR; 5.6 times to the control group) in photoacoustic imaging, both in vitro and in vivo experiments. Our work presented here not only added some novel Au-based photoacoustic contrast agents but also described a possibility of contrast agent preparation covering the whole biological NIR window.

In this study, we developed a novel photoacoustic imaging technique based on poly (ethyleneglycol)-coated (PEGylated) gold nanorods (PEG-GNRs) (as the contrast agent) combined with traditional Chinese medicine (TCM) acupuncture (as the auxiliary method) for quantitatively monitoring contrast enhancement in the vasculature of a mouse brain in vivo. This study takes advantage of the strong near-infrared absorption (peak at ∼700nm) of GNRs and the ability to adjust the hemodynamics of acupuncture. Experimental results show that photoacoustic tomography (PAT) successfully reveals the optical absorption variation of the vasculature of the mouse brain in response to intravenous administration of GNRs and acupuncture at the Zusanli acupoint (ST36) both individually and combined. The quantitative measurement of contrast enhancement indicates that the composite contrast agents (integration of acupuncture and GNRs) would greatly enhance the photoacoustic imaging contrast. The quantitative results also have the potential to estimate the local concentration of GNRs and even the real-time effects of acupuncture.

Photoacoustic imaging (PAI) is drawing extensive attention and gaining rapid development as an emerging biomedical imaging technology because of its high spatial resolution, large imaging depth, and rich optical contrast. PAI has great potential applications in endoscopy, but the progress of endoscopic PAI was hindered by the challenges of manufacturing and assembling miniature imaging components. Over the last decade, microelectromechanical systems (MEMS) technology has greatly facilitated the development of photoacoustic endoscopes and extended the realm of applicability of the PAI. As the key component of photoacoustic endoscopes, micromachined ultrasound transducers (MUTs), including piezoelectric MUTs (pMUTs) and capacitive MUTs (cMUTs), have been developed and explored for endoscopic PAI applications. In this article, the recent progress of pMUTs (thickness extension mode and flexural vibration mode) and cMUTs are reviewed and discussed with their applications in endoscopic PAI. Current PAI endoscopes based on pMUTs and cMUTs are also introduced and compared. Finally, the remaining challenges and future directions of MEMS ultrasound transducers for endoscopic PAI applications are given.

We present a method that allows for hybrid microwave-excited thermoacoustic and ultrasound (HMTAU) imaging without an additional ultrasound transmitting circuitry. The same microwave pulse is used to simultaneously generate thermoacoustic (TA) signals from the sample by the thermoacoustic effect, and ultrasound (US) signals from the piezoelectric transducer by the inverse piezoelectric effect. The same transducer collects the US signals reflected from the sample as a result of the US pulse (pulse-echo) and the TA signals as a result of the sample absorbing microwaves. Experiments are conducted to show how the microwave pulse-width significantly impacts the excitation efficiency of ultrasonic waves, which can reduce the requirement for microwave power. We found that the mechanical response of the US transducer to this transient expansion shows a maximum if the pulse-width of the microwave is close to half of the center period of the US transducer. We also use phantom experiments to demonstrate the complementary contrast mechanisms of the two modalities. The results obtained indicate that our method offers the potential of a low-cost dual-modality technique for noninvasive biomedical imaging.

We described a novel handheld device (termed FMTPen) for three-dimensional (3D) fluorescence molecular tomography (FMT). The FMTpen is characterized by its bendable structure and miniaturized size (10 mm in diameter) that can be potentially used as an intraoperative tool for the detection of tumor margins and for image-guided surgery. Several phantom experiments based on indocyanine green (ICG), an FDA approved near-infrared (NIR) fluorescent dye, were conducted to evaluate the imaging ability of this device. Two tumor-bearing mice were systematically injected with tumor-targeted NIR fluorescent probes (NIR-830-ATF68-IONP and NIR-830-ZHER2:343-IONP, respectively) and were then imaged to further demonstrate the ability of this FMT probe for imaging small animals.

We present a single element-based dual focused photoacoustic microscopy (PAM) that shows improved signal-to-noise ratio and lateral resolution compared to conventional single focused PAM in the out-of-focus region. This dual focused PAM is based on the novel design of a single element-based dual focused transducer coupled with improved image reconstruction method using synthetic aperture dual focusing technique (SADFT). Polyvinylidene fluoride (PVDF) was used to fabricate the dual-focused transducer and phantom experiments were conducted to demonstrate the advantages of this novel transducer design. Experimental results obtained show that the signal-to-noise ratio and lateral resolution can be improved with a factor of 2X in the conventionally out-of-focus region using this technique.

We present for the first time in vivo imaging of rat brain using microwave-induced thermoacoustic tomography (TAT). The in vivo imaging of rat brain was realized through an unconventional delivery of microwave energy from the front of rat brain (while the transducer was scanned along coronal plane of the animal brain), which maximized the microwave penetration into the brain. In addition, we found that the imaging contrast was highly dependent on the direction of the electric field polarization (EFP) and that more tissue structures/compositions could be revealed when both X- and Y-EFPs were used for TAT. The in vivo TAT images of rat brain obtained were compared with the 3.0 T MRI images and histological photographs, and numerous important brain anatomical structures were identified. An example of our TAT approach for imaging a foreign object embedded in a rat brain was also demonstrated. This study suggests that TAT has a great potential to be used in neuroscience studies and in noninvasive imaging of brain disorders.

Here, we report a new method using combined magnetic resonance (MR)–Photoacoustic (PA)–Thermoacoustic (TA) imaging techniques, and demonstrate its unique ability for in vivo cancer detection using tumor-bearing mice. Circular scanning TA and PA imaging systems were used to recover the dielectric and optical property distributions of three colon carcinoma bearing mice While a 7.0-T magnetic resonance imaging (MRI) unit with a mouse body volume coil was utilized for high resolution structural imaging of the same mice. Three plastic tubes filled with soybean sauce were used as fiducial markers for the co-registration of MR, PA and TA images. The resulting fused images provided both enhanced tumor margin and contrast relative to the surrounding normal tissues. In particular, some finger-like protrusions extending into the surrounding tissues were revealed in the MR/TA infused images. These results show that the tissue functional optical and dielectric properties provided by PA and TA images along with the anatomical structure by MRI in one picture make accurate tumor identification easier. This combined MR–PA–TA-imaging strategy has the potential to offer a clinically useful triple-modality tool for accurate cancer detection and for intraoperative surgical navigation.

We report our study that shows selection in operating frequency of US-transducer used for boundary detection of PA-signals, which result due to the contrast in elastic property distribution ( E ( r → ) ) in sample material other than that of optical absorption coefficient (μa). Studies were carried out, experimentally, in tissue-mimicking Agar phantoms employing acoustic resolution photoacoustic microscopy (AR-PAM) system as an imaging unit. In the experiments, various transducers having different operating frequencies, ranging from 1MHz to 50MHz, were employed for studying frequency response of the photoacoustic signals. The study shows that, for detecting photoacoustic signals due to the contrast in elastic property, ultrasound transducer with higher operating frequency (∼50MHz) is demanded.

It is highly desirable to develop novel approaches to improve patient survival rate of pancreatic cancer through early detection. Here, we present such an approach based on photoacoustic and fluorescence molecular imaging of pancreatic tumor using a miniature multimodal endoscope in combination with targeted multifunctional iron oxide nanoparticles (IONPs). A novel fan-shaped scanning mechanism was developed to minimize the invasiveness for endoscopic imaging of pancreatic tumors. The results show that the enhancements in photoacoustic and fluorescence signals using amino-terminal fragment (ATF) targeted IONPs were ~four to six times higher compared to that using non-targeted IONPs. Our study indicates the potential of the combination of the multimodal photoacoustic-fluorescence endoscopy and targeted multifunctional nanoparticles as an efficient tool to provide improved specificity and sensitivity for pancreatic cancer detection.

While functional imaging is widely used in studies of the brain, how well the hemodynamic signal represents the underlying neural activity is still unclear. And there is a debate on whether hemodynamic signal is more tightly related to synaptic activity or action potentials. This study intends to address these questions by examining neurovascular coupling driven by pyramidal cells in the motor cortex of rats. Pyramidal cells in the motor cortex of rats were selectively transduced with the light sensitive cation channel channelrhodopsin-2 (ChR2). Electrophysiological recordings and optical intrinsic signal imaging were performed simultaneously and synchronously to capture the neural activity and hemodynamics induced by optical stimulation of ChR2-expressing pyramidal cells. Our results indicate that both synaptic activity (local field potential, LFP) and action potentials (multi-unit activity, MUA) are tightly related to hemodynamic signals. While LFPs in γ band are better in predicting hemodynamic signals elicited by short stimuli, MUA has better predictions to hemodynamic signals elicited by long stimuli. Our results also indicate that strong nonlinearity exists in neurovascular coupling.

Breast cancer is the most prevalent cancer and the main cause of cancer-related death in women worldwide. There are limitations associated with the existing clinical tools for breast cancer detection and alternative modalities for early detection and classification of breast cancer are urgently needed. Here we describe an optical imaging technique, called multispectral diffuse optical tomography (DOT), and demonstrate its ability of non-invasively evaluating nuclear morphometry for differentiating benign from malignant lesions. Photon densities along the surface of the breast were measured to allow for the extraction of three statistical parameters including the size, elongation and density of nuclei inside the breast tissue. The results from 14 patients (4 malignant and 10 benign lesions) show that there exist significant contrasts between the diseased and surrounding normal nuclei and that the recovered nuclear morphological parameters agree well the pathological findings. We found that the nuclei of cancer cells were less-spherical compared with those of surrounding normal cells, while the nuclear density or volume fraction provided the highest contrast among the three statistical parameters recovered. This pilot study demonstrates the potential of multispectral DOT as a cellular imaging method for accurate determination of breast cancer.