Gold nanorod-assisted theranostic solution for nonvisible residual disease in bladder cancer.

Residual nonvisible bladder cancer after proper treatment caused by technological and therapeutic limitations is responsible for tumor relapse and progression. This study aimed to demonstrate the feasibility of a solution for simultaneous detection and treatment of bladder cancer lesions smaller than one millimeter. The α5ß1 integrin was identified as a specific marker in 81% of human high-grade nonmuscle invasive bladder cancers and used as a target for the delivery of targeted gold nanorods (GNRs). In a preclinical model of orthotopic bladder cancer expressing the α5ß1 integrin, the photoacoustic imaging of targeted GNRs visualized lesions smaller than one millimeter, and their irradiation with continuous laser was used to induce GNR-assisted hyperthermia. Necrosis of the tumor mass, improved survival, and computational modeling were applied to demonstrate the efficacy and safety of this solution. Our study highlights the potential of the GNR-assisted theranostic strategy as a complementary solution in clinical practice to reduce the risk of nonvisible residual bladder cancer after current treatment. Further validation through clinical studies will support the findings of the present study.

Advanced Techniques for Liver Fibrosis Detection: Spectral Photoacoustic Imaging and Superpixel Photoacoustic Unmixing Analysis for Collagen Tracking.

Liver fibrosis, a major global health issue, is marked by excessive collagen deposition that impairs liver function. Noninvasive methods for the direct visualization of collagen content are crucial for the early detection and monitoring of fibrosis progression. This study investigates the potential of spectral photoacoustic imaging (sPAI) to monitor collagen development in liver fibrosis. Utilizing a novel data-driven superpixel photoacoustic unmixing (SPAX) framework, we aimed to distinguish collagen presence and evaluate its correlation with fibrosis progression. We employed an established diethylnitrosamine (DEN) model in rats to study liver fibrosis over various time points. Our results revealed a significant correlation between increased collagen photoacoustic signal intensity and advanced fibrosis stages. Collagen abundance maps displayed dynamic changes throughout fibrosis progression. These findings underscore the potential of sPAI for the noninvasive monitoring of collagen dynamics and fibrosis severity assessment. This research advances the development of noninvasive diagnostic tools and personalized management strategies for liver fibrosis.

A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5ß1-targeted gold nanorods.

BACKGROUND: Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. RESULTS: In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5ß1 integrin expressed by bladder cancer cells. This product (called GNRs@PEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5ß1 and α5ß1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5ß1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5ß1-negative), pointing to a specific targeting mechanism. CONCLUSION: GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions.

Near-Infrared Spectroscopy for the In Vivo Monitoring of Biodegradable Implants in Rats.

Magnesium (Mg) alloys possess unique properties that make them ideal for use as biodegradable implants in clinical applications. However, reports on the in vivo assessment of these alloys are insufficient. Thus, monitoring the degradation of Mg and its alloys in vivo is challenging due to the dynamic process of implant degradation and tissue regeneration. Most current works focus on structural remodeling, but functional assessment is crucial in providing information about physiological changes in tissues, which can be used as an early indicator of healing. Here, we report continuous wave near-infrared spectroscopy (CW NIRS), a non-invasive technique that is potentially helpful in assessing the implant-tissue dynamic interface in a rodent model. The purpose of this study was to investigate the effects on hemoglobin changes and tissue oxygen saturation (StO2) after the implantation of Mg-alloy (WE43) and titanium (Ti) implants in rats' femurs using a multiwavelength optical probe. Additionally, the effect of changes in the skin on these parameters was evaluated. Lastly, combining NIRS with photoacoustic (PA) imaging provides a more reliable assessment of tissue parameters, which is further correlated with principal component analysis.

Mass, composition, and sources of particulate matter in residential and traffic sites of an urban environment.

Present study aims to assess the mass, composition, and sources of PM10 and PM2.5 (particulate matter having aerodynamic diameter less than or equal to 10 and 2.5 µm aerodynamic diameter, respectively) in Vellore city. Seasonal samples collected in traffic and residential sites were analyzed for ions, elements, organic carbon (OC), and elemental carbon (EC). Source apportionment of PM10 and PM2.5 is carried out using Chemical Mass Balance, Unmix, Positive Matrix Factorization and Principal Component Analysis receptor models. Results showed that traffic site had higher annual concentration (PM2.5 = 62 ± 32 and PM10 = 112 ± 23 µg m-3) when compared to residential site (PM2.5 = 54 ± 22 and PM10 = 98 ± 20 µg m-3). Al, Ca, Fe, K, and Mg known to have crustal origin dominated the element composition irrespective of PM size and sampling site. Among ions, SO42- accounted highest in both sites with an average of 70 and 60% to PM2.5 and PM10 ionic mass. Elemental carbon contribution to PM mass was found highest in traffic site (PM2.5 = 17 to 23% and PM10 = 8 to 10%) than residential site (PM2.5 = 9 to 17% and PM10 = 4 to 8%). Elements, ions, OC, and EC accounted 12, 28, 34, and 16% of PM2.5 mass and 12, 21, 20, and 8% of PM10 mass, respectively. Different sources identified by the receptor models are resuspended road dust, crustal material, secondary aerosol, traffic, non-exhaust vehicular emissions, secondary nitrate, construction, cooking, and biomass burning. Since Vellore is aspiring to be a smart city, this study can help the policymakers in effectively curbing PM.

An Automatic Unmixing Approach to Detect Tissue Chromophores from Multispectral Photoacoustic Imaging.

Multispectral photoacoustic imaging has been widely explored as an emerging tool to visualize and quantify tissue chromophores noninvasively. This modality can capture the spectral absorption signature of prominent tissue chromophores, such as oxygenated, deoxygenated hemoglobin, and other biomarkers in the tissue by using spectral unmixing methods. Currently, most of the reported image processing algorithms use standard unmixing procedures, which include user interaction in the form of providing the expected spectral signatures. For translational research with patients, these types of supervised spectral unmixing can be challenging, as the spectral signature of the tissues can differ with respect to the disease condition. Imaging exogenous contrast agents and accessing their biodistribution can also be problematic, as some of the contrast agents are susceptible to change in spectral properties after the tissue interaction. In this work, we investigated the feasibility of an unsupervised spectral unmixing algorithm to detect and extract the tissue chromophores without any a-priori knowledge and user interaction. The algorithm has been optimized for multispectral photoacoustic imaging in the spectral range of 680-900 nm. The performance of the algorithm has been tested on simulated data, tissue-mimicking phantom, and also on the detection of exogenous contrast agents after the intravenous injection in mice. Our finding shows that the proposed automatic, unsupervised spectral unmixing method has great potential to extract and quantify the tissue chromophores, and this can be used in any wavelength range of the multispectral photoacoustic images.

Investigation of road dust characteristics and its associated health risks from an urban environment.

Globally, road dust is a major source of inhalable particulate matter in any urban environment. This research seeks to assess the elemental composition of road dust at Vellore city, India, and to evaluate its health risks. For this, dust samples are collected from 18 locations in the study region. The collected samples are digested and analysed for about 25 elements using inductively coupled plasma-optical emission spectroscopy, of which 19 elements have concentration greater than the detection limit of the instrument (Al, Ba, Ca, Mg, Sr, Co, Cr, Cu, Fe, Ga, Zn, In, K, Li, Mn, Na, Ni, Pb and Rb). The highest mean concentration is noted for Fe (22,638.23 mg/kg) followed by Ca (13,439.47 mg/kg), Al (8445.89 mg/kg) and Mg (3381.20 mg/kg). Enrichment factor (EF) and contamination factor (CF) are calculated for 10 trace elements: Cu, Co, Cr, Ga, Mn, Ni, Pb, Rb, Sr and Zn. Elements Ga and Zn show the highest EF and CF. Source identification recognized that crustal material and traffic as the major sources of potentially toxic elements (PTEs). Further, the health risk assessment is performed for nine PTEs and identifies that Fe, Pb, Cr and Co are elements with the highest health index. Health index of these elements suggests a possible health risk. Ingestion is the major pathway, and children are found to be at a higher risk compared to adults.

Topographic modification of the extracellular matrix precedes the onset of bladder cancer.

Background: Non-muscle invasive bladder cancer (NMIBC) patients are affected by a high risk of recurrence. The topography of collagen fibers represents a hallmark of the neoplastic extracellular microenvironment. Objective: Assess the topographic change associated with different stages of bladder cancer (from neoplastic lesions to bona fide tumor) and whether those changes favour the development of NMIBC. Design Setting and Participants: Seventy-one clinical samples of urothelial carcinoma at different stages were used. Topographic changes preceding tumor onset and progression were evaluated in the rat bladder cancer model induced by nitrosamine (BBN), a bladder-specific carcinogen. The preclinical model of actinic cystitis was also used in combination with BBN. Validated hematoxylin-eosin sections were used to assess the topography of collagen fibrils associated with pre-tumoral steps, NMIBC, and MIBC. Findings: Linearization of collagen fibers was higher in Cis and Ta vs. dysplastic urothelium, further increased in T1 and greatest in T2 tumors. In the BBN preclinical model, an increase in the linearization of collagen fibers was established since the beginning of inflammation, such as the onset of atypia of a non-univocal nature and dysplasia, and further increased in the presence of the tumor. Linearization of collagen fibers in the model of actinic cystitis was associated with earlier onset of BBN-induced tumor. Conclusions: The topographic modification of the extracellular microenvironment occurs during the inflammatory processes preceding and favoring the onset of bladder cancer. The topographic reconfiguration of the stroma could represent a marker for identifying and treating the non-neoplastic tissue susceptible to tumor recurrence.

Contrast enhanced photoacoustic detection of fibrillar collagen in the near infrared region-I.

Fibrillar collagen accumulation emerges as a promising biomarker in several diseases, such as desmoplastic tumors and unstable atherosclerotic plaque. Gold nanorods (GNRs) hold great potential as contrast agents in high-resolution, biomedically safe, and non-invasive photoacoustic imaging (PAI). This study presents the design and characterization of a specialized imaging tool which exploits GNR assisted targeted photoacoustic imaging that is tailored for the identification of fibrillar collagen. In addition to the photoacoustic characterization of collagen in the NIR 1 and 2 regions, we demonstrate the detailed steps of conjugating a decoy to GNRs. This study serves as a proof of concept, that demonstrates that conjugated collagenase-1 (MMP-1) generates a distinct and collagen-specific photoacoustic signal, facilitating real-time visualization in the wavelength range of 700-970 nm (NIR I). As most of the reported studies utilized the endogenous contrast of collagen in the NIR II wavelength that has major limitations to perform in vivo deep tissue imaging, the approach that we are proposing is unique and it highlights the promise of MMP-1 decoy-functionalized GNRs as novel contrast agents for photoacoustic imaging of collagen in the NIR 1 region. To our knowledge this is the first time functionalized GNRs are optimized for the detection of fibrillar collagen and utilized in the field of non-invasive photoacoustic imaging that can facilitate a better prognosis of desmoplastic tumors and broken atherosclerotic plaques.

Development of a morphologically realistic mouse phantom for pre-clinical photoacoustic imaging.

BACKGROUND: Characterizations based on anatomically realistic phantoms are highly effective to perform accurate technical validation of imaging systems. Specifically for photoacoustic imaging (PAI), although a variety of phantom models with simplified geometries are reported, an unmet need still exists to establish morphologically realistic heterogeneous pre-clinical phantoms. So the development of a mouse-mimicking phantom can reduce the use of animals for the validation and standardization studies of pre-clinical PAI systems and thus eventually translate the PAI technology to clinical research. PURPOSE: Here we designed, developed, and fabricated a stable phantom that mimics the detailed morphology of a mouse, to be used as a realistic tool for PAI. METHODS: The mouse phantom, has been designed by using a combination of image modeling and 3D-printing techniques. As a tissue-mimicking material, we have used copolymer-in-oil-based material that was recently proposed by the International Photoacoustic Standardization Consortium (IPASC). In particular, the anatomically realistic phantom has been modeled by using the real atlas of a mouse as a reference. The mouse phantom includes a 3D-printed skeleton and the main abdominal organs such as the liver, spleen, and kidneys obtained by using doped copolymer-in-oil material with 3D-printed molds. In addition, the acoustic and optical properties of the tissue-mimicking material and the long-term stability have been broadly characterized. RESULTS: Furthermore, our studies showed that the phantom is durable and stable for more than 200 days, under normal storage and repeated use. Fabrication protocol is easy to reproduce. As a result, the proposed morphologically realistic mouse phantom offers durability, material compatibility, and an unprecedented realistic resemblance to the actual rodents' anatomy in PAI. CONCLUSION: This durable morphologically realistic mouse phantom would minimize the animal experiments in compliance with the 3R principle of Replacement, Reduction, and Refinement. To our knowledge, this is the first time an anatomically realistic heterogeneous mouse phantom has been proposed for PAI in pre-clinical animal imaging and tested its durability over 200 days.

Land Use and Land Cover Change Detection Using the Random Forest Approach: The Case of The Upper Blue Nile River Basin, Ethiopia.

Monitoring land use change dynamics is critical for tackling food security, climate change, and biodiversity loss on a global scale. This study is designed to classify land use and land cover in the upper Blue Nile River Basin (BNRB) using a random forest (RF) algorithm. The Landsat images for Landsat 45, Landsat 7, and Landsat 8 are used for classification purposes. The study area is classified into seven land use/land cover classes: cultivated lands, bare lands, built-ups, forests, grazing lands, shrublands, and waterbodies. The accuracy of classified images is 83%, 85%, and 91% using the Kappa index of agreements. From 1983 to 2022 periods, cultivated lands and built-up areas increased by 47541 and 1777 km2, respectively, at the expense of grazing lands, shrublands, and forests. Furthermore, the area of water bodies has increased by 662 km2 due to the construction of small and large-scale irrigation and hydroelectric power generation dams. The main factors that determine agricultural land expansion are related to population growth. Therefore, land use and land cover change detection using a random forest is an important technique for multispectral satellite data classification to understand the optimal use of natural resources, conservation practices, and decision-making for sustainable development.

Speed-of-sound compensated photoacoustic tomography for accurate imaging.

PURPOSE: In most photoacoustic (PA) tomographic reconstructions, variations in speed-of-sound (SOS) of the subject are neglected under the assumption of acoustic homogeneity. Biological tissue with spatially heterogeneous SOS cannot be accurately reconstructed under this assumption. The authors present experimental and image reconstruction methods with which 2D SOS distributions can be accurately acquired and reconstructed, and with which the SOS map can be used subsequently to reconstruct highly accurate PA tomograms. METHODS: The authors begin with a 2D iterative reconstruction approach in an ultrasound transmission tomography setting, which uses ray refracted paths instead of straight ray paths to recover accurate SOS images of the subject. Subsequently, they use the SOS distribution in a new 2D iterative PA reconstruction approach, where refraction of rays originating from PA sources is accounted for in accurately retrieving the distribution of these sources. Both the SOS reconstruction and SOS-compensated PA reconstruction methods utilize the Eikonal equation to model acoustic wavefront propagation. The equation is solved using a high accuracy fast marching method. RESULTS: The authors validated the new reconstruction algorithms using numerical phantoms. For experiments they utilized the recently introduced PER-PACT method which can be used to simultaneously acquire SOS and PA data from subjects. CONCLUSIONS: It is first confirmed that it is important to take SOS inhomogeneities into account in high resolution PA tomography. The iterative reconstruction algorithms, that model acoustic refractive effects, in reconstructing SOS distributions, and subsequently using these distributions to correct PA tomograms, yield artifact-free highly accurate images. The approach of using the hybrid measurement method and the new reconstruction algorithms is successful in substantially improving the quality of PA images with a minimization of blurring and artifacts.

Superpixel spectral unmixing framework for the volumetric assessment of tissue chromophores: A photoacoustic data-driven approach.

The assessment of tissue chromophores at a volumetric scale is vital for an improved diagnosis and treatment of a large number of diseases. Spectral photoacoustic imaging (sPAI) co-registered with high-resolution ultrasound (US) is an innovative technology that has a great potential for clinical translation as it can assess the volumetric distribution of the tissue components. Conventionally, to detect and separate the chromophores from sPAI, an input of the expected tissue absorption spectra is required. However, in pathological conditions, the prediction of the absorption spectra is difficult as it can change with respect to the physiological state. Besides, this conventional approach can also be hampered due to spectral coloring, which is a prominent distortion effect that induces spectral changes at depth. Here, we are proposing a novel data-driven framework that can overcome all these limitations and provide an improved assessment of the tissue chromophores. We have developed a superpixel spectral unmixing (SPAX) approach that can detect the most and less prominent absorber spectra and their volumetric distribution without any user interactions. Within the SPAX framework, we have also implemented an advanced spectral coloring compensation approach by utilizing US image segmentation and Monte Carlo simulations, based on a predefined library of optical properties. The framework has been tested on tissue-mimicking phantoms and also on healthy animals. The obtained results show enhanced specificity and sensitivity for the detection of tissue chromophores. To our knowledge, this is a unique framework that accounts for the spectral coloring and provides automated detection of tissue spectral signatures at a volumetric scale, which can open many possibilities for translational research.

Early diagnosis of bladder cancer by photoacoustic imaging of tumor-targeted gold nanorods.

Detection and removal of bladder cancer lesions at an early stage is crucial for preventing tumor relapse and progression. This study aimed to develop a new technological platform for the visualization of small and flat urothelial lesions of high-grade bladder carcinoma in situ (CIS). We found that the integrin α5ß1, overexpressed in bladder cancer cell lines, murine orthotopic bladder cancer and human bladder CIS, can be exploited as a receptor for targeted delivery of GNRs functionalized with the cyclic CphgisoDGRG peptide (Iso4). The GNRs@Chit-Iso4 was stable in urine and selectively recognized α5ß1 positive neoplastic urothelium, while low frequency ultrasound-assisted shaking of intravesically instilled GNRs@Chit-Iso4 allowed the distribution of nanoparticles across the entire volume of the bladder. Photoacoustic imaging of GNRs@Chit-Iso4 bound to tumor cells allowed for the detection of neoplastic lesions smaller than 0.5 mm that were undetectable by ultrasound imaging and bioluminescence.

Passive element enriched photoacoustic computed tomography (PER PACT) for simultaneous imaging of acoustic propagation properties and light absorption.

We present a 'hybrid' imaging approach which can image both light absorption properties and acoustic transmission properties of an object in a two-dimensional slice using a computed tomography (CT) photoacoustic imager. The ultrasound transmission measurement method uses a strong optical absorber of small cross-section placed in the path of the light illuminating the sample. This absorber, which we call a passive element acts as a source of ultrasound. The interaction of ultrasound with the sample can be measured in transmission, using the same ultrasound detector used for photoacoustics. Such measurements are made at various angles around the sample in a CT approach. Images of the ultrasound propagation parameters, attenuation and speed of sound, can be reconstructed by inversion of a measurement model. We validate the method on specially designed phantoms and biological specimens. The obtained images are quantitative in terms of the shape, size, location, and acoustic properties of the examined heterogeneities.

Multiple passive element enriched photoacoustic computed tomography.

Recently, we presented a method using laser-induced ultrasound from an external absorber (passive element) to image the ultrasound transmission parameters of an object under photoacoustic tomographic investigation. The method suffers from long measurement times due to the requirement for a large number of views and consequently physical projections around the object. Here we propose and validate an approach that permits a multitude of views to be obtained within a limited projection scenario. The approach uses a plurality of spatially distributed external absorbers in the path of the light, that results in multiple laser-induced ultrasound sources to interrogate the object from a number of angles. This reduces the required number of rotation angles or physical projections around the object, permitting a considerable reduction in imaging time without significant degradation in image quality. The approach brings the concept of hybrid imaging of ultrasound transmission parameters together with photoacoustic imaging, into the realm of practical application.

An overview of assessment tools for determination of biological Magnesium implant degradation.

Medical implants made of biodegradable materials are advantageous for short-term applications as fracture fixation and mechanical support during bone healing. After completing the healing process, the implant biodegrades without any long-term side effects nor any need for surgical removal. In particular, Magnesium (Mg) implants, while degrading, can cause physiological changes in the tissues surrounding the implant. The evaluation of structural remodeling is relevant, however, the functional assessment is crucial to provide information about physiological changes in tissues, which can be applied as an early marker during the healing process. Hence, non-invasive monitoring of structural and functional changes in the surrounding tissue during the healing process is essential, and the need for new assessing methods is emerging. This paper provides an assessment of Mg based implants, and an extensive review of the literature is presented with the focus on the imaging techniques for investigation of the Mg implants' biodegradation. The potential of a hybrid analysis, including Near-Infrared Spectroscopy (NIRS) and photoacoustic imaging (PAI) technology, is further discussed. A hybrid solution may play a significant role in monitoring implants and have several advantages for monitoring tissue oxygenation in addition to tissue's acidity, which is directly connected to the Mg implants degradation process. Such a hybrid assessment system can be a simple, ambulant, and less costly technology with the potential for clinically monitoring of Mg implants at site.

Assessment of the Theranostic Potential of Gold Nanostars-A Multimodal Imaging and Photothermal Treatment Study.

Gold nanoparticles offer the possibility to combine both imaging and therapy of otherwise difficult to treat tumors. To validate and further improve their potential, we describe the use of gold nanostars that were functionalized with a polyethyleneglycol-maleimide coating for in vitro and in vivo photoacoustic imaging (PAI), computed tomography (CT), as well as photothermal therapy (PTT) of cancer cells and tumor masses, respectively. Nanostar shaped particles show a high absorption coefficient in the near infrared region and have a hydrodynamic size in biological medium around 100 nm, which allows optimal intra-tumoral retention. Using these nanostars for in vitro labeling of tumor cells, high intracellular nanostar concentrations could be achieved, resulting in high PAI and CT contrast and effective PTT. By injecting the nanostars intratumorally, high contrast could be generated in vivo using PAI and CT, which allowed successful multi-modal tumor imaging. PTT was successfully induced, resulting in tumor cell death and subsequent inhibition of tumor growth. Therefore, gold nanostars are versatile theranostic agents for tumor therapy.

Preoperative measurement of cutaneous melanoma and nevi thickness with photoacoustic imaging.

Photoacoustic imaging (PAI) is an emerging biomedical imaging technology, which can potentially be used in the clinic to preoperatively measure melanoma thickness and guide biopsy depth and sample location. We recruited 27 patients with pigmented cutaneous lesions suspicious for melanoma to test the feasibility of a handheld linear-array photoacoustic probe in imaging lesion architecture and measuring tumor depth. The probe was assessed in terms of measurement accuracy, image quality, and ease of application. Photoacoustic scans included single wavelength, spectral unmixing, and three-dimensional (3-D) scans. The photoacoustically measured lesion thickness gave a high correlation with the histological thickness measured from resected surgical samples ([Formula: see text], [Formula: see text] for melanomas, [Formula: see text], [Formula: see text] for nevi). Thickness measurements were possible for 23 of 26 cases for nevi and all (6) cases for melanoma. Our results show that handheld, linear-array PAI is highly reliable in measuring cutaneous lesion thickness in vivo, and can potentially be used to inform biopsy procedure and improve patient management.

Clinician Adherence to Hypertension Screening and Care Guidelines.

This quality improvement study assesses opportunistic blood pressure measurement, communication of blood pressure reading to adult patients, and recommendation for a follow-up visit at health care facilities in 2 major cities in India.