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Purpose: Augmented reality (AR) is an innovative approach that could assist percutaneous procedures; by directly seeing "through" a phantom, targeting a lesion might be more intuitive than using ultrasound (US). The objective of this study was to compare the performance of experienced interventional radiologists and operators untrained in soft tissue lesion puncture using AR guidance and standard US guidance. Material and Methods: Three trained interventional radiologists with 5–10 years of experience and three untrained operators performed punctures of five targets in an abdominal phantom, with US guidance and AR guidance. Correct targeting, accuracy (defined as the Euclidean distance between the tip and the center of the target), planning time, and puncture time were documented. Results: Accuracy was higher for the trained group than the untrained group using US guidance (1 mm versus 4 mm, p = 0.001), but not when using AR guidance (4 mm vs. 4 mm, p = 0.76). All operators combined, no significant difference was found concerning accuracy between US and AR guidance (2 mm vs. 4 mm, p = 0.09), but planning time and puncture time were significantly shorter using AR (respectively, 15.1 s vs. 74 s, p < 0.001; 16.1 s vs. 59 s; p < 0.001). Conclusion: Untrained and trained operators obtained comparable accuracy in percutaneous punctures when using AR guidance whereas US performance was better in the experienced group. All operators together, accuracy was similar between US and AR guidance, but shorter planning time, puncture time were found for AR guidance. [ABSTRACT FROM AUTHOR]

Accurate and sensitive analysis of cancer‐associated microRNAs in living tissue is of great significance for the early diagnosis and treatment of cancer. Herein, a hierarchical nanoprobe denoted as UCNP‐QDs‐GNPs is delicately designed, where a near‐infrared (NIR) absorptive upconversion nanoparticle (UCNP) serves as the core, broad‐absorptive and bright emissive quantum dots (QDs) and emission‐quencher gold nanoparticles (GNPs) surround as satellites for microRNA imaging and image‐guided cancer therapy. Through the programmed assembly of heterobivalent DNA‐conjugated QDs with DNA‐modified GNPs and UCNPs, the well‐defined nanostructured UCNP‐QDs‐GNPs are generated with quenched fluorescence. Upon encountering the microRNA‐21 target, GNPs underwent catalytic disassembly, resulting in the concurrent recovery and amplification of fluorescence from QDs and UCNPs, which enabled sensitive imaging and quantification of microRNA‐21 within living cells. Furthermore, dithiol‐constituted aggregation‐induced emission (AIE) photosensitizers bonded on the surface of QDs, are effectively photosensitized by the QDs. The NIR excitation harvested by UCNPs is therefore efficiently transferred to QDs and subsequently converged on the AIE photosensitizers, boosting photodynamic activity for image‐guided therapy in deep‐seated tumors. The DNA‐programmed (de)hybridization strategy, facilitating the conversion of NIR excitation into imaging signals and photodynamic activity, offers a promising avenue for the early theranostics of malignancies. [ABSTRACT FROM AUTHOR]

High‐performance theranostic systems are of paramount importance for achieving precise image‐guided cancer immunotherapy. Here, a novel nanoplatform is presented that integrates aggregation‐induced emission luminogen (AIEgen) with prussian blue (PB) nanocatalyzer for robust cancer immunotherapy. The AIEgen with dimethylamine substitution demonstrates compelling near‐infrared (NIR) light‐induced photothermal conversion and photodynamic therapy (PDT) capabilities. By incorporating AIEgen into porous PBNPs, and further enveloped within M1 macrophage membrane, a tumor‐specific theranostic nanoagent is constructed. This strategic integration effectively constrains the molecular motion of AIEgen, leading to amplified NIR‐II fluorescence brightness and PDT attributes. Moreover, PBNPs can catalyze tumor‐overexpressed H2O2 to generate oxygen to boost PDT efficacy, and PB's NIR absorption also intensifies photoacoustic imaging and photothermal effect. The integration of NIR‐II fluorescence and photoacoustic imaging provides comprehensive information for photoimmunotherapy in orthotopic breast cancer‐bearing mice. Leveraging its potent immunogenic cell death effect, the nanoagent not only significantly inhibits cancer growth, but also generates a whole‐cell therapeutic cancer vaccine to protect mice from tumor rechallenge. In highly malignant post‐surgery breast cancer models, the nanoagent enables both accurate identification of residual tumors and efficient inhibition of postoperative tumor recurrence and pulmonary metastasis. This study will offer valuable insights for creating highly efficacious and multifaceted photoimmunotherapy protocols. [ABSTRACT FROM AUTHOR]

Image-guided disease treatment not only significantly enhances the efficacy of disease treatment but also minimizes unnecessary medication doses. Near-infrared II (NIR-II, 1000–1700 nm) bioimaging has been considered as one of the ideal bioimaging techniques in recent years due to its deep tissue penetration and low tissue fluorescence scattering. Here, we design the highly biocompatible lanthanide-doped nanoparticles NaYF4:Ce/Er@NaYbF4:Er@NaYF4:Nd-ZnPc/RB/mPEG-FA (RENPs-ZnPc/RB/mPEG-FA). Under an 808 nm excitation, the internal rare earth-doped nanoparticles (RENPs) can emit NIR-II luminescence for imaging. In addition, the generated upconversion luminescence in the visible region can be used as an excitation light source to excite the photosensitizers on the surface of the RENPs to generate singlet oxygen for antitumor photodynamic therapy. Based on the guidance of NIR-II imaging, the intratumoral injection approach is selected. During the treatment (day 7) after the second dose of RENPs-ZnPc/RB/mPEG-FA injection, the tumors are almost inhibited and eliminated, and there is no sign of recurrence in the follow-up observations. Interestingly, intravenously injected nanoparticles also enable high-resolution skeletal imaging with a high signal-to-background ratio, which holds promise for the clinical translation of RENPs-ZnPc/RB/mPEG-FA as versatile probes for imaging and therapy. [ABSTRACT FROM AUTHOR]

Targeted medicine uses the distinctive features of cancer cells to find and destroy tumors. We present human epidermal growth factor receptor 2 (HER2)-targeted PLGA–chitosan nanoparticles for cancer therapy and visualization. Loading with two near-infrared (NIR) dyes provides imaging in the NIR transparency window and phototherapy triggered by 808 nm light. Nile Blue (NB) is a biocompatible solvatochromic NIR dye that serves as an imaging agent. Laser irradiation of IR-780 dye leads to a temperature rise and the generation of reactive oxygen species (ROS). Resonance energy transfer between two dyes allows visualization of tumors in a wide range of visible and IR wavelengths. The combination of two NIR dyes enables the use of nanoparticles for diagnostics only or theranostics. Modification of poly(lactic-co-glycolic acid) (PLGA)–chitosan nanoparticles with trastuzumab provides an efficient nanoparticle uptake by tumor cells and promotes more than sixfold specificity towards HER2-positive cells, leading to a synergistic anticancer effect. We demonstrate optical imaging of the HER2-positive mouse mammary tumor and tumor-specific accumulation of PLGA–IR-780–NB nanoparticles in vivo after intravenous administration. We managed to achieve almost complete suppression of the proliferative activity of cells in vitro by irradiation with an 808 nm laser with a power of 0.27 W for 1 min at a concentration at which nanoparticles are nontoxic to cells in the dark. [ABSTRACT FROM AUTHOR]

Peripheral arterial diseases are commonly managed with endovascular procedures, which often face limitations in device control and visualization under X-ray fluoroscopy guidance. In response, we developed the CathCam, an angioscope integrated into an expandable cable-driven parallel mechanism to enhance real-time visualization, precise device positioning and catheter support for successful plaque crossing. The primary objective of this study was to assess and compare the performance of the novel CathCam with respect to conventional catheters and the CathPilot (i.e., CathCam without the angioscope), for applications in crossing chronic total occlusions (CTO). We first assessed the system in 3D-printed phantom models, followed by an ex vivo evaluation with CTO samples from a patient's superficial femoral artery. We measured and compared success rates, crossing times, and fluoroscopy times in both experiments. The CathCam demonstrated a 100% success rate in phantom experiments and a 75% success rate in ex vivo experiments with CTO samples, compared to conventional catheters, with 35% and 25% success rates, respectively. The average crossing times for the CathCam and the conventional catheter were 31 s and 502 s for the phantom experiments and 210 s and 511 s for the actual CTO lesions. The Cathcam also showed to be a reliable endovascular imaging approach in an in vivo experiment. Compared to conventional catheters, the CathCam significantly increased the success rate and reduced crossing and fluoroscopy times in both phantom and ex vivo setups. CathCam can potentially improve clinical outcomes for minimally invasive endovascular interventions by offering high-resolution real-time imaging alongside accurate device control. [ABSTRACT FROM AUTHOR]

Abstract Near-infrared (NIR) organic small molecule dyes (OSMDs) are effective photothermal agents for photothermal therapy (PTT) due to their advantages of low cost and toxicity, good biodegradation, and strong NIR absorption over a wide wavelength range. Nevertheless, OSMDs have limited applicability in PTT due to their low photothermal conversion efficiency and inadequate destruction of tumor regions that are nonirradiated by NIR light. However, they can also act as photosensitizers (PSs) to produce reactive oxygen species (ROS), which can be further eradicated by using ROS-related therapies to address the above limitations of PTT. In this review, the synergistic mechanism, composition, and properties of photodynamic therapy (PDT)–PTT nanoplatforms were comprehensively discussed. In addition, some specific strategies for further improving the combined PTT and PDT based on OSMDs for cancer to completely eradicate cancer cells were outlined. These strategies include performing image-guided co-therapy, enhancing tumor infiltration, increasing H2O2 or O2 in the tumor microenvironment, and loading anticancer drugs onto nanoplatforms to enable combined therapy with phototherapy and chemotherapy. Meanwhile, the intriguing prospects and challenges of this treatment modality were also summarized with a focus on the future trends of its clinical application. Graphical Abstract

Abstract Background Nano-photothermal therapy (NPTT) has gained wide attention in cancer treatment due to its high efficiency and selective treatment strategy. The biggest challenges in the clinical application are the lack of (i) a reliable platform for mapping the thermal dose and (ii) efficient photothermal agents (PTAs). This study developed a 3D treatment planning for NPTT to reduce the uncertainty of treatment procedures, based on our synthesized nanohybrid. Methods This study aimed to develop a three-dimensional finite element method (FEM) model for in vivo NPTT in mice using magneto-plasmonic nanohybrids, which are complex assemblies of superparamagnetic iron oxide nanoparticles and gold nanorods. The model was based on Pennes' bio-heat equation and utilized a geometrically correct mice whole-body. CT26 colon tumor-bearing BALB/c mice were injected with nanohybrids and imaged using MRI (3 Tesla) before and after injection. MR images were segmented, and STereoLithography (STL) files of mice bodies and nanohybrid distribution in the tumor were established to create a realistic geometry for the model. The accuracy of the temperature predictions was validated by using an infrared (IR) camera. Results The photothermal conversion efficiency of the nanohybrids was experimentally determined to be approximately 30%. The intratumoral (IT) injection group showed the highest temperature increase, with a maximum of 17 °C observed at the hottest point on the surface of the tumor-bearing mice for 300 s of laser exposure at a power density of 1.4 W/cm2. Furthermore, the highest level of tissue damage, with a maximum value of Ω = 0.4, was observed in the IT injection group, as determined through a simulation study. Conclusions Our synthesized nanohybrid shows potential as an effective agent for MRI-guided NPTT. The developed model accurately predicted temperature distributions and tissue damage in the tumor. However, the current temperature validation method, which relies on limited 2D measurements, may be too lenient. Further refinement is necessary to improve validation. Nevertheless, the presented FEM model holds great promise for clinical NPTT treatment planning.

Cancer is one of the most well-studied diseases and there have been significant advancements over the last few decades in understanding its molecular and cellular mechanisms. Although the current treatments (e.g., chemotherapy, radiotherapy, gene therapy and immunotherapy) have provided complete cancer remission for many patients, cancer still remains one of the most common causes of death in the world. The main reasons for the poor response rates for different cancers include the lack of drug specificity, drug resistance and toxic side effects (i.e., in healthy tissues). For addressing the limitations of conventional cancer treatments, nanotechnology has shown to be an important field for constructing different nanoparticles for destroying cancer cells. Due to their size (i.e., less than 1 μm), nanoparticles can deliver significant amounts of cancer drugs to tumors and are able to carry moieties (e.g., folate, peptides) for targeting specific types of cancer cells (i.e., through receptor-mediated endocytosis). Liposomes, composed of phospholipids and an interior aqueous core, can be used as specialized delivery vehicles as they can load different types of cancer therapy agents (e.g., drugs, photosensitizers, genetic material). In addition, the ability to load imaging agents (e.g., fluorophores, radioisotopes, MRI contrast media) enable these nanoparticles to be used for monitoring the progress of treatment. This review examines a wide variety of different liposomes for cancer theranostics, with the different available treatments (e.g., photothermal, photodynamic) and imaging modalities discussed for different cancers. [ABSTRACT FROM AUTHOR]

Near-infrared (NIR) organic small molecule dyes (OSMDs) are effective photothermal agents for photothermal therapy (PTT) due to their advantages of low cost and toxicity, good biodegradation, and strong NIR absorption over a wide wavelength range. Nevertheless, OSMDs have limited applicability in PTT due to their low photothermal conversion efficiency and inadequate destruction of tumor regions that are nonirradiated by NIR light. However, they can also act as photosensitizers (PSs) to produce reactive oxygen species (ROS), which can be further eradicated by using ROS-related therapies to address the above limitations of PTT. In this review, the synergistic mechanism, composition, and properties of photodynamic therapy (PDT)–PTT nanoplatforms were comprehensively discussed. In addition, some specific strategies for further improving the combined PTT and PDT based on OSMDs for cancer to completely eradicate cancer cells were outlined. These strategies include performing image-guided co-therapy, enhancing tumor infiltration, increasing H2O2 or O2 in the tumor microenvironment, and loading anticancer drugs onto nanoplatforms to enable combined therapy with phototherapy and chemotherapy. Meanwhile, the intriguing prospects and challenges of this treatment modality were also summarized with a focus on the future trends of its clinical application. [ABSTRACT FROM AUTHOR]

Background: Nano-photothermal therapy (NPTT) has gained wide attention in cancer treatment due to its high efficiency and selective treatment strategy. The biggest challenges in the clinical application are the lack of (i) a reliable platform for mapping the thermal dose and (ii) efficient photothermal agents (PTAs). This study developed a 3D treatment planning for NPTT to reduce the uncertainty of treatment procedures, based on our synthesized nanohybrid. Methods: This study aimed to develop a three-dimensional finite element method (FEM) model for in vivo NPTT in mice using magneto-plasmonic nanohybrids, which are complex assemblies of superparamagnetic iron oxide nanoparticles and gold nanorods. The model was based on Pennes' bio-heat equation and utilized a geometrically correct mice whole-body. CT26 colon tumor-bearing BALB/c mice were injected with nanohybrids and imaged using MRI (3 Tesla) before and after injection. MR images were segmented, and STereoLithography (STL) files of mice bodies and nanohybrid distribution in the tumor were established to create a realistic geometry for the model. The accuracy of the temperature predictions was validated by using an infrared (IR) camera. Results: The photothermal conversion efficiency of the nanohybrids was experimentally determined to be approximately 30%. The intratumoral (IT) injection group showed the highest temperature increase, with a maximum of 17 °C observed at the hottest point on the surface of the tumor-bearing mice for 300 s of laser exposure at a power density of 1.4 W/cm2. Furthermore, the highest level of tissue damage, with a maximum value of Ω = 0.4, was observed in the IT injection group, as determined through a simulation study. Conclusions: Our synthesized nanohybrid shows potential as an effective agent for MRI-guided NPTT. The developed model accurately predicted temperature distributions and tissue damage in the tumor. However, the current temperature validation method, which relies on limited 2D measurements, may be too lenient. Further refinement is necessary to improve validation. Nevertheless, the presented FEM model holds great promise for clinical NPTT treatment planning. [ABSTRACT FROM AUTHOR]

Multifunctional phototheranostics that integrate several diagnostic and therapeutic strategies into one platform hold great promise for precision medicine. However, it is really difficult for one molecule to possess multimodality optical imaging and therapy properties that all functions are in the optimized mode because the absorbed photoenergy is fixed. Herein, a smart one‐for‐all nanoagent that the photophysical energy transformation processes can be facilely tuned by external light stimuli is developed for precise multifunctional image‐guided therapy. A dithienylethene‐based molecule is designed and synthesized because it has two light‐switchable forms. In the ring‐closed form, most of the absorbed energy dissipates via nonradiative thermal deactivation for photoacoustic (PA) imaging. In the ring‐open form, the molecule possesses obvious aggregation‐induced emission features with excellent fluorescence and photodynamic therapy properties. In vivo experiments demonstrate that preoperative PA and fluorescence imaging help to delineate tumors in a high‐contrast manner, and intraoperative fluorescence imaging is able to sensitively detect tiny residual tumors. Furthermore, the nanoagent can induce immunogenic cell death to elicit antitumor immunity and significantly suppress solid tumors. This work develops a smart one‐for‐all agent that the photophysical energy transformation and related phototheranostic properties can be optimized by light‐driven structure switch, which is promising for multifunctional biomedical applications. [ABSTRACT FROM AUTHOR]

Microwave ablation (MWA) is becoming an increasingly important minimally invasive treatment option for localized tumors in many organ systems due to recent advancements in microwave technology that have conferred many advantages over other tumor ablation modalities. Despite these improvements in technology and development of applicators for site-specific tumor applications, the vast majority of commercially available MWA applicators are generally designed to create large-volume, symmetric, ellipsoid or spherically-shaped treatment zones and often lack the consistency, predictability, and spatial control needed to treat tumor targets near critical structures that are vulnerable to inadvertent thermal injury. The relatively new development and ongoing translation of directional microwave ablation (DMWA) technology, however, has the potential to confer an added level of control over the treatment zone shape relative to applicator position, and shows great promise to expand MWA’s clinical applicability in treating tumors in challenging locations. This paper presents a review of the industry-standard commercially available MWA technology, its clinical applications, and its limitations when used for minimally-invasive tumor treatment in medical practice followed by discussion of new advancements in experimental directional microwave ablation (DMWA) technology, various techniques and approaches to its use, and examples of how this technology may be used to treat tumors in challenging locations that may otherwise preclude safe treatment by conventional omni-directional MWA devices.

Abstract Molecular imaging technologies are increasingly used to diagnose, monitor, and guide treatment of i.e., cancer. In this review, the current status and future prospects of the use of molecular imaging as an instrument to help realize precision surgery is addressed with focus on the main components that form the conceptual basis of intraoperative molecular imaging. Paramount for successful interventions is the relevance and accessibility of surgical targets. In addition, selection of the correct combination of imaging agents and modalities is critical to visualize both microscopic and bulk disease sites with high affinity and specificity. In this context developments within engineering/imaging physics continue to drive the growth of image-guided surgery. Particularly important herein is enhancement of sensitivity through improved contrast and spatial resolution, features that are critical if sites of cancer involvement are not to be overlooked during surgery. By facilitating the connection between surgical planning and surgical execution, digital surgery technologies such as computer-aided visualization nicely complement these technologies. The complexity of image guidance, combined with the plurality of technologies that are becoming available, also drives the need for evaluation mechanisms that can objectively score the impact that technologies exert on the performance of healthcare professionals and outcome improvement for patients.

This paper provides an overview of current robot-assisted high-intensity focused ultrasound (HIFU) systems for image-guided therapies. HIFU is a minimally invasive technique that relies on the thermo-mechanical effects of focused ultrasound waves to perform clinical treatments, such as tumor ablation, mild hyperthermia adjuvant to radiation or chemotherapy, vein occlusion, and many others. HIFU is typically performed under ultrasound (USgHIFU) or magnetic resonance imaging guidance (MRgHIFU), which provide intra-operative monitoring of treatment outcomes. Robot-assisted HIFU probe manipulation provides precise HIFU focal control to avoid damage to surrounding sensitive anatomy, such as blood vessels, nerve bundles, or adjacent organs. These clinical and technical benefits have promoted the rapid adoption of robot-assisted HIFU in the past several decades. This paper aims to present the recent developments of robot-assisted HIFU by summarizing the key features and clinical applications of each system. The paper concludes with a comparison and discussion of future perspectives on robot-assisted HIFU. [ABSTRACT FROM AUTHOR]

Background: The medical technical innovations over the last decade have made operations in the highly sensitive regions of the brain much safer. Objective: Presentation of how far computer assistance and robotics have become incorporated into clinical neurosurgery. Material and method: Evaluation of the scientific literature and analysis of the certification status of the corresponding medical devices. Results: The rapid development of computer technology and the switch to digital imaging has led to the widespread introduction of neurosurgical planning software and intraoperative neuronavigation. In the field of robotics, the penetration into clinical neurosurgery is currently still largely limited to the automatic setting of trajectories. Conclusion: The digitalization of imaging has fundamentally transformed neurosurgery. In the field of cranial neurosurgery, computer-assisted procedures can now be distinguished from noncomputer-assisted procedures only in a handful of cases. In the coming years important innovations for the clinical implementation can be expected in the field of robotics. [ABSTRACT FROM AUTHOR]

Phantoms are physical models that mimic biological tissue and its properties in medical imaging. They play an important role in medical quality assurance, research, education, and training, since they can offer an adequate test environment. As the use of medical imaging modalities is a growing field in medicine phantoms are likewise evolving very rapidly. The variety of these phantoms is as wide as the modalities and applications, thus ranging from simple to highly detailed in the representation of anatomy. The objective of this paper is to propose a categorization of the objects defined under the term "phantom" in the literature, to reduce the misuse of this term and maintain a common understanding of the topic as well as ensure that future research efforts are based on solid foundations. This field of expertise is driven by the connection between engineering design and the field of medical technology since engineers are essential in the development of phantoms and require a clear understanding of terminology and applications. Based on a literature analysis a novel classification into distinct categories for phantoms, consisting of possible purposes, applications, manufacturing techniques, and custom design features, is developed. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging using external contrast agents is emerging as a powerful modality for real-time molecular imaging of deep-seated tumors. There are several chromophores, such as indocyanine green and IRDye800, that can potentially be used for photoacoustic imaging; however, their use is limited due to several drawbacks, particularly photostability. There is, therefore, an urgent need to design agents to enhance contrast in photoacoustic imaging. Naphthalocyanine dyes have been demonstrated for their use as photoacoustic contrast agents; however, their low solubility in aqueous solvents and high aggregation propensity limit their application. In this study, we report the synthesis and characterization of silicon-centered naphthalocyanine dyes with high aqueous solubility and near infra-red (NIR) absorption in the range of 850–920 nm which make them ideal candidates for photoacoustic imaging. A series of Silicon-centered naphthalocyanine dyes were developed with varying axial and peripheral substitutions, all in an attempt to enhance their aqueous solubility and improve photophysical properties. We demonstrate that axial incorporation of charged ammonium mesylate group enhances water solubility. Moreover, the incorporation of peripheral 2-methoxyethoxy groups at the α-position modulates the electronic properties by altering the π-electron delocalization and enhancing photoacoustic signal amplitude. In addition, all the dyes were synthesized to incorporate an N-hydroxysuccinimidyl group to enable further bioconjugation. In summary, we report the synthesis of water-soluble silicon-centered naphthalocyanine dyes with a high photoacoustic signal amplitude that can potentially be used as contrast agents for molecular photoacoustic imaging. [ABSTRACT FROM AUTHOR]

A longstanding problem with conventional cancer therapy is the nonspecific distribution of chemotherapeutics. Monitoring drug release in vivo via noninvasive bioimaging can thus have value, but it is difficult to distinguish loaded from released drug in live tissue. Here, this work describes an injectable supramolecular hydrogel that allows slow and trackable release of doxorubicin (Dox) via photoacoustic (PA) tomography. Dox is covalently linked with photoacoustic methylene blue (MB) to monitor Dox before, during, and after release from the hydrogel carrier. The conjugate (MB‐Dox) possesses an IC50 of 161.4 × 10−9 m against human ovarian carcinoma (SKOV3) cells and loads into a DNA‐clad hydrogel with 91.3% loading efficiency due to MB‐Dox's inherent intramolecular affinity to DNA. The hydrogel is biodegradable by nuclease digestion, which causes gradual release of MB‐Dox. This release rate is tunable based on the wt% of the hydrogel. This hydrogel maintains distinct PA contrast on the order of days when injected in vivo and demonstrates activatable PA spectral shifts during hydrogel degradation. The released and loaded payload can be imaged relative to live tissue via PA and ultrasound signal being overlaid in real‐time. The hydrogel slowed the rate of the murine intraperitoneal tumor growth 72.2% more than free Dox. [ABSTRACT FROM AUTHOR]

The extreme aggressiveness and lethality of many cancer types appeal to the problem of the development of new-generation treatment strategies based on smart materials with a mechanism of action that differs from standard treatment approaches. The targeted delivery of nanoparticles to specific cancer cell receptors is believed to be such a strategy; however, there are no targeted nano-drugs that have successfully completed clinical trials to date. To meet the challenge, we designed an alternative way to eliminate tumors in vivo. Here, we show for the first time that the targeting of lectin-equipped polymer nanoparticles to the glycosylation profile of cancer cells, followed by photodynamic therapy (PDT), is a promising strategy for the treatment of aggressive tumors. We synthesized polymer nanoparticles loaded with magnetite and a PDT agent, IR775 dye (mPLGA/IR775). The magnetite incorporation into the PLGA particle structure allows for the quantitative tracking of their accumulation in different organs and the performing of magnetic-assisted delivery, while IR775 makes fluorescent in vivo bioimaging as well as light-induced PDT possible, thus realizing the theranostics concept. To equip PLGA nanoparticles with targeting modality, the particles were conjugated with lectins of different origins, and the flow cytometry screening revealed that the most effective candidate for breast cancer cell labeling is ConA, a lectin from Canavalia ensiformis. In vivo experiments showed that after i.v. administration, mPLGA/IR775–ConA nanoparticles efficiently accumulated in the allograft tumors under the external magnetic field; produced a bright fluorescent signal for in vivo bioimaging; and led to 100% tumor growth inhibition after the single session of PDT, even for large solid tumors of more than 200 mm3 in BALB/c mice. The obtained results indicate that the mPLGA/IR775 nanostructure has great potential to become a highly effective oncotheranostic agent. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) is a type of cancer treatment capable of damaging tumors using laser irradiation. This procedure can be a promising approach to complement current cancer therapies, due in part to its minimal invasiveness. One of the challenges of photothermal therapy is the potential collateral damage to the surrounding healthy tissue, as well as excessive temperature increase in the target tumor region that can cause tissue carbonization and evaporation. With the aim of increasing the performance of photothermal therapy in damaging targeted tumor while keeping healthy nearby tissue unaffected, this research proposes the use of a feedback control system that considers the cumulative thermal damage to both types of tissue. Two separate control algorithms (fuzzy logic and PI) were designed and tested in silico using simulations made in MATLAB® and Python. Results showed that both controllers successfully accomplished the proposed goals. Therefore, the feasibility of using these automated systems to improve the efficacy and safety of PTT was demonstrated. [ABSTRACT FROM AUTHOR]

Cancer is one of the most well-studied diseases and there have been significant advancements over the last few decades in understanding its molecular and cellular mechanisms. Although the current treatments (e.g., chemotherapy, radiotherapy, gene therapy and immunotherapy) have provided complete cancer remission for many patients, cancer still remains one of the most common causes of death in the world. The main reasons for the poor response rates for different cancers include the lack of drug specificity, drug resistance and toxic side effects (i.e., in healthy tissues). For addressing the limitations of conventional cancer treatments, nanotechnology has shown to be an important field for constructing different nanoparticles for destroying cancer cells. Due to their size (i.e., less than 1 μm), nanoparticles can deliver significant amounts of cancer drugs to tumors and are able to carry moieties (e.g., folate, peptides) for targeting specific types of cancer cells (i.e., through receptor-mediated endocytosis). Liposomes, composed of phospholipids and an interior aqueous core, can be used as specialized delivery vehicles as they can load different types of cancer therapy agents (e.g., drugs, photosensitizers, genetic material). In addition, the ability to load imaging agents (e.g., fluorophores, radioisotopes, MRI contrast media) enable these nanoparticles to be used for monitoring the progress of treatment. This review examines a wide variety of different liposomes for cancer theranostics, with the different available treatments (e.g., photothermal, photodynamic) and imaging modalities discussed for different cancers.

Abstract A longstanding problem with conventional cancer therapy is the nonspecific distribution of chemotherapeutics. Monitoring drug release in vivo via noninvasive bioimaging can thus have value, but it is difficult to distinguish loaded from released drug in live tissue. Here, this work describes an injectable supramolecular hydrogel that allows slow and trackable release of doxorubicin (Dox) via photoacoustic (PA) tomography. Dox is covalently linked with photoacoustic methylene blue (MB) to monitor Dox before, during, and after release from the hydrogel carrier. The conjugate (MB‐Dox) possesses an IC50 of 161.4 × 10−9 m against human ovarian carcinoma (SKOV3) cells and loads into a DNA‐clad hydrogel with 91.3% loading efficiency due to MB‐Dox's inherent intramolecular affinity to DNA. The hydrogel is biodegradable by nuclease digestion, which causes gradual release of MB‐Dox. This release rate is tunable based on the wt% of the hydrogel. This hydrogel maintains distinct PA contrast on the order of days when injected in vivo and demonstrates activatable PA spectral shifts during hydrogel degradation. The released and loaded payload can be imaged relative to live tissue via PA and ultrasound signal being overlaid in real‐time. The hydrogel slowed the rate of the murine intraperitoneal tumor growth 72.2% more than free Dox.

Recently, robots have assisted and contributed to the biomedical field. Scaling down the size of robots to micro/nanoscale can increase the accuracy of targeted medications and decrease the danger of invasive operations in human surgery. Inspired by the motion pattern and collective behaviors of the tiny biological motors in nature, various kinds of sophisticated and programmable microrobots are fabricated with the ability for cargo delivery, bio-imaging, precise operation, etc. In this review, four types of propulsion—magnetically, acoustically, chemically/optically and hybrid driven—and their corresponding features have been outlined and categorized. In particular, the locomotion of these micro/nanorobots, as well as the requirement of biocompatibility, transportation efficiency, and controllable motion for applications in the complex human body environment should be considered. We discuss applications of different propulsion mechanisms in the biomedical field, list their individual benefits, and suggest their potential growth paths. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the feasibility, efficacy, and safety of doxorubicin-eluting bead transarterial chemoembolization (DEB-TACE) as an alternative local treatment for extra-abdominal desmoid tumors (DTs). Methods: Eleven adult female patients (mean age = 40.1 years) with symptomatic, progressively enlarging extra-abdominal DTs were determined ineligible for cryoablation after failing observation or systemic therapy and treated with a single session doxorubicin DEB-TACE. Six rectus sheath, one chest wall, three axilla, and one upper extremity DTs were included. The median follow-up was 155.0 ± 52.3 days. Treatment response was assessed by MRIs and maximum visual analog scale (VAS). Results: All procedures were technically successful without immediate complications. The average size of treated DT was 161.8 ml (range: 28.3–420.0 ml). The mean doxorubicin dose was 13.3 mg/m2. All patients experienced skin changes which improved over time without treatments. No higher-grade adverse events were observed. Initial one-month follow-up MRI demonstrated partial to near-complete tumor necrosis, ranging from 1.4 to 97.6% (mean: 36.4%). Additional follow-up revealed a further reduction of overall tumor volume (mean: − 38.1%, p < 0.0001) and maximum VAS (mean: − 2.6, p = 0.0026) in 10 out of 11 patients (90.9%). After the first month, the residual tumors exhibited continued volume reduction in 10 out of 11 patients (mean: − 16.5%, p = 0.0230). There was also a significant decrease of T2 signal intensity within residual tumor on the latest follow-up (mean: − 29.6%, p = 0.0217), suggesting a reduction in tumor cellularity. Conclusion: DEB-TACE may be a safe and effective local treatment alternative in DT patients. [ABSTRACT FROM AUTHOR]

Nanoparticle-mediated light-activated therapies, such as photodynamic therapy and photothermal therapy, are earnestly being viewed as efficient interventional strategies against several cancer types. Theranostics is a key hallmark of cancer nanomedicine since it allows diagnosis and therapy of both primary and metastatic cancer using a single nanoprobe. Advanced in vivo diagnostic imaging using theranostic nanoparticles not only provides precise information about the location of tumor/s but also outlines the narrow time window corresponding to the maximum tumor-specific drug accumulation. Such information plays a critical role in guiding light-activated therapies with high spatio-temporal accuracy. Furthermore, theranostics facilitates monitoring the progression of therapy in real time. Herein, we provide a general review of the application of theranostic nanoparticles for in vivo image-guided light-activated therapy in cancer. The imaging modalities considered here include fluorescence imaging, photoacoustic imaging, thermal imaging, magnetic resonance imaging, X-ray computed tomography, positron emission tomography, and single-photon emission computed tomography. The review concludes with a brief discussion about the broad scope of theranostic light-activated nanomedicine.

Developing image-guided robotic systems requires access to flexible, open-source software. For image guidance, the open-source medical imaging platform 3D Slicer is one of the most adopted tools that can be used for research and prototyping. Similarly, for robotics, the open-source middleware suite robot operating system (ROS) is the standard development framework. In the past, there have been several "ad hoc" attempts made to bridge both tools; however, they are all reliant on middleware and custom interfaces. Additionally, none of these attempts have been successful in bridging access to the full suite of tools provided by ROS or 3D Slicer. Therefore, in this paper, we present the SlicerROS2 module, which was designed for the direct use of ROS2 packages and libraries within 3D Slicer. The module was developed to enable real-time visualization of robots, accommodate different robot configurations, and facilitate data transfer in both directions (between ROS and Slicer). We demonstrate the system on multiple robots with different configurations, evaluate the system performance and discuss an image-guided robotic intervention that can be prototyped with this module. This module can serve as a starting point for clinical system development that reduces the need for custom interfaces and time-intensive platform setup. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging using energy conversion from light to ultrasound waves has been developed as a powerful tool to investigate in vivo phenomena due to their complex characteristics. In photoacoustic imaging, endogenous chromophores such as oxygenated hemoglobin, deoxygenated hemoglobin, melanin, and lipid provide useful biomedical information at the molecular level. However, these intrinsic absorbers show strong absorbance only in visible or infrared optical windows and have limited light transmission, making them difficult to apply for clinical translation. Therefore, the development of novel exogenous contrast agents capable of increasing imaging depth while ensuring strong light absorption is required. We report here the application of carbon nanomaterials that exhibit unique physical, mechanical, and electrochemical properties as imaging probes in photoacoustic imaging. Classified into specific structures, carbon nanomaterials are synthesized with different substances according to the imaging purposes to modulate the absorption spectra and highly enhance photoacoustic signals. In addition, functional drugs can be loaded into the carbon nanomaterials composite, and effective in vivo monitoring and photothermal therapy can be performed with cell-specific targeting. Diverse applied cases suggest the high potential of carbon nanomaterial-based photoacoustic imaging in in vivo monitoring for clinical research. [ABSTRACT FROM AUTHOR]

Image-guided nanotheranostics have the potential to represent a new paradigm in the treatment of cancer. Recent developments in modern imaging and nanoparticle design offer an answer to many of the issues associated with conventional chemotherapy, including their indiscriminate side effects and susceptibility to drug resistance. Imaging is one of the tools best poised to enable tailoring of cancer therapies. The field of image-guided nanotheranostics has the potential to harness the precision of modern imaging techniques and use this to direct, dictate, and follow site-specific drug delivery, all of which can be used to further tailor cancer therapies on both the individual and population level. The use of image-guided drug delivery has exploded in preclinical and clinical trials although the clinical translation is incipient. This review will focus on traditional mechanisms of targeted drug delivery in cancer, including the use of molecular targeting, as well as the foundations of designing nanotheranostics, with a focus on current clinical applications of nanotheranostics in cancer. A variety of specially engineered and targeted drug carriers, along with strategies of labeling nanoparticles to endow detectability in different imaging modalities will be reviewed. It will also introduce newer concepts of image-guided drug delivery, which may circumvent many of the issues seen with other techniques. Finally, we will review the current barriers to clinical translation of image-guided nanotheranostics and how these may be overcome. [ABSTRACT FROM AUTHOR]

Abstract Background Adoptive T cell transfer-based immunotherapy yields unsatisfactory results in the treatment of solid tumors, partially owing to limited tumor infiltration and the immunosuppressive microenvironment in solid tumors. Therefore, strategies for the noninvasive tracking of adoptive T cells are critical for monitoring tumor infiltration and for guiding the development of novel combination therapies. Methods We developed a radiolabeling method for cytotoxic T lymphocytes (CTLs) that comprises metabolically labeling the cell surface glycans with azidosugars and then covalently conjugating them with 64Cu-1,4,7-triazacyclononanetriacetic acid-dibenzo-cyclooctyne (64Cu-NOTA-DBCO) using bioorthogonal chemistry. 64Cu-labeled control-CTLs and ovalbumin-specific CTLs (OVA-CTLs) were tracked using positron emission tomography (PET) in B16-OVA tumor-bearing mice. We also investigated the effects of focal adhesion kinase (FAK) inhibition on the antitumor efficacy of OVA-CTLs using a poly(lactic-co-glycolic) acid (PLGA)-encapsulated nanodrug (PLGA-FAKi). Results CTLs can be stably radiolabeled with 64Cu with a minimal effect on cell viability. PET imaging of 64Cu-OVA-CTLs enables noninvasive mapping of their in vivo behavior. Moreover, 64Cu-OVA-CTLs PET imaging revealed that PLGA-FAKi induced a significant increase in OVA-CTL infiltration into tumors, suggesting the potential for a combined therapy comprising OVA-CTLs and PLGA-FAKi. Further combination therapy studies confirmed that the PLGA-FAKi nanodrug markedly improved the antitumor effects of adoptive OVA-CTLs transfer by multiple mechanisms. Conclusion These findings demonstrated that metabolic radiolabeling followed by PET imaging can be used to sensitively profile the early-stage migration and tumor-targeting efficiency of adoptive T cells in vivo. This strategy presents opportunities for predicting the efficacy of cell-based adoptive therapies and for guiding combination regimens. Graphic Abstract

This paper provides an overview of current robot-assisted high-intensity focused ultrasound (HIFU) systems for image-guided therapies. HIFU is a minimally invasive technique that relies on the thermo-mechanical effects of focused ultrasound waves to perform clinical treatments, such as tumor ablation, mild hyperthermia adjuvant to radiation or chemotherapy, vein occlusion, and many others. HIFU is typically performed under ultrasound (USgHIFU) or magnetic resonance imaging guidance (MRgHIFU), which provide intra-operative monitoring of treatment outcomes. Robot-assisted HIFU probe manipulation provides precise HIFU focal control to avoid damage to surrounding sensitive anatomy, such as blood vessels, nerve bundles, or adjacent organs. These clinical and technical benefits have promoted the rapid adoption of robot-assisted HIFU in the past several decades. This paper aims to present the recent developments of robot-assisted HIFU by summarizing the key features and clinical applications of each system. The paper concludes with a comparison and discussion of future perspectives on robot-assisted HIFU.

Minimally invasive image-guided interventions have changed the face of procedural medicine. For these procedures, safety and efficacy depend on precise needle placement. Needle targeting devices help improve the accuracy of needle placement, but their use has not seen broad penetration. Some of these devices are costly and require major modifications to the clinical workflow. In this article, we developed a low-cost, disposable, and easy-to-use angulation tracking device, which was based on a redesigned commercial passive needle holder. The new design provided real-time angulation information for needle tracking. In this design, two potentiometers were used as angulation sensors, and they were connected to two axes of the passive needle holder's arch structure through a 3 D-printed bridge structure. A control unit included an Arduino Pro Mini, a Bluetooth module, and two rechargeable batteries. The angulation was calculated and communicated in real time to a novel developed smartphone app, where real-time angulation information was displayed for guiding the operator to position the needle to the planned angles. The open-air test results showed that the average errors are 1.03° and 1.08° for left–right angulation and head–foot angulation, respectively. The animal cadaver tests revealed that the novel system had an average angular error of 3.2° and a radial distance error of 3.1 mm. The accuracy was comparable with some commercially available solutions. The novel and low-cost needle tracking device may find a role as part of a real-time precision approach to both planning and implementation of image-guided therapies. [ABSTRACT FROM AUTHOR]

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Nanocarriers hold great promise for the controlled release of therapeutic payloads to target organs/tissues and extended duration of anticancer agents in the bloodstream. However, limited data on their in vivo pharmacokinetics and delivery process hamper clinical applications. Here we report a series of micellar nanocarriers self-assembled from new-generation thiophenthiadiazole (TTD)-based NIR-II fluorophores HLAnP (n = 1–4) for simultaneous bioimaging and drug delivery. The NIR-II HLA4P nanocarrier displays exceptional non-fouling performance, minimal immunogenicity, ultralong blood half-life, and high tumor accumulation even with different administration routes. When used as a drug carrier, HLA4P with encapsulated doxorubicin (DOX) realized accurate tumor targeting and continuous real-time in vivo NIR-II tracking of drug delivery and therapy, showing a sustained release rate, improved therapeutic effect, and diminished cardiotoxicity as compared to free DOX. This study provides a new perspective on the design of dual-functional NIR-II fluorophores for diagnostic and therapeutic applications. An ultralow fouling NIR-II probe HLA4P self-assembled into micelles with long-circulation persistence and ultrahigh signal-background ratio for routine preoperative tumor assessment and trackable drug delivery. [Display omitted] • A new TTD-based NIR-II dye (HLA4P) with a high fluorescence QY, exceptional nonfouling performance and low immunogenicity. • HLA4P exhibited ultralong blood circulation, super-contrast ratio and long tumor retention by various injection routes. • HLA4P could be simultaneously used for long-term in vivo NIR-II tracking of drug delivery and therapy. • HLA4P@DOX showed sustained DOX release behavior, enhanced therapeutic effect and diminished toxicity. [ABSTRACT FROM AUTHOR]

Background: Nasal septum perforations (NSP) have many uncomfortable symptoms for the patient and a highly negative impact on quality of life. NSPs are closed using patient-specific implants or surgery. Implants are created either under anesthesia using silicone impressions or using 3D models from CT data. Disadvantages for patient safety are the increased risk of morbidity or radiation exposure. Materials and methods: In the context of otorhinolaryngologic surgery, we present a gentle approach to treating NSP with a new image-based, contactless, and radiation-free measurement method using a 3D endoscope. The method relies on image information only and makes use of real-time capable computer vision algorithms to compute 3D information. This endoscopic method can be repeated as often as desired in the clinical course and has already proven its accuracy and robustness for robotic-assisted surgery (RAS) and surgical microscopy. We expand our method for nasal surgery, as there are additional spatial and stereoperspective challenges. Results: After measuring 3 relevant parameters (NSP extension: axial, coronal, and NSP circumference) of 6 patients and comparing the results of 2 stereoendoscopes with CT data, it was shown that the image-based measurements can achieve comparable accuracies to CT data. One patient could be only partially evaluated because the NSP was larger than the endoscopic field of view. Conclusion: Based on the very good measurements, we outline a therapeutic procedure which should enable the production of patient-specific NSP implants based on endoscopic data only. [ABSTRACT FROM AUTHOR]

Hepatocellularcarcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. Radiofrequency ablation (RFA) is an effective method for treating tumors less than 5 cm. However, manually placing the RFA needle at the site of the tumor is challenging due to the complicated respiratory induced motion of the liver. This article presents the design, fabrication, and benchtop characterization of a patient mounted, respiratory compensated robotic needle insertion platform to perform percutaneous needle interventions. The robotic platform consists of a four degrees of freedom (DoF) dual-stage Cartesian platform used to control the pose of a one-DoF needle insertion module. The active needle insertion module consists of a 3-D printed flexible fluidic actuator capable of providing a steplike, grasp–insert–release actuation that mimics the manual insertion procedure. Force characterization of the needle insertion module indicates that the device is capable of producing 22.6 ± 0.40 N before the needle slips between the grippers. Static phantom targeting experiments indicate a positional error of 1.14 ± 0.30 mm and orientational error of 0.99° ± 0.36°. Static ex vivo porcine liver targeting experiments indicate a positional error of 1.22 ± 0.31 mm and orientational error of 1.16° ± 0.44°. Dynamic targeting experiments with the proposed active motion compensation in dynamic phantom and ex vivo porcine liver show 66.3% and 69.6% positional accuracy improvement, respectively. Future work will continue to develop this platform with the long-term goal of applying the system to RFA for HCC. [ABSTRACT FROM AUTHOR]

Purpose: Ultrasound (US) imaging is an established imaging modality capable of offering video‐rate volumetric images without ionizing radiation. It has the potential for intra‐fraction motion tracking in radiation therapy. In this study, a deep learning‐based method has been developed to tackle the challenges in motion tracking using US imaging. Methods: We present a Markov‐like network, which is implemented via generative adversarial networks, to extract features from sequential US frames (one tracked frame followed by untracked frames) and thereby estimate a set of deformation vector fields (DVFs) through the registration of the tracked frame and the untracked frames. The positions of the landmarks in the untracked frames are finally determined by shifting landmarks in the tracked frame according to the estimated DVFs. The performance of the proposed method was evaluated on the testing dataset by calculating the tracking error (TE) between the predicted and ground truth landmarks on each frame. Results: The proposed method was evaluated using the MICCAI CLUST 2015 dataset which was collected using seven US scanners with eight types of transducers and the Cardiac Acquisitions for Multi‐structure Ultrasound Segmentation (CAMUS) dataset which was acquired using GE Vivid E95 ultrasound scanners. The CLUST dataset contains 63 2D and 22 3D US image sequences respectively from 42 and 18 subjects, and the CAMUS dataset includes 2D US images from 450 patients. On CLUST dataset, our proposed method achieved a mean tracking error of 0.70 ± 0.38 mm for the 2D sequences and 1.71 ± 0.84 mm for the 3D sequences for those public available annotations. And on CAMUS dataset, a mean tracking error of 0.54 ± 1.24 mm for the landmarks in the left atrium was achieved. Conclusions: A novel motion tracking algorithm using US images based on modern deep learning techniques has been demonstrated in this study. The proposed method can offer millimeter‐level tumor motion prediction in real time, which has the potential to be adopted into routine tumor motion management in radiation therapy. [ABSTRACT FROM AUTHOR]

Purpose: On‐treatment kV images have been used in tracking patient motion. One challenge of markerless motion tracking in paraspinal SBRT is the reduced contrast when the X‐ray beam needs to pass through a large portion of the patient's body, for example, from the lateral direction. Besides, due to the spine's overlapping with the surrounding moving organs in the X‐ray images, auto‐registration could lead to potential errors. This work aims to automatically extract the spine component from the conventional 2D X‐ray images, to achieve more robust and more accurate motion management. Methods: A ResNet generative adversarial network (ResNetGAN) consisting of one generator and one discriminator was developed to learn the mapping between 2D kV image and the reference spine digitally reconstructed radiograph (DRR). A tailored multi‐channel multi‐domain loss function was used to improve the quality of the decomposed spine image. The trained model took a 2D kV image as input and learned to generate the spine component of the X‐ray image. The training dataset included 1347 2D kV thoracic and lumbar region X‐ray images from 20 randomly selected patients, and the corresponding matched reference spine DRR. Another 226 2D kV images from the remaining four patients were used for evaluation. The resulted decomposed spine images and the original X‐ray images were registered to the reference spine DRRs, to compare the spine tracking accuracy. Results: The decomposed spine image had the mean peak signal‐to‐noise ratio (PSNR) and structural similarity index measure (SSIM) of 60.08 and 0.99, respectively, indicating the model retained and enhanced the spine structure information in the original 2D X‐ray image. The decomposed spine image matching with the reference spine DRR had submillimeter accuracy (in mm) with a mean error of 0.13, 0.12, and a maximum of 0.58, 0.49 in the x‐ and y‐directions (in the imager coordinates), respectively. The accuracy improvement is robust in all lateral and anteroposterior X‐ray beam angles. Conclusion: We developed a deep learning‐based approach to remove soft tissues in the kV image, leading to more accurate spine tracking in paraspinal SBRT. [ABSTRACT FROM AUTHOR]

Background and Aim: Precise needle puncture of the renal collecting system is an essential step for effective percutaneous nephrolithotomy (PCNL). The use of ultrasound for puncture is receiving increased attention. Ultrasound has recognized limitations related to poor observation of the needle tip. We aimed to assess whether an affordable open-source computerized needle navigation training system, using optically tracked ultrasonography, could improve performance of simulated PCNL puncture by urologic trainees, compared with conventional free hand manual sonographic puncture. Materials and Methods: This study describes a PCNL navigation system that can be recreated with any standard ultrasound machine using relatively inexpensive components. The system allows the needle tip to be precisely appreciated in the ultrasound image, its trajectory planned, and the appreciation of needle tip to target calix proximity sound effect. Eight participants (six trainees and two qualified urologists) assessed the PCNL training model. Alternating starting with freehand (control) and tracked needle (experimental) punctures were performed on a phantom kidney. Total procedure and the number of reinsertions required were recorded. Results: The mean time for freehand puncture was 89 seconds (range 13–173), whereas that of the optically tracked needle was 36 seconds (range 12–72). Thus, puncture time was significantly reduced by an average of 53 seconds (p = 0.045) in the experimental arm. The mean number of needle reinsertions was 3.3 with freehand compared with 1.3 in the optically tracked puncture (p = 0.005). The mean square root error of the optical tracking system was 1.8 mm (four calibrations averaged). Conclusion: This study demonstrates that affordable hardware and open-source software can be used to construct an optically tracked ultrasound navigation system for PCNL training. Statistically significant reduced puncture time and number of passes required for effective puncture are demonstrated. We feel that computerized needle tracking during PCNL puncture deserves further evaluation in a training and, potentially, in a clinical setting. [ABSTRACT FROM AUTHOR]

Image-guided therapies have been on the rise in recent years as they can achieve higher accuracy and are less invasive than traditional methods. By combining augmented reality technology with image-guided therapy, more organs, and tissues can be observed by surgeons to improve surgical accuracy. In this review, 233 publications (dated from 2015 to 2020) on the design and application of augmented reality-based systems for image-guided therapy, including both research prototypes and commercial products, were considered for review. Based on their functions and applications. Sixteen studies were selected. The engineering specifications and applications were analyzed and summarized for each study. Finally, future directions and existing challenges in the field were summarized and discussed. [ABSTRACT FROM AUTHOR]

Yaotai Wang,1 Chun Chen,1 Yong Luo,1 Jie Xiong,1 Yu Tang,1 Haiyan Yang,1 Lu Wang,1 Fujie Jiang,1 Xuan Gao,2 Die Xu,2 Huanan Li,1 Qi Wang,1 Jianzhong Zou1,2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Jianzhong ZouState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel +86-13708302390Email zoujzh@cqmu.edu.cnPurpose: The high-intensity focused ultrasound (HIFU) ablation of tumors is inseparable from synergistic agents and image monitoring, but the existing synergistic agents have the defects of poor targeting and a single imaging mode, which limits the therapeutic effects of HIFU. The construction of a multifunctional biological targeting synergistic agent with high biosafety, multimodal imaging and targeting therapeutic performance has great significance for combating cancer.Methods: Multifunctional biological targeting synergistic agent consisting of Bifidobacterium longum (B. longum), ICG and PFH coloaded cationic lipid nanoparticles (CL-ICG-PFH-NPs) were constructed for targeting multimode imaging, synergistic effects with HIFU and imaging-guided ablation of tumors, which was evaluated both in vitro and in vivo.Results: Both in vitro and in vivo systematical studies validated that the biological targeting synergistic agent can simultaneously achieve tumor-biotargeted multimodal imaging, HIFU synergism and multimodal image monitoring in HIFU therapy. Importantly, the electrostatic adsorption method and the targeting of B. longum to tumor tissues allow the CL-ICG-PFH-NPs to be retained in the tumor tissue, achieve the targeting ability of synergistic agent. Multimodal imaging chose the best treatment time according to the distribution of nanoparticles in the body to guide the efficient and effective treatment of HIFU. CL-ICG-PFH-NPs could serve as a phase change agent and form microbubbles that can facilitate HIFU ablation by mechanical effects, acoustic streaming and shear stress. This lays a foundation for the imaging and treatment of tumors.Conclusion: In this work, a biological targeting synergistic agent was successfully constructed with good stability and physicochemical properties. This biological targeting synergistic agent can not only provide information for early diagnosis of tumors but also realize multimodal imaging monitoring during HIFU ablation simultaneously with HIFU treatment, which improves the shortcomings of HIFU treatment and has broad application prospects.Keywords: high-intensity focused ultrasound, nanoparticles, photoacoustic imaging, fluorescence imaging, ultrasound imaging, image-guided therapy

Purpose To characterize temperature fields and tissue damage profiles of large-volume hyperthermia (HT) induced by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) in deep and superficial targets in vivo in a porcine model. Methods Nineteen HT sessions were performed in vivo with a commercial MRgHIFU system (Sonalleve® V2, Profound Medical Inc., Mississauga, ON, Canada) in hind leg muscles of eight pigs with temperature fields of cross-sectional diameter of 58-mm. Temperature statistics evaluated in the target region-of-interest (tROI) included accuracy, temporal variation, and uniformity. The impact of the number and location of imaging planes for feedback-based temperature control were investigated. Temperature fields were characterized by time-in-range (TIR, the duration each voxel stays within 40–45 °C) maps. Tissue damage was characterized by contrast-enhanced MRI, and macroscopic and histopathological analysis. The performance of the Sonalleve® system was benchmarked against a commercial phantom. Results Across all HT sessions, the mean difference between the average temperature (Tavg) and the desired temperature was −0.4 ± 0.5 °C; the standard deviation of temperature 1.2 ± 0.2 °C; the temporal variation of Tavg for 30-min HT was 0.6 ± 0.2 °C, and the temperature uniformity was 1.5 ± 0.2 °C. A difference of 2.2-cm (in pig) and 1.5-cm (in phantom) in TIR dimensions was observed when applying feedback-based plane(s) at different locations. Histopathology showed 62.5% of examined HT sessions presenting myofiber degeneration/necrosis within the target volume. Conclusion Large-volume MRgHIFU-mediated HT was successfully implemented and characterized in a porcine model in deep and superficial targets in vivo with heating distributions modifiable by user-definable parameters.

IR780 is a near-infrared fluorescent dye, which can be applied as a photosensitizer in photodynamic (PDT) and photothermal (PTT) therapies and as a biodistribution tracer in imaging techniques. We investigated the growth and migration inhibition and mechanism of death of breast tumor cells, MCF-7 and MDA-MB-231, exposed to polymeric nanocapsules (NC) comprising IR780 covalently linked to the biodegradable polymer PLA (IR-PLA) and IR780 physically encapsulated (IR780-NC) in vitro. Both types of NC had mean diameters around 120 nm and zeta potentials around −40 mV. IR-PLA-NC was less cytotoxic than IR780 NC to a non-tumorigenic mammary epithelial cell line, MCF-10A, which is an important aspect of selectivity. Free-IR780 was more cytotoxic than IR-PLA-NC for MCF-7 and MDA-MB-231 cells after illumination with a 808 nm laser. IR-PLA NC was effective to inhibit colony formation (50%) and migration (30–40%) for both cancer cell lines. MDA-MB-231 cells were less sensitive to all IR780 formulations compared to MCF-7 cells. Cell uptake was higher with IR-PLA-NC than with IR780-NC and free-IR780 in both cancer cell lines (p

Photoacoustic imaging using external contrast agents is emerging as a powerful modality for real-time molecular imaging of deep-seated tumors. There are several chromophores, such as indocyanine green and IRDye800, that can potentially be used for photoacoustic imaging; however, their use is limited due to several drawbacks, particularly photostability. There is, therefore, an urgent need to design agents to enhance contrast in photoacoustic imaging. Naphthalocyanine dyes have been demonstrated for their use as photoacoustic contrast agents; however, their low solubility in aqueous solvents and high aggregation propensity limit their application. In this study, we report the synthesis and characterization of silicon-centered naphthalocyanine dyes with high aqueous solubility and near infra-red (NIR) absorption in the range of 850–920 nm which make them ideal candidates for photoacoustic imaging. A series of Silicon-centered naphthalocyanine dyes were developed with varying axial and peripheral substitutions, all in an attempt to enhance their aqueous solubility and improve photophysical properties. We demonstrate that axial incorporation of charged ammonium mesylate group enhances water solubility. Moreover, the incorporation of peripheral 2-methoxyethoxy groups at the α-position modulates the electronic properties by altering the π-electron delocalization and enhancing photoacoustic signal amplitude. In addition, all the dyes were synthesized to incorporate an N-hydroxysuccinimidyl group to enable further bioconjugation. In summary, we report the synthesis of water-soluble silicon-centered naphthalocyanine dyes with a high photoacoustic signal amplitude that can potentially be used as contrast agents for molecular photoacoustic imaging.

Purpose: Ultrasound (US) imaging has been widely used in diagnosis, image‐guided intervention, and therapy, where high‐quality three‐dimensional (3D) images are highly desired from sparsely acquired two‐dimensional (2D) images. This study aims to develop a deep learning‐based algorithm to reconstruct high‐resolution (HR) 3D US images only reliant on the acquired sparsely distributed 2D images. Methods: We propose a self‐supervised learning framework using cycle‐consistent generative adversarial network (cycleGAN), where two independent cycleGAN models are trained with paired original US images and two sets of low‐resolution (LR) US images, respectively. The two sets of LR US images are obtained through down‐sampling the original US images along the two axes, respectively. In US imaging, in‐plane spatial resolution is generally much higher than through‐plane resolution. By learning the mapping from down‐sampled in‐plane LR images to original HR US images, cycleGAN can generate through‐plane HR images from original sparely distributed 2D images. Finally, HR 3D US images are reconstructed by combining the generated 2D images from the two cycleGAN models. Results: The proposed method was assessed on two different datasets. One is automatic breast ultrasound (ABUS) images from 70 breast cancer patients, the other is collected from 45 prostate cancer patients. By applying a spatial resolution enhancement factor of 3 to the breast cases, our proposed method achieved the mean absolute error (MAE) value of 0.90 ± 0.15, the peak signal‐to‐noise ratio (PSNR) value of 37.88 ± 0.88 dB, and the visual information fidelity (VIF) value of 0.69 ± 0.01, which significantly outperforms bicubic interpolation. Similar performances have been achieved using the enhancement factor of 5 in these breast cases and using the enhancement factors of 5 and 10 in the prostate cases. Conclusions: We have proposed and investigated a new deep learning‐based algorithm for reconstructing HR 3D US images from sparely acquired 2D images. Significant improvement on through‐plane resolution has been achieved by only using the acquired 2D images without any external atlas images. Its self‐supervision capability could accelerate HR US imaging. [ABSTRACT FROM AUTHOR]

Immunotherapies have been established as safe and efficient modalities for numerous tumor treatments. The lymphatic system, which is an important system, can modulate the immune system via a complex network, which includes lymph nodes, vessels, and lymphocytes. With the deepening understanding of tumor immunology, a plethora of immunotherapies, which include vaccines, photothermal therapy, and photodynamic therapy, have been established for antitumor treatments. However, the deleterious off-target effects and nonspecific targeting of therapeutic agents result in low efficacy of immunotherapy. Fortunately, nanoparticle-based approaches for targeting the lymphatic system afford a unique opportunity to manufacture drugs that can simultaneously tackle both aspects, thereby improving tumor treatments. Over the past decades, great strides have been made in the development of DC vaccines and nanomedicine as antitumor treatments in the field of lymphatic therapeutics and diagnosis. In this review, we summarize the current strategies through which nanoparticle technology has been designed to target the lymphatic system and describe applications of lymphatic imaging for the diagnosis and image-guided surgery of tumor metastasis. Moreover, improvements in the tumor specificity of nanovaccines and medicines, which have been realized through targeting or stimulating the lymphatic system, can provide amplified antitumor immune responses and reduce side effects, thereby promoting the paradigm of antitumor treatment into the clinic to benefit patients. [ABSTRACT FROM AUTHOR]

Background: Adoptive T cell transfer-based immunotherapy yields unsatisfactory results in the treatment of solid tumors, partially owing to limited tumor infiltration and the immunosuppressive microenvironment in solid tumors. Therefore, strategies for the noninvasive tracking of adoptive T cells are critical for monitoring tumor infiltration and for guiding the development of novel combination therapies. Methods: We developed a radiolabeling method for cytotoxic T lymphocytes (CTLs) that comprises metabolically labeling the cell surface glycans with azidosugars and then covalently conjugating them with 64Cu-1,4,7-triazacyclononanetriacetic acid-dibenzo-cyclooctyne (64Cu-NOTA-DBCO) using bioorthogonal chemistry. 64Cu-labeled control-CTLs and ovalbumin-specific CTLs (OVA-CTLs) were tracked using positron emission tomography (PET) in B16-OVA tumor-bearing mice. We also investigated the effects of focal adhesion kinase (FAK) inhibition on the antitumor efficacy of OVA-CTLs using a poly(lactic-co-glycolic) acid (PLGA)-encapsulated nanodrug (PLGA-FAKi). Results: CTLs can be stably radiolabeled with 64Cu with a minimal effect on cell viability. PET imaging of 64Cu-OVA-CTLs enables noninvasive mapping of their in vivo behavior. Moreover, 64Cu-OVA-CTLs PET imaging revealed that PLGA-FAKi induced a significant increase in OVA-CTL infiltration into tumors, suggesting the potential for a combined therapy comprising OVA-CTLs and PLGA-FAKi. Further combination therapy studies confirmed that the PLGA-FAKi nanodrug markedly improved the antitumor effects of adoptive OVA-CTLs transfer by multiple mechanisms. Conclusion: These findings demonstrated that metabolic radiolabeling followed by PET imaging can be used to sensitively profile the early-stage migration and tumor-targeting efficiency of adoptive T cells in vivo. This strategy presents opportunities for predicting the efficacy of cell-based adoptive therapies and for guiding combination regimens. [ABSTRACT FROM AUTHOR]

A prominent goal of neuroscience is to improve our understanding of how brain structure and activity interact to produce perception, emotion, behavior, and cognition. The brain's network activity is inherently organized in distinct spatiotemporal patterns that span scales from nanometer-sized synapses to meter-long nerve fibers and millisecond intervals between electrical signals to decades of memory storage. There is currently no single imaging method that alone can provide all the relevant information, but intelligent combinations of complementary techniques can be effective. Here, we thus present the latest advances in biomedical and biological engineering on photoacoustic neuroimaging in the context of complementary imaging techniques. A particular focus is placed on recent advances in whole-brain photoacoustic imaging in rodent models and its influential role in bridging the gap between fluorescence microscopy and more non-invasive techniques such as magnetic resonance imaging (MRI). We consider current strategies to address persistent challenges, particularly in developing molecular contrast agents, and conclude with an overview of potential future directions for photoacoustic neuroimaging to provide deeper insights into healthy and pathological brain processes. [ABSTRACT FROM AUTHOR]