Photonic control of image-guided ferroptosis cancer nanomedicine.

Photonic nanomaterials, characterized by their remarkable photonic tunability, empower a diverse range of applications, including cutting-edge advances in cancer nanomedicine. Recently, ferroptosis has emerged as a promising alternative strategy for effectively killing cancer cells with minimizing therapeutic resistance. Novel design of photonic nanomaterials that can integrate photoresponsive-ferroptosis inducers, -diagnostic imaging, and -synergistic components provide significant benefits to effectively trigger local ferroptosis. This review provides a comprehensive overview of recent advancements in photonic nanomaterials for image-guided ferroptosis cancer nanomedicine, offering insights into their strengths, constraints, and their potential as a future paradigm in cancer treatment.

3D modeling of in vivo MRI-guided nano-photothermal therapy mediated by magneto-plasmonic nanohybrids.

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.

Molecular imaging of tumor hypoxia: Evolution of nitroimidazole radiopharmaceuticals and insights for future development.

Though growing evidence has been collected in support of the concept of dose escalation based on the molecular level images indicating hypoxic tumor sub-volumes that could be radio-resistant, validation of the concept is still a work in progress. Molecular imaging of tumor hypoxia using radiopharmaceuticals is expected to provide the required input to plan dose escalation through Image Guided Radiation Therapy (IGRT) to kill/control the radio-resistant hypoxic tumor cells. The success of the IGRT, therefore, is heavily dependent on the quality of images obtained using the radiopharmaceutical and the extent to which the image represents the true hypoxic status of the tumor in spite of the heterogeneous nature of tumor hypoxia. Available literature on radiopharmaceuticals for imaging hypoxia is highly skewed in favor of nitroimidazole as the pharmacophore given their ability to undergo oxygen dependent reduction in hypoxic cells. In this context, present review on nitroimidazole radiopharmaceuticals would be immensely helpful to the researchers to obtain a birds-eye view on what has been achieved so far and what can be tried differently to obtain a better hypoxia imaging agent. The review also covers various methods of radiolabeling that could be utilized for developing radiotracers for hypoxia targeting applications.

Near-infrared photodynamic and photothermal co-therapy based on organic small molecular dyes.

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.

Review of Robot-Assisted HIFU Therapy.

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.

Optimizing Axial and Peripheral Substitutions in Si-Centered Naphthalocyanine Dyes for Enhancing Aqueous Solubility and Photoacoustic Signal Intensity.

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.

Therapeutic Agent Delivery Across the Blood-Brain Barrier Using Focused Ultrasound.

Specialized features of vasculature in the central nervous system greatly limit therapeutic treatment options for many neuropathologies. Focused ultrasound, in combination with circulating microbubbles, can be used to transiently and noninvasively increase cerebrovascular permeability with a high level of spatial precision. For minutes to hours following sonication, drugs can be administered systemically to extravasate in the targeted brain regions and exert a therapeutic effect, after which permeability returns to baseline levels. With the wide range of therapeutic agents that can be delivered using this approach and the growing clinical need, focused ultrasound and microbubble (FUS+MB) exposure in the brain has entered human testing to assess safety. This review outlines the use of FUS+MB-mediated cerebrovascular permeability enhancement as a drug delivery technique, details several technical and biological considerations of this approach, summarizes results from the clinical trials conducted to date, and discusses the future direction of the field.

Shaping the future of microwave tumor ablation: a new direction in precision and control of device performance.

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.

Nanoparticle-based approaches to target the lymphatic system for antitumor treatment.

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.

Small molecule based EGFR targeting of biodegradable nanoparticles containing temozolomide and Cy5 dye for greatly enhanced image-guided glioblastoma therapy.

Current glioblastoma multiforme (GBM) treatment is insufficient, facing obstacles like poor tumor accumulation and dose limiting side effects of chemotherapeutic agents. Targeted nanomaterials offer breakthrough potential in GBM treatment; however, traditional antibody-based targeting poses challenges for live brain application. To overcome current obstacles, we introduce here the development of a small molecule targeting agent, CFMQ, coupled to biocompatible chitosan coated poly(lactic-co-glycolic) acid nanoparticles. These targeted nanoparticles enhance cellular uptake and show rapid blood-brain barrier (BBB) permeability in-vitro, demonstrating the ability to effectively deliver their load to tumor cells. Encapsulation of the chemotherapeutic agent, temozolomide (TMZ), decreases the IC50 ~34-fold compared to free-drug. Also, CFMQ synergistically suppresses tumor cell progression, reducing colony formation (98%), cell migration (84%), and cell invasion (77%). Co-encapsulation of Cy5 enables optical image guided therapy. This biocompatible theranostic nanoformulation shows early promise in significantly enhancing the efficacy of TMZ, while providing potential for image-guided therapy for GBM.

Rhomboidal Pt(II) metallacycle-based NIR-II theranostic nanoprobe for tumor diagnosis and image-guided therapy.

Fluorescent theranostics probes at the second near-IR region (NIR-II; 1.0-1.7 µm) are in high demand for precise theranostics that minimize autofluorescence, reduce photon scattering, and improve the penetration depth. Herein, we designed and synthesized an NIR-II theranostic nanoprobe 1 that incorporates a Pt(II) metallacycle 2 and an organic molecular dye 3 into DSPE-mPEG5000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]). This design endows 1 with good photostability and passive targeting ability. Our studies show that 1 accurately diagnoses cancer with high resolution and selectively delivers the Pt(II) metallacycle to tumor regions via an enhanced permeability and retention effect. In vivo studies reveal that 1 efficiently inhibits the growth of tumor with minimal side effects. At the same time, improved fluorescent imaging quality and signal-to-noise ratios are shown due to the long emission wavelengths. These studies demonstrate that 1 is a potential theranostic platform for tumor diagnosis and treatment in the NIR-II region.

Bridging 3D Slicer and ROS2 for Image-Guided Robotic Interventions.

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.

Endoscopic measurement of nasal septum perforations.

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.

[Endoscopic measurement of nasal septum perforations. German version]. / Endoskopische Vermessung von Nasenseptumdefekten.

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.

Angular needle tracker and stabilizer for image-guided interventions.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

MRI-guided lumbar spinal injections with body-mounted robotic system: cadaver studies.

INTRODUCTION: This paper reports the system integration and cadaveric assessment of a body-mounted robotic system for MRI-guided lumbar spine injections. The system is developed to enable MR-guided interventions in closed bore magnet and avoid problems due to patient movement during cannula guidance. MATERIAL AND METHODS: The robot is comprised by a lightweight and compact structure so that it can be mounted directly onto the lower back of a patient using straps. Therefore, it can minimize the influence of patient movement by moving with the patient. The MR-Conditional robot is integrated with an image-guided surgical planning workstation. A dedicated clinical workflow is created for the robot-assisted procedure to improve the conventional freehand MRI-guided procedure. RESULTS: Cadaver studies were performed with both freehand and robot-assisted approaches to validate the feasibility of the clinical workflow and to assess the positioning accuracy of the robotic system. The experiment results demonstrate that the root mean square (RMS) error of the target position to be 2.57 ± 1.09 mm and of the insertion angle to be 2.17 ± 0.89°. CONCLUSION: The robot-assisted approach is able to provide more accurate and reproducible cannula placements than the freehand procedure, as well as to reduce the number of insertion attempts.

Initial single centre experience of Aquablation of the prostate using the AquaBeam system with athermal haemostasis for the treatment of benign prostatic hyperplasia: 1-year outcomes.

PURPOSE: Aquablation using the AquaBeam system combines real-time image guidance and robotics to enable precise and heat-free removal of prostatic tissue with a high velocity water jet. The aim of this study is to report the outcomes of Aquablation up to 1 year in a single centre within the UK employing an athermal approach to haemostasis. METHODS: Fifty-five consecutive men underwent Aquablation between September 2017 and December 2018 (as part of OPEN WATER trial). Standard Aquablation was performed with the AquaBeam system (PROCEPT® BioRobotics) with 2 passes of Aquablation followed by bladder washout with application of continuous bladder irrigation via a catheter on a continuous traction device. Patients were followed up at 3 and 12 months. The data were prospectively collected on patient demographics, uroflowmetry, prostate volume, International Prostate Symptom Score (IPSS), Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD) and International Index of Erectile Function (IIEF-15). RESULTS: The mean age was 64.1 ± 7.9 years. Operating time was 26.9 ± 9.2 min. Mean prostate volume decreased from 58.2 ± 23.9 cc to 33.2 ± 12.9 cc (p < 0.0001). There were significant improvements at the 12 month follow-up in maximum urinary flow rate (9.9 ± 5.1 ml/s vs. 23.9 ± 11.6 ml/s), IPSS (21.7 ± 7.4 vs. 6.1 ± 4.2) and quality of life score (4.8 ± 1.1 vs. 1.4 ± 1.4) (p < 0.0001). There was no significant change in IIEF-15 and MSHQ-EjD scores. There were 8 (14.5%) Clavien grade 2 or higher complications. CONCLUSION: Our single centre experience suggests Aquablation using an entirely athermal approach is a safe cavitating procedure resulting in significant LUTS improvement comparable to standard cavitating procedures with greater preservation of sexual function.

Recent advances in assembled AIEgens for image-guided anticancer therapy.

Image-guided therapy, with simultaneous imaging and therapy functions, has the potential to greatly enhance the therapeutic efficacy of anticancer therapy, and reduce the incidence of side effects. Fluorescence imaging has the advantages of easy operation, abundant signal, high contrast, and fast response for real-time and non-invasive tracking. Luminogens with aggregation-induced emission characteristics (AIEgens) can emit strong luminescence in an aggregate state, which makes them ideal materials to construct applicative fluorophores for fluorescence imaging. The opportunity for image-guided cancer treatment has inspired researchers to explore the theranostic application of AIEgens combined with other therapy methods. In recent years, many AIEgens with efficient photosensitizing or photothermal abilities have been designed by precise molecular engineering, with superior performance in image-guided anticancer therapy. Owing to the hydrophobic property of most AIEgens, an assembly approach has been wildly utilized to construct biocompatible AIEgen-based nanostructures in aqueous systems, which can be used for image-guided anticancer therapy. In the present review, we summarize the recent advances in the assembled AIEgens for image-guided anticancer therapy. Five types of image-guided anticancer therapy using assembled AIEgens are included: chemotherapy, photodynamic therapy, photothermal therapy, gene therapy, and synergistic therapy. Moreover, a brief conclusion with the discussion of current challenges and future perspectives in this area is further presented.

Metabolic radiolabeling and in vivo PET imaging of cytotoxic T lymphocytes to guide combination adoptive cell transfer cancer therapy.

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.

A Fully Actuated Robotic Assistant for MRI-Guided Precision Conformal Ablation of Brain Tumors.

This paper reports the development of a fully actuated robotic assistant for magnetic resonance imaging (MRI)-guided precision conformal ablation of brain tumors using an interstitial high intensity needle-based therapeutic ultrasound (NBTU) ablator probe. The robot is designed with an eight degree-of-freedom (DOF) remote center of motion (RCM) manipulator driven by piezoelectric actuators, five for aligning the ultrasound thermal ablator to the target lesions and three for inserting and orienting the ablator and its cannula to generate a desired ablation profile. The 8-DOF fully actuated robot can be operated in the scanner bore during imaging; thus, alleviating the need of moving the patient in or out of the scanner during the procedure, and therefore potentially reducing the procedure time and streamlining the workflow. The free space positioning accuracy of the system is evaluated with the OptiTrack motion capture system, demonstrating the root mean square (RMS) error of the tip position to be 1.11±0.43mm. The system targeting accuracy in MRI is assessed with phantom studies, indicating the RMS errors of the tip position to be 1.45±0.66mm and orientation to be 1.53±0.69°. The feasibility of the system to perform thermal ablation is validated through a preliminary ex-vivo tissue study with position error less than 4.3mm and orientation error less than 4.3°.