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Radiotherapy is one of the most effective modalities for the treatment of cancer. However, there is a high degree of uncertainty associated with the target volume of most cancer sites. The sources of these uncertainties include, but are not limited to, the motion of the target, patient setup errors, patient movements, and the delineation of the target volume. Recently, many imaging techniques have been introduced to track the motion of tumors. The treatment delivery using these techniques is collectively called image-guided radiation therapy (IGRT). Ultimately, IGRT is only as good as the accuracy with which the target is known. There are reports of interobserver variability in tumor delineation across anatomical sites, but the widest ranges of variations have been reported for the delineation of head and neck tumors as well as esophageal and lung carcinomas. Significant interobserver variability in target delineation can be attributed to many factors including the impact of imaging and the influence of the observer (specialty, training, and personal bias). The visibility of the target can be greatly improved with the use of multimodality imaging by co-registration of CT with a second modality such as magnetic resonance imaging (MRI) and/or positron emission tomography. Also, continuous education, training, and cross-collaboration of the radiation oncologist with other specialties can reduce the degree of variability in tumor delineation.

Purpose: Percutaneous ablation under MRI-guidance allows treating otherwise inoperable liver tumors locally using a catheter probe. However, manually placing the probe is an error-prone and time consuming task that requires a considerable amount of training. The aim of this paper was to present a pneumatically actuated robotic instrument that can assist clinicians in MRI-guided percutaneous intervention of the liver and to assess its functionality in a clinical setting. The robot positions a needle-guide inside the MRI scanner bore and assists manual needle insertions outside the bore. Methods: The robot supports double oblique insertions that are particularly challenging for less experienced clinicians. Additionally, the system employs only standard imaging sequences and can therefore be used on different MRI scanners without requiring prior integration. The repeatability and the accuracy of the robot were evaluated with an optical tracking system. The functionality of the robot was assessed in an initial pilot study on two patients that underwent MRI-guided laser ablation of the liver. Results: The robot positioned the needle-guide in a repeatable manner with a mean error of 0.35 mm and a standard deviation of 0.32 mm. The mean position error corresponding to the needle tip, measured for an equivalent needle length of 195 mm over 25 fixed points, was 2.5 mm with a standard deviation of 1.2 mm. The pilot study confirmed that the robot does not interfere with the equipment used for MRI-guided laser ablation and does not visibly affect the MR images. The robot setup integrated seamlessly within the established clinical workflow. The robot-assisted procedure was successfully completed on two patients, one of which required a complex double oblique insertion. For both patients, the insertion depth and the tumor size were within the range reported for previous MRI-guided percutaneous interventions. A third patient initially enrolled in the pilot study and was considerably heavier than the others, preventing the use of the robot and requiring several freehand insertion attempts. Conclusions: The robot repeatability and accuracy are appropriate for liver tumors normally treated with MRI-guided ablation. The results of the pilot study endorse the clinical use of the robot in its current form: the robot is fully functional and MRI-compatible in a clinical setting and is suitable for double-oblique needle insertions. [ABSTRACT FROM AUTHOR]

Navigation technology is changing the clinical standards in medical interventions by making existing procedures more accurate, and new procedures possible. Navigation is based on preoperative or intraoperative imaging combined with 3-dimensional position tracking of interventional tools registered to the images. Research of navigation technology in medical interventions requires significant engineering efforts. The difficulty of developing such complex systems has been limiting the clinical translation of new methods and ideas. A key to the future success of this field is to provide researchers with platforms that allow rapid implementation of applications with minimal resources spent on reimplementing existing system features. A number of platforms have been already developed that can share data in real time through standard interfaces. Complete navigation systems can be built using these platforms using a layered software architecture. In this paper, we review the most popular platforms, and show an effective way to take advantage of them through an example surgical navigation application. [ABSTRACT FROM AUTHOR]

Nanotechnology has enabled the development of many alternative anti-cancer approaches, such as thermal therapies, which cause minimal damage to healthy cells. Current challenges in cancer treatment are the identification of the diseased area and its efficient treatment without generating many side effects. Image-guided therapies can be a useful tool to diagnose and treat the diseased tissue and they offer therapy and imaging using a single nanostructure. The present review mainly focuses on recent advances in the field of thermal therapy and imaging integrated with multifunctional inorganic nanoparticles. The main heating sources for heat-induced therapies are the surface plasmon resonance (SPR) in the near infrared region and alternating magnetic fields (AMFs). The different families of inorganic nanoparticles employed for SPR- and AMF-based thermal therapies and imaging are described. Furthermore, inorganic nanomaterials developed for multimodal therapies with different and multi-imaging modalities are presented in detail. Finally, relevant clinical perspectives and the future scope of inorganic nanoparticles in image-guided therapies are discussed. [ABSTRACT FROM AUTHOR]

Purpose: CustusX is an image-guided therapy (IGT) research platform dedicated to intraoperative navigation and ultrasound imaging. In this paper, we present CustusX as a robust, accurate, and extensible platform with full access to data and algorithms and show examples of application in technological and clinical IGT research. Methods: CustusX has been developed continuously for more than 15 years based on requirements from clinical and technological researchers within the framework of a well-defined software quality process. The platform was designed as a layered architecture with plugins based on the CTK/OSGi framework, a superbuild that manages dependencies and features supporting the IGT workflow. We describe the use of the system in several different clinical settings and characterize major aspects of the system such as accuracy, frame rate, and latency. Results: The validation experiments show a navigation system accuracy of $$<$$ 1.1 mm, a frame rate of 20 fps, and latency of 285 ms for a typical setup. The current platform is extensible, user-friendly and has a streamlined architecture and quality process. CustusX has successfully been used for IGT research in neurosurgery, laparoscopic surgery, vascular surgery, and bronchoscopy. Conclusions: CustusX is now a mature research platform for intraoperative navigation and ultrasound imaging and is ready for use by the IGT research community. CustusX is open-source and freely available at . [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) has been increasingly investigated. However, there are still challenges in strategies that can further enhance photoconversion efficiency and improve photothermal tumor ablation effect of current nanomaterials. Herein, we developed a fluorescent/photoacoustic imaging guided PTT agent by seeding Gold (Au) nanoparticles onto graphene oxide (GO). Near infrared dye (Cy5.5) labeled-matrix metalloproteinase-14 (MMP-14) substrate (CP) was conjugated onto the GO/Au complex (GA) forming tumor targeted theranostic probe (CPGA), whereCy5.5 fluorescent signal is quenched by Surface Plasmon Resonance (SPR) capacity from both GO and Au, yet it can boost strong fluorescence signals after degradation by MMP-14. The photothermal effect of GA hybrid was found significantly elevated compared with Au or GO alone. After intravenous administration of CPGA into SCC7 tumor-bearing mice, high fluorescence and PA signals were observed in the tumor area over time, which peaked at the 6 h time point (tumor-to-normal tissue ratio of 3.64 ± 0.51 for optical imaging and 2.5 ± 0.27 for PA imaging). The tumors were then irradiated with a laser, and an excellent tumor inhibition was observedwithoutrecurrence. Our studies further encourage applications of the hybrid nanocomposite for image-guided enhanced PTT in biomedical applications, especially in cancer theranostics. [ABSTRACT FROM AUTHOR]

Purpose: Image-guided cryotherapy of renal cancer is an emerging alternative to surgical nephrectomy, particularly for those who cannot sustain the physical burden of surgery. It is well known that the outcome of this therapy depends on the accurate placement of the cryotherapy probe. Therefore, a robotic instrument guide may help physicians aim the cryotherapy probe precisely to maximize the efficacy of the treatment and avoid damage to critical surrounding structures. The objective of this paper was to propose a robotic instrument guide for orienting cryotherapy probes in image-guided cryotherapy of renal cancers. The authors propose a body-mounted robotic guide that is expected to be less susceptible to guidance errors caused by the patient's whole body motion. Methods: Keeping the device's minimal footprint in mind, the authors developed and validated a body-mounted, robotic instrument guide that can maintain the geometrical relationship between the device and the patient's body, even in the presence of the patient's frequent body motions. The guide can orient the cryotherapy probe with the skin incision point as the remote-center-of-motion. The authors' validation studies included an evaluation of the mechanical accuracy and position repeatability of the robotic instrument guide. The authors also performed a mock MRI-guided cryotherapy procedure with a phantom to compare the advantage of robotically assisted probe replacements over a free-hand approach, by introducing organ motions to investigate their effects on the accurate placement of the cryotherapy probe. Measurements collected for performance analysis included accuracy and time taken for probe placements. Multivariate analysis was performed to assess if either or both organ motion and the robotic guide impacted these measurements. Results: The mechanical accuracy and position repeatability of the probe placement using the robotic instrument guide were 0.3 and 0.1 mm, respectively, at a depth of 80 mm. The phantom test indicated that the accuracy of probe placement was significantly better with the robotic instrument guide (4.1 mm) than without the guide (6.3 mm, p < 0.001), even in the presence of body motion. When independent organ motion was artificially added, in addition to body motion, the advantage of accurate probe placement using the robotic instrument guide disappeared statistically [i.e., 6.0 mm with the robotic guide and 5.9 mm without the robotic guide (p = 0.906)]. When the robotic instrument guide was used, the total time required to complete the procedure was reduced from 19.6 to 12.7 min (p < 0.001). Multivariable analysis indicated that the robotic instrument guide, not the organ motion, was the cause of statistical significance. The statistical power the authors obtained was 88% in accuracy assessment and 99% higher in duration measurement. Conclusions: The body-mounted robotic instrument guide allows positioning of the probe during image-guided cryotherapy of renal cancer and was done in fewer attempts and in less time than the free-hand approach. The accuracy of the placement of the cryotherapy probe was better using the robotic instrument guide than without the guide when no organ motion was present. The accuracy between the robotic and free-hand approach becomes comparable when organ motion was present. [ABSTRACT FROM AUTHOR]

Angioplasty and stenting of a stenosed artery enable acute restoration of blood flow. However, restenosis or a lack of re-endothelization can subsequently occur depending on the stent type. Cavitation-mediated drug delivery is a potential therapy for these conditions, but requires that particular types of cavitation be induced by ultrasound insonation. Because of the heterogeneity of tissue and stochastic nature of cavitation, feedback mechanisms are needed to determine whether the sustained bubble activity is induced. The objective of this study was to determine the feasibility of passive cavitation imaging through a metal stent in a flow phantom and an animal model. In this study, an endovascular stent was deployed in a flow phantom and in porcine femoral arteries. Fluorophore-labeled echogenic liposomes, a theragnostic ultrasound contrast agent, were injected proximal to the stent. Cavitation images were obtained by passively recording and beamforming the acoustic emissions from echogenic liposomes insonified with a low-frequency (500 kHz) transducer. In vitro experiments revealed that the signal-to-noise ratio for detecting stable cavitation activity through the stent was greater than 8 dB. The stent did not significantly reduce the signal-to-noise ratio. Trans-stent cavitation activity was also detected in vivo via passive cavitation imaging when echogenic liposomes were insonified by the 500-kHz transducer. When stable cavitation was detected, delivery of the fluorophore into the arterial wall was observed. Increased echogenicity within the stent was also observed when echogenic liposomes were administered. Thus, both B-mode ultrasound imaging and cavitation imaging are feasible in the presence of an endovascular stent in vivo. Demonstration of this capability supports future studies to monitor restenosis with contrast-enhanced ultrasound and pursue image-guided ultrasound-mediated drug delivery to inhibit restenosis. [ABSTRACT FROM AUTHOR]

This paper presents a fully actuated robotic system for percutaneous prostate therapy under continuously acquired live magnetic resonance imaging (MRI) guidance. The system is composed of modular hardware and software to support the surgical workflow of intraoperative MRI-guided surgical procedures. We present the development of a 6-degree-of-freedom (DOF) needle placement robot for transperineal prostate interventions. The robot consists of a 3-DOF needle driver module and a 3-DOF Cartesian motion module. The needle driver provides needle cannula translation and rotation (2-DOF) and stylet translation (1-DOF). A custom robot controller consisting of multiple piezoelectric motor drivers provides precision closed-loop control of piezoelectric motors and enables simultaneous robot motion and MR imaging. The developed modular robot control interface software performs image-based registration, kinematics calculation, and exchanges robot commands and coordinates between the navigation software and the robot controller with a new implementation of the open network communication protocol OpenIGTLink. Comprehensive compatibility of the robot is evaluated inside a $3$-T MRI scanner using standard imaging sequences and the signal-to-noise ratio loss is limited to $15\%$ . The image deterioration due to the present and motion of robot demonstrates unobservable image interference. Twenty-five targeted needle placements inside gelatin phantoms utilizing an 18-gauge ceramic needle demonstrated $0.87$-mm root-mean-square (RMS) error in 3-D Euclidean distance based on MRI volume segmentation of the image-guided robotic needle placement procedure. [ABSTRACT FROM PUBLISHER]

Stereotaxy is a neurosurgical technique that can take several hours to reach a specific target, typically utilizing a mechanical frame and guided by preoperative imaging. An error in any one of the numerous steps or deviations of the target anatomy from the preoperative plan such as brain shift (up to $20$ mm), may affect the targeting accuracy and thus the treatment effectiveness. Moreover, because the procedure is typically performed through a small burr hole opening in the skull that prevents tissue visualization, the intervention is basically “blind” for the operator with limited means of intraoperative confirmation that may result in reduced accuracy and safety. The presented system is intended to address the clinical needs for enhanced efficiency, accuracy, and safety of image-guided stereotactic neurosurgery for deep brain stimulation lead placement. The study describes a magnetic resonance imaging (MRI)-guided, robotically actuated stereotactic neural intervention system for deep brain stimulation procedure, which offers the potential of reducing procedure duration while improving targeting accuracy and enhancing safety. This is achieved through simultaneous robotic manipulation of the instrument and interactively updated in situ MRI guidance that enables visualization of the anatomy and interventional instrument. During simultaneous actuation and imaging, the system has demonstrated less than $15$% signal-to-noise ratio variation and less than $0.20\%$ geometric distortion artifact without affecting the imaging usability to visualize and guide the procedure. Optical tracking and MRI phantom experiments streamline the clinical workflow of the prototype system, corroborating targeting accuracy with three-axis root mean square error $1.38\pm 0.45$ mm in tip position and $2.03\pm 0.58^\circ$ in insertion angle. [ABSTRACT FROM AUTHOR]

The classical accelerated Demons algorithm uses Gaussian smoothing to penalize oscillatory motion in the displacement fields during registration. This well known method uses the L2 norm for regularization. Whereas the L2 norm is known for producing well behaving smooth deformation fields it cannot properly deal with discontinuities often seen in the deformation field as the regularizer cannot differentiate between discontinuities and smooth part of motion field. In this paper we propose replacement the Gaussian filter of the accelerated Demons with a bilateral filter. In contrast the bilateral filter not only uses information from displacement field but also from the image intensities. In this way we can smooth the motion field depending on image content as opposed to the classical Gaussian filtering. By proper adjustment of two tunable parameters one can obtain more realistic deformations in a case of discontinuity. The proposed approach was tested on 2D and 3D datasets and showed significant improvements in the Target Registration Error (TRE) for the well known POPI dataset. Despite the increased computational complexity, the improved registration result is justified in particular abdominal data sets where discontinuities often appear due to sliding organ motion. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine whether localised drug release using thermosensitive liposomal doxorubicin (TLD) and mild hyperthermia produced by a clinical magnetic resonance high intensity focused ultrasound (MR-HIFU) system improves anti-tumour efficacy over TLD alone in rabbit Vx2 tumours. Materials and methods: Rabbits bearing one Vx2 thigh tumour ( n = 6 per group) were administered TLD (1.67 mg/kg) either with or without MR-HIFU mild hyperthermia (20 min, 42.0 °C). Tumour progression was measured using contrast-enhanced T1-weighted MR imaging. Toxicity was evaluated by changes in body weight, blood counts, and blood chemistry. Tumour volume, body weight, and blood data were acquired weekly for the first month and biweekly thereafter. Results: Rabbits treated with TLD plus MR-HIFU mild hyperthermia had target region temperatures with spatial-median, temporal-mean of 41.4° ± 0.6 °C; 10th and 90th percentile temperatures were 40.2 and 42.7 °C. All six rabbits that received TLD alone had rapid tumour progression and reached the tumour size end point (maximum dimension >6 cm) within 24 days. Four of six rabbits treated with TLD plus MR-HIFU mild hyperthermia survived to the study end point of 60 days; one reached tumour size end point, one had hyperthermia-related toxicity, all had at least a transient decrease in tumour volume. Weekly body weight, complete blood counts, and blood chemistry did not reveal additional evidence of drug or hyperthermia-related toxicity. Conclusions: Rabbit Vx2 tumours treated with a single infusion of TLD during MR-HIFU mild hyperthermia had reduced tumour growth vs. tumours treated with TLD alone. These findings are an important step toward clinical translation of localised drug delivery using MR-HIFU and TLD. [ABSTRACT FROM AUTHOR]

Purpose: Electromagnetic (EM) tracking of instruments within a clinical setting is notorious for fluctuating measurement performance. Position location measurement uncertainty of an EM system was characterized in various environments, including control, clinical, cone beam computed tomography (CBCT), and CT scanner environments. Static and dynamic effects of CBCT and CT scanning on EM tracking were evaluated. Methods: Two guidance devices were designed to solely translate or rotate the sensor in a non-interfering fit to decouple pose-dependent tracking uncertainties. These devices were mounted on a base to allow consistent and repeatable tests when changing environments. Using this method, position and orientation measurement accuracies, precision, and 95 % confidence intervals were assessed. Results: The tracking performance varied significantly as a function of the environment-especially within the CBCT and CT scanners-and sensor pose. In fact, at a fixed sensor position in the clinical environment, the measurement error varied from 0.2 to 2.2 mm depending on sensor orientations. Improved accuracies were observed along the vertical axis of the field generator. Calibration of the measurements improved tracking performance in the CT environment by 50-85 %. Conclusion: EM tracking can provide effective assistance to surgeons or interventional radiologists during procedures performed in a clinical or CBCT environment. Applications in the CT scanner demand precalibration to provide acceptable performance. [ABSTRACT FROM AUTHOR]

Activatable photosensitizers (PSs) have been widely used for the simultaneous fluorescence imaging and photodynamic ablation of cancer cells. However, the ready aggregation of traditional PSs in aqueous media can lead to fluorescence quenching as well as reduced phototoxicity even in the activated form. We have developed a series of PSs that show aggregation-enhanced emission and phototoxicity and thus the exact opposite behavior to that of previously reported PSs. We further developed a dual-targeted enzyme-activatable bioprobe based on the optimized photosensitizer and describe simultaneous light-up fluorescence imaging and activated photodynamic therapy for specific cancer cells. The design of smart probes should thus open new opportunities for targeted and image-guided photodynamic therapy. [ABSTRACT FROM AUTHOR]

After a substantial advancement in single drug nanocarrier, nanomedicine now demands an integration of nanotechnology with combination therapy to achieve synergistic therapeutic effects. In this respect, a smart and multiple drug shuttling nanotheranostic system is developed which transport diverse kinds of anticancer drugs to cancer cells in a controlled and responsive manner respectively. Synthetically, a significantly high dose of hydrophobic camptothecin (CPT) is first loaded into the porous structure of quantum dots (CdS) coupled mesoporous silica nanocomposite. Subsequently, fluorescent doxorubicin (DOX) molecules are exclusively anchored onto the surface of CdS; as a result, the fluorescence of both CdS and DOX is quenched. Upon exposing to mildly acidic conditions, the fluorescence of both species is recovered, such fluorescent “on–off” states provides an added opportunity to real time sense drug release. In-vitro cell experiment reveals an excellent anticancer efficacy of drug cocktail, merely 3 μg/ml concentration of multiple drugs loaded nanocarrier reduces the cell viability to 30%. Furthermore, confocal imaging indicates a successful release of both therapeutic entities. We visualize that our newly fabricated multifunctional double drug-carrying nanoparticles can be a valuable addition to next generation of materials that simultaneously deliver cocktail of drugs with imaging functionality. [ABSTRACT FROM AUTHOR]

Purpose: Soft-tissue deformations can severely degrade the validity of preoperative planning data during computer assisted interventions. Intraoperative imaging such as stereo endoscopic, time-offlight or, laser range scanner data can be used to compensate these movements. In this context, the intraoperative surface has to be matched to the preoperative model. The shape matching is especially challenging in the intraoperative setting due to noisy sensor data, only partially visible surfaces, ambiguous shape descriptors, and real-time requirements. Methods: A novel physics-based shape matching (PBSM) approach to register intraoperatively acquired surface meshes to preoperative planning data is proposed. The key idea of the method is to describe the nonrigid registration process as an electrostatic-elastic problem, where an elastic body (preoperative model) that is electrically charged slides into an oppositely charged rigid shape (intraoperative surface). It is shown that the corresponding energy functional can be efficiently solved using the finite element (FE) method. It is also demonstrated how PBSM can be combined with rigid registration schemes for robust nonrigid registration of arbitrarily aligned surfaces. Furthermore, it is shown how the approach can be combined with landmark based methods and outline its application to image guidance in laparoscopic interventions. Results: A profound analysis of the PBSM scheme based on in silico and phantom data is presented. Simulation studies on several liver models show that the approach is robust to the initial rigid registration and to parameter variations. The studies also reveal that the method achieves submillimeter registration accuracy (mean error between 0.32 and 0.46 mm). An unoptimized, single core implementation of the approach achieves near real-time performance (2 TPS, 7-19 s total registration time). It outperforms established methods in terms of speed and accuracy. Furthermore, it is shown that the method is able to accurately match partial surfaces. Finally, a phantom experiment demonstrates how the method can be combined with stereo endoscopic imaging to provide nonrigid registration during laparoscopic interventions. Conclusions: The PBSM approach for surface matching is fast, robust, and accurate. As the technique is based on a preoperative volumetric F E model, it naturally recovers the position of volumetric structures (e.g., tumors and vessels). It cannot only be used to recover soft-tissue deformations from intraoperative surface models but can also be combined with landmark data from volumetric imaging. In addition to applications in laparoscopic surgery, the method might prove useful in other areas that require soft-tissue registration from sparse intraoperative sensor data (e.g., radiation therapy). [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Hyperpolarized ³He magnetic resonance imaging (MRI) previously revealed the temporal and spatial hetero-geneity of ventilation defects in asthmatics, but these findings have not been used in treatment studies or to guide personalized therapy. Our objective was to exploit the temporal and spatial information inherent to ³He MRI and develop image processing methods to generate pulmonary ventilation temporal-spatial maps that could be used to measure, optimize, and guide asthma therapy. Materials and Methods: In this proof-of-concept study, seven asthmatics provided written informed consent to an approved protocol and underwent spirometry and ³He MRI on three occasions, each 5 ± 2 days apart. A registration and segmentation pipeline was developed to generate three-dimensional, temporal-spatial, pulmonary function maps. Briefly, ³He ventilation images were segmented to generate ventilation masks that were coregisfered and voxels classified according to their temporal behavior. This enabled the regional mapping of temporally persistent and intermittent ventilation defects that were normalized to the ¹H MRI thoracic cavity volume to generate persis-tent ventilation defect percent (VDPP) and intermittent ventilation defect percent (VDP|). Results: ³He temporal-spatial pulmonary function maps identified temporally persistent and intermittent ventilation defects. VDP| was significantly greater in the posterior (P = .04) and inferior (P = .04) lung as compared to the anterior and superior lung. Persistent and inter-mittent ventilation defect percent were strongly correlated with forced expiratory volume in one second/forced vital capacity (VDPP: r = -0.87, P = .01 ; VDP,: r = -0.96, P = .0008). Conclusions: Temporal-spatial pulmonary maps generated from ³He MRI can be used to quantify temporally persistent and intermittent ventilation defects as asthma intermediate end points and targets for therapy. [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 mm 3 in BALB/c mice. The obtained results indicate that the mPLGA/IR775 nanostructure has great potential to become a highly effective oncotheranostic agent.

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., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Nanotechnology has enabled the development of many alternative anti-cancer approaches, such as thermal therapies, which cause minimal damage to healthy cells. Current challenges in cancer treatment are the identification of the diseased area and its efficient treatment without generating many side effects. Image-guided therapies can be a useful tool to diagnose and treat the diseased tissue and they offer therapy and imaging using a single nanostructure. The present review mainly focuses on recent advances in the field of thermal therapy and imaging integrated with multifunctional inorganic nanoparticles. The main heating sources for heat-induced therapies are the surface plasmon resonance (SPR) in the near infrared region and alternating magnetic fields (AMFs). The different families of inorganic nanoparticles employed for SPR- and AMF-based thermal therapies and imaging are described. Furthermore, inorganic nanomaterials developed for multimodal therapies with different and multi-imaging modalities are presented in detail. Finally, relevant clinical perspectives and the future scope of inorganic nanoparticles in image-guided therapies are discussed.

Objective Few studies report long-term follow-up of renal cancer treated by radiofrequency ablation (RFA), thus limiting the comparison of this modality to well-established long-term follow-up series of surgically resected renal masses. Herein, we report long-term oncologic outcomes of renal cancer treated with RFA in a single institution. Methods and materials We retrospectively reviewed patients treated between November 2001 and October 2012 with laparoscopic-guided or computed tomography–guided RFA. All treatments were performed with real-time thermometry ensuring target ablation temperature (>60°C) was adequately reached. Only patients with biopsy-confirmed T1a-category cancer and a follow-up period>48 months were included in our analysis. Follow-up included office visits, laboratory work, and periodic contrast-enhanced imaging. Survival was calculated using the Kaplan-Meier analysis. Overall complications were reported using the Clavien-Dindo scale. Results Of 434 RFA cases, 53 treatments in 50 patients met the inclusion criteria. Of these, 29 were treated with computed tomography–guided RFA and 24 with laparoscopic-guided RFA. The mean follow-up interval was 65.6 months (48.5–120.2), and the mean renal mass size was 2.3 cm (0.3–4.0). There were 4 (7.5%) local recurrences and 1 case of distant metastases with no local recurrence. The 5-year overall survival was 98%, cancer-specific survival was 100%, and recurrence-free survival was 92.5%. The complication rate was 26.4%, which included 71% of Clavien-Dindo grade I and 29% of grade II. Mean estimated glomerular filtration rate preoperatively and at the most recent follow-up visit was 77 and 66 ml/min, respectively. Conclusions When performed on selected patients, while monitoring real-time temperatures to ensure adequate treatment end points, RFA offers favorable long-term oncologic outcomes approaching those reported for partial nephrectomy. [ABSTRACT FROM AUTHOR]