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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.

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.

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 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 respectively trained with paired original US images and two sets of low-resolution US images. The two sets of low-resolution US images are respectively obtained through down sampling the original US images along the two axes. In US imaging, in-plane spatial resolution is generally much higher than through-plane resolution. By learning the mapping from down-sampled in-plane low-resolution images to original high-resolution US images, cycleGAN can generate through-plane high-resolution images from original sparely distributed 2D images. Finally, high-resolution 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 factor of 5 and 10 in the prostate cases. Conclusions We have proposed and investigated a new deep learning-based algorithm for reconstructing high-resolution 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 high-resolution US imaging.

This case report describes the novel use of ultrasound-guided MRI-fusion biopsy to sample an extraluminal perirectal mass. This is a 64-year-old man with a history of pT3N2b mucinous adenocarcinoma of the right colon with metastatic disease to the mesocolic lymph nodes. Two years after initial resection he was found on restaging CT to have a mass measuring ∼4.0 × 4.8 cm superior to the seminal vesicles. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) showed a moderately FDG avid soft tissue mass interposed between the prostate and the rectum. Multiparametric MRI revealed a 6.2 × 4.6 × 2.8 cm heterogeneous lobulated T2 hyperintense mass with enhancement just superior to the seminal vesicles. This mass was unable to be viewed using sigmoidoscopy. Using UroNAV technology, we were able to biopsy the mass in the clinic setting. Biopsy was confirmed as recurrent mucinous adenocarcinoma.

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.

Image-guided locoregional therapies have an important role in the management of patients with hepatocellular carcinoma (HCC). Recent advances in the ablative as well as endovascular therapies have expanded the role of interventional radiologists in the treatment of HCC. Following image-guided therapy, an accurate response assessment is vital. Knowledge regarding normal postprocedure changes and subtle signs of residual or recurrent disease is important. In this review, we discuss various response evaluation criteria currently employed for HCC. We also discuss the postprocedure imaging features suggestive of residual disease or recurrence and imaging biomarkers for response assessment.

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.

Endoscopic visualization in brain tumor removal is challenging because tumor tissue is often visually indistinguishable from healthy tissue. Fluorescence imaging can improve tumor delineation, though this impairs reflectance-based visualization of gross anatomical features. To accurately navigate and resect tumors, we created an ultrathin/flexible, scanning fiber endoscope (SFE) that acquires reflectance and fluorescence wide-field images at high-resolution. Furthermore, our miniature imaging system is affixed to a robotic arm providing programmable motion of SFE, from which we generate multimodal surface maps of the surgical field. To test this system, synthetic phantoms of debulked tumor from brain are fabricated having spots of fluorescence representing residual tumor. Three-dimension (3D) surface maps of this surgical field are produced by moving the SFE over the phantom during concurrent reflectance and fluorescence imaging (30Hz video). SIFT-based feature matching between reflectance images is implemented to select a subset of key frames, which are reconstructed in 3D by bundle adjustment. The resultant reconstruction yields a multimodal 3D map of the tumor region that can improve visualization and robotic path planning. Efficiency of creating these maps is important as they are generated multiple times during tumor margin clean-up. By using pre-programmed vector motions of the robot arm holding the SFE, the computer vision algorithms are optimized for efficiency by reducing search times. Preliminary results indicate that the time for creating these 3D multimodal maps of the surgical field can be reduced to one third by using known trajectories of the surgical robot moving the image-guided tool.

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.

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.

PURPOSE: This paper presents the development of a body-mounted robotic assistant for magnetic resonance imaging (MRI)-guided low back pain injection. Our goal was to eliminate the radiation exposure of traditional X-ray guided procedures while enabling the exquisite image quality available under MRI. The robot is designed with a compact and lightweight profile that can be mounted directly on the patient's lower back via straps, thus minimizing the effect of patient motion by moving along with the patient. The robot was built with MR-conditional materials and actuated with piezoelectric motors so it can operate inside the MRI scanner bore during imaging and therefore streamline the clinical workflow by utilizing intraoperative MR images. METHODS: The robot is designed with a four degrees of freedom parallel mechanism, stacking two identical Cartesian stages, to align the needle under intraoperative MRI-guidance. The system targeting accuracy was first evaluated in free space with an optical tracking system, and further assessed with a phantom study under live MRI-guidance. Qualitative imaging quality evaluation was performed on a human volunteer to assess the image quality degradation caused by the robotic assistant. RESULTS: Free space positioning accuracy study demonstrated that the mean error of the tip position to be [Formula: see text] mm and needle angle to be [Formula: see text]. MRI-guided phantom study indicated the mean errors of the target to be [Formula: see text] mm, entry point to be [Formula: see text] mm, and needle angle to be [Formula: see text]. Qualitative imaging quality evaluation validated that the image degradation caused by the robotic assistant in the lumbar spine anatomy is negligible. CONCLUSIONS: The study demonstrates that the proposed body-mounted robotic system is able to perform MRI-guided low back injection in a phantom study with sufficient accuracy and with minimal visible image degradation that should not affect the procedure. ispartof: INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY vol:15 issue:2 pages:321-331 ispartof: location:Germany status: published

PURPOSE: Transcranial focused ultrasound (FUS) is increasingly being explored to modulate neuronal activity. To target neuromodulation, researchers often localize the FUS beam onto the brain region(s) of interest using spatially tracked tools overlaid on pre-acquired images. Here, we quantify the accuracy of optically tracked image-guided FUS with magnetic resonance imaging (MRI) thermometry, evaluate sources of error, and demonstrate feasibility of these procedures to target the macaque somatosensory region. METHODS: We developed an optically tracked FUS system capable of projecting the transducer focus onto a pre-acquired MRI volume. To measure the target registration error (TRE), we aimed the transducer focus at a desired target in a phantom under image guidance, heated the target while imaging with MR thermometry, and then calculated the TRE as the difference between the targeted and heated locations. Multiple targets were measured using either an unbiased or bias-corrected calibration. We then targeted the macaque S1 brain region, where displacement induced by the acoustic radiation force was measured using MR acoustic radiation force imaging (MR-ARFI). RESULTS: All calibration methods enabled registration with TRE on the order of 3mm. Unbiased calibration resulted in an average TRE of 3.26 mm (min – max: 2.80 – 4.53 mm), which was not significantly changed by prospective bias correction (TRE of 3.05 mm; 2.06 – 3.81 mm, p=0.55). Restricting motion between the transducer and target and increasing the distance between tracked markers reduced the TRE to 2.43 mm (min-max: 0.79 – 3.88 mm). MR-ARFI images showed qualitatively similar shape and extent as projected beam profiles in a living non-human primate. CONCLUSIONS: Our study describes methods for image guidance of FUS neuromodulation and quantifies errors associated with this method in a large animal. The workflow is efficient enough for in vivo use, and we demonstrate transcranial MR-ARFI in vivo in macaques for the first time.

Magnetic nanoparticle (MNP)-induced hyperthermia is currently being evaluated for localized prostate cancer. We evaluated the feasibility of tumor-selective delivery of prostate-specific membrane antigen (PSMA)-targeted MNPs in a murine model with high-resolution magnetic resonance imaging (MRI) after intravenous administration of MNPs at a concentration necessary for hyperthermia. A PSMA-targeted MNP was synthesized and evaluated using T2-weighted MRI, after intravenous administration of 50 mg/kg of the MNP. Significant contrast enhancement ( P < 0.0002, n = 5) was observed in PSMA(+) tumors compared to PSMA(-) tumors 24 h and 48 h after contrast agent administration. Mice were also imaged with near-infrared fluorescence imaging, to validate the MRI results. Two-photon microscopy revealed higher vascular density at the tumor periphery, which resulted in higher peripheral accumulation of PSMA-targeted MNPs. These results suggest that the delivery of PSMA-targeted MNPs to PSMA(+) tumors is both actively targeted and passively mediated.

Purpose: To evaluate the feasibility and assess safety parameters of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated hyperthermia (HT; heating to 40–45 °C) in various pelvic targets in a porcine model in vivo. Methods: Thirteen HT treatments were performed in six pigs with a commercial MRgHIFU system (Sonalleve V2, Profound Medical Inc., Mississauga, Canada) to muscle adjacent to the ventral/dorsal bladder wall and uterus to administer 42 °C (±1°) for 30 min (±5%) using an 18-mm target diameter and 100 W power. Feasibility was assessed using accuracy, uniformity, and MR-thermometry performance-based metrics. Safety parameters were assessed for tissues in the targets and beam-path by contrast-enhanced MRI, gross-pathology and histopathology. Results: Across all HT sessions, the mean difference between average temperature (Tavg) and the target temperature within the target region-of-interest (tROI, the cross-section of the heated volume at focal depth) was 0.51 ± 0.33 °C. Within the tROI, the temperature standard deviation averaged 1.55 ± 0.31 °C, the average 30-min Tavg variation was 0.80 ± 0.17 °C, and the maximum difference between Tavg and the 10th- or 90th-percentile temperature averaged 2.01 ± 0.44 °C. The average time to reach ≥41 °C and cool to ≤40 °C within the tROI at the beginning and end of treatment was 47.25 ± 27.47 s and 66.37 ± 62.68 s, respectively. Compared to unheated controls, no abnormally-perfused tissue or permanent damage was evident in the MR images, gross pathology or histological analysis. Conclusions: MRgHIFU-mediated HT is feasible and safety assessment is satisfactory for treating an array of clinically-mimicking pelvic geometries in a porcine model in vivo, implying the technique may have utility in treating pelvic targets in human patients.

Photoacoustic imaging is a rapidly maturing imaging modality in biological research and medicine. This modality uses the photoacoustic effect (“light in, sound out”) to combine the contrast and specificity of optical imaging with the high temporal resolution of ultrasound. The primary goal of image-guided therapy, and theranostics in general, is to transition from conventional medicine to precision strategies that combine diagnosis with therapy. Photoacoustic imaging is well-suited for noninvasive guidance of many therapies and applications currently being pursued in three broad areas. These include the image-guided resection of diseased tissue, monitoring of disease states, and drug delivery. In this review, we examine the progress and strategies for development of photoacoustics in these three key areas with an emphasis on the value photoacoustics has for image-guided 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. Graphic Abstract

Intravascular optical coherence tomography (IVOCT) images have the necessary resolution and contrast to assess atherosclerotic plaque, and our group has created machine/deep learning techniques to analyze plaques in pre-stent IVOCT images. Such software can be used to aid numerous research studies and clinical treatment planning. Here we extend our work to images obtained following stent implantation, where opaque metallic stent struts obstruct the view of portions of the plaque, making it difficult to visualize/analyze plaques. We created a generative adversarial network (GAN)-based method to fill in the missing image data. Applications include analysis of plaque progression/regression behind the stent to evaluate drugs, drug eluting stents, and the anatomical registration of pre- and post-stent image data for further post stent optimization. We used conditional GAN (cGAN) to correct the presence of the guide wire and stent struts shadows, creating full images for visualization and analyses. To train/test software, we created synthetic post-stent images by interjecting realistic stent strut shadows in images without a stent in place. Results show the capability of cGAN to generate plausible and realistic images. To assess results, we used deep learning segmentation models to segment calcifications in corrected, synthesized images and compared results to the original images with stent. DICE scores were typically above 0.79 ± 0.03 with correction and 0.71 ± 0.02 without correction. The co-registration errors improved to be ranged between 0.52 mm to 0.69 mm. Compared with images with shadows, the new method offers lower errors in both location and orientation registration.

Purpose: The objective of this paper is to present heatmaps from the likelihood of clinically significant prostate cancer with a deep learning model. This will give radiologists more information on the location of prostate lesions. Methods: 3D Slicer module was developed using a machine learning model to predict pixel-by-pixel PI-RADS scores. The working hypothesis is that the machine learning algorithm will be capable of producing heatmaps with hotspots within a typical size of a lesion with PI-RAD score of 4. Discussion and conclusion: The study provided insight into the future of MRI assessment using Deep Learning models.

MR-guided high-intensity focused ultrasound (MR-HIFU) is a non-invasive therapeutic technology which has demonstrated clinical potential for tissue ablation. The application of this therapeutic approach facilitated to be a promising option to achieve faster pain palliation in patients with bone metastasis. However, its clinical adoption is still hampered by a lack of workflow integration. Currently, to ensure sufficient positioning, MR images have to be repeatedly acquired in between patient re-positioning tasks, leading to a time-consuming preparation phase of at least 30 minutes, involving extra costs and time to the available treatment time. Augmented reality (AR) is a promising technology that enables the fusion of medical images, such as MRI, with the view of an external camera. AR represents a valid tool for a faster localization and visualization of the lesion during positioning. The aim of this work is the implementation of a novel AR setup for accelerating the patient positioning during MRHIFU treatments by enabling adequate target positioning outside the MRI scanner. A marker-based approach was investigated for fusing the MR data with video data for providing an augmented view. Initial experiments on four volunteers show that MR images were overlaid on the camera views with an average re-projection error of 3.13 mm, which matches the clinical requirements for this specific application. It can be concluded that the implemented system is suitable for MR-HIFU procedures and supports its clinical adoption by improving the patient positioning, thereby offering potential for faster treatment time.

Prostate cancer is the most frequently diagnosed non-cutaneous cancer and the second leading cause of cancer-related deaths in men. Whole gland surgical and radiation treatments for prostate cancer are highly effective for long-term cancer control. However, these are often associated with overtreatment, resulting in urinary complications and sexual dysfunction, adversely impacting the quality of life. Focal laser ablation (FLA) under magnetic resonance imaging (MRI)-guidance is an alternative minimally invasive treatment method for localized prostate tumors while preserving surrounding structures and healthy tissues. Accurate needle positioning and delivery are critical for the therapeutic success of MRI-guided FLA. We propose an MRI-compatible mechatronic system for in-bore transperineal FLA needle guidance to localized prostate lesions. This paper presents the mechatronic system design, including a remotely actuated, four degree-of-freedom transperineal positioning and needle guidance mechanism, and adaptable needle guide. We demonstrate its MR compatibility and evaluated its mechanical bias in free-space testing using an external optical tracking system with several measurement points (N=40) over its range-of-motion. Free-space testing resulted in a root-mean-square error of 0.71 ± 0.30 mm. Within an MR environment, in-bore testing to virtual targets (N=10) with projected needle trajectories resulted in a mean needle tip error of 1.81 ± 0.56 mm and needle trajectory error of 0.78 ± 0.75°. This suggests that localized ablation regions can be accurately targeted within 2.16 mm within 95% confidence. An extensive in-bore analysis and correction for systematic bias across the range-of-motion may improve this accuracy. This study shows that our proposed mechatronic needle guidance system may be a feasible alternative for accurate MR-guided FLA for localized prostate therapy.

Brachytherapy is often used in gynecologic cancer treatment to provide high radiation doses to tumors and spare nearby healthy tissues. Intracavitary applicators, including tandem-and-ovoid and tandem-and-ring, are commonly used to position the radioactive sources appropriately. Three-dimensional (3D) transrectal ultrasound (TRUS) imaging has been demonstrated to allow for consistent delineation of the clinical target volume; however, the ability to visualize applicators and relevant structures following applicator insertion has not been investigated. We propose the use of a 3D TRUS system to visualize applicators at the time of placement. In two patient images, the key components of the tandem-and-ovoid applicators were clearly visualized, as well as the uterus, cervix, and vagina, with the potential to identify the tumor and organs-at-risk in these images. Although the tandem-and-ring applicator (one patient) obscured the cervix and anterior anatomy, the posterior applicator edges were visualized and we propose combining the 3D TRUS image with a 3D transabdominal ultrasound (TAUS) image for more complete visualization of the necessary structures. We designed a multimodality application-specific pelvic phantom to assess the feasibility of the image fusion and performed preliminary feasibility assessment on a tandem-and-ovoids applicator and a tandem-and-ring applicator with an interstitial ring cap. The resulting phantom images showed promising features for future image fusion. Intraoperative assessment of applicator placement has the potential to improve the treatment quality and reduce the risk of complications from overexposure of nearby normal tissues, as well as provides a promising approach for accessible image-guided brachytherapy, facilitating broader adoption to healthcare cost-constrained settings.

Focused ultrasound (FUS) is a promising method to open the blood brain barrier (BBB) for treatment of neurodegenerative diseases. Accurate targeting is essential for a successful BBB opening (BBBo). We aim to develop a robust therapy planning for BBBo in mice, which is challenging due to the size of the brain and the influence of the skull on the ultrasound pressure distribution. For enabling mouse individual therapy planning, a simulation tool is proposed, developed and validated. We used the k-Wave toolbox to enable 3D acoustic simulations of the commercial FUS system from Image Guided Therapy (IGT). Micro-CT scans were used to model the geometry of skulls. Simulations using a mouse skull showed an attenuation of approx. 20–24% depending on the position of penetration, which was validated by hydrophone measurements in the same range. Based on these validations we planned BBBo in m ice by placing the transducer at different positions over the mouse brain and varying the excitation amplitude. With different transducer positions, the peak pressure in the brain varied between 0.54 MPa and 0.62 MPa at 11% output level, which is expected to enable safe BBBo. Subsequently, in vivo experiments were conducted using the aforementioned simulation parameters. BBBo was confirmed by contrast enhanced T1 weighted magnetic resonance images immediately after sonication.

MRI-Linac is a new device that combines an MRI unit and a 6 MV linear accelerator (on a single circular gantry) very similar to a tomotherapy unit for image-guided and adaptive therapy. It uses MRI for planning and image guidance. This device is most useful for treating soft tissue tumors such as liver, pancreas, kidney, and so on. The MRI signal is converted to a pseudo-CT called synthetic CT for planning and dose calculation. Using a fast MLC on a linac, this device provides on-line image verification and IMRT/VMAT treatment.

Focused ultrasound (FUS) exposure of micro-bubble (MB) contrast agents can transiently increase microvascular permeability allowing anticancer drugs to extravasate into a targeted tumor tissue. Either fixed or mechanically steered in space, most studies to date have used a single element focused transducer to deliver the ultrasound (US) energy. The goal of this study was to investigate various multi-FUS strategies implemented on a programmable US scanner (Vantage 256, Verasonics Inc.) equipped with a linear array for image guidance and a 128-element therapy transducer (HIFUPlex-06, Sonic Concepts). The multi-FUS strategies include multi-FUS with sequential excitation (multi-FUS-SE) and multi-FUS with temporal sequential excitation (multi-FUS-TSE) and were compared to single-FUS and sham treatment. This study was performed using athymic mice implanted with breast cancer cells ( ${N} = 20$ ). FUS therapy experiments were performed for 10 min after a solution containing MBs (Definity, Lantheus Medical Imaging Inc.) and near-infrared (NIR, surrogate drug) dye were injected via the tail vein. The fluorescent signal was monitored using an in vivo optical imaging system (Pearl Trilogy, LI-COR) to quantify intratumoral dye accumulation at baseline and again at 0.1, 24, and 48 h after receiving US therapy. Animals were then euthanized for ex vivo dye extraction analysis. At 48 h, fluorescent tracer accumulation within the tumor space for the multi-FUS-TSE therapy group animals was found to be 67.3%, 50.3%, and 36.2% higher when compared to sham, single-FUS, and multi-FUS-SE therapy group measures, respectively. Also, dye extraction and fluorescence measurements from excised tumor tissue found increases of 243.2%, 163.1%, and 68.1% for the multi-FUS-TSE group compared to sham, single-FUS, and multi-FUS-SE therapy group measures, respectively. In summary, experimental results revealed that for a multi-FUS sequence, increased microvascular permeability was considerably influenced by both the spatial and temporal aspects of the applied US therapy.

Objective: The application of bubble-based ablation with the focus ultrasound therapy histotripsy is gaining traction for the treatment of venous thrombosis, among other pathologies. For extensive clot burden, the histotripsy source must be translated to ensure uniform bubble activity throughout the vascular obstruction. The purpose of this study was to evaluate the targeting accuracy of a histotripsy system comprised of a focused source, ultrasound image guidance, and a collaborative robot (cobot) positioner. The system was designed with a primary emphasis for treating deep vein thrombosis. Methods: Studies to test treatment planning and targeting bubble activity with the histotripsy-cobot system were conducted in an in vitro clot model. A tissue-mimicking phantom was also targeted with the system, and the predicted and actual areas of liquefaction were compared to gauge the spatial accuracy of ablation. Results: The system provided submillimeter accuracy for both tracking along an intended path (within 0.6 mm of a model vessel) and targeting bubble activity within the venous clot model (0.7 mm from the center of the clot). Good correlation was observed between the planned and actual liquefaction locations in the tissue phantom, with an average Dice similarity coefficient of 77.8%, and average Hausdorff distance of 1.6 mm. Conclusion: Cobots provide an effective means to apply histotripsy pulses over a treatment volume, with the ablation precision contingent on the quality of image guidance. Significance: Overall, these results demonstrate cobots can be used to guide histotripsy ablation for targets that extend beyond the natural focus of the transducer.

Intraoperative radiation therapy (IORT) involves the application of high dose radiation (HDR) to adjacent tissue following surgical resection of a tumor. Recently, it was shown that X-ray CT provides clinically useful image guidance to better verify the presence of air voids, or adjacency to skin or bone, that determine optimal, and safe, dosing. As a lower cost, safer and real-time alternative, we assembled a prototype ultrasound device to provide real-time intraoperative image guidance, viewed from within the minimally invasive HDR applicator, as a substitute for X-ray CT. Sequences of offset 2D image planes were interpolated to a 3D grid image data set. Imaging resolution was spatially variant (approximately 0.5 mm axial, 2 mm azimuth). We successfully conducted a single human patient study, involving a breast cancer resection, in an intraoperative setting. Despite a number of practical challenges relating to the dimensions and materials of the components employed, the prototype device worked satisfactorily. Air voids were readily evident in the reconstructed images. In addition to breast cancer, the method has applicability in other cancers involving tumor resection - e.g. prostate cancer.

Focused ultrasound (FUS) is being explored for a variety of non-thermal transcranial applications, such as neuromodulation and blood-brain barrier opening. Although MRI is the gold standard for image guidance during FUS procedures, researchers are increasingly exploring other navigation methods, such as optical tracking, to guide ultrasound beam placement based on pre-acquired images for targeting outside the MRI setting. Current offline neuronavigation methods perform guidance based on the free-field ultrasound beam and do not incorporate attenuation and aberration effects of the skull. Here, we developed a pipeline that combines optical tracking and acoustic simulations to obtain accurate maps of the acoustic pressure within the skull.

X-ray imaging has proved invaluable in medical diagnoses and non-destructive testing (NDT) in the past century. However, there remain two major limitations: radiation harm and inaccessibility to the sample. A recent imaging modality, X-ray induced acoustic computed tomography (XACT), allows a novel solution. In XACT, x-ray induced excitation causes localized heating (

Accurate definition of the extent and severity of left-ventricular assist device (LVAD) infection may facilitate therapeutic decision making and targeted surgical intervention. Here, we explore the value of (18)F-FDG PET/CT for guidance of patient management. Methods: Fifty-seven LVAD-carrying patients received 85 whole-body (18)F-FDG PET/CT scans for the work-up of device infection. Clinical follow-up was obtained for up to 2 y. Results: PET/CT showed various patterns of infectious involvement of the 4 LVAD components: driveline entry point (77% of patients), subcutaneous driveline path (87%), pump pocket (49%), and outflow tract (58%). Driveline smears revealed Staphylococcus or Pseudomonas strains as the underlying pathogen in most cases (48 and 34%, respectively). At receiver-operating-characteristic analysis, an (18)F-FDG SUV of more than 2.5 was most accurate to identify smear-positive driveline infection. Infection of 3 or all 4 LVAD components showed a trend toward lower survival than did infection of 2 or fewer components (P = 0.089), whereas involvement of thoracic lymph nodes was significantly associated with an adverse outcome (P = 0.001 for nodal SUV above vs. below median). Finally, patients who underwent early surgical revision within 3 mo after PET/CT (n = 21) required significantly less inpatient hospital care during follow-up than did those receiving delayed surgical revision (n = 11; P < 0.05). Conclusion: Whole-body (18)F-FDG PET/CT identifies the extent of LVAD infection and predicts adverse outcome. Initial experience suggests that early image-guided surgical intervention may facilitate a less complicated subsequent course.

Successful visualization of prostate cancer (PCa) tumor margins during surgery remains a major challenge. The visualization of these tumors during surgery via near infrared fluorescence (NIRF) imaging would greatly enhance surgical resection, minimizing tumor recurrence and improving outcome. Furthermore, chemotherapy is typically administered to patients after surgery to treat any missed tumor tissue around the surgical area, minimizing metastasis and increasing patient survival. For these reasons, a theranostics fluorescent nanoparticle could be developed to assist in the visualization of PCa tumor margins, while also delivering chemotherapeutic drug after surgery. Methods: Ferumoxytol (FMX) conjugated to the fluorescent dye and PCa targeting agent, heptamethine carbocyanine (HMC), yielded the HMC-FMX nanoprobe that was tested in vitro with various PCa cell lines and in vivo with both subcutaneous and orthotopic PCa mouse models. Visualization of these tumors via NIRF imaging after administration of HMC-FMX was performed. In addition, delivery of chemotherapeutic drug and their effect on tumor growth was also assessed. Results: HMC-FMX internalized into PCa cells, labeling these cells and PCa tumors in mice with near infrared fluorescence, facilitating tumor margin visualization. HMC-FMX was also able to deliver drugs to these tumors, reducing cell migration and slowing down tumor growth. Conclusion: HMC-FMX specifically targeted PCa tumors in mice allowing for the visualization of tumor margins by NIRF imaging. Furthermore, delivery of anticancer drugs by HMC-FMX effectively reduced prostate tumor growth and reduced cell migration in vitro. Thus, HMC-FMX can potentially translate into the clinic as a nanotheranostics agent for the intraoperative visualization of PCa tumor margins, and post-operative treatment of tumors with HMC-FMX loaded with anticancer drugs.

Transcranial magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) thermal ablation is under clinical investigation for non-invasive neurosurgery, though its use is restricted to central brain targets due primarily to skull heating effects. The combination of FUS and contrast agent microbubbles greatly reduces the ultrasound exposure levels needed to ablate brain tissue and may help facilitate the use of transcranial FUS ablation throughout the brain. However, sources of variability exist during microbubble-mediated FUS procedures that necessitate the continued development of systems and methods for online treatment monitoring and control, to ensure that excessive and/or off-target bioeffects are not induced from the exposures. Methods: Megahertz-rate three-dimensional (3D) microbubble imaging in vivo was performed during nonthermal ablation in rabbit brain using a clinical-scale prototype transmit/receive hemispherical phased array system. Results: In-vivo volumetric acoustic imaging over microsecond timescales uncovered spatiotemporal microbubble dynamics hidden by conventional whole-burst temporal averaging. Sonication-aggregate ultrafast 3D source field intensity data were predictive of microbubble-mediated tissue damage volume distributions measured post-treatment using MRI and confirmed via histopathology. Temporal under-sampling of acoustic emissions, which is common practice in the field, was found to impede performance and highlighted the importance of capturing adequate data for treatment monitoring and control purposes. Conclusion: The predictive capability of ultrafast 3D microbubble imaging, reported here for the first time, will enable future microbubble-mediated FUS treatments with unparalleled precision and accuracy, and will accelerate the clinical translation of nonthermal tissue ablation procedures both in the brain and throughout the body.

Purpose Image-guided focal ablation procedures are first-line therapy options in the treatment of liver cancer tumors that provide advantageous reductions in patient recovery times and complication rates relative to open surgery. However, extensive physician training is required and image guidance variabilities during freehand therapy applicator placement limit the sufficiency of ablation volumes and the overall potential of these procedures. We propose the use of three-dimensional ultrasound (3D US) to provide guidance and localization of therapy applicators, augmenting current ablation therapies without the need for specialized procedure suites. We have developed a novel scanning mechanism for geometrically variable 3D US images, a mechanical tracking system, and a needle applicator insertion workflow using a custom needle applicator guide for targeted image-guided procedures. Methods A three-motor scanner was designed to use any commercially available US probe to generate accurate, consistent, and geometrically variable 3D US images. The designed scanner was mounted on a counterbalanced stabilizing and mechanical tracking system for determining the US probe orientation, which was assessed using optical tracking. Further exploiting the utility of the motorized scanner, an image-guidance workflow was developed that moved the probe to any identified target within an acquired 3D US image. The complete 3D US guidance system was used to perform mock targeted interventional procedures on a phantom by selecting a target in a 3D US image, navigating to the target, and performing needle insertion using a custom 3D-printed needle applicator guide. Registered postinsertion 3D US images and cone-beam computed tomography (CBCT) images were used to evaluate tip targeting errors when using the motors, tracking system, or mixed navigation approaches. Two 3D US image geometries were investigated to assess the accuracy of a small-footprint tilt approach and a large field-of-view hybrid approach for a total of 48 targeted needle insertions. 3D US image quality was evaluated in a healthy volunteer and compared to a commercially available matrix array US probe. Results A mean positioning error of 1.85 ± 1.33 mm was observed when performing compound joint manipulations with the mechanical tracking system. A combined approach for navigation that incorporated the motorized movement and the in-plane tracking system corrections performed the best with a mean tip error of 3.77 ± 2.27 mm and 4.27 ± 2.47 mm based on 3D US and CBCT images, respectively. No significant differences were observed between hybrid and tilt image acquisition geometries with all mean registration errors ≤1.2 mm. 3D US volunteer images resulted in clear reconstruction of clinically relevant anatomy. Conclusions A mechanically tracked system with geometrically variable 3D US provides a utility that enables enhanced applicator guidance, placement verification, and improved clinical workflow during focal liver tumor ablation procedures. Evaluations of the tracking accuracy, targeting capabilities, and clinical imaging feasibility of the proposed 3D US system, provided evidence for clinical translation. This system could provide a workflow for improving applicator placement and reducing local cancer recurrence during interventional procedures treating liver cancer and has the potential to be expanded to other abdominal interventions and procedures.

Colonoscopies are routine, low-risk procedures that are used to screen patients for diseases like colorectal cancer. However, often times they are performed with moderate sedation (i.e. conscious sedation) which may result in pain for patients. With moderate sedation, these procedures can be extremely painful, with one study reporting that more than 20% of patients experienced severe pain. This pain is usually the result of a phenomenon called “endoscopic looping,” which occurs when the scope loops within the patient’s bowels and stretches out their intestines. Looping is extremely common, and can occur in up to 90% of procedures. This study reports a low-cost endoscopy visualization device aimed to decrease patient pain during colonoscopies and time lost due to complications experienced during procedures. The device consists of a flexible piezoelectric sensor to detect applied forces during looping, bending, or compression. In order to use the device, the endoscopist inserts the piezoelectric cable fully within the working channel of the colonoscope before the colonoscopy begins. The piezoelectric cable is connected to an external monitor. If extreme forces or bends are detected by the piezoelectric cable, a notification can appear on screen that a loop is forming. Once the colonoscope reaches the desired location, the endoscopist removes the piezoelectric cable, leaving the working channel open for use by other tools, such as biopsy forceps.

Objective: In recent years, there has been increasing interest in the use of ultrasound guidance for endoscopic and percutaneous procedures. Kidney mockups could be used for training, however, available mockups are normally incompatible with ultrasound imaging. We developed a reproducible method to manufacture an ultrasound-compatible collecting system mockup that can be made at urology laboratories. Methods: Positive and negative molding methods were used. A three-dimensional (3D) digital model of a urinary collecting system and the overlying skin surface were segmented from computed tomography. A containment mold (negative) was made following the shape of the skin surface using 3D printing. A collecting system mold (positive) was also 3D printed, but made of a dissolvable material. The containment mold was filled with a gelatin formula with the collecting system mold submersed in situ within. After the gelatin solidified, a solution was used to dissolve the collecting system mold, but not the gelatin, leaving a cavity with the shape of the collecting system. The gelatin was extracted from the container mockup and the collecting system cavity was filled with water. The mockup was imaged with ultrasound to assess echogenicity and suitability for simulating ultrasound-guided procedures. Results: A clear shape corresponding to the collecting system was observed inside the gel structure. Structural integrity was maintained with no observable manufacturing marks or separation seams. Ultrasound images of the mockup demonstrated clear differentiation at the gelatin/water interface. A mock stone was placed in the collecting system and needle targeted to simulate percutaneous needle access. Conclusion: We developed a simple method to manufacture a personalized mockup of the renal collecting system of a patient that can be used for ultrasound-guided percutaneous needle access. Generic collecting system mockups can be used for training, and patient-specific models can be used to simulate and decide the best access path before a clinical case.

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

IntroductionEndovascular aortic repair (EVAR) is a minimal-invasive technique that prevents life-threatening rupture in patients with aortic pathologies by implantation of an endoluminal stent graft. During the endovascular procedure, device navigation is currently performed by fluoroscopy in combination with digital subtraction angiography. This study presents the current iterative process of biomedical engineering within the disruptive interdisciplinary project Nav EVAR, which includes advanced navigation, image techniques and augmented reality with the aim of reducing side effects (namely radiation exposure and contrast agent administration) and optimising visualisation during EVAR procedures. This article describes the current prototype developed in this project and the experiments conducted to evaluate it.MethodsThe current approach of the Nav EVAR project is guiding EVAR interventions in real-time with an electromagnetic tracking system after attaching a sensor on the catheter tip and displaying this information on Microsoft HoloLens glasses. This augmented reality technology enables the visualisation of virtual objects superimposed on the real environment. These virtual objects include three-dimensional (3D) objects (namely 3D models of the skin and vascular structures) and two-dimensional (2D) objects [namely orthogonal views of computed tomography (CT) angiograms, 2D images of 3D vascular models, and 2D images of a new virtual angioscopy whose appearance of the vessel wall follows that shown in ex vivo and in vivo angioscopies]. Specific external markers were designed to be used as landmarks in the registration process to map the tracking data and radiological data into a common space. In addition, the use of real-time 3D ultrasound (US) is also under evaluation in the Nav EVAR project for guiding endovascular tools and updating navigation with intraoperative imaging. US volumes are streamed from the US system to HoloLens and visualised at a certain distance from the probe by tracking augmented reality markers. A human model torso that includes a 3D printed patient-specific aortic model was built to provide a realistic test environment for evaluation of technical components in the Nav EVAR project. The solutions presented in this study were tested by using an US training model and the aortic-aneurysm phantom.ResultsDuring the navigation of the catheter tip in the US training model, the 3D models of the phantom surface and vessels were visualised on HoloLens. In addition, a virtual angioscopy was also built from a CT scan of the aortic-aneurysm phantom. The external markers designed for this study were visible in the CT scan and the electromagnetically tracked pointer fitted in each marker hole. US volumes of the US training model were sent from the US system to HoloLens in order to display them, showing a latency of 259±86 ms (mean±standard deviation).ConclusionThe Nav EVAR project tackles the problem of radiation exposure and contrast agent administration during EVAR interventions by using a multidisciplinary approach to guide the endovascular tools. Its current state presents several limitations such as the rigid alignment between preoperative data and the simulated patient. Nevertheless, the techniques shown in this study in combination with fibre Bragg gratings and optical coherence tomography are a promising approach to overcome the problems of EVAR interventions.

Purpose We describe the acceptance testing, commissioning, periodic quality assurance, and workflow procedures developed for the first clinically implemented magnetic resonance imaging-guided radiation therapy (MR-IGRT) system for real-time tracking and beam control. Methods The system utilizes real-time cine imaging capabilities at 4 frames per second for real-time tracking and beam control. Testing of the system was performed using an in-house developed motion platform and a commercially available motion phantom. Anatomical tracking is performed by first identifying a target (a region of interest that is either tissue to be treated or a critical structure) and generating a contour around it. A boundary contour is also created to identify tracking margins. The tracking algorithm deforms the anatomical contour (target or a normal organ) on every subsequent cine frame and compares it to the static boundary contour. If the anatomy of interest moves outside the boundary, the radiation delivery is halted until the tracked anatomy returns to treatment portal. The following were performed to validate and clinically implement the system: (a) spatial integrity evaluation; (b) tracking accuracy; (c) latency; (d) relative point dose and spatial dosimetry; (e) development of clinical workflow for gating; and (f) independent verification by an outside credentialing service. Results The spatial integrity of the MR system was found to be within 2 mm over a 45-cm diameter field-of-view. The tracking accuracy for geometric targets was within 1.2 mm. The average system latency was measured to be within 394 ms. The dosimetric accuracy using ionization chambers was within 1.3% ± 1.7%, and the dosimetric spatial accuracy was within 2 mm. The phantom irradiation for the outside credentialing service had satisfactory results, as well. Conclusions The first clinical MR-IGRT system was validated for real-time tracking and gating capabilities and shown to be reliable and accurate. Patient workflow methods were developed for efficient treatment. Periodic quality assurance tests can be efficiently performed with commercially available equipment to ensure accurate system performance.

Background: Chest tube drainage with fibrinolytics is a cost-effective treatment option for parapneumonic effusion and empyema in children. Although the additional use of ultrasound (US) guidance is recommended, this is rarely performed in real time to direct drain insertion. Objective: To evaluate the effectiveness and safety of real-time US-guided, radiologically placed chest drains at a tertiary university hospital. Materials and methods: This was a retrospective review over a 16-year period of all children with parapneumonic effusion or empyema undergoing percutaneous US-guided drainage at our centre. Results: Three hundred and three drains were placed in 285 patients. Treatment was successful in 93% of patients after a single drain (98.2% success with 2 or 3 drains). Five children had peri-insertion complications, but none was significant. The success rate improved with experience. Although five patients required surgical intervention, all children treated since 2012 were successfully treated with single-tube drainage only and none has required surgery. Conclusion Our technique for inserting small-bore (≤8.5 F) catheter drains under US guidance is effective and appears to be a safe procedure for first-line management of complicated parapneumonic effusion and empyema.

Liver-directed therapy is a critical component of treatment strategies for hepatocellular carcinoma. These therapies included percutaneous image-guided ablation, transarterial chemoembolization, and transarterial radioembolization, and are administered by interventional radiologists. Depending on the stage of disease, a particular treatment modality, or a combination thereof, is expected to be most efficacious in achieving the goals of treatment for a particular patient. This article seeks to review the various liver-directed treatment modalities for treatment of hepatocellular carcinoma, with attention to their efficacy and patient selection criteria.

BACKGROUND: Opening of the blood-brain barrier (BBB) induced with MRI-guided focused ultrasound has been shown in experimental animal models to reduce amyloid-β plaque burden, improve memory performance, and facilitate delivery of therapeutic agents to the brain. However, physiologic effects of this procedure in humans with Alzheimer disease (AD) require further investigation. PURPOSE: To assess imaging effects of focused ultrasound–induced BBB opening in the hippocampus of human participants with early AD and to evaluate fluid flow patterns after BBB opening by using serial contrast-enhanced MRI. MATERIALS AND METHODS: Study participants with early AD recruited to a Health Insurance Portability and Accountability Act–compliant, prospective, ongoing phase II clinical trial (ClinicalTrials.gov identifier, NCT03671889) underwent three separate focused ultrasound–induced BBB opening procedures that used a 220-kHz transducer with a concomitant intravenous microbubble contrast agent administered at 2-week intervals targeting the hippocampus and entorhinal cortex between October 2018 and May 2019. Posttreatment effects and gadolinium-based contrast agent enhancement patterns were evaluated by using 3.0-T MRI. RESULTS: Three women (aged 61, 72, and 73 years) consecutively enrolled in the trial successfully completed repeated focused ultrasound–induced BBB opening of the hippocampus and entorhinal cortex. Postprocedure contrast enhancement was clearly identified within the targeted brain volumes, indicating immediate spatially precise BBB opening. Parenchymal enhancement resolved within 24 hours after all treatments, confirming BBB closure. Transient perivenous enhancement was consistently observed during the acute phase after BBB opening. Notably, contrast enhancement reappeared in the perivenular regions after BBB closure. This imaging marker is consistent with blood-meningeal barrier permeability and persisted for 24–48 hours before spontaneous resolution. No evidence of intracranial hemorrhage or other adverse effect was identified. CONCLUSION: MRI-guided focused ultrasound–induced blood-brain barrier opening was safely performed in the hippocampi of three participants with Alzheimer disease without any adverse effects. Posttreatment MRI reveals a unique spatiotemporal contrast enhancement pattern that suggests a perivenular immunologic healing response downstream from targeted sites. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Klibanov in this issue.

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.

With the advancement of early detection tools for prostate cancer and ability to better localize disease, there has been increased interest in focal or targeted therapies that carry less morbidity than traditional whole-gland treatments. The Sonablate

The role of retinal photocoagulation as a first line therapy for various retinal pathologies has decreased with the introduction of anti-vascular endothelial growth factor therapy. However, retinal laser therapy remains an important treatment modality, especially with the emergence of micropulse subthreshold treatment and the integration of newer technology such as augmented reality and semi-automated delivery. This review summarizes current evidence for micropulse laser as a treatment modality and discusses the role of new technology such as augmented reality in the future of laser therapy.

Brachytherapy is a radiotherapy modality associated with a highly focal dose distribution. Brachytherapy treats the cancer tissue from the inside, and the radiation does not travel through healthy tissue to reach the target as with external beam radiotherapy techniques. The nature of brachytherapy makes it attractive for boosting limited size target volumes to very high doses while sparing normal tissues. Significant developments over the last decades have increased the use of 3D image guided procedures with the utilization of CT, MRI, US and PET. This has taken brachytherapy to a new level in terms of controlling dose and demonstrating excellent clinical outcome. Interests in focal, hypofractionated and adaptive treatments are increasing, and brachytherapy has significant potential to develop further in these directions with current and new treatment indications.

Contains fulltext : 173118.pdf (Publisher’s version ) (Open Access) PURPOSE: To assess whether laser guidance can reduce fluoroscopy and procedure time of cone-beam computed tomography (CBCT)-guided radiofrequency (RF) ablations of osteoid osteoma compared to freehand CBCT guidance. MATERIALS AND METHODS: 32 RF ablations were retrospectively analyzed, 17 laser-guided and 15 procedures using the freehand technique. Subgroup selection of 18 ablations in the hip-pelvic region with a similar degree of difficulty was used for a direct comparison. Data are presented as median (ranges). RESULTS: Comparison of all 32 ablations resulted in fluoroscopy times of 365 s (193-878 s) for freehand and 186 s (75-587 s) for laser-guided procedures (p = 0.004). Corresponding procedure times were 56 min (35-97 min) and 52 min (30-85 min) (p = 0.355). The subgroup showed comparable target sizes, needle path lengths, and number of scans between groups. Fluoroscopy times were lower for laser-guided procedures, 215 s (75-413 s), compared to 384 s (193-878 s) for freehand (p = 0.012). Procedure times were comparable between groups, 51 min (30-72 min) for laser guidance and 58 min (35-79 min) for freehand (p = 0.172). CONCLUSION: Adding laser guidance to CBCT-guided osteoid osteoma RF ablations significantly reduced fluoroscopy time without increasing procedure time. LEVEL OF EVIDENCE: Level 4, case series.

To quantify through environmental audit the radiation dose that urologists receive during surgery in the lithotomy position, and to quantify the dose reduction achieved by altering exposure techniques and personal protective equipment use.Simulated surgery in the lithotomy position using an anthropomorphic phantom as a patient and a SimManIncreasing FSD leads to a rise in surgeon eye dose, and table end lead protection increases the patient skin dose. Use of all the dose-reduction techniques together reduces the dose to the patient, and a surgeon's trunk dose is decreased by 95%, external genitalia dose by 99%, and leg dose by 97%. Sitting to perform fluoroscopically guided surgery in the lithotomy position increases surgeon dose by a median value of 17%, with the external genitalia dose increased by 78% compared with the standing position.This study describes effective methods of dose reduction that are easy to instigate. The resulting reduction in radiation dose during urology procedures meets the requirements of international guidelines and legislation. This change in practice improves patient care and reduces risk to urologists from occupational exposure to radiation. By combining all of the dose-reduction techniques, urologists should never reach the threshold for deterministic radiation effects to their eyes during their career, and they will have a significantly lower chance of stochastic risks such as cancer.

Recently, nanotechnology has provided significant advances in biomedical applications including diagnosis and therapy. In particular, nanoparticles have emerged as valuable outcomes of nanotechnology due to their unique physicochemical properties based on size, shape, and surface properties. Among them, a large amount of research has reported imaging and therapeutic applications using inorganic nanoparticles with special properties. Inorganic nanoparticles developed for imaging and therapy contain metal (Au), metal oxide (Fe3O4, WO3, WO2.9), semiconductor nanocrystal (quantum dots (QDs)), and lanthanide-doped upconversion nanoparticles (UCNPs). Based on their intrinsic properties, they can generate heat, reactive oxygen species (ROS), or energy transfer, so that they can be used for both imaging and therapy. In this review, we introduce biocompatible inorganic nanoparticles for image-guided thermal and photodynamic therapy, and discuss their promising results from in vitro and in vivo studies for biomedical applications.