Magnetic Resonance Imaging Guidance Research Articles

HeaDax: A simple pre-surgical procedure for localizing superficial brain lesions in resource-limited environments

Background: Intracranial convexity lesions are poorly defined by recognizable anatomical landmarks. Even in expert hands, exact localization of small subcortical lesion and its projection to the skull is sometimes unreliable and can cause potential surgical complications. In this report, a simple and handy technique for localizing superficial intracranial lesions on the scalp under computed tomography (CT)-scan guidance is described.Methods: This technique, HeaDax, is based on using extracranial landmarks. We constructed an isosceles square triangle with three pieces of copper electrical wire and placed it on the skin scalp. Then, we took a CT-scan but without the need of the classic head reference planes (e.g., orbitomeatal or along the orbital roof).Results: For the measurements, we need to have the intracranial lesion located on the CT slice with respect to the two landmarks which are the height and hypotenuse of the triangle. The promising preliminary results of HeaDax applied to a phantom skull model encourage us to use it successfully for our first patient presenting a right subcortial supramarginal retrorolandic cavernoma.Conclusion: HeaDax procedure is a good alternative for localizing superficial intracranial lesions on the skin scalp under CT-scan or magnetic resonance imaging guidance. It can be used as a substitute when stereotactic and neuronavigation systems are not easily available, especially in developing countries and in resource-limited environments. HeaDax has a true potential for further developments and applications in cranial surgery.

Magnetic Resonance Imaging-Compatible Optically Powered Miniature Wireless Modular Lorentz Force Actuators.

Minimally invasive medical procedures under magnetic resonance imaging (MRI) guidance have significant clinical promise. However, this potential has not been fully realized yet due to challenges regarding MRI compatibility and miniaturization of active and precise positioning systems inside MRI scanners, i.e., restrictions on ferromagnetic materials and long conductive cables and limited space around the patient for additional instrumentation. Lorentz force‐based electromagnetic actuators can overcome these challenges with the help of very high, axial, and uniform magnetic fields (3–7 Tesla) of the scanners. Here, a miniature, MRI‐compatible, and optically powered wireless Lorentz force actuator module consisting of a solar cell and a coil with a small volume of 2.5 × 2.5 × 3.0 mm3 is proposed. Many of such actuator modules can be used to create various wireless active structures for future interventional MRI applications, such as positioning needles, markers, or other medical tools on the skin of a patient. As proof‐of‐concept prototypes toward such applications, a single actuator module that bends a flexible beam, four modules that rotate around an axis, and six modules that roll as a sphere are demonstrated inside a 7 Tesla preclinical MRI scanner.

Focused Ultrasound-Mediated Blood Brain Barrier Opening is Safe and Feasible in Diffuse Intrinsic Pontine Glioma after Radiation Treatment

Diffuse intrinsic pontine glioma (DIPG), also known as diffuse midline glioma, is a fatal disease in children. Unlike glioblastoma for adults, there are no effective systemic therapies and radiotherapy is the only modality of treatment. With radiation, overall survival improves as compared to supportive care; however, all patients succumb to disease recurrence and ultimately die. The challenge is that the disease is heterogeneous with extensive infiltrative microscopic disease that extends to regions in which the blood brain barrier (BBB) remains relatively intact. Focused ultrasound (FUS) is a novel technology that allows for non-invasive opening of the BBB that is reversible. The question remains whether this can be performed safely in the brainstem after standard radiation. The purpose of this study is to examine the safety and feasibility of BBB-opening with FUS following radiation in a mouse model. A mouse syngeneic DIPG cell line harboring H3.3K27M, PDGF-B (+), and p53 (-/-) was used to factor the potential inflammatory effects of radiation and ultrasound that may contribute to harm. 10,000 cells in 1 μl was injected into the brainstem. At 3 weeks after implantation, magnetic resonance imaging (MRI) T1-post contrast and T2 sequences were obtained to confirm tumor growth. Using the small animal radiation research platform (SARRP), 9 Gy in 3 fractions was delivered to the brainstem. FUS-mediated BBB-opening with microbubbles was performed within 5 day of completion of radiation. Vitals were continuously monitored during FUS. MRI was obtained to confirm BBB-opening. An additional MRI was obtained at 48 hours to show BBB-closure. Mice were observed daily for neurological deficits, including motor dysfunction, seizure, irregular breathing and death. Daily weights were recorded. Kondziela’s inverted screen test was performed before and after FUS to assess for motor strength. Kaplan Meier methods were used to assess survival. Using MRI guidance, radiation to the brainstem was tolerated by mice harboring DIPG. FUS-mediated BBB-opening in the brainstem was feasible and confirmed on MRI. BBB closure was seen by 48-hours after BBB-opening. Compared to radiation alone, FUS did not alter vitals, motor function, weight change, neurological deficit and survival. This is the first study to demonstrate that FUS-guided BBB-opening in the brainstem to target DIPG is safe and feasible after radiation. These results are currently being translated into the clinic to assess the safety and feasibility of FUS in children with DIPG.

Cryoanalgesia of the anterior femoral cutaneous nerve (AFCN) for the treatment of neuropathy-mediated anterior thigh pain: anatomy and technical description.

To describe and illustrate the magnetic resonance imaging (MRI) anatomy of the anterior femoral cutaneous nerve (AFCN) and a new technique for cryoanalgesia of the AFCN for long-term analgesic treatment of recalcitrant AFCN-mediated neuropathic pain. Using a procedural high-resolution MRI technique, we describe the MRI anatomy of the AFCN. Three patients (mean age, 48years; range, 41-67years) with selective nerve block-verified recalcitrant AFCN-mediated anterior thigh pain were enrolled to undergo cryoanalgesia of the AFCN. Procedures were performed under MRI guidance using clinical wide-bore MR imaging systems and commercially available cryoablation system with MR-conditional probes. Outcome variables included technical success, clinical effectiveness including symptom relief measured on an 11-point visual analog scale, frequency of complications, and procedure time. Procedural MRI allowed to successfully demonstrate the course of the AFCN, accurate cryoprobe placement, and monitoring of the ice ball, which resulted in technically successful iceball growth around the AFCN in all cases. All procedures were clinically effective, with median pain intensity decreasing from 8 (7-9) before the procedure to 1 (0-2) after the procedure. The cryoanalgesia effect persisted during a 12-month follow-up period in all three patients. No major complications occurred. The average total procedure time was 98min (range, 85-125min). We describe the MRI anatomy of the AFCN and a new technique for cryoanalgesia of the AFCN using MRI guidance, which permits identification of the AFCN, selective targeting, and iceball monitoring to achieve long-term AFCN-mediated neuropathic pain relief.

Safety Profile of Infinity Deep Brain Stimulation Electrode Placement in a 1.5T Interventional MRI Suite: Consecutive Single-Institution Case Series.

"Asleep" deep brain stimulation using general anesthesia and intraoperative MR imaging guidance is considered "off-label" use by current FDA guidelines but is widely used in neurosurgical practice, and excellent safety has been demonstrated using first-generation, omnidirectional electrodes. Safety data for second-generation, directional electrodes in the interventional MR imaging environment have not yet been published. Herein, we report 34 cases of asleep deep brain stimulation using second-generation, directional electrodes in an interventional MR imaging suite at a single institution. Procedural complications and imaging data are described. All patients underwent postoperative MR imaging with fully implanted ("internalized") electrodes after scalp closure; 4 patients also underwent MR imaging with "externalized" electrodes before scalp closure. No MR imaging-related complications were observed, and procedural complication rates were comparable to prior series. This suggests that the use of second-generation, directional electrodes in the interventional MR imaging environment appears to be safe when following manufacturer-published imaging guidelines.

International survey; current practice in On-line adaptive radiotherapy (ART) delivered using Magnetic Resonance Image (MRI) guidance.

The uptake of new technologies has varied internationally and there have often been barriers to implementation. On-line adaptive radiotherapy (ART) promises to improve patient outcome. This survey focuses on the implementation phase of delivering ART and professional roles and responsibilities currently involved in the workflow and changes which may be expected in the future. A 38 question survey included aspects on current practice; professional responsibilities; benefits and barriers; and decision making and responsibilities. For the purposes of the questionnaire and paper, ART was considered where tumour and /or organs at risk were contoured and re-planning was performed on-line. The questionnaire was electronically distributed via radiotherapy networks. Nineteen international responses were received. Europe (n = 11), United States of America (n = 4); Canada (n = 2), Australia (n = 1) and Hong Kong (n = 1). The majority of centres started using ART in either 2018 (n = 7) or 2019 (n = 6). Four centres started treating with ART between 2015 and 2017, and the first was in 2014. Centres initially treated prostate and oligometastases patients, expanding to treat prostate, oligometastases, pancreas and rectum. The majority of centres were working in conventional roles, however moving towards radiographers taking more responsibility in contouring organs at risk (OAR), target and dosimetry. The three most important criteria chosen by medical doctors to determine if ART should be used were overall gross anatomy changes of target and OAR, target not covered by planning target volume (PTV) and OAR close to the high dose area. There was no clear consensus on the minimum improvement in dose to target or reduction in dose to OAR to warrant adaption. On-line ART has been implemented successfully internationally. Initial practice maintains conventional professional roles and responsibilities, however there is trend to changing roles for the future. There is little consensus regarding the triggers of adaption.

Safety and Oncologic Outcomes of Magnetic Resonance Imaging-Guided Cryoablation of Renal Cell Carcinoma: A 10-Year Single-Center Experience.

Magnetic resonance imaging guidance has been sporadically reported for renal tumor cryoablation (CA); therefore, clinical experience with this modality is still limited.The aim of this study is to retrospectively analyze our 10-year experience with renal tumor CA performed on a 1.5 T magnetic resonance imaging unit with the intent of reporting procedural safety and oncologic outcomes. We included 143 patients (102 men; 41 women; median age, 73 years; range, 34-91 years) with 149 tumors (median size, 2.6 cm; range, 0.6-6.0 cm), treated between 2009 and 2019. Patient, tumor, procedure, and follow-up data were collected and analyzed. The Kaplan-Meier method was used to estimate local recurrence-free (LRFS), metastasis-free (MFS), disease-free (DFS), cancer-specific, and overall (OS) survival. Univariate and multivariate models were used to identify factors associated with complications, LRFS, MFS, DFS, and OS. The overall complication rate was 10.7% (16/149 tumors), with 1 major (1/149 [0.7%]; 95% confidence interval, 0.0%-3.7%) hemorrhagic complication. Other minor complications (15/149 [10.1%]; 95% confidence interval, 0.6%-16.1%) did not include any cases of injury to nearby organs. There were no factors associated with complications.Five-year estimates of LRFS (primary/secondary), MFS, DFS, cancer-specific survival, and OS were 82.8%/91.5%, 91.1%, 75.1%, 98.2%, and 89.6%, respectively. Increasing tumor size (hazard radio [HR], 1.8; P = 0.02) and intraparenchymal tumor location (HR, 5.6; P < 0.01) were associated with lower LRFS; increasing patient's age (HR, 0.5; P = 0.01), high tumor grade (HR, 23.3; P < 0.01) and non-clear-cell/nonpapillary histology (HR, 20.1; P < 0.01) with metastatic disease; and high tumor grade (HR, 3.2; P = 0.04) with lower DFS. Magnetic resonance imaging-guided CA of renal tumors is associated with acceptable morbidity and high survival estimates at 5-year follow-up. Given the absence of complications resulting from injuries to nearby organs, further studies are required to evaluate whether the potential reduced incidence of these adverse events justifies large-scale implementation of this interventional modality.

MR-Conditional Actuations: A Review.

Magnetic resonance imaging (MRI) is one of the most prevailing technologies to enable noninvasive and radiation-free soft tissue imaging. Operating a robotic device under MRI guidance is an active research area that has the potential to provide efficient and precise surgical therapies. MR-conditional actuators that can safely drive these robotic devices without causing safety hazards or adversely affecting the image quality are crucial for the development of MR-guided robotic devices. This paper aims to summarize recent advances in actuation methods for MR-guided robots and each MR-conditional actuator was reviewed based on its working principles, construction materials, the noteworthy features, and corresponding robotic application systems, if any. Primary characteristics, such as torque, force, accuracy, and signal-to-noise ratio (SNR) variation due to the variance of the actuator, are also covered. This paper concludes with a perspective on the current development and future of MR-conditional actuators.

Diagnostic accuracy and safety of percutaneous MRI-guided biopsy of solid renal masses: single-center results after 4.5years.

To retrospectively evaluate diagnostic accuracy and complications of magnetic resonance imaging (MRI)-guided biopsy of radiologically indeterminate solid renal masses (RM). Electronic records of all consecutive patients undergoing MRI-guided biopsy of solid RM (using free-breathing T2-BLADE and BEAT-IRTTT sequences) between April 2014 and October 2018 were reviewed; 101 patients (69 men, 32 women; median age 68years; range 32-76) were included. Patient and RM characteristics, procedural details/complications, pathologic diagnosis, and clinical management were recorded. Diagnostic accuracy was calculated on an intention-to-diagnose basis. Diagnostic yield was also evaluated. Multi-variable analysis was performed for variables with p < .20, including patient age/sex; RM size/location/contact with vascular pedicle, RENAL score, number and total length of biopsy samples, and biopsy tract embolization, to determine factors associated with diagnostic samples, diagnostic accuracy, and complications. Median RM size was 2.4cm (range 1-8.4cm). There were 86 (85%; 95%CI 77-91%) diagnostic and 15 (15%; 95%CI 9-23%) non-diagnostic samples; 6/15 (40%) non-diagnostic biopsies were repeated with 50% malignancy rate. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 96% (95%CI 89-99%), 100% (95%CI 77-100%), 100% (95%CI 95-100%), 82% (95%CI 57-96%), and 97% (95%CI 90-99%), respectively. Primary and secondary diagnostic yields were 85% (95%CI 77-91%) and 91% (95%CI 84-96%), respectively. Seven (7%; 95%CI 1-10%) complications were observed. No tested variables were associated with diagnostic samples, diagnostic accuracy, or complications. MRI-guided biopsy of solid RM is associated with high diagnostic accuracy and low complication rate. The technique might be helpful for inaccessible tumors. • MRI-guided biopsy of radiologically indeterminate solid renal masses (RM) appears safe, with a low rate of minor self-limiting hemorrhagic complications. • Diagnostic accuracy and primary/secondary diagnostic yield are high and appear similar to reported estimates for US- and CT-guided RM biopsy. • MRI guidance may be particularly useful for RM with poor conspicuity on US and CT, for relatively inaccessible tumors (e.g., tumors requiring double-oblique steep-angled approaches), and for young patients or those with renal failure.

Identification of risk factors for poor language outcome in surgical resection of glioma involving the arcuate fasciculus: an observational study.

The arcuate fasciculus is a critical component of the neural substrate of human language function. Surgical resection of glioma adjacent to the arcuate fasciculus likely damages this region. In this study, we evaluated the outcome of surgical resection of glioma adjacent to the arcuate fasciculus under the guidance of magnetic resonance imaging and diffusion tensor imaging, and we aimed to identify the risk factors for postoperative linguistic deficit. In total, 54 patients with primary glioma adjacent to the arcuate fasciculus were included in this observational study. These patients comprised 38 men and 16 women (aged 43 ± 11 years). All patients underwent surgical resenction of glioma under the guidance of magnetic resonance imaging and diffusion tensor imaging. Intraoperative images were updated when necessary for further resection. The gross total resection rate of the 54 patients increased from 38.9% to 70.4% by intraoperative magnetic resonance imaging. Preoperative language function and glioma-to-arcuate fasciculus distance were associated with poor language outcome. Multivariable logistic regression analyses showed that glioma-to-arcuate fasciculus distance was the major independent risk factor for poor outcome. The cutoff point of glioma-to-arcuate fasciculus distance for poor outcome was 3.2 mm. These findings suggest that intraoperative magnetic resonance imaging combined with diffusion tensor imaging of the arcuate fasciculus can help optimize tumor resection and result in the least damage to the arcuate fasciculus. Notably, glioma-to-arcuate fasciculus distance is a key independent risk factor for poor postoperative language outcome. This study was approved by the Ethics Committee of the Chinese PLA General Hospital, China (approval No. S2014-096-01) on October 11, 2014.

Core-Shell-Satellite Nanomaces as Remotely Controlled Self-Fueling Fenton Reagents for Imaging-Guided Triple-Negative Breast Cancer-Specific Therapy.

Triple-negative breast cancer (TNBC) is highly aggressive and insensitive to conventional targeted therapies, resulting in poor therapeutic outcomes. Recent studies have shown that abnormal iron metabolism is observed in TNBC, suggesting an opportunity for TNBC treatment via the iron-dependent Fenton reaction. Nevertheless, the efficiency of current Fenton reagents is largely restricted by the lack of specificity and low intracellular H2 O2 level of cancer cells. Herein, core-shell-satellite nanomaces (Au @ MSN@IONP) are fabricated, as near-infrared (NIR) light-triggered self-fueling Fenton reagents for the amplified Fenton reaction inside TNBC cells. Specifically, the Au nanorod core can convert NIR light energy into heat to induce massive production of intracellular H2 O2 , thereby the surface-decorated iron oxide nanoparticles (IONP) are being fueled for robust Fenton reaction. By exploiting the vulnerability of iron efflux in TNBC cells, such a self-fueling Fenton reaction leads to highly specific anti-TNBC efficacy with minimal cytotoxicity to normal cells. The PI3K/Akt/FoxO axis, intimately involved in the redox regulation and survival of TNBC, is demonstrated to be inhibited after the treatment. Consequently, precise in vivo orthotopic TNBC ablation is achieved under the guidance of IONP-enhanced magnetic resonance imaging. The results demonstrate the proof-of-concept of NIR-light-triggered self-fueling Fenton reagents against TNBC with low ferroportin levels.

A novel three-dimensional template combined with MR-guided 125I brachytherapy for recurrent glioblastoma

BackgroundAt present, the treatment of recurrent glioblastoma is extremely challenging. In this study, we used a novel three-dimensional non-coplanar template (3DNPT) combined with open MR to guide 125I seed implantation for recurrent glioblastoma. The aim of this study was to evaluate the feasibility, accuracy, and effectiveness of this technique.MethodsTwenty-four patients of recurrent glioblastoma underwent 3DNPT with open MR-guided 125I brachytherapy from August 2017 to January 2019. Preoperative treatment plan and 3DNPT were made according to enhanced isovoxel T1-weighted MR images. 125I seeds were implanted using 3DNPT and 1.0-T open MR imaging guidance. Dosimetry verification was performed after brachytherapy based on postoperative CT/MR fusion images. Preoperative and postoperative dosimetry parameters of D90, V100, V200, conformity index (CI), external index (EI) were compared. The objective response rate (ORR) at 6 months and 1-year survival rate were calculated. Median overall survival (OS) measured from the date of brachytherapy was estimated by Kaplan-Meier method.ResultsThere were no significant differences between preoperative and postoperative dosimetry parameters of D90, V100, V200, CI, EI (P > 0.05). The ORR at 6 months was 75.0%. The 1-year survival rate was 58.3%. Median OS was 12.9 months. One case of small amount of epidural hemorrhage occurred during the procedure. There were 3 cases of symptomatic brain edema after brachytherapy treatment, including grade three toxicity in 1 case and grade two toxicity in 2 cases. The three patients were treated with corticosteroid for 2 to 4 weeks. The clinical symptoms related to brain edema were significantly alleviated thereafter.Conclusions3DNPT combined with open MR-guided 125I brachytherapy for circumscribed recurrent glioblastoma is feasible, effective, and with low risk of complications. Postoperative dosimetry matched the preoperative treatment plan. The described method can be used as a novel implantation technique for 125I brachytherapy in the treatment of recurrent gliomas.Trial registrationThe study was approved by the Institutional Review Board of Shandong Provincial Hospital Affiliated to Shandong University (NSFC:NO.2017–058), registered 1st July 2017.

Engineering magnetosomes with chimeric membrane and hyaluronidase for efficient delivery of HIF-1 siRNA into deep hypoxic tumors

Hypoxia-inducible factor-1 (HIF-1) plays a critical role in tumor development and chemotherapy resistance, and suppression of HIF-1 has emerged as a captivating antitumor approach. To efficiently silence HIF-1 in deep hypoxic tumors, we herein developed a versatile small interfering RNA delivery system that could overcome multiple physiological barriers. The system is comprised of an Fe3O4 magnetic nanocluster as the core, pre-engineered chimeric membrane for the cloak, and decorated hyaluronidase on the surface, which succeeded in prolonged circulation time, magnetic resonance imaging guidance, magnetic tumor accumulation, hypoxic site penetration, homotypic tumor targeting, and cytoplasmic trafficking. Such versatile and programmed delivery performance enabled the engineered magnetosomes to achieve the remarkable silencing of HIF-1, potent therapeutic effect and chemoresistance amelioration with few abnormalities, showing a promising modality for anticancer therapy.

Asleep Deep Brain Stimulation of the Nucleus Ventralis Intermedius for Essential Tremor Using Indirect Targeting and Interventional Magnetic Resonance Imaging: Single-Institution Case Series.

Literature on asleep deep brain stimulation (DBS) of the ventralis intermedius (Vim) nucleus in essential tremor is relatively sparse. Furthermore, controversy exists as to whether indirect ("consensus" or "atlas-based") targeting of the Vim requires physiologic adjustment for effective clinical outcomes in DBS surgery. The objective of this study was to evaluate the clinical results of asleep Vim DBS using indirect coordinates and real-time interventional magnetic resonance imaging guidance. Retrospective review of a prospectively collected database was performed to identify patients with essential tremor undergoing asleep Vim DBS using interventional magnetic resonance imaging guidance. Stereotactic and clinical outcomes were abstracted and analyzed using descriptive statistics. A total of 12 consecutive patients were identified, all of whom were available for 6-month clinical follow-up. Stereotactic (radial) error was 0.5 ± 0.2 mm on the left and 0.5 ± 0.3 mm on the right. Fahn-Tolosa-Marin tremor scores in the treated limb(s) decreased by 71.2% ± 31.0% (P = 0.0088), The Essential Tremor Rating Assessment Scale activities of daily living improved by 74.9% ± 23.7% (P < 0.0001), and The Essential Tremor Rating Assessment Scale performance improved by 64.3 ± 16.2% (P = 0.0004). Surgical complications were mild and generally transient. Stimulation-related side effects were similar to those reported in historical series of awake Vim DBS. Asleep Vim DBS using indirect targeting and interventional magnetic resonance imaging-guided placement is safe and effective, with 6-month clinical results similar to those achieved with awake placement. These data support the use of asleep surgery in essential tremor and represent a baseline for comparison with future studies using more advanced targeting techniques.

MRI-guided percutaneous sclerotherapy of venous malformations: initial clinical experience using a 3T MRI system

PurposeVenous malformations (VMs) are low-flow vascular anomalies that are commonly treated with image-guided percutaneous sclerotherapy. Although many VMs can be safely accessed and treated using ultrasonography and fluoroscopy, some lesions may be better treated with magnetic resonance imaging (MRI)–guided sclerotherapy. The aim of this study is to evaluate the feasibility, efficiency, and outcomes of MRI-guided sclerotherapy of VMs using a 3T MRI system. MethodsSix patients with VMs in the neck (n = 2), chest (n = 1), and extremities (n = 3) underwent sclerotherapy with 3T MRI guidance. Feasibility was assessed by calculating the technical success rate and procedural efficiency. Efficiency was evaluated by using planning, targeting, intervention, and total procedure times. Outcomes were assessed by measuring VM volumes before and after sclerotherapy, patient-reported pain scores, and occurrence of complications. ResultsTechnical success was achieved in all 6 procedures. There was a non-significant 30% decrease in mean VM volume after the procedure (P = .350). The procedure resulted in a decrease in mean pain score (on an 11-point scale) of 2.6 points (P = .003). After the procedure, 4 patients reported complete pain resolution, 1 reported partial pain resolution, and 1 reported no change in pain. Procedural efficiency was consistent with similar sclerotherapy procedures performed at our institution. There were no major or minor complications. Conclusion3T MRI guidance is feasible for percutaneous sclerotherapy of VMs, with promising initial technical success rates, procedural efficiency, and therapeutic outcomes without complications.

Tumor-Specific Endogenous FeII-Activated, MRI-Guided Self-Targeting Gadolinium-Coordinated Theranostic Nanoplatforms for Amplification of ROS and Enhanced Chemodynamic Chemotherapy.

Low drug payload and lack of tumor-targeting for chemodynamic therapy (CDT) result in an insufficient reactive oxygen species (ROS) generation, which seriously hinders its further clinical application. Therefore, how to improve the drug payload and tumor targeting for amplification of ROS and combine it with chemotherapy has been a huge challenge in CDT. Herein, methotrexate (MTX), gadolinium (Gd), and artesunate (ASA) were used as theranostic building blocks to be coordinately assembled into tumor-specific endogenous FeII-activated and magnetic resonance imaging (MRI)-guided self-targeting carrier-free nanoplatforms (NPs) for amplification of ROS and enhanced chemodynamic chemotherapy. The obtained ASA-MTX-GdIII NPs exhibited extremely high drug payload (∼96 wt %), excellent physiological stability, long circulating ability (half-time: ∼12 h), and outstanding tumor accumulation. Moreover, ASA-MTX-GdIII NPs could be specifically uptaken by tumor cells via folate (FA) receptors and subsequently be disassembled via lysosomal acidity-induced coordination breakage, resulting in drug burst release. Most strikingly, the produced ASA could be catalyzed by tumor-specific overexpressed endogenous FeII ions to generate sufficient ROS for enhancing the main chemodynamic efficacy, which could exert a synergistic effect with the assistant chemotherapy of MTX. Interestingly, ASA-MTX-GdIII NPs caused a lower ROS generation and toxicity on normal cell lines that seldom expressed endogenous FeII ions. Under MRI guidance with assistance of self-targeting, significantly superior synergistic tumor therapy was performed on FA receptor-overexpressed tumor-bearing mice with a higher ROS generation and an almost complete elimination of tumor. This work highlights ASA-MTX-GdIII NPs as an efficient chemodynamic-chemotherapeutic agent for MRI imaging and tumor theranostics.

Sonoselective transfection of cerebral vasculature without blood–brain barrier disruption

Treatment of many pathologies of the brain could be improved markedly by the development of noninvasive therapeutic approaches that elicit robust, endothelial cell-selective gene expression in specific brain regions that are targeted under MR image guidance. While focused ultrasound (FUS) in conjunction with gas-filled microbubbles (MBs) has emerged as a noninvasive modality for MR image-guided gene delivery to the brain, it has been used exclusively to transiently disrupt the blood-brain barrier (BBB), which may induce a sterile inflammation response. Here, we introduce an MR image-guided FUS method that elicits endothelial-selective transfection of the cerebral vasculature (i.e., "sonoselective" transfection), without opening the BBB. We first determined that activating circulating, cationic plasmid-bearing MBs with pulsed low-pressure (0.1 MPa) 1.1-MHz FUS facilitates sonoselective gene delivery to the endothelium without MRI-detectable disruption of the BBB. The degree of endothelial selectivity varied inversely with the FUS pressure, with higher pressures (i.e., 0.3-MPa and 0.4-MPa FUS) consistently inducing BBB opening and extravascular transfection. Bulk RNA sequencing analyses revealed that the sonoselective low-pressure regimen does not up-regulate inflammatory or immune responses. Single-cell RNA sequencing indicated that the transcriptome of sonoselectively transfected brain endothelium was unaffected by the treatment. The approach developed here permits targeted gene delivery to blood vessels and could be used to promote angiogenesis, release endothelial cell-secreted factors to stimulate nerve regrowth, or recruit neural stem cells.

Real-time 3T MRI-guided cardiovascular catheterization in a porcine model using a glass-fiber epoxy-based guidewire.

PurposeReal-time magnetic resonance imaging (MRI) is a promising alternative to X-ray fluoroscopy for guiding cardiovascular catheterization procedures. Major challenges, however, include the lack of guidewires that are compatible with the MRI environment, not susceptible to radiofrequency-induced heating, and reliably visualized. Preclinical evaluation of new guidewire designs has been conducted at 1.5T. Here we further evaluate the safety (device heating), device visualization, and procedural feasibility of 3T MRI-guided cardiovascular catheterization using a novel MRI-visible glass-fiber epoxy-based guidewire in phantoms and porcine models.MethodsTo evaluate device safety, guidewire tip heating (GTH) was measured in phantom experiments with different combinations of catheters and guidewires. In vivo cardiovascular catheterization procedures were performed in both healthy (N = 5) and infarcted (N = 5) porcine models under real-time 3T MRI guidance using a glass-fiber epoxy-based guidewire. The times for each procedural step were recorded separately. Guidewire visualization was assessed by measuring the dimensions of the guidewire-induced signal void and contrast-to-noise ratio (CNR) between the guidewire tip signal void and the blood signal in real-time gradient-echo MRI (specific absorption rate [SAR] = 0.04 W/kg).ResultsIn the phantom experiments, GTH did not exceed 0.35°C when using the real-time gradient-echo sequence (SAR = 0.04 W/kg), demonstrating the safety of the glass-fiber epoxy-based guidewire at 3T. The catheter was successfully placed in the left ventricle (LV) under real-time MRI for all five healthy subjects and three out of five infarcted subjects. Signal void dimensions and CNR values showed consistent visualization of the glass-fiber epoxy-based guidewire in real-time MRI. The average time (minutes:seconds) for the catheterization procedure in all subjects was 4:32, although the procedure time varied depending on the subject’s specific anatomy (standard deviation = 4:41).ConclusionsReal-time 3T MRI-guided cardiovascular catheterization using a new MRI-visible glass-fiber epoxy-based guidewire is feasible in terms of visualization and guidewire navigation, and safe in terms of radiofrequency-induced guidewire tip heating.

Abstract No. 468 Cost analysis of focal laser ablation for prostate cancer: in magnetic resonance imaging versus transrectal ultrasound fusion guidance outside magnetic resonance imaging

Abstract No. 468 Cost analysis of focal laser ablation for prostate cancer: in magnetic resonance imaging versus transrectal ultrasound fusion guidance outside magnetic resonance imaging

FeS@BSA Nanoclusters to Enable H2S-Amplified ROS-Based Therapy with MRI Guidance.

Therapeutic systems to induce reactive oxygen species (ROS) have received tremendous success in the research of tumor theranostics, but suffered daunting challenges in limited efficacy originating from low presence of reactants and reaction kinetics within cancer cells. Here, ferrous sulfide‐embedded bovine serum albumin (FeS@BSA) nanoclusters, in an amorphous nature, are designed and synthesized via a self‐assembly approach. In acidic conditions, the nanoclusters degrade and simultaneously release H2S gas and Fe2+ ions. The in vitro study using Huh7 cancer cells reveals that Fe2+ released from FeS@BSA nanoclusters induces the toxic hydroxyl radical (·OH) effectively via the Fenton reaction. More interestingly, H2S gas released intracellularly presents the specific suppression effect to catalase activity of cancer cells, resulting in the promoted presence of H2O2 that facilitates the Fenton reaction of Fe2+ and consequently promotes ROS induction within the cells remarkably. After intravenous administration, the nanoclusters accumulate in the tumors of mice via the enhanced permeability and retention effect and present strong magnetic resonance imaging (MRI) signals. The findings confirm this therapeutic system can enable superior anti‐tumor performance with MRI guidance and negligible side effects. This study, therefore, offers an alternative gas‐amplified ROS‐based therapeutic platform for synergetic tumor treatment.