Multimodal Imaging Guidance Research Articles

Biocompatible nanomicelles for sensitive detection and photodynamic therapy of early-stage cancer.

The lack of sensitive detection techniques and agents for early-stage tumors, which are characterized by small size, juvenile blood vessels and scarce secreted markers, has hampered timely cancer therapy and human well-being. Herein, the natural product pyropheophorbide-a (PPa) and FDA-approved Pluronic F127 are organized to develop F127-PPa nanomicelles with favorable size, red-shifted fluorescence and decent biocompatibility. After intravenous (i.v.) injection, the F127-PPa nanomicelles could not only accurately identify early-stage xenografted tumors, but also sensitively detect cancer metastasis in lungs through near-infrared (NIR) fluorescence imaging. The fluorescence signals are consistent with radionuclide imaging, photoacoustic (PA) imaging and bioluminescence imaging of tumors, consolidating the reliability of using F127-PPa nanomicelles for sensitive cancer diagnosis in a non-invasive and low-cost manner. Moreover, the fluorescence intensity of small tumors is linearly correlated with the tumoral mass ranging from 10 to 120 mg with a fluorescence coefficient of 4.5 × 107 mg-1. Under the guidance of multimodal imaging, the tumors could be thoroughly eradicated by F127-PPa under laser irradiation due to efficient reactive oxygen species (ROS) generation. These findings may provide clinically translatable agents and strategies for sensitive diagnosis of early-stage tumors and timely cancer therapy.

A versatile nanoagent for multimodal imaging-guided photothermal and anti-inflammatory combination cancer therapy.

Photothermal therapy (PTT) has drawn great attention in cancer treatment because of its minimal invasiveness and high spatiotemporal selectivity, but it still encounters severe obstacles like heat-resistance, metastasis and recurrence. A key reason for the treatment failure is the highly inflammatory tumor microenvironment caused by hyperthermia. A simultaneous anti-inflammatory therapy alongside the PTT has great potential for overcoming the drawbacks of PTT; however, it has been less reported and further study is urgently needed. In addition, as many inorganic photothermal agents have no inherent imaging capability, diagnostic strategies should be introduced to help identify cancerous lesions and find the best treatment time period for PTT. Herein, we developed a versatile theranostic nanoagent (named T-lipos-CPAuNCs) for synergistic multimodal imaging-guided photothermal/anti-inflammatory cancer therapy. Perfluorohexane (PFH) loaded AuNCs and the anti-inflammatory drug celecoxib were encapsulated into the tumor-targeting cyclic Arg-Gly-Asp (cRGD) peptide modified liposomes to form T-lipos-CPAuNCs. The T-lipos-CPAuNCs accumulated in the tumor tissue and selectively targeted the cancer cells, and converted photo to thermal energy under near-infrared (NIR) laser irradiation to kill the cancer cells by PTT. The high temperature further accelerated the release of celecoxib to exert an anti-inflammatory effect, while on the other hand led to liquid to gas phase transition of PFH to facilitate ultrasound (US) imaging. The T-lipos-CPAuNCs also exhibited photoacoustic (PA) imaging capability. In vitro and in vivo experiments established that under the guidance of multimodal imaging, T-lipos-CPAuNCs significantly suppressed the tumor growth by PTT and prevented tumor metastasis with non-apparent tumor inflammation. The developed theranostic nanosystem (T-lipos-CPAuNCs) shows great potential for PA/US multimodal imaging guided photothermal/anti-inflammatory combination cancer therapy.

Multifunctional nanozyme for multimodal imaging-guided enhanced sonodynamic therapy by regulating the tumor microenvironment.

Sonodynamic therapy (SDT) is a highly promising approach for cancer therapy, but its efficacy is severely hampered by the low specificity of sonosensitizers and the unfavorable characteristics of the tumor microenvironment (TME), such as hypoxia and glutathione (GSH) overexpression. To solve these problems, in this work, we encapsulated IR780 and MnO2 in PLGA and linked Angiopep-2 (Ang) to synthesize a multifunctional nanozyme (Ang-IR780-MnO2-PLGA, AIMP) to enhance SDT. With Ang functionalization to facilitate blood-brain barrier (BBB) penetration and glioma targeting, and through the function of IR780, these nanoparticles (NPs) showed improved targeting of cancer cells, especially mitochondria, and spread deep into tumor centers. Upon low-intensity focused ultrasound (LIFU) irradiation, reactive oxygen species (ROS) were produced and induced tumor cell apoptosis. Combined with the specific mitochondria-targeting ability of IR780, the sonodynamic effects were amplified because mitochondria are sensitive to ROS. In addition, MnO2 exhibited enzyme-like activity, reacting with the high levels of hydrogen protons (H+), H2O2 and GSH in the TME to continuously produce oxygen and consume GSH, which further enhanced the effect of SDT. Moreover, Mn2+ can be released in response to TME stimulation and used as a magnetic resonance (MR) contrast agent. In addition, IR780 has photoacoustic (PA)/fluorescence (FL) imaging capabilities. Our results demonstrated that AIMP NPs subjected to LIFU triggering maximally enhanced the therapeutic effect of SDT by multiple mechanisms, including multiple targeting, deep penetration, oxygen supply in situ and GSH depletion, thereby significantly inhibiting tumor growth and distal metastasis without systemic toxicity. In summary, this multifunctional nanozyme provides a promising strategy for cancer diagnosis and treatment under the intelligent guidance of multimodal imaging (PA/FL/MR) and may be a safe clinical translational method.

On-demand drug release nanoplatform based on fluorinated aza-BODIPY for imaging-guided chemo-phototherapy

Intelligent drug delivery systems (DDS), integrating with multi-modal imaging guidance and controlled drug release, have practical significance in enhancing the therapeutic efficiency of tumors. Herein, fluorinated aza-boron-dipyrromethene (NBF) with high near-infrared absorption is synthesized by introducing nonadecafluorodecanoic acid into aza-BODIPY via the amide bond. Through the co-precipitation methods, nanoparticles (NPs) based on NBF are fabricated and the obtained NBF NPs can not only load with DOX with a high loading efficiency (25%, DNBF NPs), but also absorb PFC droplets (1H-perfluoropentane) with bp of 42 °C because of the fluorinated chains inside NBF NPs (PDNBF NPs). Under 808-nm laser irradiation, the hyperthermia effect of NBF could induce the liquid-gas phase transition of PFC droplets, triggering the burst release of DOX and enhancing echo signals for ultrasound imaging as well. With efficient enrichment of PDNBF NPs at tumor site as revealed by in vivo ultrasound imaging and photoacoustic imaging, significant improvement in inhibiting tumor growth is achieved with PDNBF NPs under laser irradiation without noticeable side effects. The work presents a multifunctional organic DDS with great biocompatibility, high drug loading efficiency and light-stimuli-responsive drug release, which provides a new strategy for the manufacture of intelligent composite theranostic nanoplatform.

Inhibited Metastasis and Amplified Chemotherapeutic Effects by Epigene-Transfection Based on a Tumor-Targeting Nanoparticle.

PurposeTumor metastasis and drug resistance have always been vital aspects to cancer mortality and prognosis. To compromise metastasis and drug resistance, a nanoparticle IPPD-PHF2 (IR780/PLGA-PEI(Dox)-PHF2) has been engineered to accomplish efficient targeted epigenotherapy forced by PHF2-induced MET (mesenchymal to epithelial transition).Materials and MethodsIPPD-PHF2 nanoparticle was synthesized and characterized by several analytical techniques. The transfection efficiency of IPP-PHF2 (IR780/PLGA-PEI-PHF2) was compared with PP-PHF2 (PLGA-PEI-PHF2) in vitro by WB and in vivo by IHC, and the cytotoxicity of IPP was compared with Lipo2000 in vitro by CCK8 assay. The inhibition of cancer cell migration caused by PHF2-upregulation was tested by wound healing assay, and the enhanced chemotherapeutic sensitivity was detected by flow cytometry. Tumor-targeting property of IPPD-PHF2 was proved by fluorescent imaging in vivo with MDA-MB-231 tumor-bearing nude mice. Except for fluorescent imaging ability, considerable photoacoustic signals of IPPD-PHF2 at tumor sites were verified. The anti-tumor activity of IPPD-PHF2 was investigated using in vivo human breast cancer MDA-MB-231 cell models.ResultsTumor-targeting nanoparticle IPPD-PHF2 had an average size of about 319.2 nm, a stable zeta potential at about 38 mV. The encapsulation efficiency of doxorubicin was around 39.28%, and the adsorption capacity of plasmids was about 64.804 μg/mg. Significant up-regulation of PHF2 induced MET and caused reduced migration as well as enhanced chemotherapeutic sensitivity. Either IPPD (IR780/PLGA-PEI(Dox)) or IPP-PHF2 (IR780/PLGA-PEI-PHF2) presented minor therapeutic effects, whereas IPPD-PHF2 specifically accumulated within tumors, showed extraordinary transfection efficiency specifically in tumor sites, acted as inhibitors of metastasis and proliferation, and presented good multimodality imaging potentials in vivo.ConclusionIPPD-PHF2 NPs is a promising tool to bring epigenotherapy into a more practical era, and the potential application of harm-free multimodality imaging guidance is of great value.

Application of Robot-Assisted Frameless Stereoelectroencephalography Based on Multimodal Image Guidance in Pediatric Refractory Epilepsy: Experience of a Pediatric Center in a Developing Country

To introduce the application of robot-assisted frameless stereoelectroencephalography (SEEG) based on multimodal image fusion technology in pediatric refractory epilepsy in a pediatric center from a developing country. We retrospectively evaluated pediatric patients with drug-resistant epilepsy who underwent SEEG monitoring at the Children's Hospital of Fudan University from July 2014 to August 2017. Application of multimodal image fusion technology in SEEG was described in detail. Seizure outcomes were assessed according to the International League Against Epilepsy classification. A total of 208 patients were initially eligible and underwent a rigorous phase I evaluation. SEEG explorations were performed in 20 patients who entered phase II assessment (11 male and 9 female patients) with a median age of 7.99 ± 4.07 years. In total, 181 electrodes were implanted (9 per implantation), among which 16 implantations were unilateral (6 left and 10 right) and 4 were bilateral. The mean operating time was 3 hours and no obvious hemorrhage occurred. Electrode displacement and pneumocephalus were observed in 1 and 2 patients, respectively. Thirteen and 7 patients underwent tailored resection and radiofrequency thermocoagulation, respectively. Among resection cases, focal cortical dysplasia was the predominant pathologic type. The overall seizure outcome after a mean follow-up of 2.65 years was International League Against Epilepsy class 1 in 13, class 2 in 2, class 3 in 3, class 4 in 1, and class 5 in 1 patient, respectively. The combination of multimodal image fusion and frameless robot-assisted SEEG is demonstrated to be safe and effective on children with refractory epilepsy in developing countries.

Cytokine-induced killer cells-assisted tumor-targeting delivery of Her-2 monoclonal antibody-conjugated gold nanostars with NIR photosensitizer for enhanced therapy of cancer

Maximizing the accumulation of anticancer medicine in the tumor is the priority to achieve minimal invasive cancer therapy, which raises high demands on tumor-targeting ability of drug delivery systems. Herein, we adopted an emerging "cell-drug" strategy via the nanoplatform construction to achieve high aggregation and intratumoral distribution. We fabricated gold nanostars (GNSs) with HER-2 monoclonal antibody (trastuzumab) and near-infrared region (NIR) photosensitizer indocyanine green (ICG) to obtain GNS@ICG-Ab, which combined the photothermal therapy with photodynamic therapy (PTT/PDT) that rely on enhanced photothermal conversion efficiency of GNS and 1O2 generator ICG under the exposure of a NIR laser. Tumor-tropism CIK cells loaded with GNS@ICG-Ab were able to migrate into tumors and make a difference in efficient accumulation and uniform distribution of the GNS@ICG-Ab-CIK nanoplatform inside tumors based on fluorescence, photoacoustic (PA), and computed tomography (CT) imaging observations. Encouraged by the improvements in tumor targeting and retention presented by real-time imaging, we employed the novel nanoplatform to synergistically inhibit the progression of tumors in SK-BR-3 tumor-bearing mice via PTT/PDT and immunotherapy-implemented by CIK cells for activating the immune response, and with the specific linkage between trastuzumab and SK-BR-3 tumor cells, our platform could exert a precise strike of PDT/PTT. Taken together, the integrating tri-modal imaging with tri-modal therapy endows CIK-GNS@ICG-Ab with promising potential in cancer theranostics and lays a solid foundation for the development of immune cell application in nanomedicine delivery.

Reverse Microemulsion Synthesis of Fe3O4-Ag2S Heteronanocrystals for Dual-Modal Imaging-Guided Photothermal Tumor Ablation.

Heterojunction nanomaterials have revealed a significant possibility in tumor diagnosis and therapeutic owing to tightly combining two parts of different chemical properties. Herein, we successfully synthesized heterogenous Fe3O4-Ag2S nanocrystals through a reverse microemulsion. Based on the prepared heterostructure, a new drug nanoplatform was developed, which served as a contrast agent for T2-weighted magnetic resonance imaging, computed tomography imaging, and photothermal imaging. In addition, these Fe3O4-Ag2S heteronanocrystals exhibited a high photothermal conversion efficiency of 75.5% irradiated by a laser of 808 nm wavelength. After injection into glioma cancer mode in vivo, efficient tumor accumulation of Fe3O4-Ag2S heteronanocrystals was observed under triple-modal imaging. The prepared heteronanocrystals further showed an excellent ablated tumor destruction effect through the generated hyperthermia with the irradiation of an 808 nm laser. Our work suggests that the potential of Fe3O4-Ag2S heteronanocrystals may be a promising theranostic agent for multimodal imaging guidance and photothermal therapy toward cancer.

IBS20.02 Airway Stenosis

Tracheal stenosis is suspected in individuals with risk factors presenting with signs and symptoms of airway narrowing. The condition may be suspected based on spirometry with a flow-volume loop and CT imaging of the neck and chest but fiberoptic bronchoscopy is required to confirm the presence and severity of tracheal stenosis. The symptoms of tracheal stenosis are similar to those of other conditions so it is important to carefully evaluate patients history. The symptoms of tracheal stenosis typically are wheezing, coughing or shortness of breath, cornage, upper respiratory infections, asthma that doesn’t respond to treatment. Benign tracheal stenoses are more commonly the result of an injury to the trachea due to prolonged intubation or tracheostomy but also Infections (tuberculosis), autoimmune disorders such as Granulomatosis with polyangiitisand amyloidosis or radiation therapy to the neck or chest. The morphological classification of airway stenosis includes granulomas, pseudoglottic stenosis, and “true stenosis” divided into web-like and complex stenoses. Web-like stenoses are circumferential strictures of the trachea involving the mucosa of a short segment (maximum 1 cm long)without any damage to the cartilages. Complex stenosesare sleeve strictures of the trachea more than 1 cm long, often associated with various degrees of cartilage involvement, malacia and inflammation. Several treatment options that can be used for tracheal stenosis depending on the cause, location and severity of the tracheal narrowing. Resection and anastomosis of the involved tract of the trachea is the gold standard treatment. Interventional Pulmonology (IP) offers minimally invasive techniques. Some IP treatment options can provide immediate relief but are considered temporary solutions, while others can provide a better long-term solution. Short-term treatment options for the condition include laser surgery and mechanical dilation with rigid scopes.Treatment options that are generally considered to work long term include stenting and tracheal reconstruction when only a short portion of the trachea is involved. Choice of procedure depends on the exact location and extent of the stenosis, but also on patient age and comorbidities.The most common treatment options for tracheal stenosis include: In 2007 Cavaliere et al. published the results of Laser Assisted Mechanical Dilation in 113 post-intubation tracheal stenosesTab 1Patient carachterstics Therapeutic bronchoscopies were performed using rigid bronchoscopes (Efer, Dumon-Harrel type; FR) and general anesthesia.Endoscopic treatment was based on the use of three main techniques: laser photo-resection (multiple radial incisions), gentle dilation and removable silicon stents.SexAge(Y)Cause of stenosisType of stenosisM 4750±21 (12-84)Intubation 38Tracheotomy 35Web-like 13Complex 60 Open table in a new tab View Large Image Figure ViewerDownload Hi-res image Download (PPT) Most web-like stenoses were successfully treated with Laser Assisted Mechanical Dilation (LAMD) alone; among complex stenoses LAMD was sufficient to treat 13 patients (22%), whereas 47 patients (78%) required stent placement: 22 had their stent removed after one year and did not require any further therapy, 13 inoperable patients required permanent stent and 12 were referred to surgery after failure of multiple endoscopic treatments. No permanent complications secondary to endoscopic treatment were observed. Forty-eight patients (66%) obtained a stable, good result with the endoscopic procedure, 13 (18%) required a permanent stent while 12 patients (16%) were referred to surgery. These authors indicate that bronchoscopic treatment of post-intubation tracheal stenoses can be considered a safe first-line therapy, leaving some selected cases and the relapsing stenosis for surgical resection. 1.Shapshay SM, Beamis JF, Jr, Hybels RL, Bohigian RK. Endoscopic treatment of subglottic and tracheal stenosis by radial laser incision and dilation. Ann Otol Rhinol Laryngol. 1987;96:661–664. 2. Bacon JL, Patterson CM, Madden BP. Indications and interventional options for non-resectable tracheal stenosis. J Thorac Dis. 2014;6:258–70. 3. Galluccio G, Lucantoni G, Battistoni P, Paone G, Batzella S, Lucifora V et al. Interventional endoscopy in the management of benign tracheal stenoses: definitive treatment at long-term follow-up. Eur J Cardiothorac Surg. 2009;35:429–33. 4. Murgu SD, Colt HG, Mukai D, Brenner M. Multimodal imaging guidance for laser ablation in tracheal stenosis. Laryngoscope. 2010;120:1840–6. 5. Cavaliere S, Bezzi M, Toninelli C, Foccoli P Management of post-intubation tracheal stenoses using the endoscopic approach. Follow-up of 73consecutive patients over a four-year period. Monaldi arch Chest Dis 2007 Jun; 67(2):73-80

Challenging the osseous component of sphenoorbital meningiomas

BackgroundIntraosseous growth is a unique feature of sphenoorbital meningiomas (SOM). Its close relation to neurovascular structures limits complete surgical resection and possibly contributes to the high recurrence rate.ObjectiveTo evaluate the growth behavior of intraosseous remnants and develop a protocol for precise intraoperative visualization of intraosseous SOM.MethodsWe included 31 patients operated for SOM from 2004 to 2017. The growth velocity of the intraosseous tumor component was volumetrically calculated in 20 cases. To improve accuracy of image guidance, we implemented a specialized bone surface-based registration algorithm. For intraoperative bone visualization, we included CT in multimodality continuous image guidance in 23 patients. The extent of resection (EOR) was compared with a standard MR-only navigation group (n = 8).ResultsIn 11/20 cases (55%), a progressive regrowth of the intraosseous SOM remnant was noted during a mean follow-up of 52 months (range 20–132 months). We observed a mean increase of 6.2 cm3 (range 0.2–23.7 cm3) per patient and side during the follow-up period. Bone surface-based registration was significantly more accurate than skin surface-based registration (mean 0.7 ± 0.4 mm and 1.9 ± 0.7 mm, p < 0.001). The EOR of the intraosseous component was significantly higher using CT + MRI navigation compared with controls (96% vs. 81%, p = 0.044).ConclusionQuantitative assessment of the biological behavior of intraosseous remnants revealed a continuous slow growth rate independent of the soft tumor component of more than half of SOM. According to our data, application of a multimodal image guidance provided high accuracy and significantly increased the resection rate of the intraosseous component of SOM.

Towards a novel small animal proton irradiation platform: the SIRMIO project

Background: Precision small animal radiotherapy research is a young emerging field aiming to provide new experimental insights into tumor and normal tissue models in different microenvironments, to unravel complex mechanisms of radiation damage in target and non-target tissues and assess efficacy of novel therapeutic strategies. For photon therapy, modern small animal radiotherapy research platforms have been developed over the last years and are meanwhile commercially available. Conversely, for proton therapy, which holds potential for an even superior outcome than photon therapy, no commercial system exists yet.Material and methods: The project SIRMIO (Small Animal Proton Irradiator for Research in Molecular Image-guided Radiation-Oncology) aims at realizing and demonstrating an innovative portable prototype system for precision image-guided small animal proton irradiation, suitable for installation at existing clinical treatment facilities. The proposed design combines precise dose application with in situ multi-modal anatomical image guidance and in vivo verification of the actual treatment delivery.Results and conclusions: This manuscript describes the status of the different components under development, featuring a dedicated beamline for degradation and focusing of clinical proton beams, along with novel detector systems for in situimaging and range verification. The foreseen workflow includes pre-treatment proton transmission imaging, complemented by ultrasonic tumor localization, for treatment planning and position verification, followed by image-guided delivery with on site range verification by means of ionoacoustics (for pulsed beams) and positron-emission-tomography (PET, for continuous beams). The proposed compact and cost-effective system promises to open a new era in small animal proton therapy research, contributing to the basic understanding of in vivo radiation action to identify areas of potential breakthroughs for future translation into innovative clinical strategies.

Awake Transcortical Approach Resection of Dominant Posterior Cingulate Gyrus Glioma: 2-Dimensional Operative Video.

Two techniques, the translongitudinal cerebral fissure and transfrontal cortical approach, can be employed to resect posterior cingulate gyrus tumors. We demonstrate the transcortical technique comprising of multimodal imaging guidance and awake brain mapping which enabled maximum safe resection of dominant cingulate gyrus glioma. The patient, a 49-yr-old female, came to clinic after experiencing headache for a month. Initial magnetic resonance imaging (MRI) scans revealed a nonenhancing lesion of the left posterior cingulate gyrus. Three-dimensional magnetic resonance spectroscopy was used to analyze the choline/N-acetyl-aspartate index (CNI) which strongly suggested a low-grade glioma diagnosis. In surgery, after creating a tailed bone window and dural opening, strip electrode was placed across the central sulcus for continuous motor evoked potential monitoring. Next, direct cortical stimulation was done to map functional cortical areas. The transcortical approach was chosen at this point because many veins hindered hemisphere retraction. Noneloquent cortical incisions were made and the tumor was carefully debunked with a cavitron ultrasonic surgical aspirator. The corpus callosum marked the deep end of dissection. Subcortical mapping combined with diffusion tensor imaging tractography-based navigation was performed to localize motor and language tracks. Intraoperative MRI evaluation confirmed a gross total resection. Pathological and molecular analysis revealed a World Health Organization Grade II IDH-wildtype Diffuse Astrocytoma diagnosis. Since the patient falls in high-risk group, she was also administered radiation and chemotherapy. Long-term cognitive evaluation follow-up of the patient showed she had good functional recovery with no obvious long-term deficits. Informed patient consent was obtained.

Multimodality imaging guidance for percutaneous paravalvular leak closure: Insights from the multicenter FFPP register

Percutaneous paravalvular leakages (PVL) closure has emerged as a palliative alternative to surgical management in selected high-risk patients. Percutaneous procedures are challenging especially for mitral PVL. An accurate imaging of the morphologies of the defects is mandatory together with a precise guiding in the catheterization laboratory to enhance success rate. We aimed to describe imaging modalities used in clinical practice to guide percutaneous PVL closure and assess the potential interest of new imaging tools. Data from the FFPP (“Fermeture de Fuite paraprothétique”) register were used. The FFPP register is an international multi-institutional collaborative register started in 2017. A descriptive analysis of multimodality imaging used to guide PVL closure in clinical practice was performed. Data from 173 procedures performed in 19 centers from 3 countries (France, Belgium, Poland) were collected and included 8 cases of PVL following transcatheter valve replacement. Transesophageal echocardiography was used in 167 cases (96.5%) including 87.4% of cases with use of 3D-echocardiography. In one case 3D- echocardiography was combined and fused in real time with fluoroscopy images using echonavigator software. From a sample of 31 patients, details about multimodality imaging were available. Cardiac tomodensitometry (CT) was done before 10 procedures. In one case, fusion between pre-procedural cardiac CT angiography data and fluoroscopy data was used. In 2 cases, printing of a 3D model of the valve with PVL was done ( Fig. 1 ). Echocardiography and in particular the 3D mode, is the cornerstone of paravalvular leakages imaging. Other imaging modalities such as cardiac computed tomography and cardiac magnetic resonance imaging may be of complementary interest. New techniques such as imaging fusion and printing may further facilitate the percutaneous approach of paravalvular leakages.

An Extendable Star-Like Nanoplatform for Functional and Anatomical Imaging-Guided Photothermal Oncotherapy.

Combining informative imaging methodologies with effective treatments to destroy tumors is of great importance for oncotherapy. Versatile nanotheranostic agents that inherently possess both diagnostic imaging and therapeutic capabilities are highly desirable to meet these requirements. Here, a simple but powerful nanoplatform based on polydopamine-coated gold nanostar (GNS@PDA), which can be easily diversified to achieve various function extensions, is designed to realize functional and anatomical imaging-guided photothermal oncotherapy. This nanoplatform intrinsically enables computed tomography/photoacoustic/two-photon luminescence/infrared thermal tetramodal imaging and can further incorporate fibroblast activation protein (FAP, a protease highly expressed in most of tumors) activatable near-infrared fluorescence imaging and Fe3+-based magnetic resonance imaging for comprehensive diagnosis. Moreover, GNS@PDA exhibits excellent photothermal performance and efficient tumor accumulation. Under the precise guidance of multimodal imaging, GNS@PDA conducts homogeneous photothermal ablation of bulky solid tumors (∼200 mm3) in a xenograft mouse model. These results suggest great promise of this extendable nanoplatform for cancer theranostics.

NCTN clinical trial standardization for radiotherapy through IROC and CIRO.

Evidence-based practice is the cornerstone of modern medicine. Randomized clinical trials across multiple institutions are the gold standard for modern evidence collection. National Cancer Trials Network (NCTN) instruments the clinical trials through the new infrastructure for improvements in cancer treatment. Radiation therapy is an integral component of cancer treatment and is involved in many of the NCTN clinical trials. Radiotherapy is experiencing exciting developments in new treatment modalities and multi-modality image guidance. One of NCTN network groups NRG Oncology brings together the research areas of the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG). The Imaging and Radiation Oncology Core (IROC) and Center for Innovation in Radiation Oncology(CIRO) of NRG Oncology complement each other's functions in development and implementation of the new radiotherapy and imaging technologies in clinical trials with standardization and other strategies for quality. The standardization process is the essential step to make the data collected for clinical trials of high quality, interoperable, and reusable.

A Self-Assembled Biocompatible Nanoplatform for Multimodal MR/Fluorescence Imaging Assisted Photothermal Therapy and Prognosis Analysis.

The need for better imaging assisted cancer therapy calls for new biocompatible agents with excellent imaging and therapeutic capabilities. This study successfully fabricates albumin-cooperated human serum albumin (HSA)-GGD-ICG nanoparticles (NPs), which are comprised of a magnetic resonance (MR) contrast agent, glycyrrhetinic-acid-modified gadolinium (III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (GGD), and a fluorescence (FL) dye, indocyanine green (ICG), for multimodal MR/FL imaging assisted cancer therapy. These HSA-GGD-ICG NPs with excellent biocompatibility are stable under physiological conditions, and exhibit enhanced T1 contrast capability and improved fluorescence imaging capacity. In vitro experiments reveal an apparent effect of the NPs in killing tumor cells under low laser irradiation, due to the enhanced photothermal conversion efficiency (≈85.1%). Importantly, multimodal MR/FL imaging clearly shows the in vivo behaviors and the efficiency of tumor accumulation of HSA-GGD-ICG NPs, as confirmed by a pharmacokinetic study. With the guidance of multimodal imaging, photothermal therapy is subsequently conducted, which demonstrates again high photothermal conversion capability for eliminating tumors without relapse. Notably, real-time monitoring of tumor ablation for prognosis and therapy evaluation is also achieved by MR imaging. This strategy of constructing nanoplatforms through albumin-mediated methods is both convenient and efficient, which would enlighten the design of multimodal imaging assisted cancer therapy for potential clinical translation.

Is ultrasound guided spine injection safe?

Ultrasound has gained recognition within the field of pain intervention owing to its definite advantage of visually localizing the specified target and additionally owing to perceived advantages of safety, accuracy, and potency. Ultrasound permits satisfactory imaging of the posterior parts of the spine and paraspinal soft tissues. Despite the introduction of newer and less consuming time’s methods with the possibility of intravascular injection, there is still insufficient clinical evidence to prove the safety of the ultrasound as a sole image guide intervention, especially for transforaminal injection. It is essential to considering safety tips and be aware of complications that are typically terribly unpleasant and cause unwanted social and legal consequence. The most important injection warnings are damage to the spinal cord and nerve roots, intravascular injection and vascular damage, loss of consciousness, paraplegia and incontinence. The object of this review article is to discuss the untoward dangerous complication which can happen after ultrasound-guided spine injections and explain how to diagnosis and manage them. Further technical and equipment advancements are needed to improve and reduce the existing limitations associated with the ultrasound-guided spine injection technique until that time the multimodality imaging guidance is safer.

PH-sensitive radiolabeled and superfluorinated ultra-small palladium nanosheet as a high-performance multimodal platform for tumor theranostics

Radiolabeled nanomaterials, especially those with ultra-small structures, have been the research focus in recent years, and thus may open up new prospects for clinical diseases theranostics. Herein, fluorinated Pd nanosheets labeled with Gd or radionuclides are developed as multimodal platforms for tumor theranostics. These nanomaterials decorated by functional polyethylene glycol demonstrate ultrahigh 19F MRI signal, ultrasmall size and good dispersibility. These ultrasmall materials exhibit good biocompatibility and easily to be modified for multimodal imaging (SPECT/MRI/PAI) by assembling the functional groups like building blocks. Furthermore, with high accumulation in tumor sites, under the guidance of multimodal imaging, combined photothermal therapy and radiotherapy are performed and synergistic effects are obtained. By comparing the in vivo behaviors of nanostructures labeled by different nuclides, the present study suggests the pH-sensitive radioiodinated Pd nanosheet which has unexpected T/NT ratio (>4-fold tumor-to-muscle ratio) in SPECT imaging and solves the critical high background issue of nanoprobes, could improve diagnostic accuracy and guide combination therapy. In summary, this functionalized nanoplatform with promising imaging and therapeutic efficacy has great potential for precision theranostic nanomedicines.

Multimodality imaging guidance for percutaneous paravalvular leak closure: Insights from the multi-centre FFPP register

Percutaneous paravalvular leak (PVL) closure has emerged as a palliative alternative to surgical management in selected high-risk patients. Percutaneous procedures are challenging, especially for mitral PVL. Accurate imaging of the morphologies of the defects is mandatory, together with precise guidance in the catheterization laboratory to enhance success rates. To describe imaging modalities used in clinical practice to guide percutaneous PVL closure and assess the potential of new imaging tools. Data from the 'Fermeture de Fuite paraprothétique' (FFPP) register were used. The FFPP register is an international multi-institutional collaborative register started in 2017 with a retrospective and a prospective part. A descriptive analysis of multimodality imaging used to guide PVL closure in clinical practice was performed. Data from 173 procedures performed in 19 centres from three countries (France, Belgium and Poland) were collected, which included eight cases of PVL following transcatheter valve replacement. Transoesophageal echocardiography was used in 167 cases (96.5%) and 3D echocardiography in 87.4% of cases. In one case, 3D-echocardiography was fused with fluoroscopy images in real time using echonavigator software. Details about multimodality imaging were available from a sample of 31 patients. Cardiac computed tomography (CT) was performed before 10 of the procedures. In one case, fusion between preprocedural cardiac CT angiography data and fluoroscopy data was used. In two cases, a 3D model of the valve with PVL was printed. Echocardiography, particularly the 3D mode, is the cornerstone of PVL imaging. Other imaging modalities, such as cardiac CT and cardiac magnetic resonance imaging, may be of complementary interest. New techniques such as imaging fusion and printing may further facilitate the percutaneous approach of PVLs.

Characterization of a novel liquid fiducial marker for multimodal image guidance in stereotactic body radiotherapy of prostate cancer.

Liquid fiducial markers have shown to be a promising alternative to solid gold markers in terms of imaging artifact reduction, patient comfort, and compatibility with different imaging modalities. This study aims to investigate the performance of the novel BioXmark® liquid marker for state-of-the-art multimodal imaging used in prostate cancer (PCa) radiotherapy, encompassing kV CT/CBCT, multiparametric MRI, and kV x-ray imaging. In addition, automatic detection of the liquid markers in x-ray imaging for prostate motion monitoring during treatment was investigated. A total of eight BioXmark® liquid markers with varying volumes (range 5-300 μL) were casted on a square grid into a gelatin phantom insert. A cylindrical gold marker (QLRAD, length = 7 mm, Ø = 1 mm) was inserted for reference. Liquid marker visibility and streaking artifacts in CT/CBCT imaging were evaluated by placing the gelatin phantom into a CIRS anthropomorphic phantom. Relevant MRI characteristics such as the T2 and T1 relaxation times, the ADC value, and the relative proton density (ρH) were quantified by placing the gelatin phantom insert next to a T1MES mapping phantom and a water-filled syringe for reference. Ex vivo multiparametric MRI images were acquired by placing the gelatin phantom next to a resected prostate specimen. Anterior-posterior x-ray projection images were obtained by placing the gelatin phantom insert on top of an anthropomorphic pelvic phantom with internal pelvic bony structures and were acquired for five positions relative to the bony anatomy and 24 clinically relevant x-ray exposure settings. To quantify individual automatic marker detection, single markers were artificially isolated in the x-ray images using postprocessing. Markers of all sizes were clearly visible on CT and CBCT images with only the largest marker volumes (100-300 μL) displaying artifacts similar in size to the gold fiducial marker. Artifact size increased with increasing liquid marker volume. Liquid markers displayed good contrast in ex vivo T1-weighted and ρH-weighted images. The markers were not visible in the ex vivo T2-weighted image. The liquid markers induced a chemical shift artifact in the obtained ADC-map. Automated detection in x-ray imaging was feasible with high detection success (four of five positions) for marker volumes in the range of 25-200 μL. None of the liquid markers were detected successfully when superimposed on a bony edge, independent of their size. This study is the first to show the compatibility of BioXmark® liquid markers with multimodal image-guided radiotherapy for PCa. Compared to a solid gold marker, they had favorable results in both visibility and induced imaging artifacts. Liquid marker visibility in MRI imaging of the prostate does not solely depend on the low ρH value (not visible on T2-weighted image) but is also influenced by its relaxation times. Automated marker detection in x-ray images was feasible but better adapted marker detection algorithms are necessary for marker localization in the presence of bony edges. Hence, the liquid marker provides a minimally invasive (fine needles) and highly applicable alternative to current solid gold markers for multimodal image-guided prostate radiotherapy treatments.