Feasibility of real-time magnetic resonance imaging-guided endomyocardial biopsies:An in-vitro study

AIM: To investigate if magnetic resonance(MR)-guided biopsy can improve the performance and safety of such procedures. METHODS: A novel MR-compatible bioptome was evaluated in a series of in-vitro experiments in a 1.5T magnetic resonance imaging(MRI) system. The bioptome was inserted into explanted porcine and bovine hearts under real-time MR-guidance employing a steady state free precession sequence. The artifact produced by the metal element at the tip and the signal voids caused by the bioptome were visually tracked for navigation and allowed its constant and precise localization. RESULTS: Cardiac structural elements and the target regions for the biopsy were clearly visible. Our method allowed a significantly better spatial visualization of the bioptoms tip compared to conventional X-ray guidance. The specific device design of the bioptome avoided inducible currents and therefore subsequent heating. The novel MR-compatible bioptome provided a superior cardiovascular magnetic resonance(imaging) soft-tissue visualization for MR-guided myocardial biopsies. Not at least the use of MRI guidance for endomyocardial biopsies completely avoided radiation exposure for both patients and interventionalists.CONCLUSION: MRI-guided endomyocardial biopsies provide a better than conventional X-ray guided navigation and could therefore improve the specificity and reproducibility of cardiac biopsies in future studies.

Imaging-guided precision oncotherapy mediated by nanoprobes: From seeing to curing

Malignant tumors are the main diseases threatening human life. Using precise theranostics to diagnose and cure tumors has emerged as a new method to improve patient survival. Based on the current development of precise tumor imaging, image-guided tumor therapy has received widespread attention because it is beneficial for developing precise treatment of tumors, has the potential to improve the efficacy of tumor therapy and reduce the incidence of adverse side effects. Nanoprobes, which are nanomaterial functionalized with specific biomolecules, have intrigued intense interest due to their great potential in monitoring biorecognition and biodetection evens. Benefiting from the unique advantages of nanomaterials, including the easy surface functionalization, the unique imaging performances, and the high drug loading capacity, nanoprobes have become a powerful tool to simultaneously realize tumor precise imaging, diagnosis, and therapy. This review introduces the non-invasive tumor precise imaging and highlights the recent advances of image-guided oncotherapy mediated by nanoprobes in anti-tumor drug delivery, tumor precise surgical navigation, chemodynamic therapy, and phototherapy. Finally, a perspective on the challenge and future direction of nanoprobes in imaging-guided tumor theranostics is also discussed.

Pure photosensitizer-driven nanoassembly with core-matched PEGylation for imaging-guided photodynamic therapy

Pure drug-assembled nanomedicines(PDANs)are currently under intensive investigation as promising nanoplatforms for cancer therapy.However,poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation.Herein,we report a core-matched nanoassembly of pyropheophorbide a(PPa)for photodynamic therapy(PDT).Pure PPa molecules are found to self-assemble into nanoparticles(NPs),and an amphiphilic PEG polymer(PPaPEG_(2K))is utilized to achieve core-matched PEGylating modification via the p-p stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG_(2K) shell.Compared to PCL-PEG_(2K) with similar molecular weight,PPa-PEG_(2K) significantly increases the stability,prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly.As a result,PPa/PPa-PEG_(2K) NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model.Together,such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines.

Targeted and imaging-guided in vivo photodynamic therapy for tumors using dual-function, aggregation- induced emission nanoparticles

Imaging-guided photodynamic therapy （PDT） has been regarded as a promising strategy for precise cancer treatment. Because of their excellent modifiability and drug-loading capacity, nanoparticles have played an important role in PDT. Nonetheless, when traditional photosensitizers are made into nanoparticles, both their fluorescence and reactive oxygen species generation efficacy decrease due to a phenomenon known as aggregation-caused quenching. Fortunately, in recent years, several kinds of organic dyes with ＂abnormal＂ properties （termed aggregation-induced emission, AIE） were developed. With enhanced fluorescence emission in the nanoaggregation state, the traditional obstacles mentioned above may be overcome by AIE luminogens. Herein, we provide a better combination of photosensitizers and nanoparticles, namely, dual-function AIE nanopartides capable of producing reactive oxygen species, to implement targeted and imaging-guided in vivo PDT. Good contrast of in vivo imaging and obvious therapeutic efficacy were observed at a low dose of AIE nanoparticles and low irradiance of light, thus resulting in negligible side effects. Our work shows that AIE nanopartides may play a promising role in imaging-guided clinical PDT for cancer in the near future.

Mitochondrion-anchoring AIEgen with Large Stokes Shift for Imaging-guided Photodynamic Therapy

Photosensitizers that can target and accumulate in mitochondria are expected to achieve good therapeutic effects in photodynamic therapy,as mitochondria are the energy generation factory in cells.Herein,we designed and synthesized a novel mitochondrion-targeting photosensitizer TPC-Py with aggregation-induced emission characteristics for image-guided photodynamic therapy.TPC-Py possessed an efficient production of 1O2,with a quantum yield of 11.65%,upon mild white light irradiation(6 mW/cm^(2)).TPC-Py exhibited good biocompatibility under dark condition,but showed remarkable cytotoxicity towards human cervical carcinoma(HeLa)cells with a half maximal inhibitory concentration(IC50)of 3.2µmol/L when exposed to white light irradiation(14.4 J/cm^(2)).In addition,the Stokes shift of TPC-Py was as high as 150 nm,so that it could prevent self-absorption and increase the signal-to-noise ratio of fluorescence imaging.The excellent performance of TPC-Py makes it a promising candidate in imaging-guided clinical PDT for cancer in the near future.

“Dual-Lock-Dual-Key”Controlled Second Near-Infrared Molecular Probe for Specific Discrimination of Orthotopic Colon Cancer and Imaging-Guided Tumor Excision

Fluorescence imaging in the second infrared window(1000-1700 nm)has emerged as a promising approach to tumor diagnosis.However,the currently available second near-infrared(NIR-II)imaging agents are based on the“always on”modality or single biomarker activation,which are subject to limited imaging contrast,nonspecific response,and even false-positive diagnosis.Here,we developed a H2S/H+dual-stimuli responsive NIR-II fluorescent probe,WH-N3,for precise tumor delimitation and intraoperative fluorescence-guided surgical resection.WH-N3 itself is nonfluorescent,and it can only light up through synergistic activation by H2S and in the tumor acidic environment(TEM).Such a“duallock-dual-key”strategy-based activatable probe exhibited significantly higher tumor-to-normal tissue(T/N)ratios than the“always on”agent(ICG)and single parameter responsive counterpart probes in the imaging of colon tumors,which overexpresses H2S.WH-N3 was also able to visualize the tumor-derived endogenous H2S fluctuation and accurately differentiate tumor types based on H2S content discrepancy.More excitingly,under the guidance of the probe’s highly specific NIR-II fluorescence,a tiny orthotopic colon tumor with diameter down to 0.8 mm was facilely resected.We expect our dual-stimuli responsive strategy will contribute more reliable tools for specific discrimination and imaging-guided excision of tumor.

Neurosurgical and pharmacological management of dystonia

Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements,often with repetitive or sustained contraction resulting in abnormal posturing.Different types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given intervention.For most patients afflicted with these disorders,an exact cause is rarely identified,so treatment mainly focuses on symptomatic alleviation.Pharmacological agents,such as oral anticholinergic administration and botulinum toxin injection,play a major role in the initial treatment of patients.In more severe and/or refractory cases,focal areas for neurosurgical intervention are identified and targeted to improve quality of life.Deep brain stimulation(DBS)targets these anatomical locations to minimize dystonia symptoms.Surgical ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to DBS.These management options grant providers and patients the ability to weigh the benefits and risks for each individual patient profile.This review article explores these pharmacological and neurosurgical management modalities for dystonia,providing a comprehensive assessment of each of their benefits and shortcomings.

Precision radiotherapy for brain tumors A 10-year bibliometric analysis

OBJECTIVE： Precision radiotherapy plays an important role in the management of brain tumors. This study aimed to identify global research trends in precision radiotherapy for brain tumors using a bibliometric analysis of the Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of data retrievals for precision radiotherapy for brain tumors containing the key words cerebral tumor, brain tumor, intensity-modulated radiotherapy, stereotactic body radiation therapy, stereotactic ablative radiotherapy, imaging-guided radiotherapy, dose-guided radiotherapy, stereotactic brachytherapy, and stereotactic radiotherapy using the Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed articles on precision radiotherapy for brain tumors which were published and indexed in the Web of Science; （b） type of articles： original research articles and reviews; （c） year of publication： 2002-2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） Corrected papers or book chapters. MAIN OUTCOME MEASURES： （1） Annual publication output; （2） distribution according to country; （3） distribution according to institution; （4） top cited publications; （5） distribution according to journals; and （6） comparison of study results on precision radiotherapy for brain tumors. RESULTS： The stereotactic radiotherapy, intensity-modulated radiotherapy, and imaging-guided radiotherapy are three major methods of precision radiotherapy for brain tumors. There were 260 research articles addressing precision radiotherapy for brain tumors found within the Web of Science. The USA published the most papers on precision radiotherapy for brain tumors, followed by Germany and France. European Synchrotron Radiation Facility, German Cancer Research Center and Heidelberg University were the most prolific research institutes for publications on precision radiotherapy for brain tumors. Among the top 13 research institutes publishing in this field, seven are in the USA, three are in Germany, two are in France, and there is one institute in India. Research interests including urology and nephrology, clinical neurology, as well as rehabilitation are involved in precision radiotherapy for brain tumors studies. CONCLUSION： Precision radiotherapy for brain tumors remains a highly active area of research and development.

Cardiac involvement in disseminated diffuse large B-cell lymphoma,successful management with chemotherapy dose reduction guided by cardiac imaging: A case report and review of literature

BACKGROUND Secondary cardiac involvement by lymphoma has received limited attention in the medical literature, despite its grave prognosis. Although chemotherapy improves patients' survival, a subgroup of treated patients dies suddenly due to myocardial rupture following chemotherapy initiation. Reducing the initial chemotherapy dose with dose escalation to standard doses may be effective in minimizing this risk but the data are limited. We report on the successful management of a patient with disseminated diffuse large B-cell lymphoma(DLBCL) involving the heart using such approach.CASE SUMMARY An 18-year-old male presented to our hospital with six months history of progressive dyspnea, orthopnea and cough. On physical examination, the patient was found to have a plethoric and mildly edematous face, fixed elevation of the right internal jugular vein, suggestive of superior vena cava obstruction, and a pelvic mass. Investigations during admission including a thoracoabdominal computed tomography(CT) scan with CT guided biopsy of the pelvic mass,echocardiography and cardiac magnetic resonance imaging led to the diagnosis of disseminated DLBCL with cardiac involvement. The patients were successfully treated with chemotherapy dose reduction followed by dose escalation to standard doses, under the guidance of cardiac imaging. The patient completed chemotherapy and underwent a successful bone marrow transplant. He is currently in remission and has a normal left ventricular function.CONCLUSION Imaging-guided chemotherapy dosing may minimize the risk of myocardial rupture in cardiac lymphoma. Data are limited. Management should be individualized.

Brachytherapy in cancer cervix: Time to move ahead from point A?

Brachytherapy forms an integral part of the radiation therapy in cancer cervix. The dose prescription for intracavitary brachytherapy(ICBT) in cancer cervix is based on Tod and Meredith's point A and has been in practice since 1938. This was proposed at a time when accessibility to imaging technology and dose computation facilities was limited. The concept has been in practice worldwide for more than half a century and has been the fulcrum of all ICBT treatments, strategies and outcome measures. The method is simple and can be adapted by all centres practicing ICBT in cancer cervix. However, with the widespread availability of imaging techniques, clinical use of different dose-rates, availability of a host of applicators fabricated with image compatible materials, radiobiological implications of dose equivalence and its impact on tumour and organs at risk; more and more weight is being laid down on individualised image based brachytherapy. Thus, computed tomography, magnetic-resonance imaging and even positron emission computerized tomographyalong with brachytherapy treatment planning system are being increasingly adopted with promising outcomes. The present article reviews the evolution of dose prescription concepts in ICBT in cancer cervix and brings forward the need for image based brachytherapy to evaluate clinical outcomes. As is evident, a gradual transition from "point" based brachytherapy to "profile" based image guided brachytherapy is gaining widespread acceptance for dose prescription, reporting and outcome evaluation in the clinical practice of ICBT in cancer cervix.

High-intensity focused ultrasound tumor ablation:Review of ten years of clinical experience

High-intensity focused ultrasound(HIFU)is a technique to destroy tissue at depth within the body,selectively and without harming overlying and adjacent structures within the path of the beam because the ultrasonic intensity at the beam focus is much higher than that outside of the focus.Diagnostic ultrasound is the first imaging modality used for guiding HIFU ablation.In 1997,a patient with osteosarcoma was first successfully treated with ultrasound imaging-guided HIFU in Chongqing,China.Over the last decade,thousands of patients with uterine fibroids,liver cancer,breast cancer,pancreatic cancer,bone tumors,and renal cancer have been treated with ultrasound imaging-guided HIFU.Based on several research groups’reports,as well as our ten-year clinical experience,we conclude that this technique is safe and effective in treating human solid tumors.HIFU is a promising technique.Most importantly,HIFU offers patients another alternative when those patients have no other treatment available.

Liposome-based multifunctional nanoplatform as effective therapeutics for the treatment of retinoblastoma

Photothermal therapy has the characteristics of minimal invasiveness,controllability,high efficiency,and strong specificity,which can effectively make up for the toxic side effects and tumor resistance caused by traditional drug treatment.However,due to the limited tissue penetration of infrared light,it is difficult to promote and apply in clinical practice.The eye is the only transparent tissue in human,and infrared light can easily penetrate the eye tissue,so it is expected that photothermal therapy can be used to treat fundus diseases.Here in,a new nano-platform assembled by liposome and indocyanine green(ICG) was used to treat retinoblastoma.ICG was assembled in liposomes to overcome some problems of ICG itself.For example,ICG is easily quenched,self-aggregating and instability.Moreover,liposomes can prevent free ICG from being cleared through the systemic circulation.The construction of the nano-platform not only ensured the stability of ICG in vivo,but also realized imaging-guide photothermal therapy,which created a new strategy for the treatment of retinoblastoma.

Exo/endogenous factors co-activatable nanodevice for spatiotem-porally controlled miRNA imaging and guided tumor ablation

Remote activation of biomarker sensing holds a great promise of shifting the success of in vitro diagnostics to spatiotemporally controlled in vivo visualization of tumor,and in turn,imaging guided therapy.Herein,a"dual-key-one-lock"nanodevice was designed and built by assembling thermo-activatable probe of trimeric DNA hybrids into a mesoporous polydopamine nanoparticle-based multifunctional nanotransducer(probe host,fluorescence quencher,and photothermal conversion agent),enabling precisely switchable theranostic operations under the co-activation of exo/endogenous stimulations(near-infrared(NIR)light and microRNA(miRNA)).By this design,the NIR irradiation-induced local heat through the porous nanotransducer can be transferred to the DNA nanothermometer for triggering the exposure of the miRNA recognition segment,as well as the subsequent fluorescence activation by strand displacement reactions(SDR).A programmable application of short-(3 min)and long-duration(10 min)NIR irradiation was administered sequentially to induce a milder and a stronger hyperthermia,respectively,to activate the localized miRNA imaging,and in turn,tumor thermoablation under the fluorescence guidance in vivo.By reducing nonspecific activation,dual factor co-activatable nanodevices exhibited a high tumor-to-background ratio(TBR)value of 8.9,as well as a significantly lower(6-9-fold)normal tissue fluorescence as compared with those sensing miRNA solely.The in vivo results show that the tumors were significantly suppressed after the photothermal therapy with the assistance of the accurate miRNA diagnosis.This rationally integrated nanoplatform may pave a new avenue for advanced theranostic systems with high spatiotemporal precision by activatable designs.