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Targeting Glioma with a Dual Mode Optical and Paramagnetic Nanoprobe across the Blood-brain Tumor Barrier
摘要： In brain tumors, delivering nanoparticles across the blood-tumor barrier presents major hurdles. A clinically relevant MRI contrast agent, GdDOTA and a near-infrared (NIR) fluorescent dye, DL680 were conjugated to a G5 PAMAM dendrimer, thus producing a dual-mode MRI and NIR imaging agent. Systemic delivery of the subsequent nano-sized agent demonstrated glioma-specific accumulation, probably due to the enhanced permeability and retention effect. In vivo MRI detected the agent in glioma tissue, but not in normal contralateral tissue; this observation was validated with in vivo and ex vivo fluorescence imaging. A biodistribution study showed the agent to have accumulated in the glioma tumor and the liver, the latter being the excretion path for a G5 dendrimer-based agent.
关键词： Tumor blood-brain barrier,MRI,Dual modality,Glioma,Optical imaging
更新于2025-09-23 15:21:21
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Photoacoustic imaging of gold nanorods in the brain delivered via microbubble-assisted focused ultrasound: a tool for <i>in vivo</i> molecular neuroimaging
摘要： The protective barriers of the CNS present challenges during the treatment and monitoring of diseases. In particular, the blood brain barrier is a major hindrance to the delivery of imaging contrast agents and therapeutics to the brain. In this work, we use gas microbubble-assisted focused ultrasound to transiently open the blood brain barrier and locally deliver silica coated gold nanorods across the barrier. This particular nanoagent possesses a strong optical absorption which enables in vivo and ex vivo visualization of the delivered particles using ultrasound-guided photoacoustic imaging. The results of these studies demonstrate the potential of ultrasound-guided photoacoustics to image contrast agents delivered via microbubble-assisted focused ultrasound for longitudinal diagnostic imaging and for therapeutic monitoring of neurological diseases.
关键词： focused ultrasound,blood brain barrier opening,nanoparticles,ultrasound and photoacoustic imaging
更新于2025-09-19 17:15:36
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Laser interstitial thermal therapy in gliomas
摘要： Laser interstitial thermal therapy (LITT) has been used for brain metastasis, epilepsy, and necrosis, as well as gliomas as a minimally invasive treatment for many years. With the improvement of the thermal monitoring and ablation precision, especially the application of magnetic resonance (MR) thermography in the procedure and the available of two commercial laser systems nowadays, LITT is gradually accepted by more neurosurgical centers. Recently, some new concepts, for example the adjuvant chemotherapy or radiation following LITT, the combination of immunotherapy and LITT regarding the glioma treatment are proposed and currently being investigated. The aim of this study is to summarize the evolution of LITT especially for brain gliomas and a possible outlook of the future.
关键词： gliomas,immunotherapy,blood brain barrier,Laser interstitial thermal therapy
更新于2025-09-16 10:30:52
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First Steps towards Localized Opening of the Blood-Brain-Barrier by IR Laser Illumination Through the Rodent Skull
摘要： Glioblastoma, an aggressive malign tumor of the brain, is one of the most shattering diagnoses due to its very poor prognosis and limited treatment options. These options mainly consist of surgical or radiation therapeutic removal of as much tumor mass as possible, which unfortunately is almost always incomplete. Even worse, chemotherapy is of little use, as the special setup of the brain′s vessels severely limits the transit into the parenchyma of elsewhere efficient cytostatica. This Blood-Brain-Barrier (BBB) is for quite some time the target of sophisticated and nano-particle based transport mechanisms, however it is reported, that a boost of permeability for most of the brain can be achieved based on moderate temperature increase. One means to locally and reversibly increase the brain′s temperature and thus potentially opening the BBB may be achieved by illuminating the skull with infrared laser light, thus causing punctual heating and heat diffusion into the cortex. In extension of the common laser light guiding by glass fibres, we use a micro-positioned simple optics to focus a 1470 nm laser beam of approximately 500 ??m in diameter on the skull. The apparent opening of the BBB is evidenced by the localized spread of Evans Blue injected into the tail vein of said rat, binding to Albumin (64,6 kDa) in the body. This marker molecule is usually blocked from passing through the intact BBB, but under IR illumination for half a minute, it appeared in post mortem visible blobs. Temperature profiles and potential tissue damage are now under investigation by high speed thermal camera and post mortem histology.
关键词： Infrared Laser Illumination,Blood Brain Barrier Opening,Evans Blue
更新于2025-09-16 10:30:52
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Fluorine-18 Isotope Labeling for Positron Emission Tomography Imaging. Direct Evidence for DBPR211 as a Peripherally Restricted CB1 Inverse Agonist
摘要： The [18F] isotope-labelled CB1 inverse agonist 3 was elaborated and synthesized for positron emission tomography scanning studies. After immediate purification and calibration with its unlabeled counterpart, compound 3 was intravenously injected in mice and revealed that its distribution percentage in brain over 90-min scans among five region of interests, including brain, liver, heart, thigh muscle and kidney was lower than 1%, thus providing direct evidence to justify itself as a peripherally restricted CB1 antagonist.
关键词： Peripherally restricted CB1 inverse agonist,Cannabinoid-1 antagonist,Positron emission tomography,Blood-brain barrier
更新于2025-09-10 09:29:36
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In vivo monitoring blood-brain barrier permeability using spectral imaging through optical clearing skull window
摘要： The blood–brain barrier (BBB) plays a key role in the health of the central nervous system. Opening the BBB is very important for drug delivery to brain tissues to enhance the therapeutic effect on brain diseases. It is necessary to in vivo monitor the BBB permeability for assessing drug release with high resolution; however, an effective method is lacking. In this work, we developed a new method that combined spectral imaging with an optical clearing skull window to in vivo dynamically monitor BBB opening caused by 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT), in which the Evans blue dye (EBd) acted as an indicator of the BBB permeability. Using this method, we effectively monitored the cerebrovascular EBd leakage process. Moreover, the analysis of changes in the vascular and extravascular EBd concentrations demonstrated that the PDT-induced BBB opening exhibited spatiotemporal differences in the cortex. This spectral imaging method based on the optical clearing skull window provides a low-cost and simply-operated tool for in vivo monitoring BBB opening process. This has a high potential for the visualization of drug delivery to the central nervous system. Thus, it is of tremendous significance in brain disease therapy.
关键词： spectral imaging,blood-brain barrier,skull optical clearing,in vivo optical imaging
更新于2025-09-10 09:29:36
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Changes in Vascular and Immune Cell Content of an LPS Treated Rat Olfactory Bulb PD Model, Measured by Fluorescence Deconvolution Microscopy
摘要： Objective: We have previously shown changes in protein, immune cell, nitric oxide a neurotrophic factor content and distribution in the olfactory bulb of an endotoxin-treated rat model, as all these factors have been shown to be involved in neurodegeneration. We expanded our studies by fluorescently imaging smooth muscle actin and endothelial nitric oxide synthase (eNOS), both markers of blood vessels, to investigate loss of vasculature content, as well as imaging locations and quantities of immune cells. The work was performed to shed further light on associations between vessel integrity and immune cell initiated endothelial disruption. Our goal was to demonstrate that cytokine production, NOS induction and immune cell increases, are likely part of the process that leads to a loss of olfaction and dopaminergic signaling and includes vascular perturbations. Methods: Rats were sacrificed following lipopolysaccharide (LPS) treatment. Olfactory bulbs were harvested, sectioned from top to bottom to include the tract and sensory neurons, and probed for markers of inflammation. Inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), eNOS, interleukin-1 beta (IL-1β), TNF-α, interleukin-6, glial cell derived neurotrophic factor (GDNF) and circulating nitric oxide (NO) were imaged together with tagged macrophages, T-cells, B-cells and neutrophils. Results: Serum NO levels indicated that an inflammatory episode had occurred, being significantly higher in treated animals, with tissue levels of NOS elevated for an extended period of time. Immune cell clusters were seen in a number of areas and the localization of NOS isomers suggests that they have divergent roles in neurodegeneration. For instance, eNOS was associated with blood vessels, iNOS with glial and matrix cells and nNOS with glial cells and neurons. T and B-cell numbers showed a sustained increase; neutrophil numbers rapidly increased then returned to baseline levels; macrophage numbers increased and remained high; LAMP positive cell numbers (NK-cells) increased and remained high; GDNF content increased; IL-6, TNF-α and IL-1β levels all rapidly increased, before dropping to untreated levels, while circulating, NO levels increased dramatically. Of interest, the images of vascular content, immune cell content, eNOS and smooth muscle actin, allowed us to show detrimental interactions between cells, factors and vessels. Our data show that the majority of the vessels were intact, though sections of interest were ‘extracted’ to reveal possible leaky areas. Specific sites of IL-6 positive lymphocyte clustering were noted around vessels, suggesting that interactions are occurring that lead to disruptions of blood vessel tunicae, allowing the internalization of circulating cells and subsequent cytokine-initiated endothelial cell death. Conclusion: Our findings suggest that protective GDNF and eNOS, which maintains vascular tone, are possibly synthesized too late to combat cytokine initiated neuron damage, glial activation and chronic loss of vascular integrity.
关键词： Blood-brain-barrier,Cytokines,Neurodegeneration,Nitric oxide,Olfaction
更新于2025-09-09 09:28:46
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Multimodal imaging of retinal metastasis masquerading as an acute retinal necrosis
摘要： Background: To report the multimodal imaging and histology of a case of metastatic esophageal cancer with vitreo? retinal involvement resembling acute retinal necrosis (ARN) in a patient receiving systemic chemotherapy. Case presentation: A 69?year?old Japanese man with a history of stage 4 esophageal carcinoma, treated with three cycles of 5?fluorouracil (5?FU) and cisplatin (CDDP) chemotherapy as well as 30 sessions of radiation therapy, presented with new onset of blurry vision in the right eye (OD). Visual acuity was 20/200 OD. Fundus examination OD revealed 2+ nuclear cataract, veil?like vitreous opacity, a tractional retinal detachment, and white retinal lesions in the macula and periphery masquerading as an ARN. Due to the poor view and uncertainty regarding diagnosis, combined cataract extraction and 25 gauge pars plana vitrectomy was performed. Polymerase chain reaction and cytologic analysis were performed on the vitreous samples, which was negative for all infectious entities but positive for poorly differentiated malignant cells. The vitreous biopsy was consistent with the primary endoscopic esophageal biopsy. Ultra?wide view fundus imaging revealed multifocal white intraretinal lesions in the macula and periphery. Optical coherence tomography through these white opacities displayed hyper?reflective inner retinal lesions with no choroidal involvement, suggestive of retinal metastasis. Observation and palliative support was continued until the patient passed away 3 months after diagnosis. Conclusion: Retinal metastasis may mimic infectious syndromes such as ARN and are associated with a very poor prognosis. Outside of the retina, no further central nervous system metastasis was found. 5?FU is known to cross the blood–brain?barrier but may be inadequate in preventing retinal metastasis.
关键词： Acute retinal necrosis,Vitrectomy,Retina,Metastasis,Fluorouracil,Cisplatin,Blood–brain barrier
更新于2025-09-09 09:28:46