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Recanalization of the occluded artery is the gold standard treatment for acute ischemic stroke, which includes enzymatic fibrinolytic treatment with the use of recombinant tissue plasminogen activators (rtPAs) to disrupt the occluding clot, the use of mechanical thrombectomy to physically remove the clot, or a combination of both. Fibrin is one of the main components of blood clots causing ischemic stroke and is the target of rtPA upon activation of plasminogen in the clot. In addition, fibrin content also influences the efficacy of mechanical thrombectomy. Current imaging methods can successfully identify occlusions in large vessels; however, there is still a need for contrast agents capable of visualizing small thrombi in ischemic stroke patients. In this work, we describe the synthesis and the in vitro characterization of a new diagnostic nanoparticle, as well as the in vivo evaluation in an animal model of thromboembolic stroke. Gd-labeled KCREKA peptides were synthesized and attached onto the surface of PEGylated superparamagnetic nanoparticles. Magnetic resonance imaging (MRI) of blood clots was performed in vitro and in vivo in animal models of thromboembolic stroke. KCREKA-NPs were synthesized by attaching the peptide to the amino (N) termini of the PEG-NPs. The sizes of the nanoparticles, measured via DLS, were similar for both KCREKA-NPs and PEG-NPs (23 ± 4 nm, PDI = 0.11 and 25 ± 8 nm, PDI = 0.24, respectively). In the same line, r2 relaxivities were also similar for the nanoparticles (149 ± 2 mM Fe s−1 and 151 ± 5 mM Fe s−1), whereas the r1 relaxivity was higher for KCREKA-NPs (1.68 ± 0.29 mM Fe s−1 vs. 0.69 ± 0.3 mM Fe s−1). In vitro studies showed that blood clots with low coagulation times were disrupted by rtPA, whereas aged clots were almost insensitive to the presence of rtPA. MRI in vitro studies showed a sharp decrease in the T1 × T2 signals measured for aged clots incubated with KCREKA-NPs compared with fresh clots (47% [22, 80] to 26% [15, 51]). Furthermore, the control blood showed a higher value of the T1 × T2 signal (39% [20, 61]), being the blood clots with low coagulation times the samples with the lowest values measured by MRI. In vivo studies showed a significant T1 × T2 signal loss in the clot region of 24% after i.v. injection of KCREKA-NPs. The thrombus age (2.5% ± 6.1% vs. 81.3% ± 19.8%, p < 0.01) confirmed our ability to identify in vivo fresh blood clots. In this study, we developed and tested a dual MRI nanoparticle, acting as T1 and T2 contrast agents in MRI analyses. The developed KCREKA-NPs showed affinity for the fibrin content of blood clots, and the MRI signals provided by the nanoparticles showed significant differences depending on the clot age. The developed KCREKA-NPs could be used as a tool to predict the efficacy of a recanalization treatment and improve the triage of ischemic stroke patients.

Neurological diseases (Alzheimer’s disease, Parkinson’s disease, and stroke) are becoming a major concern for health systems in developed countries due to the increment of ageing in the population, and many resources are devoted to the development of new therapies and contrast agents for selective imaging. However, the strong isolation of the brain by the brain blood barrier (BBB) prevents not only the crossing of pathogens, but also a large set of beneficial drugs. Therefore, an alternative strategy is arising based on the anchoring to vascular endothelial cells of nanoplatforms working as delivery reservoirs. In this work, novel injectable mesoporous nanorods, wrapped by a fluorescent magnetic nanoparticles envelope, are proposed as biocompatible reservoirs with an extremely high loading capacity, surface versatility, and optimal morphology for enhanced grafting to vessels during their diffusive flow. Wet chemistry techniques allow for the development of mesoporous silica nanostructures with tailored properties, such as a fluorescent response suitable for optical studies, superparamagnetic behavior for magnetic resonance imaging MRI contrast, and large range ordered porosity for controlled delivery. In this work, fluorescent magnetic mesoporous nanorods were physicochemical characterized and tested in preliminary biological in vitro and in vivo experiments, showing a transversal relaxivitiy of 324.68 mM−1 s−1, intense fluorescence, large specific surface area (300 m2 g−1), and biocompatibility for endothelial cells’ uptake up to 100 µg (in a 80% confluent 1.9 cm2 culture well), with no liver and kidney disability. These magnetic fluorescent nanostructures allow for multimodal MRI/optical imaging, the allocation of therapeutic moieties, and targeting of tissues with specific damage.

Acute ischemic stroke (AIS) is the loss of neurological function due to a sudden reduction in cerebral blood flow and is a leading cause of disability and death worldwide. The field of radiological imaging has experienced growth in recent years, which could be boosted by the advent of artificial intelligence. One of the latest innovations in artificial intelligence is radiomics, which is based on the fact that a large amount of quantitative data can be extracted from radiological images, from which patterns can be identified and associated with specific pathologies. Since its inception, radiomics has been particularly associated with the field of oncology and has shown promising results in a wide range of clinical situations. The performance of radiomics in non-tumour pathologies has been increasingly explored in recent years, and the results continue to be promising. The aim of this review is to explore the potential applications of radiomics in AIS patients and to theorize how radiomics may change the paradigm for these patients in the coming years.