Iron Oxide Nanoparticles as Theranostic Agents in Cancer Immunotherapy

Starting from the mid-1990s, several iron oxide nanoparticles (NPs) were developed as MRI contrast agents. Since their sizes fall in the tenths of a nanometer range, after i.v. injection these NPs are preferentially captured by the reticuloendothelial system of the liver. They have therefore been proposed as liver-specific contrast agents. Even though their unfavorable cost/benefit ratio has led to their withdrawal from the market, innovative applications have recently prompted a renewal of interest in these NPs. One important and innovative application is as diagnostic agents in cancer immunotherapy, thanks to their ability to track tumor-associated macrophages (TAMs) in vivo. It is worth noting that iron oxide NPs may also have a therapeutic role, given their ability to alter macrophage polarization. This review is devoted to the most recent advances in applications of iron oxide NPs in tumor diagnosis and therapy. The intrinsic therapeutic effect of these NPs on tumor growth, their capability to alter macrophage polarization and their diagnostic potential are examined. Innovative strategies for NP-based drug delivery in tumors (e.g., magnetic resonance targeting) will also be described. Finally, the review looks at their role as tracers for innovative, and very promising, imaging techniques (magnetic particle imaging-MPI)

The contribution of the 1H-MRS lipid signal to cervical cancer prognosis: a preliminary study

Background The aim of this study was to investigate the role of the lipid peak derived from H-1 magnetic resonance (MR) spectroscopy in assessing cervical cancer prognosis, particularly in assessing response to neoadjuvant chemotherapy (NACT) of locally advanced cervical cancer (LACC). Methods We enrolled 17 patients with histologically proven cervical cancer who underwent 3-T MR imaging at baseline. In addition to conventional imaging sequences for pelvic assessment, the protocol included a single-voxel point-resolved spectroscopy (PRESS) sequence, with repetition time of 1,500 ms and echo times of 28 and 144 ms. Spectra were analysed using the LCModel fitting routine, thus extracting multiple metabolites, including lipids (Lip) and total choline (tCho). Patients with LACC were treated with NACT and reassessed by MRI at term. Based on tumour volume reduction, patients were classified as good responder (GR; tumour volume reduction > 50%) and poor responder or nonresponder (PR-or-NR; tumour volume reduction <= 50%). Results Of 17 patients, 11 were LACC. Of these 11, only 6 had both completed NACT and had good-quality H-1-MR spectra; 3 GR and 3 PR-or-NR. A significant difference in lipid values was observed in the two groups of patients, particularly with higher Lip values and higher Lip/tCho ratio in PR-NR patients (p =0.040). A significant difference was also observed in choline distribution (tCho), with higher values in GR patients (p = 0.040). Conclusions Assessment of lipid peak at H-1-MR spectroscopy could be an additional quantitative parameter in predicting the response to NACT in patients with LACC

Study of the effect of different breast implant surfaces on capsule formation and host inflammatory response in an animal model

Background: Breast implants are biomaterials eliciting a physiological and mandatory foreign body response. Objectives: The authors designed an animal study to investigate the impact of different implant surfaces on the formation of the periprosthetic capsule, the inflammatory response, and the cellular composition. Methods: The authors implanted 1 scaled-down version of breast implants by different manufactures on 70 female Sprague Dawley rats. Animals were divided into 5 groups of 14 animals. Group A received a smooth implant (Ra ≈ 0.5 µm) according to the ISO 14607-2018 classification, Group B a smooth implant (Ra ≈ 3.2 µm), Group C a smooth implant (Ra ≈ 5 µm), Group D a macrotextured implant (Ra ≈ 62 µm), and Group E a macrotextured implant (Ra ≈ 75 µm). At 60 days, all animals received a magnetic resonance imaging (MRI), and 35 animals were killed and their capsules sent for histology (capsule thickness, inflammatory infiltrate) and immunohistochemistry analysis (cellular characterization). The remaining animals repeated the MRI at 120 days and were killed following the same protocol. Results: MRI showed a thinner capsule in the smooth implants (Groups A-C) at 60 days (P < .001) but not at 120 days (P = .039), confirmed with histology both at 60 days (P = .005) and 120 days (P < .001). Smooth implants (Groups A-C) presented a mild inflammatory response at 60 days that was maintained at 120 days and a high M2-Macrophage concentration (anti-inflammatory). Conclusions: Our study confirms that smooth implants form a thinner capsule, inferior inflammatory infiltrate, and a cellular composition that indicates a mild host inflammatory response. A new host inflammatory response classification is elaborated classifying breast implants into mild, moderate, and high

the role of molecular and imaging biomarkers in the evaluation of inflammation in oncology

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Mice repeatedly exposed to Group-A \u3b2-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon

Repeated exposure to Group-A \u3b2-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities

Developing and validating in vivo 1H MRS methodology for monitoring tumour growth and metabolism

SIGLEAvailable from British Library Document Supply Centre- DSC:DXN055509 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

The role of proton magnetic resonance spectroscopy (1H-MRS) in Mild Cognitive Impairment and in Alzheimer's disease: a review on the most recent literature

The role of proton magnetic resonance spectroscopy (1H-MRS) in Mild Cognitive Impairment and in Alzheimer's disease: a review on the most recent literature Introduction Neurochemical changes, measured through 1H-MRS, are present in several neurodegenerative diseases, in which aging is the primary risk factor. Alzheimer's disease (AD) is the most common cause of dementia, while Mild Cognitive Impairment (MCI) represents its prodromal stage. 1H-MRS represents an important tool useful to quantify metabolites (including N-acetyl-aspartate (NAA), glutamate, glutamine, g-aminobutyric-acid, myoinositol, choline, creatine (Cr) and glutathione) in different regions of brain in order to diagnose early AD and to monitor its progression in the clinical stages. Aim The aim of this work was the identification by 1H-MRS of possible metabolic biomarkers which could help in distinguishing among normal aging, MCI patients and AD patients. Methods We have selected clinical trials of the last ten years from PubMed and Scopus based on inclusion criteria. We have chosen studies in which levels of metabolites are estimated in different brain regions: posterior cingulate gyrus, anterior cingulate gyrus, left hippocampus, right cortical area, left dorsolateral prefrontal cortex, left parietal lobe, left lateral temporal lobe. We have selected clinical studies obtained using 1.5 T or 3.0 T imager MRS in normal aging, MCI patients and in AD patients. Results Twenty articles satisfy the inclusion criteria. The most studied region present in the literature is the posterior cingulate gyrus which showed a significant reduction in NAA/Cr ratio and an increased level of myoinositol in the AD group than the control group. These metabolic alterations are in agreement with the hypothesis of neuron reduction and glia activation in this region which is related to emotions and memory. Brain bioenergetics are defective in AD. Glutamate (major excitatory neurotransmitter in the central nervous system), glutamine (precursor of glutamate), glutathione (primary antioxidant that plays a role in cell protection against oxidative damage) and g-aminobutyric-acid (with an important role in the inhibition of the central nervous system) undergo changes between the different groups. Conclusions 1H-MRS represents an important tool for the evaluation of metabolites changes, used as potentially biomarkers and associated with the loss of neuronal integrity. 1H-MRS can detect cognitive deterioration and assess the conversion from MCI to AD, evaluating different pathophysiology stages. References (max 3, optional) - A comparative study of posterior cingulate metabolism in patients with mild cognitive impairment due to Parkinson’s disease or Alzheimer’s disease, Mingming Huang, HuiYu, Xi Cai, Yong Zhang, Wei Pu, Bo Gao, Scientific Reports, 2023 - Predicting conversion from mild cognitive impairment to Alzheimer's disease using brain 1 H-MRS and volumetric changes: A two- year retrospective follow-up study Micaela Mitolo, Michelangelo Stanzani-Maserati, Sabina Capellari, Claudia Testa, Paola Rucci, Roberto Poda, Federico Oppi, Roberto Gallassi, Luisa Sambati, Giovanni Rizzo, Piero Parchi, Stefania Evangelisti, Lia Talozzi, Caterina Tonona, Raffaele Lodi, Rocco Liguori, NeuroImage Clinical, 201

Prenatal stress and peripubertal stimulation of the endocannabinoid system differentially regulate emotional responses and brain metabolism in mice.

The central endocannabinoid system (ECS) and the hypothalamic-pituitary-adrenal-axis mediate individual responses to emotionally salient stimuli. Their altered developmental adjustment may relate to the emergence of emotional disturbances. Although environmental influences regulate the individual phenotype throughout the entire lifespan, their effects may result particularly persistent during plastic developmental stages (e.g. prenatal life and adolescence). Here, we investigated whether prenatal stress--in the form of gestational exposure to corticosterone supplemented in the maternal drinking water (100 mg/l) during the last week of pregnancy--combined with a pharmacological stimulation of the ECS during adolescence (daily fatty acid amide hydrolase URB597 i.p. administration--0.4 mg/kg--between postnatal days 29-38), influenced adult mouse emotional behaviour and brain metabolism measured through in vivo quantitative magnetic resonance spectroscopy. Compared to control mice, URB597-treated subjects showed, in the short-term, reduced locomotion and, in the long term, reduced motivation to execute operant responses to obtain palatable rewards paralleled by reduced levels of inositol and taurine in the prefrontal cortex. Adult mice exposed to prenatal corticosterone showed increased behavioural anxiety and reduced locomotion in the elevated zero maze, and altered brain metabolism (increased glutamate and reduced taurine in the hippocampus; reduced inositol and N-Acetyl-Aspartate in the hypothalamus). Present data further corroborate the view that prenatal stress and pharmacological ECS stimulation during adolescence persistently regulate emotional responses in adulthood. Yet, whilst we hypothesized these factors to be interactive in nature, we observed that the consequences of prenatal corticosterone administration were independent from those of ECS drug-induced stimulation during adolescence

The impact of functional connectivity on behaviour: insight from the Welsh Advanced Neuroimaging Database

The impact of functional connectivity on behaviour: insight from the Welsh Advanced Neuroimaging Database Functional connectivity, which impacts all brain functions including cognition, can be assessed using resting-state functional magnetic resonance imaging (rsfMRI). This non-invasive technique provides high spatial resolution for evaluating brain connectivity. Loss of functional connectivity often occurs in neurological diseases and can precede measurable brain atrophy. We present preliminary results from the Welsh Advanced Neuroimaging Database (WAND), which aims to generate a comprehensive description of brain coupling across multiple domains. WAND includes data on macro- and micro-structural, functional, metabolic, chemical, and behavioural measures from a large population of healthy participants aged 18-65 years. In this study, we analyze rsfMRI data from a subset of 103 participants in the WAND study. Eyes-open rsfMRI data were acquired on a Siemen’s 3T Prisma scanner, with repetition time=2000ms, echo time=30ms and multiband factor=4. Physiological data such as heart rate and respiration were monitored during the scan. Data processing and analysis were performed using SPM, the PhysIO package, fMRIprep and FSL. Motion and physiological noise parameters were estimated for each participant. Noise regressors were used to remove physiological noise from the data following preprocessing with fMRIprep. Group ICA was used to reconstruct the main resting-state networks, and subject-specific network maps were obtained using dual regression. The relationship between the resting-state networks and behavioural data will be assessed using FSL’s randomise. Although the analysis is still ongoing, we have successfully identified physiological noise regressors for all participants. We anticipate finding significant associations between functional connectivity and age, as well as with behavioural test results

How functional connectivity influences behaviour: a study from the Welsh Advanced Neuroimaging Database

How functional connectivity influences behaviour: a study from the Welsh Advanced Neuroimaging Database Functional connectivity, which impacts all brain functions including cognition, can be assessed using resting-state functional magnetic resonance imaging (rsfMRI). This non-invasive technique provides high spatial resolution for evaluating brain connectivity. Loss of functional connectivity often occurs in neurological diseases and can precede measurable brain atrophy. We present preliminary results from the Welsh Advanced Neuroimaging Database (WAND), which aims to generate a comprehensive description of brain coupling across multiple domains. WAND includes data on macro- and micro-structural, functional, metabolic, chemical, and behavioural measures from a large population of healthy participants aged 18-65 years. In this study, we analyze rsfMRI data from a subset of 103 participants in the WAND study. Eyes-open rsfMRI data were acquired on a Siemen’s 3T Prisma scanner, with repetition time=2000ms, echo time=30ms and multiband factor=4. Physiological data such as heart rate and respiration were monitored during the scan. Data processing and analysis were performed using SPM, the PhysIO package, fMRIprep and FSL. Motion and physiological noise parameters were estimated for each participant. Noise regressors were used to remove physiological noise from the data following preprocessing with fMRIprep. Group ICA was used to reconstruct the main resting-state networks, and subject-specific network maps were obtained using dual regression. The relationship between the resting-state networks and behavioural data will be assessed using FSL’s randomise. Although the analysis is still ongoing, we have successfully identified physiological noise regressors for all participants. We anticipate finding significant associations between functional connectivity and age, as well as with behavioural test results