Disentangling the intrinsic relaxivities of highly purified graphene oxide.

The chemistry of contrast agents (CAs) for magnetic resonance imaging (MRI) applications is an active area of research and, in recent work, it was shown that CA-based graphene oxide (GO) has valuable properties for biomedical uses. GO has a potential as MRI CAs thanks to several functionalities, like its ability to penetrate tissues and cell membranes, as well as easy coupling with therapeutic agents, therefore showing the potential for both a diagnostic and therapeutic role. In this study, we performed a thorough cleaning of the GO sample (synthesized using a modified Hummers method), minimizing the amount of residual manganese down to 73 ppm. Using a wide range of physical-chemical methods (morphology, chemical composition, elemental analysis, spectroscopies, and imaging), we characterized the intrinsic longitudinal and transverse relaxivities of highly purified GO nanosheets. X-band electron paramagnetic resonance allowed to recognize the paramagnetic species involved, and 1.0 T MRI was used to disentangle the relative contributions to the MRI contrast of pristine GO nanosheets arising from structural defects and residual paramagnetic manganese impurities embedded in the nanomaterial. Although experiments show that the MRI relaxivity of GO nanosheets arises from the cumulative effect of structural defects and paramagnetic impurities, we conclude that the latter contribution to the longitudinal and transverse relaxivities becomes irrelevant for highly purified (pristine) GO. This novel finding clearly demonstrates that, apart from trivial manganese inclusion, pristine GO produces an inherent MRI response via structural defects, and therefore it is on its own a suitable candidate as MRI contrast agent.

Dual-Channel Transverse Fields Radiofrequency Coils for 1.5 T Magnetic Resonance Imaging.

This theoretical study presents the design and analytical/numerical optimization of novel dual-channel transverse fields radiofrequency (RF) surface coils for 1.5 T Magnetic Resonance Imaging (MRI). The research explores a planar setup with two channels on a row with aligned spatial orientation of the RF coils, aiming to solve a common design drawback of single-channel transverse field RF coils: the reduced Field Of View (FOV) along the direction of the RF field. A significant challenge in this design is the efficient decoupling of two sets of transverse field RF coils to prevent mutual interference. Our modeling approach integrates thin wire theoretical modeling, magnetostatic computation for strip conductor coils, and their full-wave electromagnetic simulation. Key findings at 64 MHz demonstrate that strategic geometric placement among the two-channel RF coil and the introduction of geometrical asymmetry in the design of the individual RF coils does minimize the mutual inductance, paving the way for effective dual-channel MRI applications. This decoupling approach allows to enhance the FOV, providing a theoretical framework for the development of optimized dual-channel transverse field RF coil configurations. The current design was validated with full-wave numerical study at 64 MHz (1H, 1.5 T), has the potential to be extended at lower or higher frequencies, and the presence of lossy samples needs to be considered in the latter case.

Magnetostatic Simulation and Design of Novel Radiofrequency Coils Based on Transverse Field Current Elements for Magnetic Resonance Applications.

Radiofrequency (RF) coils are key components in Magnetic Resonance (MR) systems and can be categorized into volume and surface coils according to their shapes. Volume RF coils can generate a uniform field in a large central sample's region, while surface RF coils, usually smaller than volume coils, typically have a higher Signal-to-Noise Ratio (SNR) in a reduced Region Of Interest (ROI) close to the coil plane but a relatively poorer field homogeneity. Circular and square loops are the simplest and most used design for developing axial field surface RF coils. However, for specific MR applications, the use of dedicated transverse field RF coils can be necessary or advantageous. Building on a previously developed and validated RF coil simulator, based on the magnetostatic approach, here we explore the potential applications of novel multiple axial field and transverse field surface RF coils in non-standard configurations. We demonstrate via numerical simulations that simple volume RF coils, matching a Helmholtz-like design, can be built with two identical transverse field RF coils separated by a given distance. Following well-known principles, the SNR of such novel configurations can be improved by a factor of up to √2 by combining two 90° rotated coils, producing, inside a central ROI, a circularly polarized B1 field.

Comparison between Tail Suspension Swing Test and Standard Rotation Test in Revealing Early Motor Behavioral Changes and Neurodegeneration in 6-OHDA Hemiparkinsonian Rats.

The unilateral 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD) is one of the most commonly used in rodents. The anatomical, metabolic, and behavioral changes that occur after severe and stable 6-OHDA lesions have been extensively studied. Here, we investigated whether early motor behavioral deficits can be observed in the first week after the injection of 6-OHDA into the right substantia nigra pars compacta (SNc), and if they were indicative of the severity of the dopaminergic (DAergic) lesion in the SNc and the striatum at different time-points (day 1, 3, 5, 7, 14, 21). With this aim, we used our newly modified tail suspension swing test (TSST), the standard rotation test (RT), and immunohistochemical staining for tyrosine hydroxylase (TH). The TSST, but not the standard RT, revealed a spontaneous motor bias for the 6-OHDA-lesioned rats from the day 1 post-surgery. Both tests detected the motor asymmetry induced by (single and repeated) apomorphine (APO) challenges that correlated, in the first week, with the DAergic neuronal degeneration. The described TSST is fast and easy to perform, and in the drug-free condition is useful for the functional assessment of early motor asymmetry appearing after the 6-OHDA-lesion in the SNc, without the confounding effect of APO challenges.

PPARß/δ and γ in a rat model of Parkinson's disease: possible involvement in PD symptoms.

Parkinson's disease is one of the most common neurologic disorder, affecting about 1-4% of persons older than 60 years. Among the proposed mechanisms of PD generation, free radical damage is believed to play a pivotal role in the development and/or progression of the disease. Recently, PPARs, a class of transcription factors involved in several pathways both in physiological and pathological conditions, have been linked by us and others to neurodegeneration. Particularly, PPARγ and its ligands have been indicated as potential therapeutic targets for the treatment of several pathological conditions associated with neuroinflammation within the CNS. The anti-inflammatory function of PPARγ has attracted attention since agonists exert a broad spectrum of protective effects in several animal models of neurological diseases, including psychiatric diseases. On the other hand a detrimental role for PPARß/δ has been proposed in Alzheimer, being closely related to the decrease of BDNF and Trkfl. On these bases, in this work we used a 6-OHDA hemi-lesioned rat model, inducing loss of dopaminergic neurons, to study the effects of the lesion at three time points from the lesion (1, 2, and 3 weeks), in relevant areas of PD motor symptoms, such as substantia nigra and globus pallidus and in the area of reward and mood control, the nucleus accumbens. In particular, it was studied: (i) the expression of BDNF and its downstream signals; (ii) the modulation of PPARs levels. The results obtained indicate the possible use of a dual PPARß/δ antagonist/PPARγ agonist to counteract primary and secondary signs of PD neurodegeneration.

Point-Of-Care low-field MRI in acute Stroke (POCS): protocol for a multicentric prospective open-label study evaluating diagnostic accuracy.

INTRODUCTION: Fast and accurate diagnosis of acute stroke is crucial to timely initiate reperfusion therapies. Conventional high-field (HF) MRI yields the highest accuracy in discriminating early ischaemia from haemorrhages and mimics. Rapid access to HF-MRI is often limited by contraindications or unavailability. Low-field (LF) MRI (<0.5T) can detect several types of brain injury, including ischaemic and haemorrhagic stroke. Implementing LF-MRI in acute stroke care may offer several advantages, including extended applicability, increased safety, faster administration, reduced staffing and costs. This multicentric prospective open-label trial aims to evaluate the diagnostic accuracy of LF-MRI, as a tool to guide treatment decision in acute stroke. METHODS AND ANALYSIS: Consecutive patients accessing the emergency department with suspected stroke dispatch will be recruited at three Italian study units: Azienda Sanitaria Locale (ASL) Abruzzo 1 and 2, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital. The estimated sample size is 300 patients. Anonymised clinical and LF-MRI data, along with conventional neuroimaging data, will be independently assessed by two external units: Marche Polytechnic University and 'G. Martino' Polyclinic University Hospital. Both units will independently adjudicate the best treatment option, while the latter will provide historical HF-MRI data to develop artificial intelligence algorithms for LF-MRI images interpretation (Free University of Bozen-Bolzano). Agreement with conventional neuroimaging will be evaluated at different time points: hyperacute, acute (24 hours), subacute (72 hours), at discharge and chronic (4 weeks). Further investigations will include feasibility study to develop a mobile stroke unit equipped with LF-MRI and cost-effectiveness analysis. This trial will provide necessary data to validate the use of LF-MRI in acute stroke care. ETHICS AND DISSEMINATION: The study was approved by the Research Ethics Committee of the Abruzzo Region (CEtRA) on 11 May 2023 (approval code: richyvgrg). Results will be disseminated in peer-reviewed journals and presented in academic conferences. TRIAL REGISTRATION NUMBER: NCT05816213; Pre-Results.

Numerical and Workbench Design of 2.35 T Double-Tuned (¹H/²³Na) Nested RF Birdcage Coils Suitable for Animal Size MRI.

The birdcage Radio Frequency (RF) coil is one of the most used configurations in Magnetic Resonance Imaging (MRI) scanners for the detection of the proton (1H) signal over a large homogeneous volume. More recently, birdcage RF coils have been successfully used also in the field of X-nuclei MRI, where the signal of a second nucleus (e.g. 13C, 23Na, 31P, and many others) needs to be detected with high sensitivity and spatial homogeneity. To this purpose several technical solutions have been adopted to design Double Tuned (DT) volume RF coils, including the recent configuration of the nested birdcage RF coils. One of the main problems in the design of DT RF coils is the decoupling between the 1H and X channels, and a number of solutions have been adopted over the years. In this work, based on numerical and workbench methods, we report the decoupling optimization of DT (1H/23Na) nested RF birdcage coils suitable for 2.35 T MRI scanners encompassing an inner Low-Pass (LP) birdcage used for X-nuclei, an outer High-Pass (HP) birdcage for 1H and an external cylindrical RF shield. We show that a suitable geometrical selection of the two coaxial RF birdcage coils (relative angular orientation, diameters and lengths) and RF shield (diameter, length) allows a significant decoupling optimization. We also provide valuable information about the RF B1+ field homogeneity and efficiency. Our approach was validated both with numerical simulations and workbench testing using DT nested RF coil prototypes.

Design of Distributed Spiral Resonators for the Decoupling of MRI Double-Tuned RF Coils.

OBJECTIVE: A systematic analytical approach to design Spiral Resonators (SRs), acting as distributed magnetic traps (DMTs), for the decoupling of concentric Double-Tuned (DT) RF coils suitable for Ultra-High Field (7 T) MRI is presented. METHODS: The design is based on small planar SRs placed in between the two RF loops (used for signal detection of the two nuclei of interest). We developed a general framework based on a fully analytical approach to estimate the mutual coupling between the RF coils and to provide design guidelines for the geometry and number of SRs to be employed. Starting from the full-analytical estimations of the SRs geometry, electromagnetic simulations for improving and validating the performance can be carried out. RESULTS AND CONCLUSION: We applied the method to a test case of a DT RF coil consisting of two concentric and coplanar loops used for 7 T MRI, tuned at the Larmor frequencies of the proton (1H, 298 MHz) and sodium (23Na, 79 MHz) nuclei, respectively. We performed numerical simulations and experimental measurements on fabricated prototypes, which both demonstrated the effectiveness of the proposed design procedure. SIGNIFICANCE: The decoupling is achieved by printing the SRs on the same dielectric substrate of the RF coils thus allowing a drastic simplification of the fabrication procedure. It is worth noting that there are no physical connections between the decoupling SRs and the 1H/23Na RF coils, thus providing a mechanically robust experimental set-up, and improving the transceiver design with respect to other traditional decoupling techniques.

Effects of Substantia Nigra pars compacta lesion on the behavioral sequencing in the 6-OHDA model of Parkinson's disease.

The basal ganglia circuitry plays a crucial role in the sequential organization of behavior. Here we studied the behavioral structure of the animals after 21 days of 6-OHDA-induced lesion of the dopaminergic nigrostriatal system. Frequencies and durations of individual components of the behavioral repertoire were calculated; moreover, whether a temporal organization of the activity was present, it was investigated by using T-pattern analysis, a multivariate approach able to detect the real-time sequential organization of behavior. Six sham-depleted and six rats with unilateral 6-OHDA-lesion of the Substantia Nigra pars compacta were used. As to quantitative evaluations, the comparison between lesioned and unlesioned rats revealed significant differences only for the mean occurrences of Walking, Immobile Sniffing and Stretched Sniffing, reduced in lesioned subjects. All the remaining components of the behavior did not show significant changes. On the other hand, results from T-pattern analysis showed a reduction of the number of different T-patterns, of their mean length and of their occurrences in 6-OHDA-lesioned rats. Overall, these results suggest that the main deficit in 6-OHDA-lesioned subjects, rather than in the production of individual behavioral components, lies in deficiencies of their sequential organization.

The Basal Ganglia: More than just a switching device.

The basal ganglia consist of a variety of subcortical nuclei engaged in motor control and executive functions, such as motor learning, behavioral control, and emotion. The striatum, a major basal ganglia component, is particularly useful for cognitive planning of purposive motor acts owing to its structural features and the neuronal circuitry established with the cerebral cortex. Recent data indicate emergent functions played by the striatum. Indeed, cortico-striatal circuits carrying motor information are paralleled by circuits originating from associative and limbic territories, which are functionally integrated in the striatum. Functional integration between brain areas is achieved through patterns of coherent activity. Coherence belonging to cortico-basal ganglia circuits is also present in Parkinson's disease patients. Excessive synchronization occurring in this pathology is reduced by dopaminergic therapies. The mechanisms through which the dopaminergic effects may be addressed are the object of several ongoing investigations. Overall, the bulk of data reported in recent years has provided new vistas concerning basal ganglia role in the organization and control of movement and behavior, both in physiological and pathological conditions. In this review, basal ganglia functions involved in the organization of main movement categories and behaviors are critically discussed. Comparatively, the multiplicity of Parkinson's disease symptomatology is also revised.

Sequential, co-registered fluorine and proton field-cycled Overhauser imaging at a detection field of 59 mT.

In this work we show the feasibility of sequential, co-registered fluorine and proton field-cycled Overhauser imaging at a detection field of 59 mT. To this purpose we have built an RF coil assembly comprising an Alderman-Grant resonator for EPR irradiation at 127.7 MHz (evolution field of 4.5 mT) and a solenoidal coil for (19)F or (1)H MRI acquisition at the detection field of 59 mT. A removable tuning/matching circuit that allows the solenoid to be tuned to the (19)F frequency (2.346 MHz, FEDRI) or the (1)H frequency (2.494 MHz, PEDRI) without removing the sample was built and tested. Switching of the solenoid between the (19)F and (1)H frequency is thus achieved in less than 1 min. The co-registered FC-FEDRI and FC-PEDRI images show higher enhancement in the sample regions with higher free radical concentration. This work is the first methodological step towards the development of an MRI scanner capable of acquiring morphological ((1)H) and physiological ((19)F) images in animal models at very low fields.

Targeting CXCR1 on breast cancer stem cells: signaling pathways and clinical application modelling.

In breast cancer it has been proposed that the presence of cancer stem cells may drive tumor initiation, progression and recurrences. IL-8, up-regulated in breast cancer, and associated with poor prognosis, increases CSC self-renewal in cell line models. It signals via two cell surface receptors, CXCR1 and CXCR2. Recently, the IL-8/CXCR1 axis was proposed as an attractive pathway for the design of specific therapies against breast cancer stem cells. Reparixin, a powerful CXCR1 inhibitor, was effective in reducing in vivo the tumour-initiating population in several NOD/SCID mice breast cancer models, showing that the selective targeting of CXCR1 and the combination of reparixin and docetaxel resulted in a concomitant reduction of the bulk tumour mass and CSC population. The available data indicate that IL-8, expressed by tumour cells and induced by chemotherapeutic treatment, is a key regulator of the survival and self-renewal of the population of CXCR1-expressing CSC. Consequently, this investigation on the mechanism of action of the reparixin/paclitaxel combination, was based on the observation that reparixin treatment contained the formation of metastases in several experimental models. However, specific data on the formation of breast cancer brain metastases, which carry remarkable morbidity and mortality to a substantial proportion of advanced breast cancer patients, have not been generated. The obtained data indicate a beneficial use of the drug combination reparixin and paclitaxel to counteract brain tumour metastasis due to CSC, probably due to the combined effects of the two drugs, the pro-apoptotic action of paclitaxel and the cytostatic and anti-migratory effects of reparixin.

An open volume, high isolation, radio frequency surface coil system for pulsed magnetic resonance.

We present an open volume, high isolation, RF system suitable for pulsed NMR and EPR spectrometers with reduced dead time. It comprises a set of three RF surface coils disposed with mutually parallel RF fields and a double-channel receiver (RX). Theoretical and experimental results obtained with a prototype operating at about 100 MHz are reported. Each surface RF coil (diameter 5.5 cm) was tuned to f0=100.00+/-0.01 MHz when isolated. Because of the mutual coupling and the geometry of the RF coils, only two resonances at f1=97.94 MHz and f2=101.85 MHz were observed. We show they are associated with two different RF field spatial distributions. In continuous mode (CW) operation the isolation between the TX coil and one of the RX coils (single-channel) was about -10 dB. By setting the double-channel RF assembly in subtraction mode the isolation values at f1 or f2 could be optimised to about -75 dB. Following a TX RF pulse (5 micros duration) an exponential decay with time constant of about 600 ns was observed. The isolation with single-channel RX coil was about -11 dB and it increased to about -47 dB with the double-channel RX in subtraction mode. Similar results were obtained with the RF pulse frequency selected to f2 and also with shorter (500 ns) RF pulses. The above geometrical parameters and operating frequency of the RF assembly were selected as a model for potential applications in solid state NMR and in free radical EPR spectroscopy and imaging.

Post-processing noise removal algorithm for magnetic resonance imaging based on edge detection and wavelet analysis.

A post-processing noise suppression technique for biomedical MRI images is presented. The described procedure recovers both sharp edges and smooth surfaces from a given noisy MRI image; it does not blur the edges and does not introduce spikes or other artefacts. The fine details of the image are also preserved. The proposed algorithm first extracts the edges from the original image and then performs noise reduction by using a wavelet de-noise method. After the application of the wavelet method, the edges are restored to the filtered image. The result is the original image with less noise, fine detail and sharp edges. Edge extraction is performed by using an algorithm based on Sobel operators. The wavelet de-noise method is based on the calculation of the correlation factor between wavelet coefficients belonging to different scales. The algorithm was tested on several MRI images and, as an example of its application, we report the results obtained from a spin echo (multi echo) MRI image of a human wrist collected with a low field experimental scanner (the signal-to-noise ratio, SNR, of the experimental image was 12). Other filtering operations have been performed after the addition of white noise on both channels of the experimental image, before the magnitude calculation. The results at SNR = 7, SNR = 5 and SNR = 3 are also reported. For SNR values between 5 and 12, the improvement in SNR was substantial and the fine details were preserved, the edges were not blurred and no spikes or other artefacts were evident, demonstrating the good performances of our method. At very low SNR (SNR = 3) our result is worse than that obtained by a simpler filtering procedure.

First imaging results obtained with a multimodal apparatus combining low-field (35.7 mT) MRI and pulsed EPRI.

Nuclear magnetic resonance imaging (MRI) provides excellent images of organs and is an essential diagnostic tool in the medical field. Electron paramagnetic resonance imaging (EPRI) is being increasingly used in the biomedical field because of recent hardware advances. We present the first images obtained with a low-field (35.7 mT) multimodal apparatus that combines MRI and pulsed EPRI. For this purpose, the sample is composed of two sections, one sensitive to MRI and the other sensitive to EPRI. The MRI section of the sample is composed of three tubes containing 7 ml of a 10 mM CuSO4 water solution. The EPR section of the sample is composed of two tubes containing 350 mg of lithium phthalocyanine. The EPR image represents the two-dimensional projection of the whole sample and is reconstructed from 32 one-dimensional projections by using the Fourier reconstruction method. The MRI image is obtained by selecting a sample slice, 10 mm in thickness, by using a spin-echo sequence and the two-dimensional fast Fourier transform. The experimental results obtained with this apparatus show that the spatial resolution is better than 1 mm for the MRI section and better than 7 mm for the EPRI section. The measured SNR of the MRI and EPRI images were about 60 and 160, respectively. A detailed description of the hardware, pulse sequences and image reconstruction techniques is reported.

A general algorithm for magnetic resonance imaging simulation: a versatile tool to collect information about imaging artefacts and new acquisition techniques.

An innovative algorithm for Magnetic Resonance Imaging (MRI) capable of demonstrating the source of various artefacts and driving the hardware and software acquisition process is presented. The algorithm is based on the application of the Bloch equations to the magnetization vector of each point of the simulated object, as requested by the instructions of the MRI pulse sequence. The collected raw data are then used to reconstruct the image of the object. The general structure of the algorithm makes it possible to simulate a great range of imaging situations in order to explain the nature of unwanted artefacts and to study new acquisition techniques. The way the algorithm structures the sequence has also allowed the easy implementation of MRI data acquisition on a commercial general-purpose DSP-based data acquisition board, thus facilitating the comparison between simulated and experimental results.

Switching ability of over trained movements in a Parkinson's disease rat model.

Patients with Parkinson's disease show unbalanced capability to manage self-paced vs externally driven movements, or automatic-associated movements with respect to the intended voluntary movements. We studied the effect of a selective loss of dopaminergic terminals within the striatum and the execution of a well-learned set-shifting task as revealed using tyrosine hydroxylase immunoreactivity and magnetic resonance imaging in the rat. We found that, both in the externally cued condition, and in the externally-internally driven switching task, the cue-dependent constraints interfered with motor readiness in over training condition. The unilateral dopaminergic striatal depletion enhanced the switch-induced performance differences in favour of the internally-externally cued transition. Dopamine depleted rats, in fact, were impaired to produce an alternative motion when task switching required to change from an over trained behaviour, towards an alternative self-paced response. The comparative analysis of behavioural, tyrosine hydroxylase immunoreactivity and magnetic resonance imaging data, revealed a shrinkage of the lesioned striatum, and an enlargement of the ipsilateral ventricle that could provide useful markers for monitoring pathological changes occurring during early stages of Parkinson's disease in vivo.

Characterization and reduction of gradient-induced eddy currents in the RF shield of a TEM resonator.

Radiofrequency (RF) shields that surround MRI transmit/receive coils should provide effective RF screening, without introducing unwanted eddy currents induced by gradient switching. Results are presented from a detailed examination of an effective RF shield design for a prototype transverse electromagnetic (TEM) resonator suitable for use at 3 Tesla. It was found that effective RF shielding and low eddy current sensitivity could be achieved by axial segmentation (gap width = 2.4 mm) of a relatively thick (35 microm) copper shield, etched on a kapton polyimide substrate. This design has two main advantages: first, it makes the TEM less sensitive to the external environment and RF interference; and second, it makes the RF shield mechanically robust and easy to handle and assemble.

Theoretical and experimental evaluation of detached endcaps for 3 T birdcage coils.

The use of detached endcaps for 3 T birdcage coils was investigated both theoretically and experimentally. Finite difference time domain analysis, along with workbench and MRI techniques, were used to map the radiofrequency (RF) B(1) distribution along the coil axis with and without an endcap. Without an endcap the measured B(1) value at the service end of the birdcage was only 45% of the value at the coil's center. This was improved to 85% with a detached endcap of maximum achievable diameter (375 mm), positioned 4 mm from the RF shield. The B(1) field distribution on the patient side of the coil was unaffected by the presence of the endcap. The dependence of the B(1) distribution as a function of endcap diameter was also investigated. Surprisingly, simulations and experiments show that there is an optimum ratio of endcap-to-birdcage coil diameter (approximately 1.08) that gives the best B(1) homogeneity. In the human head the optimized endcap, positioned 16 mm from the RF shield, improves the MRI signal amplitude from 55% to 85% of maximum toward the service end. This novel endcap design is easy to implement with existing birdcage coils, and could prove useful when flexibility in access to the RF coil is required.