Disrupted autonomic pathways in spinal cord injury: Implications for the immune regulation.

Spinal Cord Injury (SCI) disrupts critical autonomic pathways responsible for the regulation of the immune function. Consequently, individuals with SCI often exhibit a spectrum of immune dysfunctions ranging from the development of damaging pro-inflammatory responses to severe immunosuppression. Thus, it is imperative to gain a more comprehensive understanding of the extent and mechanisms through which SCI-induced autonomic dysfunction influences the immune response. In this review, we provide an overview of the anatomical organization and physiology of the autonomic nervous system (ANS), elucidating how SCI impacts its function, with a particular focus on lymphoid organs and immune activity. We highlight recent advances in understanding how intraspinal plasticity that follows SCI may contribute to aberrant autonomic activity in lymphoid organs. Additionally, we discuss how sympathetic mediators released by these neuron terminals affect immune cell function. Finally, we discuss emerging innovative technologies and potential clinical interventions targeting the ANS as a strategy to restore the normal regulation of the immune response in individuals with SCI.

Repeatability of Open-MOLLI: An open-source inversion recovery myocardial T1 mapping sequence for fast prototyping.

PURPOSE: To develop an open-source prototype of myocardial T1 mapping (Open-MOLLI) to improve accessibility to cardiac T1 mapping and evaluate its repeatability. With Open-MOLLI, we aim to enable faster implementation and testing of sequence modifications and to facilitate inter-scanner and cross-vendor reproducibility studies. METHODS: Open-MOLLI is an inversion-recovery sequence using a balanced SSFP (bSSFP) readout, with inversion and triggering schemes based on the 5(3)3 MOLLI sequence, developed in Pulseq. Open-MOLLI and MOLLI sequences were acquired in the ISMRM/NIST phantom and 21 healthy volunteers. In 18 of those subjects, Open-MOLLI and MOLLI were repeated in the same session (test-retest). RESULTS: Phantom T1 values were comparable between methods, specifically for the vial with reference T1 value most similar to healthy myocardium T1 (T1vial3 = 1027 ms): T1MOLLI = 1011 ± 24 ms versus T1Open-MOLLI = 1009 ± 20 ms. In vivo T1 estimates were similar between Open-MOLLI and MOLLI (T1MOLLI = 1004 ± 33 ms vs. T1Open-MOLLI = 998 ± 52 ms), with a mean difference of -17 ms (p = 0.20), despite noisier Open-MOLLI weighted images and maps. Repeatability measures were slightly higher for Open-MOLLI (RCMOLLI = 3.0% vs. RCOpen-MOLLI = 4.4%). CONCLUSION: The open-source sequence Open-MOLLI can be used for T1 mapping in vivo with similar mean T1 values to the MOLLI method. Open-MOLLI increases the accessibility to cardiac T1 mapping, providing also a base sequence to which further improvements can easily be added and tested.

Impact of truncating diffusion MRI scans on diffusional kurtosis imaging.

OBJECTIVE: Diffusional kurtosis imaging (DKI) extends diffusion tensor imaging (DTI), characterizing non-Gaussian diffusion effects but requires longer acquisition times. To ensure the robustness of DKI parameters, data acquisition ordering should be optimized allowing for scan interruptions or shortening. Three methodologies were used to examine how reduced diffusion MRI scans impact DKI histogram-metrics: 1) the electrostatic repulsion model (OptEEM); 2) spherical codes (OptSC); 3) random (RandomTRUNC). MATERIALS AND METHODS: Pre-acquired diffusion multi-shell data from 14 female healthy volunteers (29±5 years) were used to generate reordered data. For each strategy, subsets containing different amounts of the full dataset were generated. The subsampling effects were assessed on histogram-based DKI metrics from tract-based spatial statistics (TBSS) skeletonized maps. To evaluate each subsampling method on simulated data at different SNRs and the influence of subsampling on in vivo data, we used a 3-way and 2-way repeated measures ANOVA, respectively. RESULTS: Simulations showed that subsampling had different effects depending on DKI parameter, with fractional anisotropy the most stable (up to 5% error) and radial kurtosis the least stable (up to 26% error). RandomTRUNC performed the worst while the others showed comparable results. Furthermore, the impact of subsampling varied across distinct histogram characteristics, the peak value the least affected (OptEEM: up to 5% error; OptSC: up to 7% error) and peak height (OptEEM: up to 8% error; OptSC: up to 11% error) the most affected. CONCLUSION: The impact of truncation depends on specific histogram-based DKI metrics. The use of a strategy for optimizing the acquisition order is advisable to improve DKI robustness to exam interruptions.

Identifying subgroups in heart failure patients with multimorbidity by clustering and network analysis.

This study presents a workflow for identifying and characterizing patients with Heart Failure (HF) and multimorbidity utilizing data from Electronic Health Records. Multimorbidity, the co-occurrence of two or more chronic conditions, poses a significant challenge on healthcare systems. Nonetheless, understanding of patients with multimorbidity, including the most common disease interactions, risk factors, and treatment responses, remains limited, particularly for complex and heterogeneous conditions like HF. We conducted a clustering analysis of 3745 HF patients using demographics, comorbidities, laboratory values, and drug prescriptions. Our analysis revealed four distinct clusters with significant differences in multimorbidity profiles showing differential prognostic implications regarding unplanned hospital admissions. These findings underscore the considerable disease heterogeneity within HF patients and emphasize the potential for improved characterization of patient subgroups for clinical risk stratification through the use of EHR data.

Open-source myocardial T1 mapping with simultaneous multi-slice acceleration: Combining an auto-calibrated blipped-bSSFP readout with VERSE-MB pulses.

PURPOSE: Enabling fast and accessible myocardial T1 mapping is crucial for extending its clinical application. We introduce Open-MOLLI-SMS combining simultaneous multi-slice (SMS) with auto-calibration and variable-rate selective excitation (VERSE)-multiband pulses to obtain all slices in a fast single-shot T1 mapping sequence. METHODS: Open-MOLLI-SMS was developed by integrating SMS with the open-source method Open-MOLLI previously implemented in Pulseq. Three methods were integrated for Open-MOLLI-SMS: (1) auto-calibration blip patterns to ensure consistency between the data and coil information; (2) a blipped-balanced SSFP (bSSFP) readout to induce controlled aliasing in parallel imaging shifts without disturbing the bSSFP frequency response; and (3) a VERSE-multiband pulse for minimizing the achievable TR and the specific absortion rate (SAR) impact of SMS. Two (SMS2) or three (SMS3) slices were excited simultaneously and encoded with an in-plane acceleration factor of 2. Experiments were performed in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology phantom and five healthy volunteers. RESULTS: Phantom results show accurate T1 estimates for reference values between 400 to 2200 ms. Artifacts were visible for Open-MOLLI-SMS3 but not replicated in vivo. In vivo Open-MOLLI-SMS (T1 SMS2 = 993 ± 10 ms; T1 SMS3 = 1031 ± 17 ms) provided similar values to mean T1 single-band Open-MOLLI estimates (T1 Open-MOLLI = 1005 ± 47 ms). Open-MOLLI-SMS2 provided the closest estimates to the reference. CONCLUSION: This proof-of-principle implementation study demonstrates the feasibility of speeding up T1 -mapping acquisitions and increasing coverage by combining auto-calibration strategies with a blipped-bSFFP readout and VERSE multiband RF excitation pulses. The proposed methodology was built on the Open-MOLLI mapping sequence, which provides a fast means for prototyping and enables open-source sharing of the method.

Characterization of Functional Coatings on Cork Stoppers with Laser-Induced Breakdown Spectroscopy Imaging.

Evaluating the efficiency of surface treatments is a problem of paramount importance for the cork stopper industry. Generically, these treatments create coatings that aim to enhance the impermeability and lubrification of cork stoppers. Yet, current methods of surface analysis are typically time-consuming, destructive, have poor representativity or rely on indirect approaches. In this work, the use of a laser-induced breakdown spectroscopy (LIBS) imaging solution is explored for evaluating the presence of coating along the cylindrical surface and in depth. To test it, several cork stoppers with different shaped areas of untreated surface were analyzed by LIBS, making a rectangular grid of spots with multiple shots per spot, to try to identify the correspondent shape. Results show that this technique can detect the untreated area along with other features, such as leakage and holes, allowing for a high success rate of identification and for its performance at different depths, paving the way for future industry-grade quality control solutions with more complex surface analysis.

The Central Nervous System Source Modulates Microglia Function and Morphology In Vitro.

The regional heterogeneity of microglia was first described a century ago by Pio del Rio Hortega. Currently, new information on microglia heterogeneity throughout central nervous system (CNS) regions is being revealed by high-throughput techniques. It remains unclear whether these spatial specificities translate into different microglial behaviors in vitro. We cultured microglia isolated from the cortex and spinal cord and analyzed the effect of the CNS spatial source on behavior in vitro by applying the same experimental protocol and culture conditions. We analyzed the microglial cell numbers, function, and morphology and found a distinctive in vitro phenotype. We found that microglia were present in higher numbers in the spinal-cord-derived glial cultures, presenting different expressions of inflammatory genes and a lower phagocytosis rate under basal conditions or after activation with LPS and IFN-γ. Morphologically, the cortical microglial cells were more complex and presented longer ramifications, which were also observed in vivo in CX3CR1+/GFP transgenic reporter mice. Collectively, our data demonstrated that microglial behavior in vitro is defined according to specific spatial characteristics acquired by the tissue. Thus, our study highlights the importance of microglia as a source of CNS for in vitro studies.

Full polarization random drift compensation method for quantum communication.

Long-term quantum key distribution (QKD) using polarization encoding requires a random drift compensation method. We propose a method to compensate any state of polarization based on the quantum bit error rate (QBER) of two states from two non-orthogonal mutually unbiased bases. The proposed method does not require dedicated equipment, and through a simple but highly efficient feedback loop it compensates the polarization random drift suffered by photons while transmitted over the optical fiber quantum channel. A QBER lower than 2% was observed even considering imperfect single photon detectors. Besides, we verify a 82% secret key rate generation improvement in a finite-key size BB84 implementation for a 40 km fiber-optics quantum channel.

Probabilistic shaped 128-APSK CV-QKD transmission system over optical fibres.

In this Letter we present a discrete modulated, continuous variables quantum key distribution implementation using two probabilistically shaped, 128-symbol, amplitude and phase shift keying constellations. At Bob's detection side, a polarization diverse, true heterodyne receiver architecture is implemented for symbol recovery. We demonstrate experimentally that our system is capable of achieving security against collective attacks, while using accessible, telecom-grade material, and of functioning for an indefinitely long period of time at distances in excess of 185 km, in the asymptotic regime.

Pathophysiology and Therapeutic Approaches for Spinal Cord Injury.

Spinal cord injury (SCI) is a disabling condition that disrupts motor, sensory, and autonomic functions. Despite extensive research in the last decades, SCI continues to be a global health priority affecting thousands of individuals every year. The lack of effective therapeutic strategies for patients with SCI reflects its complex pathophysiology that leads to the point of no return in its function repair and regeneration capacity. Recently, however, several studies started to uncover the intricate network of mechanisms involved in SCI leading to the development of new therapeutic approaches. In this work, we present a detailed description of the physiology and anatomy of the spinal cord and the pathophysiology of SCI. Additionally, we provide an overview of different molecular strategies that demonstrate promising potential in the modulation of the secondary injury events that promote neuroprotection or neuroregeneration. We also briefly discuss other emerging therapies, including cell-based therapies, biomaterials, and epidural electric stimulation. A successful therapy might target different pathologic events to control the progression of secondary damage of SCI and promote regeneration leading to functional recovery.

Secret key rate of multi-ring M-APSK continuous variable quantum key distribution.

Discrete modulation continuous variable quantum key distribution (DM-CV-QKD) is highly considered in real implementations to avoid the complexity of Gaussian modulation (GM), which is optimum in terms of the key rate. DM-CV-QKD systems usually consider M-symbol phase shift keying (M-PSK) constellations. However, this type of constellation cannot reach transmission distances and key rates as high as GM, limiting the practical implementation of CV-QKD systems. Here, by considering M-symbol amplitude and phase shift keying (M-APSK) constellations, we can approximate GM. Indeed, considering finite-size effects, 4 ring 64-APSK can reach 52.0 km, only 7.2 km less than GM and 282% the maximum achievable transmission distance for 8-PSK.

Splenic sympathetic signaling contributes to acute neutrophil infiltration of the injured spinal cord.

BACKGROUND: Alterations in the immune system are a complication of spinal cord injury (SCI) and have been linked to an excessive sympathetic outflow to lymphoid organs. Still unknown is whether these peripheral immune changes also contribute for the deleterious inflammatory response mounted at the injured spinal cord. METHODS: We analyzed different molecular outputs of the splenic sympathetic signaling for the first 24 h after a thoracic compression SCI. We also analyzed the effect of ablating the splenic sympathetic signaling to the innate immune and inflammatory response at the spleen and spinal cord 24 h after injury. RESULTS: We found that norepinephrine (NE) levels were already raised at this time-point. Low doses of NE stimulation of splenocytes in vitro mainly affected the neutrophils' population promoting an increase in both frequency and numbers. Interestingly, the interruption of the sympathetic communication to the spleen, by ablating the splenic nerve, resulted in reduced frequencies and numbers of neutrophils both at the spleen and spinal cord 1 day post-injury. CONCLUSION: Collectively, our data demonstrates that the splenic sympathetic signaling is involved in the infiltration of neutrophils after spinal cord injury. Our findings give new mechanistic insights into the dysfunctional regulation of the inflammatory response mounted at the injured spinal cord.

Reversal operator to compensate polarization random drifts in quantum communications.

A quantum bit error rate (QBER) based algorithm for polarization random drift compensation is proposed. For a transmission window of 8 ms, for instance in aerial fiber installations, the algorithm overhead is below 1%. In an extreme turbulent situation, where the transmission window is as shorter as 0.8 ms, the overhead is still below 10%. Besides being able to operate smoothly, even in a very extreme situation, the algorithm overhead is also insensitive to the length of the communication system. It is upper layer protocol agnostic, and it is based on the mapping of the QBER on the Poincaré sphere. The algorithm finds the polarization reversal operator, which results in much lower overhead contrary to the blind methods currently used. The algorithm reverts the polarization random drift performing two QBER estimations and applying three rotations, at most. The uncertainty on the two QBER estimations defines an area over the sphere surface that is related with upper-layer protocols QBER threshold.

Citalopram Administration Does Not Promote Function or Histological Recovery after Spinal Cord Injury.

Citalopram is a selective serotonin reuptake inhibitor, and although widely used as an antidepressant, this drug has also demonstrated interesting repairing properties leading to motor recovery and pathology amelioration in animal models of stroke and degeneration. Here, we tested the efficacy of both 7-day and 8-week citalopram treatment in a contusive spinal cord injury (SCI) rat model. A combination of behavioral tests, histological and serum cytokine analysis was used to assess overall recovery. Despite promoting a mild reduction of inflammatory cells as well as an early, but transient increase of specific serum cytokines, citalopram administration showed no overall beneficial effects on motor performance or lesion extension. Our results do not support citalopram treatment as a therapeutic strategy for SCI.

Co-Transplantation of Adipose Tissue-Derived Stromal Cells and Olfactory Ensheathing Cells for Spinal Cord Injury Repair.

Patients suffering from spinal cord injury (SCI) still have a dismal prognosis. Despite all the efforts developed in this area, currently there are no effective treatments. Therefore, cell therapies have been proposed as a viable alternative to the current treatments used. Adipose tissue-derived stromal cells (ASCs) and olfactory ensheathing cells (OECs) have been used with promising results in different models of SCI, namely due to the regenerative properties of the secretome of the first, and the guidance capability of the second. Using an in vitro model of axonal growth, the dorsal root ganglia explants, we demonstrated that OECs induce neurite outgrowth mainly through cell-cell interactions, while ASCs' effects are strongly mediated by the release of paracrine factors. A proteomic analysis of ASCs' secretome revealed the presence of proteins involved in VEGF, PI3K, and Cadherin signaling pathways, which may be responsible for the effects observed. Then, the cotransplantation of ASCs and OECs showed to improve motor deficits of SCI-rats. Particular parameters of movement such as stepping, coordination, and toe clearance were improved in rats that received the transplant of cells, in comparison to nontreated rats. A histological analysis of the spinal cord tissues revealed that transplantation of ASCs and OECs had a major effect on the reduction of inflammatory cells close the lesion site. A slight reduction of astrogliosis was also evident. Overall, the results obtained with the present work indicate that the cotransplantation of ASCs and OECs brings important functional benefits to the injured spinal cord. Stem Cells 2018;36:696-708.

Dynamic susceptibility contrast parametric imaging using accelerated dual-contrast echo planar imaging with keyhole.

BACKGROUND: Echo planar imaging (EPI) is one of the methods of choice in dynamic susceptibility contrast MRI (DSC-MRI) because it provides a sufficient temporal resolution. However, the relatively long readout duration of EPI often imposes limitations on increased spatial coverage or the use of multiple contrasts. PURPOSE: To develop a DSC-MRI method using EPIK (EPI with keyhole) to provide dual-contrast (TE1 and TE2 ) information with a higher spatial coverage than EPI. To compare results from the community-standard EPI method and the proposed EPIK method. STUDY TYPE: Prospective. SUBJECTS: One healthy subject and 17 brain tumor patients. FIELD STRENGTH/SEQUENCE: 3 T/accelerated EPI and dual-contrast EPIK sequences. ASSESSMENT: After an initial evaluation using healthy in vivo images, the use of the proposed method for DSC-MRI was verified with brain tumor patients. The parametric images (eg, CBF and CBV) and arterial input function (AIF), obtained from both the EPI and EPIK, were compared. STATISTICAL TESTS: The ratio of AIF peak height of the proposed method to that of EPI was computed. The ratio computation was also performed for the time-to-peak (TTP) in the AIF curves. From the obtained CBF and CBV maps, the tumor-to-brain (TBR) ratio was also calculated for each imaging method and the results were compared. RESULTS: For the same temporal resolution (1.5 sec), EPIK yielded dual-contrast (TEs of 13/33 msec) with an increased spatial coverage (24 slices) and less geometric distortions than EPI; EPI provided single contrast (TE of 32 msec) with 20 slices. The obtained parametric values (eg, AIF peak, TTP, and TBR) had similar characteristics between EPI and the proposed method. DATA CONCLUSION: The dual-contrast data produced by EPIK in DSC-MRI allowed T1 -corrected parametric images without the need of second contrast injection and an enhanced estimation of the AIF. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:628-640.

Combinatorial therapies for spinal cord injury repair.

ABSTRACT: Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.

Identification of Relevant Spectral Ranges in Laser-Induced Breakdown Spectroscopy Imaging Using the Fourier Space.

Laser-induced breakdown spectroscopy (LIBS) imaging has now a well-established position in the subject of spectral imaging, leveraging multi-element detection capabilities and fast acquisition rates to support applications both at academic and technological levels. In current applications, the standard processing pipeline to explore LIBS imaging data sets revolves around identifying an element that is suspected to exist within the sample and generating maps based on its characteristic emission lines. Such an approach requires some previous expert knowledge both on the technique and on the sample side, which hinders a wider and more transparent accessibility of the LIBS imaging technique by non-specialists. To address this issue, techniques based on visual analysis or peak finding algorithms are applied on the average or maximum spectrum, and may be employed for automatically identifying relevant spectral regions. Yet, maps containing relevant information may often be discarded due to low signal-to-noise ratios or interference with other elements. In this context, this work presents an agnostic processing pipeline based on a spatial information ratio metric that is computed in the Fourier space for each wavelength and that allows for the identification of relevant spectral ranges in LIBS. The results suggest a more robust and streamlined approach to feature extraction in LIBS imaging compared with traditional inspection of the spectra, which can introduce novel opportunities not only for spectral data analysis but also in the field of data compression.

From sensor fusion to knowledge distillation in collaborative LIBS and hyperspectral imaging for mineral identification.

Multimodal spectral imaging offers a unique approach to the enhancement of the analytical capabilities of standalone spectroscopy techniques by combining information gathered from distinct sources. In this manuscript, we explore such opportunities by focusing on two well-known spectral imaging techniques, namely laser-induced breakdown spectroscopy, and hyperspectral imaging, and explore the opportunities of collaborative sensing for a case study involving mineral identification. In specific, the work builds upon two distinct approaches: a traditional sensor fusion, where we strive to increase the information gathered by including information from the two modalities; and a knowledge distillation approach, where the Laser Induced Breakdown spectroscopy is used as an autonomous supervisor for hyperspectral imaging. Our results show the potential of both approaches in enhancing the performance over a single modality sensing system, highlighting, in particular, the advantages of the knowledge distillation framework in maximizing the potential benefits of using multiple techniques to build more interpretable models and paving for industrial applications.

Assessing Different Histological Preparations for Reconstruction of Astrocyte Tridimensional Structure.

Astrocytes are ubiquitous in the brain and spinal cord and display a complex morphology important for the local interactions with neighboring cells, resulting in the modulation of circuit function. Thus, studies focusing on astrocyte physiology in the healthy and diseased brain generally present analyses of astrocytic structure. The labeling method used to visualize the astrocytic structure defines the morphological level to observe and may vary depending on the anatomical sub-regions. The method choice may significantly affect our understanding of their structural diversity. The main goal of this work was to identify a straightforward and efficient protocol for labeling and reconstructing a detailed astrocytic structure to apply and validate in different brain tissue preparations across laboratories. For that, we explored different tissue processing protocols before GFAP labeling to determine the most effective method for reconstructing astrocytic backbones in the mouse hippocampus. Our results show that the reconstruction of astrocytic structure in vibratome sections labeled by free-floating immunofluorescence protocol provides a more practical method to achieve a higher level of detail and arbor complexity in astrocyte backbone reconstruction. Free-floating immunofluorescence labeling is the most reliable method for obtaining better antibody penetration and more detailed astrocyte structure. Finally, we also show that introducing an antigen retrieval step appears useful for visualizing more complete structural details.