Reduced dose helical CT scout imaging on next generation wide volume CT system decreases scan length and overall radiation exposure.

Purpose: Traditional CT acquisition planning is based on scout projection images from planar anterior-posterior and lateral projections where the radiographer estimates organ locations. Alternatively, a new scout method utilizing ultra-low dose helical CT (3D Landmark Scan) offers cross-sectional imaging to identify anatomic structures in conjunction with artificial intelligence based Anatomic Landmark Detection (ALD) for automatic CT acquisition planning. The purpose of this study is to quantify changes in scan length and radiation dose of CT examinations planned using 3D Landmark Scan and ALD and performed on next generation wide volume CT versus examinations planned using traditional scout methods. We additionally aim to quantify changes in radiation dose reduction of scans planned with 3D Landmark Scan and performed on next generation wide volume CT. Methods: Single-center retrospective analysis of consecutive patients with prior CT scan of the same organ who underwent clinical CT using 3D Landmark Scan and automatic scan planning. Acquisition length and dose-length-product (DLP) were collected. Data was analyzed by paired t-tests. Results: 104 total CT examinations (48.1 % chest, 15.4 % abdomen, 36.5 % chest/abdomen/pelvis) on 61 individual consecutive patients at a single center were retrospectively analyzed. 79.8 % of scans using 3D Landmark Scan had reduction in acquisition length compared to the respective prior acquisition. Median acquisition length using 3D Landmark Scan was 26.7 mm shorter than that using traditional scout methods (p < 0.001) with a 23.3 % median total radiation dose reduction (245.6 (IQR 150.0-400.8) mGy cm vs 320.3 (IQR 184.1-547.9) mGy cm). CT dose index similarly was overall decreased for scans planned with 3D Landmark and ALD and performed on next generation CT versus traditional methods (4.85 (IQR 3.8-7) mGy vs. 6.70 (IQR 4.43-9.18) mGy, respectively, p < 0.001). Conclusion: Scout imaging using reduced dose 3D Landmark Scan images and Anatomic Landmark Detection reduces acquisition range in chest, abdomen, and chest/abdomen/pelvis CT scans. This technology, in combination with next generation wide volume CT reduces total radiation dose.

Estimating Disability in Patients with Essential Tremor: Comparison of Tremor Rating Scale, Spiral Drawing, and Accelerometric Tremor Power.

BACKGROUND: Although performance rating scales, spiral drawing, water pouring, and accelerometry are commonly used to assess tremor severity, the extent to which their results correlate with impairment in activities of daily living (ADL) remains unclear. OBJECTIVE: The aim was to identify the most effective predictors of ADL in essential tremor (ET). METHODS: Forty ET patients were examined using The Essential Tremor Rating Assessment Scale (TETRAS), spiral drawing, volume of water spilled, and accelerometric tremor power. Root-mean-square error, R2, and F-test were calculated for models predicting TETRAS ADL subscore. RESULTS: TETRAS Performance Subscale explained the variability in TETRAS ADL with an R2 value of 0.686. Models incorporating spiral rating and accelerometric tremor power (R2 = 0.731) and water spillage volume (R2 = 0.756) were not statistically superior. CONCLUSIONS: TETRAS performance subscore predicted nearly 70% ADL impairment in ET patients. Incorporating the spiral rating, accelerometric tremor power, and water pouring test did not enhance ADL estimation.

Patient radiation risk reduction by controlling the tube start angle in single and dual source spiral CT scans: A simulation study.

BACKGROUND: Organ doses in spiral CT scans depend on the tube start angle. PURPOSE: To determine the effective dose in single source CT (SSCT) and dual source CT (DSCT) scans as a function of tube start angle and spiral pitch value to identify the dose reduction potential by selecting the optimal start angle. METHODS: Using Monte Carlo simulations, dose values for different tube positions with an angular increment of 10 ∘ $10^\circ$ and a longitudinal increment of 4.5 m m $4.5 \,\mathrm{m}\mathrm{m}$ were simulated over a range of 31.5 c m $31.5 \,\mathrm{c}\mathrm{m}$ with collimations of 40 mm $40\, \mathrm{mm}$ , 60 mm $60\, \mathrm{mm}$ , and 80 m m $80 \,\mathrm{m}\mathrm{m}$ . The simulations were performed for the thorax region of six adult patients based on clinical CT data. From the resulting dose distributions, organ doses and effective dose were determined as a function of tube angle and longitudinal position. Using these per-view dose data, the individual organ doses, as well as the total effective dose, were determined for spiral scans with and without tube current modulation (TCM) with pitch values ranging from 0.5 to 1.5 for SSCT and up to 3.0 for DSCT. The dose of the best and worst tube start angle in terms of dose was determined and compared to the mean dose over all tube start angles. RESULTS: With increasing pitch and collimation, the dose variations from the effective dose averaged over all start angles increase. While for a collimation of 40 m m $40 \,\mathrm{m}\mathrm{m}$ , the variations from the mean dose value stay below 5 % $5 \%$ for SSCT, we find that for a spiral scan with a pitch of 3.0 for DSCT with TCM and collimation of 80 m m $80 \,\mathrm{m}\mathrm{m}$ , the dose for the best starting angle is on average 16 % $16 \%$ lower than the mean value and 28 % $28 \%$ lower than the maximum value. CONCLUSIONS: Variation of the tube start angle in spiral scans exhibits substantial differences in radiation dose especially for high pitch values and for high collimations. Therefore, we suggest to control the tube start angle to minimize patient risk.

Relationship Between Cochlear Lateral Wall Changes and Endolymphatic Hydrops in Otitis Media.

OBJECTIVES: Despite otitis media and various disease processes being associated with endolymphatic hydrops (EH), an exact explanation of the pathophysiology has yet to be reported. This study aimed to investigate the changes in the cochlear lateral wall structures and their potential correlation with the presence and severity of cochlear EH in acute and chronic otitis media cases. The investigations were conducted in both chinchilla animal model and human temporal bone specimens. METHODS: We studied a total of 15 chinchilla and 25 human temporal bones from our collection, which were categorized into acute otitis media, chronic otitis media (COM), and control groups. Through quantitative analysis, we measured the area of cochlear lateral wall structures and observed the presence and the degree of EH using light microscopy. RESULTS: No significant changes were determined in the area of the spiral ligament (p > 0.05) across the species. However, a significant (p < 0.05) decrease in the mean area of the stria vascularis in the basal turn was identified in COM groups compared to controls of both species. Chinchilla model additionally exhibited pathology extending to the lower mid turn. A negative correlation was found between the mean strial area and the severity of EH in both the animal model and human samples. CONCLUSIONS: COM associated with significant changes in the stria vascularis that may lead to significant increase in the degree of EH. The presented animal model exhibited parallel findings with human samples, suggesting its viability as a valuable model for future studies. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Nipple reconstruction using spiral-peeling technique during oncoplastic breast-conserving surgery for a patient with small breasts.

Treatment of early breast cancer using breast-conserving surgery (BCS) commonly leads to local control and acceptable cosmetic results. We report a useful technique to achieve symmetry of the breast shape and nipple-areola, with excellent results. A Japanese patient with early breast cancer located in the inner central area of the breast was enrolled in this study. Intraductal spread of breast cancer to the nipple was suspected; however, no invasion was observed outside the nipple wall. We preserved the cylindrical surface, but resected the inner tissue with the top surface of the nipple. After coring the nipple, the remnant cylindrical surface was cut into a spiral shape. Nipple reconstruction using the spiral-peeling technique during oncoplastic breast-conserving surgery (OPBCS) may be useful for patients who desire nipple preservation.

Potential role of the sella turcica X-ray imaging aspects for sex estimation in the field of forensic anthropology: a systematic review and meta-analysis.

Several studies have evaluated the parameters of normality of the sella turcica (ST), which is important to face different craniofacial syndromes that may affect this structure. Therefore, this research summarized the scientific evidence on the role of ST in the sex estimation of non-syndromic individuals. The research protocol was registered (Prospective International Registry of Systematic Reviews # CRD42021256469), followed by an electronic search in six databases (PubMed, LILACS, Web of Science, Scopus, EMBASE, and LIVIVO) and gray literature (Google Scholar and OpenGrey). Meta-analysis of linear (width, length, height, and diameter) and volumetric measurements, in addition to an assessment of risk of bias (RoB) and certainty of evidence, were performed. After the screening of 986 articles, 13 were evaluated by meta-analysis (1 307 males and 1 231 females). In subgroup analysis, females had lower values for width (lateral radiograph; -0.67 mm; P = 0.040), length (computed tomography; -0.23 mm; P = 0.020), and diameter (computed tomography; -0.27 mm; P < 0.001) compared to males. There was no statistically significant difference regarding height (P = 0.95), area (P = 0.72), and volume (P = 0.21). Most studies exhibited moderate RoB, and the certainty of evidence of the outcomes was very low. In this review, significant differences were observed between the sexes for the length and diameter of the ST; however, the heterogeneity of the studies must be considered. Key points: Studies from different geographic regions evaluated the morphology of ST according to sex and showed this anatomical structure as an important indicator of dimorphism.Meta-analysis showed shorter ST length and diameter in women.Subgroup analysis found lower ST width in women based on lateral skull radiographs.Subgroup analysis found smaller lengths and diameters in women based on CT scans.

Experimental and Numerical Simulation of Reinforced Concrete-Filled Square GFRP Tubular Columns under Axial Compression.

To investigate the axial compressive behavior of reinforced concrete-filled square glass-fiber-reinforced polymer(GFRP) tubular (RCFSGT) columns, 17 specimens were designed with variations in GFRP tube wall thickness, spiral reinforcement yield strength, and spiral reinforcement ratio. A detailed model was developed using the finite element software ABAQUS, enabling in-depth mechanistic analysis and expanded parameter studies. The results indicate that the failure types of the specimens are all manifested as GFRP square tube cracking, and the core concrete is subjected to crushing or shear failure. The inclusion of a reinforcement cage can significantly enhance the load-bearing capacity and ductility of the specimen. Furthermore, as the yield strength and reinforcement ratio of the spiral reinforcement increase, so does the load-bearing capacity of the specimen. The finite element simulation results align well with the experimental findings. As the wall thickness of the GFRP square tube increases from 2 mm to 6 mm, the load-bearing capacity improves by approximately 19.69%. With the yield strength of the spiral reinforcement rising from 200 MPa to 400 MPa, the specimen's load-bearing capacity shows an increase of approximately 7.55%. However, as its yield strength continues to increase, there is minimal change in the load-bearing capacity. When the stirrup ratio of spiral reinforcement rises from 0.33% to 2.26%, the specimen's load-bearing capacity experiences an increase of approximately 56.90%.

Ultrafast T2 and T2* mapping using single-shot spatiotemporally encoded MRI with reduced field of view and spiral out-in-out-in trajectory.

BACKGROUND: T2 and T2* mapping are crucial components of quantitative magnetic resonance imaging, offering valuable insights into tissue characteristics and pathology. Single-shot methods can achieve ultrafast T2 or T2* mapping by acquiring multiple readout echo trains. However, the extended echo trains pose challenges, such as compromised image quality and diminished quantification accuracy. PURPOSE: In this study, we develop a single-shot method for ultrafast T2 and T2* mapping with reduced echo train length. METHODS: The proposed method is based on ultrafast single-shot spatiotemporally encoded (SPEN) MRI combined with reduced field of view (FOV) and spiral out-in-out-in (OIOI) trajectory. Specifically, a biaxial SPEN excitation scheme was employed to excite the spin signal into the spatiotemporal encoding domain. The OIOI trajectory with high acquisition efficiency was employed to acquire signals within targeted reduced FOV. Through non-Cartesian super-resolved (SR) reconstruction, 12 aliasing-free images with different echo times were obtained within 150 ms. These images were subsequently fitted to generate T2 or T2* mapping simultaneously using a derived model. RESULTS: Accurate and co-registered T2 and T2* maps were generated, closely resembling the reference maps. Numerical simulations demonstrated substantial consistency (R2 > 0.99) with the ground truth values. A mean difference of 0.6% and 1.7% was observed in T2 and T2*, respectively, in in vivo rat brain experiments compared to the reference. Moreover, the proposed method successfully obtained T2 and T2* mappings of rat kidney in free-breathing mode, demonstrating its superiority over multishot methods lacking respiratory navigation. CONCLUSIONS: The results suggest that the proposed method can achieve ultrafast and accurate T2 and T2* mapping, potentially facilitating the application of T2 and T2* mapping in scenarios requiring high temporal resolution.

Frequency-Selective, Multi-Channel, Self-Powered Artificial Basilar Membrane Sensor with a Spiral Shape and 24 Critical Bands Inspired by the Human Cochlea.

A spiral-artificial basilar membrane (S-ABM) sensor is reported that mimics the basilar membrane (BM) of the human cochlea and can detect sound by separating it into 24 sensing channels based on the frequency band. For this, an analytical function is proposed to design the width of the BM so that the frequency bands are linearly located along the length of the BM. To fabricate the S-ABM sensor, a spiral-shaped polyimide film is used as a vibrating membrane, with maximum displacement at locations corresponding to specific frequency bands of sound, and attach piezoelectric sensor modules made of poly(vinylidene fluoride-trifluoroethylene) film on top of the polyimide film to measure the vibration amplitude at each channel location. As the result, the S-ABM sensor implements a characteristic frequency band of 96-12,821 Hz and 24-independent critical bands. Using real-time signals from discriminate channels, it is demonstrated that the sensor can rapidly identify the operational noises from equipment processes as well as vehicle sounds from environmental noises on the road. The sensor can be used in a variety of applications, including speech recognition, dangerous situation recognition, hearing aids, and cochlear implants, and more.

Integration of Functional Human Auditory Neural Circuits Based on a 3D Carbon Nanotube System.

The physiological interactions between the peripheral and central auditory systems are crucial for auditory information transmission and perception, while reliable models for auditory neural circuits are currently lacking. To address this issue, mouse and human neural pathways are generated by utilizing a carbon nanotube nanofiber system. The super-aligned pattern of the scaffold renders the axons of the bipolar and multipolar neurons extending in a parallel direction. In addition, the electrical conductivity of the scaffold maintains the electrophysiological activity of the primary mouse auditory neurons. The mouse and human primary neurons from peripheral and central auditory units in the system are then co-cultured and showed that the two kinds of neurons form synaptic connections. Moreover, neural progenitor cells of the cochlea and auditory cortex are derived from human embryos to generate region-specific organoids and these organoids are assembled in the nanofiber-combined 3D system. Using optogenetic stimulation, calcium imaging, and electrophysiological recording, it is revealed that functional synaptic connections are formed between peripheral neurons and central neurons, as evidenced by calcium spiking and postsynaptic currents. The auditory circuit model will enable the study of the auditory neural pathway and advance the search for treatment strategies for disorders of neuronal connectivity in sensorineural hearing loss.

Impact of Combined Modulation of Two Potassium Ion Currents on Spiral Waves and Turbulent States in the Heart.

In the realm of cardiac research, the control of spiral waves and turbulent states has been a persistent focus for scholars. Among various avenues of investigation, the modulation of ion currents represents a crucial direction. It has been proved that the methods involving combined control of currents are superior to singular approaches. While previous studies have proposed some combination strategies, further reinforcement and supplementation are required, particularly in the context of controlling arrhythmias through the combined regulation of two potassium ion currents. This study employs the Luo-Rudy phase I cardiac model, modulating the maximum conductance of the time-dependent potassium current and the time-independent potassium current, to investigate the effects of this combined modulation on spiral waves and turbulent states. Numerical simulation results indicate that, compared to modulating a single current, combining reductions in the conductance of two potassium ion currents can rapidly control spiral waves and turbulent states in a short duration. This implies that employing blockers for both potassium ion currents concurrently represents a more efficient control strategy. The control outcomes of this study represent a novel and effective combination for antiarrhythmic interventions, offering potential avenues for new antiarrhythmic drug targets.

Rac1 and Nectin3 are essential for PCP-directed axon guidance in the peripheral auditory system.

Our sense of hearing is critically dependent on the spiral ganglion neurons (SGNs) that connect the sound receptors in the organ of Corti (OC) to the cochlear nuclei of the hindbrain. Type I SGNs innervate inner hair cells (IHCs) to transmit sound signals, while type II SGNs (SGNIIs) innervate outer hair cells (OHCs) to detect moderate-to-intense sound. During development, SGNII afferents make a characteristic 90-degree turn toward the base of the cochlea and innervate multiple OHCs. It has been shown that the Planar Cell Polarity (PCP) pathway acts non-autonomously to mediate environmental cues in the cochlear epithelium for SGNII afferent turning towards the base. However, the underlying mechanisms are unknown. Here, we present evidence that PCP signaling regulates multiple downstream effectors to influence cell adhesion and the cytoskeleton in cochlear supporting cells (SCs), which serve as intermediate targets of SGNII afferents. We show that the core PCP gene Vangl2 regulates the localization of the small GTPase Rac1 and the cell adhesion molecule Nectin3 at SC-SC junctions through which SGNII afferents travel. Through in vivo genetic analysis, we also show that loss of Rac1 or Nectin3 partially phenocopied SGNII peripheral afferent turning defects in Vangl2 mutants, and that Rac1 plays a non-autonomous role in this process in part by regulating PCP protein localization at the SC-SC junctions. Additionally, epistasis analysis indicates that Nectin3 and Rac1 likely act in the same genetic pathway to control SGNII afferent turning. Together, these experiments identify Nectin3 and Rac1 as novel regulators of PCP-directed SGNII axon guidance in the cochlea.

Assessment of Two Different Obturation Systems in Primary Teeth: A Comparative Study.

Aim: The purpose of this study was to evaluate the efficacy of two distinct obturation techniques in primary teeth. Materials and Methods: For this investigation, 40 primary molar teeth were taken into consideration. Every sample underwent sample preparation. All teeth were evenly split into two groups: Group 1-obturation using the lentulospiral method and Group 2-obturation using the NaviTip method. The comparison between the two procedures was established through radiographic evaluation of the obturation quality and voids in the obturated canals. Results: In the lentulospiral method, 12 (60%) were optimal filling, 6 (30%) were underfilling, and 2 (10%) were overfilling. In the lentulo spiral method, 40% voids were present, and in the NaviTip method, 15% voids were present. Conclusion: The present study concluded that the NaviTip syringe method was sufficiently effective in regulating voids and yielded the best results for the apical seal, whereas the lentulo spiral approach generated the best results in terms of length of obturation.

Cyclic AMP signaling promotes regeneration of cochlear synapses after excitotoxic or noise trauma.

Introduction: Cochlear afferent synapses connecting inner hair cells to spiral ganglion neurons are susceptible to excitotoxic trauma on exposure to loud sound, resulting in a noise-induced cochlear synaptopathy (NICS). Here we assessed the ability of cyclic AMP-dependent protein kinase (PKA) signaling to promote cochlear synapse regeneration, inferred from its ability to promote axon regeneration in axotomized CNS neurons, another system refractory to regeneration. Methods: We mimicked NICS in vitro by applying a glutamate receptor agonist, kainic acid (KA) to organotypic cochlear explant cultures and experimentally manipulated cAMP signaling to determine whether PKA could promote synapse regeneration. We then delivered the cAMP phosphodiesterase inhibitor rolipram via implanted subcutaneous minipumps in noise-exposed CBA/CaJ mice to test the hypothesis that cAMP signaling could promote cochlear synapse regeneration in vivo. Results: We showed that the application of the cell membrane-permeable cAMP agonist 8-cpt-cAMP or the cAMP phosphodiesterase inhibitor rolipram promotes significant regeneration of synapses in vitro within twelve hours after their destruction by KA. This is independent of neurotrophin-3, which also promotes synapse regeneration. Moreover, of the two independent signaling effectors activated by cAMP - the cAMP Exchange Protein Activated by cAMP and the cAMP-dependent protein kinase - it is the latter that mediates synapse regeneration. Finally, we showed that systemic delivery of rolipram promotes synapse regeneration in vivo following NICS. Discussion: In vitro experiments show that cAMP signaling promotes synapse regeneration after excitotoxic destruction of cochlear synapses and does so via PKA signaling. The cAMP phosphodiesterase inhibitor rolipram promotes synapse regeneration in vivo in noise-exposed mice. Systemic administration of rolipram or similar compounds appears to provide a minimally invasive therapeutic approach to reversing synaptopathy post-noise.

Spiral time-of-flight magnetic resonance angiography for intracranial vascular imaging: performance compared to conventional Cartesian angiogram.

Background: Computed tomography angiography (CTA) and digital subtraction angiography (DSA) usually raise the risk of potential malignancies with cumulative radiation doses. Current time-of-flight magnetic resonance angiography (TOF-MRA) (dubbed as cTOF), which is based on Cartesian sampling mode, may show limited diagnostic conspicuity at sinuous or branching regions. It is also prone to relatively high false positive diagnoses and undesirable display of distal intracranial vessels. This study aimed to use spiral TOF-MRA (sTOF) as a noninvasive alternative to explore possible improvement, such that the application of magnetic resonance angiography (MRA) can be extended to facilitate clinical examination or cerebrovascular disease diagnosis and follow-up studies. Methods: Initially, 37 patients with symptoms of dizziness or transient ischemic attack were consecutively recruited for suspected intracranial vascular disease examination from Zhongshan Hospital of Xiamen University between July 2020 and April 2021 in this cross-sectional prospective study. After excluding 1 patient with severe scanning artifacts, 1 patient whose scanning scope did not meet the requirement, and 1 patient with confounding tumor lesions, a total of 34 participants were included according to the inclusion and exclusion criteria. Each participant underwent intracranial vascular imaging with both sTOF and cTOF sequences on a 3.0 T MR scanner with a conventional head-neck coil of 16 channels. Contrast CTA or DSA was also performed for 15 patients showing pathology. Qualitative comparisons in terms of image quality and diagnostic efficacy ratings, quantitative comparisons in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel length, and sharpness were evaluated. Pair-wise Wilcoxon test was performed to evaluate the imaging quality derived from cTOF and sTOF acquisitions and weighted Cohen's Kappa was conducted to assess the rating consistency between different physicians. Results: Compared to cTOF, sTOF showed better performance with fewer artifacts. It can effectively alleviate false positives of normal vessels being misdiagnosed as aneurysm or stenosis. Improved conspicuity was observed in cerebral distal regions with more clearly identifiable vasculature at finer scales. Quantitative comparisons in selected regions revealed significant improvement of sTOF in SNR (P<0.01 or P<0.001), CNR (P<0.001), vessel length (P<0.001), and sharpness (P<0.001) as compared to cTOF. Besides, sTOF can depict details of M1 and M2 segments of middle cerebral artery (MCA) at metallic implant region, showing its resistance to magnetic susceptibility. Conclusions: The sTOF shows higher imaging quality and lesion detectability with reduced artifacts and false positives, representing a potentially feasible surrogate in intracranial vascular imaging for future clinic routines.

Clinical application of high-resolution spiral CT scanning in the diagnosis of auriculotemporal and ossicle.

Precision and intelligence in evaluating the complexities of middle ear structures are required to diagnose auriculotemporal and ossicle-related diseases within otolaryngology. Due to the complexity of the anatomical details and the varied etiologies of illnesses such as trauma, chronic otitis media, and congenital anomalies, traditional diagnostic procedures may not yield accurate diagnoses. This research intends to enhance the diagnosis of diseases of the auriculotemporal region and ossicles by combining High-Resolution Spiral Computed Tomography (HRSCT) scanning with Deep Learning Techniques (DLT). This study employs a deep learning method, Convolutional Neural Network-UNet (CNN-UNet), to extract sub-pixel information from medical photos. This method equips doctors and researchers with cutting-edge resources, leading to groundbreaking discoveries and better patient healthcare. The research effort is the interaction between the CNN-UNet model and high-resolution Computed Tomography (CT) scans, automating activities including ossicle segmentation, fracture detection, and disruption cause classification, accelerating the diagnostic process and increasing clinical decision-making. The suggested HRSCT-DLT model represents the integration of high-resolution spiral CT scans with the CNN-UNet model, which has been fine-tuned to address the nuances of auriculotemporal and ossicular diseases. This novel combination improves diagnostic efficiency and our overall understanding of these intricate diseases. The results of this study highlight the promise of combining high-resolution CT scanning with the CNN-UNet model in otolaryngology, paving the way for more accurate diagnosis and more individualized treatment plans for patients experiencing auriculotemporal and ossicle-related disruptions.

Development of a Semi-Automated Approach for the Quantification of Neuronal Cells in the Spiral Ganglion of the Whole Implanted Gerbil Cochlea, Acquired by Light-Sheet Microscopy.

INTRODUCTION: Assessing cochlear implantation's impact on cell loss and preventing post-implant cochlear damage are key areas of focus for hearing preservation research. The preservation of auditory neuronal and sensory neural hearing cells has a positive impact on auditory perception after implantation. This study aimed to provide details on a semi-automated spiral ganglion neuronal cell counting method, developed using whole implanted gerbil cochlea acquisitions with light-sheet microscopy. METHODS: Mongolian gerbils underwent right cochlear implantation with an electrode array whose silicone was loaded with dexamethasone or not and were euthanized 10 weeks after implantation. The cochleae were prepared according to a 29-day protocol, with the electrode array in place. Light-sheet microscopy was used for acquisition, and Imaris software was employed for three-dimensional analysis of the cochleas and semi-automatic quantification of spiral ganglion cells. The imaJ software was used for the manual quantification of these cells. RESULTS: Six cochleae were acquired by light-sheet microscopy, allowing good identification of cells. There was no significant difference between the mean number of spiral ganglion cells obtained by manual and semi-automatic counting (p = 0.25). CONCLUSION: Light-sheet microscopy provided complete visualization of the spiral ganglion and cell identification. The semi-automated counting method developed using Imaris software tools proved reliable and efficient and could be applied to a larger sample to assess post-cochlear implant cell damage and the efficacy of protective drugs delivered to the inner ear.

Early Loss of Spiral Ganglion Neurons in the Auditory System after Noise Trauma.

INTRODUCTION: Noise-induced hearing loss is one of the most frequent recognized occupational diseases. The time course of the involved pathologies is still under investigation. Several studies have demonstrated an acute damage of the sensory tissue, but only few experiments investigated the degeneration of (type I) spiral ganglion neurons (SGNs), representing the primary neurons in the auditory system. The aim of the present study was to investigate the time course of SGN degeneration within a 7-day period after traumatic noise exposure starting immediately after trauma. METHODS: Young adult normal hearing mice were noise exposed for 3 h with a broadband noise (5-20 kHz) at 115 dB SPL. Auditory threshold shift was measured by auditory brainstem recordings, and SGN densities were analyzed at different time points during the first week after acoustic trauma. RESULTS: Significant reduction of SGN densities was detected and is accompanied by a significant hearing loss. Degeneration starts within hours after the applied trauma, further progressing within days post-exposure. DISCUSSION: Early neurodegeneration in the auditory periphery seems to be induced by direct overstimulation of the auditory nerve fibers. SGN loss is supposed to be a result of inflammatory responses and neural deprivation, leading to permanent hearing loss and auditory processing deficits.

Suppression of the TGF-ß signaling exacerbates degeneration of auditory neurons in kanamycin-induced ototoxicity in mice.

Transforming growth factor-ß (TGF-ß) signaling plays a significant role in multiple biological processes, including inflammation, immunity, and cell death. However, its specific impact on the cochlea remains unclear. In this study, we aimed to investigate the effects of TGF-ß signaling suppression on auditory function and cochlear pathology in mice with kanamycin-induced ototoxicity. Kanamycin and furosemide (KM-FS) were systemically administered to 8-week-old C57/BL6 mice, followed by immediate topical application of a TGF-ß receptor inhibitor (TGF-ßRI) onto the round window membrane. Results showed significant TGF-ß receptor upregulation in spiral ganglion neurons (SGNs) after KM-FA ototoxicity, whereas expression levels in the TGF-ßRI treated group remained unchanged. Interestingly, despite no significant change in cochlear TGF-ß expression after KM-FS ototoxicity, TGF-ßRI treatment resulted in a significant decrease in TGF-ß signaling. Regarding auditory function, TGF-ßRI treatment offered no therapeutic effects on hearing thresholds and hair cell survival following KM-FS ototoxicity. However, SGN loss and macrophage infiltration were significantly increased with TGF-ßRI treatment. These results imply that inhibition of TGF-ß signaling after KM-FS ototoxicity promotes cochlear inflammation and SGN degeneration.

IL1ß-NFκß-Myocardin signaling axis governs trophoblast-directed plasticity of vascular smooth muscle cells.

Vascular smooth muscle cell (VSMC) plasticity is fundamental in uterine spiral artery remodeling during placentation in Eutherian mammals. Our previous work showed that the invasion of trophoblast cells into uterine myometrium coincides with a phenotypic change of VSMCs. Here, we elucidate the mechanism by which trophoblast cells confer VSMC plasticity. Analysis of genetic markers on E13.5, E16.5, and E19.5 in the rat metrial gland, the entry point of uterine arteries, revealed that trophoblast invasion is associated with downregulation of MYOCARDIN, α-smooth muscle actin, and calponin1, and concomitant upregulation of Smemb in VSMCs. Myocardin overexpression or knockdown in VSMCs led to upregulation or downregulation of contractile markers, respectively. Co-culture of trophoblast cells with VSMCs decreased MYOCARDIN expression along with compromised expression of contractile markers in VSMCs. However, co-culture of trophoblast cells with VSMCs overexpressing MYOCARDIN inhibited their change in phenotype, whereas, overexpression of transactivation domain deleted MYOCARDIN failed to elicit this response. Furthermore, the co-culture of trophoblast cells with VSMCs led to the activation of NFκß signaling. Interestingly, despite producing IL-1ß, trophoblast cells possess only the decoy receptor, whereas, VSMCs possess the IL-1ß signaling receptor. Treatment of VSMCs with exogenous IL-1ß led to a decrease in MYOCARDIN and an increase in phosphorylation of NFκß. The effect of trophoblast cells in the downregulation of MYOCARDIN in VSMCs was reversed by blocking NFκß translocation to the nucleus. Together, these data highlight that trophoblast cells direct VSMC plasticity, and trophoblast-derived IL-1ß is a key player in downregulating MYOCARDIN via the NFκß signaling pathway.