Signal Intensity Changes Research Articles

Water distribution in human hair microstructure elucidated by spin contrast variation small-angle neutron scattering

Dynamic nuclear polarization (DNP) is effective for controlling the neutron scattering length of protons and can be utilized for contrast variation in small-angle neutron scattering (SANS). Using the TEMPOL solution soaking method as electron spin doping, the DNP–SANS technique was applied to human hair fiber for the first time. For dry and D2O-swollen hair samples, a drastic change in the SANS profile was observed at high polarization conditions (|P H P N| ∼ 60%, where P H and P N are the proton and neutron spin polarization, respectively). The SANS profile as a function of the magnitude of the scattering vector, q, was composed of a low-q upturn, a middle-q oscillation and a high-q flat region. The low-q upturn was assumed to be a combination of two power-law functions, q −4 due to a large structure interface (Porod's law) and q −2 due to random coil. The middle-q oscillation was well reproduced by numerical calculation based on the structure model of intermediate filaments (IFs) as proposed by Er Rafik et al. [Biophys. J. (2004), 86, 3893–3904]: one pair of keratin coiled-coils is located at the center and surrounded by seven pairs of keratin coiled-coils located in a circle (called the `7 + 1' model), and a collection of IFs is arranged in a quasi-hexagonal manner. For the observed SANS profiles for different P H P N, the IF term contribution maintained a constant q-dependent profile, despite significant changes in intensity. This indicates that the macrofibril is composed of two domains (keratin coiled-coils and matrix). In addition, D2O swelling enhanced the IF term intensity and shifted the polarization-dependent local minimum to higher P H P N. This behavior was reproduced by contrast factor calculation based on the two-domain model. Scattering length densities of keratin coiled-coil and surrounding matrix domains were calculated by use of the known amino acid composition, considering the hydrogen–deuterium exchange reaction during soaking with D2O solution of TEMPOL. As a result, it was found that for keratin coiled-coil domains, about 40% of the peptide backbone amide NH protons were replaced with deuterons. This means that 68% of the α-helix domain is rigid, but the rest is flexible to allow dynamic dissociation of the hydrogen bond. Furthermore, the local mass density of each domain was precisely evaluated. The obtained data are expected to be a guide for further detailed investigation of keratin and keratin-associated protein distribution. This approach is expected to be applied to a wide variety of bio-derived materials, which are water absorbing in general.

High field brain proton magnetic resonance spectroscopy and volumetry in children with chronic, compensated liver disease – A pilot study

BackgroundThere is increasing evidence that children or young adults having acquired liver disease in childhood display neurocognitive impairment which may become more apparent as they grow older. The molecular, cellular and morphological underpinnings of this clinical problem are incompletely understood. AimTherefore, we used the advantages of highly-resolved proton magnetic resonance spectroscopy at ultra-high magnetic field to analyze the neurometabolic profile and brain morphometry of children with chronic, compensated liver disease, hypothesizing that with high field spectroscopy we would identify early evidence of rising brain glutamine and decreased myoinositol, such as has been described both in animals and humans with more significant liver disease. MethodsPatients (n = 5) and age-matched controls (n = 19) underwent 7T MR scans and short echo time 1H MR spectra were acquired using the semi-adiabatic SPECIAL sequence in two voxels located in gray and white matter dominated prefrontal cortex, respectively. A 3D MP2RAGE sequence was also acquired for brain volumetry and T1 mapping. Liver disease had to have developed at least 6 months before entering the study. Subjects underwent routine blood analysis and neurocognitive testing using validated methods within 3 months of MRI and MRS. ResultsFive children aged 8–16 years with liver disease acquired in childhood were included. Baseline biological characteristics were similar among patients. There were no statistically significant differences between subjects and controls in brain metabolite levels or brain volumetry. Finally, there were minor neurocognitive fluctuations including attention deficit in one child, but none fell in the statistically significant range. ConclusionChildren with chronic, compensated liver disease did not display an abnormal neurometabolic profile, neurocognitive abnormalities, or signal intensity changes in the globus pallidus. Despite the absence of neurometabolic changes, it is an opportunity to emphasize that it is only by developing the use of 1H MRS at high field in the clinical arena that we will understand the significance and generalizability of these findings in children with CLD. Healthy children displayed neurometabolic regional differences as previously reported in adult subjects.

Spinal Cord Signal Intensity Predicts Functional Outcomes in the Operative Management of Degenerative Cervical Myelopathy.

Prospective single institutional cohort study on degenerative cervical myelopathy (DCM) from 2009 to 2022. This study aims to assess the relationship among preoperative spinal cord signal change, postoperative signal change evolution, and functional outcome in patients undergoing surgery for DCM. There is conflicting evidence on whether spinal cord signal intensity influences functional outcomes in patients with DCM. This prospective study investigated 104 patients with DCM that underwent both preoperative and routine postoperative cervical spine magnetic resonance imaging (MRI) as part of a research protocol. Signal intensity/grade, modified Japanese Orthopedic Association (mJOA) scores, signal resolution, and patient demographics were assessed. Sixty-eight of the subjects were found to have abnormal T2 spinal cord signal intensity changes on their preoperative MRI. The total mean preoperative mJOA score was 13.6, increasing postoperatively to 16 (P < 0.001). The presence or absence of preoperative spinal cord signal change was not associated with the change in mJOA score or neurological recovery rate after surgery. Of the 68 patients with preoperative T2 signal change, 36 were found to have an improvement in the T2-weighted signal grade after surgery and 32 had no change in postoperative signal grade. The mean improvement in mJOA score (3.7) and neurological recovery rate (70.3%) was significantly higher in the patients with preoperative signal change whose postoperative MRI signal change grade improved by at least one point compared with those that did not (2.0, 50.5%), (P < 0.001, P < 0.003). The presence of preoperative T2-weighted signal change was associated with lower preoperative mJOA scores, but no change in mJOA after surgery or postoperative neurological recovery rate. However, improvement in T2-weighted spinal cord signal grade on postoperative MRI was significantly associated with a degree of neurological improvement after surgery.

Hydration and dehydration behaviors of poly(N-isopropylacrylamide)-grafted silica beads

The use of poly(N-isopropyl acrylamide) (PNIPAAm) in thermoresponsive interfaces for biomedical applications has been extensively investigated. Understanding the hydration and dehydration characteristics of PNIPAAm-grafted interfaces is crucial for the development of highly functional thermoresponsive interfaces. In this study, four PNIPAAm-grafted silica beads were prepared using atom transfer radical polymerization and radical polymerization techniques, with varying amounts of PNIPAAm grafted onto the beads. These PNIPAAm-grafted silica beads were used as samples, and their hydration and dehydration behaviors were analyzed using FTIR spectroscopy. Through the analysis of FTIR spectra obtained from the PNIPAAm-grafted silica beads prepared in this study, distinct observations were made under varying relative humidity and temperature conditions. Specifically, an elevation in the peak intensity of the broad peak at 3700–3000 cm−1, associated with the O-H group of hydrated water on PNIPAAm, was noted at higher humidity levels at 10°C. This increase in humidity resulted in an amplified peak intensity at 3700–3000 cm−1, indicative of the presence of the hydrated water molecules bonded to the PNIPAAm. Concurrently, shifts in the amide I and II peaks were observed with increasing relative humidity, signifying enhanced hydration and increased hydrogen bonding to C=O and N-H groups. Conversely, increasing the temperature at relatively high humidity led to a decreased in the intensity of the broad peak at 3700–3000 cm−1; this was attributed to the dehydration of the grafted PNIPAAm and subsequent water loss. The dehydration of PNIPAAm resulted in significant peak shifts for the amide I and II peaks, indicating a decrease in hydrogen bonding with the amide group. A significant change in peak intensity and shifts were evident, underscoring PNIPAAm brush's heightened propensity for hydration. These findings confirm the effectiveness of FTIR spectroscopy as a valuable approach for studying the hydration and dehydration behaviors of thinly grafted PNIPAAm layers on substrates.

Treatment-Induced Bone Marrow Enhancement at MRI in Breast Cancer Patients Receiving Granulocyte-Colony Stimulating Factor Adjunct to Chemotherapy

Granulocyte-colony stimulating factor (G-CSF) induces the reconversion of fatty bone marrow to hematopoietic bone marrow. The bone marrow changes are detectable as signal intensity changes at MRI. The aim of this study was to evaluate sternal bone marrow enhancement following G-CSF and chemotherapy treatment in women with breast cancer. This retrospective study included breast cancer patients who received neoadjuvant chemotherapy with adjunct G-CSF. The signal intensity of sternal bone marrow at MRI on T1-weighted contrast-enhanced subtracted images was measured before treatment, at the end of treatment, and at 1-year follow-up. The bone marrow signal intensity (BM SI) index was calculated by dividing the signal intensity of sternal marrow by the signal intensity of the chest wall muscle. Data were collected between 2012 and 2017, with follow-up until August 2022. Mean BM SI indices were compared before and after treatment, and at 1-year follow-up. Differences in bone marrow enhancement between time points were analyzed using a one-way repeated measures ANOVA. A total of 109 breast cancer patients (mean age 46.1±10.4 years) were included in our study. None of the women had distal metastases at presentation. A repeated-measures ANOVA determined that mean BM SI index scores differed significantly across the three time points(F[1.62, 100.67]=44.57, p<.001). At post hoc pairwise comparison using the Bonferroni correction BM SI index significantly increased between initial assessment and following treatment (2.15 vs 3.33, p<.001), and significantly decreased at 1-yearfollow-up (3.33 vs 1.45, p<.001). In a subgroup analysis, while women younger than 50 years had a significant increase in marrow enhancement after G-CSF treatment, in women aged 50 years and older, the difference was not statistically significant. Treatment with G-CSF as an adjunct to chemotherapy can result in increased sternal bone marrow enhancement due to marrow reconversion. Radiologists should be aware of this effect in order to avoid misinterpretation as false marrow metastases.

Tumor volume and T2 hyperintensity changes from DeFi: A phase 3, randomized, controlled trial of nirogacestat in patients with desmoid tumors.

11514 Background: MRI tumor volume or T2 signal intensity changes may represent novel imaging techniques that could have a prognostic or predictive value for assessing response in desmoid tumors (DT). For example, hyperintense areas on T2-weighted images have been associated with active fibroblastic proliferation and ≥90% hyperintensity is associated with DT disease progression, whereas iso- or hypo-intense areas are associated with inactive sites of disease. In DeFi (NCT03785964), the novel gamma secretase inhibitor nirogacestat (n=70 patients) significantly improved the primary endpoint of PFS compared with placebo (n=72 patients; hazard ratio, 0.29 [95% CI, 0.15, 0.55; P&lt;0.001]) and significantly improved the secondary endpoint of ORR per blinded, independent central review (41% vs 8%; P&lt;0.001). Complete responses were achieved in 7% with nirogacestat and 0% with placebo. Here, we present an exploratory analysis of MRI tumor volume and T2 signal intensity changes in DeFi. Methods: Eligible adults had histologically confirmed DT that had progressed ≥20% per RECIST v1.1 within 12 months of screening. Patients were randomized 1:1 to receive nirogacestat 150 mg or placebo twice daily taken continuously in 28-day cycles. Volumetric MRI and T2 hyperintensity of the largest target tumor were evaluated at screening and every 6 cycles during the double-blind phase. MRI T2 signal intensity is represented as the ratio of hyperintensity in total tumor volume to muscle background. A blinded, independent, central radiologist reviewed all MRI scans. Results: Nirogacestat treatment led to more substantial reductions versus placebo in tumor volume and T2 hyperintensity ratio (Table). At baseline, similar proportions of patients in each arm had a T2 hyperintensity ratio ≥90% (95% vs 97%). This ratio changed from ≥90% at baseline to &lt;90% at any time after baseline in 34% of patients in the nirogacestat arm and 15% of those on placebo. Conclusions: In DeFi, nirogacestat demonstrated substantial reduction of tumor volume and T2 hyperintensity of the largest target tumors by MRI compared with placebo in adults with DT. These results are consistent with the significant improvement in ORR achieved with nirogacestat. These data suggest that volumetric MRI and T2 hyperintensity might provide additional information in the evaluation of treatment response in DT. The prognostic or predictive value of these imaging techniques in DT should be further studied. Clinical trial information: NCT03785964 . [Table: see text]

Development of ratiometric fluorescent probes based on peptides for sensing Pb2+ in aquatic environments and human serum.

The detection of Pb2+ ions in aquatic environments and biofluid samples is crucial for assessment of human health. Herein, we synthesized two fluorescent probes (1 and 2) consisting of the peptide receptor for Pb2+ and a benzothiazolyl-cyanovinylene fluorophore that exhibited excimer-like emission when it aggregated. The peptide-based probes sensitively detected Pb2+ in purely aqueous solution (1% DMF) through ratiometric fluorescent response with a decrease in monomer emission at 520nm and an increase in excimer emission at 570nm. Specially, probe 2 showed remarkable detection features such as high selectivity for Pb2+over 15 metal ions, high binding affinity (Kd=5.83×10-7 M) for Pb2+, significant emission intensity changes, low detection limit (3.8nM) of Pb2+, high water solubility, and visible light excitation (450nm). Probe 2 was successfully used to quantify nanomolar concentration (0∼800nM) of Pb2+ in real water samples (ground water and tap water). Specially, 2 was successfully applied for the quantification of Pb2+ in human serum by combination of microwave-assisted human serum digestion and filtration of digested serum by anion exchange cartridge. We clearly investigated the binding mode of 2 with Pb2+ using 1H NMR, IR spectroscopy, pH titration, confocal microscopy, and size analysis. The peptide-based fluorescent probe might have great application potential for sensing Pb2+ in aquatic environments and biofluid samples.

Visualising and semi-quantitatively measuring brain fluid pathways, including meningeal lymphatics, in humans using widely available MRI techniques

Brain fluid dynamics remains poorly understood with central issues unresolved. In this study, we first review the literature regarding points of controversy, then pilot study if conventional MRI techniques can assess brain fluid outflow pathways and explore potential associations with small vessel disease (SVD). We assessed 19 subjects participating in the Mild Stroke Study 3 who had FLAIR imaging before and 20–30 minutes after intravenous Gadolinium (Gd)-based contrast. Signal intensity (SI) change was assessed semi-quantitatively by placing regions of interest, and qualitatively by a visual scoring system, along dorsal and basal fluid outflow routes. Following i.v. Gd, SI increased substantially along the anterior, middle, and posterior superior sagittal sinus (SSS) (82%, 104%, and 119%, respectively), at basal areas (cribriform plate, 67%; jugular foramina, 72%), and in narrow channels surrounding superficial cortical veins separated from surrounding cerebrospinal fluid (CSF) (96%) (all p < 0.001). The SI increase was associated with higher intraparenchymal perivascular spaces (PVS) scores (Std. Beta 0.71, p = 0.01). Our findings suggests that interstitial fluid drainage is visible on conventional MRI and drains from brain parenchyma via cortical perivenous spaces to dural meningeal lymphatics along the SSS remaining separate from the CSF. An association with parenchymal PVS requires further research, now feasible in humans.

Ratiometric Sensing of Glyphosate in Water Using Dual Fluorescent Carbon Dots.

Glyphosate is a broad-spectrum pesticide used in crops and is found in many products used by industry and consumers. Unfortunately, glyphosate has been shown to have some toxicity toward many organisms found in our ecosystems and has been reported to have carcinogenic effects on humans. Hence, there is a need to develop novel nanosensors that are more sensitive and facile and permit rapid detection. Current optical-based assays are limited as they rely on changes in signal intensity, which can be affected by multiple factors in the sample. Herein, we report the development of a dual emissive carbon dot (CD) system that can be used to optically detect glyphosate pesticides in water at different pH levels. The fluorescent CDs emit blue and red fluorescence, which we exploit as a ratiometric self-referencing assay. We observe red fluorescence quenching with increasing concentrations of glyphosate in the solution, ascribed to the interaction of the glyphosate pesticide with the CD surface. The blue fluorescence remains unaffected and serves as a reference in this ratiometric approach. Using fluorescence quenching assays, a ratiometric response is observed in the ppm range with detection limits as low as 0.03 ppm. Our CDs can be used to detect other pesticides and contaminants in water, as cost-effective and simple environmental nanosensors.

Influence of non-magnetic ions doping on structural, morphological, optical, and magnetic properties of nanocrystalline zinc oxide powders

In this research study, nanocrystalline non-magnetic ion-doped zinc oxide powders are synthesized through sol-gel auto combustion with a variety of different ions (Mg, Al, and Ca) at a range of concentrations (0, 5%, 10%, 20% mol). X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), filed-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray photoelectron spectrometer (XPS), UV–visible diffuse reflectance spectroscopy (UV-DRS), photoluminescence spectroscopy (PL), and vibrating sample magnetometry (VSM) were then used to investigate the calcined products, whereupon the structures, chemical bonds, surface texture, chemical composition, morphologies, particle size, surface elemental composition, electronic state, optical and fluorescence properties including magnetism were reported for each of the samples. From XRD it could be determined that the introduction of minuscule quantities of magnesium and calcium ions to the zinc oxide powder produced solutions of hexagonal solid MgZnO and CaZnO, while composites of Mg/ZnO, CaO/ZnO, Al2O3/ZnO could also be observed, without impurity phases. Textural properties of these modified samples observed from SEM, FE-SEM, and TEM were superior to that of the pure ZnO. XPS studies confirmed the substitution of Zn2+ by Mg2+ and Ca2+ for the samples of low doping concentration. UV-DRS analysis showed that samples which had been optimally modified exhibited improved levels of absorption when compared to visible spectral observations of the pure sample. In comparison to the pure sample, the modified samples also showed higher bandgap energy (Eg). In the pure sample, violet and blue emission bands were seen in the PL spectra ranging from 350 to 430 nm, but these emissions showed significant changes in intensity as the concentration of non-magnetic ions was increased. Furthermore, VSM results revealed that diamagnetism of zinc oxide can be adjusted through the introduction of non-magnetic ions to paramagnetism and ferromagnetism.

Role of virtual reality distraction technique to improve chest burns with acute respiratory distress syndrome (ARDS) following smoke inhalation in middle-aged adults – A randomized controlled study

BackgroundBurns of the chest region constitute a common burn and develops skin contractures around the thorax region. Inhalation of toxic gases and chemical irritants during the fire leads to Acute Respiratory Distress Syndrome (ARDS). Breathing exercises are painful but are needed to help counteract contractures and increase lung capacity. These patients are usually in pain and extremely anxious about chest physiotherapy. Virtual reality distraction is one such technique that is gaining immense popularity when compared to other pain distraction techniques. However, studies examining the efficacy of the virtual reality distraction technique in this population are lacking. ObjectivesTo find and compare the effects of the virtual reality distraction technique as a pain alleviation tool for reducing pain during chest physiotherapy in chest burns patients with ARDS in middle-aged adults. MethodsA randomized controlled study was conducted at the physiotherapy department between 1st Sep 2020 and 30th Dec 2022. The eligible sixty subjects were randomized into two groups: The virtual reality distraction group (n = 30) received virtual reality distraction technique and the control group (n = 30) received progressive relaxation technique before chest physiotherapy as a pain distraction technique. All the participants received chest physiotherapy as a common treatment (treatment as usual). Primary (Visual Analogue Scale – VAS) and secondary (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, peak expiratory flow (PEF), residual volume (RV), functional residual capacity (FRC), total lung capacity (TLC), RV/TLC, and diffusing capacity for carbon monoxide of the lungs (DLCO) outcome measures were measured at baseline, after four weeks, eight weeks and at six months follow up. The effects between the two groups were analyzed using the independent t-test and chi-square test. The intra-group effect was analyzed with a repeated measure ANOVA test. ResultsBaseline demographic characters and study variables show homogenous distribution between the groups (p > 0.05). Four weeks following two different training protocols virtual reality distraction group shows more significant changes in pain intensity, FVC, FEV1, FEV1/FVC, PEF, RV, FRC, TLC, RV/TLC, and DLCO (p = 0.001) but not in RV (p = 0.541). The similar improvements were noted in the 8 weeks and 6 months follow up. ConclusionThe reports of the study concluded that virtual reality distraction is an effective and useful technique in reducing pain and increasing lung capacity in chest burn patient with ARDS following smoke inhalation in community-dwelling middle-aged adults. In the virtual reality distraction group, the patients reported significantly less pain and clinically meaningful changes in pulmonary functions as compared to the control group (physiotherapy + relaxation).

A Holistic Approach from Systems Biology Reveals the Direct Influence of the Quorum-Sensing Phenomenon on Pseudomonas aeruginosa Metabolism to Pyoverdine Biosynthesis.

Computational modeling and simulation of biological systems have become valuable tools for understanding and predicting cellular performance and phenotype generation. This work aimed to construct, model, and dynamically simulate the virulence factor pyoverdine (PVD) biosynthesis in Pseudomonas aeruginosa through a systemic approach, considering that the metabolic pathway of PVD synthesis is regulated by the quorum-sensing (QS) phenomenon. The methodology comprised three main stages: (i) Construction, modeling, and validation of the QS gene regulatory network that controls PVD synthesis in P. aeruginosa strain PAO1; (ii) construction, curating, and modeling of the metabolic network of P. aeruginosa using the flux balance analysis (FBA) approach; (iii) integration and modeling of these two networks into an integrative model using the dynamic flux balance analysis (DFBA) approximation, followed, finally, by an in vitro validation of the integrated model for PVD synthesis in P. aeruginosa as a function of QS signaling. The QS gene network, constructed using the standard System Biology Markup Language, comprised 114 chemical species and 103 reactions and was modeled as a deterministic system following the kinetic based on mass action law. This model showed that the higher the bacterial growth, the higher the extracellular concentration of QS signal molecules, thus emulating the natural behavior of P. aeruginosa PAO1. The P. aeruginosa metabolic network model was constructed based on the iMO1056 model, the P. aeruginosa PAO1 strain genomic annotation, and the metabolic pathway of PVD synthesis. The metabolic network model included the PVD synthesis, transport, exchange reactions, and the QS signal molecules. This metabolic network model was curated and then modeled under the FBA approximation, using biomass maximization as the objective function (optimization problem, a term borrowed from the engineering field). Next, chemical reactions shared by both network models were chosen to combine them into an integrative model. To this end, the fluxes of these reactions, obtained from the QS network model, were fixed in the metabolic network model as constraints of the optimization problem using the DFBA approximation. Finally, simulations of the integrative model (CCBM1146, comprising 1123 reactions and 880 metabolites) were run using the DFBA approximation to get (i) the flux profile for each reaction, (ii) the bacterial growth profile, (iii) the biomass profile, and (iv) the concentration profiles of metabolites of interest such as glucose, PVD, and QS signal molecules. The CCBM1146 model showed that the QS phenomenon directly influences the P. aeruginosa metabolism to PVD biosynthesis as a function of the change in QS signal intensity. The CCBM1146 model made it possible to characterize and explain the complex and emergent behavior generated by the interactions between the two networks, which would have been impossible to do by studying each system's individual components or scales separately. This work is the first in silico report of an integrative model comprising the QS gene regulatory network and the metabolic network of P. aeruginosa.

Use of Thalamus L-Sign to Differentiate Periventricular Leukomalacia From Neurometabolic Disorders.

To assess the diagnostic value of the thalamus L-sign on magnetic resonance imaging (MRI) in distinguishing between periventricular leukomalacia and neurometabolic disorders in pediatric patients. In this retrospective study, clinical and imaging information was collected from 50 children with periventricular leukomalacia and 52 children with neurometabolic disorders. MRI was used to evaluate the L-sign of the thalamus (ie, injury to the posterolateral thalamus) and the lobar distribution of signal intensity changes. Age, sex, gestational age, and level of Gross Motor Function Classification System (only for periventricular leukomalacia) constituted the clinical parameters. Statistical evaluation of group differences for imaging and clinical variables were conducted using univariable statistical methods. The intra- and inter-observer agreement was evaluated using Cohen's kappa. Univariable or multivariable logistic regression was employed for selection of variables, determining independent predictors, and modeling. The thalamus L-sign was observed in 70% (35/50) of patients in the periventricular leukomalacia group, but in none of the patients with neurometabolic disorder (P < .001). The gestational age between groups varied significantly (P < .001). Involvement of frontal, parietal, and occipital lobes differed significantly between groups (P < .001). In the logistic regression, the best model included negative thalamus L-sign and gestational age, yielding an area under the curve, accuracy, sensitivity, specificity, and precision values of 0.995, 96.1%, 96%, 96.2%, and 96%, respectively. Both the lack of thalamus L-sign and gestational age were independent predictors (P < .001). The thalamus L-sign and gestational age may be useful in distinguishing between periventricular leukomalacia and neurometabolic disorders.

Correlation of bone mineral density using the dual energy x-ray absorptiometry and the magnetic resonance imaging of the lumbar spine in Indian patients

BackgroundDual-energy x-ray absorptiometry (DEXA) scan is extensively used to diagnose osteoporosis. But surprisingly, osteoporosis remains an underdiagnosed condition with many fragility fracture patients who have failed to undergo DEXA or received concomitant treatment for osteoporosis. Magnetic resonance imaging (MRI) of the lumbar spine is a routine radiological investigation bring done for low back pain. MRI can detect changes in the bone marrow signal intensity on the standard T1-weighted images. This correlation can be explored to measure osteoporosis in elderly and post-menopausal patients. The present study aims to find any correlation of bone mineral density using the DEXA and MRI of the lumbar spine in Indian patients. MethodsFive regions of interest (ROI) of size 130–180 mm2 were placed in the vertebral body in the mid-sagittal section and parasagittal sections on either side (four in L1-L4 and one outside body) of elderly patients who underwent MRI for back pain. They also underwent a DEXA scan for osteoporosis. Signal to Noise Ratio (SNR) was calculated by dividing the mean signal intensity obtained for each vertebra by the standard deviation of the noise. Similarly, SNR was measured for 24 controls. An MRI-based “M score” was calculated by getting the difference in SNR patients to SNR controls and then dividing it by the control's standard deviation (SD). Correlation between the T score on DEXA and M scores on MRI was found out. ResultsWith the M score greater than or equal to 2.82, the sensitivity was 87.5%, and the specificity was 76.5%. M scores negatively correlated with the T score. With the increase in the T score, the M score decreased. The Spearman correlation coefficient for the spine T score was −0.651, with a p-value of <0.001, and the hip T score was −0.428, with a p-value of 0.013. ConclusionOur study indicates that MRI investigations are helpful in Osteoporosis assessments. Even though MRI may not replace DEXA, it can give insight into elderly patients who get an MRI routinely for back pain. It may also have a prognostic value.

Transrectal Absorber Guide Raster-Scanning Optoacoustic Mesoscopy for Label-Free In Vivo Assessment of Colitis.

Optoacoustic imaging (OAI) enables microscale imaging of endogenous chromophores such as hemoglobin at significantly higher penetration depths compared to other optical imaging technologies. Raster-scanning optoacoustic mesoscopy (RSOM) has recently been shown to identify superficial microvascular changes associated with human skin pathologies. In animal models, the imaging depth afforded by RSOM can enable entirely new capabilities for noninvasive imaging of vascular structures in the gastrointestinal tract, but exact localization of intra-abdominal organs is still elusive. Herein the development and application of a novel transrectal absorber guide for RSOM (TAG-RSOM) is presented to enable accurate transabdominal localization and assessment of colonic vascular networks in vivo. The potential of TAG-RSOM is demonstrated through application during mild and severe acute colitis in mice. TAG-RSOM enables visualization of transmural vascular networks, with changes in colon wall thickness, blood volume, and OAI signal intensities corresponding to colitis-associated inflammatory changes. These findings suggest TAG-RSOM can provide a novel monitoring tool in preclinical IBD models, refining animal procedures and underlines the capabilities of such technologies to address inflammatory bowel diseases in humans.

Canal narrowing in adult patients with cervical spinal cord injury without computed tomography evidence of trauma

PurposeCervical spinal cord injury can be a particularly devastating sequela of trauma. The purpose of this study was to describe the imaging findings of adult patients with cervical spinal cord injury without computed tomography evidence of trauma (SCIWOCTET). MethodsAll adult patients (≥18 years) treated for acute cervical SCIWOCTET at a single Level I adult trauma center over an eight-year period were retrospectively identified. CT imaging was evaluated for degenerative changes narrowing the midsagittal canal diameter (SCD) of the cervical spine and relative congenital cervical stenosis (CCS; congenital narrowing of the SCD <13 mm). Magnetic resonance imaging (MRI) scans were evaluated for signal intensity change (SIC) suspicious for cord edema/contusion as well as ligamentous injury, hemorrhage, and epidural hematoma. ResultsNinety-six patients with cervical SCIWOCTET met inclusion criteria. The most common mechanism of injury was fall from standing (47.9%). On CT, 86 patients (89.6%) had CCS. Degenerative changes were present in 95 patients (99.0%). In 98/99 patients (99.0%), the point of narrowest cervical SCD was ≤8 mm. On MRI, 79 patients (82.3%) demonstrated signal intensity change (SIC) indicative of cord edema/contusion, while 16 (16.7%) had ligamentous injury. Intramedullary cord hemorrhage was seen in two patients (2.1%) and epidural hematoma in three (3.1%). ConclusionDegenerative changes or CCS may narrow the minimum cervical SCD beyond the threshold at which low-energy trauma results in C-SCI. Adult patients with cervical spinal stenosis, whether congenital and/or degenerative, and neurologic findings referable to the cervical spine should be assessed for C-SCI.

Diagnostic performance of multiparametric magnetic resonance imaging in the differentiation of clear cell renal cell cancer.

This study aimed to evaluate the diagnostic performance of multiparametric magnetic resonance imaging (mpMRI) in the differentiation of renal cell carcinoma (RCC) subtypes. This is a retrospective diagnostic performance study, in which the diagnostic performances of mpMRI features were evaluated to differentiate clear cell RCC (ccRCC) from non-clear cell RCC (non-ccRCC). Adult patients who were evaluated using a 3-Tesla dynamic contrast-enhanced mpMRI before undergoing partial or radical nephrectomy for possible malignant renal tumors were included in the study. Signal intensity change percentages (SICP) between contrast-enhanced phases and pre-administration period for both the tumor and normal renal cortex, and tumor-to-cortex enhancement index (TCEI); tumor apparent diffusion coefficient (ADC) values; tumor-to-cortex ADC ratio; and a scale which was developed according to the tumor signal intensities on the axial fat-suppressed T2-weighted Half-Fourier Acquisition Single-shot Turbo spin Echo (HASTE) images were used in ROC analysis to estimate the presence of ccRCC in the patients. The reference test positivity was the histopathologic examination of the surgical specimens. Ninety-eight tumors from 91 patients were included in the study, and 59 of them were ccRCC, 29 were pRCC, and 10 were chRCC. The mpMRI features that had the three highest sensitivity rates were excretory phase SICP, T2-weighted HASTE scale score, and corticomedullary phase TCEI (93.2%, 91.5%, and 86.4%, respectively). However, those with the three highest specificity rates were nephrographic phase TCEI, excretory phase TCEI, and tumor ADC value (94.9%, 94.9%, and 89.7%, respectively). Several parameters on mpMRI showed an acceptable performance to differentiate ccRCC from non-ccRCC.

What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

Hemophilic arthropathy can cause recurrent hemarthroses and severe damage to the synovium and articular cartilage. Previous studies have shown that vascular endothelial growth factor (VEGF) plays an essential role in neoangiogenesis. Bevacizumab, a monoclonal VEGF inhibitor, is used clinically to prevent angiogenesis. However, its effects on hemophilic arthropathy are unknown. Using a hemophilic arthropathy rabbit model, we asked: Does an intra-articular injection of bevacizumab (1) inhibit VEGF, (2) decrease signal intensity in dynamic contrast-enhanced MRI (DCE-MRI) as an assessment of capillary permeability and neoangiogenesis, (3) reduce cartilage damage, (4) reduce synovial changes, and (5) affect macroscopic changes during the development of hemophilic arthropathy? Twenty-five male New Zealand rabbits were divided into four groups. Eight knees from four rabbits were used as the control group. We used an established animal model for hemophilic arthropathy in the remaining 21 rabbits. Animals were assigned randomly to three groups with seven rabbits in each group. One group was used to establish mild arthropathy, and the other two were used to establish severe arthropathy. Autologous blood from the rabbits' ears was injected into the right and left knees twice per week for 8 weeks to represent mild arthropathy and for 16 weeks to represent severe arthropathy. In the mild arthropathy group, bevacizumab was injected into the right knee once every 2 weeks. Bevacizumab was injected into the right knee of rabbits in one of the severe arthropathy groups once every 2 weeks for 16 weeks, and intra-articular bevacizumab injections were administered to the right knees of rabbits in the other severe arthropathy group once every 2 weeks after the eighth week. An equal volume of 0.9% saline was injected into the left knee of rabbits in all arthropathy groups. To explore the efficacy of bevacizumab, joint diameters were quantitatively measured, and cartilage and synovial changes were examined. Degeneration of articular cartilage was evaluated with the semiquantitative Osteoarthritis Research Society International grading system. Synovial damage was analyzed with a semiquantitative microscopic scoring system. In addition, we evaluated perfusion and angiogenesis using DCE-MRI (quantitative signal intensity changes). Immunohistochemical testing was used to measure VEGF levels (analyzed by Western blotting). Intra-articular bevacizumab treatment inhibited VEGF in our rabbit model of hemophilic arthropathy. VEGF protein expression levels were lower in the mild arthropathy group that received intra-articular bevacizumab (0.89 ± 0.45) than the mild arthropathy control group (1.41 ± 0.61) (mean difference -0.52 [95% CI -0.898 to -0.143]; p = 0.02). VEGF levels were lower in the severe arthropathy group that received treatment for 16 weeks (0.94 ± 0.27) than in the control knees (1.49 ± 0.36) (mean difference -0.55 [95% CI -0.935 to -0.161]; p = 0.01). In the severe arthropathy group, the Osteoarthritis Research Society International score indicating cartilage damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than in the control group (median 17 [range 13 to 18] versus 18 [range 17 to 20]; difference of medians 1; p = 0.02). Additionally, the scores indicated synovial damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than the control group (median 5 [range 4 to 9] versus 9 [range 8 to 12]; difference of medians 4; p = 0.02). The mean of mean values for signal intensity changes was higher in the nontreated severe groups than in the group of healthy knees. The signal intensity changes were higher in the severe arthropathy control groups (Groups BC and CC) (median 311.6 [range 301.4 to 361.2] and 315.1 [range 269.7 to 460.4]) than in the mild arthropathy control group (Group AC) (median 234.1 [range 212.5 to 304.2]; difference of medians 77.5 and 81, respectively; p = 0.02 and p = 0.04, respectively). In the severe arthropathy group, discoloration caused by hemosiderin deposition in the cartilage and synovium was more pronounced than in the mild arthropathy group. In the severe arthropathy group treated with intra-articular bevacizumab, joint diameters were smaller than in the control group (Group BT median 12.7 mm [range 12.3 to 14.0] versus Group BC median 14.0 mm [range 13.1 to 14.5]; difference of medians 1.3 mm; p = 0.02). Hemarthrosis damages the synovial tissues and cartilage in the knees of rabbits, regardless of whether they are treated with intra-articular bevacizumab. However, intra-articular injection of bevacizumab may reduce cartilage and synovial damage in rabbits when treatment is initiated early during the development of hemophilic arthropathy. If the findings in this study are replicated in larger-animal models that consider the limitations of our work, then a trial in humans might be appropriate to ascertain whether intra-articular injection of bevacizumab could reduce cartilage damage and synovial changes in patients with hemophilia whose hemarthroses cannot otherwise be controlled.

Abstract 3439: Evaluating nuclear receptor heterodimerization using live cell proximity assays: Implications for novel therapeutic approaches for hormone driven cancers

Abstract Breast and prostate cancer are the leading cancer diagnoses for women and men, respectively, second only to cutaneous cancers. Breast and prostate cancer arise from aberrant estrogen/estrogen receptor (ER) and testosterone/androgen receptor signaling (AR), respectively. These sex hormone receptors are members of the steroid hormone receptor family, which also includes the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and progesterone receptor (PR). Although these receptors canonically function through homodimerization, recent evidence has suggested that receptor crosstalk can amplify or dampen the actions of heterologous receptors. However, these interactions have not been extensively studied in all possible combinations of steroid hormone receptor crosstalk. In this project, we hypothesize that heterodimerization may amplify or repress the transcriptional response(s) elicited by the various receptor complexes depending upon conditions such as concentration of ligands, type of ligand, physiological states, and the types/functions of promoter regions. To test this hypothesis, we investigated the significance of ligand-induced interactions between different homo- and heterodimer combinations of AR, ARV7, GR, MR, PR, and ERα in HEK293 cells using IncuCyte live-cell imaging and NanoBRET technology. Ultimately, the combination of transfection experiments, live-cell imaging, and NanoBRET assays provided insight into which combination of steroid receptors successfully interact to amplify (or dampen) the HaloTag expression, luminescence intensity at 450nM (i.e., NanoLuc expression), and NanoBRET ratio (i.e., acceptor emission luminescence at 610nM divided by donor emission luminescence at 450nM) in HEK293 cells. Our studies revealed that heterodimerization of ERα-PR, ERα-MR, AR-GR, AR-PR, ARV7-MR, ARV7-PR, and GR-MR produced significant ligand-induced changes in signaling intensity compared to no ligand conditions for each fusion protein construct. Additionally, to demonstrate the value of the NanoBRET method for modelling clinically relevant disease conditions, we assessed the physical interaction of ERα and PR in the context of the ERα Y537S mutation - a mutation associated with endocrine therapy resistance in breast cancer that results in a constitutively active ERα. The results showed that ERα-Y537S mutation increases ERα/PR physical interaction upon PR-B stimulation in a NanoBRET proximity-based assay. Future directions include testing these interactions in breast and prostate cancer cell lines and identifying the receptors’ localization within the cell, the results of which may be of clinical importance. Citation Format: Amira Ishag-Osman, David Hosfield, Rosemary Huggins, Geoffrey Greene. Evaluating nuclear receptor heterodimerization using live cell proximity assays: Implications for novel therapeutic approaches for hormone driven cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3439.

Broadband Full-Spectrum Raman Excitation Mapping Reveals Intricate Optoelectronic-Vibrational Resonance Structure of Chirality-Pure Single-Walled Carbon Nanotubes.

The Raman excitation spectra of chirality-pure (6,5), (7,5), and (8,3) single-walled carbon nanotubes (SWCNTs) are explored for homogeneous solid film samples over broad excitation energy and scattering energy ranges using a rapid and relatively simple full spectrum Raman excitation mapping technique. Identification of variation in scattering intensity with sample type and phonon energy related to different vibrational bands is clearly realized. Excitation profiles are found to vary strongly for different phonon modes. Some modes' Raman excitation profiles are extracted, with the G band profile compared to earlier work. Other modes, such as the M and iTOLA modes, have quite sharp resonance profiles and strong resonances. Conventional fixed wavelength Raman spectroscopy can miss these effects on the scattering intensities entirely due to the significant intensity changes observed for small variations in excitation wavelength. Peak intensities for phonon modes traceable to a pristine carbon lattice forming a SWCNT sidewall were greater for high-crystallinity materials. In the case of highly defective SWCNTs, the scattering intensities of the G band and the defect-related D band are demonstrated to be affected both in absolute intensities and in relative ratio, with the ratio that would be measured by single wavelength Raman scattering dependent on the excitation wavelength due to differences in the resonance energy profiles of the two bands. Lastly it is shown that the approach of this contribution yields a clear path toward increasing the rigor and quantification of resonance Raman scattering intensity measurements through tractable corrections of excitation and emission side variations in efficiency with excitation wavelength.