IDDSI-compliant recipes containing oral contrast agents for radiological dysphagia diagnostics.

Videofluoroscopic swallowing study (VFSS), alongside flexible endoscopic evaluation of swallowing, represents the gold standard for diagnosing swallowing disorders and to determine severity, pathophysiology, and effective interventions, including texture modification. The clinical swallowing examination and assessment supplements these instrumental methods and serves as the basis for the modules of swallowing diagnostics. The adaptation of food and drink consistencies in dysphagia management has become widespread. For valid results of a VFSS with respect to confirming swallowing safety and efficiency of different liquid and food consistencies and textures, the use of uniform recipes containing radio-opaque contrast media is important. Our goal was to identify recipes that would produce consistencies that conform to the liquid and food levels of 0-7, as defined by the International Dysphagia Diet Standardization Initiative (IDDSI), with barium- and iodine-based contrast media, xanthan gum-based thickeners, and other edible components, which also show sufficient contrast on VFSS. In this study, we determined the different recipes using IDDSI testing methods and explored their radiological characteristics using a Philips MultiDiagnost Eleva fluoroscopy system and two different fluid contrast agents: barium- (Micropaque®) and iodine-based (Telebrix®). All recipes showed sufficient contrast on fluoroscopy and could be visualized in the amounts used for swallowing examinations. They were practical and easy to implement in terms of production and availability of the components. The homogeneity of the recipes diminished with higher IDDSI levels, which represent transitional food, but appeared still sufficient for fluoroscopic examination. The opacity did not significantly differ between the barium- and iodine-based contrast media.

Microvascular changes following exposure to iodinated contrast media in vitro. A qualitative comparison to serum creatinine concentrations in post-cardiac catheterization patients.

INTRODUCTION: Contrast-associated acute kidney injury (CA-AKI) is characterized as a loss of renal function following radiological contrast media administration. While all contrast media induce variable changes in microvascular endothelial cells in vitro, only few studies report clinical significance of their findings. A comprehensive assessment of the effect of iodinated contrast media on the renal function in vitro and in vivo is essential. The aim of our study was to morphometrically quantify the effect of two different contrast media (Iobitridol and Iodixanol) on vascular endothelial capillaries in vitro and to analyze their effect on the renal function of patients who underwent cardiac catheterization including the intra-arterial administration of contrast media, by measuring serum creatinine concentration (SCr), a byproduct of muscle metabolism, primarily excreted by the kidneys. Our hypothesis suggests that conducting a qualitative comparison of both outcomes will enable identification of differences and similarities between in vitro and in vivo exposure. MATERIAL AND METHODS: In vitro, co-cultures of human dermal fibroblasts and human dermal microvascular endothelial cells forming capillary beds were exposed to a mixture of phosphate buffered saline and either Iobitridol, Iodixanol, or one of their supplements EDTA or Trometamol for 1.5 or 5 min. Negative control co-cultures were exposed exclusively to phosphate buffered saline. Co-cultures were either directly fixed or underwent a regeneration time of 1, 3 or 7 days. An artificial intelligence software was trained for detection of labeled endothelial capillaries (CD31) on light microscope images and measurements of morphometric parameters. In vivo, we retrospectively analyzed data from patients who underwent intra-arterial administration of contrast media and for whom SCr values were available pre- and post-contrast exposition (1, 3, and 7 days following procedure). Temporal development of SCr and incidence of CA-AKI were assessed. Both exposure types were qualitatively compared. RESULTS: In vitro, Iobitridol, Iodixanol and EDTA induced a strong decrease of two morphometric parameters after 3 days of regeneration. In vivo, a significant increase of SCr and incidence of CA-AKI was observed 3 days following procedure in the post-contrast media patients. No difference was observed between groups. DISCUSSION: Two of the morphometric parameters were inversely proportional to the SCr of the patients. If the endothelial damages observed in vitro occur in vivo, it may result in renal hypoxia, inducing a loss of kidney function clinically translated into an increase of SCr. Further development of our in vitro model could allow closer replication of the internal structure of a kidney and bridge the gap between in vitro studies and their clinical findings.

Is proctoscopy sufficient for the evaluation of colorectal anastomosis prior to ileostomy reversal? A nationwide retrospective analysis of the Italian Society of Surgical Oncology Colorectal Cancer Network Collaborative group (SICO-CCN).

AIM: Several methods for assessing anastomotic integrity have been proposed, but the best is yet to be defined. The aim of this study was to compare the different methods to assess the integrity of colorectal anastomosis prior to ileostomy reversal. METHOD: A retrospective cohort analysis on patients between 1 January 2010 and 31 December 2020 with a defunctioning stoma for middle and low rectal anterior resection was performed. A propensity score matching comparison between patients who underwent proctoscopy alone and patients who underwent proctoscopy plus any other preoperative method to assess the integrity of colorectal anastomosis prior to ileostomy reversal (transanal water-soluble contrast enema via conventional radiology, transanal water-soluble contrast enema via CT, and magnetic resonance) was performed. RESULTS: The analysis involved 1045 patients from 26 Italian referral colorectal centres. The comparison between proctoscopy alone versus proctoscopy plus any other preoperative tool showed no significant differences in terms of stenoses (p = 0.217) or leakages (p = 0.103) prior to ileostomy reversal, as well as no differences in terms of misdiagnosed stenoses (p = 0.302) or leakages (p = 0.509). Interestingly, in the group that underwent proctoscopy and transanal water-soluble contrast enema the comparison between the two procedures demonstrated no significant differences in detecting stenoses (2 vs. 0, p = 0.98), while there was a significant difference in detecting leakages in favour of transanal water-soluble contrast enema via CT (3 vs. 12, p = 0.03). CONCLUSIONS: We can confirm that proctoscopy alone should be considered sufficient prior to ileostomy reversal. However, in cases in which the results of proctoscopy are not completely clear or the surgeon remains suspicious of an anastomotic leakage, transanal water-soluble contrast enema via CT could guarantee its detection.

Multisize Electrode Field-of-View: Validation by High Resolution Gadolinium-Enhanced Cardiac Magnetic Resonance.

BACKGROUND: Voltage mapping to detect ventricular scar is important for guiding catheter ablation, but the field-of-view of unipolar, bipolar, conventional, and microelectrodes as it relates to the extent of viable myocardium (VM) is not well defined. OBJECTIVES: The purpose of this study was to evaluate electroanatomic voltage-mapping (EAVM) with different-size electrodes for identifying VM, validated against high-resolution ex-vivo cardiac magnetic resonance (HR-LGE-CMR). METHODS: A total of 9 swine with early-reperfusion myocardial infarction were mapped with the QDOT microcatheter. HR-LGE-CMR (0.3-mm slices) were merged with EAVM. At each EAVM point, the underlying VM in multisize transmural cylinders and spheres was quantified from ex vivo CMR and related to unipolar and bipolar voltages recorded from conventional and microelectrodes. RESULTS: In each swine, 220 mapping points (Q1, Q3: 216, 260 mapping points) were collected. Infarcts were heterogeneous and nontransmural. Unipolar and bipolar voltage increased with VM volumes from >175 mm3 up to >525 mm3 (equivalent to a 5-mm radius cylinder with height >6.69 mm). VM volumes in subendocardial cylinders with 1- or 3-mm depth correlated poorly with all voltages. Unipolar voltages recorded with conventional and microelectrodes were similar (difference 0.17 ± 2.66 mV) and correlated best to VM within a sphere of radius 10 and 8 mm, respectively. Distance-weighting did not improve the correlation. CONCLUSIONS: Voltage increases with transmural volume of VM but correlates poorly with small amounts of VM, which limits EAVM in defining heterogeneous scar. Microelectrodes cannot distinguish thin from thick areas of subendocardial VM. The field-of-view for unipolar recordings for microelectrodes and conventional electrodes appears to be 8 to 10 mm, respectively, and unexpectedly similar.

Protease-Mediated T1 Contrast Enhancement of Multilayered Magneto-Gadolinium Nanostructures for Imaging and Magnetic Hyperthermia.

In this work, we constructed a multifunctional composite nanostructure for combined magnetic hyperthermia therapy and magnetic resonance imaging based on T1 and T2 signals. First, iron oxide nanocubes with a benchmark heating efficiency for magnetic hyperthermia were assembled within an amphiphilic polymer to form magnetic nanobeads. Next, poly(acrylic acid)-coated inorganic sodium gadolinium fluoride nanoparticles were electrostatically loaded onto the magnetic nanobead surface via a layer-by-layer approach by employing a positively charged enzymatic-cleavable biopolymer. The positive-negative multilayering process was validated through the changes occurring in surface ζ-potential values and structural characterization by transmission electron microscopy (TEM) imaging. These nanostructures exhibit an efficient heating profile, in terms of the specific absorption rates under clinically accepted magnetic field conditions. The addition of protease enzyme mediates the degradation of the surface layers of the nanostructures with the detachment of gadolinium nanoparticles from the magnetic beads and exposure to the aqueous environment. Such a process is associated with changes in the T1 relaxation time and contrast and a parallel decrease in the T2 signal. These structures are also nontoxic when tested on glioblastoma tumor cells up to a maximum gadolinium dose of 125 µg mL-1, which also corresponds to a iron dose of 52 µg mL-1. Nontoxic nanostructures with such enzyme-triggered release mechanisms and T1 signal enhancement are desirable for tracking tumor microenvironment release with remote T1-guidance and magnetic hyperthermia therapy actuation to be done at the diseased site upon verification of magnetic resonance imaging (MRI)-guided release.

[Trends and Prospects for Photoreactivation in Health Promotion].

The use of light to promote health, reduce harm, and restore functionality is a novel, non-accumulative physical strategy that contrasts with the predominantly chemical approaches used in Western medicine. This strategy may serve as an independent function for healthcare professionals and warrants further exploration. Photoreactivation, achieved by adjusting patients' physiological clocks at different times, utilizing specific wavelengths, varying color temperatures, and using illuminance, is a potent tool for improving mood and sleep quality, regulating autonomic nervous system balance, enhancing attention, and delaying cognitive decline. Light therapy is a rapidly expanding field in healthcare that offers new opportunities to enhance quality of life, prevent diseases, and improve overall well-being. This article elucidates the fundamental concepts of photoreactivation, explores its application across diverse health domains, examines its future development prospects, and discusses the challenges faced by photoreactivation and related solutions to ensure the responsible use of light to enhance and restore physiological and psychological functions.

Carbon Dots for Multiuse Platform: Intracellular pH Sensing and Complementary Intensified T1-T2 Dual Imaging Contrast Nanoprobes.

Measurement of pH in living cells is a great and decisive factor for providing an early and accurate diagnosis factor. Along with this, the multimodal transverse and longitudinal relaxivity enhancement potentiality over single modality within a single platform in the magnetic resonance imaging (MRI) field is a very challenging issue for diagnostic purposes in the biomedical field of application. Therefore, this work aims to design a versatile platform by fabricating a novel nanoprobe through holmium- and manganese-ion doping in carbon quantum dots (Ho-Mn-CQDs), which can show nearly neutral intracellular pH sensing and MRI imaging at the same time. These manufactured Ho-Mn-CQDs acted as excellent pH sensors in the near-neutral range (4.01-8.01) with the linearity between 6.01 and 8.01, which could be useful for the intracellular pH-sensing capability. An innumerable number of carboxyl and amino groups are present on the surface of the prepared nanoprobe, making it an excellent candidate for pH sensing through fluorescence intensity quenching phenomena. Cellular uptake and cell viability experiments were also executed to affirm the intracellular accepting ability of Ho-Mn-CQDs. Furthermore, with this pH-sensing quality, these Ho-Mn-CQDs are also capable of acting as T1-T2 dual modal imaging contrast agents in comparison with pristine Ho-doped and Mn-doped CQDs. The Ho-Mn-CQDs showed an increment of r1 and r2 relaxivity values simultaneously compared with only the negative contrast agent, holmium in holmium-doped CQDs, and the positive contrast agent, manganese in manganese-doped CQDs. The above-mentioned observations elucidate that its tiny size, excitation dependence of fluorescence behavior, low cytotoxicity, and dual modal contrast imaging capability make it an ideal candidate for pH monitoring in the near-neutral range and also as a dual modal MRI imaging contrast enhancement nanoprobe at the same time.

Dual/Multi-Modal Image-Guided Diagnosis and Therapy Based on Luminogens with Aggregation-Induced Emission.

The combination of multiple imaging methods has made an indelible contribution to the diagnosis, surgical navigation, treatment, and prognostic evaluation of various diseases. Due to the unique advantages of luminogens with aggregation-induced emission (AIE), their progress has been significant in the field of organic fluorescent contrast agents. Herein, this manuscript summarizes the recent advancements in AIE molecules as contrast agents for optical image-based dual/multi-modal imaging. We particularly focus on the exceptional properties of each material and the corresponding application in the diagnosis and treatment of diseases.

Fluid-attenuated inversion-recovery sequence with fat suppression as an alternative to contrast-enhanced MRI in pediatric synovitis.

BACKGROUND: Non-contrast magnetic resonance imaging (MRI) fluid-attenuated inversion-recovery sequence (FLAIR) with fat suppression (FS) has not been validated in children. OBJECTIVE: Compare FLAIR to T1-weighted post contrast (T1CE) in the detection of knee synovitis. METHODS AND MATERIALS: Institutional review board (IRB) waived consent. Children who underwent T1CE and FLAIR sequences of the knee on a 3-T magnet from April 2021 to December 2021 were included. Two pediatric radiologists assessed axial FLAIR and T1CE images for synovitis and synovial thickness. Reliability and agreement were assessed. Sensitivities, specificities, and accuracy were calculated for FLAIR using T1CE as reference standard. RESULTS: In total, 42 knees (39 patients) were assessed (median age 12.9 years (2.3-17.8 years); 62% male, 38% female). Readers judged 20/42 (48%) knees to have synovitis. Sensitivity of FLAIR for reader 1 was 79% (19/24; 95% CI 0.58, 0.93) and 84% (16/19; 95% CI 0.60, 0.97) for reader 2. Specificity of FLAIR for reader 1 was 94% (17/18; 95% CI 0.73, 1) and 83% (19/23; 95% CI 0.61, 0.95) for reader 2. Accuracy for readers 1 and 2 was 86% (36/42; 95% CI 0.71, 0.95) and 83% (35/42; 95% CI 0.69, 0.93), respectively. Inter-reader reliability was good (0.75-0.90) for synovial measurements for FLAIR (ICC = 0.80; 95% CI 0.71, 0.86) and moderate for T1 CE (ICC = 0.62 (95% CI 0.48, 0.73)). CONCLUSION: FLAIR FS depicts synovium in the pediatric knee with similar reliability to T1 CE and may be an acceptable alternative to contrast in the initial diagnosis of synovitis.

Polymerisation of cyanoacrylates: The effect of sclero-embolic and contrast agents.

OBJECTIVES: The objective is to investigate the interaction of sclero-embolic and contrast agents with the polymerisation of medical grade n-butyl-cyanoacrylates. METHODS: An in vitro spectrophotometric absorbance method was developed to detect changes in light transmission to measure n-BCA polymerisation. The initiation and the rate-of-polymerisation of mixtures of n-BCA with sclero-embolic and contrast agents were investigated. RESULTS: Initiation of polymerisation: VENABLOCK™ and HISTOACRYL® were the fastest agents to polymerise, while VENASEAL™ was the slowest. Rate of polymerisation: Hypertonic saline inhibited the polymerisation of all n-BCAs, while hypertonic glucose prolonged the polymerisation rate. ETHANOL and detergent sclerosants had no effect. Contrast agents OMNIPAQUE™ and ULTRAVIST® initiated and prolonged the polymerisation of n-BCA, but in contrast, LIPIODOL® failed to initiate the process. CONCLUSIONS: The commercially available medical cyanoacrylates differ in their polymerisation rates. These polymerisation rates are further affected when these products are used in conjunction with other compounds, such as sclero-embolic and contrast agents.

Photoacoustic Imaging Endometriosis Lesions with Nanoparticulate Polydopamine as a Contrast Agent.

Endometriosis (EM) is a prevalent and debilitating gynecological disorder primarily affecting women of reproductive age. The diagnosis of EM is historically hampered by delays, owing to the absence of reliable diagnostic and monitoring techniques. Herein, it is reported that photoacoustic imaging can be a noninvasive modality for deep-seated EM by employing a hyaluronic-acid-modified polydopamine (PDA@HA) nanoparticle as the contrast agent. The PDA@HA nanoparticles exhibit inherent absorption and photothermal effects when exposed to near-infrared light, proficiently converting thermal energy into sound waves. Leveraging the targeting properties of HA, distinct photoacoustic signals emanating from the periphery of orthotopic EM lesions are observed. These findings are corroborated through anatomical observations and in vivo experiments involving mice with green fluorescent protein-labeled EM lesions. Moreover, the changes in photoacoustic intensity over a 24 h period reflect the dynamic evolution of PDA@HA nanoparticle biodistribution. Through the utilization of a photoacoustic ultrasound modality, in vivo assessments of EM lesion volumes are conducted. This innovative approach not only facilitates real-time monitoring of the therapeutic kinetics of candidate drugs but also obviates the need for the sacrifice of experimental mice. As such, this study presents a promising avenue for enhancing the diagnosis and drug-screening processes of EM.

Differences in the Diagnosis and Treatment of Patients with Early-Stage Hepatocellular Liver Cancer by Multi-Row Spiral CTMDCT and Gd-EOB-DTPA-Enhanced MRI.

Objective: The assessment of liver cancer lesion characteristics mainly relies on multi-row spiral computed tomography (MDCT) and magnetic resonance imaging (MRI). MDCT suffers from a series of problems, such as low soft tissue contrast and large tumor boundary errors, which lead to its limited practical application value in liver cancer. In contrast, Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI has better soft-tissue contrast than MDCT and increases the clarity of liver cancer lesions. To investigate the differences between MDCT and Gd-EOB-DTPA-enhanced MRI in managing patients with hepatocellular liver cancer. Methods: A total of 80 patients diagnosed with hepatocellular carcinoma of the liver, who received treatment at our hospital between September 2020 and September 2022, were included in this study. These patients were evenly divided into two groups: the observation group and the control group, with 40 cases in each. The aim of this study was to compare the differences in signal indices of hepatobiliary stage between the two groups in patients with hepatocellular carcinoma. Results: A total of 89 cancer nodules were detected in patients by MDCT, and 109 cancer nodules were detected in patients by Gd-EOB-DTPA-enhanced MRI. When the number of nodules detected by both imaging modalities was statistically analyzed, the differences in the number of hepatocellular carcinoma (HCC) nodules detected by MDCT and Gd-EOB-DTPA-enhanced MRI were statistically significant (P < .05). Further analysis of the data by single cancer nodule, multiple cancer nodules, and cancer nodule size showed that the difference between the two imaging modalities was statistically significant (P < .05) in the diagnosis of patients with a single liver cancer nodule or multiple liver cancer nodules (94.8% vs.81.3%). The difference in the comparison was statistically significant (P < .05). Conclusion: Gd-EOB-DTPA-enhanced MRI demonstrates superior diagnostic efficacy in detecting small hepatocellular carcinoma, offers improved staging capabilities for hepatocellular carcinoma, and provides more precise guidance for treatment planning.Consequently, Gd-EOB-DTPA-enhanced MRI exhibits exceptional diagnostic value and serves as a valuable tool for guiding treatment decisions in patients with hepatocellular carcinoma.

Iodine density mapping for the diagnosis of acute bowel ischemia using fast kV-switching dual-energy CT.

PURPOSE: To evaluate the diagnostic capabilities of a supplementary color ramped iodine density map compared to virtual monoenergetic images (VMIs) at 74 keV in the diagnosis of acute bowel ischemia (ABI). METHODS: Data for this study were prospectively gathered and retrospectively evaluated. Patients referred to the Department of Diagnostic Radiology between October 2020 and August 2022 on the suspicion of ABI and underwent surgery < 12 h following fast kV-switching venous phase abdominal dual-energy CT (DECT) were consecutively included. Images were evaluated by two board-certified radiologists and two radiology residents. First round included only 74 keV VMIs resembling conventional 120 kVp images, and the second round included a supplementary iodine density map. Readers were asked to register presence of ABI as well as their confidence in their diagnosis based on a 5-point Likert scale. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each observer with the surgical findings as the gold-standard. McNemar's and Wilcoxon signed-rank test were used to compare registrations and diagnostic confidence across assessment rounds. RESULTS: A total of 29 patients resulting in 31 DECT scans were included. Fourteen cases of ischemic/necrotic bowel were reported following surgery. Sensitivity and NPV were decreased with the use of supplementary iodine map images compared to 120 kVp-like images without supplementary iodine map images for three of four observers (round 1 range: 71.4-92.9% and 78.0-94.8%; round 2 range: 57.1-78.6% and 70.1-83.3%, respectively), while specificity and PPV were increased for three of four observers (round 1 range: 64.7-94.1% and 67.4-93.1%; round 2 range: 88.2-94.1% and 73.8-91.1%, respectively). However, no significant difference in ABI diagnosis or diagnostic confidence was found (p-value range: 0.07-1.00 and 0.23-0.58, respectively). CONCLUSION: No significant difference for the diagnosis of ABI was found using supplementary iodine mapping. Our study may suggest a trend of increased specificity and decreased sensitivity, hence, the use of supplementary iodine mapping should be carefully considered.

Cardiothoracic Magnetic Resonance Angiography.

Catheter-based angiography is regarded as the clinical reference imaging technique for vessel imaging; however, it is invasive and is currently used for intervention or physiologic measurements. Contrast enhanced magnetic resonance angiography (MRA) with gadolinium-based contrast agents can be performed as a three-dimensional (3D) MRA or as a time resolved 3D (4D) MRA without physiologic synchronization, in which case cardiac and respiratory motion may blur the edges of the vessels and cardiac chambers. Ferumoxytol has recently been a popular contrast agent for MRA in patients with chronic renal failure. Noncontrast 3D MRA with ECG gating and respiratory navigation are safe and accurate noninvasive cross-sectional imaging techniques for the visualization of great vessels of the heart and coronary arteries in a variety of cardiovascular disorders including complex congenital heart diseases. Noncontrast flow dependent MRA techniques such as time of flight, phase contrast, and black-blood MRA techniques can be used as complementary or primary techniques. Here we review both conventional and relatively new contrast enhanced and non-contrast enhanced MRA techniques including ferumoxytol enhanced MRA, and bright-blood and water-fat separation based noncontrast 3D MRA techniques.

Is contrast-enhanced mammography (CEM) an alternative to MRI in assessing the response to primary systemic therapy of breast cancer?

PURPOSE: To evaluate the accuracy of contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) in the assessing radiological response to primary systemic therapy (PST). METHOD: Prospective study between February 2021 and October 2022. Women with breast cancer and indication of PST were enrolled. CEM and MRI were performed before and after PST, and the findings, including size and radiological response pattern, were compared with the size of the residual lesion measured in surgical specimens and its Miller-Payne classification (considered the gold standard). Two of four independent radiologists, with 2 years of CEM experience and 10 years of MRI experience, reviewed the images while being blinded to the results of the other technique. The agreement between measurements was evaluated using the Pearson correlation coefficient (r) and Lin's coefficient. RESULTS: Forty-eight women with breast cancer who required PST were enrolled in the study, with a mean age of 57.21 ± 10.14 years. A total of thirty-three participants (68.75 %) completed the study. The correlation between CEM and MRI measurements was high before PST (r: 0.97), and local staging was identical for 45 out of 48 patients. MRI demonstrated better accuracy in predicting residual tumor size than CEM, with Lin's coefficient 0.91 and 0.73, respectively. However, no significant differences were observed in predicting response to therapy. Both methods tended to overestimate the size and degree of response in our study, with mean overestimations of 2.87 mm in CEM and 0.51 mm in MRI. CONCLUSION: CEM was found to be as accurate as MRI in predicting response to PST, indicating its potential as an alternative imaging technique, but further research is necessary.

Comprehensive Analysis of the Spatial Distribution of Gadolinium, Iron, Manganese, and Phosphorus in the Brain of Healthy Rats After High-Dose Administrations of Gadodiamide and Gadobutrol.

OBJECTIVES: After the administration of gadolinium-based contrast agents (GBCAs), residual gadolinium (Gd) has been detected in a few distinct morphological structures of the central nervous system (CNS). However, a systematic, comprehensive, and quantitative analysis of the spatial Gd distribution in the entire brain is not yet available. The first aim of this study is to provide this analysis in healthy rats after administration of high GBCA doses. The second aim is to assess the spatial distributions and possible Gd colocalizations of endogenous iron (Fe), manganese (Mn), and phosphorus (P). In addition, the presence of Gd in proximity to blood vessels was assessed by immunohistochemistry. MATERIALS AND METHODS: Male rats were randomly assigned to 3 groups (n = 3/group): saline (control), gadodiamide (linear GBCA), and gadobutrol (macrocyclic GBCA) with cumulative Gd doses of 14.4 mmol/kg of body mass. Five weeks after the last administration, the brains were collected and cryosectioned. The spatial distributions of Gd, Fe, Mn, and P were analyzed in a total of 130 sections, each covering the brain in 1 of the 3 perpendicular anatomical orientations, using laser ablation coupled with inductively coupled plasma mass spectrometry. Quantitative spatial element maps were generated, and the concentrations of Gd, Fe, and Mn were measured in 31 regions of interest covering various distinct CNS structures. Correlation analyses were performed to test for possible colocalization of Gd, Fe, and Mn. The spatial proximity of Gd and blood vessels was studied using metal-tagged antibodies against von Willebrand factor with laser ablation coupled with inductively coupled plasma mass spectrometry. RESULTS: After administration of linear gadodiamide, high Gd concentrations were measured in many distinct structures of the gray matter. This involved structures previously reported to retain Gd after linear GBCA, such as the deep cerebellar nuclei or the globus pallidus, but also structures that had not been reported so far including the dorsal subiculum, the retrosplenial cortex, the superior olivary complex, and the inferior colliculus. The analysis in all 3 orientations allowed the localization of Gd in specific subregions and layers of certain structures, such as the hippocampus and the primary somatosensory cortex. After macrocyclic gadobutrol, the Gd tissue concentration was significantly lower than after gadodiamide. Correlation analyses of region of interest concentrations of Gd, Fe, and Mn revealed no significant colocalization of Gd with endogenous Fe or Mn in rats exposed to either GBCA. Immunohistochemistry revealed a colocalization of Gd traces with vascular endothelium in the deep cerebellar nuclei after gadobutrol, whereas the majority of Gd was found outside the vasculature after gadodiamide. CONCLUSIONS: In rats exposed to gadodiamide but not in rats exposed to gadobutrol, high Gd concentrations were measured in various distinct CNS structures, and structures not previously reported were identified to contain Gd, including specific subregions and layers with different cytoarchitecture and function. Knowledge of these distinct spatial patterns may pave the way for tailored functional neurological testing. Signs for the localization of the remaining Gd in the vascular endothelium were prominent for gadobutrol but not gadodiamide. The results also indicate that local transmetalation with endogenous Fe or Mn is unlikely to explain the spatial patterns of Gd deposition in the brain, which argues against a general role of these metals in local transmetalation and release of Gd ions in the CNS.

Effects of foam rolling on vastus intermedius and lateralis microvascular blood flow.

INTRODUCTION: Foam Rolling (FR) as a technique of self-massage has become a widely used intervention in clinical and sports practice. It is assumed that FR leads to an increased intramuscular microvascular blood flow (MBF), and therefore is commonly recommended as a warm-up or regeneration method. However, no data validate the effects of FR on MBF. This study aimed to assess whether FR increases intramuscular MBF using contrast-enhanced ultrasound (CEUS). METHODS: Ten healthy athletes performed a standardized FR intervention applied to the lateral thigh (3 sets: 45 s FR, 20 s rest). Intramuscular perfusion was determined by CEUS under resting conditions (t0), immediately (t1), and 30 min (t2) after the intervention. Peak enhancement (PE), wash-in rate (WiR), and wash-in perfusion index (WiPI) were evaluated as quantitative perfusion parameters in vastus lateralis (VL) and intermedius (VI) muscle separately via regions of interest mapping. RESULTS: Immediately after the intervention (t1), perfusion parameters showed a non-significant decrease in VL (p = 0.3; PE: -32.1%, WiPI: -29.6%, WiR: -50.4%) and VI (p = 0.4; PE: -10.3%, WiPI: -6.4%, WiR: -35.6%). A non-significant decrease was found at t2 in VL (p = 0.2; PE: -34%, WiPI -33.9%, WiR -61.2%) and VI (p = 0.2; PE -17.6%, WiPI -13.8%, WiR -43.2%). CONCLUSIONS: The common assumption of intramuscular MBF improvement due to FR could not be confirmed for up to 30 min after the intervention. If an increase in intramuscular metabolism or MBF is intended, we recommend that alternative methods (i.e., traditional warm-up) should be preferred.

Predictive Value of Carotid Plaque Contrast-Enhanced Ultrasound Score and Homocysteine in Senile Metabolic Syndrome Complicated by Cerebral Infarction.

OBJECTIVE: To investigate the predictive value of the carotid plaque contrast-enhanced ultrasound (CEUS) score and blood homocysteine (HCY) in senile metabolic syndrome (MetS) complicated by cerebral infarction. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Ultrasound Imaging, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, China, from July 2020 to December 2021. METHODOLOGY: A total of 118 senile MetS patients complicated by cerebral infarction were selected as Group A, and 103 senile MetS patients without cerebral infarction were selected as Group B. Both groups were compared in terms of cardiovascular risk factors and ultrasonic examination of carotid plaques. The independent risk factors for cerebral infarction among senile MetS patients were analysed using logistic regression. An ROC curve was used to assess the predictive value of statistically significant risk factors in senile MetS complicated by cerebral infarction. RESULTS: Significant differences were observed in smoking, abdominal circumference, blood pressure, HCY, fasting blood glucose, high-density and low-density lipoprotein cholesterol, triacylglycerol, carotid plaque thickness, CEUS score, lumen stenosis, and ulcer plaque between the two groups. Logistic regression analysis showed that the plaque CEUS score and HCY were independent risk factors for senile MetS complicated by cerebral infarction. The areas under the ROC curve for the CEUS score and HCY were 0.795 and 0.812, respectively, and was 0.858 for the combined diagnosis of both. When the CEUS score was ≥2 and HCY was ≥16.45 mmol/l, the sensitivity and specificity of predicted senile MetS complicated by cerebral infarction were 83.1% and 74.8%, respectively. CONCLUSION: The carotid plaque CEUS score and blood HCY exhibit a substantial predictive capacity for cerebral infarction in elderly MetS patients. The combined diagnostic efficacy of the two is superior. KEY WORDS: Contrast-enhanced ultrasound, Homocysteine, Elderly, Metabolic syndrome, Cerebral infarction, Carotid plaque.

Expression of clMagR/clCry4 protein in mBMSCs provides T2-contrast enhancement of MRI.

Here, we propose for the first time the evaluation of magnetosensitive clMagR/clCry4 as a magnetic resonance imaging (MRI) reporter gene that imparts sensitivity to endogenous contrast in eukaryotic organisms. Using a lentiviral vector, we introduced clMagR/clCry4 into C57BL/6 mice-derived bone marrow mesenchymal stem cells (mBMSCs), which could specifically bind with iron, significantly affected MRI transverse relaxation, and generated readily detectable contrast without adverse effects in vivo. Specifically, clMagR/clCry4 makes mBMSCs beneficial for enhancing the sensitivity of MRI-R2 for iron-bearing granules, in which cells recruit exogenous iron and convert these stores into an MRI-detectable contrast; this is not achievable with control cells. Additionally, Prussian blue staining was performed together with ultrathin cell slices to provide direct evidence of natural iron-bearing granules being detectable on MRI. Hence, it was inferred that the sensitivity of MRI detection should be correlated with clMagR/clCry4 and exogenous iron. Taken together, the clMagR/clCry4 has great potential as an MRI reporter gene. STATEMENT OF SIGNIFICANCE: In this study, we propose the evaluation of magnetosensitive clMagR/clCry4 as an MRI reporter gene, imparting detection sensitivity to eukaryotic mBMSCs for endogenous contrast. At this point, the clMagR and clCry4 were located within the cytoplasm and possibly influence each other. The clMagR/clCry4 makes mBMSCs beneficial for enhancing the sensitivity of MRI-R2 for iron-bearing granules, in which protein could specifically bind with iron and convert these stores into MRI-detectable contrast; this is not achieved by control cells. The viewpoint was speculated that the clMagR/clCry4 and exogenous iron were complementary to each other. Additionally, Prussian blue staining was performed together with TEM observations to provide direct evidence that the iron-bearing granules were sensitive to MRI.

Holmium (III)-doped multifunctional nanotheranostic agent for ultra-high-field magnetic resonance imaging-guided chemo-photothermal tumor therapy.

Ultra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Despite being the most commonly used MRI contrast agents, gadolinium chelates perform poorly in high magnetic fields, which significantly weakens their T1 intensity. In comparison, the rare element Holmium (Ho)-based nanoparticles (NPs) have demonstrated great potential as T2-weighted MRI contrast agents in UHF MRI due to their extremely short electron relaxation times (∼ 10-13s). In this study, a multifunctional nanotherapeutic probe was designed for UHF MRI-guided chemotherapy and photothermal therapy. The Ho (III)-doped mesoporous polydopamine (Ho-MPDA, HM) nanosphere was loaded with the chemotherapeutic drug mitoxantrone (MTO) and then coated with 4T1 cell membranes to enhance active targeting delivery to breast cancer. The prepared nanotherapeutic probe MTO@HMM@4T1 (HMM@T) exhibited good biocompatibility, high drug-loading capability and great potential as Ho (III)-based UHF MRI contrast agents. Moreover, the biodegradation of HMM@T in response to the intratumor pH and glutathione (GSH) promotes MTO release. Near-infrared (NIR) light irradiation of HM induced photothermal therapy and further enhanced drug release. Consequently, HMM@T effectively acted as an MRI-guided tumor-targeting chemo-photothermal therapy against 4T1 breast cancer. STATEMENT OF SIGNIFICANCE: Ultra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Although gadolinium chelates are the most commonly used MRI contrast agents in clinical practice, they exhibit a significantly decreased T1 relaxivity at UHF. Holmium exhibits outstanding UHF magnetic resonance capabilities in comparison with gadolinium chelates currently used in clinic. Herein, a theranostic nanodrug (HMM@T) was designed for UHF MRI-guided chemo-photothermal therapy. The nanodrug possessed remarkable UHF T2 MRI properties (r2 = 152.13 mM-1s-1) and high drug loading capability of 18.4 %. The biodegradation of HMM@T NPs under triple stimulations of pH, GSH, and NIR led to an efficient release of MTO in tumor microenvironment. Our results revealed the potential of a novel UHF MRI-guided multifunctional nanosystem in cancer treatment.