Contrast Agent Research Articles

Nanoarchitectonics of Copper Sulfide Nanoplating for Improvement of Computed Tomography Efficacy of Bismuth Oxide Constructs towards Drugless Theranostics

Abstract Triple-negative breast cancer (TNBC) has emerged as one of the dreadful metastatic tumors in women due to complexity, specificity, and high recurrence, resulting in poor therapeutic outcomes and requiring real-time monitoring for improved theranostics. Despite the success as efficient radiosensitizers and computed tomography (CT)-based contrast agents, bismuth (Bi)-based composites suffer from poor colloidal stability, dose-dependent toxicity, and pharmacokinetic shortcomings, leading to poor therapeutic monitoring. In addition, several small molecule-based therapeutics, including nanoparticle-based delivery systems, suffer from several limitations of poor therapeutic delivery and acquired multidrug resistance by cancer cells, depriving the therapeutic needs. To overcome this aspect, this study demonstrates the fabrication of drug-like/drugless nanoarchitectures based on copper sulfide-nanoplated bismuth oxide (Bi2O3@CuS, shortly BC) composites for improved theranostic efficacy against TNBC. These systematically characterized BC nanocomposites exhibited pH-/near-infrared (NIR, 808 nm) light-responsive degradability towards dual modal therapies. Due to the band transition of Cu species, the designed BC composites displayed exceptional photothermal (PTT) conversion efficiency towards localized PTT effects. In addition to pH-/NIR-responsiveness, the internally overexpressed glutathione (GSH)-responsiveness facilitated the release of Cu2+ species for chemodynamic therapy (CDT) effects. To this end, the Bi3+ species in the core could be fully hydrated in the acidic tumor microenvironment (TME), resulting in GSH depletion and reducing CDT-induced reactive oxygen species (ROS) clearance, thereby ablating tumors. The acid-responsive degradability of CuS resulted in the intratumoral enrichment of BC, demonstrating remarkable CT imaging efficacy in vivo. Together, these pH-/NIR-/GSH-responsive biodegradable BC composites could realize the integrated PTT/CDT/CT theranostics against breast carcinoma.

Preliminary application results of laparoscopic assisted proximal gastrectomy λ-shaped double tract anastomosis

Objective: To share the results of laparoscopic assisted proximal gastrectomy λ- shaped modified double tract reconstruction. Method: This study retrospectively included 3 patients during January 2024 from the Department of Gastric Surgery at the First Affiliated Hospital of Nanjing Medical University using the λ-shaped modified double tract reconstruction. The procedure of the λ-shaped modified double tract reconstruction is as follows. After completing proximal gastrectomy, the jejunum is transected 15 cm from the Treitz ligament. A suture is made 18-20 cm from the distal jejunum to mark the esophagojejunal anastomosis site. A circular stapler anvil is inserted through the distal jejunum, and the remaining end of the jejunum is turned to the right. The circular stapler is pierced through the marked site for an esophagojejunal end-to-end anastomosis, which is reinforced with a barbed suture continuously. A 60mm linear stapler is used to close the remaining end of the jejunum. We then mark the gastric side of the gastrojejunal anastomosis with suture in the middle of the anterior wall of the residual stomach, and mark the jejunal side of the gastrojejunal anastomosis at a distance of about 2 cm and 8 cm from the residual end of the distal jejunum. We make an opening of about 0.5 cm and use a 60 mm linear stapler to perform anastomosis on the jejunal side of the anterior wall of the residual stomach according to the markings, so that the distance between the esophagojejunal anastomosis and the gastrojejunal anastomosis is 10-12 cm. The common opening is closed with barbed wire. About 50 cm below the esophagojejunal anastomosis, the small intestine opening is anastomosed side to side using a circular stapler and the common opening is closed. Return the jejunum into the abdominal cavity to complete the reconstruction of the λ-shaped double tract reconstruction. We analyzed the surgery and postoperative conditions, including surgery time, anastomosis time, intraoperative bleeding, tumor size and pathology, postoperative mobilization, passage of gas and water intake time, discharge time, postoperative complications, and postoperative gastrointestinal imaging to observe the passage of food through the gastric and intestinal loops. Results: Three patients successfully received laparoscopic assisted proximal gastrectomy with λ-shaped modified double tract reconstruction. The surgical time was 155 minutes, 240 minutes, and 160 minutes, respectively; The postoperative time for first ambulation was 20 hours, 18 hours, and 26 hours, respectively. The time for passage of gas was 59 hours, 83 hours, and 75 hours, respectively. The drinking time was 66 hours, 87 hours, and 90 hours, respectively. The postoperative discharge days were all 7 days. No surgical related complications occurred. On the 6th day and 3 months after surgery, gastrointestinal angiography was performed. The contrast agent passed smoothly through the jejunal loop and residual stomach jejunal loop, and both sides were unobstructed. No contrast agent was found to retrograde to the esophagojejunal anastomosis. Conclusion: Laparoscopic assisted proximal gastrectomy with λ-shaped modified double tract reconstruction is safe and feasible, as it improves the diversion of food through the residual stomach while ensuring anti-reflux effects.

INCIDENCE OF CONTRAST-INDUCED NEPHROPATHY FOLLOWING CHRONIC TOTAL OCCLUSION PERCUTANEOUS CORONARY INTERVENTION

Contrast-induced nephropathy (CIN) is a potentially serious complication following percutaneous coronary intervention (PCI), particularly in patients with chronic total occlusion (CTO). It is characterized by an acute deterioration in renal function after exposure to contrast media. CIN is associated with increased morbidity, hospital stays, and long-term renal outcomes, making it crucial to identify and mitigate its incidence. This study aimed to evaluate the incidence of CIN in patients undergoing CTO-PCI and its associated complications. Objective: To assess the incidence of contrast-induced nephropathy (CIN) following percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) and evaluate in-hospital complications, hospital stay duration, and short-term mortality. Methods: This cross-sectional study was conducted with ethical approval at a tertiary care hospital, including 118 patients who underwent PCI for CTO at the Department of Cardiology, Lady Reading Hospital Peshawar, Pakistan from 10th June 2023 to 09th June 2024. Standardized pre- and post-procedural hydration protocols were implemented to reduce the risk of CIN, and non-ionic, iso-osmolar contrast agents were used. CIN was defined as a 25% increase in serum creatinine or an absolute increase of ≥0.5 mg/dL within 48–72 hours post-procedure. Data on demographic characteristics, complications, and mortality were collected and analyzed using SPSS Version 25, with categorical variables expressed as percentages and continuous variables as means. Chi-square tests were used to assess statistical significance, with P-values < 0.05 considered significant. Results: Of the 118 patients included, the mean age was 56.34 years, and 52.5% were male. Age distribution showed that 43.2% were between 51-60 years, while 33.1% were between 61-70 years. CIN was observed in 6.8% of patients, with 9.7% of males and 3.6% of females affected (P=0.188). In-hospital complications included arrhythmias in 4.2% of patients, heart failure in 0.8%, and mortality in 0.8%. Hospital stay averaged 5.94 days, with no significant differences in CIN incidence across age groups (P=0.186). Conclusion: The incidence of contrast-induced nephropathy following PCI for chronic total occlusion is a clinically significant issue, affecting 6.8% of patients despite preventative measures. This emphasizes the need for ongoing risk assessment, monitoring, and the implementation of effective prevention strategies. Further research is warranted to refine risk stratification tools and develop targeted interventions to minimize CIN incidence, particularly in high-risk patient populations.

Engineering Protein-Nanoparticle Hybrids as Targeted Contrast Agents.

Iron oxide nanoparticles (IONPs) have shown great promise in biomedical applications, particularly as MRI contrast agents due to their magnetic properties and biocompatibility. Although several IONPs have been approved by regulatory agencies as MRI contrast agents, their primary application as negative contrast agents limits their usage. Additionally, there is an emerging need for the development of molecular contrast agents that can specifically target biomarkers, enabling more accurate and sensitive diagnostics. To address these challenges, we exploited the engineerability of proteins to stabilize IONPs with tailored magnetic properties, creating protein-stabilized iron oxide nanoparticles (Prot-IONPs) and leveraged the chemical diversity of proteins to functionalize Prot-IONPs with targeting moieties. As a proof-of-concept, we used alendronate (Ald) to target atherosclerotic plaques in the aorta. Simple protein functionalization allowed targeting while maintaining the stability and relaxation properties of the Prot-IONPs. Prot-IONPs-Ald successfully enabled positive contrast imaging of atherosclerotic plaques in vivo in an atherosclerotic mouse model (ApoE-/- mice on a high-fat diet). This study demonstrates the potential of engineering protein-nanoparticle hybrids as versatile platforms for developing targeted in vivo MRI contrast agents.

Changes in tissues and organs through PMCTA carrier substances.

To date, lipophilic contrast agents mixed with oil, usually paraffin oil, are the most commonly used contrast agents in post-mortem computed tomography angiography (PMCTA). Iodine-based hydrophilic contrast media in combination with a water-soluble carrier, e.g. polyethylene glycol (PEG), are also common. However, their influence on different tissues and organs is poorly understood. In order to analyse the changes in the cadavers caused by the different carrier substances, we evaluated the effects of PEG 200 and oil on the different tissues and organs. Therefore, during a forensic autopsy, liquid femoral vein blood and samples of different organs and vessels were taken and preserved at room temperature in the two liquids mentioned. The condition of the samples was documented during the autopsy and 24, 48 and 72h after preservation. Microscopic examination took place after 72h. After 24h, the samples placed in PEG 200 already showed a clear solidification of almost all structures. Crumbly blood agglomerates had formed in the previously liquid blood. In contrast, the samples stored in oil showed signs of classic cadaveric decomposition after 24h, which increased with time. The microscopic and immunohistochemical evaluation of the samples stored in PEG showed a good diagnostic quality. The analysis of tissues stored in oil was much more difficult due to putrefaction. PEG and oil show significantly different effects on human tissues, mainly conservation and dehydration are affected. It is crucial to be aware of these differences in order to choose the most appropriate PMCTA method for each forensic case.

Scalable Copper Sulfide Formulations for Super-Resolution Optoacoustic Brain Imaging in the Second Near-Infrared Window.

Optoacoustic imaging offers label-free multi-parametric characterization of cerebrovascular morphology and hemodynamics at depths and spatiotemporal resolution unattainable with optical microscopy. Effective imaging depth can greatly be enhanced by employing photons in the second near-infrared (NIR-II) window. However, diminished absorption by hemoglobin along with a lack of suitable contrast agents hinder an efficient application of the technique in this spectral range. Herein, copper sulfide (CuS) micro- and nano-formulations for multi-scale optoacoustic imaging in the NIR-II window are introduced. Dynamic contrast enhancement induced by intravenously administered CuS nanoparticles facilitated visualization of blood perfusion in murine cerebrovascular networks. The individual calcium carbonate microparticles carrying CuS are further shown to generate sufficient responses to enable super-resolution microvascular imaging and blood flow velocity mapping with localization optoacoustic tomography.

On the lifespan of Enchytraeus crypticus - impact of iron (nanomaterial and salt) on aging.

Iron oxide nanomaterials (Fe3O4 NMs) have important biomedical and environmental applications, e.g. drug delivery, chemotherapy, magnetic resonance imaging contrast agents, etc. However, the environmental risks of such Fe3O4 are not fully assessed, particularly for soil living invertebrates, which are among the ones in the first line of exposure. Research has showed that longer-term exposure time is required to assess hazards of NMs, not predicted when based on shorter time and are therefore recommended. Thus, in the present study the effects of Fe3O4 NMs and FeCl3 were assessed in the terrestrial environment, using the soil model species Enchytraeus crypticus (Oligochaeta), throughout its entire lifespan (202 days). Two animals' density were used: 1 (D1) and 40 (D40) animals per replicate, in LUFA 2.2 soil. The endpoints were survival and reproduction monitored over-time, up to 202 days. Results showed that density clearly affected the toxicity response, with higher toxicity and lower lifespan in D1 compared to D40. Overall, FeCl3 was more toxic than Fe3O4 NM in terms of reproduction, however, adult animals can be at higher (long-term) risk when exposed to Fe3O4 NM. Differences might be linked to slower Fe kinetics for the Fe3O4 NMs, i.e., slower Fe dissolution and release of ions.

Enhancing biomedical imaging: the role of nanoparticle-based contrast agents.

Biomedical imaging plays a critical role in early detection, precise diagnosis, treatment planning, and monitoring responses, but traditional methods encounter challenges such as limited sensitivity, specificity, and inability to monitor therapeutic responses due to factors like short circulation half-life and potential toxicity. Nanoparticles are revolutionizing biomedical imaging as contrast agents across modalities like computed tomography (CT), optical, magnetic resonance imaging (MRI), and ultrasound, exploiting unique attributes such as those of metal-based, polymeric, and lipid nanoparticles. They shield imaging agents from immune clearance, extending circulation time, and enhancing bioavailability at tumor sites. This results in improved imaging sensitivity. The study highlights advancements in multifunctional nanoparticles for targeted imaging, tackling concerns regarding toxicity and biocompatibility. Critically evaluating conventional contrast agents, emphasizes the shortcomings that nanoparticles aim to overcome. This review provides insight into the current status of nanoparticle-based contrast agents, illuminating their potential to reshape therapeutic monitoring and precision diagnostics.

X-ray coronary angiography background subtraction by adaptive weighted total variation regularized online RPCA

Objective.X-ray coronary angiograms (XCA) are widely used in diagnosing and treating cardiovascular diseases. Various structures with independent motion patterns in the background of XCA images and limitations in the dose of injected contrast agent have resulted in low-contrast XCA images. Background subtraction methods have been developed to enhance the visibility and contrast of coronary vessels in XCA sequences, consequently reducing the requirement for excessive contrast agent injections.Approach.The current study proposes an adaptive weighted total variation regularized online RPCA (WTV-ORPCA) method, which is a low-rank and sparse subspaces decomposition approach to subtract the background of XCA sequences. In the proposed method, the images undergo initial preprocessing using morphological operators to eliminate large-scale background structures and achieve image homogenization. Subsequently, the decomposition algorithm decomposes the preprocessed images into background and foreground subspaces. This step applies an adaptive weighted TV constraint to the foreground subspace to ensure the spatial coherency of the finally extracted coronary vessel images.Main results.To evaluate the effectiveness of the proposed background subtraction method, some qualitative and quantitative experiments are conducted on two clinical and synthetic low-contrast XCA datasets containing videos from 21 patients. The obtained results are compared with six state-of-the-art methods employing three different assessment criteria. By applying the proposed method to the clinical dataset, the mean values of the global contrast-to-noise ratio, local contrast-to-noise ratio, structural similarity index, and reconstruction error (RE) are obtained as5.976,3.173,0.987, and0.026, respectively. These criteria over the low-contrast synthetic dataset were4.851,2.942,0.958, and0.034, respectively.Significance.The findings demonstrate the superiority of the proposed method in improving the contrast and visibility of coronary vessels, preserving the integrity of the vessel structure, and minimizing REs without imposing excessive computational complexity.

Magnetic resonance imaging tracing of superparamagnetic iron oxide nanoparticle-labeled mesenchymal stromal cells for repairing spinal cord injury.

Mesenchymal stromal cell transplantation Is an effective and promising approach for treating various systemic and diffuse diseases. However, the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear, including cell viability, distribution, migration, and fate. Conventional cell tracing methods cannot be used in the clinic. The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging. In 2016, the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle, Ruicun, for use as a contrast agent in clinical trials.In the present study, an acute hemi-transection spinal cord injury model was established in beagle dogs. The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells. The results indicated that Ruicun-labeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury. T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord. The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks. These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.

Application of nanoliposome as contrast agents for magnetic resonance imaging technique

AbstractLiposomes, nano‐sized vesicles primarily comprising phospholipids and cholesterol, have emerged as pivotal tools in medical imaging, notably in magnetic resonance imaging (MRI), due to their biocompatibility and ability to encapsulate diverse molecules. Tailorable properties like size, surface charge, and encapsulation capacity make liposomes ideal for targeted delivery of imaging agents and drugs to specific tissues, improving pharmacokinetics. As MRI contrast agent (CA) carriers, liposomes encapsulate gadolinium, mitigating toxicity and boosting relaxivity and circulation times. Functionalization with targeting ligands and stimuli‐responsive designs enhances their controlled release and targeted delivery capabilities, crucial for cancer imaging and therapy. Benefits include reduced toxicity, prolonged circulation, targeted delivery, enhanced bioavailability, and potential for multimodal imaging. Challenges remain, such as stability, clearance, and manufacturing intricacies, requiring further research. Nonetheless, liposomal MRI CAs hold promise for enhancing diagnostic precision and therapeutic effectiveness in oncology and neurology, offering a robust pathway for future biomedical advancements. Addressing existing limitations could unlock their full potential in improving patient care and outcomes.

CT/MRI technical pitfalls for diagnosis and treatment response assessment using LI-RADS and how to optimize.

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is a significant global health burden. Accurate imaging is crucial for diagnosis and treatment response assessment, often eliminating the need for biopsy. The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation and reporting of liver imaging for diagnosis and treatment response assessment, categorizing observations using defined categories that are based on the probability of malignancy or post-treatment tumor viability. Optimized imaging protocols are essential for accurate visualization and characterization of liver findings by LI-RADS. Common technical pitfalls, such as suboptimal postcontrast phase timing, and MRI-specific challenges like subtraction misregistration artifacts, can significantly reduce image quality and diagnostic accuracy. The use of hepatobiliary contrast agents introduces additional challenges including arterial phase degradation and suboptimal uptake in advanced cirrhosis. This review provides radiologists with comprehensive insights into the technical aspects of liver imaging for LI-RADS. We discuss common pitfalls encountered in routine clinical practice and offer practical solutions to optimize imaging techniques. We also highlight technical advances in liver imaging, including multi-arterial MR acquisition and compressed sensing. By understanding and addressing these technical aspects, radiologists can improve accuracy and confidence in the diagnosis and treatment response assessment for hepatocellular carcinoma.

Ultrasound protein-copolymer microbubble library engineering through poly(vinylpyrrolidone-co-acrylic acid) structure

HypothesisWhile albumin-coated microbubbles are routine contrast agents for ultrasound imaging, their short duration of contrast enhancement limits their use, yet can be improved by incorporating protein-copolymer hybrids into microbubble shells. The incorporation of N-vinyl-2-pyrrolidone and acrylic acid copolymer (P(VP–AA)) has been shown to enhance the performance of bovine serum albumin (BSA)-coated microbubbles. However, the impact of the copolymer structural properties on key microbubble characteristics (i.e., concentration, mean diameter and acoustic response) remains poorly understood. Therefore, we hypothesize that the copolymer structure affects its capacity to form micelle-like nanoaggregates, protein-copolymer hybrids, and microbubble shells, ultimately influencing the physicochemical and acoustic properties of the microbubbles. ExperimentsHere we evaluate the production and performance of BSA@P(VP–AA) microbubbles synthesized using a series of P(VP–AA) copolymers with –C8H17 and –C18H37 end groups and molecular weight cutoffs between 3.5 and 15 kDa. Both simulation and experimental data demonstrate that interactions between BSA and the copolymers significantly influence the performance of the resulting microbubbles across the library of 60 formulations. FindingsThe introduction of –C8H17 terminated copolymers into microbubble shells resulted in up to 200-fold higher concentration, 7-fold greater acoustic response, and 5-fold longer ultrasound contrast enhancement compared to plain BSA microbubbles. The enhanced acoustic performance was sustained during in vivo cardiac ultrasound imaging, without altering liver accumulation after copolymer introduction. These findings underscore how optimizing copolymer structure (specifically the terminal end group and molecular weight) can tailor the formation and performance of protein-copolymer-coated microbubbles, offering valuable insights for designing ultrasound contrast agents.

Differentiation of MS lesions through analysis of microvascular distribution

Abstract Conventional MRI is crucial for diagnosing multiple sclerosis (MS) but lacks precision, leading to the clinico-radiological paradox and misdiagnosis risk, especially when confronted with unspecific lesions not related to MS. Advancements in perfusion-weighted imaging (PWI) with an algorithm designed for diseases with anticipated contrast agent extravasation offer insight into microvascular impairment and flow heterogeneity. Our study aimed to assess these factors in MS patients and their association with clinically relevant white matter injury and disease course. We evaluated 60 adults with white matter lesions (WML), including 50 diagnosed with MS or MS syndromes and 10 non-diseased symptomatic controls (SC) with unspecific WML. MRI included conventional three-dimensional (3D) T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), 3D magnetization-prepared 2 rapid acquisition gradient-echo (MP2RAGE), post-contrast 3D T1-weighted (T1) images and Dynamic Susceptibility Contrast (DSC) PWI at 3T. WML masks of “unspecific T2-FLAIR lesions”, “MS T2-FLAIR lesions”, and “MS T1-lesions” were manually outlined and validated by a neuroradiologist. DSC-derived parameters were analyzed in WML masks and healthy-appearing tissue. MS T2-FLAIR lesions showed increased flow heterogeneity and vasodilation compared to unspecific T2-FLAIR lesions in SC, as well as compared to unspecific T2-FLAIR lesions within the MS group. MS T1-lesions exhibited more homogenized flow. Our findings suggest that DSC-PWI combined with lesion delineation, can provide clinically relevant differentiation of MS lesions from unspecific WML, highlighting potential microvascular pathology previously overlooked in MS.

Management of anticoagulant-related soft tissue bleeding

Spontaneous, severe, and life-threatening soft tissue bleeding (STB) in patients taking anticoagulants is associated with high morbidity and mortality due to the substantial blood loss and nonspecific clinical symptoms. The optimal management of these predominantly older patients with multiple comorbidities has not yet been unanimously clarified. This work comprises aliterature search and analysis of the pertinent retrospective studies and case series. Structured diagnostic workup with contrast-enhanced computed tomography (CT) is essential for planning transarterial embolization (TAE). Contrast agent extravasation, the signal flare phenomenon, and the hematocrit effect are all indicative of active bleeding or an anticoagulant-related hematoma. For TAE, coils, particles, and liquid embolic agents can be used alone or in combination. Aback door/front door embolization should be strived for. Transarterial embolization is the method of choice for managing anticoagulant-related localized or diffuse spontaneous soft tissue bleeding in the context of hemodynamic stabilization of the patient.

Preoperative prediction of diffuse glioma type and grade in adults: a gadolinium-free MRI-based decision tree.

To develop a gadolinium-free MRI-based diagnosis prediction decision tree (DPDT) for adult-type diffuse gliomas and to assess the added value of gadolinium-based contrast agent (GBCA)enhanced images. This study included preoperative grade 2-4 adult-type diffuse gliomas (World Health Organization 2021) scanned between 2010 and 2021. The DPDT, incorporating eleven GBCA-free MRI features, was developed using 18% of the dataset based on consensus readings. Diagnosis predictions involved grade (grade 2 vs. grade 3/4) and molecular status (isocitrate dehydrogenase (IDH) and 1p/19q). GBCA-free diagnosis was predicted using DPDT, while GBCA-enhanced diagnosis included post-contrast images. The accuracy of these predictions was assessed by three raters with varying experience levels in neuroradiology using the test dataset. Agreement analyses were applied to evaluate the prediction performance/reproducibility. The test dataset included 303 patients (age (SD): 56.7 (14.2) years, female/male: 114/189, low-grade/high-grade: 54/249, IDH-mutant/wildtype: 82/221, 1p/19q-codeleted/intact: 34/269). Per-rater GBCA-free predictions achieved ≥ 0.85 (95%-CI: 0.80-0.88) accuracy for grade and ≥ 0.75 (95%-CI: 0.70-0.80) for molecular status, while GBCA-enhanced predictions reached ≥ 0.87 (95%-CI: 0.82-0.90) and ≥ 0.77 (95%-CI: 0.71-0.81), respectively. No accuracy difference was observed between GBCA-free and GBCA-enhanced predictions. Group inter-rater agreement was moderate for GBCA-free (0.56 (95%-CI: 0.46-0.66)) and substantial for GBCA-enhanced grade prediction (0.68 (95%-CI: 0.58-0.78), p = 0.008), while substantial for both GBCA-free (0.75 (95%-CI: 0.69-0.80) and GBCA-enhanced (0.77 (95%-CI: 0.71-0.82), p = 0.51) molecular status predictions. The proposed GBCA-free diagnosis prediction decision tree performed well, with GBCA-enhanced images adding little to the preoperative diagnostic accuracy of adult-type diffuse gliomas. Question Given health and environmental concerns, is there a gadolinium-free imaging protocol to preoperatively evaluate gliomas comparable to the gadolinium-enhanced standard practice? Findings The proposed gadolinium-free diagnosis prediction decision tree for adult-type diffuse gliomas performed well, and gadolinium-enhanced MRI demonstrated only limited improvement in diagnostic accuracy. Clinical relevance Even inexperienced raters effectively classified adult-type diffuse gliomas using the gadolinium-free diagnosis prediction decision tree, which, until further validation, can be used alongside gadolinium-enhanced images to respect standard practice, despite this study showing that gadolinium-enhanced images hardly improved diagnostic accuracy.

Ultrasonography of the salivary glands in Sjögren's disease: own data analysis

Objective: to investigate feasibility of using ultrasonography (US) to evaluate structural changes of salivary glands (SG) in patients with Sjögren's disease (SD).Material and methods. The study included 159 patients who were examined in V.A. Nasonova Research Institute of Rheumatology from 2016 to 2022 who met V.A. Nasonova Research Institute of Rheumatology 2001, and/or ACR 2012, and/or ACR/EULAR 2016 criteria for SD, and who had not previously received immunosuppressive therapy. All patients underwent a comprehensive classical examination (ophthalmological, dental, immunological) to diagnose SD. Disease activity was determined using ESSDAI index. US of the parotid gland (PG) and submandibular SGs was performed using a GE LOGIQ 9 device, and the images obtained were scored according to the OMERACT SGUS scoring system (SGUS SS).Results and discussion. All SGUS SS scores statistically significantly correlated (p<0.05) with mouth sicca symptoms, enlargement of PG, ESSDAI activity index, presence of lymphohistiocytic infiltrate and focus score in labial SG biopsy, and parenchymatous parotitis according to sialography. No significant correlation was found with the results of sialometry. There was a significant correlation between the changes detected by US and sialography (r=0.422; p=0.001). Considering the data obtained, the consistency of the results of the different examination methods was analyzed. Bland-Altman diagrams were created to reflect the dependence of the differences between the results of US and sialography. At various stages of the comparison, not all data points were within the standardized range. In addition, 5% of the parameters were not within the interval of two standard deviations. The Bland-Altman analysis revealed a systematic discrepancy indicating a low degree of agreement between the two methods for determining structural changes in SG. According to the ROC analysis, sensitivity of ultrasound was 94% and specificity 51%. The area under the curve (AUC) was 0.787 (95% confidence interval 0.700–0.875).Conclusion. SG US and sialography are not interchangeable, but complement each other in the assessment of SG structure. SG US is a safer and non-invasive method of SG examination that does not require contrast agent administration and is likely to play an important role in the dynamic monitoring of patients during the therapy. However, sialography is a more accurate method of diagnostics and assessment of the extent of SG lesions.

Validation of an UPLC-PDA Method for the Simultaneous Quantification of Phenol and Iomeprol in a Sterile Parenteral Preparation Used for Coeliac Plexus Block, and Its Application to a Pharmaceutical Stability Study

Objectives: A commonly applied analgesic therapy for patients with severe abdominal pain due to cancer-related pain in the upper abdomen, is coeliac plexus neurolysis (CPN). Herein, a combination product of phenol and an iodine contrast agent are injected simultaneously. The chemical stability of such a combination product is unknown, and no chromatographic method is yet available that describes the simultaneous quantification of phenol and iomeprol. The aim of this study was to develop and validate a stability-indicating UPLC method for the simultaneous quantification of both phenol and iomeprol and to determine the chemical stability of a sterile 100 mg/mL phenol in 350 mg I/mL iomeprol solution for injection during shelf life. Methods: The product was compounded and sterilized in a GMP certified facility. The pharmaceutical analysis was validated by determination of the accuracy, precision, specificity, selectivity, carry-over and linearity. Pharmaceutical product stability was determined before and after sterilization, and during shelf life of 36 months at 25°C ± 2°C. Results: The accuracy for phenol and iomeprol was 97.1% to 99.3% and 100.0% to 100.2%, respectively. The RSD for repeatability and reproducibility for phenol were 0.65% and 1.17%, and for iomeprol 0.61% and 1.49%, respectively. All other tested parameters met the predefined validation criteria. All concentrations at all tested time points remained within ±2% of the initial concentrations for phenol and ±4% for iomeprol. No additional peaks were visible on the chromatograms. Conclusion: A stability-indicating method for the simultaneous quantification of phenol and iomeprol in a parental pharmaceutical preparation was developed and validated. This method was used to demonstrate the chemical stability of a newly developed sterile solution of 100 mg/mL phenol and 350 mg I/mL iomeprol. Chemical product stability was demonstrated during shelf life of up to 36 months.

Gadolinium-based coronary CT angiography on a clinical photon-counting-detector system: a dynamic circulating phantom study

BackgroundCoronary computed tomography angiography (CCTA) offers non-invasive diagnostics of the coronary arteries. Vessel evaluation requires the administration of intravenous contrast. The purpose of this study was to evaluate the utility of gadolinium-based contrast agent (GBCA) as an alternative to iodinated contrast for CCTA on a first-generation clinical dual-source photon-counting-detector (PCD)-CT system.MethodsA dynamic circulating phantom containing a three-dimensional-printed model of the thoracic aorta and the coronary arteries were used to evaluate injection protocols using gadopentetate dimeglumine at 50%, 100%, 150%, and 200% of the maximum approved clinical dose (0.3 mmol/kg). Virtual monoenergetic image (VMI) reconstructions ranging from 40 keV to 100 keV with 5 keV increments were generated on a PCD-CT. Contrast-to-noise ratio (CNR) was calculated from attenuations measured in the aorta and coronary arteries and noise measured in the background tissue. Attenuation of at least 350 HU was deemed as diagnostic.ResultsThe highest coronary attenuation (441 ± 23 HU, mean ± standard deviation) and CNR (29.5 ± 1.5) was achieved at 40 keV and at the highest GBCA dose (200%). There was a systematic decline of attenuation and CNR with higher keV reconstructions and lower GBCA doses. Only reconstructions at 40 and 45 keV at 200% and 40 keV at 150% GBCA dose demonstrated sufficient attenuation above 350 HU.ConclusionCurrent PCD-CT protocols and settings are unsuitable for the use of GBCA for CCTA at clinically approved doses. Future advances to the PCD-CT system including a 4-threshold mode, as well as multi-material decomposition may add new opportunities for k-edge imaging of GBCA.Relevance statementPatients allergic to iodine-based contrast media and the future of multicontrast CT examinations would benefit greatly from alternative contrast media, but the utility of GBCA for coronary photon-counting-dector-CT angiography remains limited without further optimization of protocols and scanner settings.Key PointsGBCA-enhanced coronary PCD-CT angiography is not feasible at clinically approved doses.GBCAs have potential applications for the visualization of larger vessels, such as the aorta, on PCD-CT angiography.Higher GBCA doses and lower keV reconstructions achieved higher attenuation values and CNR.Graphical

A Comprehensive and Repeatable Contrast-Enhanced Ultrasound Quantification Approach for Clinical Evaluations of Tumor Blood Flow.

The aim of this study is to define a comprehensive and repeatable contrast-enhanced ultrasound (CEUS) imaging protocol and analysis method to quantitatively assess lesional blood flow. Easily repeatable CEUS evaluations are essential for longitudinal treatment monitoring. The quantification method described here aims to provide a structure for future clinical studies. This retrospective analysis study included liver CEUS studies in 80 patients, 40 of which contained lesions (primarily hepatocellular carcinoma, n = 28). Each patient was given at least 2 injections of a microbubble contrast agent, and 60-second continuous loops were acquired for each injection to enable evaluation of repeatability. For each bolus injection, 1.2 mL of contrast was delivered, whereas continuous, stationary scanning was performed. Automated respiratory gating and motion compensation algorithms dealt with breathing motion. Similar in size regions of interest were drawn around the lesion and liver parenchyma, and time-intensity curves (TICs) with linearized image data were generated. Four bolus transit parameters, rise time (RT), mean transit time (MTT), peak intensity (PI), and area under the curve (AUC), were extracted either directly from the actual TIC data or from a lognormal distribution curve fitted to the TIC. Interinjection repeatability for each parameter was evaluated with coefficient of variation. A 95% confidence interval was calculated for all fitted lognormal distribution curve coefficient of determination (R2) values, which serves as a data quality metric. One-sample t tests were performed between values obtained from injection pairs and between the fitted lognormal distribution curve and direct extraction from the TIC calculation methods to establish there were no significant differences between injections and measurement precision, respectively. Average interinjection coefficient of variation with both the fitted curve and direct calculation of RT and MTT was less than 21%, whereas PI and AUC were less than 40% for lesion and parenchyma regions of interest. The 95% confidence interval for the R2 value of all fitted lognormal curves was [0.95, 0.96]. The 1-sample t test for interinjection value difference showed no significant differences, indicating there was no relationship between the order of the repeated bolus injections and the resulting parameters. The 1-sample t test between the values from the fitted lognormal distribution curve and the direct extraction from the TIC calculation found no statistically significant differences (α = 0.05) for all perfusion-related parameters except lesion and parenchyma PI and lesion MTT. The scanning protocol and analysis method outlined and validated in this study provide easily repeatable quantitative evaluations of lesional blood flow with bolus transit parameters in CEUS data that were not available before. With vital features such as probe stabilization ideally performed with an articulated arm and an automated respiratory gating algorithm, we were able to achieve interinjection repeatability of blood flow parameters that are comparable or surpass levels currently established for clinical 2D CEUS scans. Similar values and interinjection repeatability were achieved between calculations from a fitted curve or directly from the data. This demonstrated not only the strength of the protocol to generate TICs with minimal noise, but also suggests that curve fitting might be avoided for a more standardized approach. Utilizing the imaging protocol and analysis method defined in this study, we aim for this methodology to potentially assist clinicians to assess true perfusion changes for treatment monitoring with CEUS in longitudinal studies.