Injection Of Agent Research Articles

The Current Role of Contrast-Enhanced Ultrasound (CEUS) in the Diagnosis and Staging of Bladder Cancer: A Review of the Available Literature.

Contrast-enhanced ultrasound (CEUS) is an advanced imaging technique that integrates conventional US with the intravenous injection of specific US contrast agents (UCAs), combining the non-invasiveness of US with the higher accuracy of contrast-enhanced imaging. In contrast with magnetic resonance imaging (MRI), computed tomography (CT) and cystoscopy, CEUS has few contraindications, and UCAs are non-nephrotoxic agents that can be safely used in patients with kidney failure. CEUS is a well-established method for the detection of liver lesions and for echocardiography, and its indications are expanding. The updated 2018 WFUMB-EFSUMB guidelines have added the urinary bladder under non-hepatic applications of CEUS. The technique is able to distinguish between benign tissue, such as clots or hematoma, and malignant lesions by perfusing the mass with contrast agent. Thanks to the different perfusion rates of the various layers of the bladder wall, CEUS is also able to predict tumor invasion depth and stage. Despite that, current urological guidelines do not include CEUS as a plausible imaging technique for bladder urothelial carcinoma. The main reason for this omission might be the presence of scarce randomized evidence and the absence of large validated series. In this review, we describe the rationale behind the use of CEUS in bladder cancer and the added value of this imaging technique in the detection and staging of bladder lesions. In addition, we researched the available literature on the topic and then described the results of randomized clinical trials and a meta-analysis investigating the accuracy of CEUS in bladder cancer diagnosis and staging. The reported studies show that CEUS is a highly accurate diagnostic and staging tool for BC, reaching levels of specificity and sensitivity in differentiating between Ta-T1, or low-grade BC, and T2, or high-grade BC, that are comparable to those shown by the reference standard methods. Nonetheless, several limitations were found and are highlighted in this review. The aim of this study is to further validate and promote the use of CEUS as a quick, economic and effective diagnostic tool for this high-impact disease.

Prevention of bone dehiscence associated with orthodontic tooth movement by prophylactic injection of bone anabolic agents in mice

Although bone dehiscence may occur during orthodontic tooth movement into the narrow alveolar ridge, a non-invasive prevention method is yet to be fully established. We show for the first time prevention of bone dehiscence associated with orthodontic tooth movement by prophylactic injection of bone anabolic agents in mice. In this study, we established a bone dehiscence mouse model by applying force application and used the granular type of scaffold materials encapsulated with bone morphogenetic protein (BMP)-2 and OP3-4, the receptor activator of NF-κB ligand (RANKL)-binding peptide, for the prophylactic injection to the alveolar bone. In vivo micro-computed tomography revealed bone dehiscence with decreased buccal alveolar bone thickness and height after force application, whereas no bone dehiscence was observed with the prophylactic injection after force application, and alveolar bone thickness and height were kept at similar levels as those in the control group. Bone histomorphometry analyses revealed that both bone formation and resorption parameters were significantly higher in the injection with force application group than in the force application without the prophylactic injection group. These findings suggest that the prophylactic local delivery of bone anabolic reagents can prevent bone dehiscence with increased bone remodelling activity.

Diagnostic accuracy of the Xpert® MTB/XDR assay for detection of Isoniazid and second-line antituberculosis drugs resistance at central TB reference laboratory in Tanzania

IntroductionEarly diagnosis of tuberculosis (TB) and universal access to drug-susceptibility testing (DST) are critical elements of the WHO End TB Strategy. Current rapid tests (e.g., Xpert® MTB/RIF and Ultra-assays) can detect rifampicin resistance-conferring mutations, but cannot detect resistance to Isoniazid and second-line anti-TB agents. Although Line Probe Assay is capable of detecting resistance to second-line anti-TB agents, it requires sophisticated laboratory infrastructure and advanced skills which are often not readily available in settings replete with TB. A rapid test capable of detecting Isoniazid and second-line anti-TB drug resistance is highly needed.MethodsWe conducted a diagnostic accuracy study to evaluate a new automated Xpert MTB/XDR 10-colour assay for rapid detection of Isoniazid and second-line drugs, including ethionamide, fluoroquinolones, and injectable drugs (Amikacin, Kanamycin, and Capreomycin). Positive Xpert MTB/RIF respiratory specimens were prospectively collected through routine diagnosis and surveillance of drug resistance at the Central TB Reference Laboratory in Tanzania. Specimens were tested by both Xpert XDR assay and LPA against culture-based phenotypic DST as the reference standard.FindingsWe analysed specimens from 151 TB patients with a mean age (SD) of 36.2 (12.7) years. The majority (n = 109, 72.2%) were males. The sensitivity for Xpert MTB/XDR was 93.5% (95% CI, 87.4–96.7); for Isoniazid, 96.6 (95% CI, 92.1–98.6); for Fluoroquinolone, 98.7% (95% Cl 94.8–99.7); for Amikacin, 96.6%; and (95% CI 92.1–98.6) for Ethionamide. Ethionamide had the lowest specificity of 50% and the highest was 100% for Fluoroquinolone. The diagnostic performance was generally comparable to that of LPA with slight variations between the two assays. The non-determinate rate (i.e., invalid M. tuberculosis complex detection) of Xpert MTB/XDR was 2·96%.ConclusionThe Xpert MTB/XDR demonstrated high sensitivity and specificity for detecting resistance to Isoniazid, Fluoroquinolones, and injectable agents. This assay can be used in clinical settings to facilitate rapid diagnosis of mono-isoniazid and extensively drug-resistant TB.

Particles versus Other Embolic Agents in Emergency Renal Artery Embolization, Various Indications And Techniques

Abstract Background Renal artery embolization (RAE) refers to the occlusion of the renal artery, or some of its branches, by injection of an embolic agent through an endovascular catheter. Aim and Objectives to compare various embolic agents such as metallic microcoils, microspheres (embospheres), polyvinyl alcohol (PVA), gelfoam and histoacryl in emergent indications and techniques for RAE in management of emergency renal diseases. Subjects and Methods This combined retrospective and prospective observational study was conducted at Egyptian Military Hospitals, Radiodiagnosis and Intervention departments, and Ain Shams hospitals. The study included 18 patients with clinical and radiological confirmation of symptomatic indications for urgent RAE from 2019 to 2022. The duration of the study was 3 years. Result small sample sized and emergent cases showing mean embolization time was 12.6 minutes with no detected recanalization nor post embolic syndrome. Conclusion Renal artery embolization has become an effective, versatile therapeutic and adjuvant tool for many urologic conditions, both acute and chronic. It can be applied successfully in improving preoperative management of renal tumors prior to nephrectomy, achieving hemostasis in cases of hemorrhage from trauma or from tumors such as angiomyolipomas, treating complications of renal transplantation and biopsies such as arteriovenous fistulas and pseudoaneurysms, improving symptoms in patients with arteriovenous malformations and certain chronic renal parenchymal diseases, and for treating renal artery aneurysms.

Prostate tissue ablation and drug delivery by an image-guided injectable ionic liquid in ex vivo and in vivo models.

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.

Comparison of intravitreal bevacizumab monotherapy and combined laser photocoagulation and intravitreal bevacizumab therapy in the same session in the treatment of aggressive retinopathy of prematurity.

To compare the results of intravitreal bevacizumab (IVB) monotherapy and combined intravitreal bevacizumab and laser photocoagulation (LPC) therapies applied in the same session to patients with aggressive retinopathy of prematurity (A-ROP) in our clinic. The study included 67 eyes of 37 patients diagnosed with A-ROP and treated. Forty-nine eyes treated with anti-vascular endothelial growth factor agent injection monotherapy for A-ROP treatment were included in the first group. The second group consisted of 18 eyes that received injection therapy and LPC treatment. The clinical findings of the two groups were investigated, and their treatment results were compared. Recurrence was observed in 19 of the 49 (38%) eyes in the first group, but there was no recurrence in any of the cases in the second group. While only IVB was applied to eight cases with recurrence, the combination of LPC and IVB treatment was applied to 11 cases. A second recurrence was detected in two of the eight cases that had received IVB monotherapy as a treatment for recurrence and in three of the 11 cases that had received LPC and IVB. The treatment outcomes of the two groups did not statistically significantly differ (P = 0.181). We consider that the combined simultaneous LPC and IVB treatment we applied in A-ROP cases is an effective approach, particularly for cases where there are concerns about the patient's ability to attend follow-up appointments.

Using four-point subcutaneous injection of lymphatic contrast-enhanced ultrasound to diagnose lymphedema of lower extremity.

The diagnosis of lymphedema primarily relies on the clinical symptoms, signs, medical history and imaging. Objective lymphatic imaging helps improving the diagnosis of lymphedema. This study aimed to develop an effective imaging tool to diagnose lymphedema. This is a single-center retrospective study. From September 2022 to November 2023, we enrolled thirty-two patients, involving 40 lower extremities who underwent lymphatic contrast-enhanced ultrasound (CEUS) following a subcutaneous injection of contrast agent at four points in the First Affiliated Hospital of Sun Yat-sen University. Cohen's kappa value, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. Lymphoscintigraphy was the reference standard. Successful lymphatic-CEUS detection was defined as the situation that lymphatic drainage of medial or lateral lower limbs were observed. The successful detection rate was 100% (40 of 40). The diagnosis of lymphedema was based on the presence of either medial or lateral lymphatic obstructions, or subcutaneous lymphatic enhancement. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for diagnosing lymphedema by lymphatic-CEUS were as follows: 91.2% (31 of 34), 100% (6 of 6), 100% (31 of 31), 66.7% (6 of 9) and 92.5% (37 of 40), respectively. The Cohen's Kappa value was 0.756. The area under the receiver operating characteristic curve (AUC) for the subcutaneous injection of four-point lymphatic-CEUS was 0.956. This study put forward a novel four-point lymphatic-CEUS method to detect the functions of the lymphatics of lower extremities and established a lymphatic-CEUS standard for diagnosing lymphedema of lower extremities. Four-point lymphatic-CEUS is a considerable option for diagnosing lymphedema of lower extremities.

Intratumoral Injection of Immunotherapeutics: State of the Art and Future Directions.

Systemic immunotherapies have led to tremendous progress across the cancer landscape. However, several challenges exist, potentially limiting their efficacy in the treatment of solid tumors. Direct intratumoral injection can increase the therapeutic index of immunotherapies while overcoming many of the barriers associated with systemic administration, including limited bioavailability to tumors and potential systemic safety concerns. However, challenges remain, including the lack of standardized approaches for administration, issues relating to effective drug delivery, logistical hurdles, and safety concerns specific to this mode of administration. This article reviews the biologic rationale for the localized injection of immunotherapeutic agents into tumors. It also addresses the existing limitations and practical considerations for safe and effective implementation and provide recommendations for optimizing logistics and treatment workflows. It also highlights the critical role that radiologists, interventional radiologists, and medical physicists play in intratumoral immunotherapy with respect to target selection, image-guided administration, and response assessment.

Utilization of Lower-Dose Cyclobenzaprine in the Older Inpatient.

Background In older inpatients, anticholinergic medications can increase the risk of complications that may increase length of stay (LOS). Cyclobenzaprine is an anticholinergic medication associated with mental status changes, falls, and injuries in older patients. Objective The purpose of this study is to determine whether use of a lower cyclobenzaprine dose (5 mg) compared with higher dosing (10 mg) will affect LOS, 30-day readmission rates, and need for injectable psychotropic agents in inpatients 65 years of age and older. Methods This was a retrospective cohort analysis comparing outcomes in patients 65 years of age and older who received either a 5 mg or 10 mg cyclobenzaprine dose during their inpatient admission over a 2.5-year period. The primary outcome was hospital LOS, adjusted using multivariate linear regression. Secondary outcomes included 30-day readmission rate adjusted using logistic regression and use of injectable antipsychotics or benzodiazepines. A sub-analysis evaluated the impact of the institution's implementation of a geriatric prescribing context (GEM-CON) on cyclobenzaprine dose selection. Results The adjusted LOS was 32.7% longer (95% CI 25.9%-39.9%) for patients exposed to higher-dose cyclobenzaprine. Use of injectable antipsychotics or benzodiazepines was also significantly greater in the higher-dose group (P < 0.001; P = 0.025). Cyclobenzaprine dose was not significantly associated with readmission on multivariate analysis (OR = 0.93, 95% CI 0.45-1.93). After GEM-CON implementation, there was a significant increase in use of the recommended lower cyclobenzaprine dose (P < 0.001). Conclusion Use of lower cyclobenzaprine dosing in older inpatients is associated with reduced hospital LOS and need for injectable antipsychotics and benzodiazepines.

LIVER CANCER IMAGE PREPROCESSING AND FEATURE SELECTION USING A HYBRID DEEP LEARNING NETWORK

A liver's primary duties include producing bile, which is necessary for the breakdown of fats, filtering and changing potentially harmful compounds in the blood, and storing vitamins and nutrients. The diagnosis of malignant liver lesions can be made using a variety of techniques, including magnetic resonance imaging (MRI) and/or CT scanning with multiphase contrast agent injection. focuses on the methods for creating tumor and liver segmentation with the IVGG19-UNeT hybrid deep learning network. The suggested model's deep learning network scheme structure is made up of preprocessing, feature extraction, classification, and segmentation. With over 98% accuracy in tumor categorization, the suggested method accurately identifies the greatest number of tumor regions.

A Prodrug Strategy to Reposition Atovaquone as a Long-Acting Injectable for Malaria Chemoprotection.

Recent malaria drug discovery approaches have been extensively focused on the development of oral, smallmolecule inhibitors for disease treatment whereas parenteral routes of administration have been avoided due to limitations in deploying a shelf-stable injectable even though it could be dosed less frequently. However, an updated target candidate profile from Medicines for Malaria Venture (MMV) and stakeholders have advocated for long-acting injectable chemopreventive agents as an important interventive tool to improve malaria prevention. Here, we present strategies for the development of a long-acting, intramuscular, injectable atovaquone prophylactic therapy. We have generated three prodrug approaches that are contrasted by their differential physiochemical properties and pharmacokinetic profiles: mCBK068, a docosahexaenoic acid ester of atovaquone formulated in sesame oil, mCKX352, a heptanoic acid ester of atovaquone formulated as a solution in sesame oil, and mCBE161, an acetic acid ester of atovaquone formulated as an aqueous suspension. As a result, from a single 20 mg/kg intramuscular injection, mCKX352 and mCBE161 maintain blood plasma exposure of atovaquone above the minimal efficacious concentration for >70 days and >30 days, respectively, in cynomolgus monkeys. The differences in plasma exposure are reflective of the prodrug strategy, which imparts altered chemical properties that ultimately influence aqueous solubility and depot release kinetics. On the strength of the pharmacokinetic and safety profiles, mCBE161 is being advanced as a first-in-class clinical candidate for first-in-human trials.

Evaluation of pancreatic iodine uptake and related influential factors in multiphase dual-energy CT.

To establish normative values and identify potential factors influencing pancreatic iodine uptake using dual-energy CT (DECT). This retrospective study included participants without pancreatic diseases undergoing DECT at two institutions with different platforms. Their protocols both included arterial phase (AP), portal venous phase (PP), and equilibrium phase (EP), defined as 35 s-40 s, 60 s-70 s, and 150 s-180 s after injection of contrast agent, respectively. Both iodine concentration (IC) and normalised IC (NIC) were measured. Demographic features, local measurements of the pancreas and visceral fat area (VFA) were considered as potential factors influencing iodine uptake using multivariate linear regression analyses. A total of 562 participants (median age 58 years [interquartile range: 47-67], with 282 men) were evaluated. The mean IC differed significantly between two institutions (all p < 0.001) across three contrast-enhanced phases, while the mean NIC showed no significant differences (all p > 0.05). The mean values of NIC were 0.22 at AP, 0.43 at PP and 0.45 at EP. NICAP was independently affected by VFA (β = 0.362, p < 0.001), smoking (β = -0.240, p = 0.001), and type-II diabetes (β = -0.449, p < 0.001); NICPP by VFA (β = -0.301, p = 0.017) and smoking (β = -0.291, p < 0.001); and NICEP by smoking (β = -0.154, p = 0.10) and alcohol consumption (β = -0.350, p < 0.001) with statistical power values over 0.81. NIC values were consistent across institutions. Abdominal obesity, smoking, alcohol consumption, and diabetes are independent factors influencing pancreatic iodine uptake. This study has provided reference normative values, influential factors and effective normalisation methods of pancreatic iodine uptake in multiphase dual-energy CT for future studies in this area as a new biological marker. Evaluation of pancreatic iodine uptake measured by dual-energy CT is a promising method for future studies. Abdominal obesity, smoking, alcohol consumption, diabetes, and sex are independent factors influencing pancreatic iodine uptake. Utility of normalised iodine concentration is necessary to ensure the consistency across different institutions.

Optical coherence tomography-derived texture-based radiomics features identify eyes with intraocular inflammation in the HAWK clinical trial

Background and objectiveIntravitreal injection of anti-VEGF agents is the first-line treatment for patients with neovascular-age related macular degeneration (nAMD). One unique serious adverse event that may be associated with these agents is intraocular inflammation (IOI). The main purpose of this analysis was to evaluate the potential presence of texture-based radiomics features characterizing heterogeneity within the vitreous compartment of spectral domain optical coherence tomography (SD-OCT) images that may precede or develop in association with IOI and might serve as OCT biomarkers for IOI. MethodsThis is a post-hoc analysis of a subset of cases (N = 67) involving IOI, endophthalmitis, and/or retinal vascular occlusion in the phase 3 HAWK trial. These were investigator determined diagnoses that were also confirmed by the safety review committee. Intraocular inflammation was any signs of inflammation within the eye, endophthalmitis was inflammation associated with presumed infection, and retinal vascular occlusions consisted of intraocular inflammation with concurrent vascular occlusions/vasculitis. Out of 67 eyes, 34 belonged to the Safety group with an IOI event and 33 were propensity-matched Controls. A total of 481 texture-based radiomics features were extracted from the vitreous compartment of the SD-OCT scans at pre-IOI time point (i.e., much earlier than the actual event). Most discriminating five features, selected by the Wilcoxon Rank Sum feature selection were evaluated using Random Forest (RF) classifier on the training set (Str, N = 47) to differentiate between the two patient groups. Classifier performance was subsequently validated on the independent test set (St, N = 20). Additionally, the classifier performance in discriminating the Control and Safety group was also validated on St at the IOI event timepoint. ResultsThe RF classifier yielded area under the Receiver Operating Characteristics curve (AUC) of 0.76 and 0.81 on St using texture-based radiomics features at pre-IOI and event time-point, respectively. ConclusionsIn this analysis, the presence of a pre-IOI safety signal was detected in the form of textural heterogeneity within the vitreous compartment even prior to the actual event being identified by the investigator. This finding may help the clinicians to assess for underlying posterior inflammation.

Influence of Phase Change Droplet Activation and Microbubble Cavitation on the Microenvironment of Hepatocellular Carcinoma

ObjectiveBoth microbubble ultrasound contrast agents and acoustic phase change droplets (APCD) have been explored in hepatocellular carcinoma (HCC). This work aimed to evaluate changes to the HCC microenvironment following either microbubble or APCD destruction in a syngeneic pre-clinical model. MethodsMouse RIL-175 HCC tumors were grown in the right flank of 64 immunocompetent mice. Pre-treatment, photoacoustic volumetric tumor oxygenation, and power Doppler measurements were obtained using a Vevo 3100 system (VisualSonics, Toronto, Canada). The experimental groups received a 0.1 mL bolus injection of either Definity ultrasound contrast agent (Lantheus Medical Imaging) or APCD fabricated by condensing Definity. Following injection, ultrasound destruction was performed using flash-replenishment sequences on a Sequoia with a 10L4 probe (Siemens) for the duration of enhancement. Tumor oxygenation and power Doppler measurements were then repeated immediately post-ultrasound treatment. Twenty-four hours post-treatment, animals were euthanized, and tumors were harvested and stained for CD31, Cleaved Caspase 3 and CD45. ResultsImaging biomarkers demonstrated a significant reduction in percent vascularity following either microbubble or APCD destruction in the tumor microenvironment ( p < 0.022) but no significant changes in tumor oxygenation (p = 0.12). Similarly, immunohistochemistry data demonstrated a significant decrease in CD31 expression (p < 0.042) and an increase in apoptosis (p < 0.014) in tumors treated with destroyed microbubbles or APCD relative to controls. Finally, a significant increase in CD45 expression was observed in tumors treated with APCD (p = 0.046), indicating an increase in tumor immune response. ConclusionUltrasound-triggered destruction of both microbubbles and APCD reduces vascularity, increases apoptosis, and may also increase immune response in this HCC model.

Establishment of a selective puncture method of the temporomandibular joint targeting the superior and inferior joint spaces using a human cadaver under the guidance of an ultrasound device

To investigate an ultrasound-guided selective puncture method for the temporomandibular joint (TMJ), targeting superior (SJS) and inferior joint spaces (IJS), using a human cadaver. The study utilized five cadavers donated by members of our university. The cadaver's left side was aimed at the SJS, while the right side was at the IJS. Nonionic contrast was injected into each joint using a crossing technique, with the linear ultrasound probe placed parallel to the long axis of the mandibular branch and punctured perpendicularly into the joint cavity. Cone-beam computed tomography scans assessed both the TMJs examining discs and other components for damage using a gross anatomical technique. Computed tomography images confirmed successful contrast agent injection into all joint spaces without damaging the articular discs or cartilage of the mandibular head. Our findings suggest that the ultrasound device can selectively puncture the TMJ in the SJS and IJS. In the future, the success rate is expected to improve with additional cadaver punctures. We aim to establish this technique as a viable treatment method that can be performed by oral surgeons with limited clinical experience in cadaver surgery training and a surgical technique training program using human cadavers.

Comparison of Safety and Diagnostic Efficacy of Iohexol 240 mgI/mL, Iopamidol 250 mgI/mL, and Iodixanol 270 mgI/mL in Cerebral Angiography: A Prospective, Multicenter Study.

This multicenter prospective study aimed to evaluate the quality and diagnostic effectiveness of cerebral angiography images obtained using low-concentration iodinated contrast agents (iohexol 240 mgI/mL, iopamidol 250 mgI/mL, and iodixanol 270 mgI/mL) and to assess the safety thereof. The study addresses the need for safer contrast agent alternatives without compromising the diagnostic quality of identifying cerebrovascular disease. Conducted in 5 medical centers in South Korea, we enrolled patients aged 19 years or older who were referred for diagnostic cerebral angiography under non-emergency conditions, excluding those with specific health conditions and sensitivities. The study design included a prospective, observational approach with a 1-way analysis of variance (ANOVA) for sample size calculation, aiming for a total sample of 231 participants for adequate power. Image quality was evaluated using a 4-level scale by 2 independent, blinded radiologists, and adverse reactions were monitored both immediately and up to 7 days post-procedure. Statistical analysis involved 1-way ANOVA and Kruskal-Wallis tests to assess the image quality and safety profiles of the contrast agents. Among 266 patients screened, 243 were included in the final analysis. The evaluation revealed no statistically significant differences in image quality among the 3 types of low-concentration contrast agents. Adverse events were observed in 28.8% of patients, with 27.2% experiencing acute reactions, primarily mild reactions, and 3.3% experiencing delayed reactions. The overall safety profile showed no significant changes in vital signs or electrocardiogram readings before and after contrast agent injection. Using low-concentration iodinated contrast agents for cerebral angiography provides image quality comparable to that of conventional high-concentration agents, with no significant increase in adverse events, suggesting a safer alternative for patients.

Oligomeric amyloid-β targeted contrast agent for MRI evaluation of Alzheimer's disease mouse models.

Oligomeric amyloid beta (oAβ) is a toxic factor that acts in the early stage of Alzheimer's disease (AD) and may initiate the pathologic cascade. Therefore, detecting oAβ has a crucial role in the early diagnosis, monitoring, and treatment of AD. The purpose of this study was to evaluate MRI signal changes in different mouse models and the time-dependent signal changes using our novel gadolinium (Gd)-dodecane tetraacetic acid (DOTA)- ob5 aptamer contrast agent. We developed an MRI contrast agent by conjugating Gd-DOTA-DNA aptamer called ob5 to evaluate its ability to detect oAβ deposits in the brain using MRI. A total of 10 control mice, 9 3xTg AD mice, and 11 APP/PS/Tau AD mice were included in this study, with the age of each model being 16 or 36 weeks. A T1-weighted image was acquired at the time points before (0min) and after injection of the contrast agent at 5, 10, 15, 20, and 25min. The analyses were performed to compare MRI signal differences among the three groups and the time-dependent signal differences in different mouse models. Both 3xTg AD and APP/PS/Tau AD mouse models had higher signal enhancement than control mice at all scan-time points after injection of our contrast media, especially in bilateral hippocampal areas. In particular, all Tg AD mouse models aged 16 weeks showed a higher contrast enhancement than those aged 36 weeks. For 3xTg AD and APP/PS/Tau AD groups, the signal enhancement was significantly different among the five time points (0min, 5min, 10min, 15min, 20min, and 25min) in multiple ROI areas, typically in the bilateral hippocampus, left thalamus, and left amygdala. The findings of this study suggest that the expression of the contrast agent in different AD models demonstrates its translational flexibility across different species. The signal enhancement peaked around 15-20min after injection of the contrast agent. Therefore, our novel contrast agent targeting oAβ has the potential ability to diagnose early AD and monitor the progression of AD.

Patient-specific arterial input function for accurate perfusion assessment in intraoperative fluorescence imaging.

The arterial input function (AIF) plays a crucial role in correcting the time-dependent concentration of the contrast agent within the arterial system, accounting for variations in agent injection parameters (speed, timing, etc.) across patients. Understanding the significance of the AIF can enhance the accuracy of tissue vascular perfusion assessment through indocyanine green-based dynamic contrast-enhanced fluorescence imaging (DCE-FI). We evaluate the impact of the AIF on perfusion assessment through DCE-FI. A total of 144 AIFs were acquired from 110 patients using a pulse dye densitometer. Simulation and patient intraoperative imaging were conducted to validate the significance of AIF for perfusion assessment based on kinetic parameters extracted from fluorescence images before and after AIF correction. The kinetic model accuracy was evaluated by assessing the variability of kinetic parameters using individual AIF versus population-based AIF. Individual AIF can reduce the variability in kinetic parameters, and population-based AIF can potentially replace individual AIF for estimating wash-out rate ( ), maximum intensity ( ), ingress slope with lower differences compared with those in estimating blood flow, volume transfer constant ( ), and time to peak. Individual AIF can provide the most accurate perfusion assessment compared with assessment without AIF or based on population-based AIF correction.

#708 Retrospective analysis of the real-world experience of desidustat in the treatment of chronic kidney disease induced anemia

Abstract Background and Aims Chronic kidney disease (CKD) is commonly associated with an increased risk of anemia, which significantly impacts patients' quality of life and increases morbidity and mortality. Current treatment options for anemia in CKD, such as injectable erythropoiesis-stimulating agents (ESAs) have limitations and safety concerns. Desidustat, a novel oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) has shown promise in stimulating endogenous erythropoiesis and addressing anemia in CKD. Therefore, the present study assesses the real-world clinical efficacy and safety of the desidustat treatment for a short duration of 6 months (24 weeks) in CKD patients with anemia. Method This is a retrospective analysis of 140 patients at our center who received Desidustat as a treatment for CKD anemia. Desidustat was initiated in all patients at 100 mg three times a week. Dose adjustment was done every 4 weeks as per the Hb level of the patient. The duration of the study was 6 months. The primary endpoint of the present study was a change in Hb from baseline with desidustat therapy and the secondary endpoint was safety of the treatment. Results The majority of the patients were Pre-dialysis 74.28% (n = 104) and 25.72% (n = 36) were dialysis-dependent patients. Of 36 dialysis-dependent patients; 75% (n = 27) were on dialysis three times a week, rest were on twice-a-week dialysis. In the current study, the majority of patients had Hypertension (95.7%) and diabetes (68.57%) as co-morbidities. All the patients in the current study were maintained with 100 mg Desidustat, however, 9.2% (n = 13) required dose reduction, and 11.42% (n = 16) required an increased dose of desidustat on the follow-up visit. In both Pre-Dialysis and dialysis-dependent patients, there was a sustainable rise in the mean Hb levels at the end of 24 weeks from baseline (1.05 g/dL; p &amp;lt; 0.05) All the patients tolerated desidustat well. In the present study, we didn't observe significant side effects related to the therapy apart from 2.41% (n = 3) cases of Diarrhoea and Vomiting. Conclusion Desidustat is effective in increasing Hb in CKD Anemia patients in the short run. However, Long-term studies are required to establish the efficacy and safety of this novel therapy.

Time conditioning for arbitrary contrast phase generation in interventional computed tomography

Minimally invasive ablation techniques for renal cancer are becoming more popular due to their low complication rate and rapid recovery period. Despite excellent visualisation, one drawback of the use of computed tomography (CT) in these procedures is the requirement for iodine-based contrast agents, which are associated with adverse reactions and require a higher x-ray dose. The purpose of this work is to examine the use of time information to generate synthetic contrast enhanced images at arbitrary points after contrast agent injection from non-contrast CT images acquired during renal cryoablation cases. To achieve this, we propose a new method of conditioning generative adversarial networks with normalised time stamps and demonstrate that the use of a HyperNetwork is feasible for this task, generating images of competitive quality compared to standard generative modelling techniques. We also show that reducing the receptive field can help tackle challenges in interventional CT data, offering significantly better image quality as well as better performance when generating images for a downstream segmentation task. Lastly, we show that all proposed models are robust enough to perform inference on unseen intra-procedural data, while also improving needle artefacts and generalising contrast enhancement to other clinically relevant regions and features.