Fast detection of liver fibrosis with collagen-binding single-nanometer iron oxide nanoparticles via T1-weighted MRI.

SNIO-CBP, a single-nanometer iron oxide (SNIO) nanoparticle functionalized with a type I collagen-binding peptide (CBP), was developed as a T1-weighted MRI contrast agent with only endogenous elements for fast and noninvasive detection of liver fibrosis. SNIO-CBP exhibits 6.7-fold higher relaxivity compared to a molecular gadolinium-based collagen-binding contrast agent CM-101 on a per CBP basis at 4.7 T. Unlike most iron oxide nanoparticles, SNIO-CBP exhibits fast elimination from the bloodstream with a 5.7 min half-life, high renal clearance, and low, transient liver enhancement in healthy mice. We show that a dose of SNIO-CBP that is 2.5-fold lower than that for CM-101 has comparable imaging efficacy in rapid (within 15 min following intravenous injection) detection of hepatotoxin-induced liver fibrosis using T1-weighted MRI in a carbon tetrachloride-induced mouse liver injury model. We further demonstrate the applicability of SNIO-CBP in detecting liver fibrosis in choline-deficient L-amino acid-defined high-fat diet mouse model of nonalcoholic steatohepatitis. These results provide a platform with potential for the development of high relaxivity, gadolinium-free molecular MRI probes for characterizing chronic liver disease.

DNA-Mediated Magnetic-Dimer Assembly for Fault-Free Ultra-High-Field Magnetic Resonance Imaging of Tumors.

Ultra-high-field (UHF) magnetic resonance imaging (MRI) stands as a pivotal cornerstone in biomedical imaging, yet the challenge of false imaging persists, constraining its full potential. Despite the development of dual-mode contrast agents improving conventional MRI, their effectiveness in UHF remains suboptimal due to the high magnetic moment, resulting in diminished T1 relaxivity and excessively enhanced T2 relaxivity. Herein, we report a DNA-mediated magnetic-dimer assembly (DMA) of iron oxide nanoparticles that harnesses UHF-tailored nanomagnetism for fault-free UHF-MRI. DMA exhibits a dually enhanced longitudinal relaxivity of 4.42 mM-1·s-1 and transverse relaxivity of 26.23 mM-1·s-1 at 9 T, demonstrating a typical T1-T2 dual-mode UHF-MRI contrast agent. Importantly, DMA leverages T1-T2 dual-modality image fusion to achieve artifact-free breast cancer visualization, effectively filtering interference from hundred-micrometer-level false-positive signals with unprecedented precision. The UHF-tailored T1-T2 dual-mode DMA contrast agents hold promise for elevating the accuracy of MR imaging in disease diagnosis.

Cationic tantalum oxide nanoparticle contrast agent for micro computed tomography reveals articular cartilage proteoglycan distribution and collagen architecture alterations.

OBJECTIVE: Cationic tantalum oxide nanoparticles (Ta2O5-cNPs), as a newly introduced contrast agent for computed tomography of cartilage, offer quantitative evaluation of proteoglycan (PG) content and biomechanical properties. However, knowledge on the depth-wise impact of cartilage constituents on nanoparticle diffusion, particularly the influence of the collagen network, is lacking. In this study, we aim to establish the depth-dependent relationship between Ta2O5-cNP diffusion and cartilage constituents (PG content, collagen content and network architecture). METHODS: Osteochondral samples (n = 30) were harvested from healthy equine stifle joints (N = 15) and the diffusion of 2.55 nm diameter cationic Ta2O5-cNPs into the cartilage was followed with micro computed tomography (µCT) imaging for up to 96 hours. The diffusion-related parameters, Ta2O5-cNP maximum partition (Pmax) and diffusion time constant, were compared against biomechanical and depth-wise structural properties. Biomechanics were assessed using stress-relaxation and sinusoidal loading protocols, whereas PG content, collagen content and collagen network architecture were determined using digital densitometry, Fourier-transform infrared spectroscopy and polarized light microscopy, respectively. RESULTS: The Pmax correlates with the depth-wise distribution of PGs (bulk Spearman's ρ = 0.87, p < 0.001). More open collagen network architecture at the superficial zone enhances intake of Ta2O5-cNPs, but collagen content overall decreases the intake. The Pmax values correlate with the equilibrium modulus (ρ = 0.80, p < 0.001) of articular cartilage. CONCLUSION: This study establishes the feasibility of Ta2O5-cNPs for the precise and comprehensive identification of biomechanical and structural changes in articular cartilage via contrast-enhanced µCT.

Diagnostic efficacy of contrast-enhanced gastric ultrasonography in staging gastric cancer: a meta-analysis.

BACKGROUND: As comprehensive surgical management for gastric cancer becomes increasingly specialized and standardized, the precise differentiation between ≤T1 and ≥T2 gastric cancer before endoscopic intervention holds paramount clinical significance. OBJECTIVE: To evaluate the diagnostic efficacy of contrast-enhanced gastric ultrasonography in differentiating ≤T1 and ≥T2 gastric cancer. METHODS: PubMed, Web of Science, and Medline were searched to collect studies published from January 1, 2000 to March 16, 2023 on the efficacy of either double contrast-enhanced gastric ultrasonography (D-CEGUS) or oral contrast-enhanced gastric ultrasonography (O-CEGUS) in determining T-stage in gastric cancer. The articles were selected according to specified inclusion and exclusion criteria, and the quality of the included literature was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 scale. Meta-analysis was performed using Stata 12 software with data from the 2 × 2 crosslinked tables in the included literature. RESULTS: In total, 11 papers with 1124 patients were included in the O-CEGUS analysis, which revealed a combined sensitivity of 0.822 (95% confidence interval [CI] = 0.753-0.875), combined specificity of 0.964 (95% CI = 0.925-0.983), and area under the summary receiver operating characteristic (sROC) curve (AUC) of 0.92 (95% CI = 0.89-0.94). In addition, five studies involving 536 patients were included in the D-CEGUS analysis, which gave a combined sensitivity of 0.733 (95% CI = 0.550-0.860), combined specificity of 0.982 (95% CI = 0.936-0.995), and AUC of 0.93 (95% CI = 0.91-0.95). According to the I2 and P values ​​of the forest plot, there was obvious heterogeneity in the combined specificities of the included papers. Therefore, the two studies with the lowest specificities were excluded from the O-CEGUS and D-CEGUS analyses, which eliminated the heterogeneity among the remaining literature. Consequently, the combined sensitivity and specificity of the remaining studies were 0.794 (95% CI = 0.710-0.859) and 0.976 (95% CI = 0.962-0.985), respectively, for the O-CEDUS studies and 0.765 (95% CI = 0.543-0.899) and 0.986 (95% CI = 0.967-0.994), respectively, for the D-CEGUS studies. The AUCs were 0.98 and 0.99 for O-CEGUS and D-CEGUS studies, respectively. CONCLUSION: Both O-CEGUS and D-CEGUS can differentiate ≤T1 gastric cancer from ≥T2 gastric cancer, thus assisting the formulation of clinical treatment strategies for patients with very early gastric cancer. Given its simplicity and cost-effectiveness, O-CEGUS is often favored as a staging method for gastric cancer prior to endoscopic intervention.

Gadolinium Contrast Agent Deposition in Children.

Over the past few years, a large number of studies have evidenced increased signal intensity in the deep brain nuclei on unenhanced T1-MRI images achieved by the application of gadolinium-based contrast agents (GBCAs). The deposition of gadolinium in the brain, bone, and other tissues following administration of GBCAs has also been confirmed in histological studies in rodents and in necropsy studies in adults and children. Given the distinct physiological characteristics of children, this review focuses on examining the current research on gadolinium deposition in children, particularly studies utilizing novel methods and technologies. Furthermore, the article compares safety research findings of linear GBCAs and macrocyclic GBCAs in children, with the aim of offering clinicians practical guidance based on the most recent research outcomes. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

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.

Magnetic Resonance Imaging of Fibroblast Activation Protein Using a Targeted Gadolinium-Based Contrast Agent.

The aim of this study was to synthesize a quinoline-based MRI contrast agent, Gd-DOTA-FAPI04, and assess its capacity for targeting fibroblast activation protein (FAP)-positive tumors in vivo. Gd-DOTA-FAPI04 was synthesized by attaching a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complex of gadolinium(III) to FAP inhibitor FAPI04. The longitudinal relaxation time (T1) of the contrast agent was measured using a Siemens Prisma 3.0T MR system, and the CCK-8 assay was performed to evaluate its potential cytotoxicity. Male nude mice bearing tumors grown from FAP-expressing fibrosarcoma cells were divided into experimental (n = 4) and control (n = 4) groups, and T1-weighted image enhancement was measured at different times (0, 10, 30, 60, 90, and 120 min) postinjection of Gd-DOTA-FAPI04. The control group received an additional preinjection of excess FAPI04. FAP expression in tumor tissue was investigated by using immunohistochemistry with an anti-FAP antibody. The longitudinal relaxivities of gadodiamide and Gd-DOTA-FAPI04 were measured to be 3.734 mM-1 s-1 and 5.323 mM-1 s-1, respectively. The CCK-8 assay demonstrated that Gd-DOTA-FAPI04 has minimal toxicity to cultured human fibrosarcoma cells. In vivo MRI showed that peak accumulation of Gd-DOTA-FAPI04 in FAP-expressing tumors occurred 1 h postinjection and could be blocked by preinjection of excess FAPI04. Immunohistochemical analysis of harvested tumor tissue supported the above findings. Gd-DOTA-FAPI04 is a promising contrast agent for in vivo imaging of FAP.

The value of non-enhanced MRI in the evaluation of patients with suspected idiopathic inflammatory myopathy.

INTRODUCTION/AIMS: The performance of magnetic resonance imaging (MRI) for diagnosing suspected idiopathic inflammatory myopathy (IIM) remains controversial. Furthermore, the role of contrast-enhanced magnetic resonance imaging (CE-MRI) sequences is unclear. The aim of this study was to evaluate the sensitivity and specificity of a non-enhanced magnetic resonance imaging (NE-MRI) protocol compared to a CE-MRI protocol in adult patients with confirmed IIM. METHODS: This study retrospectively enrolled patients with suspected IIM who underwent MRI of the upper thigh between 2008 and 2020. The protocol consisted of a T1-weighted (T1w) sequence, a turbo inversion recovery magnitude (TIRM) sequence and a contrast-enhanced T1-weighted sequence (CE-T1w). After randomly stratifying patients into a group with only the T1w and TIRM sequences available and another group with additional availability of CE-T1w, three blinded readers assessed the presence of IIM based on characteristic imaging features. Confirmation of the diagnosis was determined based on the 2017 ACR/EULAR criteria. RESULTS: Of the 80 patients (mean age 49.0 ± 21.1 years; 42 female, 38 male) included, 54 (67.5%) had a positive diagnosis of IIM. Cumulated sensitivity and specificity for MRI to detect IIM was 87.1% and 83.3% in the NE-MRI group versus 87.0% and 63.0% in the CE-MRI group. The group differences for sensitivity and specificity were non-significant for each of the three readers, respectively (p ≥ .081). DISCUSSION: NE-MRI detects suspected IIM with high diagnostic accuracy and performs equivalently to CE-MRI. Therefore, it may be appropriate to omit the use of contrast agents in MRI scans performed for suspected IIM.

Computational peptide discovery with a genetic programming approach.

The development of peptides for therapeutic targets or biomarkers for disease diagnosis is a challenging task in protein engineering. Current approaches are tedious, often time-consuming and require complex laboratory data due to the vast search spaces that need to be considered. In silico methods can accelerate research and substantially reduce costs. Evolutionary algorithms are a promising approach for exploring large search spaces and can facilitate the discovery of new peptides. This study presents the development and use of a new variant of the genetic-programming-based POET algorithm, called POET Regex , where individuals are represented by a list of regular expressions. This algorithm was trained on a small curated dataset and employed to generate new peptides improving the sensitivity of peptides in magnetic resonance imaging with chemical exchange saturation transfer (CEST). The resulting model achieves a performance gain of 20% over the initial POET models and is able to predict a candidate peptide with a 58% performance increase compared to the gold-standard peptide. By combining the power of genetic programming with the flexibility of regular expressions, new peptide targets were identified that improve the sensitivity of detection by CEST. This approach provides a promising research direction for the efficient identification of peptides with therapeutic or diagnostic potential.

Aminolysis-mediated single-step surface functionalization of poly (butyl cyanoacrylate) microbubbles for ultrasound molecular imaging.

Molecular ultrasound imaging with actively targeted microbubbles (MB) proved promising in preclinical studies but its clinical translation is limited. To achieve this, it is essential that the actively targeted MB can be produced with high batch-to-batch reproducibility with a controllable and defined number of binding ligands on the surface. In this regard, poly (n-butyl cyanoacrylate) (PBCA)-based polymeric MB have been used for US molecular imaging, however, ligand coupling was mostly done via hydrolysis and carbodiimide chemistry, which is a multi-step procedure with poor reproducibility and low MB yield. Herein, we developed a single-step coupling procedure resulting in high MB yields with minimal batch-to-batch variation. Actively targeted PBCA-MB were generated using an aminolysis protocol, wherein amine-containing cRGD was added to the MB using lithium methoxide as a catalyst. We confirmed the successful conjugation of cRGD on the MB surface, while preserving their structure and acoustic signal. Compared to the conventional hydrolysis protocol, aminolysis resulted in higher MB yields and better reproducibility of coupling efficiency. Optical imaging revealed that under flow conditions, cRGD- and rhodamine-labelled MB, generated by aminolysis, specifically bind to tumor necrosis factor-alpha (TNF-α) activated endothelial cells in vitro. Furthermore, US molecular imaging demonstrated a markedly higher binding of the cRGD-MB than of control MB in TNF-α activated mouse aortas and 4T1 tumors in mice. Thus, using the aminolysis based conjugation approach, important refinements on the production of cRGD-MB could be achieved that will facilitate the production of clinical-scale formulations with excellent binding and ultrasound imaging performance.

Chitosan-modified manganese oxide-conjugated methotrexate nanoparticles delivering 5-aminolevulinic acid as a dual-modal T1-T2* MRI contrast agent in U87MG cell detection.

OBJECTIVE: Glioblastoma multiforme is a highly aggressive form of brain cancer, and early diagnosis plays a pivotal role in improving patient survival rates. In this regard, molecular magnetic resonance imaging has emerged as a promising imaging modality due to its exceptional sensitivity to minute tissue changes and the ability to penetrate deep into the brain. This study aimed to assess the efficacy of a novel contrast agent in detecting gliomas during MRI scans. MATERIALS AND METHODS: The contrast agent utilized modified chitosan coating on manganese oxide nanoparticles. The modification included adding methotrexate and 5-aminolevulinic acid (MnO2/CS@5-ALA-MTX) to target cells with overexpressed folate receptors and breaking down excess hydrogen peroxide in tumor tissue, resulting in enhanced signal intensity in T1-weighted MR images but diminished signal intensity in T2*-weighted MR images. RESULTS: The nanosystem was characterized and evaluated in MR imaging, safety, and ability to target cells both in vivo and in vitro. MTX-free nanoparticles (MnO2/CS@5-ALA NPs) had no obvious cytotoxicity on cell lines U87MG and NIH3T3 after 24/48 h at a concentration of up to 160 µgr/mL (cell viability more than 80%). In this system, methotrexate enables tumor targeting and the MnO2/5-ALA improves T1-T2*-weighted MRI. In addition, MRI scans of mice with M109 carcinoma indicated significant tumor uptake and NP capacity to improve the positive contrast effect. CONCLUSION: This developed MnO2/CS@5-ALA-MTX nanoparticle system may exhibit great potential in the accurate diagnosis of folate receptor over-expressing cancers such as glioblastoma.

The feasibility of half-dose contrast-enhanced scanning of brain tumours at 5.0 T: a preliminary study.

PURPOSE: This study investigated and compared the effects of Gd enhancement on brain tumours with a half-dose of contrast medium at 5.0 T and with a full dose at 3.0 T. METHODS: Twelve subjects diagnosed with brain tumours were included in this study and underwent MRI after contrast agent injection at 3.0 T (full dose) or 5.0 T (half dose) with a 3D T1-weighted gradient echo sequence. The postcontrast images were compared by two independent neuroradiologists in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and subjective image quality score on a ten-point Likert scale. Quantitative indices and subjective quality ratings were compared with paired Student's t tests, and interreader agreement was assessed with the intraclass correlation coefficient (ICC). RESULTS: A total of 16 enhanced tumour lesions were detected. The SNR was significantly greater at 5.0 T than at 3.0 T in grey matter, white matter and enhanced lesions (p < 0.001). The CNR was also significantly greater at 5.0 T than at 3.0 T for grey matter/tumour lesions, white matter/tumour lesions, and grey matter/white matter (p < 0.001). Subjective evaluation revealed that the internal structure and outline of the tumour lesions were more clearly displayed with a half-dose at 5.0 T (Likert scale 8.1 ± 0.3 at 3.0 T, 8.9 ± 0.3 at 5.0 T, p < 0.001), and the effects of enhancement in the lesions were comparable to those with a full dose at 3.0 T (7.8 ± 0.3 at 3.0 T, 8.7 ± 0.4 at 5.0 T, p < 0.001). All subjective scores were good to excellent at both 5.0 T and 3.0 T. CONCLUSION: Both quantitative and subjective evaluation parameters suggested that half-dose enhanced scanning via 5.0 T MRI might be feasible for meeting clinical diagnostic requirements, as the image quality remains optimal. Enhanced scanning at 5.0 T with a half-dose of contrast agents might benefit patients with conditions that require less intravenous contrast agent, such as renal dysfunction.

Sodium selenite attenuates inflammatory response and oxidative stress injury by regulating the Nrf2/ARE pathway in contrast-induced acute kidney injury in rats.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is an acute renal complication that occurs after intravascular contrast agent administration. Sodium selenite (SS) is an inorganic source of Se and has potent antioxidant properties. This study intends to examine its anti-inflammatory and antioxidant effects in CI-AKI. METHODS: A rat CI-AKI model was established with the pretreatment of SS (0.35 mg/kg). Hematoxylin-eosin staining was employed for histopathological analysis of rat kidney specimens. Biochemical analysis was conducted for renal function detection. Tissue levels of oxidative stress-related markers were estimated. Reverse transcription-quantitative polymerase chain reaction revealed the mRNA levels of proinflammatory cytokines. Western blotting showed the Nrf2 signaling-related protein expression in the rat kidney. RESULTS: SS administration alleviated the renal pathological changes and reduced the serum levels of serum creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin, cystatin C, and urinary level of kidney injury molecule-1 in CI-AKI rats. SS attenuated oxidative stress and inflammatory response in CI-AKI rat kidney tissues. SS activated the Nrf2 signaling transduction in the renal tissues of rats with CI-AKI. CONCLUSION: SS ameliorates CI-AKI in rats by reducing oxidative stress and inflammation via the Nrf2 signaling.

Detecting insulitis in type 1 diabetes with ultrasound phase-change contrast agents.

Type 1 diabetes (T1D) results from immune infiltration and destruction of insulin-producing ß cells within the pancreatic islets of Langerhans (insulitis). Early diagnosis during presymptomatic T1D would allow for therapeutic intervention prior to substantial ß-cell loss at onset. There are limited methods to track the progression of insulitis and ß-cell mass decline. During insulitis, the islet microvasculature increases permeability, such that submicron-sized particles can extravasate and accumulate within the islet microenvironment. Ultrasound is a widely deployable and cost-effective clinical imaging modality. However, conventional microbubble contrast agents are restricted to the vasculature. Submicron nanodroplet (ND) phase-change agents can be vaporized into micron-sized bubbles, serving as a microbubble precursor. We tested whether NDs extravasate into the immune-infiltrated islet microenvironment. We performed ultrasound contrast-imaging following ND infusion in nonobese diabetic (NOD) mice and NOD;Rag1ko controls and tracked diabetes development. We measured the biodistribution of fluorescently labeled NDs, with histological analysis of insulitis. Ultrasound contrast signal was elevated in the pancreas of 10-wk-old NOD mice following ND infusion and vaporization but was absent in both the noninfiltrated kidney of NOD mice and the pancreas of Rag1ko controls. High-contrast elevation also correlated with rapid diabetes onset. Elevated contrast was also observed as early as 4 wk, prior to mouse insulin autoantibody detection. In the pancreata of NOD mice, infiltrated islets and nearby exocrine tissue were selectively labeled with fluorescent NDs. Thus, contrast ultrasound imaging with ND phase-change agents can detect insulitis prior to diabetes onset. This will be important for monitoring disease progression, to guide and assess preventative therapeutic interventions for T1D.

Enhancement of the lymphatic system following intravenous administration of ferumoxytol.

BACKGROUND: Lymphatic imaging is becoming increasingly important in the management of patients with congenital heart disease. However, the influence of the intravenous contrast agent ferumoxytol on lymphatic imaging is not well understood. OBJECTIVE: To evaluate the impact of intravenous ferumoxytol on T1-weighted and T2-weighted lymphatic imaging in patients with congenital heart disease. MATERIALS AND METHODS: We included consecutive patients receiving ferumoxytol-enhanced 3D angiography for congenital heart disease evaluation. The visibility of the thoracic duct was reviewed on the T1-weighted 3D inversion recovery balanced-steady-state free precession (SSFP) with respiratory navigator gating sequence which is routinely used for angiography and the heavily T2-weighted turbo spin echo sequence which is employed for lymphatic imaging. Data on demographics and time interval between contrast administration and imaging were collected. Statistical analyses were performed using t-tests for continuous variables and chi-squared tests for categorical variables. RESULTS: One hundred nineteen consecutive patients with a mean age of 12.46 years±7.7 years were included. Of these, 45 cases underwent both T1-weighted and T2-weighted imaging; the other 74 underwent only T1-weighted imaging. Of the 45 patients, 20 had thoracic duct enhancement on T1-weighted imaging; among the 26 sedated, only 2 showed enhancement, while 18 of 19 non-sedated patients showed enhancement (P<0.001), indicating a strong association between sedation and reduced thoracic duct visibility. If T2-weighted imaging was performed after contrast administration, the thoracic duct was not visible on those images. For all 45 cases of visible thoracic duct in the entire cohort, the time from contrast administration to imaging ranged from 8 min up to 75 min. CONCLUSION: The enhancement of the thoracic lymphatic duct on T1-weighted imaging, coupled with degradation observed on T2-weighted imaging, suggests that intravenously administered ferumoxytol rapidly enters the lymphatic fluid. To prevent T2 shortening from degrading the imaging results, T2-weighted imaging for lymphatic evaluation should be performed prior to the administration of ferumoxytol. Sedation and, by inference, fasting may influence this property and warrant further investigation in future studies.

Contrast Echocardiography in Heart Failure: Update 2023.

PURPOSE OF REVIEW: The application of ultrasound-enhancing agents (contrast agents) has improved the accuracy and reproducibility of echocardiography. The review focuses on the currently approved and evolving indications for contrast echocardiography in patients with heart failure, specifically examining clinical studies conducted after the publication of the guidelines in 2017 and 2018. RECENT FINDINGS: The current ASE/EACVI recommendations for contrast echocardiography are based on its accuracy and reproducibility in comparison to non-enhanced echocardiography or other imaging modalities like cardiac MRI. However, tissue characterization remains limited with contrast echocardiography. During the last few years, several studies have demonstrated the clinical impact of using contrast agents on the management of patients with heart failure. There is growing evidence on the benefit of using contrast echocardiography in critically ill patients where echocardiography without contrast agents is often suboptimal and other imaging methods are less feasible. There is no risk of worsening renal function after the administration of ultrasound-enhancing agents, and these agents can be administered even in patients with end-stage renal disease. Contrast echocardiography has become a valuable tool for first-line imaging of patients with heart failure across the spectrum of patients with chronic heart failure to critically ill patients.

No gadolinium K-edge detected on the first clinical photon-counting computed tomography scanner.

PURPOSE: This study aimed to elucidate whether gadolinium contrast in clinically relevant doses can be used with photon-counting computed tomography (PCCT) as an alternative contrast agent in clinical applications. MATERIAL/METHODS: A CTDI phantom with 3D printed rods filled with different concentrations of gadolinium and iodine contrast was scanned in a PCCT and an energy-integrated computed tomography (EICT). Attenuation values at different monoenergetic steps were extracted for each contrast concentration. RESULTS: For PCCT, gadolinium reached an attenuation >100 HU (103 HU) at 40 keV with a concentration 5 mmol/L whereas the same level was reached at 50 keV (118 HU) for 10 mmol/L and 90 keV (114 HU) for 25 mmol/L. For iodine, the same level of attenuation was reached at 100 keV (106 HU) with a concentration 8.75 mg I/mL. For EICT the lowest gadolinium contrast concentration needed to reach >100 HU (108 HU) was 10 mmol/L at 50 keV. For 25 mmol/L 100 HU was reached at 100 keV. For iodine contrast 108 HU was reached at 110 keV for 8.75 mg I/mL. CONCLUSION: No K-edge potential or difference in attenuation curves between iodine and gadolinium contrast is detected on the first clinical available PCCT. Clinically relevant attenuation levels were barely achieved in this setting with gadolinium concentrations approved for human use. The results of this study suggest that, given current scanning technology, gadolinium is not a clinically useful contrast agent for computed tomography because no K-edge was detected.

Prognostic value of CT findings for conservative treatment failure in adhesive small bowel obstruction.

PURPOSE: This study aimed to identify the radiological CT findings that are significantly correlated with the outcome of conservative management with oral water-soluble contrast medium in patients presenting with Adhesive Small Bowel Obstruction (ASBO) to the Emergency Room. METHODS: In this retrospective single-center study, we considered all consecutive patients admitted to the ER from February 2019 to February 2023 for ASBO with an available contrast-enhanced CT scan performed at diagnosis and treated with conservative management. The investigated CT findings were type and location of transition zone, ASBO degree, fat notch sign, beak sign, small bowel feces sign, presence of peritoneal free fluid and pneumatosis intestinalis. Radiological parameters were analyzed using univariable and multivariable logistic regression to test the significant association between the CT parameters and the target. RESULTS: Among the 106 included patients (median age 74.5 years), conservative treatment was effective in 59 (55.7%) and failed in 47 (44.3%), needing delayed surgery. In the failure group, there was a higher prevalence of patients who had previous ASBO episodes (p = 0.03), a greater proportion of females (p = 0.04) and a longer hospital stay (p < 0.001). At multivariable analysis, two CT findings were significantly correlated with failure of conservative treatment: fat notch sign (OR = 2.95; p = 0.04) and beak sign (OR = 3.42; p = 0.04). CONCLUSIONS: Two radiological signs correlate with failure of non-operative management in ASBO, suggesting their importance in surgical decision-making. Patients presenting with these signs are at higher risk of unsuccessful conservative treatment and may require undelayed surgical intervention.

Pancreatic ductal adenocarcinoma: CEUS characteristics are correlated with pathological findings and help predict early recurrence after resection.

OBJECTIVES: To identify characteristics of preoperative contrast-enhanced ultrasound (CEUS) that could predict early recurrence after curative resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: From January 2017 to September 2022, a total of 110 patients with PDAC (all confirmed by samples obtained via operation) who underwent CEUS within 1 month before surgery were enrolled. We proposed five CEUS enhancement patterns (Pattern I, homogeneous enhancement; Pattern II, heterogeneous enhancement without cystic components; pattern III, ring enhancement; Pattern IV, starry enhancement; Pattern V, heterogeneous enhancement with cystic components) of PDAC. Clinical-pathologic and CEUS characteristics for predicting early recurrence (recurrence within 1 year after curative resection) were analyzed. Important CEUS characteristics were compared with the pathological findings. RESULTS: Tumor size and TNM stage were closely associated with early recurrence. Incomplete-enhancement and enhancement pattern III, IV and V at CEUS imaging were more prone to early recurrence. Incomplete-enhancement lesions had higher histological tumor grades, less frequent remaining acini, and more frequent necrosis within the tumor. PDACs with pattern I and II had lower histological tumor grades, and pattern III, IV and V had higher histological tumor grades. PDACs with pattern I, II and IV had less frequent intratumoral necrosis than PDACs with pattern III and V, and PDACs with pattern IV had lower MVD values. CONCLUSIONS: PDACs with incomplete enhancement and enhancement pattern III, IV and V were more prone to early recurrence after attempted curative resection, and these important CEUS characteristics were closely related to the pathological findings of PDAC.

Effectiveness of contrast-enhanced duplex ultrasound for detecting renal artery stenosis: A systematic review.

PURPOSE: Contrast-enhanced duplex ultrasound (CEUS) might be a useful tool to diagnosing renal artery stenosis (RAS). We amalgamated and reviewed the evidence assessing the diagnostic accuracy of CEUS on detecting RAS compared to angiography. METHODS: This preregistered systematic review included studies that compared the presence of RAS via CEUS with angiography. Sources were searched in November 2022 and included Scopus, EMBASE, MEDLINE, CINAHL, and Academic Search Premier (n = 1717). The Quality Assessment of Diagnostic Studies 2 tool assessed study quality. Results are presented narratively. RESULTS: The studies included (n = 11) had a total of 447 unique participants (193 females) and average age of 56 ± 9 years. Five of eleven studies investigated CEUS using SonoVue contrast agent and reported an average accuracy (91% ± 2%), sensitivity (91% ± 3%), specificity (90% ± 5%), negative predictive value (86% ± 6%), and positive predictive value (94% ± 1%) with all values >80%. The accuracy of CEUS using other types of contrast agent (n = 6), including Levovsit (n = 3/6), Definity (n = 1/6), perfienapent emulsion (n = 1/6), and perfluorocarbon-exposed sonicated dextrose albumin (n = 1/6) was mixed. These studies detected an average accuracy of 91 ± 11% (n = 2/3% > 80%), sensitivity of 98% ± 4%, (n = 3/3% > 80%), and specificity of 86% ± 10% (n = 2/3% > 80%). Included studies had generally low risk of bias and applicability concerns except for unclear flow and timing (n = 7/11) and applicability of patient selection (n = 4/11). CONCLUSION: Despite being limited by the heterogeneity of included studies, our review indicates a high overall diagnostic accuracy for CEUS to detect RAS compared to angiography, with the largest evidence-base for SonoVue contrast. Radiologists and hospital decision makers should consider CEUS as an acceptable alternative to angiography.