Application Of Contrast Agent Research Articles

Microscopic Characterization and Fractal Analysis of Pore Systems for Unconventional Reservoirs

The complex pore structure of unconventional oil and gas reservoirs is one of the reasons for the difficulties in resource evaluation and development. Therefore, it is crucial to comprehensively characterize the pore structure, understand reservoir heterogeneity from multiple perspectives, and gain an in-depth understanding of fluid migration and accumulation mechanisms. This review outlines the methods and basic principles for characterizing microporous systems in unconventional reservoirs, summarizes the fractal analysis corresponding to the different methods, sorts out the relationship between the fractals and reservoir macroscopic physical properties (porosity, permeability, etc.) with the reservoir microscopic pore structures (pore structure parameters, pore connectivity, etc.). The research focuses on cutting-edge applications of characterization techniques, such as improved characterization accuracy, calibration of PSD ranges, and identification of different hydrogen compositions in pore systems for dynamic assessment of unconventional reservoirs. Fractal dimension analysis can effectively identify the quality level of the reservoir; complex pore-throat structures reduce permeability and destroy free fluid storage space, and the saturation of removable fluids is negatively correlated with Df. As for the mineral composition, the fractal dimension is positively correlated with quartz, negatively correlated with feldspar, and weakly correlated with clay mineral content. In future qualitative characterization studies, the application and combination of contrast agents, molecular dynamics simulations, artificial intelligence techniques, and 4D imaging techniques can effectively improve the spatial resolution of the images and explore the adsorption/desorption of gases within the pores, and also help to reduce the computational cost of these processes; these could also attempt to link reservoir characterization to research on supercritical carbon dioxide-enhanced integrated shale gas recovery, carbon geological sequestration, and advanced underground hydrogen storage.

Rising sun or strangled in the cradle？A narrative review of near-infrared fluorescence imaging-guided surgery for pancreatic tumors.

Near-infrared fluorescence (NIRF)-guided surgical navigation has become a promising and effective detection method in pancreatic tumor surgery. The imaging technique has gradually transitioned from the NIR-I region to the NIR-II region. Real-time assessment of the tumor boundary and determination of the ideal resection plane are essential for preserving the pancreatic parenchyma and its secretory functions. However, since the pancreatic parenchyma has a less rich blood supply than the liver, the application of contrast agents in pancreatic tumor surgery is still in its infancy. The application of indocyanine green (ICG) and methylene blue (MB) in intraoperative NIRF imaging of pancreatic tumors has become more mature, but due to the characteristics of non-specific imaging, the imaging efficiency and depth need to be improved. Many tumor-specific imaging agents have been designed, but most of them have not gone past animal trials because of their high development and imaging costs, biotoxicity, and other limitations. In this article, we review recent reports of ICG, MB and newly developed contrast agents and imaging devices. We focus on the current status and new developments in the application of these contrast agents and summarize the current clinical and preclinical studies on specific contrast agents. We synthesize relevant reports to discuss the difficulties and prospects of the application of fluorescent imaging agents in pancreatic tumors. We hope that reviewing previous studies and the current progress on contrast imaging technology will provide new perspectives for its future application and development in pancreatic tumor surgery, which should translate into better patient prognoses. The manuscript was written according to the Scale for the Assessment of Narrative Review Articles (SANRA).

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.

Repeatable Acoustic Vaporization of Coated Perfluorocarbon Bubbles for Micro-Actuation Inspired by Polypodium aureum.

Polypodium aureum, a fern, possesses a specialized spore-releasing mechanism like a catapult induced by the quick expansion of vaporized bubbles. This study introduces lipid-coated perfluorocarbon droplets to enable repeatable vaporization-condensation cycles, inspired by the repeatable vaporization of Polypodium aureum. Lipid-perfluorocarbon droplets have been considered not to exhibit repeatable oscillations due to bubble collapse of the low surface tension of lipid layers. However, a single lipid-dodecafluoropentane droplet with a diameter of 9.17 µm shows expansion-contraction oscillations over 4000 cycles by changing lipid composition and applying a low-power 1.7 MHz ultrasound to induce the partial vaporization of the droplets. The optimal combinations of shell composition, droplet fabrication, and acoustic conditions can minimize the damage on shell structure and promote a quick recovery of damaged shell layers. The highly expanding oscillatory microbubbles provide a new direction for fuel-free micro- or nanobots, as well as biomedical applications of contrast agents and drug delivery.

Key Insights on the Classification and Theranostic Applications of Magnetic Resonance Imaging Contrast Agents.

Magnetic resonance imaging (MRI) is a non-invasive molecular imaging tool being extensively employed in clinical and biomedical research for the detection of a broad spectrum of diseases. This technique offers remarkable spatial resolution, good tissue penetration and a high soft tissue contrast. Contrast agents (CAs) have been regularly used in MRI tests to enhance the resolution of MR images and to visualize the diseased sites in the body. In the past years, considerable efforts have been devoted towards developing new theranostic MRI agents that can be tailored to integrate the targeting and therapeutic functions in a single agent. In this review, we have underlined the role of the MRI CAs in the developing field of 'theranostics' and their recent applications in the combined imaging and therapy of different types of tumors. In addition, this review also outlines the different categories of MRI CAs and their comprehensive classification based on different criteria such as chemical composition, relaxation mechanism and biodistribution with clinically relevant examples.

The Influence of Computed Tomography Contrast Agent on Radiation-Induced Gene Expression and Double-Strand Breaks.

After nuclear scenarios, combined injuries of acute radiation syndrome (ARS) with, e.g., abdominal trauma, will occur and may require contrast-enhanced computed tomography (CT) scans for diagnostic purposes. Here, we investigated the effect of iodinated contrast agents on radiation-induced gene expression (GE) changes used for biodosimetry (AEN, BAX, CDKN1A, EDA2R, APOBEC3H) and for hematologic ARS severity prediction (FDXR, DDB2, WNT3, POU2AF1), and on the induction of double-strand breaks (DSBs) used for biodosimetry. Whole blood samples from 10 healthy donors (5 males, 5 females, mean age: 28 ± 2 years) were irradiated with X rays (0, 1 and 4 Gy) with and without the addition of iodinated contrast agent (0.016 ml contrast agent/ml blood) to the blood prior to the exposure. The amount of contrast agent was set to be equivalent to the blood concentration of an average patient (80 kg) during a contrast-enhanced CT scan. After irradiation, blood samples were incubated at 37°C for 20 min (DSB) and 8 h (GE, DSB). GE was measured employing quantitative real-time polymerase chain reaction. DSB foci were revealed by γH2AX + 53BP1 immunostaining and quantified automatically in >927 cells/sample. Radiation-induced differential gene expression (DGE) and DSB foci were calculated using the respective unexposed sample without supplementation of contrast agent as the reference. Neither the GE nor the number of DSB foci was significantly (P = 0.07-0.94) altered by the contrast agent application. However, for some GE and DSB comparisons with/without contrast agent, there were weakly significant differences (P = 0.03-0.04) without an inherent logic and thus are likely due to inter-individual variation. In nuclear events, the diagnostics of combined injuries can require the use of an iodinated contrast agent, which, according to our results, does not alter or influence radiation-induced GE changes and the quantity of DSB foci. Therefore, the gene expression and γH2AX focus assay can still be applied for biodosimetry and/or hematologic ARS severity prediction in such scenarios.

Subharmonic resonance of phospholipid coated ultrasound contrast agent microbubbles

Phospholipid encapsulated ultrasound contrast agents have proven to be a powerful addition in diagnostic imaging and show emerging applications in targeted therapy due to their resonant and nonlinear scattering. Microbubble response is affected by their intrinsic (e.g. bubble size, encapsulation physics) and extrinsic (e.g. boundaries) factors. One of the major intrinsic factors at play affecting microbubble vibration dynamics is the initial phospholipid packing of the lipid encapsulation. Here, we examine how the initial phospholipid packing affects the subharmonic response of either individual or a system of two closely-placed microbubbles. We employ a finite element model to investigate the change in subharmonic resonance under ‘small’ and ‘large’ radial excursions. For microbubbles ranging between 1.5 and 2.5 µm in diameter and in its elastic state (σ0 = 0.01 N/m), we demonstrate up to a 10 % shift towards lower frequencies in the peak subharmonic response as the radial excursion increases. However, for a bubble initially in its buckled state (σ0 = 0 N/m), we observe a maximum shift of 8 % towards higher frequencies as the radial excursion increases over the same range of bubble sizes – the opposite trend. We studied the same scenario for a system of two individual microbubbles for which we saw similar results. For microbubbles that are initially in their elastic state, in both cases of a) two identically sized bubbles and b) a bubble in proximity to a smaller bubble, we observed a 6 % and 9 % shift towards lower frequencies respectively; while in the case of a neighboring larger bubble no change in subharmonic resonance frequency was observed. Microbubbles that are initially in a buckled state exert no change, 5 % and 19 % shift towards higher frequencies, in two-bubble systems consisting of a) same-size, b) smaller, and c) larger neighboring bubble respectively. Furthermore, we examined the effect of two adjacent bubbles with non-equal initial phospholipid states. The results presented here have important implications in ultrasound contrast agent applications.

Clinical Case of IVUS-Guided Coronary Artery Stenting in a Patient with Chronic Renal Failure

Introduction. An expanding number of indications for PCI in patients with coronary heart disease and severe concomitant pathology are accompanied by a growing number of patients with chronic renal failure. Contrast-induced nephropathy (CIN) is recognized as a severe complication, aggravating the course of the underlying disease, and, moreover, reducing the life expectancy of the patients. Modern intravascular imaging technologies are widely implemented in real clinical practice of endovascular surgery. In the context of increasing number of PCI performed in patients with severe concomitant pathology, the IVUS-guidance will improve the quality of stenting, and, importantly, lessen the risks of CIN due to the reduction in contrast volume. Materials and methods. The paper presents a clinical case of IVUSguided stenting of the right coronary artery without contrast agent in a patient with chronic kidney disease and the following diagnosis: “Coronary heart disease. Effort angina, class III (dyspnea as anginal equivalent). Balloon angioplasty and stenting of circumflex artery and LAD. Hyperlipidemia 2a. Atherosclerosis of the aorta, brachiocephalic and coronary arteries. Stage 3 hypertension. Controlled Hypertension. Level IV CVD risk. Type 2 diabetes mellitus. Target glycated hemoglobin is less than 7.5%. Grade 2 obesity, exogenous-constitutional. Renal microlithiasis. CKD stage 4 (GFR 29 ml/min/1.73m2). Cerebrovascular disease. Chronic cerebral ischemia.” Results and discussion. In the described clinical case, a complete myocardial revascularization was achieved using IVUS-guidance and minimal amount of contrast agent in a patient with severe CKD. The advantage of minimally invasive endovascular interventions in a complex category of patients, demonstrated by the case, implies expanded possibilities for providing high-tech care to patients with significant limitations in the use of contrast agents due to severe CKD with a high risk of CIN. Conclusion. Today, an increasing number of X-ray operating rooms in Russia are equipped with intravascular technologies, ensuring their wider use. The skills and knowledge in using IVUS imply rare application of contrast agents, thereby lessening the risk of CKD and, as a consequence, improving the prognosis of patients with reduced renal function and high risk of CKD.

Application of liver-specific contrast agents for evaluation of focal liver lesions - Expert recommendations from the Gastrointestinal and Abdominal Imaging Workgroup of the German Roentgen Society.

Contrast-enhanced MRI is the imaging modality of choice for the detection and differential diagnosis of focal liver lesions. Liver-specific contrast agents (CAs) are now well established in addition to extracellular contrast agents. However, there is a lack of explicit recommendations reflecting the pros and cons of each specific contrast agent in the daily routine. Development of recommendations for the clinical application of liver-specific CAs by members of the Gastrointestinal and Abdominal Imaging Workgroup within the Germany Radiological Society, using methodology comparable to that of an S1 guideline with informal consensus. The diagnostic criteria for the evaluation of liver lesions are intentionally outside the scope of this article, as there are already plenty of excellent publications available. The application of liver-specific CAs in the daily routine is associated with advantages and disadvantages due to the specific pharmacokinetic and pharmacodynamic properties and necessitates adjustment of the imaging technique as well consideration during image interpretation. Recommendations for the application of liver-specific CAs are presented based on different clinical scenarios, taking into account current evidence and guidelines. · Both liver-specific and extracellular contrast agents are established. · Liver-specific contrast agents make it possible to draw conclusions about the hepatocellular function of a lesion. · Recommendations for the use of liver-specific contrast agents in the daily routine are presented. · Ringe KI, Fischbach F, Grenacher L et al. Einsatz leberspezifischer Kontrastmittel in der MRT zur Beurteilung von Leberläsionen - Expertenempfehlungen der AG Gastrointestinal- und Abdominaldiagnostik der Deutschen Röntgengesellschaft. Fortschr Röntgenstr 2023; DOI: 10.1055/a-2192-9921.

Personalized Cancer Therapeutics Using Photoacoustic Imaging-Guided Sonodynamic Therapy.

Sonodynamic therapy (SDT) is a promising approach for cancer treatment that uses sonosensitizers (SNSs) to generate reactive oxygen species (ROS) in the presence of ultrasound. However, SDT is oxygen-dependent and requires an imaging tool to monitor the tumor microenvironment and guide treatment. Photoacoustic imaging (PAI) is a noninvasive and powerful imaging tool that offers high spatial resolution and deep tissue penetration. PAI can quantitatively assess tumor oxygen saturation (sO2) and guide SDT by monitoring time-dependent sO2 changes in the tumor microenvironment. Here, we discuss recent advances in PAI-guided SDT for cancer therapy. We discuss various exogenous contrast agents and nanomaterial-based SNSs developed for PAI-guided SDT. Additionally, combining SDT with other therapies, including photothermal therapy, can enhance its therapeutic effect. However, the application of nanomaterial-based contrast agents in PAI-guided SDT for cancer therapy remains challenging due to the lack of simple designs, the need for extensive pharmacokinetic studies, and high production costs. Integrated efforts from researchers, clinicians, and industry consortia are necessary for the successful clinical translation of these agents and SDT for personalized cancer therapy. PAI-guided SDT shows the potential to revolutionize cancer therapy and improve patient outcomes, but further research is necessary to realize its full potential.

Reliability of signal intensity in the basal ganglia on non-contrast T1-weighted MR scans after repetitive application of a gadolinium-based contrast agent in pediatric neuro-oncology patients

PurposeTo evaluate the reliability of signal intensity (SI) changes in the basal ganglia as a supposed indicator of gadolinium deposition in the brain after repetitive application of gadolinium-based contrast agents (GBCAs) in a pediatric neuro-oncological collective. MethodsOne hundred and eight neuropediatric patients (54 male, 54 female, 0–17 years old), with repetitive GBCA-enhanced cranial MRIs between 2003 and 2017, were retrospectively analyzed. Two radiologists measured SI in the nucleus dentatus (ND), globus pallidus (GP), thalamus (T), and the pons (P). The NDP and GPT ratio were calculated. An intraclass correlation coefficient, and multiple linear regressions with subsequent stepwise backward variable selection were performed to evaluate the influence of gender, patient’s age at the first MRI, time interval between the first and last MRI, linear or macrocyclic GBCAs, residual pathology, treatments, and magnet field strengths. ResultsThe inter-reader agreement was good for GPT and NDP in the whole collective (ICC = 0.837 and ICC = 0.793) and for children >2 years of age (ICC = 0.874 and ICC = 0.790), but poor to moderate for children ≤2 years of age (ICC = 0.397 and ICC = 0.748). The intra-reader agreement was good (ICC = 0.910 and ICC = 0.882). An SI increase was only observed for both readers in GPT (p = 0.003, or p < 0.001). None of the considered cofactors showed a consistent effect on SI changes for either readers or regions. ConclusionMeasurements of SI changes in the basal ganglia are not a reliable parameter with which to evaluate or estimate gadolinium deposition in the brain or to identify suspicious influential factors after repeated GBCA applications.

4Dimensional XStrain Echocardiography: Comprehensive Evaluation of Non-obstructive Hypertrophic Cardiomyopathy- A Case Report and Review of Literature

Hypertrophic cardiomyopathy (HCM) is a relatively common inherited cardiomyopathy, which is occasionally challenging to differentiate from hypertensive heart disease and athletes heart on the basis of morphologic or functional abnormalities alone. Imaging studies provide solution for majority of clinical presentations. Generally, transthoracic echocardiography (TTE) is employed as a first line imaging tool and contrast enhanced echocardiography (CEE), contrast tuned imaging echocardiography (CTIE), cardiac magnetic resonance (CMR), cardiac computed tomography (CCT), cardiac nuclear imaging and speckle tracking echocardiography (STE) are encouraged for either suboptimal studies because of poor visualization of left ventricular (LV) cavity or for comprehensive delineation of the cardiac anatomy, its widespread left and right ventricular involvement, associations and complications. We are reporting a case of 48-year old male presenting to us with atypical chest pain and a history of suspicious solitary episode of syncope. His routine ECG was indicative of left ventricular hypertrophy with strain pattern, and his TTE was substandard and inadequate in the apical four chamber (4CH) and five chamber (5CH) views, hence CTIE was performed without the application of intravenous contrast agents, to produce a remarkable illustration of HCM.&#x0D; Keywords: Hypertrophic cardiomyopathy, contrast echocardiography, contrast tuned imaging, speckle tracking echocardiography, 4Dimensional XStrain, Non obstructive HCM

Elemental Bioimaging of Sheep Bone and Articular Cartilage After Single Application of Gadolinium-Based Contrast Agents.

Gadolinium-based contrast agents (GBCAs) are applied to enhance magnetic resonance imaging. Gadolinium (Gd), a rare earth metal, is used in a chelated form when administered as GBCA to patients. There is an ongoing scientific debate about the clinical significance of Gd retention in tissues after administration of GBCAs. It is known that bone serves as Gd reservoir, but only sparse information on localization of Gd in bone is available. The aim of this study was to compare Gd tissue concentration and spatial distribution in femoral epiphysis and diaphysis 10 weeks after single-dose injection of linear and macrocyclic GBCAs in a large animal model. In this prospective animal study, Swiss-Alpine sheep (n = 36; age range, 4-10 years) received a single injection (0.1 mmol/kg) of macrocyclic (gadobutrol, gadoteridol, and gadoterate meglumine), linear (gadodiamide and gadobenate dimeglumine) GBCAs, or saline. Ten weeks after injection, sheep were killed, and femur heads and shafts were harvested. Gadolinium spatial distribution was determined in 1 sample of each treatment group by laser ablation-inductively coupled plasma-mass spectrometry. All bone specimens were analyzed histopathologically. Injection of GBCAs in female Swiss-Alpine sheep (n = 36) resulted in Gd localization at the endosteal and periosteal surface and in a subset of GBCAs additionally at the cement lines and the bone cartilage junction. No histopathological alterations were observed in the investigated tissue specimens. Ten weeks after single injection of a clinically relevant dose in adult sheep, both linear species of GBCA resulted in considerably higher accumulation than macrocyclic GBCAs. Gadolinium deposits were restricted to distinct bone and cartilage compartments, such as in bone linings, cement lines, and bone cartilage junctions. Tissue histology remained unaffected.

The clinical predictive value and regulation mechanism of microRNA-188-5p in contrast-induced acute kidney injury

Contrast-induced acute kidney injury (CI-AKI), also known as contrast-induced nephropathy (CIN), has become the third leading cause of iatrogenic AKI. Serum creatinine (Scr) is currently used in CIN clinical diagnosis. Patients with increased Scr have developed severe kidney injury, so there is an urgent need to find a bio-marker for CIN early diagnosis. To investigate the changes in circulating microRNA-188-5p (miR-188-5p) after coronary angiography and its predictive value for the CIN occurrence, miR-188-5p expression in CIN rats from the GEO database and CIN patients and control patients from Lianshui People's Hospital was analyzed. The results showed that miR-188-5p expression in plasma and renal was higher in CIN group than in control group. Further, a total of 36 CIN patients and 108 non-CIN patients were included. There were significant differences in age, hypertension, diabetes, and contrast agent dosage. After 12 h of contrast agent application, circulating miR-188-5p expression in CIN group was higher than control group. Univariate and multivariate logistic regression analysis showed that age, hypertension, diabetes, contrast media dosage and postoperative miR-188-5p expression were closely related to CIN occurrence. For in vitro experiments, intracellular miR-188-5p expression was decreased with ioversol treatment, while miR-188-5p expression in supernatant was increased. To explore the potential mechanism of miR-188-5p in CIN, HK-2 cells were treated with NC mimic, ioversol, or miR-188-5p mimic. The results showed that the application of miR-188-5p mimic reduced apoptosis, reactive oxygen species and MDA, enhanced SOD and GSH contents. Further, it was confirmed that mRNA and protein levels of PTEN were up-regulated in ioversol-treated HK-2 cells, and down-regulated after miR-188-5p administration. Dual-luciferase reporter gene assay confirmed that PTEN was direct target gene of miR-188-5p. Above results suggest that circulating miR-188-5p has the potential to serve as a predictor of CIN.

Magnetic Resonance-guided Procedures: Consensus on Rationale, Techniques, and Outcomes

Magnetic resonance (MR) image guidance has demonstrated significant potential in the field of interventional radiology in several applications. This article covers the main points of MR-guided hepatic tumor ablation as a representative of MR-guided procedures. Patient selection and appropriate equipment utilization are essential for successful MR-guided tumor ablation. Intra-procedural planning imaging enables the visualization of the tumor and surrounding anatomical structures in most cases without application of contrast agent, ensuring optimal planning of the applicator tract. MRI enables real-time, multiplanar imaging, thus simultaneous observation of the applicator and target tumor is possible during targeting with adaptable slice angulations in case of challenging tumor positions. Typical ablation zone appearance during therapy monitoring with MRI enables save assessment of the therapy result, resulting in a high primary efficacy rate. Recent advancements in ablation probes have shortened treatment times, while technical strategies address applicator visibility issues. MR-imaging immediately after the procedure is used to rule out complications and to assess technical success. Especially in smaller neoplasms, MRI-guided liver ablation demonstrates positive outcomes in terms of technical success rates, as well as promising survival and recurrence rates. Additionally, percutaneous biopsy under MR guidance offers an alternative to classic guidance modalities, providing high soft tissue contrast and thereby increasing the reliability of lesion detection, particularly in cases involving smaller lesions. Despite these advantages, use of MR-guidance in clinical routine is still limited to few indications and centers, due to by high costs, extended duration, and the need for specialized expertise. In conclusion, MRI-guided interventions could benefit from ongoing advancements in hardware, software and devices. Such progress has the potential to expand diagnostic and treatment options in the field of interventional radiology.

Redox Properties and in Vivo Magnetic Resonance Imaging of Cyclodextrin-Polynitroxides Contrast Agents.

This paper reports the synthesis, characterization and in vivo application of water-soluble supramolecular contrast agents (Mw: 5-5.6 kDa) for MRI obtained from β-cyclodextrin functionalized with different kinds of nitroxide radicals, both with piperidine structure (CD2 and CD3) and with pyrrolidine structure (CD4 and CD5). As to the stability of the radicals in presence of ascorbic acid, CD4 and CD5 have low second order kinetic constants (≤0.05 M-1 s-1 ) compared to CD2 (3.5 M-1 s-1 ) and CD3 (0.73 M-1 s-1 ). Relaxivity (r1 ) measurements on compounds CD3-CD5 were carried out at different magnetic field strength (0.7, 3, 7 and 9.4 T). At 0.7 T, r1 values comprised between 1.5 mM-1 s-1 and 1.9 mM-1 s-1 were found while a significant reduction was observed at higher fields (r1 ≈0.6-0.9 mM-1 s-1 at 9.4 T). Tests in vitro on HEK293 human embryonic kidney cells, L929 mouse fibroblasts and U87 glioblastoma cells indicated that all compounds were non-cytotoxic at concentrations below 1 μmol mL-1 . MRI in vivo was carried out at 9.4 T on glioma-bearing rats using the compounds CD3-CD5. The experiments showed a good lowering of T1 relaxation in tumor with a retention of the contrast for at least 60 mins confirming improved stability also in vivo conditions.

18F]FDG PET/MRI in children suffering from lymphoma: does MRI contrast media make a difference?

ObjectivesEvaluate the influence of an MRI contrast agent application on primary and follow-up staging in pediatric patients with newly diagnosed lymphoma using [18F]FDG PET/MRI to avoid adverse effects and save time and costs during examination.MethodsA total of 105 [18F]FDG PET/MRI datasets were included for data evaluation. Two different reading protocols were analyzed by two experienced readers in consensus, including for PET/MRI-1 reading protocol unenhanced T2w and/or T1w imaging, diffusion-weighted imaging (DWI), and [18F]FDG PET imaging and for PET/MRI-2 reading protocol an additional T1w post contrast imaging. Patient-based and region-based evaluation according to the revised International Pediatric Non-Hodgkin’s Lymphoma (NHL) Staging System (IPNHLSS) was performed, and a modified standard of reference was applied comprising histopathology and previous and follow-up cross-sectional imaging. Differences in staging accuracy were assessed using the Wilcoxon and McNemar tests.ResultsIn patient-based analysis, PET/MRI-1 and PET/MRI-2 both determined a correct IPNHLSS tumor stage in 90/105 (86%) exams. Region-based analysis correctly identified 119/127 (94%) lymphoma-affected regions. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for PET/MRI-1 and PET/MRI-2 were 94%, 97%, 90%, 99%, 97%, respectively. There were no significant differences between PET/MRI-1 and PET/MRI-2.ConclusionsThe use of MRI contrast agents in [18F]FDG PET/MRI examinations has no beneficial effect in primary and follow-up staging of pediatric lymphoma patients. Therefore, switching to a contrast agent–free [18F]FDG PET/MRI protocol should be considered in all pediatric lymphoma patients.Clinical relevance statementThis study gives a scientific baseline switching to a contrast agent–free [18F]FDG PET/MRI staging in pediatric lymphoma patients. This could avoid side effects of contrast agents and saves time and costs by a faster staging protocol for pediatric patients.Key Points• No additional diagnostic benefit of MRI contrast agents at [18F]FDG PET/MRI examinations of pediatric lymphoma primary and follow-up staging• Highly accurate primary and follow-up staging of pediatric lymphoma patients at MRI contrast–free [18F]FDG PET/MRI

Disentangling the impact of cerebrospinal fluid formation and neuronal activity on solute clearance from the brain

BackgroundDespite recent attention, pathways and mechanisms of fluid transposition in the brain are still a matter of intense discussion and driving forces underlying waste clearance in the brain remain elusive. Consensus exists that net solute transport is a prerequisite for efficient clearance. The individual impact of neuronal activity and cerebrospinal fluid (CSF) formation, which both vary with brain state and anesthesia, remain unclear.MethodsTo separate conditions with high and low neuronal activity and high and low CSF formation, different anesthetic regimens in naive rat were established, using Isoflurane (ISO), Medetomidine (MED), acetazolamide or combinations thereof. With dynamic contrast-enhanced MRI, after application of low molecular weight contrast agent (CA) Gadobutrol to cisterna magna, tracer distribution was monitored as surrogate for solute clearance. Simultaneous fiber-based Ca2+-recordings informed about the state of neuronal activity under different anesthetic regimen. T2-weighted MRI and diffusion-weighted MRI (DWI) provided size of subarachnoidal space and aqueductal flow as surrogates for CSF formation. Finally, a pathway and mechanism-independent two-compartment model was introduced to provide a measure of efficiency for solute clearance from the brain.ResultsAnatomical imaging, DWI and Ca2+-recordings confirmed that conditions with distinct levels of neuronal activity and CSF formation were achieved. A sleep-resembling condition, with reduced neuronal activity and enhanced CSF formation was achieved using ISO+MED and an awake-like condition with high neuronal activity using MED alone. CA distribution in the brain correlated with the rate of CSF formation. The cortical brain state had major influence on tracer diffusion. Under conditions with low neuronal activity, higher diffusivity suggested enlargement of extracellular space, facilitating a deeper permeation of solutes into brain parenchyma. Under conditions with high neuronal activity, diffusion of solutes into parenchyma was hindered and clearance along paravascular pathways facilitated. Exclusively based on the measured time signal curves, the two-compartment model provided net exchange ratios, which were significantly larger for the sleep-resembling condition than for the awake-like condition.ConclusionsEfficiency of solute clearance in brain changes with alterations in both state of neuronal activity and CSF formation. Our clearance pathway and mechanism agnostic kinetic model informs about net solute transport, solely based on the measured time signal curves. This rather simplifying approach largely accords with preclinical and clinical findings.

Excitability and glymphatic function in an animal model of Alzheimer’s disease

AbstractBackgroundAPPswe/PS1dE9 mice reproduce features of amyloid β (Aβ) pathology and neuronal dysfunction as reflected in electrophysiological recordings of neuronal hyperexcitability. This leads to changes in sleep‐wake‐rhythm, downstream affecting brain clearance functionality. Our objective is to investigate the effect of circadian rhythm and Aβ pathology on clearance efficacy in APPswe/PS1dE9 mice.MethodFirst, we examined the brain wide distribution of an intrahippocampal injected fluorescent dye. Dye was injected at 6 am (post wake period) or 6 pm (post sleep period) and sampled 1 or 3 h post injection for histological analysis (Figure 1A) in n = 3 transgenic mice and n = 3 non‐transgenic mice per group. Secondly, in an in vivo approach we analyzed the brain wide distribution of a gadolinium based contrast agent using a T2‐RARE sequence in a 7 Tesla small animal MRI scanner (Bruker BioSpin GmbH, Germany) (Figure 1B) in n = 4 transgenic mice and n = 4 non‐transgenic mice. We measured values for brightness in manually defined regions of interest with PMOD software (version 3.7; PMOD Technologies LLC, Switzerland).ResultIn the first experiment, we were able to observe dye distribution in the brain parenchyma as surrogate for interstitial clearance net flux. Preliminary results point to an effect of circadian rhythm, as a trend of better dye distribution shortly after the sleep period was observed. Furthermore, a possible detrimental effect of the Aβ phenotype on clearance was observed in transgenic mice. In comparison to non‐transgenic mice they showed a trend of lesser dye distribution independent of day‐time. With the second approach, we were able to observe influx and efflux of applied contrast agent into cerebrospinal fluid. Preliminary data point to a trend of an increased slope of the influx as well as decreased slope of the efflux in transgenic mice.ConclusionHistological analysis of a stereotactic injected dye is a feasible method for investigation of dye distribution outlining a possible effect of daytime and amyloid pathology. However, MR‐imaging is a promising tool as we will be able to observe the disease progression in mice longitudinally. Further experiments will be needed to ensure these preliminary results and maybe also point to underlying mechanistic basis.

Relevance of dedicated multiple sclerosis serum biomarkers in predicting contrast enhancement with gadolinium: Results from the REDUCE-GAD trial.

The presence of contrast enhancement (CE) on magnetic resonance imaging (MRI) is one of the principal criteria for diagnosis and disease activity of multiple sclerosis (MS). Therefore, MS patients are frequently exposed to contrast agents, which may cause deposition in the brain, restricting its use in repeat examinations. Thus, serum biomarkers may be valuable as surrogate parameters to evaluate MS activity. REDUCE-GAD was a prospective, multicentric, biobanking study to determine whether established serum markers (neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP], tau protein, ubiquitin-carboxyl-terminal-hydrolase (UCH-L1), S100B and matrix-metalloproteinase 9 [MMP9]) are predictive of CE-positive MRI lesions. Blood samples were obtained from patients undergoing MRI 5 days before or after collection. Patients (N = 102) from four different centers with confirmed MS or related disorders were included; n = 57 (55.9%) showed CE on MRI versus n = 45 (44.1%) without CE. Only higher NfL values indicated CE (odds ratio [OR] 1.05; 95% CI 1.0-1.09) and were correlated with number (ρ = 0.47; p < 0.001) and diameter of CE lesions (ρ = 0.58; p < 0.001). Nfl Z-scores improved diagnostic accuracy (OR 1.52; 95% CI 1.06-2.18). Receiver operator characteristic analysis revealed a reasonable cut-off value for NfL at 14.1 pg/mL (sensitivity 49.1%; specificity 82.2%; positive predictive value 77.8%; negative predictive value 56.0%). NfL ≥59.2 pg/mL was exclusively observed in patients with CE. Evaluation of several possible serum biomarkers for CE in MS patients provided the most robust results for NfL, particularly as Z-scores. Following further evaluation, biomarkers may help stratify the application of contrast agents for brain imaging in MS patients.