Dynamic rubidium-82 PET/CT as a novel tool for quantifying hemodynamic differences in renal blood flow using a one-tissue compartment model.

PURPOSE: Assessing renal perfusion in-vivo is challenging and quantitative information regarding renal hemodynamics is hardly incorporated in medical decision-making while abnormal renal hemodynamics might play a crucial role in the onset and progression of renal disease. Combining physiological stimuli with rubidium-82 positron emission tomography/computed tomography (82Rb PET/CT) offers opportunities to test the kidney perfusion under various conditions. The aim of this study is: (1) to investigate the application of a one-tissue compartment model for measuring renal hemodynamics with dynamic 82Rb PET/CT imaging, and (2) to evaluate whether dynamic PET/CT is sensitive to detect differences in renal hemodynamics in stress conditions compared to resting state. METHODS: A one-tissue compartment model for the kidney was applied to cardiac 82Rb PET/CT scans that were obtained for ischemia detection as part of clinical care. Retrospective data, collected from 17 patients undergoing dynamic myocardial 82Rb PET/CT imaging in rest, were used to evaluate various CT-based volumes of interest (VOIs) of the kidney. Subsequently, retrospective data, collected from 10 patients (five impaired kidney functions and five controls) undergoing dynamic myocardial 82Rb PET/CT imaging, were used to evaluate image-derived input functions (IDIFs), PET-based VOIs of the kidney, extraction fractions, and whether dynamic 82Rb PET/CT can measure renal hemodynamics differences using the renal blood flow (RBF) values in rest and after exposure to adenosine pharmacological stress. RESULTS: The delivery rate (K1) values showed no significant (p = 0.14) difference between the mean standard deviation (SD) K1 values using one CT-based VOI and the use of two, three, and four CT-based VOIs, respectively 2.01(0.32), 1.90(0.40), 1.93(0.39), and 1.94(0.40) mL/min/mL. The ratio between RBF in rest and RBF in pharmacological stress for the controls were overall significantly lower compared to the impaired kidney function group for both PET-based delineation methods (region growing and iso-contouring), with the smallest median interquartile range (IQR) of 0.40(0.28-0.66) and 0.96(0.62-1.15), respectively (p < 0.05). The K1 of the impaired kidney function group were close to 1.0 mL/min/mL. CONCLUSIONS: This study demonstrated that obtaining renal K1 and RBF values using 82Rb PET/CT was feasible using a one-tissue compartment model. Applying iso-contouring as the PET-based VOI of the kidney and using AA as an IDIF is suggested for consideration in further studies. Dynamic 82Rb PET/CT imaging showed significant differences in renal hemodynamics in rest compared to when exposed to adenosine. This indicates that dynamic 82Rb PET/CT has potential to detect differences in renal hemodynamics in stress conditions compared to the resting state, and might be useful as a novel diagnostic tool for assessing renal perfusion.

Contrast media for hysterosalpingography: systematic search and review providing new guidelines by the Contrast Media Safety Committee of the European Society of Urogenital Radiology.

OBJECTIVES: Hysterosalpingography (HSG) is widely used for evaluating the fallopian tubes; however, controversies regarding the use of water- or oil-based iodine-based contrast media (CM) remain. The aim of this work was (1) to discuss reported pregnancy rates related to the CM type used, (2) to validate the used CM in published literature, (3) to discuss possible complications and side effects of CM in HSG, and (4) to develop guidelines on the use of oil-based CM in HSG. METHODS: A systematic literature search was conducted for original RCT studies or review/meta-analyses on using water-based and oil-based CM in HSG with fertility outcomes and complications. Nine randomized controlled trials (RCTs) and 10 reviews/meta-analyses were analyzed. Grading of the literature was performed based on the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 classification. RESULTS: An approximately 10% higher pregnancy rate is reported for oil-based CM. Side effects are rare, but oil-based CM have potentially more side effects on the maternal thyroid function and the peritoneum. CONCLUSIONS: 1. HSG with oil-based CM gives approximately 10% higher pregnancy rates. 2. External validity is limited, as in five of nine RCTs, the CM used is no longer on the market. 3. Oil-based CM have potentially more side effects on the maternal thyroid function and on the peritoneum. 4. Guideline: Maternal thyroid function should be tested before HSG with oil-based CM and monitored for 6 months after. CLINICAL RELEVANCE STATEMENT: Oil-based CM is associated with an approximately 10% higher chance of pregnancy compared to water-based CM after HSG. Although side effects are rare, higher iodine concentration and slower clearance of oil-based CM may induce maternal thyroid function disturbance and peritoneal inflammation and granuloma formation. KEY POINTS: • It is unknown which type of contrast medium, oil-based or water-based, is the optimal for HSG. • Oil-based contrast media give a 10% higher chance of pregnancy after HSG, compared to water-based contrast media. • From the safety perspective, oil-based CM can cause thyroid dysfunction and an intra-abdominal inflammatory response in the patient.

Late/delayed gadolinium enhancement in MRI after intravenous administration of extracellular gadolinium-based contrast agents: is it worth waiting?

The acquisition of images minutes or even hours after intravenous extracellular gadolinium-based contrast agents (GBCA) administration ("Late/Delayed Gadolinium Enhancement" imaging; in this review, further termed LGE) has gained significant prominence in recent years in magnetic resonance imaging. The major limitation of LGE is the long examination time; thus, it becomes necessary to understand when it is worth waiting time after the intravenous injection of GBCA and which additional information comes from LGE. LGE can potentially be applied to various anatomical sites, such as heart, arterial vessels, lung, brain, abdomen, breast, and the musculoskeletal system, with different pathophysiological mechanisms. One of the most popular clinical applications of LGE regards the assessment of myocardial tissue thanks to its ability to highlight areas of acute myocardial damage and fibrotic tissues. Other frequently applied clinical contexts involve the study of the urinary tract with magnetic resonance urography and identifying pathological abdominal processes characterized by high fibrous stroma, such as biliary tract tumors, autoimmune pancreatitis, or intestinal fibrosis in Crohn's disease. One of the current areas of heightened research interest revolves around the possibility of non-invasively studying the dynamics of neurofluids in the brain (the glymphatic system), the disruption of which could underlie many neurological disorders.

Leisure time physical activity is associated with improved diastolic heart function and is partly mediated by unsupervised quantified metabolic health.

Objectives: To investigate the association between leisure time physical activity (LTPA) and MRI-based diastolic function and the mediating role of metabolic health. Methods: This cross-sectional analysis comprised 901 participants (46% women, mean age (SD): 56 (6) years (The Netherlands, 2008-2012)). LTPA was assessed via questionnaire, quantified in metabolic equivalent of tasks (METs)-minutes per week and participants underwent abdominal and cardiovascular MRI. Confirmatory factor analysis was used to construct the metabolic load factor. Piecewise structural equation model with adjustments for confounders was used to determine associations between LTPA and diastolic function and the mediating effect of metabolic load. Results: Significant differences in mitral early/late peak filling rate (E/A) ratio per SD of LTPA (men=1999, women=1870 MET-min/week) of 0.18, (95% CI= 0.03 to 0.33, p=0.021) were observed in men, but not in women: -0.01 (-0.01 to 0.34, p=0.058). Difference in deceleration time of mitral early filling (E-DT) was 0.13 (0.01 to 0.24, p=0.030) in men and 0.17 (0.05 to 0.28, p=0.005) in women. Metabolic load, including MRI-based visceral and subcutaneous adipose tissue, fasting glucose, high-density lipoprotein cholesterol and triglycerides, mediated these associations as follows: E/A-ratio of 0.030 (0.000 to 0.067, 19% mediated, p=0.047) in men but not in women: 0.058 (0.027 to 0.089, p<0.001) and E-DT not in men 0.004 (-0.012 to 0.021, p=0.602) but did in women 0.044 (0.013 to 0.057, 27% mediated, p=0.006). Conclusions: A larger amount of LTPA was associated with improved diastolic function where confirmatory factor analysis-based metabolic load partly mediated this effect. Future studies should assess whether improving indicators of metabolic load alongside LTPA will benefit healthy diastolic function even more.

Noninvasive Advanced Cardiovascular Magnetic Resonance-Derived Fontan Hemodynamics Are Associated With Reduced Kidney Function But Not Albuminuria.

BACKGROUND: Kidney disease is the most important predictor of death in patients with a Fontan circulation, yet its clinical and hemodynamic correlates have not been well established. METHODS AND RESULTS: A total of 53 ambulatory patients with a Fontan circulation (median age, 16.2 years, 52.8% male patients) underwent advanced cardiovascular magnetic resonance assessment, including 4-dimensional flow imaging and computational fluid dynamics. Estimated glomerular filtration rate (eGFR) <90 mL/min per 1.73 m2 was observed in 20.8% and albumin-to-creatinine ratio >3 mg/mmol in 39.6%. The average eGFR decline rate was -1.83 mL/min per 1.73 m2 per year (95% CI, -2.67 to -0.99; P<0.001). Lower eGFR was associated with older age, larger body surface area at examination, longer time since Fontan procedure, and lower systemic ventricular ejection fraction. Higher albumin-to-creatinine ratio was associated with absence of fenestration at the Fontan operation, and older age and lower systemic ventricular ejection fraction at the assessment. Lower cross-sectional area of the Fontan conduit indexed to flow (r=0.32, P=0.038), higher inferior vena cava-conduit velocity mismatch factor (r=-0.35, P=0.022), higher kinetic energy indexed to flow in the total cavopulmonary connection (r=-0.59, P=0.005), and higher total cavopulmonary connection resistance (r=-0.42, P=0.005 at rest; r=-0.43, P=0.004 during exercise) were all associated with lower eGFR but not with albuminuria. CONCLUSIONS: Kidney dysfunction and albuminuria are common among clinically well adolescents and young adults with a Fontan circulation. Advanced cardiovascular magnetic resonance-derived metrics indicative of declining Fontan hemodynamics are associated with eGFR and might serve as targets to improve kidney health. Albuminuria might be driven by other factors that need further investigation.

Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee.

The Contrast Media Safety Committee of the European Society of Urogenital Radiology has, together with the Preanalytical Phase Working Group of the EFLM Science Committee, reviewed the literature and updated its recommendations to increase awareness and provide insight into these interferences.

The role of gadolinium-based contrast agents in magnetic resonance imaging structured reporting and data systems (RADS).

Among the 28 reporting and data systems (RADS) available in the literature, we identified 15 RADS that can be used in Magnetic Resonance Imaging (MRI). Performing examinations without using gadolinium-based contrast agents (GBCA) has benefits, but GBCA administration is often required to achieve an early and accurate diagnosis. The aim of the present review is to summarize the current role of GBCA in MRI RADS. This overview suggests that GBCA are today required in most of the current RADS and are expected to be used in most MRIs performed in patients with cancer. Dynamic contrast enhancement is required for correct scores calculation in PI-RADS and VI-RADS, although scientific evidence may lead in the future to avoid the GBCA administration in these two RADS. In Bone-RADS, contrast enhancement can be required to classify an aggressive lesion. In RADS scoring on whole body-MRI datasets (MET-RADS-P, MY-RADS and ONCO-RADS), in NS-RADS and in Node-RADS, GBCA administration is optional thanks to the intrinsic high contrast resolution of MRI. Future studies are needed to evaluate the impact of the high T1 relaxivity GBCA on the assignment of RADS scores.

Waiting times between examinations with intravascularly administered contrast media: a review of contrast media pharmacokinetics and updated ESUR Contrast Media Safety Committee guidelines.

The pharmacokinetics of contrast media (CM) will determine how long safe waiting intervals between successive CT or MRI examinations should be. The Contrast Media Safety Committee has reviewed the data on pharmacokinetics of contrast media to suggest safe waiting intervals between successive contrast-enhanced imaging studies in relation to the renal function of the patient. CLINICAL RELEVANCE STATEMENT: Consider a waiting time between elective contrast-enhanced CT and (coronary) angiography with successive iodine-based contrast media administrations in patients with normal renal function (eGFR > 60 mL/min/1.73 m2) of optimally 12 h (near complete clearance of the previously administered iodine-based contrast media) and minimally 4 h (if clinical indication requires rapid follow-up). KEY POINTS: • Pharmacokinetics of contrast media will guide safe waiting times between successive administrations. • Safe waiting times increase with increasing renal insufficiency. • Iodine-based contrast media influence MRI signal intensities and gadolinium-based contrast agents influence CT attenuation.

Ten years of gadolinium retention and deposition: ESMRMB-GREC looks backward and forward.

In 2014, for the first time, visible hyperintensities on unenhanced T1-weighted images in the nucleus dentatus and globus pallidus of the brain were associated with previous Gadolinium-based contrast agent (GBCA) injections and gadolinium deposition in patients with normal renal function. This led to a frenzy of retrospective studies with varying methodologies that the European Society of Magnetic Resonance in Medicine and Biology Gadolinium Research and Educational Committee (ESMRMB-GREC) summarised in 2019. Now, after 10 years, the members of the ESMRMB-GREC look backward and forward and review the current state of knowledge of gadolinium retention and deposition. CLINICAL RELEVANCE STATEMENT: Gadolinium deposition is associated with the use of linear GBCA but no clinical symptoms have been associated with gadolinium deposition. KEY POINTS : • Traces of Gadolinium-based contrast agent-derived gadolinium can be retained in multiple organs for a prolonged time. • Gadolinium deposition is associated with the use of linear Gadolinium-based contrast agents. • No clinical symptoms have been associated with gadolinium deposition.

Safe use of contrast media in myasthenia gravis: systematic review and updated European Society of Urogenital Radiology Contrast Media Safety Committee guidelines.

OBJECTIVES: It is uncertain whether modern iodine-based or gadolinium-based contrast media (CM) administration can lead to increased symptoms in patients with myasthenia gravis. METHODS: A systematic search in Medline was conducted for studies describing the symptomatology of myasthenia gravis patients before and after receiving intravenous (IV) CM and having a matched control group of myasthenia gravis patients who did not receive IV CM. RESULTS: Three retrospective studies were selected with a total of 374 myasthenia gravis patients who received iodine-based CM and a total of 313 myasthenia gravis patients who underwent unenhanced CT and served as controls. Pooling of the data from the three retrospective studies showed that in 23 of 374 patients, increased symptoms after iodine-based CM administration were described (6.1%). Increased symptomatology also occurred in 11 of 313 patients after unenhanced CT (3.5%). When looking more deeply into the data of the three studies, conflicting results were found, as two articles did not find any relationship between CM and myasthenia gravis symptoms. The remaining study only found a significant increase in symptomatology within 1 day after CT scanning: seven patients (6.3%) in the contrast-enhanced CT group and one patient (0.6%) in the unenhanced CT group (p = 0.01). CONCLUSIONS: There is limited evidence on the relationship between CM and myasthenia gravis symptoms. In the vast majority of myasthenia gravis patients, CM are safe. Probably, in less than 5% of the patients, iodine-based CM administration may lead to increased severity of the symptoms within the first 24 h after administration. CLINICAL RELEVANCE STATEMENT: Be aware that intravenous administration of iodine-based contrast media can lead to an increase of symptoms in patients with myasthenia gravis within the first 24 h. This can probably happen in less than 5% of the patients. KEY POINTS: • It is unclear whether modern contrast media can lead to increased symptoms in myasthenia gravis patients after intravenous administration. • There seems to be a small risk of increased myasthenia gravis symptoms within 24 h after intravenous administration of iodine-based contrast media, probably in less than 5% of the administrations. • Gadolinium-based contrast media are safe for patients with myasthenia gravis.

MR Assessed Changes of Renal Sinus Fat in Response to Glucose Regulation in West European and South Asian Patients With Type 2 Diabetes.

BACKGROUND: Ethnic differences in the progression and outcome of diabetic kidney disease (DKD) remain to be elucidated. MRI-quantified renal sinus fat volume could be a potential biomarker to help investigate the changes of DKD risk in response to glucose regulation. PURPOSE: To evaluate whether the effect of glucose-lowering treatment on renal sinus fat volume differed in West Europeans (WE) compared to South Asians (SA), and whether ethnic-related difference exists regarding the effect of liraglutide on renal sinus fat. STUDY TYPE: Retrospective. POPULATION: Ninety-three patients with type 2 diabetes mellitus, including 47 WE (27 males) aged 59.3 ± 6.5 years, and 46 SA (19 males) aged 54.4 ± 9.8 years. FIELD STRENGTH/SEQUENCE: 3.0 T dual-echo fast gradient-echo pulse sequence using two-point Dixon technique with a phase-correction algorithm. ASSESSMENT: Changes of renal sinus fat volume were measured by a radiologist (LL) with 4-years' experience, and were compared between the two ethnic groups, together with glycemic level, metabolic risk factors and renal function. The effects of liraglutide were assessed. STATISTICAL TESTS: Normality of the data was visually evaluated by histograms and Q-Q plots. Within-group and between-group differences were analyzed using paired t-tests and analysis of covariance. Associations were analyzed by person's correlation and multiple linear regression models. RESULTS: Renal sinus fat decreased in SA patients (Δ% = -7.6% ± 14.8%), but increased in WE patients (Δ% = 5.0% ± 13.1%), with a significant difference between the two ethnic groups. In the WE group, the increase of sinus fat volume was significant in the placebo subgroup (Δ% = 6.8% ± 12.5%), in contrast to the nonsignificant increase in the liraglutide subgroup (Δ% = 3.0% ± 13.8%, P = 0.444). DATA CONCLUSION: Renal sinus fat accumulation responds differently to glucose regulation, showing a reduction in SA patients in contrast to a persistent accumulation in WE patients. A trend of less accumulation of sinus fat in WE patients receiving liraglutide has been observed. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 4.

Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee.

The Contrast Media Safety Committee of the European Society of Urogenital Radiology has, together with the Preanalytical Phase Working Group of the EFLM Science Committee, reviewed the literature and updated its recommendations to increase awareness and provide insight into these interferences. CLINICAL RELEVANCE STATEMENT: Contrast Media may interfere with clinical laboratory tests. Awareness of potential interference may prevent unwanted misdiagnosis. KEY POINTS: • Contrast Media may interfere with clinical laboratory tests; therefore awareness of potential interference may prevent unwanted misdiagnosis. • Clinical Laboratory tests should be performed prior to radiological imaging with contrast media or alternatively, blood or urine collection should be delayed, depending on kidney function.

Artificial Intelligence to Reduce or Eliminate the Need for Gadolinium-Based Contrast Agents in Brain and Cardiac MRI: A Literature Review.

ABSTRACT: Brain and cardiac MRIs are fundamental noninvasive imaging tools, which can provide important clinical information and can be performed without or with gadolinium-based contrast agents (GBCAs), depending on the clinical indication. It is currently a topic of debate whether it would be feasible to extract information such as standard gadolinium-enhanced MRI while injecting either less or no GBCAs. Artificial intelligence (AI) is a great source of innovation in medical imaging and has been explored as a method to synthesize virtual contrast MR images, potentially yielding similar diagnostic performance without the need to administer GBCAs. If possible, there would be significant benefits, including reduction of costs, acquisition time, and environmental impact with respect to conventional contrast-enhanced MRI examinations. Given its promise, we believe additional research is needed to increase the evidence to make these AI solutions feasible, reliable, and robust enough to be integrated into the clinical framework. Here, we review recent AI studies aimed at reducing or replacing gadolinium in brain and cardiac imaging while maintaining diagnostic image quality.

Skin Toxicity After Exposure to Gadolinium-Based Contrast Agents in Normal Renal Function, Using Clinical Approved Doses: Current Status of Preclinical and Clinical Studies.

OBJECTIVES: The aim of this study was to summarize the current preclinical and clinical evidence on the association between exposure to gadolinium (Gd) compounds and skin toxicity in a setting similar to clinical practice. MATERIALS AND METHODS: A search of MEDLINE and PubMed references from January 2000 to December 2022 was performed using keywords related to gadolinium deposition and its effects on the skin, such as "gadolinium," "gadolinium-based contrast agents," "skin," "deposition," and "toxicity." In addition, cross-referencing was added when appropriate. For preclinical in vitro studies, we included all the studies that analyzed the response of human dermal fibroblasts to exposure to various gadolinium compounds. For preclinical animal studies and clinical studies, we included only those that analyzed animals or patients with preserved renal function (estimated glomerular filtration rate >30 mL/min/1.73 m 2 ), using a dosage of gadolinium-based contrast agents (GBCAs) similar to that commonly applied (0.1 mmol/kg). RESULTS: Forty studies were selected. Preclinical findings suggest that Gd compounds can produce profibrotic responses in the skin in vitro, through the activation and proliferation of dermal fibroblasts and promoting their myofibroblast differentiation. Gadolinium influences the process of collagen production and the collagen content of skin, by increasing the levels of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1. Preclinical animal studies show that Gd can deposit in the skin with higher concentrations when linear GBCAs are applied. However, these deposits decrease over time and are not associated with obvious macroscopic or histological modifications. The clinical relevance of GBCAs in inducing small fiber neuropathy remains to be determined. Clinical studies show that Gd is detectable in the skin and hair of subjects with normal renal function in higher concentrations after intravenous administration of linear compared with macrocyclic GBCA. However, these deposits decrease over time and are not associated with cutaneous or histological modifications. Also, subclinical dermal involvement related to linear GBCA exposure may be detectable on brain MRI. There is no conclusive evidence to support a causal relationship between GBCA administration at the clinical dose and cutaneous manifestations in patients with normal renal function. CONCLUSIONS: Gadolinium can produce profibrotic responses in the skin, especially acting on fibroblasts, as shown by preclinical in vitro studies. Gadolinium deposits are detectable in the skin even in subjects with normal renal function with higher concentrations when linear GBCAs are used, as confirmed by both preclinical animal and human studies. There is no proof to date of a cause-effect relationship between GBCA administration at clinical doses and cutaneous consequences in patients with normal renal function. Multiple factors, yet to be determined, should be considered for sporadic patients with normal renal function who develop clinical skin manifestations temporally related to GBCA administration.

Confirmatory factor analysis including MRI-derived adipose tissues quantification improves associations of metabolic dysregulation to diastolic dysfunction.

AIMS: To quantify metabolic impairment via a one-factor approach with confirmatory factor analysis (CFA) including MRI-derived visceral and subcutaneous adipose tissues and to associate it with diastolic dysfunction. METHODS: In this cross-sectional analysis, 916 participants (53% female, mean age (SD): 56 (6)) underwent abdominal and cardiovascular MRI. With CFA a metabolic-load factor of metabolic-syndrome variables and visceral and subcutaneous adipose tissues was constructed. A piecewise structural equation model approach with adjustment for confounding factors was used to determine associations with left-ventricular diastolic function, cardiac morphology and hemodynamics. RESULTS: Model fitting excluding blood pressure and waist circumference but including visceral and subcutaneous adipose tissues, fasting glucose, HDL-c and triglycerides was used to construct the metabolic-load factor. Evaluating measurement invariance demonstrated sex-specificity. Change in mitral early/late peak filling rate ratio was -0.12 for both males [-0.20; -0.05, p > 0.05] and females [-0.17; -0.07, p > 0.001] per SD of metabolic-load factor. Change in deceleration time of mitral early filling was -11.83 ms in females [-17.38; -6.27] per SD of metabolic-load factor. CONCLUSION: A single latent metabolic-load factor via CFA including MRI-derived adipose tissues increased sensitivity for metabolic impairment obsoleting waist circumference and is associated with a decreased left-ventricular diastolic function, more apparent in females than in males.