Absolute and relative GFR and contrast medium dose/GFR ratio: cornerstones when predicting the risk of acute kidney injury.

Glomerular filtration rate (GFR) is considered the best overall index of kidney function in health and disease and its use is recommended to evaluate the risk of iodine contrast medium-induced acute kidney injury (CI-AKI) either as a single parameter or as a ratio between the total contrast medium dose (gram iodine) and GFR. GFR may be expressed in absolute terms (mL/min) or adjusted/indexed to body surface area, relative GFR (mL/min/1.73 m2). Absolute and relative GFR have been used interchangeably to evaluate the risk of CI-AKI, which may be confusing and a potential source of errors. Relative GFR should be used to assess the GFR category of renal function as a sign of the degree of kidney damage and sensitivity for CI-AKI. Absolute GFR represents the excretion capacity of the individual and may be used to calculate the gram-iodine/absolute GFR ratio, an index of systemic drug exposure (amount of contrast medium in the body) that relates to toxicity. It has been found to be an independent predictor of AKI following percutaneous coronary angiography and interventions but has not yet been fully validated for computed tomography (CT). Prospective studies are warranted to evaluate the optimal gram-iodine/absolute GFR ratio to predict AKI at various stages of renal function at CT. Only GFR estimation (eGFR) equations based on standardized creatinine and/or cystatin C assays should be used. eGFRcystatin C/eGFRcreatinine ratio < 0.6 indicating selective glomerular hypofiltration syndrome may have a stronger predictive power for postcontrast AKI than creatinine-based eGFR. CLINICAL RELEVANCE STATEMENT: Once the degree of kidney damage is established by estimating relative GFR (mL/min/1.73 m2), contrast dose in relation to renal excretion capacity [gram-iodine/absolute GFR (mL/min)] may be the best index to evaluate the risk of contrast-induced kidney injury. KEY POINTS: • Relative glomerular filtration rate (GFR; mL/min/1.73 m2) should be used to assess the GFR category as a sign of the degree of kidney damage and sensitivity to contrast medium-induced acute kidney injury (CI-AKI). • Absolute GFR (mL/min) is the individual's actual excretion capacity and the contrast-dose/absolute GFR ratio is a measure of systemic exposure (amount of contrast medium in the body), relates to toxicity and should be expressed in gram-iodine/absolute GFR (mL/min). • Prospective studies are warranted to evaluate the optimal contrast medium dose/GFR ratio predicting the risk of CI-AKI at CT and intra-arterial examinations.

[New solutions for an old problem : Current developments in oral contrast agents]. / Neue Lösung für ein altes Problem : Aktuelle Entwicklungen bei oralen Kontrastmitteln.

BACKGROUND: Several radiological societies in Europe have so far spoken out in favor of MRI of the small intestine over CT, since MRI is said to provide more detailed image information. Due to the limited availability of MRI machines, long waiting times arise for many patients who clinically require small bowel imaging. OBJECTIVES: These circumstances guided our search for an improved CT technique that would provide scans that mimic the image impression of T1 sequence in MRI, i.e. with IV contrast-enhanced intestinal wall versus low/no signal lumen. MATERIAL AND METHODS: The oral use of fat or oil is poorly tolerated by patients, as is the placement of a naso-duodenal tube for air insufflation. We have now succeeded in creating a foamy drink with 44% air content, which is kept stable by protein together with buffers, and can be easily administered orally. CT with the Lumentin® beverage as bowel filling agent has been tested on healthy adult volunteers; oncology patients; and Crohn's disease patients who, for comparison, also underwent MRI of the small bowel with conventional oral contrast. RESULTS: The results so far with Lumentin® show a very good distribution throughout the entire small intestine with good lumen distension, images with strongly enhanced contrast of the intestinal mucosa, and lesions that are detected at the same or increased frequency as compared with MRI. Side effects were few and mild, and overall fewer than with commonly used oral agents. Lumentin's foamy consistency was unfamiliar to a few patients, but it wasn't difficult to drink. CONCLUSIONS: The new and innovative luminal HU-negative contrast agent Lumentin® improves the diagnostic CT image quality. In addition, Lumentin® experimental MRI tests have provided promising results, which are currently leading to further clinical MRI studies.

Revised Swedish guidelines on intravenous iodine contrast medium-induced acute kidney injury 2022: A summary.

The Swedish Society of Uroradiology has revised their computed tomography (CT) guidelines regarding iodine contrast media-induced acute kidney injury (CI-AKI). They are more cautious compared to the European Society of Urogenital Radiology and the American College of Radiology since the actual risk of CI-AKI remains uncertain in patients with moderate to severe kidney damage due to a lack of prospective controlled studies and mainly based on retrospective propensity score-matched studies with low-grade evidence. Another source of uncertainty is the imprecision of glomerular filtration rate (GFR) estimating equations. However, randomized hydration studies indictae an upper limit risk of CI-AKI of about 5% for outpatients with a GFR in the range of 30-44 or 45-59 mL/min/1.73m2 combined with multiple risk factors. Apart from GFR limits, the guideline also includes limits for systemic contrast medium exposure expressed in gram-iodine/GFR ratio.

A novel food-based negative oral contrast agent compared with two conventional oral contrast agents in abdominal CT: a three-arm parallel blinded randomised controlled single-centre trial.

BACKGROUND: A negative oral contrast agent (OCA) has been long sought for, to better delineate the bowel and visualise surrounding structures. Lumentin® 44 (L44) is a new OCA formulated to fill the entire small bowel. The aim of this study was to compare L44 with positive and neutral conventional OCA in abdominal computed tomography (CT). METHODS: Forty-five oncologic patients were randomised to receive either L44 or one of the two comparators (MoviPrep® or diluted Omnipaque®). Abdominal CT examinations with intravenous contrast agent were acquired according to standard protocols. The studies were read independently by two senior radiologists. RESULTS: The mean intraluminal Hounsfield units (HU)-values of regions-of-interest (ROIs) for each subsegment of small bowel and treatment group were -404.0 HU for L44, 166.1 HU for Omnipaque®, and 16.7 HU for MoviPrep® (L44 versus Omnipaque, p < 0.001: L44 versus MoviPrep p < 0.001; Omnipaque versus MoviPrep, p = 0.003). Adverse events, only mild, using L44 were numerically fewer than for using conventional oral contrast agents. Visualisation of abdominal structures beyond the small bowel was similar to the comparators. CONCLUSIONS: L44 is a negative OCA with luminal radiodensity at approximately -400 HU creating a unique small bowel appearance on CT scans. The high bowel wall-to-lumen contrast may enable improved visualisation in a range of pathologic conditions. L44 showed a good safety profile and was well accepted by patients studied. TRIAL REGISTRATION: EudraCT (2017-002368-42) and in ClinicalTrials.gov (NCT03326518).

Long-term safety of Gadofosveset in clinical practice.

PURPOSE: The purpose of this study was to systematically search for long-term complications, including Nephrogenic Systemic Fibrosis (NSF), in patients who were previously administered the gadolinium-based contrast agent Gadofosveset at our institute. MATERIALS AND METHODS: All patients who were administered Gadofosveset at our institute between 2006 and 2009 were identified in our Radiological Information System (RIS). Clinical data such as cause of death during follow-up, and dermatological or nephrological diseases were systematically searched for in electronic patient records (EPR). RESULTS: During 2006-2009, Gadofosveset was administered a total of 67 times to 62 patients. One patient was unavailable for follow-up. The remaining 61 patients were followed up for up to 14 (median 12) years based on RIS and EPR data. There were 13 deaths among the 61 patients, all assessed as unrelated to Gadofosveset administration. No dermatological or renal disease suggestive of NSF, or potentially related to Gadofosveset administration, was found. At the time of examination, six patients were diagnosed with various stages of renal insufficiency, three of whom were on hemodialysis. Another three patients were diagnosed with renal insufficiency during the follow-up period, but none of these diagnoses were suspected to be related to the administration of Gadofosveset. CONCLUSIONS: Based on the results of this retrospective safety analysis of up to 14 years following 1-2 exposures, we conclude that Gadofosveset in clinical practice is safe in the long-term.

Deep learning takes the pain out of back breaking work - Automatic vertebral segmentation and attenuation measurement for osteoporosis.

BACKGROUND: Osteoporosis is an underdiagnosed and undertreated disease worldwide. Recent studies have highlighted the use of simple vertebral trabecular attenuation values for opportunistic osteoporosis screening. Meanwhile, machine learning has been used to accurately segment large parts of the human skeleton. PURPOSE: To evaluate a fully automated deep learning-based method for lumbar vertebral segmentation and measurement of vertebral volumetric trabecular attenuation values. MATERIAL AND METHODS: A deep learning-based method for automated segmentation of bones was retrospectively applied to non-contrast CT scans of 1008 patients (mean age 57 years, 472 female, 536 male). Each vertebral segmentation was automatically reduced by 7 mm in all directions in order to avoid cortical bone. The mean and median volumetric attenuation values from Th12 to L4 were obtained and plotted against patient age and sex. L1 values were further analyzed to facilitate comparison with previous studies. RESULTS: The mean L1 attenuation values decreased linearly with age by -2.2 HU per year (age > 30, 95% CI: -2.4, -2.0, R2 = 0.3544). The mean L1 attenuation value of the entire population cohort was 140 HU ± 54. CONCLUSIONS: With results closely matching those of previous studies, we believe that our fully automated deep learning-based method can be used to obtain lumbar volumetric trabecular attenuation values which can be used for opportunistic screening of osteoporosis in patients undergoing CT scans for other reasons.

Quantified small bowel motility in patients with ulcerative colitis and gastrointestinal symptoms: a pilot study.

BACKGROUND: Gastrointestinal (GI) symptoms are common in patients with ulcerative colitis (UC), even when the disease is in remission, possibly due to abnormalities in GI motility. Small bowel motility can be assessed globally and in specific intestinal regions during magnetic resonance enterography (MRE) using a displacement mapping technique. PURPOSE: To investigate whether small bowel motility in MRE differs between patients with UC and controls, and if altered motility correlates with GI symptoms. MATERIAL AND METHODS: In 2016-2018, patients who were admitted for MRE, regardless of clinical indication, were consecutively invited to the study. Healthy volunteers were recruited. The participants completed a questionnaire regarding GI symptoms and relevant clinical data were reviewed in the medical records. The dynamic imaging series obtained during MRE were sent for motility mapping and a motility index (MI) was calculated in jejunum, ileum and terminal ileum in all participants. RESULTS: In total, 224 patients and healthy volunteers were enrolled in the study. Fifteen were diagnosed with UC and 22 were considered healthy controls. In UC, the prevalence of GI symptoms was higher than in controls (P < 0.001), both in remission and in active disease. There was no correlation between GI symptoms and small bowel motility in UC. Jejunal motility was lower in UC than in controls (P = 0.049). CONCLUSION: Jejunal motility is decreased in UC compared with healthy controls, but there is no relationship between small bowel motility and GI symptoms in UC.

A novel food-based foam as oral contrast agent with negative Hounsfield units for demarcation of small bowel loops on abdominal CT: tolerability and bowel distension in 25 volunteers.

BACKGROUND: Diseases of the bowel are not always displayed on conventional abdominal computed tomography (CT). The studied oral contrast agent aims to improve this. PURPOSE: To investigate whether the use of a novel oral contrast for abdominal CT enables the same diagnostic advantages as seen in magnetic resonance imaging (MRI). MATERIAL AND METHODS: Twenty-five consented volunteers drank up to 1400 mL of a stable, drinkable foam. Comments on acceptance and side effects were noted immediately and 24 h later. Foam palatability was documented through interviews, and distribution in the small bowel by Hounsfield units from the CT software. The CT results were compared with age- and sex-matched controls, pretreated according to routine. A non-enhanced abdominal CT protocol of lowest possible radiation dose was used. External referees evaluated all data obtained. RESULTS: Foam was considered odd to swallow, and fullness was reported by all volunteers after 950 mL. Five had difficulties in drinking the last 320 mL and two abstained from it. All adverse symptoms were mild. The distribution in the small bowel was on par with standard agents. Foam density revealed stability with intraluminal values of around -550 HU from stomach to terminal ileum, satisfying the requirement of a great bowel lumen-to-wall contrast. External reviewers re-evaluated all our data, and one predicted the foam to offer a potential for improved diagnostics. CONCLUSION: A CT true-negative bowel filling agent was formulated, with high acceptance, few side effects, and a potential to mimic T1-weighted MRI images.

Volumetric analysis of small bowel motility in an unselected cohort of patients with Crohn's disease.

BACKGROUND: Quantified terminal ileal motility during magnetic resonance enterography (MRE) has been suggested to be used as a biomarker of Crohn's disease (CD). The aim of the present study was to evaluate this method in clinical practice. METHODS: Healthy volunteers and all consecutive patients referred to MRE during a 2-year period were asked to participate and complete the Irritable Bowel Syndrome-Symptom Severity Scale (IBS-SSS) to assess gastrointestinal symptoms. Medical records were scrutinized, and motility indices (MIs) were calculated from MR images. KEY RESULTS: Twenty-two healthy controls and 134 examinations with CD were included (inclusion rate: 76.3%). Patients with CD had increased mural thickness of the terminal ileum, increased fecal calprotectin, and more symptoms than controls. Patients with active CD had increased mural thickness of ileum and terminal ileum, higher MR activity indices, and signs of inflammation in laboratory analyses, but similar symptoms, compared with inactive disease. After exclusion of sole colon disease (n = 13), MI inversely correlated with mural thickness in terminal ileum, and MI was lower in active disease versus controls in ileum (P = .019) and terminal ileum (P = .005), and versus inactive disease in terminal ileum (P = .044). The area under the curve of MI in terminal ileum was 0.736 for active CD against healthy controls (P = .002) and 0.682 for active against inactive CD (P = .001). MIs were similar in controls and inactive CD. CONCLUSIONS AND INTERFERENCES: MI reflects inflammatory activity in the intestine. Alterations in MI did not explain symptomatology in inactive CD, without measurable inflammatory parameters in morphology or laboratory analyses.

In vivo comparison of MRI-based and MRS-based quantification of adipose tissue fatty acid composition against gas chromatography.

PURPOSE: To compare MR-based fatty acid composition (FAC) quantification methods against the gold standard technique, gas chromatography (GC), with comparison of a free and a constrained signal model. The FAC was measured in the healthy and edematous legs of lymphedema patients. METHODS: In vivo MRS and MRI data were acquired from 19 patients at 3 T. Biopsies were collected from subcutaneous adipose tissue of both thighs during liposuction. The saturated, monounsaturated, and polyunsaturated fatty acid fractions (fSFA , fMUFA and fPUFA , respectively) were estimated with the MR-based methods using two signal models: free and constrained (number of methylene-interrupted double bonds expressed in number of double bonds, based on GC data). Linear regression, Bland-Altman plots, and correlation coefficients were used to evaluate the MR methods against the GC of the biopsies. Paired t-test was used to compare the FAC difference between edematous and healthy legs. RESULTS: The estimated parameters correlated well with the GC data (rSFA , rMUFA , and rPUFA = 0.82, 0.81 and 0.89, respectively) using the free model MRI-based approach. In comparison, the MRS-based method resulted in weaker correlations and larger biases compared with MRI. In both cases, correct estimation of fMUFA and fPUFA fractions were not possible using the constrained model. The difference in FAC of healthy and edematous legs were estimated to 0.008 (P = .01), -0.009 (P = .005), and 0.002 (P = .03) for fSFA , fMUFA , and fPUFA . CONCLUSION: In this study, MRI-based FAC quantification was highly correlated, although slightly biased, compared with GC, whereas the MRS-based approach resulted in weaker correlations. Small but significant differences could be found between the healthy and edematous legs of lymphedema patients using GC analysis.

Simulated Dose Reduction for Abdominal CT With Filtered Back Projection Technique: Effect on Liver Lesion Detection and Characterization.

OBJECTIVE: Previous studies have shown the possibility to reduce radiation dose in abdominal CT by 25-50% without negatively affecting detection of liver lesions. How radiation dose reduction affects characterization of liver metastases is not as well known. The objective of this study was to investigate how different levels of simulated dose reduction affect the detection and characterization of liver lesions, primarily hypovascular metastases. A secondary objective was to analyze the relationship between the lesion size and contrast-to-noise ratio (CNR) and the detection rate. MATERIALS AND METHODS: Thirty-nine patients (19 with metastases and 20 without) were retrospectively selected. The following radiation dose levels (DLs) were simulated: 100% (reference level), 75%, 50%, and 25%. Five readers were asked to mark liver lesions and rate the probability of malignancy on a 5-grade Likert scale. Noninferiority analysis using the jackknife free-response ROC (JAFROC) method was performed as well as direct comparison of detection rates and grades. RESULTS: JAFROC analysis showed noninferior detection and characterization of metastases at DL75 as compared with DL100. However, the number of benign lesions and false-positive localizations rated as "suspected malignancy" was significantly higher at DL75. CONCLUSION: Radiation dose can be reduced by 25% without negatively affecting diagnosis of hypovascular liver metastases. Characterization of benign lesions, however, is impaired at DL75, which may lead to unnecessary follow-up examinations. Finally, increased image noise seems to affect the detection of small lesions to a degree that cannot be explained solely by the reduction in CNR.

Preventing contrast medium-induced acute kidney injury : Side-by-side comparison of Swedish-ESUR guidelines.

A side-by-side comparison of updated guidelines regarding contrast medium-induced acute kidney injury (CI-AKI) from the Swedish Society of Uroradiology (SSUR) and the European Society of Urogenital Radiology (ESUR) is presented. The major discrepancies include a higher glomerular filtration rate (GFR) threshold as a risk factor for CI-AKI and for discontinuation of metformin by SSUR, i.e., < 45 ml/min versus < 30 ml/min/1.73 m2 by ESUR, when intravenous or intra-arterial contrast media (CM) with second-pass renal exposure is administered. SSUR also continues to recommend consideration of traditional non-renal risk factors such as diabetes and congestive heart failure, while ESUR considers these factors as non-specific for CI-AKI and does not recommend any consideration. Contrary to ESUR, SSUR also recommends discontinuation of NSAID and nephrotoxic medication if possible. Insufficient evidence at the present time motivates the more cautionary attitude taken by SSUR. Furthermore, SSUR expresses GFR thresholds in absolute values in ml/min as recommended by the National Kidney Foundation for drugs excreted by glomerular filtration, while ESUR uses the relative GFR normalised to body surface area in ml/min/1.73 m2. CM dose/GFR ratio thresholds established for coronary angiography/interventions are also applied as recommendations for CM-enhanced CT by SSUR, since SSUR regards coronary procedures as a second-pass renal exposure of CM with no obvious difference in the incidence of AKI compared with IV CM administration. Finally, SSUR recommends reducing the gram-iodine dose/GFR ratio from < 1.0 in patients not at risk to < 0.5 in patients at risk of CI-AKI, while ESUR has no such recommendation. KEY POINTS: • The more cautionary attitude taken by SSUR compared with that of ESUR is motivated by insufficient evidence regarding risk for contrast medium-induced acute kidney injuries (CI-AKI). • SSUR recommends that absolute and not relative GFR should be used when dosing drugs eliminated by the kidneys such as contrast media. • According to SSUR the gram-iodine dose/GFR ratio should be < 0.5 in patients at risk of CI-AKI, while ESUR has no such recommendation.

Evaluation of image quality and radiation dose of abdominal dual-energy CT.

Background Dual-energy computed tomography (DECT) has conceptually been known since the late 1970s and commercially available as dual-source CT (DSCT) systems since 2006; however, the technique has not yet seen widespread implementation in routine protocols. Part of the cause for this is likely due to misconceptions about radiation dose and/or image quality when using DECT. Purpose To compare image quality and radiation dose of single-energy CT (SECT) and DECT abdominal examinations obtained in clinical practice on a second generation DSCT. Material and Methods A total of 495 included patients (mean age = 70.9 years) were retrospectively analyzed after undergoing either SECT (120 kVp and age-based mAs) or DECT examinations (80/Sn140 kVp and age-based mAs). The patients were divided into two groups based on examination type (247 SECT, 248 DECT), which were then subdivided into two groups, each based on age. Image noise was measured in the liver and image quality was subjectively assessed in 100 randomly selected patients. Results Noise levels were significantly lower in DECT (13.9 HU) compared with SECT (14.7 HU) ( P < 0.05). No significant differences in subjective image quality were found between DECT and SECT, except for one criterion in the 50-74-year age group. The mean dose-length product (DLP) (376 mGy-cm) and effective dose (6.1 mSv) of DECT were significantly lower than the DLP (513 mGy-cm) and effective dose (8.4 mSv) of SECT ( P < 0.05). Conclusion DECT can be implemented in routine clinical use without negatively impacting image quality while lowering radiation dose to the patient.

Computational postprocessing quantification of small bowel motility using magnetic resonance images in clinical practice: An initial experience.

PURPOSE: To study the feasibility and to gauge the potential clinical impact of quantifying small bowel motility using magnetic resonance imaging (MRI) in a larger population with a spectra of gastrointestinal conditions with impaired small bowel motility. MATERIALS AND METHODS: Data were gathered retrospectively from a cohort of 127 patients undergoing MR enterography (1.5 Tesla) in 2011. Cine motility sequences were processed with validated motility analysis software and a parametric motility map was generated. Regions of interests were drawn in the jejunum, ileum, and terminal ileum, and Jacobian standard deviation mean motility index' score (MIS) was calculated. Patients were divided into Crohn's disease (CD), ulcerative colitis, irritable bowel syndrome, and healthy subjects. RESULTS: In CD, terminal ileum motility was lower in comparison to healthy subjects (mean difference: -0.1052 arbitrary units, 95% confidence interval: -0.1981--0.0122, P = 0.018). Subgrouping of CD showed that the difference was recognized in patients with disease limited to the small bowel (mean difference: -0.1440 arbitrary units, 95% confidence interval: -0.2491--0.0389, P = 0.002). Visible dysmotility of terminal ileum on MRI reflected a reduced MIS compared with normal motility (0.22 ± 0.09 and 0.33 ± 0.15 arbitrary units, respectively, P = 0.043). Motility correlated negatively between ileum and age (P = 0.021), and between terminal ileum and C-reactive protein in ulcerative colitis (P = 0.031). CONCLUSION: Motility quantitation revealed a significant difference in motility of terminal ileum in patients with small bowel CD compared with healthy subjects, concording with visible dysmotility and inflammatory changes. J. Magn. Reson. Imaging 2016;44:277-287.

Material Decomposition in Dual-Energy Computed Tomography Separates High-Z Elements From Iodine, Identifying Potential Contrast Media Tailored for Dual Contrast Medium Examinations.

OBJECTIVE: The aim of this study was to determine the potential of different high-Z elements to act as contrast media (CMs) alongside iodine (I) in dual-CM, dual-energy (DE) computed tomography examinations. METHODS: Gadolinium (Gd), tantalum (Ta), wolfram (W), gold (Au), and bismuth (Bi) in addition to I were examined at all available kilovolt settings in a DE computed tomography scanner. Dual-energy ratios were calculated by dividing attenuation at low kilovolt by attenuation at high kilovolt. Dual-energy data sets were loaded into material decomposition software to evaluate separation of the elements from I. RESULTS: The DE ratios of Ta, W, and Au ranged between 0.9 and 1.2, being considerably lower than I at 1.9 to 2.6. These elements were completely separated from I using material decomposition. Gadolinium and Bi were more similar to I at 1.4 to 1.9. However, separation was nearly complete for Bi and suboptimal for Gd. CONCLUSIONS: Tantalum, W, and Au are ideal candidates for dual-CM examinations, whereas Bi is a slightly weaker candidate.

Magnetic resonance imaging reveals altered distribution of hepatic fat in children with type 1 diabetes compared to controls.

INTRODUCTION: Children with type 1 diabetes have been identified as a risk group for non-alcoholic fatty liver disease (NAFLD). The aim was to compare total hepatic fat fraction and fat distribution across Couinaud segments in children with type 1 diabetes and controls and the relation of hepatic fat to plasma and anthropometric parameters. METHODS: Hepatic fat fraction and fat distribution across Couinaud segments were measured with magnetic resonance imaging (MRI) in 22 children with type 1 diabetes and 32 controls. Blood tests and anthropometric data were collected. RESULTS: No children had NAFLD. Children with type 1 diabetes had a slightly lower hepatic fat fraction (median 1.3%) than controls (median 1.8%), and their fat had a different segmental distribution. The fat fraction of segment V was the most representative of the liver as a whole. An incidental finding was that diabetes patients treated with multiple daily injections of insulin (MDI) had a fat distribution more similar to controls than patients with continuous subcutaneous insulin infusion (CSII). CONCLUSIONS: In children with type 1 diabetes, NAFLD may be less common than recent studies have suggested. Children with type 1 diabetes may have a lower fat fraction and a different fat distribution in the liver than controls. Diabetes treatment with MDI or CSII may affect liver fat, but this needs to be confirmed in a larger sample of patients. The heterogeneity of hepatic fat infiltration may affect results when liver biopsy is used for diagnosing fatty liver.

Novel nano-sized MR contrast agent mediates strong tumor contrast enhancement in an oncogene-driven breast cancer model.

The current study was carried out to test the potential of a new nanomaterial (Spago Pix) as a macromolecular magnetic MR contrast agent for tumor detection and to verify the presence of nanomaterial in tumor tissue. Spago Pix, synthesized by Spago Nanomedical AB, is a nanomaterial with a globular shape, an average hydrodynamic diameter of 5 nm, and a relaxivity (r1) of approximately 30 (mM Mn)-1 s-1 (60 MHz). The material consists of an organophosphosilane hydrogel with strongly chelated manganese (II) ions and a covalently attached PEG surface layer. In vivo MRI of the MMTV-PyMT breast cancer model was performed on a 3 T clinical scanner. Tissues were thereafter analyzed for manganese and silicon content using inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The presence of nanomaterial in tumor and muscle tissue was assessed using an anti-PEG monoclonal antibody. MR imaging of tumor-bearing mice (n = 7) showed a contrast enhancement factor of 1.8 (tumor versus muscle) at 30 minutes post-administration. Contrast was retained and further increased 2-4 hours after administration. ICP-AES and immunohistochemistry confirmed selective accumulation of nanomaterial in tumor tissue. A blood pharmacokinetics analysis showed that the concentration of Spago Pix gradually decreased over the first hour, which was in good agreement with the time frame in which the accumulation in tumor occurred. In summary, we demonstrate that Spago Pix selectively enhances MR tumor contrast in a clinically relevant animal model. Based on the generally higher vascular leakiness in malignant compared to benign tissue lesions, Spago Pix has the potential to significantly improve cancer diagnosis and characterization by MRI.