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Cardiac Magnetic Resonance (CMR) imaging is recommended as the reference diagnostic non-invasive modality for myocarditis but is often limited by patients' compliance. The purpose of this study is to evaluate the validity of Radiomics applied to Short Tau Inversion Recovery (STIR) sequences, in predicting the presence of LGE in patients with suspected acute myocarditis.171 STIR images on short-axis view were segmented with "MaZda" software ver 4.6, by placing a region of interest (ROI) on the left ventricle by two radiologists in consensus. Images were classified according to the presence of LGE in the equivalent short-axis T1-IR slice. A total of 337 ROI features were extracted for each image. Dataset was then split into two parts (train and test set) with 70:30 ratio.Eleven classification models were trained. An Ensemble Machine Learning (EML) model was obtained by averaging the predictions of models with accuracy on test set70%. The EML documented accuracy of 0.75, sensitivity of 0.8 and a specificity of 0.73 with a NPV of 0.81 and a PPV of 0.7, with AUC of 0.79 (95% CI: 0.66-0.92).Radiomics and machine learning analysis could be a promising approach in reducing scan times without reducing diagnostic accuracy in predicting LGE in patients with acute myocarditis.

To determine the capability of Gadolinium-free arterial spin labelling (ASL) sequences as novel, contrast-free, non-invasive alternative perfusion imaging method to differentiate prostate cancer (PCA) from benign prostate tissue compared to conventional DCE MRI.Thirty men with histologically confirmed PCA were included in this prospectively enrolled single center cohort study. All patients received multiparametric MRI (T2, DWI, DCE) at 3 T with additional ASL of the PCA lesion. Primary endpoint was differentiability of PCA versus benign prostate tissue by signal intensities (SI) and contrast ratios (CR) in ASL in comparison to DCE. For DCE also Signal-Enhancement-Ratio (SER) of native and early contrast enhancement SI was assessed. Secondary objectives were differences regarding PCA localisation in peripheral (PZ) or transition zone (TZ) and PCA detection.In both, ASL and DCE, average SI of PCA differed significantly from SI in benign tissue in the TZ and PZ (p 0,01, respectively). ASL had significantly higher CR discerning PCA and benign tissue in PZ and TZ (PZ = 5.19; TZ = 6.45) compared to DCE SI (PZ = 1.61; TZ = 1.43) and DCE SER (PZ = 1.59; TZ = 1.43) (p 0.01, respectively). In subjective evaluation, PCA could be detected in ASL in 28 patients, compared to 29 in DCE.ASL had significantly higher CR differentiating PCA from benign tissue in PZ and TZ compared to DCE. Visual detection of PCA does not differ significantly between the two sequences. As perfusion gadolinium-based contrast media is seen more critical in the last few years, ASL seems to be a promising alternative to DCE in PCA detection.

Purpose Develop a magnetic resonance fingerprinting (MRF) methodology with R2∗ quantification, intended for use with simultaneous contrast agent concentration mapping, particularly gadolinium (Gd) and iron labelled CD8+ T cells. Methods Variable-density spiral SSFP MRF was used, modified to allow variable TE, and with an exp.(−TE·R2∗) dictionary modulation. In vitro phantoms containing SPIO labelled cells and/or gadolinium were used to validate parameter maps, probe undersampling capacity, and verify dual quantification capabilities. A C57BL/6 mouse was imaged using MRF to demonstrate acceptable in vivo resolution and signal at 8× undersampling necessary for a 25-min scan. Results Strong agreement was found between conventional and MRF-derived values for R1, R2, and R2∗. Expanded MRF allowed quantification of iron-loaded CD8+ T cells. Results were robust to 8× undersampling and enabled recreation of relaxation profiles for both a Gd agent and iron labelled cells simultaneously. In vivo data demonstrated sufficient SNR in undersampled data for parameter mapping to visualise key features. Conclusion MRF can be expanded to include R1, R2, and R2∗ mapping required for simultaneous quantification of gadolinium and SPIO in vitro, allowing for potential implementation of a variety of future in vivo studies using dual MR contrast agents, including molecular imaging of labelled cells.

To find magnetic resonance imaging (MRI) precursors of spontaneous intracerebral hemorrhage in stroke-prone spontaneously hypertensive rats (SHRSP).SHRSP rats were used with both a low/high salt (n = 18 or 11) Japanese diet and salty drinking water to generate spontaneous intracerebral hemorrhage (ICH). Various MRI sequences, and in particular, susceptibility weighted imaging (SWI), were used and combined with a gadolinium (Gd) contrast agent or oxygen gas to identify the rupture of the blood brain barrier (BBB) and the temporal ICH.Most rats developed hypertensive ICH stroke in the high salt group during the 10-13 week period compared to only one third of rats in the low salt group during the 14-18 week period. The location of stroke for both the low/high-salt groups was highest in the striatum (58%/43%), followed by the cortex (21%/30%). The edematous enhancement on T2 weighted (T2W) imaging or Gd based T1 weighted (Gd-T1W) imaging due to the ruptured BBB preceded the striatal hemorrhages seen on SWI. The most recent bleeds were observed on temporal SWI or on oxygen-enhanced SWI. The mode of the volume of bleeds was 0.4 mmSHRSP rats with the high salt diet effectively generated a hypertensive hemorrhagic stroke which could be monitored by various MRI sequences. The venous dilation on SWI may precede any abnormality on T2W or Gd-T1W imaging. The edematous enhancement on T2W or Gd-T1W indicated a BBB breakdown that may precede striatal ICH by several days. This suggests the need for immediate treatment to improve outcome if this finding is observed. The use of oxygen with SWI was able to help differentiate old bleeds from very recent bleeds.

Ferumoxytol, an FDA-approved superparamagnetic iron oxide nanoparticle (SPION) preparation used for the treatment of iron deficiency anemia, is also known to be taken up by macrophages in areas of infection or inflammation, where it produces negative contrast changes on T2-weighted MR images.We sought to compare Ferumoxytol-induced MRI contrast changes with those observed using standard-of-care Gadolinium in patients presenting with symptoms suggestive of osteomyelitis.Out of eighteen enrolled patients, 15 had MR imaging with both ferumoxytol and gadolinium. Based on clinical and/or pathologic criteria, 7 patients were diagnosed with osteomyelitis, 5 patients had osteomyelitis ruled out, and in 3 patients a definitive diagnosis could not be made.1.5 Tesla.Used included STIR, T1-weighted and T2-weighted spin echo.The mean contrast changes upon ferumoxytol and gadolinium administration were measured from lesion regions of interest and compared with control regions.Student's t-test, propagation of errors. Data are reported as means ± S.E.The mean contrast changes, ΔC, associated with a diagnosis of osteomyelitis were found to be ΔCFe = -2.7 ± 0.7 when Ferumoxytol and T2w imaging sequences were used and ΔCGd = +3.1 ± 1.1 (P 0.001) when Gadolinium and a T1w imaging sequence was used. The MRI contrast changes for both agents correlated with systemic markers of inflammation, such as the erythrocyte sedimentation rate. In patients without osteomyelitis, no significant contrast changes were observed in T2-weighted, Ferumoxytol-contrasted MRI. The macrophages in osteomyelitic lesions were found to take up at least 16 times as much iron as benign bone marrow.We conclude that in terms of its MRI diagnostic accuracy for osteomyelitis Ferumoxytol-contrasted MRI is a promising approach for diagnosing osteomyelitis that merits further study.

The present study aimed to confirm the hypothesis that aquaporin-4 water channels (AQP4) control solute transition into the brain parenchyma using image analysis of gadolinium-based contrast agents (GBCAs) dissolved in cerebrospinal fluid (CSF) on dynamic contrast-enhanced magnetic resonance imaging (dyMRI) in live rats. Ten male Wistar ST rats were included in the study. Whole-brain dyMRI was performed for approximately 120 min after intrathecal infusion of gadolinium tetraazacyclododecane tetraacetic acid (Gd-DOTA). TGN-020, a specific AQP4 inhibitor, was used to inhibit the function of AQP4 in one group of rats (TGN-020 group, n = 4). The dyMRI after Gd-DOTA infusion in the rat, who were not treated with TGN-020 (control group, n = 6) revealed marked contrast-enhancement over time based on the distribution of the GBCA in the lateral regions of the brain surface, the ventral regions, the regions adjacent to the subarachnoid space, and the deep subcortical region. In contrast, smaller signal enhancement of the same regions in the TGN-020 group indicated poor distribution of the GBCA, suggesting a physiological consequence of the AQP4 inhibition by TGN-020. In this study, a close relationship between the function of AQP4 and the solute dynamics in the CSF was revealed from the distribution pattern of GBCA visualized in dyMRI in the living rat brain by administration of AQP4-selective inhibitor. This finding suggests that AQP4 functions to drive a glymphatic influx to transition molecules dissolved in the CSF from the subarachnoid space into the extracellular space of the brain parenchyma.

Accurate assessment of 3D models of patient-specific anatomy of the liver, including underlying hepatic and biliary tree, is critical for preparation and safe execution of complex liver resections, especially due to high variability of biliary and hepatic artery anatomies. Dynamic MRI with hepatospecific contrast agents is currently the only type of diagnostic imaging that provides all anatomical information required for generation of such a model, yet there is no information in the literature on how the complete 3D model can be generated automatically. In this work, a new automated segmentation workflow for extraction of patient-specific 3D model of the liver, hepatovascular and biliary anatomy from a single multiphase MRI acquisition is developed and quantitatively evaluated. The workflow incorporates course 4D k-means clustering estimation and geodesic active contour refinement of the liver boundary, based on organ's characteristic uptake of gadolinium contrast agents overtime. Subsequently, hepatic vasculature and biliary ducts segmentations are performed using multiscale vesselness filters. The algorithm was evaluated using 15 test datasets of patients with liver malignancies of various histopathological types. It showed good correlation with expert manual segmentation, resulting in an average of 1.76 ± 2.44 mm Hausdorff distance for the liver boundary, and 0.58 ± 0.72 and 1.16 ± 1.98 mm between centrelines of biliary ducts and liver veins, respectively. A workflow for automatic segmentation of the liver, hepatic vasculature and biliary anatomy from a single diagnostic MRI acquisition was developed. This enables automated extraction of 3D models of patient-specific liver anatomy, and may facilitating better perception of organ's anatomy during preparation and execution of liver surgeries. Additionally, it may help to reduce the incidence of intraoperative biliary duct damage due to an unanticipated variation in the anatomy.

Background Delayed gadolinium enhanced MRI of cartilage (dGEMRIC) is a quantitative method for assessment of glycosaminoglycan content in connective tissues. We hypothesize that the early diagnosis of degenerative changes in the temporomandibular joint could be diagnosed using dGEMRIC technique. Purpose To test the compositional MRI technique, dGEMRIC, at 3 Tesla to diagnosis early the degenerative changes in the fibrocartilaginous disc of the temporomandibular joint (TMJ) in patients with temporomandibular disorders (TMD) and to compare the dGEMRIC index of patients to the healthy volunteers. Methods Six volunteers (two men, four women; 20.8÷28.1 years) and eleven patients (22 TMJs, seven women, four men; 24÷54 years) were recruited for this prospective trial. Only patients with no morphological abnormality on MRI and without disc dislocations were included. Volunteers were used as a control group. The PD-weighted FSE sequence and the 3D GRE (DESS) sequence protocols were performed for morphological assessment. The Inversion recovery (IR) sequence was performed for T1 relaxation time measurements and intra-venous (IV) contrast agent administration was used according to the dGEMRIC protocol. T1 maps were calculated offline and ROIs were drawn on TMJ discs by a specialist trained in TMD disorders. Statistical evaluation was performed by ANOVA and correlations were calculated. Results The difference between the dGEMRIC values in the TMJ articular discs of the patients and the volunteers was statistically significant (P = .019). After contrast agent administration the T1 values dropped in both groups. In patient group was the T1 drop stronger (−54% from initial pre-contrast value), while in control group was the T1 drop less pronounced (−46% from initial pre-contrast value). Conclusions dGEMRIC seems to be a useful, compositional, quantitative method, suitable also for small joints, such as the articular disc of the TMJ. The results of the dGEMRIC index in the articular disc of the TMJ imply a lower GAG content in patients with TMJ disorders.

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.

Purpose Here, we are testing the hypothesis that dynamic contrast enhanced MRI (DCE-MRI) is a useful approach for non-invasively evaluating age-related changes in aqueous humor outflow and its contribution to elevated intraocular pressure in the DBA/2J model of pigmentary glaucoma. Methods A rodent-specific 7 T MRI was used to assess eye anatomy (anterior chamber (AC) and vitreous body (VB) morphology, eye size, lens size) and aqueous humor dynamics (via intravenous administration of Gd-DTPA and Gd-BOPTA contrast agents) in C57BL/6 and DBA/2J mice at 3 and 9 months of age. Results Gd-MRI was used to demonstrate an anterior solute pathway into the mouse AC. Topical latanoprost treatment in C57BL/6J mice reduced Gd-BOPTA accumulation in the AC. Age-related increases in AC area, AC depth and eye size were observed in DBA/2J mice compared to C57BL/6J mice. The rate of Gd-DTPA accumulation and peak Gd-DTPA intensity was lowest in 9-month old DBA/2J mice compared to 3-month old DBA/2J mice and C57BL/6J mice at both ages. Leakage of Gd-DTPA posteriorly into the VB was also observed in 9-month old DBA/2J mice. Conclusions These studies support the idea that age-related changes in aqueous humor outflow contribute to elevated intraocular pressure (IOP) in the DBA/2J model of pigmentary glaucoma. Gd-MRI is a valuable tool for better understanding of mechanisms and dynamics of aqueous humor circulation in normal and glaucomatous mouse eyes or following topical administration of medicines to reduce IOP.

Tissue and bone retention of gadolinium based contrast agents (GBCAs) has become a clinical concern because of the potential short and long term toxic effects of free gadolinium. This is a critical problem for most open-chain agents that more readily transmetallate in vivo, in comparison to macrocyclic compounds. Gadolinium diethylene tri-aminepentaacetic acid bis-glucosamide (Gd-DTPA-BIGA) is an experimental, open-chain contrast agent which has a significantly increased relaxivity coefficient in comparison to other GBCAs. This results in greater signal intensity and improved contrast enhancement. These superior imaging qualities initiated a search for a solution to the transmetallation of this agent. Plasma zinc is a well-known GBCA transmettalation agent. Since the base chelate of Gadodiamide (Gd-DPTA-Bis-Methylamide or Omniscan), DTPA-Bis-Methylamide (DTPA-BMA), readily transmettalates with and binds serum zinc, we hypothesized that a plasma “zinc sink,” may significantly reduce transmetallation of linear agents. 5% DTPA-BMA was added to a formulation of Gd-DTPA-BIGA, which was tested against the original formulation of Gd-DTPA-BIGA with 0.2% of the base chelate DTPA-BIGA. These formulations, including gadodiamide, were labeled with 153GdCl3 followed by infusion into cohorts of Sprague Dawley rats which were sacrificed at 1, 30 and 60 days. Internal organs were harvested, along with blood, skin and femur, and analyzed for residual gadolinium. A subset of tissues were also interrogated with ICP-MS. Labeled Gadodiamide and saline where used as controls. Conclusion: The addition of 5% DTPA-BMA, as a zinc binding agent, reduced the transmetallation of the linear agent Gd-DTPA-BIGA, in comparison to its original formulation supplemented with 0.2% BIGA. This result indicates that supplementing linear GBCAs with ancillary chelates may hold promise for reducing, or eliminating the biological archiving of gadolinium in tissues. In addition, this paper provides valuable animal data on the long term retention of gadolinium from linear based contrast agents.

Over the last years several studies reported an increased signal intensity (SI) of the dentate nucleus (DN) on unenhanced T1-weighted images after repeated application of gadolinium-based contrast agents (GBCAs), suggesting gadolinium deposition. The aim of this study was to investigate with diffusion-weighted MRI possible tissue abnormalities of the DN in multiple sclerosis (MS) patients.We retrospectively identified seventeen patients with at least six contrast-enhanced MRI examinations by using the linear GBCA gadopentate dimeglumine and twenty-three patients with the exclusive use of the macrocyclic contrast agent gadoterate meglumine followed by another 3 Tesla MRI scan including unenhanced T1-weighted and diffusion-weighted images.In the linear GBCA group, we found significant differences of the DN-to-pons SI ratio on unenhanced T1-weighted images (1.13 ± 0.05) when compared to the macrocyclic GBCA group (0.97 ± 0.03; p 0.001). However, we found no significant differences between apparent diffusion coefficient (ADC) values of the DN in both groups (linear GBCA group: 0.82 ± 0.04 × 10Our results do not suggest that there is any difference in ADC values in the T1-hyperintense DN, which does not indicate a difference in tissue integrity between patients exposed to macrocyclic or linear GBCAs.

Objectives Benign and malignant inflammatory breast lesions demonstrate similar findings on both T2 weighted imaging (T2WI) and dynamic contrast enhanced (DCE) images. We hypothesized that benign inflammatory lesions might be differentiated form malignancies using a combination of apparent diffusion coefficient (ADC) values derived from diffusion weighted images (DWI) and T2WI. Materials and methods We retrospectively reviewed 162 patients undergoing breast MRI (T2WI, DWI and DCE images) between 2008 and 2015 who had breast lesions with high T2WI signal intensity (High T2 SI) including 14 benign inflammatory lesions, 69 benign non-inflammatory lesions, 16 malignant inflammatory lesions and 63 malignant non-inflammatory lesions. On the High T2 SI and low T2WI signal intensity (Low T2 SI) areas in these breast lesions, we calculated ADC values from b values of 0 and 1000 s/mm2. Results The mean ADC values ± standard deviation (10−3 mm2/s) of the High T2 SI areas in benign inflammatory, benign non-inflammatory, malignant inflammatory and malignant non-inflammatory breast lesions were 0.75 ± 0.18, 1.77 ± 0.33, 2.06 ± 0.32 and 1.88 ± 0.41, respectively. Those of the Low T2 SI areas in benign inflammatory, benign non-inflammatory, malignant inflammatory and malignant non-inflammatory lesions were 0.89 ± 0.15, 1.31 ± 0.28, 0.87 ± 0.20 and 0.94 ± 0.27 respectively. ADC values of High T2 SI areas of the benign inflammatory lesions were significantly lower than those of benign non-inflammatory, malignant inflammatory, and malignant non-inflammatory lesions (p Conclusion For breast lesions with High T2 SI, segmenting the High T2 SI for ADC mapping distinguishes benign from malignant inflammatory conditions. Using ADC mapping of the Low T2 SI areas will not result in this distinction.

Objective: Estimation of renal filtration using dynamic contrast-enhanced imaging (DCE-MRI) requires a series of analysis steps. The possible number of distinct post-processing chains is large and grows rapidly with increasing number of processing steps or options. In this study we introduce a framework for systematic evaluation of the post-processing chains. The framework is later used to highlight the workflow processing chain sensitivity towards accuracy in estimation of glomerular filtration rate (GFR). Methods: Twenty healthy volunteers underwent DCE-MRI examinations as well as iohexol clearance for reference GFR measurements. In total, 692 different combinations of post-processing steps were explored for analysis, including options for kidney segmentation, B1 inhomogeneity correction, placement of arterial input function, gadolinium concentration estimation as well as handling of motion-corrupted volumes and breathing motion. The evaluation of various processing chains is presented using a classification tree framework and random forest ensemble learning. Results: Among the processing steps subject to testing, methods for calculating the gadolinium concentration as well as B1 inhomogeneity correction had the largest impact on accuracy of GFR estimations. Different segmentation methods did not play an important role in the post-processing of the MR data except from one processing chain where the automated segmentation outperformed the manual segmentation. Conclusion: The proposed classification trees were efficiently used as a statistical tool for visualization and communication of results to distinguish between important and less influential processing steps in renal DCE-MRI. We also identified several crucial factors in the processing chain.

To develop a high-resolution, 3D late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (MRI) technique for improved assessment of myocardial scars, and evaluate its performance against 2D breath-held (BH) LGE MRI using a surgically implanted animal scar model in the right ventricle (RV).A k-space segmented 3D LGE acquisition using CENTRA-PLUS (Contrast ENhanced Timing Robust Acquisition with Preparation of LongitUdinal Signal; or CP) ordering is proposed. 8 pigs were surgically prepared with cardiac patch implantation in the RV, followed in 60days by 1.5T MRI. LGE with Phase-Sensitive Inversion Recovery (PSIR) were performed as follows: 1) 2DBH using pneumatic control, and 2) navigator-gated, 3D free-breathing (3DFB)-CP-LGE with slice-tracking. The animal heart was excised immediately after cardiac MR for scar volume quantification. RV scar volumes were also delineated from the 2DBH and 3DFB-CP-LGE images for comparison against the surgical standard. Apparent scar/normal tissue signal-to-noise ratio (aSNR) and contrast-to-noise ratio (aCNR) were also calculated. 3DFB-CP-LGE technique was successfully performed in all animals. No difference in aCNR was noted, but aSNR was significantly higher using the 3D technique (p0.05). Against the surgical reference volume, the 3DFB-CP-LGE-derived delineation yielded significantly less volume quantification error compared to 2DBH-derived volumes (15±10% vs 55±33%; p0.05).Compared to conventional 2DBH-LGE, 3DFB-LGE acquisition using CENTRA-PLUS provided superior scar volume quantification and improved aSNR.

In the past three decades, we have learned much about the potential short-term and long-term safety issues associated with the intravenous administration of gadolinium based contrast agents (GBCAs). Yet, surprisingly, the past few years and even months have been accompanied by new discoveries in this field. This manuscript focuses predominantly on what we have learned - and are continuing to learn - about the long-term potential MR safety issues associated with the administration of the various GBCAs available today and will highlight areas in which they appear to differ from each other at least in a quantitative fashion, if not qualitatively.

In December 2013, a groundbreaking study by Kanda et al. was published showing that the serial injection of gadolinium based contrast agents (GBCAs) is correlated with a signal intensity increase in the dentate nucleus and the globus pallidus on unenhanced T1 weighted MR images. Subsequent studies by Kanda et al. and McDonald et al. on brain tissue from deceased patients provided evidence that the reported signal intensity increase in the brain correlates with gadolinium deposits in the brain tissue. In the following, multiple retrospective patient studies and animal studies assessed the potential of the marketed GBCAs to cause hyperintensities or gadolinium deposits in the brain, respectively. This review summarizes the evidence provided by these studies and additionally takes into account data from in vitro studies on the stability of GBCAs. The author concludes that there is a body of evidence suggesting that the potential of a GBCA to cause hyperintensities or gadolinium deposition in the brain corresponds with its stability and is particularly depending on the group of the specific GBCA as either linear or macrocyclic.

Until recognition of the association of nephrogenic systemic fibrosis (NSF) and gadolinium based contrast agents (GBCA) in 2006, these agents were considered extremely safe and without major adverse effects. Even after the recognition of NSF, most physicians considered all GBCAs to be safe when used in patients with normal renal function. This belief has been called into question with the discovery by Kanda in 2014 that gadolinium (Gd) is deposited in brain tissue in patients with normal kidney function. Since that initial report, there have been a number of important studies analyzing the effects of various GBCAs in brain using MR T1 signal intensity measurements and postmortem tissue analyses with inductively coupled plasma mass spectrometry. From these our knowledge and understanding of some key issues surrounding these observations has rapidly evolved. This report reviews and summarizes many recent human and animal studies in combination with past studies to better understand Gd tissue deposition not only in brain but also in bone and skin. Brain tissue deposition was initially demonstrated to occur with less stable group 1 linear agents but recent postmortem studies now confirm that Gd deposition also occurs with more stable linear agents as well as with macrocyclic agents although at much lower levels. Although no adverse health effects have been documented to date, even for the group 1 agents that deposit Gd in higher amounts, the implications for possible unrecognized toxicity is discussed. Future studies are being pursued that may provide better understanding of the various chemical forms of Gd that are deposited in tissues. This may help elucidate relative risks of different types of agents, mechanisms involved and even recognition of potential downstream toxic effects.

Anaphylaxis against gadolinium based contrast agents (GBCAs) has been reported in all severity grades but is less frequent than hypersensitivity/allergy against iodinated contrast materials. Once a patient acquires such an adverse reaction a life-long premedication is usually the consequence in concert with GBCA-enhanced MR-imaging procedures. The usefulness of this prophylaxis has been questioned, and discussed controversially during the past. The herein presented case may shed some light into the dynamic of contrast-medium-induced hypersensitivity reactions.

Purpose To evaluate the diagnostic performance of a multiparametric approach to breast lesions including apparent diffusion coefficient (ADC) from diffusion-weighted images (DWI), maximum slope (MS) from ultrafast dynamic contrast enhanced (UF-DCE) MRI, lesion size, and patient's age. Materials and methods In total, 96 lesions (73 malignant, 23 benign) were evaluated. UF-DCE MRI was acquired using a prototype 3D-gradient-echo volumetric interpolated breath-hold examination (VIBE) with compressed sensing. Images were obtained up to 1 min after gadolinium injection. MS was calculated as the percentage relative enhancement/s. An ADC map was automatically generated from DWI at b = 0 and b = 1000 s/mm2. MS and ADC values were measured by two radiologists independently. Interrater agreement was evaluated using intraclass correlation coefficients. Univariate and multivariate logistic regression analyses were performed using MS, ADC, lesion size, and the patient's age. The parameters of the prediction model were generated from the results of the multivariate logistic regression analysis. Area under the curve (AUC) was used to compare diagnostic performance of the prediction model and each parameter. Results Interrater agreements on MS and ADC were excellent (ICC 0.99 and 0.88, respectively). MS, ADC, and patient's age remained as significant parameters after univariate and multivariate logistic regression analysis. The prediction model using these significant parameters yielded an AUC of 0.90, significantly higher than that of MS (AUC 0.74, p = 0.01). The AUCs of ADC, MS, patient's age were 0.87, 0.74 and 0.73, respectively. Conclusions A multiparametric model using ADC from DWI, MS from UF-DCE MRI, and patient's age showed excellent diagnostic performance, with greater contribution of ADC. Combining DWI and UF-DCE MRI might reduce scanning time while preserving diagnostic performance.

Purpose Nephrogenic system fibrosis (NSF) is a rare complication detected in patients with renal insufficiency exposed to gadolinium-based contrast agents (GBCAs). The aim of our study is to evaluate the prevalence of NSF in a cohort of patients on renal replacement treatment who underwent GBCA-enhanced magnetic resonance imaging (MRI). Method We retrospectively reviewed all the charts of kidney transplant (KT) recipients, patients on hemodialysis (HD) and peritoneal dialysis (PD) who received a uniform protocol for contrast material enhanced-MRI with gadoteric acid at our center from January 2004 to December 2017. Results Three-hundred forty-four patients (44.1% on HD, 11.3% on PD and 44.4% KT recipients) underwent 551 gadoteric acid-enhanced MRI. The median age of the patients was 58 years (IQR, 45–70 years) and 65.1% were men. Sixty-three patients (18.3%) had skin punch biopsy after integumentary assessment performed by a dermatologist. No cases of NSF were detected after a median follow-up of 4.5 years (IQR, 1.9–8.2 years). During this period of observation, 116 (33.7%) patients died and 11 (3.1%) were lost at follow-up. Conclusions None of the patients exposed to gadoteric acid developed NSF. Our results, in line with more recent studies, suggest that the use of gadoteric acid, a macrocyclic GBCA, appears safe even in chronic kidney disease (CKD) patients receiving dialysis.

Background In MRI of formalin-fixed tissue one of the problems is the dependence of tissue relaxation properties on formalin composition and composition of embedding medium (EM) used for scanning. In this study, we investigated molecular mechanisms by which the EM composition affects T2 relaxation directly and T1 relaxation indirectly. Objective To identify principal components of formaldehyde based EM and the mechanism by which they affect relaxation properties of fixed tissue. Methods We recorded high resolution 1H NMR spectra of common formalin fixatives at temperatures in the range of 5 °C to 45 °C. We also measured T1 and T2 relaxation times of various organs of formalin fixed (FF) zebrafish at 7 T at 21 °C and 31 °C in several EM with and without fixative or gadolinium contrast agents. Results We showed that the major source of T2 variability is chemical exchange between protons from EM hydroxyls and water, mediated by the presence of phosphate ions. The exchange rate increases with temperature, formaldehyde concentration in EM and phosphate concentration in EM. Depending on which side of the coalescence the system resides, the temperature increase can lead to either shortening or prolongation of T2, or to no noticeable change at all when very close to the coalescence. Chemical exchange can be minimized by washing out from EM the fixative, the phosphate or both. Conclusion The dependence of T2 in fixed tissue on the fixative origin and composition described in prior literature could be attributed to the phosphate buffer accelerated chemical exchange among the fixative hydroxyls and the tissue water. More consistent results in the relaxation measurements could be obtained by stricter control of the fixative composition or by scanning fixed tissue in PBS without fixative.

Nowadays, it is highly desired to develop dual-modal fluorescence and magnetic resonance imaging (FI/MRI) probes in medical imaging because it unites the respective advantages of each imaging modality: high sensitivity of FI and superior spatial resolution of MRI. In this study, a facile strategy to fabricate a new bimodal imaging nanoprobe (Gd-CQDs@N-Fe3O4) was reported by integrating the fluorescence ability of carbon quantum dots (CQDs) and T1 and T2 contrast-enhancing functionality of Gd(III) ions and Fe3O4 nanoparticles into a single hybrid nanostructure. The hybrid composites were investigated by FT-IR, XRD, TEM, XPS, VSM, and so on, which confirmed that Gd-CQDs@N-Fe3O4 nanoparticles were successfully obtained and exhibited superparamagnetic property at room temperature. The derived nanoprobes presented an excitation wavelength-independent emission behavior. In addition, r1 and r2 relaxivities of the synthesized imaging nanoprobes were measured to be 5.16 and 115.6 mM−1 s−1, which nominated Gd-CQDs@N-Fe3O4 nanocomposites as a suitable T1-T2 contrast agent. The Gd-CQDs@N-Fe3O4 nanoparticles combining two synergetic imaging modalities showed great potential in FI/MRI dual-modal imaging for a more complementary and accurate detection.

Current late gadolinium enhancement (LGE) imaging of left atrial (LA) scar or fibrosis is relatively slow and requires 5-15min to acquire an undersampled (R=1.7) 3D navigated dataset. The GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) based parallel imaging method is the current clinical standard for accelerating 3D LGE imaging of the LA and permits an acceleration factor ~R=1.7. Two compressed sensing (CS) methods have been developed to achieve higher acceleration factors: a patch based collaborative filtering technique tested with acceleration factor R~3, and a technique that uses a 3D radial stack-of-stars acquisition pattern (R~1.8) with a 3D total variation constraint. The long reconstruction time of these CS methods makes them unwieldy to use, especially the patch based collaborative filtering technique. In addition, the effect of CS techniques on the quantification of percentage of scar/fibrosis is not known. We sought to develop a practical compressed sensing method for imaging the LA at high acceleration factors. In order to develop a clinically viable method with short reconstruction time, a Split Bregman (SB) reconstruction method with 3D total variation (TV) constraints was developed and implemented. The method was tested on 8 atrial fibrillation patients (4 pre-ablation and 4 post-ablation datasets). Blur metric, normalized mean squared error and peak signal to noise ratio were used as metrics to analyze the quality of the reconstructed images, Quantification of the extent of LGE was performed on the undersampled images and compared with the fully sampled images. Quantification of scar from post-ablation datasets and quantification of fibrosis from pre-ablation datasets showed that acceleration factors up to R~3.5 gave good 3D LGE images of the LA wall, using a 3D TV constraint and constrained SB methods. This corresponds to reducing the scan time by half, compared to currently used GRAPPA methods. Reconstruction of 3D LGE images using the SB method was over 20 times faster than standard gradient descent methods.

To evaluate a novel post-processing method for assessment of longitudinal mid-myocardial strain in standard cine cardiac magnetic resonance (CMR) imaging sequences.Cine CMR imaging and tagged cardiac magnetic resonance imaging (TMRI) were performed in 15 patients with acute myocardial infarction (AMI) and 15 healthy volunteers served as control group. A second group of 37 post-AMI patients underwent both cine CMR and late gadolinium enhancement (LGE) CMR exams. Speckle tracking echocardiography (STE) was performed in 36 of these patients. Cine CMR, TMRI and STE were analyzed to obtain longitudinal strain. LGE-CMR datasets were analyzed to evaluate scar extent. Comparison of peak systolic strain (PSS) measured from CMR and TMRI yielded a strong correlation (r=0.86, p0.001). PSS measured from CMR and STE correlated well (r=0.75, p0.001). A cutoff longitudinal PSS value of -13.14% differentiated non-infarction from any infarcted myocardium, with a sensitivity of 93% and a specificity of 89% (area under curve (AUC) 0.95). PSS value of -9.39% differentiated non-transmural from transmural infarcted myocardium, with a sensitivity of 75% and a specificity of 67% (AUC 0.78).The present study showed a novel off-line post-processing method for segmental longitudinal strain analysis in mid-myocardium layer based on cine CMR data. The method was found to be highly correlated with strain measurements obtained by TMRI and STE. This tool allows accurate discrimination between different transmurality states of myocardial infarction.

This study evaluates myocardial edema by quantitative T2 mapping in patients with acute myocardial infarction (AMI) and compares the lateral extent of myocardial edema with those of infarcted and dysfunctional myocardium.Cardiac magnetic resonance images (MRIs) of 31 patients (M:F=29:2, mean age: 52.5±10.8years) with AMI were reviewed. On cine-MRI, all short axis images of the left ventricle (LV) were divided into 60 sectors. The regional wall motion of each sector was calculated as follows: systolic wall thickening (SWT, %)=[(LV wall thicknessES-LV wall thicknessED)/LV wall thicknessED]*100. Dysfunctional myocardium was defined as sectors with decreased SWT lower than 40%. On LGE-images, myocardial infarction was defined as an area of hyper-enhancement more than 5 SDs from the remote myocardium. On T2 map, myocardial edema was defined as an area in which T2 values were at least 2 SDs higher than those from remote myocardium. The lateral extents of infarcted myocardium, myocardial edema, and dysfunctional myocardium were calculated as the percentage of central angles ((central angle of the involved myocardium/360)*100 (%)) and then compared.The lateral extent of myocardial edema was slightly larger than that of infarcted myocardium (37.4±13.3% vs. 35±12.9%, p0.01). The lateral extent of dysfunctional myocardium (50.6±15.3%) was significantly larger than that of infarcted myocardium or myocardial edema (p0.001).The lateral extent of myocardial edema beyond the infarcted myocardium might be narrow, but the dysfunctional myocardium could be significantly larger than myocardial edema, suggesting stunned myocardium without edema.

This summary attempts to provide forward-looking concepts regarding gadolinium related toxicity, as discussed in further detail in this issue.

Dynamic contrast enhancement (DCE)-MRI has high diagnostic performance of prostate cancer. However, it is preferable to avoid the use of MRI contrast media. A study reported that the diagnosability of the wash-in index of DCE-MRI was equivalent to the intravoxel incoherent motion of the diffusion weighted image. The purpose of this study was to examine the correlation between the slow component apparent diffusion coefficient (ADC) and the wash-out index of the DCE.Thirty-eight patients diagnosed with prostate cancer by biopsy were enrolled in this study. The fast and slow component ADCs of the DWI were calculated for 76 points of the tumor and the contralateral normal parts. Furthermore, the wash-in and wash-out indices of the DCE-MRI were calculated. The correlations for each calculated index were compared.There was a significant difference between the tumor and the contralateral normal parts for both fast (p = 0.03) and slow component (p 0.01) ADCs. In addition, the slow component ADC was correlated with the wash-out index (r = 0.64).The slow component ADC was correlated with the wash-out index, and may, therefore, be a suitable substitute for DCE-MRI.

The tumor microenvironment is characteristically acidic and this extracellular acidosis is known to play a role in carcinogenesis and metastasis and can affect tumor chemosensitivity and radiosensitivity. Intracellular pH has been used as a possible biomarker of salvageable tissue in ischemic stroke. A non-invasive MRI-based approach for the determination and imaging of cerebral pH would be a powerful tool in cancer diagnosis and monitoring, as well as stroke treatment planning. Several pH-based MRI imaging approaches have been proposed but for these to be useful, disentangling the effects of pH from other parameters which may affect the measured MRI signal is crucial to ensure accuracy and specificity. R1 relaxation in the rotating frame (R1ρ) is an example of a method that has been proposed to probe pH in vivo using MRI. In this study, we have investigated the relationship between R1ρ, pH, and macromolecular density in vitro using phantoms and in human volunteers. Here we show that the rate of R1ρ relaxation (=1/T1ρ) varies with pH but only in the presence of macromolecules. At constant pH, phantom macromolecular density inversely correlated with R1ρ. R1ρ imaging of the normal human brain demonstrated regional heterogeneity with significant differences between structurally distinct regions, which are likely to be independent of pH. For example, R1ρ was higher in the basal ganglia compared to grey matter and higher in grey matter compared to white matter. We conclude that R1ρ cannot be reliably used to image tissue pH without deconvolution from the effects of local tissue macromolecular composition.

Background The molecular structure, charge, thermodynamic and kinetic stability are approximately the same for gadodiamide and gadoversetamide, the main substantive difference is that gadodiamide is manufactured with 5% free ligand to form Omniscan® and gadoversetamide with 10% free ligand to form OptiMARK®. Purpose To determine the relative risk of Nephrogenic Systemic Fibrosis (NSF) between gadodiamide (Omniscan®) and gadoversetamide (OptiMARK®) and to explore the potential contribution of the amount of excess ligand added to their commercial formulations. Materials and methods In this retrospective observational study, the number of doses and NSF cases associated with these agents were calculated based on two different approaches: the number of doses was determined based on pharmaceutical companies' information, and the number of unconfounded NSF cases was obtained from the previously published literature based on a legal database. A second analysis estimates the number of doses and NSF cases from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Results Approximately 87 million and 12 million doses of Omniscan® and OptiMARK®, respectively, have been administered worldwide since their original approval for use in the various countries throughout the world. A total of 197 and 8 unconfounded cases of NSF have been reported with Omniscan® and OptiMARK®, rendering an incidence of 2.3/million and 0.7/million for these agents, respectively. The FAERS analysis suggested reported incidences of 13.1/million and 5.0/million. Conclusion There is an approximately 3-fold greater incidence of NSF from Omniscan® than OptiMARK®. The difference in incidence might reflect the lesser quantity of added free ligand to the formulation of Omniscan®.

Introduction Compared to standard arterial-only first-pass MR-angiography (FPMRA), imaging during the equilibrium phase of a blood pool contrast agent (steady state) has been shown to provide higher image quality and better stenosis grading. Homogenous Dixon fat-suppression promises to increase contrast by suppression of fat adjacent to vessels. This study was performed to compare diagnostic image quality and vessel-to-background contrasts in equilibrium phase Dixon-based fat-free MRA (DFSMRA) of run-off vessels to FPMRA imaging and equilibrium phase T1-weighted non-fat-suppressed ultra-high resolution MRA (SSMRA). Material and Methods In a prospective, intra-individual comparative study, 17 patients with known or suspected peripheral arterial occlusive disease (PAOD; 11 men, mean age 65.6 ± 18.1 [23–89] years) received FPMRA, DFSMRA, and SSMRA at 1.5 Tesla using a clinical whole body MRI scanner. All sequences were performed within the same session applying a single dose of a blood pool contrast agent (gadofosveset trisodium) that was injected during acquisition of FPMRA. The diagnostic image quality of the run-off vessels was evaluated on a 3-point scale. Quantitative analysis consisted of contrast-ratio (CR) measurements of vascular lumen signals compared to signals of adjacent muscle and fat. Results The average image quality of vessel visualization was rated highest in SSMRA (mean 1.34 ± 0.41), followed by standard FPMRA (mean 1.15 ± 0.33) and DFSMRA (mean 0.99 ± 0.61). Image quality was rated similarly high in the thighs and pelvic region, whereas small vessels in the lower legs and in the feet were best visualized by SSMRA. CR of vascular lumen compared to adjacent fatty tissue was 2.7 times higher in DFSMRA compared to SSMRA, whereas CR of vascular lumen to muscle was 1.3 times higher in SSMRA. Conclusion Vessel to fat contrast is strongly increased in DFSMRA compared to T1-weighted ultra-high resolution non-fat suppressed SSMRA, whereas vessel to muscle contrast is decreased in DFSMRA. Given the current technical limitations of DFSMRA, possible benefits are outweighed by advantages of first-pass imaging regarding arterial selectivity as well as advantages of SSMRA with respect to spatial resolution.

Background Myocardial fibrosis was shown to influence prognosis in hypertrophic cardiomyopathy (HCM). It is typically assessed by late gadolinium enhancement (LGE) on cardiac magnetic resonance. Native T1-mapping has been proposed, as a contrast-free method of fibrosis assessment. The aim of the study was to define a cut-off value for native T1 relaxation time that best reflects LGE quantification of myocardial fibrosis. Methods In 25 patients with HCM and 20 controls we performed T1-mapping pre-contrast using ShMOLLI technique. This was followed by LGE assessment in the studied group 10 minutes after gadolinium contrast injection. Relative myocardial fibrosis size was calculated for varying T1 time thresholds (940–1100 ms) and compared with 6 standard deviations (6SD) method for LGE. Results Median fibrosis size calculated with T1-mapping was insignificantly different from LGE only for native T1 time threshold of 1060 ms (p = 0.62). Using this threshold, Bland–Altman plots demonstrated very good agreement between fibrosis sizes from the two methods (slightly better only for 1080 ms threshold). For threshold of 1060 ms we also observed good correlation (rho = 0.73) with LGE 6SD method (insignificantly better for lower thresholds, best for threshold of 980 ms-rho = 0.88). In control group with no diagnosis of HCM, fibrosis size Conclusion Native T1-mapping can be used for non-contrast assessment of myocardial fibrosis in HCM. The 1060 ms threshold of the native T1 relaxation time is characterized by the best balance between agreement and correlation with fibrosis assessed by LGE 6SD method.

Purpose This study aims to describe the self-reporting symptoms experienced by individuals with self-reported normal renal function after gadolinium based contrast agent (GBCA) administration. Materials and methods This HIPAA-compliant, IRB-approved study consisted of an anonymous online survey of patients who believe that they suffer from gadolinium toxicity. 50 respondents completed the nine-question survey. Results Fifty (100%) of the subjects ascribed their complaints to gadolinium exposure. Thirty-three (66%) described the onset immediately following GBCA administration and 16 (32%) within 6 weeks. The most common symptoms included bone/joint pain and head/neck symptoms including headache, vision change, and hearing change (77.6% each). Other symptoms occurred with lesser incidence. Conclusions This survey represents an initial description of patients with normal renal function who self-described toxicity related to GBCA administration. Bone and joint complaints and skin changes are two of the most common complaints.

Object To enable a retrospective adjustment of image contrast and heart phase in inversion recovery prepared late gadolinium enhancement (LE) imaging in the myocardium. Materials and methods After one inversion pulse, unsegmented data were acquired over multiple cardiac cycles using a radial spoiled gradient-echo sequence with golden angle increments between subsequent readouts. Model-based acceleration of parameter mapping (MAP) was combined with an image registration technique (“MOCO-MAP”) to enable the reconstruction of images with arbitrary inversion time TI. Results MOCO-MAP allowed the reconstruction of LE images with arbitrary TI for arbitrary cardiac phases in four patients suffering from myocardial infarction. Regions with LE agreed well between the MOCO-MAP and the segmented techniques typically applied in clinical routine. Conclusions MOCO-MAP delivers LE images with arbitrary and thus retrospectively optimized contrast between vital and diseased tissue, without the need for time-consuming TI scouting.