Meningeal contrast enhancement in multiple sclerosis: Assessment of field strength, acquisition delay, and clinical relevance.

BACKGROUND/PURPOSE: Leptomeningeal enhancement (LME) on post-contrast FLAIR is described as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Here we report an assessment of the impact of MRI field strength and acquisition timing on meningeal contrast enhancement (MCE). METHODS: This was a cross-sectional, observational study of 95 participants with MS and 17 healthy controls (HC) subjects. Each participant underwent an MRI of the brain on both a 7 Tesla (7T) and 3 Tesla (3T) MRI scanner. 7T protocols included a FLAIR image before, soon after (Gd+ Early 7T FLAIR), and 23 minutes after gadolinium (Gd+ Delayed 7T FLAIR). 3T protocol included FLAIR before and 21 minutes after gadolinium (Gd+ Delayed 3T FLAIR). RESULTS: LME was seen in 23.3% of participants with MS on Gd+ Delayed 3T FLAIR, 47.4% on Gd+ Early 7T FLAIR (p = 0.002) and 57.9% on Gd+ Delayed 7T FLAIR (p < 0.001 and p = 0.008, respectively). The count and volume of LME, leptomeningeal and paravascular enhancement (LMPE), and paravascular and dural enhancement (PDE) were all highest for Gd+ Delayed 7T FLAIR and lowest for Gd+ Delayed 3T FLAIR. Non-significant trends were seen for higher proportion, counts, and volumes for LME and PDE in MS compared to HCs. The rate of LMPE was different between MS and HCs on Gd+ Delayed 7T FLAIR (98.9% vs 82.4%, p = 0.003). MS participants with LME on Gd+ Delayed 7T FLAIR were older (47.6 (10.6) years) than those without (42.0 (9.7), p = 0.008). CONCLUSION: 7T MRI and a delay after contrast injection increased sensitivity for all forms of MCE. However, the lack of difference between groups for LME and its association with age calls into question its relevance as a biomarker of meningeal inflammation in MS.

Deep-learning-based synthesis of post-contrast T1-weighted MRI for tumour response assessment in neuro-oncology: a multicentre, retrospective cohort study.

BACKGROUND: Gadolinium-based contrast agents (GBCAs) are widely used to enhance tissue contrast during MRI scans and play a crucial role in the management of patients with cancer. However, studies have shown gadolinium deposition in the brain after repeated GBCA administration with yet unknown clinical significance. We aimed to assess the feasibility and diagnostic value of synthetic post-contrast T1-weighted MRI generated from pre-contrast MRI sequences through deep convolutional neural networks (dCNN) for tumour response assessment in neuro-oncology. METHODS: In this multicentre, retrospective cohort study, we used MRI examinations to train and validate a dCNN for synthesising post-contrast T1-weighted sequences from pre-contrast T1-weighted, T2-weighted, and fluid-attenuated inversion recovery sequences. We used MRI scans with availability of these sequences from 775 patients with glioblastoma treated at Heidelberg University Hospital, Heidelberg, Germany (775 MRI examinations); 260 patients who participated in the phase 2 CORE trial (1083 MRI examinations, 59 institutions); and 505 patients who participated in the phase 3 CENTRIC trial (3147 MRI examinations, 149 institutions). Separate training runs to rank the importance of individual sequences and (for a subset) diffusion-weighted imaging were conducted. Independent testing was performed on MRI data from the phase 2 and phase 3 EORTC-26101 trial (521 patients, 1924 MRI examinations, 32 institutions). The similarity between synthetic and true contrast enhancement on post-contrast T1-weighted MRI was quantified using the structural similarity index measure (SSIM). Automated tumour segmentation and volumetric tumour response assessment based on synthetic versus true post-contrast T1-weighted sequences was performed in the EORTC-26101 trial and agreement was assessed with Kaplan-Meier plots. FINDINGS: The median SSIM score for predicting contrast enhancement on synthetic post-contrast T1-weighted sequences in the EORTC-26101 test set was 0·818 (95% CI 0·817-0·820). Segmentation of the contrast-enhancing tumour from synthetic post-contrast T1-weighted sequences yielded a median tumour volume of 6·31 cm3 (5·60 to 7·14), thereby underestimating the true tumour volume by a median of -0·48 cm3 (-0·37 to -0·76) with the concordance correlation coefficient suggesting a strong linear association between tumour volumes derived from synthetic versus true post-contrast T1-weighted sequences (0·782, 0·751-0·807, p<0·0001). Volumetric tumour response assessment in the EORTC-26101 trial showed a median time to progression of 4·2 months (95% CI 4·1-5·2) with synthetic post-contrast T1-weighted and 4·3 months (4·1-5·5) with true post-contrast T1-weighted sequences (p=0·33). The strength of the association between the time to progression as a surrogate endpoint for predicting the patients' overall survival in the EORTC-26101 cohort was similar when derived from synthetic post-contrast T1-weighted sequences (hazard ratio of 1·749, 95% CI 1·282-2·387, p=0·0004) and model C-index (0·667, 0·622-0·708) versus true post-contrast T1-weighted MRI (1·799, 95% CI 1·314-2·464, p=0·0003) and model C-index (0·673, 95% CI 0·626-0·711). INTERPRETATION: Generating synthetic post-contrast T1-weighted MRI from pre-contrast MRI using dCNN is feasible and quantification of the contrast-enhancing tumour burden from synthetic post-contrast T1-weighted MRI allows assessment of the patient's response to treatment with no significant difference by comparison with true post-contrast T1-weighted sequences with administration of GBCAs. This finding could guide the application of dCNN in radiology to potentially reduce the necessity of GBCA administration. FUNDING: Deutsche Forschungsgemeinschaft.

Assessment of gadolinium deposition in the brain tissue of pediatric and adult congenital heart disease patients after contrast enhanced cardiovascular magnetic resonance.

BACKGROUND: Contrast enhanced magnetic resonance imaging (MRI) is an important tool for the assessment of extracardiac vasculature and myocardial viability. Gadolinium (Gd) brain deposition after contrast enhanced MRI has recently been described and resulted in a warning issued by the United States Food and Drug Administration. However, the prevalence of brain deposition in children and adults with congenital heart disease (CHD) undergoing cardiovascular magnetic resonance (CMR) is unclear. We hypothesized that Gd exposure as part of one or more CMRs would lead to a low rate of brain deposition in pediatric and adult CHD patients. METHODS: We queried our institutional electronic health record for all pediatric and adult CHD patients who underwent contrast enhanced CMR from 2005 to 2018 and had a subsequent brain MRI. Cases were age- and gender-matched to controls who were never exposed to Gd and underwent brain MRIs. The total number of contrast enhanced MRIs, type of Gd, and total Gd dose were determined. Brain MRIs were reviewed by a neuroradiologist for evidence of Gd deposition using qualitative and quantitative assessment. Quantitative assessment was performed using the dentate nucleus to pons signal intensity ratio (dp-SIR) on T1 weighted imaging. Continuous variables were analyzed using Mann-Whitney U and Spearman rank correlation tests. Normal SIR was defined as the 95% CI of the control population dp-SIR. RESULTS: Sixty-two cases and 62 controls were identified. The most contrast enhanced MRIs in a single patient was five and the largest lifetime dose of Gd that any patient received was 0.75 mmol/kg. There was no significant difference in the mean dp-SIR of cases and controls (p = 0.11). The dp-SIR was not correlated with either the lifetime dose of Gd (rs = 0.21, p = 0.11) or the lifetime number of contrast enhanced studies (rs = 0.21, p = 0.11). Two cases and 2 controls had dp-SIRs above the upper bound of the 95% confidence interval for the control group. One case had qualitative imaging-based evidence of Gd deposition in the brain but had a dp-SIR within the normal range. CONCLUSION: In our cohort of pediatric and adult CHD patients undergoing contrast enhanced CMR, there was a low incidence of qualitative and no significant quantitative imaging-based evidence of Gd brain deposition.

Recent Advances in T1 and T2 Mapping in the Assessment of Fulminant Myocarditis by Cardiac Magnetic Resonance.

PURPOSE OF REVIEW: This review was undertaken to summarise recent data relating to T1 and T2 relaxation times in the assessment of myocarditis using cardiac MRI, and the effect new studies have had on the established diagnostic criteria, leading to recently proposed revised criteria for the cardiac MRI assessment of myocarditis. RECENT FINDINGS: In 2018, updates to the 2009 Lake Louise Criteria (LLC) were proposed, based on studies showing improved accuracy of T1 mapping techniques over T1 signal intensity ratio-based imaging, although for the detection of myocardial oedema either T2-weighted images or increased T2 relaxation times can be used. Non-ischaemic distribution of scar on late gadolinium-enhanced (LGE) T1-weighted imaging remains in the newly revised criteria, which, although can have low sensitivity due to fibrosis presenting diffusely or due to CMR being performed early in the disease process before scar formation, remains in the LLC due to its high specificity. Early gadolinium enhancement has been removed from the LLC, as T1 quantification has higher diagnostic accuracy for the detection of myocardial injury. In the CMR assessment of myocarditis, T1 and T2 quantifications are now recommended over T1- and T2-weighted imaging. Late gadolinium enhancement in a non-ischaemic pattern remains in the updated criteria, whereas early gadolinium enhancement has been superseded by T1 quantification.

Monte Carlo evaluation of the dose sparing and dose enhancement by combination of Gd-infused tumor and 241Am source for an endocavitary brachytherapy geometry.

In this work, the benefits in terms of dose enhancement and dose sparing via radiation shielding are evaluated, for a combined irradiation scheme with sources of 241Am and tumor-infused with Gd agents, regarding conventional 192Ir treatment. Monte Carlo simulations using PENELOPE code were implemented for endocavitary brachytherapy geometries, configuring a pelvis phantom of 15 cm radius and 30 cm length. Inside, it was defined cylindrical tumor phantoms of 2 cm radius and 4 cm-6 cm length (simulating initial stages) as well as tumors of extensive volume (2.5 and 3.0 cm radius) and difficult coverage. Tumor phantoms were doped with 68 mM and 138 mM of Gd in order to assess the effects of enhancement and protection based on the concentration and emission energy of the isotope. Obtained results for the first tumor group, shown the feasibility of achieving dose enhancements of 94.3%-117% and 160%-194% for 68 mM and 138 mM of Gd infused into the tumor and irradiation with 241Am, respectively. Similarly, reduced dose enhancements of 3.5-5.7% y 8.9%-11.2% for 68 mM and 138 mM of Gd are attained with 192Ir. In terms of dose sparing outer the tumor, the radiation shielding and dose enhancement allowed a higher reduction in the dose by 241Am of 17%-24% for 68 mM and 21%-32% for 138 mM of Gd, and non-negligible dose sparing are produced too by 192Ir of 2% and 5% for the same concentration of Gd. For the second tumors group, the combined use of 241Am and Gd agents simultaneously allowed to improve coverage and reduce the healthy tissue dose, showing the obtained results the possibility of achieving coverage of 95% of the prescribed dose in 100% of tumor volume together with dose sparing factor of 6-21% reduction in isodose of the studied point and dose enhancements of 75%-158% at the prescription point.

Dual-probe molecular MRI for the in vivo characterization of atherosclerosis in a mouse model: Simultaneous assessment of plaque inflammation and extracellular-matrix remodeling.

Molecular MRI is a promising in-vivo modality to detect and quantify morphological and molecular vessel-wall changes in atherosclerosis. The combination of different molecular biomarkers may improve the risk stratification of patients. This study aimed to investigate the feasibility of simultaneous visualization and quantification of plaque-burden and inflammatory activity by dual-probe molecular MRI in a mouse-model of progressive atherosclerosis and in response-to-therapy. Homozygous apolipoprotein E knockout mice (ApoE-/-) were fed a high-fat-diet (HFD) for up to four-months prior to MRI of the brachiocephalic-artery. To assess response-to-therapy, a statin was administered for the same duration. MR imaging was performed before and after administration of an elastin-specific gadolinium-based and a macrophage-specific iron-oxide-based probe. Following in-vivo MRI, samples were analyzed using histology, immunohistochemistry, inductively-coupled-mass-spectrometry and laser-inductively-coupled-mass-spectrometry. In atherosclerotic-plaques, intraplaque expression of elastic-fibers and inflammatory activity were not directly linked. While the elastin-specific probe demonstrated the highest accumulation in advanced atherosclerotic-plaques after four-months of HFD, the iron-oxide-based probe showed highest accumulation in early atherosclerotic-plaques after two-months of HFD. In-vivo measurements for the elastin and iron-oxide-probe were in good agreement with ex-vivo histopathology (Elastica-van-Giesson stain: y = 298.2 + 5.8, R2 = 0.83, p < 0.05; Perls' Prussian-blue-stain: y = 834.1 + 0.67, R2 = 0.88, p < 0.05). Contrast-to-noise-ratio (CNR) measurements of the elastin probe were in good agreement with ICP-MS (y = 0.11x-11.3, R² = 0.73, p < 0.05). Late stage atherosclerotic-plaques displayed the strongest increase in both CNR and gadolinium concentration (p < 0.05). The gadolinium probe did not affect the visualization of the iron-oxide-probe and vice versa. This study demonstrates the feasibility of simultaneous assessment of plaque-burden and inflammatory activity by dual-probe molecular MRI of progressive atherosclerosis. The in-vivo detection and quantification of different MR biomarkers in a single scan could be useful to improve characterization of atherosclerotic-lesions.

Non-contrast myocardial infarct scar assessment using a hybrid native T1 and magnetization transfer imaging sequence at 1.5T.

PURPOSE: To develop a gadolinium-free cardiac MR technique that simultaneously exploits native T1 and magnetization transfer (MT) contrast for the imaging of myocardial infarction. METHODS: A novel hybrid T one and magnetization transfer (HYTOM) method was developed based on the modified look-locker inversion recovery (MOLLI) sequence, with a train of MT-prep pulses placed before the balanced SSFP (bSSFP) readout pulses. Numerical simulations, based on Bloch-McConnell equations, were performed to investigate the effects of MT induced by (1) the bSSFP readout pulses, and (2) the MT-prep pulses, on the measured, "apparent," native T1 values. The HYTOM method was then tested on 8 healthy adult subjects, 6 patients, and a swine with prior myocardial infarction (MI). The resulting imaging contrast between normal myocardium and infarcted tissues was compared with that of MOLLI. Late gadolinium enhancement (LGE) images were also obtained for infarct assessment in patients and swine. RESULTS: Numerical simulation and in vivo studies in healthy volunteers demonstrated that MT effects, resulting from on-resonance bSSFP excitation pulses and off-resonance MT-prep pulses, reduce the measured T1 in both MOLLI and HTYOM. In vivo studies in patients and swine showed that the HYTOM sequence can identify locations of MI, as seen on LGE. Furthermore, the HYTOM method yields higher myocardium-to-scar contrast than MOLLI (contrast-to-noise ratio: 7.33 ± 1.67 vs. 3.77 ± 0.66, P < 0.01). CONCLUSION: The proposed HYTOM method simultaneously exploits native T1 and MT contrast and significantly boosts the imaging contrast for myocardial infarction.

Opportunistic dose amplification for proton and carbon ion therapy via capture of internally generated thermal neutrons.

This paper presents Neutron Capture Enhanced Particle Therapy (NCEPT), a method for enhancing the radiation dose delivered to a tumour relative to surrounding healthy tissues during proton and carbon ion therapy by capturing thermal neutrons produced inside the treatment volume during irradiation. NCEPT utilises extant and in-development boron-10 and gadolinium-157-based drugs from the related field of neutron capture therapy. Using Monte Carlo simulations, we demonstrate that a typical proton or carbon ion therapy treatment plan generates an approximately uniform thermal neutron field within the target volume, centred around the beam path. The tissue concentrations of neutron capture agents required to obtain an arbitrary 10% increase in biological effective dose are estimated for realistic treatment plans, and compared to concentrations previously reported in the literature. We conclude that the proposed method is theoretically feasible, and can provide a worthwhile improvement in the dose delivered to the tumour relative to healthy tissue with readily achievable concentrations of neutron capture enhancement drugs.

Feasibility of dose enhancement assessment: Preliminary results by means of Gd-infused polymer gel dosimeter and Monte Carlo study.

This work reports the experimental development of an integral Gd-infused dosimeter suitable for Gd dose enhancement assessment along with Monte Carlo simulations applied to determine the dose enhancement by radioactive and X-ray sources of interest in conventional and electronic brachytherapy. In this context, capability to elaborate a stable and reliable Gd-infused dosimeter was the first goal aimed at direct and accurate measurements of dose enhancement due to Gd presence. Dose-response was characterized for standard and Gd-infused PAGAT polymer gel dosimeters by means of optical transmission/absorbance. The developed Gd-infused PAGAT dosimeters demonstrated to be stable presenting similar dose-response as standard PAGAT within a linear trend up to 13 Gy along with good post-irradiation readout stability verified at 24 and 48 h. Additionally, dose enhancement was evaluated for Gd-infused PAGAT dosimeters by means of Monte Carlo (PENELOPE) simulations considering scenarios for isotopic and X-ray generator sources. The obtained results demonstrated the feasibility of obtaining a maximum enhancement around of (14 ±â€¯1)% for 192Ir source and an average enhancement of (70 ±â€¯13)% for 241Am. However, dose enhancement up to (267 ±â€¯18)% may be achieved if suitable filtering is added to the 241Am source. On the other hand, optimized X-ray spectra may attain dose enhancements up to (253 ±â€¯22) %, which constitutes a promising future alternative for replacing radioactive sources by implementing electronic brachytherapy achieving high dose levels.

Gadolinium Retention in the Rat Brain: Assessment of the Amounts of Insoluble Gadolinium-containing Species and Intact Gadolinium Complexes after Repeated Administration of Gadolinium-based Contrast Agents.

Purpose To evaluate the speciation of gadolinium-containing species after multiple administrations of the gadolinium-based contrast agents (GBCAs) gadodiamide and gadoteridol and to quantify the amount of intact gadolinium complexes and insoluble gadolinium-containing species. Materials and Methods A total dose of 13.2 mmol per kilogram of body weight of each GBCA was administered in healthy Wistar rats over a period of 8 weeks. Three days after the final administration, rats were sacrificed, and the brains were excised and divided into three portions. Each portion of brain homogenate was divided into two parts, one for determination of the total gadolinium concentration with inductively coupled plasma mass spectrometry and one for determination of the amount of intact GBCA and gadolinium-containing insoluble species. Relaxometric measurements of gadodiamide and gadolinium trichloride in the presence of polysialic acid were also performed. Results The mean total gadolinium concentrations for gadodiamide and gadoteridol, respectively, were 0.317 µg/g ± 0.060 (standard deviation) and 0.048 µg/g ± 0.004 in the cortex, 0.418 µg/g ± 0.078 and 0.051 µg/g ± 0.009 in the subcortical brain, and 0.781 µg/g ± 0.079 and 0.061 µg/g ± 0.012 in the cerebellum. Gadoteridol comprised 100% of the gadolinium species found in rats treated with gadoteridol. In rats treated with gadodiamide, the largest part of gadolinium retained in brain tissue was insoluble species. In the cerebellum, the amount of intact gadodiamide accounts for 18.2% ± 10.6 of the total gadolinium found therein. The mass balance found for gadolinium implies the occurrence of other soluble gadolinium-containing species (approximately 30%). The relaxivity of the gadolinium polysialic acid species formed in vitro was 97.8 mM/sec at 1.5 T and 298 K. Conclusion Gadoteridol was far less retained, and the entire detected gadolinium was intact soluble GBCA, while gadodiamide yielded both soluble and insoluble gadolinium-containing species, with insoluble species dominating. © RSNA, 2017 Online supplemental material is available for this article.

Diffusion-weighted imaging for assessment of synovial inflammation in juvenile idiopathic arthritis: a promising imaging biomarker as an alternative to gadolinium-based contrast agents.

OBJECTIVES: To compare dynamic-contrast-enhanced MRI (DCE) and diffusion-weighted imaging (DWI) in quantifying synovial inflammation in juvenile idiopathic arthritis (JIA). METHODS: Regions of interest (ROI) were drawn in the synovium of JIA patients on T1 DCE and T2 DWI, followed by extraction of the maximum enhancement (ME), maximum initial slope (MIS), time to peak (TTP), % of different time intensity curve shapes (TIC) and apparent diffusion coefficient (ADC) of the ROIs. Mann-Whitney-U test was used for comparing parameters between MRI-active and -inactive patients (defined by the juvenile arthritis MRI scoring system). Spearman's rank was used to analyse the correlation between DCE and DWI. RESULTS: Thirty-five JIA patients (18 MRI active and 17 MRI inactive) were included. Median age was 13.1 years and 71% were female. ME, MIS, TTP, % TIC 5 and ADC were significantly different in MRI-active versus MRI-inactive JIA with median ADC 1.49 × 10-3mm2/s in MRI-active and 1.25 × 10-3mm2/s in MRI-inactive JIA, p = 0.001, 95% confidence interval of difference in medians =0.11-0.53 × 10-3mm2/s. ADC correlated to ME, MIS and TIC 5 shapes (r = 0.62, r = 0.45, r = -0.51, respectively, all p < 0.05). CONCLUSIONS: Similar to DCE parameters, DWI-derived ADC is significantly different in MRI-active JIA as compared to MRI-inactive JIA. The non-invasiveness of DWI combined with its possibility to detect synovial inflammation shows the potential of DWI. KEY POINTS: • MRI can quantify: dynamic contrast-enhanced and diffusion-weighted MRI can quantify synovitis • Both DWI and DCE can differentiate active from inactive JIA • The DWI-derived apparent diffusion coefficient (ADC) is higher in active JIA • DWI is non-invasive and thus safer and more patient-friendly • DWI is a potentially powerful and non-invasive imaging biomarker for JIA.

Identification and Assessment of Cardiac Amyloidosis by Myocardial Strain Analysis of Cardiac Magnetic Resonance Imaging.

BACKGROUND: We explored the usefulness of myocardial strain analysis on cardiac magnetic resonance imaging (CMR) scans for the identification of cardiac amyloidosis.Methods and Results:The 61 patients with systemic amyloidosis underwent 3.0-T CMR, including CMR tagging and late-gadolinium enhanced (LGE) imaging. The circumferential strain (CS) of LGE-positive and LGE-negative patients was measured on midventricular short-axis images and compared. Logistic regression modeling of CMR parameters was performed to detect patients with LGE-positive cardiac amyloidosis. Of the 61 patients with systemic amyloidosis 48 were LGE-positive and 13 were LGE-negative. The peak CS was significantly lower in the LGE-positive than in the LGE-negative patients (-9.5±2.3 vs. -13.3±1.4%, P<0.01). The variability in the peak CS time was significantly greater in the LGE-positive than in the LGE-negative patients (46.1±24.5 vs. 21.2±20.1 ms, P<0.01). The peak CS significantly correlated with clinical biomarkers. The sensitivity, specificity, and accuracy of the diagnostic model using CS parameters for the identification of LGE-positive amyloidosis were 93.8%, 76.9%, and 90.2%, respectively. CONCLUSIONS: Myocardial strain analysis by CMR helped detect LGE-positive amyloidosis without the need for contrast medium. The peak CS and variability in the peak CS time may correlate with the severity of cardiac amyloid deposition and may be more sensitive than LGE imaging for the detection of early cardiac disease in patients with amyloidosis.

Myocardial Fibrosis Assessment by LGE Is a Powerful Predictor of Ventricular Tachyarrhythmias in Ischemic and Nonischemic LV Dysfunction: A Meta-Analysis.

OBJECTIVES: The authors performed a meta-analysis to evaluate the predictive value of late gadolinium enhancement (LGE) cardiac magnetic resonance for ventricular tachyarrhythmia in ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM) patients with ventricular dysfunction. BACKGROUND: The use of LGE to detect myocardial fibrosis and its related arrhythmic substrate is well established. Several recent studies have described the predictive value of LGE for ventricular tachyarrhythmias; however, their validity is limited by small sample size and low number of events. METHODS: MEDLINE and the Cochrane Library electronic databases were systematically searched to identify studies that applied LGE in ICM and NICM patients with ventricular dysfunction and reported arrhythmic clinical outcomes (sudden death, aborted sudden death, ventricular tachycardia, ventricular fibrillation, and appropriate implantable cardioverter-defibrillator [ICD] therapy, including antitachycardia pacing). A meta-analysis was performed to determine pooled odds ratios (ORs) for these arrhythmic events. RESULTS: Nineteen studies that evaluated 2,850 patients with 423 arrhythmic events over a mean/median follow-up of 2.8 years were identified. The composite arrhythmic endpoint was reached in 23.9% of patients with a positive LGE test (annualized event rate of 8.6%) versus 4.9% of patients with a negative LGE test (annualized event rate of 1.7%; p < 0.0001). LGE correlated with arrhythmic events in the different patient groups. In the overall population, the pooled OR was 5.62 (95% confidence interval [CI]: 4.20 to 7.51), with no significant differences between ICM and NICM patients. In a subgroup of 11 studies (1,178 patients) with mean ejection fraction (EF) ≤30%, the pooled OR for the arrhythmic events increased to 9.56 (95% CI: 5.63 to 16.23), with a negative likelihood ratio of 0.13 (95% CI: 0.06 to 0.30). CONCLUSIONS: LGE is a powerful predictor of ventricular arrhythmic risk in patients with ventricular dysfunction, irrespective of ICM and NICM etiology. The prognostic power of LGE is particularly strong in patients with severely depressed EF, which suggests its potential to improve patient selection for ICD implantation.

A relaxometric method for the assessment of intestinal permeability based on the oral administration of gadolinium-based MRI contrast agents.

Herein, a new relaxometric method for the assessment of intestinal permeability based on the oral administration of clinically approved gadolinium (Gd)-based MRI contrast agents (CAs) is proposed. The fast, easily performed and cheap measurement of the longitudinal water proton relaxation rate (R1) in urine reports the amount of paramagnetic probe that has escaped the gastrointestinal tract. The proposed method appears to be a compelling alternative to the available methods for the assessment of intestinal permeability. The method was tested on the murine model of dextran sulfate sodium (DSS)-induced colitis in comparison with healthy mice. Three CAs were tested, namely ProHance®, MultiHance® and Magnevist®. Urine was collected for 24 h after the oral ingestion of the Gd-containing CA at day 3-4 (severe damage stage) and day 8-9 (recovery stage) after treatment with DSS. The Gd content in urine measured by (1)H relaxometry was confirmed by inductively coupled plasma-mass spectrometry (ICP-MS). The extent of urinary excretion was given as a percentage of excreted Gd over the total ingested dose. The method was validated by comparing the results obtained with the established methodology based on the lactulose/mannitol and sucralose tests. For ProHance and Magnevist, the excreted amounts in the severe stage of damage were 2.5-3 times higher than in control mice. At the recovery stage, no significant differences were observed with respect to healthy mice. Overall, a very good correlation with the lactulose/mannitol and sucralose results was obtained. In the case of MultiHance, the percentage of excreted Gd complex was not significantly different from that of control mice in either the severe or recovery stages. The difference from ProHance and Magnevist was explained on the basis of the (known) partial biliary excretion of MultiHance in mice.

Notched QRS for the assessment of myocardial fibrosis in hypertrophic cardiomyopathy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) sometimes develop myocardial fibrosis in association with adverse cardiovascular events. Electrocardiography (ECG) could provide helpful information on myocardial fibrosis in HCM, as in coronary artery disease. METHODS AND RESULTS: A total of 60 patients with HCM without bundle branch block underwent cardiac magnetic resonance imaging (CMR). The extent or location of late gadolinium enhancement (LGE) was examined in relation to 12-lead ECG. A notch on QRS was defined as at least 2 consecutive spikes in the same polarity with a reversal of direction ≥90° and the initial negative deflection ≥0.05 mV. LGE was associated with notched QRS, leftward QRS axis, and prolonged QRS duration, but not with any other findings such as abnormal Q waves, R-wave amplitude, or ST-T changes. Notched QRS was most useful in determining the presence or absence of myocardial fibrosis, with a sensitivity of 70% and a specificity of 81% using a cut-off of the number of leads with notched QRS ≥2. The number of notched QRS leads was positively correlated with LGE volume (P<0.01) and the lead distribution of notched QRS was informative about the location of LGE. CONCLUSIONS: A notch on QRS was useful in estimating myocardial fibrosis as assessed on CMR LGE in HCM patients without bundle branch block.

Rapid dynamic R1 /R2 */temperature assessment: a method with potential for monitoring drug delivery.

Local drug delivery by hyperthermia-induced drug release from thermosensitive liposomes (TSLs) may reduce the systemic toxicity of chemotherapy, whilst maintaining or increasing its efficacy. Relaxivity contrast agents can be co-encapsulated with the drug to allow the visualization of the presence of liposomes, by means of R2 *, as well as the co-release of the contrast agent and the drug, by means of R1, on heating. Here, the mathematical method used to extract both R2 * and R1 from a fast dynamic multi-echo spoiled gradient echo (ME-SPGR) is presented and analyzed. Finally, this method is used to monitor such release events. R2 * was obtained from a fit to the ME-SPGR data. Absolute R1 was calculated from the signal magnitude changes corrected for the apparent proton density changes and a baseline Look-Locker R1 map. The method was used to monitor nearly homogeneous water bath heating and local focused ultrasound heating of muscle tissue, and to visualize the release of a gadolinium chelate from TSLs in vitro. R2 *, R1 and temperature maps were measured with a 5-s temporal resolution. Both R2 *and R1 measured were found to change with temperature. The dynamic R1 measurements after heating agreed with the Look-Locker R1 values if changes in equilibrium magnetization with temperature were considered. Release of gadolinium from TSLs was detected by an R1 increase near the phase transition temperature, as well as a shallow R2 * increase. Simultaneous temperature, R2 * and R1 mapping is feasible in real time and has the potential for use in image-guided drug delivery studies.

Magnetic resonance imaging assessment of intraventricular dyssynchrony and delayed enhancement as predictors of response to cardiac resynchronization therapy in patients with heart failure of ischaemic and non-ischaemic etiologies.

PURPOSE: To assess the value of dyssynchrony and myocardial viability assessment by cardiac magnetic resonance (CMR) in prediction of response to cardiac resynchronization therapy (CRT) in patients with heart failure (HF) of both ischaemic and non-ischaemic etiologies. MATERIALS AND METHODS: Patients scheduled for CRT in NYHA class II-IV, left ventricular ejection fraction <35%, QRS ≥ 120 ms were included. Tagged cine and late gadolinium enhancement (LGE) images were performed. Dyssynchrony was assessed with inTag toolbox and LGE was quantified using cutoff value at half of maximal signal in the scar. Cardiopulmonary exercise test, echocardiography and blood testing for NT-proBNP levels were done at baseline and 6 months after CRT. RESULTS: 52 patients (age 60.3 ± 13 years) were included. 26 patients (50%) met response criteria. The ischaemic etiology of HF was more frequent (69% vs. 31%, p=0.002), the percent of LGE was higher (7.7% [0-13.5%] vs. 19.0% (0-31.9%], p=0.013), regional vector of circumferential strain variance (RVV) was lower (0.27 ± 0.08 vs. 0.34 ± 0.09, p=0.009) and uniformity of radial strain was higher (0.72 ± 0.25 vs. 0.56 ± 0.29, p=0.046) in non-responders vs. responders. Multivariate logistic regression showed that RVV predicted response to CRT (HR 2.3, 95% CI 1.02-5.02, p=0.0430) independently of LGE and the etiology of heart failure. In the subgroup of patients with ischaemic HF the extend of transmural scar within myocardium was higher in non-responders vs. responders (26.3% vs. 15.0% respectively, p=0.01) and was a predictor of response to CRT in univariable analysis (HR 0.87, 95% CI 0.77-0.98, p=0.025) providing the sensitivity of 76% and specificity of 75% at the cutoff point of 18% in the prediction of poor response to CRT. In patients with non-ischaemic HF QRS was wider (162 ms vs. 140 ms, p=0.04), regional vector of strain variance (RVV) was higher (0.39 vs. 0.25, p=0.002) and uniformity of radial strain was lower (0.52 vs. 0.80, p=0.049) in non-responders vs. responders. Univariable logistic regression showed that RVV was a predictor of response to CRT (HR 1.50, 95% CI 1.06-2.13, p=0.022), providing the sensitivity of 94% and specificity of 85% at the cutoff point of 0.31. CONCLUSIONS: CMR derived parameters of dyssynchrony such as RVV may provide an additive value in prediction of response to CRT, especially in patients with non-ischaemic etiology of heart failure. In patients with ischaemic HF the transmurality of LGE is an important predictor of lack of response to CRT.

Assessment of vestibulocochlear organ function in patients meeting radiologic criteria of vascular compression syndrome of vestibulocochlear nerve--diagnosis of disabling positional vertigo.

BACKGROUND: This study sought to assess the vestibulo-cochlear organ in patients meeting radiologic criteria of vascular compression syndrome (VCS) of the eighth cranial nerve. MATERIAL/METHODS: The authors performed a retrospective analysis of 34 patients (18 women, 16 men; mean age, 49 years) treated in between 2000 and 2007, with VCS of the eighth cranial nerve by MRI. Contrasted magnetic resonance imaging identified an anterior inferior cerebellar artery vascular loop adhering to the vestibule-cochlear nerve in all 34 cases. All patients were given pure tone audiometry, distortion product otoacoustic emissions, auditory brainstem response, and electroneurographic examinations. RESULTS: Most-common symptoms were unilateral hearing loss (82%), unilateral tinnitus (80%), and dizziness (74%). Most-frequent abnormalities in performed examinations were specific auditory brainstem response changes (interpreted according to Möller's criteria) in 86% of cases and sensorineural hearing loss in pure tone audiometry (82%). Abnormal changes in electronystagmography were found in the absence (12%) or weakness (35%) of a caloric response. No patients were surgically treated. CONCLUSIONS: Significantly, there is no more weakness or absence of the caloric response of a vestibular organ in a patient with vascular compression of the vestibulo-cochlear nerve. Despite an absence of electrophysiologic testing of vestibular organ dysfunction, most examined patients (meeting the radiologic criteria of VCS of the eighth cranial nerve) had subjective symptoms like vertigo and dizziness. Disabling positional vertigo should be considered in the differential diagnosis of vertigo when accompanied by tinnitus or deafness.

CMR assessment of endothelial damage and angiogenesis in porcine coronary arteries using gadofosveset.

BACKGROUND: Endothelial damage and angiogenesis are essential for atherosclerotic plaque development and destabilization. We sought to examine whether contrast enhanced cardiovascular magnetic resonance (CMR) using gadofosveset could show endothelial damage and neovessel formation in balloon injured porcine coronary arteries. METHODS AND RESULTS: Data were obtained from seven pigs that all underwent balloon injury of the left anterior descending coronary artery (LAD) to induce endothelial damage and angiogenesis. Between one - 12 days (average four) after balloon injury, in vivo and ex vivo T1-weighted coronary CMR was performed after intravenous injection of gadofosveset. Post contrast, CMR showed contrast enhancement of the coronary arteries with a selective and time-dependent average expansion of the injured LAD segment area of 45% (p = 0.04; CI95 = [15%-75%]), indicating local extravasation of gadofosveset. Vascular and perivascular extravasation of albumin (marker of endothelial leakiness) and gadofosveset was demonstrated with agreement between Evans blue staining and ex vivo CMR contrast enhancement (p = 0.026). Coronary MRI contrast enhancement and local microvessel density determined by microscopic examination correlated (ρ = 0.82, p < 0.001). CONCLUSION: Contrast enhanced coronary CMR with gadofosveset can detect experimentally induced endothelial damage and angiogenesis in the porcine coronary artery wall.

Diffusion magnetic resonance imaging with gadofosveset trisodium as a negative contrast agent for lymph node metastases assessment.

PURPOSE: The aim of this study was to assess the feasibility of using intravenously administered gadofosveset trisodium as a negative contrast agent for lymph node (LN) assessment with diffusion-weighted imaging (DWI) using a VX2 tumor model in rabbits. MATERIALS AND METHODS: VX2 cells were injected in the right hind limb of five Japanese white rabbits to induce ipsilateral popliteal LN metastasis. DWI was performed before and every 7.5 min (until 1 h) after intravenous gadofosveset trisodium administration, at 1.5 T. Signal intensities (SIs) of right (metastatic) and left (nonmetastatic) popliteal LNs at each time point were measured and compared to each other using two-sided unpaired t-tests. RESULTS: The SIs of metastatic lymph nodes were significantly higher (P < 0.05) than those of nonmetastatic LNs at each time point after intravenous gadofosveset trisodium administration. Although the SI of metastatic LNs was significantly higher (P = 0.0237) than that of nonmetastatic LNs before contrast injection, this difference became even more significant (P ≤ 0.0105) after gadofosveset trisodium administration. CONCLUSION: The SI of metastatic LNs at DWI is less suppressed than that of nonmetastatic LNs after the intravenous administration of gadofosveset trisodium. Therefore, intravenously administered gadofosveset trisodium shows promise for use as a negative contrast agent for discriminating metastatic from nonmetastatic LNs at DWI.