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Methodological consensus on clinical proton MRS of the brain: Review and recommendations.
Wilson, M, Andronesi, O, Barker, PB, Bartha, R, Bizzi, A, Bolan, PJ, Brindle, KM, Choi, IY, Cudalbu, C, Dydak, U, et al
Magnetic resonance in medicine. 2019;(2):527-550
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Abstract
Proton MRS (1 H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good-quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi-adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0 ) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use.
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A new MRI marker of ataxia with oculomotor apraxia.
Ronsin, S, Hannoun, S, Thobois, S, Petiot, P, Vighetto, A, Cotton, F, Tilikete, C
European journal of radiology. 2019;:187-192
Abstract
PURPOSE Evaluate the specificity and sensitivity of disappearance of susceptibility weighted imaging (SWI) dentate nuclei (DN) hypointensity in oculomotor apraxia patients (AOA). METHOD In this prospective study, 27 patients with autosomal genetic ataxia (AOA (n = 11), Friedreich ataxia and ataxia with vitamin E deficit (n = 4), and dominant genetic ataxia (n = 12)) were included along with fifteen healthy controls. MRIs were qualitatively classified for the presence or absence of DN hypointensity on FLAIR and SWI sequences. The MRIs were then quantitatively studied, with measurement of a ratio of DN over brainstem white matter signal intensity through manual delineation. The institutional review board approved this study, and written informed consent was obtained. In the cross-sectional analysis, the Mann-Whitney test was applied. RESULTS Qualitatively, the eleven AOA patients presented absence of both DN SWI and FLAIR hyposignals; three dominant genetic ataxia patients had moderate SWI DN hyposignal and absent FLAIR hyposignal; the thirteen remaining subjects presented normal SWI and FLAIR DN hyposignal. Absence of DN SWI hypointensity was 100% sensitive and specific to AOA. Quantitative signal intensity ratio (mean ± standard deviation) of the AOA group (98·96 ± 5·37%) was significantly higher than in control subjects group (76.40 ± 8.34%; p < 0.001), dominant genetic ataxia group (81·15 ± 9·94%; p < 0·001), and Friedreich ataxia and ataxia with vitamin E deficit group (87·56 ± 2·78%; p < 0·02). CONCLUSION This small study shows that loss of the normal hypointensity in the dentate nucleus on both SWI and FLAIR imaging at 3 T is a highly sensitive and specific biomarker for AOA.
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Absolute Quantification of Phosphor-Containing Metabolites in the Liver Using 31 P MRSI and Hepatic Lipid Volume Correction at 7T Suggests No Dependence on Body Mass Index or Age.
Pfleger, L, Gajdošík, M, Wolf, P, Smajis, S, Fellinger, P, Kuehne, A, Krumpolec, P, Trattnig, S, Winhofer, Y, Krebs, M, et al
Journal of magnetic resonance imaging : JMRI. 2019;(2):597-607
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Abstract
BACKGROUND Hepatic disorders are often associated with changes in the concentration of phosphorus-31 (31 P) metabolites. Absolute quantification offers a way to assess those metabolites directly but introduces obstacles, especially at higher field strengths (B0 ≥ 7T). PURPOSE To introduce a feasible method for in vivo absolute quantification of hepatic 31 P metabolites and assess its clinical value by probing differences related to volunteers' age and body mass index (BMI). STUDY TYPE Prospective cohort. SUBJECTS/PHANTOMS Four healthy volunteers included in the reproducibility study and 19 healthy subjects arranged into three subgroups according to BMI and age. Phantoms containing 31 P solution for correction and validation. FIELD STRENGTH/SEQUENCE Phase-encoded 3D pulse-acquire chemical shift imaging for 31 P and single-volume 1 H spectroscopy to assess the hepatocellular lipid content at 7T. ASSESSMENT A phantom replacement method was used. Spectra located in the liver with sufficient signal-to-noise ratio and no contamination from muscle tissue, were used to calculate following metabolite concentrations: adenosine triphosphates (γ- and α-ATP); glycerophosphocholine (GPC); glycerophosphoethanolamine (GPE); inorganic phosphate (Pi ); phosphocholine (PC); phosphoethanolamine (PE); uridine diphosphate-glucose (UDPG); nicotinamide adenine dinucleotide-phosphate (NADH); and phosphatidylcholine (PtdC). Correction for hepatic lipid volume fraction (HLVF) was performed. STATISTICAL TESTS Differences assessed by analysis of variance with Bonferroni correction for multiple comparison and with a Student's t-test when appropriate. RESULTS The concentrations for the young lean group corrected for HLVF were 2.56 ± 0.10 mM for γ-ATP (mean ± standard deviation), α-ATP: 2.42 ± 0.15 mM, GPC: 3.31 ± 0.27 mM, GPE: 3.38 ± 0.87 mM, Pi : 1.42 ± 0.20 mM, PC: 1.47 ± 0.24 mM, PE: 1.61 ± 0.20 mM, UDPG 0.74 ± 0.17 mM, NADH 1.21 ± 0.38 mM, and PtdC: 0.43 ± 0.10 mM. Differences found in ATP levels between lean and overweight volunteers vanished after HLVF correction. DATA CONCLUSION Exploiting the excellent spectral resolution at 7T and using the phantom replacement method, we were able to quantify up to 10 31 P-containing hepatic metabolites. The combination of 31 P magnetic resonance spectroscopy imaging data acquisition and HLVF correction was not able to show a possible dependence of 31 P metabolite concentrations on BMI or age, in the small healthy population used in this study. LEVEL OF EVIDENCE 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:597-607.
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The diagnostic performance of gadoxetic acid disodium-enhanced magnetic resonance imaging and contrast-enhanced multi-detector computed tomography in detecting hepatocellular carcinoma: a meta-analysis of eight prospective studies.
Li, J, Wang, J, Lei, L, Yuan, G, He, S
European radiology. 2019;(12):6519-6528
Abstract
AIM: The purpose of this study was to determine the relative diagnostic benefit of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) over contrast-enhanced multi-detector computed tomography (CEMDCT) for the detection of hepatocellular carcinoma (HCC). METHODS Two investigators searched multiple databases from inception to January 8, 2019, for studies comparing Gd-EOB-DTPA-enhanced MRI with CEMDCT in adults suspected of HCC. Two reviewers independently selected studies and extracted data. RESULTS Eight studies were included enrolling 498 patients. MRI showed significantly higher sensitivity than CT (0.85 vs. 0.68). There was no significant difference in the specificity of MRI and CT (0.94 vs. 0.93). The negative likelihood ratio and positive likelihood ratio of MRI and CT were not significantly different (0.16 vs. 0.15 and 14.7 vs. 11.2, respectively). The summary receiver operating characteristics (SROC) of MRI was higher than that of CT at 0.96 vs. 0.91. In the subgroup analysis with a lesion diameter below 2 cm, the sensitivity of MRI was significantly higher than that of CT (0.79 vs. 0.46). CONCLUSION Gd-EOB-DTPA-enhanced MRI showed higher sensitivity and overall diagnostic accuracy than CEMDCT especially for hepatocellular carcinoma lesions smaller than 2 cm. KEY POINTS • Gd-EOB-DTPA-enhanced MRI can detect small lesions of hepatocellular carcinoma. • Gd-EOB-DTPA-enhanced MRI showed higher sensitivity and overall diagnostic accuracy than CEMDCT in patients with hepatocellular carcinoma. • Eight prospective studies showed that Gd-EOB-DTPA-enhanced MRI provides greater diagnostic confidence.
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Fast NMR method to probe solvent accessibility and disordered regions in proteins.
Faustino, AF, Barbosa, GM, Silva, M, Castanho, MARB, Da Poian, AT, Cabrita, EJ, Santos, NC, Almeida, FCL, Martins, IC
Scientific reports. 2019;(1):1647
Abstract
Understanding protein structure and dynamics, which govern key cellular processes, is crucial for basic and applied research. Intrinsically disordered protein (IDP) regions display multifunctionality via alternative transient conformations, being key players in disease mechanisms. IDP regions are abundant, namely in small viruses, allowing a large number of functions out of a small proteome. The relation between protein function and structure is thus now seen from a different perspective: as IDP regions enable transient structural arrangements, each conformer can play different roles within the cell. However, as IDP regions are hard and time-consuming to study via classical techniques (optimized for globular proteins with unique conformations), new methods are required. Here, employing the dengue virus (DENV) capsid (C) protein and the immunoglobulin-binding domain of streptococcal protein G, we describe a straightforward NMR method to differentiate the solvent accessibility of single amino acid N-H groups in structured and IDP regions. We also gain insights into DENV C flexible fold region biological activity. The method, based on minimal pH changes, uses the well-established 1H-15N HSQC pulse sequence and is easily implementable in current protein NMR routines. The data generated are simple to interpret, with this rapid approach being an useful first-choice IDPs characterization method.
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The effect of acute cocoa flavanol intake on the BOLD response and cognitive function in type 1 diabetes: a randomized, placebo-controlled, double-blinded cross-over pilot study.
Decroix, L, van Schuerbeek, P, Tonoli, C, van Cutsem, J, Soares, DD, Heyman, E, Vanderhasselt, T, Verrelst, R, Raeymaekers, H, de Mey, J, et al
Psychopharmacology. 2019;(12):3421-3428
Abstract
RATIONALE Type 1 diabetes (T1D), a chronic autoimmune disease, can result in cognitive dysfunction and is associated with vascular dysfunction. Cocoa flavanols (CFs) can stimulate nitric oxide-dependent vasodilation, resulting in enhanced hemodynamic responses and better cognitive function. OBJECTIVES To investigate whether acute CF supplementation can improve cognitive function and hemodynamic responses in T1D. METHODS In this randomized, double-blinded, cross-over pilot study, 11 patients with T1D and their healthy matched controls consumed CF (900 mg CF) and placebo (15 mg CF) 2 h before a flanker test. fMRI was used to measure blood oxygen level-dependent (BOLD) response during the cognitive test. Repeated measure ANOVAs were used to test the effects of CF and T1D on BOLD response and cognitive performance. RESULTS CF improved reaction time on the flanker test and increased the BOLD response in the supramarginal gyrus parietal lobe and inferior frontal gyrus, compared to placebo, in both groups. In patients with T1D, cognitive performance was not deteriorated while the BOLD response was smaller in T1D compared to healthy controls in the subgyral temporal lobe and the cerebellum. CONCLUSIONS Acute CF intake improved reaction time on the flanker test and increased the BOLD response in the activated brain areas in patients with T1D and their matched controls.
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Measurement of synovial tissue volume in knee osteoarthritis using a semiautomated MRI-based quantitative approach.
Perry, TA, Gait, A, O'Neill, TW, Parkes, MJ, Hodgson, R, Callaghan, MJ, Arden, NK, Felson, DT, Cootes, TF
Magnetic resonance in medicine. 2019;(5):3056-3064
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Abstract
PURPOSE Synovitis is common in knee osteoarthritis and is associated with both knee pain and progression of disease. Semiautomated methods have been developed for quantitative assessment of structure in knee osteoarthritis. Our aims were to apply a novel semiautomated assessment method using 3D active appearance modeling for the quantification of synovial tissue volume (STV) and to compare its performance with conventional manual segmentation. METHODS Thirty-two sagittal T1 -weighted fat-suppressed contrast-enhanced MRIs were assessed for STV by a single observer using 1) manual segmentation and 2) a semiautomated approach. We compared the STV analysis using the semiautomated and manual segmentation methods, including the time taken to complete the assessments. We also examined the reliability of STV assessment using the semiautomated method in a subset of 12 patients who had participated in a clinical trial of vitamin D therapy in knee osteoarthritis. RESULTS There was no significant difference in STV using the semiautomated quantitative method compared to manual segmentation, mean difference = 207.2 mm3 (95% confidence interval -895.2 to 1309.7). The semiautomated method was significantly quicker than manual segmentation (18 vs. 71 min). For the semiautomated method, intraobserver agreement was excellent (intraclass correlation coefficient (3,1) = 0.99) and interobserver agreement was very good (intraclass correlation coefficient (3,1) = 0.83). CONCLUSION We describe the application of a semiautomated method that is accurate, reliable, and quicker than manual segmentation for assessment of STV. The method may help increase efficiency of image assessment in large imaging studies and may also assist investigation of treatment efficacy in knee osteoarthritis.
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Magnetic resonance thermometry and its biological applications - Physical principles and practical considerations.
Odéen, H, Parker, DL
Progress in nuclear magnetic resonance spectroscopy. 2019;:34-61
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Abstract
Most parameters that influence the magnetic resonance imaging (MRI) signal experience a temperature dependence. The fact that MRI can be used for non-invasive measurements of temperature and temperature change deep inside the human body has been known for over 30 years. Today, MR temperature imaging is widely used to monitor and evaluate thermal therapies such as radio frequency, microwave, laser, and focused ultrasound therapy. In this paper we cover the physical principles underlying the biological applications of MR temperature imaging and discuss practical considerations and remaining challenges. For biological tissue, the MR signal of interest comes mostly from hydrogen protons of water molecules but also from protons in, e.g., adipose tissue and various metabolites. Most of the discussed methods, such as those using the proton resonance frequency (PRF) shift, T1, T2, and diffusion only measure temperature change, but measurements of absolute temperatures are also possible using spectroscopic imaging methods (taking advantage of various metabolite signals as internal references) or various types of contrast agents. Currently, the PRF method is the most used clinically due to good sensitivity, excellent linearity with temperature, and because it is largely independent of tissue type. Because the PRF method does not work in adipose tissues, T1- and T2-based methods have recently gained interest for monitoring temperature change in areas with high fat content such as the breast and abdomen. Absolute temperature measurement methods using spectroscopic imaging and contrast agents often offer too low spatial and temporal resolution for accurate monitoring of ablative thermal procedures, but have shown great promise in monitoring the slower and usually less spatially localized temperature change observed during hyperthermia procedures. Much of the current research effort for ablative procedures is aimed at providing faster measurements, larger field-of-view coverage, simultaneous monitoring in aqueous and adipose tissues, and more motion-insensitive acquisitions for better precision measurements in organs such as the heart, liver, and kidneys. For hyperthermia applications, larger coverage, motion insensitivity, and simultaneous aqueous and adipose monitoring are also important, but great effort is also aimed at solving the problem of long-term field drift which gets interpreted as temperature change when using the PRF method.
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White matter hyperintensity quantification in large-scale clinical acute ischemic stroke cohorts - The MRI-GENIE study.
Schirmer, MD, Dalca, AV, Sridharan, R, Giese, AK, Donahue, KL, Nardin, MJ, Mocking, SJT, McIntosh, EC, Frid, P, Wasselius, J, et al
NeuroImage. Clinical. 2019;:101884
Abstract
White matter hyperintensity (WMH) burden is a critically important cerebrovascular phenotype linked to prediction of diagnosis and prognosis of diseases, such as acute ischemic stroke (AIS). However, current approaches to its quantification on clinical MRI often rely on time intensive manual delineation of the disease on T2 fluid attenuated inverse recovery (FLAIR), which hinders high-throughput analyses such as genetic discovery. In this work, we present a fully automated pipeline for quantification of WMH in clinical large-scale studies of AIS. The pipeline incorporates automated brain extraction, intensity normalization and WMH segmentation using spatial priors. We first propose a brain extraction algorithm based on a fully convolutional deep learning architecture, specifically designed for clinical FLAIR images. We demonstrate that our method for brain extraction outperforms two commonly used and publicly available methods on clinical quality images in a set of 144 subject scans across 12 acquisition centers, based on dice coefficient (median 0.95; inter-quartile range 0.94-0.95; p < 0.01) and Pearson correlation of total brain volume (r = 0.90). Subsequently, we apply it to the large-scale clinical multi-site MRI-GENIE study (N = 2783) and identify a decrease in total brain volume of -2.4 cc/year. Additionally, we show that the resulting total brain volumes can successfully be used for quality control of image preprocessing. Finally, we obtain WMH volumes by building on an existing automatic WMH segmentation algorithm that delineates and distinguishes between different cerebrovascular pathologies. The learning method mimics expert knowledge of the spatial distribution of the WMH burden using a convolutional auto-encoder. This enables successful computation of WMH volumes of 2533 clinical AIS patients. We utilize these results to demonstrate the increase of WMH burden with age (0.950 cc/year) and show that single site estimates can be biased by the number of subjects recruited.
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T2* Mapping Techniques: Iron Overload Assessment and Other Potential Clinical Applications.
Menacho, K, Abdel-Gadir, A, Moon, JC, Fernandes, JL
Magnetic resonance imaging clinics of North America. 2019;(3):439-451
Abstract
T2* mapping techniques has evolved significantly since their introduction in the early 2000s and a significant amount of evidence has been gathered to support their clinical routine use for iron overload assessment. This article focuses on the most important aspects of how to perform T2* imaging, from acquisition, to postprocessing, to analyzing the data with clinical concentration. Newer techniques have made T2* mapping more robust and accurate, allowing a broader use of this technique for noncontrast ischemia imaging based on blood oxygen levels, in addition to evaluation of intramyocardial hemorrhage and microvascular obstruction.