MR and Ultrasound Elastography for Fibrosis Assessment in Children: Practical Implementation and Supporting Evidence-AJR Expert Panel Narrative Review.

Quantitative MRI and ultrasound biomarkers of liver fibrosis have become important tools in the diagnosis and clinical management of children with chronic liver disease (CLD). In particular, MR elastography (MRE) is now routinely performed in clinical practice to evaluate the liver for fibrosis. Ultrasound shear-wave elastography has also become widely performed for this purpose, especially in young children. These noninvasive methods are increasingly used to replace liver biopsy for the diagnosis, quantitative staging, and treatment monitoring of patients with CLD. Although ultrasound has advantages of portability and lower equipment cost, available evidence indicates that MRI may have greater reliability and accuracy in liver fibrosis evaluation. In this AJR Expert Panel Narrative Review, we describe how, why, and when to use MRI- and ultrasound-based elastography methods for liver fibrosis assessment in children. Practical approaches are discussed for adapting and optimizing these methods in children, with consideration of clinical indications, patient preparation, equipment requirements, acquisition technique, as well as pitfalls and confounding factors. Guidance is provided for interpretation and reporting, and representative case examples are presented.

Can Automated 3-Dimensional Dixon-Based Methods Be Used in Patients With Liver Iron Overload?

PURPOSE: Accurate quantification of liver iron concentration (LIC) can be achieved via magnetic resonance imaging (MRI). Maps of liver T2*/R2* are provided by commercially available, vendor-provided, 3-dimensional (3D) multiecho Dixon sequences and allow automated, inline postprocessing, which removes the need for manual curve fitting associated with conventional 2-dimensional (2D) gradient echo (GRE)-based postprocessing. The main goal of our study was to investigate the relationship among LIC estimates generated by 3D multiecho Dixon sequence to values generated by 2D GRE-based R2* relaxometry as the reference standard. METHODS: A retrospective review of patients who had undergone MRI scans for estimation of LIC with conventional T2* relaxometry and 3D multiecho Dixon sequences was performed. A 1.5 T scanner was used to acquire the magnetic resonance studies. Acquisition of standard multislice multiecho T2*-based sequences was performed, and R2* values with corresponding LIC were estimated. The comparison between R2* and corresponding LIC estimates obtained by the 2 methods was analyzed via the correlation coefficients and Bland-Altman difference plots. RESULTS: This study included 104 patients (51 male and 53 female patients) with 158 MRI scans. The mean age of the patients at the time of scan was 15.2 (SD, 8.8) years. There was a very strong correlation between the 2 LIC estimation methods for LIC values up to 3.2 mg/g (LIC quantitative multiecho Dixon [qDixon; from region of interest R2*] vs LIC GRE [in-house]: r = 0.83, P < 0.01; LIC qDixon [from segmentation volume R2*] vs LIC GRE [in-house]: r = 0.92, P < 0.01); and very weak correlation between the 2 methods at liver iron levels >7 mg/g. CONCLUSION: Three-dimensional-based multiecho Dixon technique can accurately measure LIC up to 7 mg/g and has the potential to replace 2D GRE-based relaxometry methods.

How we do it: Cardiac implantable devices are not a contraindication to MRI: time for a paradigm shift.

Magnetic resonance imaging (MRI) is now an indispensable diagnostic tool in medicine due to its outstanding contrast resolution and absence of radiation exposure, enabling detailed tissue characterization and three-dimensional anatomical representation. This is especially important when evaluating individuals with congenital heart disease (CHD) who frequently require cardiac implantable electrical devices (CIEDs). While MRI safety issues have previously limited its use in patients with CIEDs, new advances have called these limitations into question. However, difficulties persist in the pediatric population due to the continued lack of specific safety data both related to imaging young children and the specific CIED devices they often require. This paper discusses MRI safety considerations related to imaging patients with CIEDs, investigates pediatric-specific problems, and describes thorough methods for safe MRI access, highlighting the significance of specialized institutional guidelines.

Quantification of Liver Iron Overload with MRI: Review and Guidelines from the ESGAR and SAR.

Accumulation of excess iron in the body, or systemic iron overload, results from a variety of causes. The concentration of iron in the liver is linearly related to the total body iron stores and, for this reason, quantification of liver iron concentration (LIC) is widely regarded as the best surrogate to assess total body iron. Historically assessed using biopsy, there is a clear need for noninvasive quantitative imaging biomarkers of LIC. MRI is highly sensitive to the presence of tissue iron and has been increasingly adopted as a noninvasive alternative to biopsy for detection, severity grading, and treatment monitoring in patients with known or suspected iron overload. Multiple MRI strategies have been developed in the past 2 decades, based on both gradient-echo and spin-echo imaging, including signal intensity ratio and relaxometry strategies. However, there is a general lack of consensus regarding the appropriate use of these methods. The overall goal of this article is to summarize the current state of the art in the clinical use of MRI to quantify liver iron content and to assess the overall level of evidence of these various methods. Based on this summary, expert consensus panel recommendations on best practices for MRI-based quantification of liver iron are provided.

Imaging fibrosis in pediatric kidney transplantation: A pilot study.

BACKGROUND: Noninvasive alternatives to biopsy for assessment of interstitial fibrosis and tubular atrophy (IFTA), the major determinant of kidney transplant failure, remain profoundly limited. Elastography is a noninvasive technique that propagates shear waves across tissues to measure their stiffness. We aimed to test utility of elastography for early detection of IFTA in pediatric kidney allografts. METHODS: We compared ultrasound (USE) and MR elastography (MRE) stiffness measurements, performed on pediatric transplant recipients referred for clinically indicated biopsies, and healthy controls. RESULTS: Ten transplant recipients (median age 16 years) and eight controls (median age 16.5 years) were enrolled. Three transplant recipients had "stable" allografts and seven had Banff Grade 1 IFTA. Median time from transplantation to biopsy was 12 months. Mean estimated glomerular filtration rate was 61.5 mL/min/1.73m2 by creatinine-cystatin-C CKiD equation at time of biopsy. Mean stiffness, calculated through one-way ANOVA, was higher for IFTA allografts (23.4 kPa USE/5.6 kPa MRE) than stable allografts (13.7 kPa USE/4.4 kPa MRE) and controls (9.1 kPa USE/3.6 kPa MRE). Pearson's coefficient between USE and MRE stiffness values was strong (r = .97). AUC for fibrosis prediction in transplanted kidneys was high for both modalities (0.91 USE and 0.89 MRE), although statistically nonsignificant (p > .05). Stiffness cut-off values for USE and MRE were 13.8 kPa and 4.6 kPa, respectively. Both values yielded a sensitivity of 100% but USE specificity (72%) was slightly higher than MRE (67%). CONCLUSION: Elastography shows potential for detection of low-grade IFTA in allografts although a larger sample is imperative for clinical validation.

Magnetic resonance imaging protocols in pediatric stroke.

Neuroimaging protocols play an important role in the timely evaluation and treatment of pediatric stroke and its mimics. MRI protocols for stroke in the pediatric population should be guided by the clinical scenario and neurologic examination, with consideration of age, suspected infarct type and underlying risk factors. Acute stroke diagnosis and causes in pediatric age groups can differ significantly from those in adult populations, and delay in stroke diagnosis among children is a common problem. An awareness of pediatric stroke presentations and risk factors among pediatric emergency physicians, neurologists, pediatricians, subspecialists and radiologists is critical to ensuring timely diagnosis. Given special considerations related to unique pediatric stroke risk factors and the need for sedation in some children, expert consensus guidelines for the imaging of suspected pediatric infarct have been proposed. In this article the authors review standard and rapid MRI protocols for the diagnosis of pediatric stroke, as well as the key differences between pediatric and adult stroke imaging.

Consensus-Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI.

BACKGROUND: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool. PURPOSE: To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies. STUDY TYPE: Systematic consensus process using a modified Delphi method. POPULATION: Not applicable. SEQUENCE FIELD/STRENGTH: Renal fast gradient echo-based 2D PC-MRI. ASSESSMENT: An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4-10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated. STATISTICAL TESTS: Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60-74% agreement among the experts. RESULTS: Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting. DATA CONCLUSION: These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Basics of magnetic resonance imaging and quantitative parameters T1, T2, T2*, T1rho and diffusion-weighted imaging.

Magnetic resonance imaging is widely available and accepted as the imaging method of choice for many pediatric body imaging applications. Traditionally, it has been used in a qualitative way, where the images are reported non-numerically by radiologists. But now MRI machines have built-in post-processing software connected to the scanner and the database of MR images. This setting enables and encourages simple quantitative analysis of MR images. In this paper, the author reviews the fundamentals of MRI and discusses the most common quantitative MRI techniques for body imaging: T1, T2, T2*, T1rho and diffusion-weighted imaging (DWI). For each quantitative imaging method, this article reviews the technique, its measurement mechanism, and selected clinical applications to body imaging.

Linearity and Bias of Proton Density Fat Fraction as a Quantitative Imaging Biomarker: A Multicenter, Multiplatform, Multivendor Phantom Study.

Background Proton density fat fraction (PDFF) estimated by using chemical shift-encoded (CSE) MRI is an accepted imaging biomarker of hepatic steatosis. This work aims to promote standardized use of CSE MRI to estimate PDFF. Purpose To assess the accuracy of CSE MRI methods for estimating PDFF by determining the linearity and range of bias observed in a phantom. Materials and Methods In this prospective study, a commercial phantom with 12 vials of known PDFF values were shipped across nine U.S. centers. The phantom underwent 160 independent MRI examinations on 27 1.5-T and 3.0-T systems from three vendors. Two three-dimensional CSE MRI protocols with minimal T1 bias were included: vendor and standardized. Each vendor's confounder-corrected complex or hybrid magnitude-complex based reconstruction algorithm was used to generate PDFF maps in both protocols. The Siemens reconstruction required a configuration change to correct for water-fat swaps in the phantom. The MRI PDFF values were compared with the known PDFF values by using linear regression with mixed-effects modeling. The 95% CIs were calculated for the regression slope (ie, proportional bias) and intercept (ie, constant bias) and compared with the null hypothesis (slope = 1, intercept = 0). Results Pooled regression slope for estimated PDFF values versus phantom-derived reference PDFF values was 0.97 (95% CI: 0.96, 0.98) in the biologically relevant 0%-47.5% PDFF range. The corresponding pooled intercept was -0.27% (95% CI: -0.50%, -0.05%). Across vendors, slope ranges were 0.86-1.02 (vendor protocols) and 0.97-1.0 (standardized protocol) at 1.5 T and 0.91-1.01 (vendor protocols) and 0.87-1.01 (standardized protocol) at 3.0 T. The intercept ranges (absolute PDFF percentage) were -0.65% to 0.18% (vendor protocols) and -0.69% to -0.17% (standardized protocol) at 1.5 T and -0.48% to 0.10% (vendor protocols) and -0.78% to -0.21% (standardized protocol) at 3.0 T. Conclusion Proton density fat fraction estimation derived from three-dimensional chemical shift-encoded MRI in a commercial phantom was accurate across vendors, imaging centers, and field strengths, with use of the vendors' product acquisition and reconstruction software. © RSNA, 2021 See also the editorial by Dyke in this issue.

Temperature-corrected proton density fat fraction estimation using chemical shift-encoded MRI in phantoms.

PURPOSE: Chemical shift-encoded MRI (CSE-MRI) is well-established to quantify proton density fat fraction (PDFF) as a quantitative biomarker of hepatic steatosis. However, temperature is known to bias PDFF estimation in phantom studies. In this study, strategies were developed and evaluated to correct for the effects of temperature on PDFF estimation through simulations, temperature-controlled experiments, and a multi-center, multi-vendor phantom study. THEORY AND METHODS: A technical solution that assumes and automatically estimates a uniform, global temperature throughout the phantom is proposed. Computer simulations modeled the effect of temperature on PDFF estimation using magnitude-, complex-, and hybrid-based CSE-MRI methods. Phantom experiments were performed to assess the temperature correction on PDFF estimation at controlled phantom temperatures. To assess the temperature correction method on a larger scale, the proposed method was applied to data acquired as part of a nine-site multi-vendor phantom study and compared to temperature-corrected PDFF estimation using an a priori guess for ambient room temperature. RESULTS: Simulations and temperature-controlled experiments show that as temperature deviates further from the assumed temperature, PDFF bias increases. Using the proposed correction method and a reasonable a priori guess for ambient temperature, PDFF bias and variability were reduced using magnitude-based CSE-MRI, across MRI systems, field strengths, protocols, and varying phantom temperature. Complex and hybrid methods showed little PDFF bias and variability both before and after correction. CONCLUSION: Correction for temperature reduces temperature-related PDFF bias and variability in phantoms across MRI vendors, sites, field strengths, and protocols for magnitude-based CSE-MRI, even without a priori information about the temperature.

Pediatric Lung MRI: Currently Available and Emerging Techniques.

OBJECTIVE. The purpose of this article is to review currently available and emerging techniques for pediatric lung MRI for general radiologists. CONCLUSION. MRI is a radiation-free alternative to CT, and clearly understanding the strengths and limitations of established and emerging techniques of pediatric lung MRI can allow practitioners to select and combine the optimal techniques, apply them in clinical practice, and potentially improve early diagnostic accuracy and patient management.

Components of a magnetic resonance imaging system and their relationship to safety and image quality.

Magnetic resonance imaging (MRI) is a powerful diagnostic tool that can be optimized to display a wide range of clinical conditions. An MRI system consists of four major components: a main magnet formed by superconducting coils, gradient coils, radiofrequency (RF) coils, and computer systems. Each component has safety considerations. Unless carefully controlled, the MRI machine's strong static magnetic field could turn a ferromagnetic object into a harmful projectile or cause vertigo and headache. Switching magnetic fields in the gradients evokes loud noises in the scanner, which can be mitigated by ear protection. Gradients also generate varying magnetic fields that can cause peripheral nerve stimulation and muscle twitching. Magnetic fields produced by RF coils deposit energy in the body and can cause tissue heating (with the potential to cause skin burns). In this review, we provide an overview of the components of a typical clinical MRI scanner and its associated safety issues. We also discuss how the relationship between the scanning parameters can be manipulated to improve image quality while ensuring a safe operational environment for the patients and staff. Understanding the strengths and limitations of these parameters can enable users to choose optimal techniques for image acquisition, apply them in clinical practice, and improve the diagnostic accuracy of an MRI examination.

Safety challenges related to the use of sedation and general anesthesia in pediatric patients undergoing magnetic resonance imaging examinations.

The use of sedation and general anesthesia has facilitated the significant growth of MRI use among children over the last years. While sedation and general anesthesia are considered to be relatively safe, their use poses potential risks in the short term and in the long term. This manuscript reviews the reasons why MRI examinations require sedation and general anesthesia more commonly in the pediatric population, summarizes the safety profile of sedation and general anesthesia, and discusses an amalgam of strategies that can be implemented and can ultimately lead to the optimization of sedation and general anesthesia care within pediatric radiology departments.

Establishing a magnetic resonance safety program.

Establishing a magnetic resonance (MR) safety program is crucial to ensuring the safe MR imaging of pediatric patients. The organizational structure includes a core safety council and broader safety committee comprising all key stakeholders. These groups work in synchrony to establish a strong culture of safety; create and maintain policies and procedures; implement device regulations for entry into the MR setting; construct MR safety zones; address intraoperative MR concerns; guarantee safe scanning parameters, including complying with specific absorption rate limitations; adhere to national regulatory body guidelines; and ensure appropriate communication among all parties in the MR environment. Perspectives on the duties of the safety council members provide important insight into the organization of program oversite. Ultimately, the collective dedication and vigilance of all MR staff are crucial to the success of a safety program.

Specific Absorption Rate and Specific Energy Dose: Comparison of 1.5-T versus 3.0-T Fetal MRI.

Background MRI performed at 3.0 T offers greater signal-to-noise ratio and better spatial resolution than does MRI performed at 1.5 T; however, for fetal MRI, there are concerns about the potential for greater radiofrequency energy administered to the fetus at 3.0-T MRI. Purpose To compare the specific absorption rate (SAR) and specific energy dose (SED) of fetal MRI at 1.5 and 3.0 T. Materials and Methods In this retrospective study, all fetal MRI examinations performed with 1.5- and 3.0-T scanners at one institution between July 2012 and October 2016 were evaluated. Two-dimensional (2D) and three-dimensional (3D) steady-state free precession (SSFP), single-shot fast spin-echo, 2D and 3D T1-weighted spoiled gradient-echo (SPGR), and echo-planar imaging sequences were performed. SAR, SED, accumulated SED, and acquisition time were retrieved from the Digital Imaging and Communications in Medicine header. Data are presented as mean ± standard deviation. Two one-sided tests with equivalence bounds of 0.5 (Cohen d effect size) were performed, with statistical equivalence considered at P < .05. Results A total of 2952 pregnant women were evaluated. Mean maternal age was 30 years ± 6 (age range, 12-49 years), mean gestational age was 24 weeks ± 6 (range, 17-40 weeks). A total of 3247 fetal MRI scans were included, with 2784 (86%) obtained at 1.5 T and 463 (14%) obtained at 3.0 T. In total, 93 764 sequences were performed, with 81 535 (87%) performed at 1.5 T and 12 229 (13%) performed at 3.0 T. When comparing 1.5- with 3.0-T MRI sequences, mean SAR (1.09 W/kg ± 0.69 vs 1.14 W/kg ± 0.61), mean SED (33 J/kg ± 27 vs 38 J/kg ± 26), and mean accumulated SED (965 J/kg ± 408 vs 996 J/kg ± 366, P < .001) were equivalent. Conclusion Fetal 1.5- and 3.0-T MRI examinations were found to have equivalent energy metrics in most cases. The 3.0-T sequences, such as two-dimensional T1-weighted spoiled gradient-echo and three-dimensional steady-state free precession, may require modification to keep the energy delivered to the patient as low as possible. © RSNA, 2020 Online supplemental material is available for this article.

Normal Liver Stiffness Measured with MR Elastography in Children.

Background Stiffness thresholds for liver MR elastography in children vary between studies and may differ from thresholds in adults. Normative liver stiffness data are needed to optimize diagnostic thresholds for children. Purpose To determine normal liver stiffness, and associated normal ranges for children, as measured with MR elastography across vendors and field strengths. Materials and Methods This was a prospective multicenter cohort study (ClinicalTrials.gov identifier: NCT03235414). Volunteers aged 7-17.9 years without a known history of liver disease were recruited at four sites for a research MRI and blood draw between February 2018 and October 2019. MRI was performed on three vendor platforms and at two field strengths (1.5 T and 3.0 T). All MRI scans were centrally analyzed; stiffness, proton density fat fraction (PDFF), and R2* values were expressed as means of means. Mean and 95% confidence intervals (CIs) for liver stiffness were calculated. Pearson correlation coefficient (r), two-sample t test, or analysis of variance was used to assess univariable associations. Results Seventy-one volunteers had complete data and no documented exclusion criterion (median age, 12 years; interquartile range [IQR], 10-15 years; 39 female participants). Median body mass index percentile was 54% (IQR, 32.5%-69.5%). Mean liver stiffness was 2.1 kPa (95% CI: 2.0, 2.2 kPa) with mean ± 1.96 kPa standard deviation of 1.5-2.8 kPa. Median liver PDFF was 2.0% (IQR, 1.7%-2.6%). There was no association between liver stiffness and any patient variable or MRI scanner factor. Conclusion Mean liver stiffness measured with MR elastography in children without liver disease was 2.1 kPa (similar to that in adults). The 95th percentile of normal liver stiffness was 2.8 kPa. Liver stiffness was independent of sex, age, or body mass index and did not vary with MRI scanner vendor or field strength. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Yin in this issue.

Newly Developed Methods for Reducing Motion Artifacts in Pediatric Abdominal MRI: Tips and Pearls.

OBJECTIVE. The purpose of this article is to review established and emerging methods for reducing motion artifacts in pediatric abdominal MRI. CONCLUSION. Clearly understanding the strengths and limitations of motion reduction methods can enable practitioners of pediatric abdominal MRI to select and combine the appropriate techniques and potentially reduce the need for sedation and anesthesia.

DTI of the kidney in children: comparison between normal kidneys and those with ureteropelvic junction (UPJ) obstruction.

OBJECTIVE: To compare renal diffusion tensor imaging (DTI) parameters in patients with or without ureteropelvic junction (UPJ) obstruction. METHODS: Patients that underwent functional MR urography (MRU) with renal DTI were retrospectively selected. Kidneys deemed normal on T2-weighted images and functional parameters were used as controls and compared to those kidneys with morphologic and functional findings of UPJ obstruction. DTI included a 20-direction DTI with b values of b = 0 s/mm2 and b = 400 s/mm2. Diffusion Toolkit was used for analysis and segmentation. TrackVis was used to draw regions of interest (ROI) covering the entire volume of the renal parenchyma, excluding the collecting system. Fibers were reconstructed using a deterministic fiber tracking algorithm. Whole kidney ROI-based analysis was performed to obtain cortico-medullary measurements (FA, ADC and track length) for each kidney. T tests were performed to compare means and statistical significance was defined at p < 0.05. RESULTS: 118 normal kidneys from 102 patients (median age 7 years, IQR 6-15 years; 58 males and 44 females) were compared to 22 kidneys from 16 patients (median age 13 years, IQR 3-15 years; 9 males and 7 females) with UPJ obstruction. Mean FA values were significantly lower (0.31 ± 0.07; n = 22) in kidneys with UPJ obstruction than normal kidneys (0.40 ± 0.08; n = 118) (p < 0.001). ADC was marginally significantly increased (p = 0.01) and track length was not significantly different (p = 0.24). CONCLUSION: Our results suggest that DTI-derived metrics including FA and ADC are potential biomarkers to differentiate kidneys with UPJ obstruction and assess renal parenchymal damage.

Correction to: Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI.

The article Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI.

Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI.

OBJECTIVES: Standardization is an important milestone in the validation of DWI-based parameters as imaging biomarkers for renal disease. Here, we propose technical recommendations on three variants of renal DWI, monoexponential DWI, IVIM and DTI, as well as associated MRI biomarkers (ADC, D, D*, f, FA and MD) to aid ongoing international efforts on methodological harmonization. MATERIALS AND METHODS: Reported DWI biomarkers from 194 prior renal DWI studies were extracted and Pearson correlations between diffusion biomarkers and protocol parameters were computed. Based on the literature review, surveys were designed for the consensus building. Survey data were collected via Delphi consensus process on renal DWI preparation, acquisition, analysis, and reporting. Consensus was defined as ≥ 75% agreement. RESULTS: Correlations were observed between reported diffusion biomarkers and protocol parameters. Out of 87 survey questions, 57 achieved consensus resolution, while many of the remaining questions were resolved by preference (65-74% agreement). Summary of the literature and survey data as well as recommendations for the preparation, acquisition, processing and reporting of renal DWI were provided. DISCUSSION: The consensus-based technical recommendations for renal DWI aim to facilitate inter-site harmonization and increase clinical impact of the technique on a larger scale by setting a framework for acquisition protocols for future renal DWI studies. We anticipate an iterative process with continuous updating of the recommendations according to progress in the field.