Inhibition of the AURKA/YAP1 axis is a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells.

BACKGROUND: Primary resistance to anti-EGFR therapies affects 40% of metastatic colorectal cancer patients harbouring wild-type RAS/RAF. YAP1 activation is associated with this resistance, prompting an investigation into AURKA's role in mediating YAP1 phosphorylation at Ser397, as observed in breast cancer. METHODS: We used transcriptomic analysis along with in vitro and in vivo models of RAS/RAF wild-type CRC to study YAP1 Ser397 phosphorylation as a potential biomarker for cetuximab resistance. We assessed cetuximab efficacy using CCK8 proliferation assays and cell cycle analysis. Additionally, we examined the effects of AURKA inhibition with alisertib and created a dominant-negative YAP1 Ser397 mutant to assess its impact on cancer stem cell features. RESULTS: The RAS/RAF wild-type CRC models exhibiting primary resistance to cetuximab prominently displayed elevated YAP1 phosphorylation at Ser397 primarily mediated by AURKA. AURKA-induced YAP1 phosphorylation was identified as a key trigger for cancer stem cell reprogramming. Consequently, we found that AURKA inhibition had the capacity to effectively restore cetuximab sensitivity and concurrently suppress the cancer stem cell phenotype. CONCLUSIONS: AURKA inhibition holds promise as a therapeutic approach to overcome cetuximab resistance in RAS/RAF wild-type colorectal cancer, offering a potential means to counter the development of cancer stem cell phenotypes associated with cetuximab resistance.

Surgery for acute subdural hematoma: the value of pre-emptive decompressive craniectomy by propensity score analysis.

BACKGROUND: Acute subdural hematomas (ASDH) are found frequently following traumatic brain injury (TBI) and they are considered the most lethal type of mass lesions. The decision to perform a procedure to evacuate ASDH and the approach, either via craniotomy or decompressive craniectomy (DC), remains controversial. METHODS: We reviewed a prospectively collected series of 343 moderate to severe TBI patients in whom ASDH was the main lesion (ASDH volumes ≥10 cc). Patients with early comfort measures (early mortality prediction >50% and not ICP monitored), bilateral ASDH or the presence of another intracranial hematoma with volumes exceeding two times the volume of the ASDH were excluded. Among them, 112 were managed conservatively, 65 underwent ASDH evacuation by craniotomy and 166 by DC (103 pre-emptive DC, 63 obligatory DC). We calculated the average treatment effect by propensity score (PS) analysis using the following covariates: age, year, hypoxia, shock, pupils, major extracranial injury, motor score, midline shift, ASDH volume, swelling, intraventricular and subarachnoid hemorrhage presence. Then, multivariable binary regression and ordinal logistic regression analysis were performed to estimate associations between predictors and mortality and 12 months-GOS respectively. The patients' inverse probability weights were included as an independent variable in both regression models. RESULTS: The main variables associated with outcome were year, age, falls from patient´s own height, hypoxia, early deterioration, pupillary abnormalities, basal cistern effacement, compliance to ICP monitoring guidelines and type of surgical approach (craniotomy and pre-emptive DC). CONCLUSIONS: According to sliding dichotomy analysis, we found that patients in the intermediate or worst bands of unfavorable outcome prognosis seemed to achieve better than expected outcome if they underwent pre-emptive DC rather than craniotomy.

Serum assessment of traumatic axonal injury: the correlation of GFAP, t-Tau, UCH-L1, and NfL levels with diffusion tensor imaging metrics and its prognosis utility.

OBJECTIVE: Diagnosis of traumatic axonal injury (TAI) is challenging because of its underestimation by conventional MRI and the technical requirements associated with the processing of diffusion tensor imaging (DTI). Serum biomarkers seem to be able to identify patients with abnormal CT scanning findings, but their potential role to assess TAI has seldomly been explored. METHODS: Patients with all severities of traumatic brain injury (TBI) were prospectively included in this study between 2016 and 2021. They underwent blood extraction within 24 hours after injury and imaging assessment, including DTI. Serum concentrations of glial fibrillary acidic protein, total microtubule-associated protein (t-Tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and neurofilament light chain (NfL) were measured using an ultrasensitive Simoa multiplex assay panel, a digital form of enzyme-linked immunosorbent assay. The Glasgow Outcome Scale-Extended score was determined at 6 months after TBI. The relationships between biomarker concentrations, volumetric analysis of corpus callosum (CC) lesions, and fractional anisotropy (FA) were analyzed by nonparametric tests. The prognostic utility of the biomarker was determined by calculating the C-statistic and an ordinal regression analysis. RESULTS: A total of 87 patients were included. Concentrations of all biomarkers were significantly higher for patients compared with controls. Although the concentration of the biomarkers was affected by the presence of mass lesions, FA of the CC was an independent factor influencing levels of UCH-L1 and NfL, which positioned these two biomarkers as better surrogates of TAI. Biomarkers also performed well in determining patients who would have had unfavorable outcome. NfL and the FA of the CC are independent complementary factors related to outcome. CONCLUSIONS: UCH-L1 and NfL seem to be the biomarkers more specific to detect TAI. The concentration of NfL combined with the FA of the CC might help predict long-term outcome.

Oxidative stress protection and growth promotion activity of Pseudomonas mercuritolerans sp. nov., in forage plants under mercury abiotic stress conditions.

SAICEUPSMT strain was isolated from soils in the mining district of Almadén (Ciudad Real, Spain), subjected to a high concentration of mercury. Using the plant model of lupinus, the strain was inoculated into the rhizosphere of the plant in a soil characterized by a high concentration of mercury (1,710 ppm) from an abandoned dump in the mining district of Almadén (Ciudad Real, Spain). As a control, a soil with a minimum natural concentration of mercury, from a surrounding area, was used. Under greenhouse conditions, the effect that the inoculum of the SAICEUPSMT strain had on the antioxidant capacity of the plant was studied, through the quantification of the enzymatic activity catalase (CAT), ascorbate peroxidase (APX), superoxide dismutase (SOD), and glutathione reductase (GR). Likewise, the capacity of the plant to bioaccumulate mercury in the presence of the inoculum was studied, as well as the effect on the biometric parameters total weight (g), shoot weight (g), root weight (g), shoot length (cm), root length (cm), total number of leaves (N), and total number of secondary roots (No). Finally, in view of the results, the SAICEUPSMT strain was identified from the phenotypic and genotypic point of view (housekeeping genes and complete genome sequencing). The inoculum with the SAICEUPSMT strain in the presence of mercury produced a significant reduction in the enzymatic response to oxidative stress (CAT, APX, and SOD). It can be considered that the strain exerts a phytoprotective effect on the plant. This led to a significant increase in the biometric parameters total plant weight, root weight and the number of leaves under mercury stress, compared to the control without abiotic stress. When analyzing the mercury content of the plant with and without bacterial inoculum, it was found that the incorporation of the SAICEUPSMT strain significantly reduced the uptake of mercury by the plant, while favoring its development in terms of biomass. Given the positive impact of the SAICEUPSMT strain on the integral development of the plant, it was identified, proving to be a Gram negative bacillus, in vitro producer of siderophores, auxins and molecules that inhibit stress precursors. The most represented fatty acids were C16:0 (33.29%), characteristic aggregate 3 (22.80%) comprising C16:1 ω7c and C16: 1ω6c, characteristic aggregate 8 (13.66%) comprising C18:1 ω7c, and C18: 1 cycle ω6c and C 17:0 (11.42%). From the genotypic point of view, the initial identification of the strain based on the 16S rRNA gene sequence classified it as Pseudomonas iranensis. However, genome-wide analysis showed that average nucleotide identity (ANI, 95.47%), DNA-DNA in silico hybridization (dDDH, 61.9%), average amino acid identity (AAI, 97.13%), TETRA (0.99%) and intergenic distance (0.04) values were below the established thresholds for differentiation. The results of the genomic analysis together with the differences in the phenotypic characteristics and the phylogenetic and chemotaxonomic analysis support the proposal of the SAICEUPSMT strain as the type strain of a new species for which the name Pseudomonas mercuritolerans sp. is proposed. No virulence genes or transmissible resistance mechanisms have been identified, which reveals its safety for agronomic uses, under mercury stress conditions.

Role of miR-199a-5p in the post-transcriptional regulation of ABCA1 in response to hypoxia in peritoneal macrophages.

Hypoxia is a crucial factor contributing to maintenance of atherosclerotic lesions. The ability of ABCA1 to stimulate the efflux of cholesterol from cells in the periphery, particularly foam cells in atherosclerotic plaques, is an important anti-atherosclerotic mechanism. The posttranscriptional regulation by miRNAs represents a key regulatory mechanism of a number of signaling pathways involved in atherosclerosis. Previously, miR-199a-5p has been shown to be implicated in the endocytic and retrograde intracellular transport. Although the regulation of miR-199a-5p and ABCA1 by hypoxia has been already reported independently, the role of miR-199a-5p in macrophages and its possible role in atherogenic processes such us regulation of lipid homeostasis through ABCA1 has not been yet investigated. Here, we demonstrate that both ABCA1 and miR-199a-5p show an inverse regulation by hypoxia and Ac-LDL in primary macrophages. Moreover, we demonstrated that miR-199a-5p regulates ABCA1 mRNA and protein levels by directly binding to its 3'UTR. As a result, manipulation of cellular miR-199a-5p levels alters ABCA1 expression and cholesterol efflux in primary mouse macrophages. Taken together, these results indicate that the correlation between ABCA1-miR-199a-5p could be exploited to control macrophage cholesterol efflux during the onset of atherosclerosis, where cholesterol alterations and hypoxia play a pathogenic role.

Patients awaiting surgery for neurosurgical diseases during the first wave of the COVID-19 pandemic in Spain: a multicentre cohort study.

OBJECTIVES: The large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery. DESIGN: This was an observational retrospective study. SETTINGS: A tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020. PARTICIPANTS: A total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection. RESULTS: More than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, p<0.001), degenerative spine (OR=0.296, p=0.027) and expedited indications (OR=6.095, p<0.001) were independent factors for being operated on during the pandemic. CONCLUSIONS: Patients awaiting neurosurgery experienced significant collateral damage even when they were considered for scheduled procedures.

Intracranial Pressure Monitoring in Patients With Severe Traumatic Brain Injury: Extension of the Recommendations and the Effect on Outcome by Propensity Score Matching.

BACKGROUND: Intracranial pressure (ICP) monitoring is recommended for patients with traumatic brain injury (TBI) with a Glasgow Coma Scale (GCS) <9 on admission and revealing space-occupying lesions or swelling on computed tomography. However, previous studies that have evaluated its effect on outcome have shown conflicting results. OBJECTIVE: To study the effect of ICP monitoring on outcome after adjustment of patient's characteristics imbalance and determine the potential benefit on patients with higher GCS that deteriorates early or in the absence of computed tomography results suggesting high ICP. METHODS: We searched for adult patients with TBI admitted between 1996 and 2020 with a GCS <9 on admission or deterioration from higher scores within 24 hours after TBI. Patients were divided into groups if they fulfilled strict (Brain Trauma Foundation guidelines) or extended criteria (patients who worsened after admission or without space-occupying lesions) for ICP monitoring. Propensity score analyses based on nearest neighbor matching was performed. RESULTS: After matching, we analyzed data from 454 patients and 184 patients who fulfilled strict criteria or extended criteria for ICP monitoring, respectively. A decreased on in-hospital mortality was detected in monitored patients following strict and extended criteria . Those patients with a higher baseline risk of poor outcome showed higher odds of favorable outcome if they were monitored. CONCLUSION: ICP monitoring in patients with severe TBI within 24 hours after injury following strict and extended criteria was associated with a decreased in-hospital mortality. The identification of patients with a higher risk of an unfavorable outcome might be useful to better select cases that would benefit more from ICP monitoring.

Valorization as a biofertilizer of an agricultural residue leachate: Metagenomic characterization and growth promotion test by PGPB in the forage plant Medicago sativa (alfalfa).

The abuse of chemical fertilizers in intensive agriculture has turned out in the contamination of ground and the soil on which they are applied. Likewise, the generation, storage, and destruction of plant residues from the agri-food industry poses a threat to the environment and human health. The current situation of growing demand for food implies the urgent need to find sustainable alternatives to chemical fertilizers and the management of agricultural waste. Valorization of this plant residue to produce natural biofertilizers using microbiological treatments is presented as a sustainable alternative. The microbial activity allows the transformation into simple molecules that are easily absorbed by plants, as well as the stimulation of plant growth. This double direct and indirect action induced significant increases against the variables of germination, viability, and biomass (dry weight). To guarantee biosafety, it is necessary to use new bio-technological tools, such as metagenomics, which allow the taxonomic analysis of microbial communities, detecting the absence of pathogens. In the present paper, a physicochemical and metagenomic characterization of a fertilizer obtained from agricultural plant waste valorization is carried out. Likewise, fertigation treatments were tested to which the Plant Growth Promoting Bacteria (PGPB) Pseudomonas agronomica and Bacillus pretiosus were added, both independently and in consortium. Metagenomic analysis has identified taxa belonging to the kingdoms Bacteria and Archaea; 10 phyla, 25 families, 32 genera and 34 species, none of them previously described as pathogenic. A 1/512 dilution of the fertilizer increased the germination rate of Medicago sativa (alfalfa) by 16% at 144 h, compared to the treatment without fertilizer. Both the fertilizer and the addition of PGPB in a double direct and indirect action induced significant increases against the variables of germination, viability, and biomass (dry weight). Therefore, the use of an agricultural residue is proposed, which after the addition of two new species is transformed into a biofertilizer that significantly induces plant growth in Mendicago sativa plants.

Plant growth promotion of the forage plant Lupinus albus Var. Orden Dorado using Pseudomonas agronomica sp. nov. and Bacillus pretiosus sp. nov. added over a valorized agricultural biowaste.

Introduction: The overexploitation of natural ecosystems and the evolution of climate change currently force us to design new strategies for more sustainable agronomic uses. The recovery of plant residues, as an alternative to agrochemicals, can help alleviate these problems, for example, through its use for the synthesis of biofertilizers. In this work, the effect of the organic fertilizer matrix ORGAON® from the valorization of horticultural waste is tested, to which two strains of bacteria (and their consortium) are added (SAICEU11T identified as Bacillus pretiosus and SAICEU22T identified as Pseudomonas agronomica), selected for their demonstrated ability to promote plant growth (PGPB), on the lupine forage plant (Lupinus albus). Methods: For the synthesis of the biofertilizer, both strains were added to the ORGAON® organic matrix separately, until reaching a final optical density (OD) of 0.5 McFarland in each case in the irrigation matrix. As a control, sterile ORGAON® (ORGAON®st) was used, also supplemented with the PGPB strains and a chemical fertilizer widely used in agronomy (Chem-F). With these treatments, a 6-week experiment was started under controlled laboratory conditions and on agricultural substrate, to recreate field conditions as accurately as possible. All the tests were carried out with 9 repetitions and 3 replicates of each treatment. After harvest, the improvements on the following biometric variables were studied for each treatment: total weight (Weight_T, g), shoot weight (Weight_S, g), root weight (Weight_R, g), number of leaves (Leaves, No.), shoot length (Length_S), root length (Length_R) and number of secondary roots (Roots, No.). Likewise, the identification of the tested strains and their description as new species was carried out. For this, they were studied from the phenotypic point of view (Transmission electron microscopy (TEM), metabolic profile, PGP activities, fatty acid profile and Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)) and genotypic (sequencing of the main housekeeping genes and sequencing of the whole genome, genomic characteristics (dDDH and ANI) and phylogenetic analysis). Results and discussion: After the statistical analysis of the results, it is shown that the individual addition of both strains on the ORGAON® and ORGAON®st organic matrix improve certain biometric variables. In the case of the SAICEU11T (Bacillus pretiosus) strain, the variables root weight (Weight_R, g), total weight (Weight_T, g) and length of the plant, and number of secondary roots (Roots, No.) significantly improve, while in the case of the strain SAICEU22T (Pseudmonas agronomica), a significant improvement of root length (Length_R) and number of secondary roots (Roots, No.) is demonstrated. On the other hand, the genotaxonomic analysis showed that both species have not been described to date. The identification based on the main housekeeping genes, show that for the Bacillus strain (SAICEU11T) the sequence similarity of the 16S rRNA was 100%, gyrB 92.69%, rpoB 97.70% and rpoD 94.67%. For the Pseudomonas strain (SAICEU22T) the results were 100% for 16S rRNA, 98.43% for rpoD and 96.94% for gyrB. However, in both cases, the dDDH and ANI values, as well as the phylogenetic analysis, show that both species are below the species threshold, which would support the hypothesis that both are new species, in line with the chemotaxonomic results obtained by MALDI-TOF spectrometry and fatty acid profile. To verify the biosafety in their handling and release into the natural environment, we have ruled out the presence of genes that encode virulence factors or resistance to antibiotics, concluding that they are suitable for use in the field to improve the yield of crop plants. Type strains are SAICEU11T (= DSM 114702T = CECT30674T) for Bacillus pretiosus and SAICEU22T (= DSM 114959T = CECT30673T) for Pseudomonas agronomicae.

The influence of aneurysm morphology on the volume of hemorrhage after rupture.

OBJECTIVE: Factors determining the risk of rupture of intracranial aneurysms have been extensively studied; however, little attention is paid to variables influencing the volume of bleeding after rupture. In this study the authors aimed to evaluate the impact of aneurysm morphological variables on the amount of hemorrhage. METHODS: This was a retrospective cohort analysis of a prospectively collected data set of 116 patients presenting at a single center with subarachnoid hemorrhage due to aneurysmal rupture. A volumetric assessment of the total hemorrhage volume was performed from the initial noncontrast CT. Aneurysms were segmented and reproduced from the initial CT angiography study, and morphology indexes were calculated with a computer-assisted approach. Clinical and demographic characteristics of the patients were included in the study. Factors influencing the volume of hemorrhage were explored with univariate correlations, multiple linear regression analysis, and graphical probabilistic modeling. RESULTS: The univariate analysis demonstrated that several of the morphological variables but only the patient's age from the clinical-demographic variables correlated (p < 0.05) with the volume of bleeding. Nine morphological variables correlated positively (absolute height, perpendicular height, maximum width, sac surface area, sac volume, size ratio, bottleneck factor, neck-to-vessel ratio, and width-to-vessel ratio) and two correlated negatively (parent vessel average diameter and the aneurysm angle). After multivariate analysis, only the aneurysm size ratio (p < 0.001) and the patient's age (p = 0.023) remained statistically significant. The graphical probabilistic model confirmed the size ratio and the patient's age as the variables most related to the total hemorrhage volume. CONCLUSIONS: A greater aneurysm size ratio and an older patient age are likely to entail a greater volume of bleeding after subarachnoid hemorrhage.

Traumatic axonal injury: is the prognostic information produced by conventional MRI and DTI complementary or supplementary?

OBJECTIVE: A traumatic axonal injury (TAI) diagnosis has traditionally been based on conventional MRI, especially on those sequences with a higher sensitivity to edema and blood degradation products. A more recent technique, diffusion tensor imaging (DTI), can infer the microstructure of white matter (WM) due to the restricted diffusion of water in organized tissues. However, there is little information regarding the correlation of the findings obtained by both methods and their use for outcome prognosis. The main objectives of this study were threefold: 1) study the correlation between DTI metrics and conventional MRI findings; 2) evaluate whether the prognostic information provided by the two techniques is supplementary or complementary; and 3) determine the incremental value of the addition of these variables compared to a traditional prognostic model. METHODS: The authors studied 185 patients with moderate to severe traumatic brain injury (TBI) who underwent MRI with DTI study during the subacute stage. The number and volume of lesions in hemispheric subcortical WM, corpus callosum (CC), basal ganglia, thalamus, and brainstem in at least four conventional MRI sequences (T1-weighted, T2-weighted, FLAIR, T2* gradient recalled echo, susceptibility-weighted imaging, and diffusion-weighted imaging) were determined. Fractional anisotropy (FA) was measured in 28 WM bundles using the region of interest method. Nonparametric tests were used to evaluate the colocalization of macroscopic lesions and FA. A multivariate logistic regression analysis was performed to assess the independent prognostic value of each neuroimaging modality after adjustment for relevant clinical covariates, and the internal validation of the model was evaluated in a contemporary cohort of 92 patients. RESULTS: Differences in the lesion load between patients according to their severity and outcome were found. Colocalization of macroscopic nonhemorrhagic TAI lesions (not microbleeds) and lower FA was limited to the internal and external capsule, corona radiata, inferior frontooccipital fasciculus, CC, and brainstem. However, a significant association between the FA value and the identification of macroscopic lesions in distant brain regions was also detected. Specifically, lower values of FA of some hemispheric WM bundles and the splenium of the CC were related to a higher number and volume of hyperintensities in the brainstem. The regression analysis revealed that age, motor score, hypoxia, FA of the genu of the CC, characterization of TAI lesions in the CC, and the presence of thalamic/basal ganglia lesions were independent prognostic factors. The performance of the proposed model was higher than that of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in TBI) model in the validation cohort. CONCLUSIONS: Very limited colocalization of hyperintensities (none for microbleeds) with FA values was discovered. DTI and conventional MRI provide complementary prognostic information, and their combination can improve the performance of traditional prognostic models.

Accuracy and repeatability of QRAPMASTER and MRF-vFA.

Our purpose is to evaluate bias and repeatability of the quantitative MRI sequences QRAPMASTER, based on steady-state imaging, and variable Flip Angle MRF (MRF-VFA), based on the transient response. Both techniques are assessed with a standardized phantom and five volunteers on 1.5 T and 3 T clinical scanners. All scans were repeated eight times in consecutive weeks. In the phantom, the mean bias±95% confidence interval for T1 values with QRAPMASTER was 10 ± 10% on 1.5 T and 4 ± 13% on 3.0 T. The mean bias for T1 values with MRF-vFA was 21 ± 17% on 1.5 T and 9 ± 9% on 3.0 T. For T2 values the mean bias with QRAPMASTER was 12 ± 3% on 1.5 T and 23 ± 1% on 3.0 T. For T2 values the mean bias with MRF-vFA was 17 ± 1% on 1.5 T and 19 ± 2% on 3.0 T. QRAPMASTER estimated lower T1 and T2 values than MRF-vFA. Repeatability was good with low coefficients of variation (CoV). Mean CoV ± 95% confidence interval for T1 were 3.2 ± 0.4% on 1.5 T and 4.5 ± 0.8% on 3.0 T with QRAPMASTER and 2.7% ± 0.2% on 1.5 T and 2.5 ± 0.2% on 3.0 T with MRF-vFA. For T2 were 3.3 ± 1.9% on 1.5 T and 3.2 ± 0.6% on 3.0 T with QRAPMASTER and 2.0 ± 0.4% on 1.5 T and 5.7 ± 1.0% on 3.0 T with MRF-vFA. The in-vivo T1 and T2 are in the range of values previously reported by other authors. The in-vivo mean CoV ± 95% confidence interval in gray matter were for T1 1.7 ± 0.2% using QRAPMASTER and 0.7 ± 0.5% using MRF-vFA and for T2 were 0.9 ± 0.4% using QRAPMASTER and 2.4 ± 0.5% using MRF-vFA. In white matter were for T1 0.9 ± 0.3% using QRAPMASTER and 1.3 ± 1.1% using MRF-vFA and for T2 were 0.7 ± 0.4% using QRAPMASTER and 2.4 ± 0.4% using MRF-vFA. A GLM analysis showed that the variations in T1 and T2 mainly depend on the field strength and the subject, but not on the follow-up repetition in different days. This confirms the high repeatability of QRAPMASTER and MRF-vFA. In summary, QRAPMASTER and MRF-vFA on both systems were highly repeatable with moderate accuracy, providing results comparable to standard references. While repeatability was similar for both methods, QRAPMASTER was more accurate. QRAPMASTER is a tested commercial product but MRF-vFA is 4.77 times faster, which would ease the inclusion of quantitative relaxometry.

Accelerated 3D whole-brain T1, T2, and proton density mapping: feasibility for clinical glioma MR imaging.

PURPOSE: Advanced MRI-based biomarkers offer comprehensive and quantitative information for the evaluation and characterization of brain tumors. In this study, we report initial clinical experience in routine glioma imaging with a novel, fully 3D multiparametric quantitative transient-state imaging (QTI) method for tissue characterization based on T1 and T2 values. METHODS: To demonstrate the viability of the proposed 3D QTI technique, nine glioma patients (grade II-IV), with a variety of disease states and treatment histories, were included in this study. First, we investigated the feasibility of 3D QTI (6:25 min scan time) for its use in clinical routine imaging, focusing on image reconstruction, parameter estimation, and contrast-weighted image synthesis. Second, for an initial assessment of 3D QTI-based quantitative MR biomarkers, we performed a ROI-based analysis to characterize T1 and T2 components in tumor and peritumoral tissue. RESULTS: The 3D acquisition combined with a compressed sensing reconstruction and neural network-based parameter inference produced parametric maps with high isotropic resolution (1.125 × 1.125 × 1.125 mm3 voxel size) and whole-brain coverage (22.5 × 22.5 × 22.5 cm3 FOV), enabling the synthesis of clinically relevant T1-weighted, T2-weighted, and FLAIR contrasts without any extra scan time. Our study revealed increased T1 and T2 values in tumor and peritumoral regions compared to contralateral white matter, good agreement with healthy volunteer data, and high inter-subject consistency. CONCLUSION: 3D QTI demonstrated comprehensive tissue assessment of tumor substructures captured in T1 and T2 parameters. Aiming for fast acquisition of quantitative MR biomarkers, 3D QTI has potential to improve disease characterization in brain tumor patients under tight clinical time-constraints.

Compressive MRI quantification using convex spatiotemporal priors and deep encoder-decoder networks.

We propose a dictionary-matching-free pipeline for multi-parametric quantitative MRI image computing. Our approach has two stages based on compressed sensing reconstruction and deep learned quantitative inference. The reconstruction phase is convex and incorporates efficient spatiotemporal regularisations within an accelerated iterative shrinkage algorithm. This minimises the under-sampling (aliasing) artefacts from aggressively short scan times. The learned quantitative inference phase is purely trained on physical simulations (Bloch equations) that are flexible for producing rich training samples. We propose a deep and compact encoder-decoder network with residual blocks in order to embed Bloch manifold projections through multi-scale piecewise affine approximations, and to replace the non-scalable dictionary-matching baseline. Tested on a number of datasets we demonstrate effectiveness of the proposed scheme for recovering accurate and consistent quantitative information from novel and aggressively subsampled 2D/3D quantitative MRI acquisition protocols.

Three dimensional MRF obtains highly repeatable and reproducible multi-parametric estimations in the healthy human brain at 1.5T and 3T.

Magnetic resonance fingerprinting (MRF) is highly promising as a quantitative MRI technique due to its accuracy, robustness, and efficiency. Previous studies have found high repeatability and reproducibility of 2D MRF acquisitions in the brain. Here, we have extended our investigations to 3D MRF acquisitions covering the whole brain using spiral projection k-space trajectories. Our travelling head study acquired test/retest data from the brains of 12 healthy volunteers and 8 MRI systems (3 systems at 3 T and 5 at 1.5 T, all from a single vendor), using a study design not requiring all subjects to be scanned at all sites. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived PD T1 and T2 maps to an anatomical atlas, coefficients of variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site. Our analysis demonstrated a high repeatability (CVs 0.7-1.3% for T1, 2.0-7.8% for T2, 1.4-2.5% for normalized PD) and reproducibility (CVs of 2.0-5.8% for T1, 7.4-10.2% for T2, 5.2-9.2% for normalized PD) in gray and white matter. Both repeatability and reproducibility improved when compared to similar experiments using 2D acquisitions. Three-dimensional MRF obtains highly repeatable and reproducible estimations of T1 and T2, supporting the translation of MRF-based fast quantitative imaging into clinical applications.

Reliability and accuracy assessment of morphometric measurements obtained with software for three-dimensional reconstruction of brain aneurysms relative to cerebral angiography measures.

OBJECTIVE: To analyze the reliability and accuracy of morphological measurements of software employed to three-dimensionally reconstruct aneurysms and vessels (VMTKlab, version 1.6.1,) with computed tomography angiography (CTA) as the source of images. Agreement with measurements from three-dimensional digital subtraction angiography (3 D-DSA) was evaluated. METHODS: We evaluated 40 patients presenting with aneurysmal subarachnoid hemorrhage (aSAH). We analyzed four main variables of the aneurysm morphology: absolute height (size), neck (maximum neck width), perpendicular height, and maximum width. The CTA images were uploaded to the software and then segmented to reconstruct the aneurysm. This new method was compared to the current gold standard-3D reconstruction of pretreatment cerebral angiography. We used intraclass correlation coefficient (ICC) and Bland-Altman plot analyses to evaluate the agreement between these methods. RESULTS: The ICCs obtained for absolute height, neck, perpendicular height, and maximum width were 0.85, 0.57, 0.85, and 0.89, respectively. This implied good agreement except for the neck of the aneurysm (moderate agreement). Bland-Altman plots are presented for the four indexes. The average of the differences was not significant in terms of absolute height, perpendicular height, and maximum width indicating good agreement. However, it was significant for the neck of the aneurysm. CONCLUSIONS: We report good agreement between the values generated using VMTKlab and cerebral angiography for three of the four main variables. Discrepancies in neck diameter are not surprising and its underestimation with a traditional delineation from cerebral angiography has been reported before.

Rapid three-dimensional multiparametric MRI with quantitative transient-state imaging.

Novel methods for quantitative, transient-state multiparametric imaging are increasingly being demonstrated for assessment of disease and treatment efficacy. Here, we build on these by assessing the most common Non-Cartesian readout trajectories (2D/3D radials and spirals), demonstrating efficient anti-aliasing with a k-space view-sharing technique, and proposing novel methods for parameter inference with neural networks that incorporate the estimation of proton density. Our results show good agreement with gold standard and phantom references for all readout trajectories at 1.5 T and 3 T. Parameters inferred with the neural network were within 6.58% difference from the parameters inferred with a high-resolution dictionary. Concordance correlation coefficients were above 0.92 and the normalized root mean squared error ranged between 4.2 and 12.7% with respect to gold-standard phantom references for T1 and T2. In vivo acquisitions demonstrate sub-millimetric isotropic resolution in under five minutes with reconstruction and inference times < 7 min. Our 3D quantitative transient-state imaging approach could enable high-resolution multiparametric tissue quantification within clinically acceptable acquisition and reconstruction times.

Silent 3D MR sequence for quantitative and multicontrast T1 and proton density imaging.

This study aims to develop a silent, fast and 3D method for T1 and proton density (PD) mapping, while generating time series of T1-weighted (T1w) images with bias-field correction. Undersampled T1w images at different effective inversion times (TIs) were acquired using the inversion recovery prepared RUFIS sequence with an interleaved k-space trajectory. Unaliased images were reconstructed by constraining the signal evolution to a temporal subspace which was learned from the signal model. Parameter maps were obtained by fitting the data to the signal model, and bias-field correction was conducted on T1w images. Accuracy and repeatability of the method was accessed in repeated experiments with phantom and volunteers. For the phantom study, T1 values obtained by the proposed method were highly consistent with values from the gold standard method, R2 = 0.9976. Coefficients of variation (CVs) ranged from 0.09% to 0.83%. For the volunteer study, T1 values from gray and white matter regions were consistent with literature values, and peaks of gray and white matter can be clearly delineated on whole-brain T1 histograms. CVs ranged from 0.01% to 2.30%. The acoustic noise measured at the scanner isocenter was 2.6 dBA higher compared to the in-bore background. Rapid and with low acoustic noise, the proposed method is shown to produce accurate T1 and PD maps with high repeatability by reconstructing sparsely sampled T1w images at different TIs using temporal subspace. Our approach can greatly enhance patient comfort during examination and therefore increase the acceptance of the procedure.