Three-Minute Enantioselective Amino Acid Analysis by Ultra-High-Performance Liquid Chromatography Drift Tube Ion Mobility-Mass Spectrometry Using a Chiral Core-Shell Tandem Column Approach.

Fast liquid chromatography (LC) amino acid enantiomer separation of 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatives using a chiral core-shell particle tandem column with weak anion exchange and zwitterionic-type quinine carbamate selectors in less than 3 min was achieved. Enantiomers of all AQC-derivatized proteinogenic amino acids and some isomeric ones (24 in total plus achiral glycine) were baseline separated (Rs > 1.5 except for glutamic acid with Rs = 1.3), while peaks of distinct amino acids and structural isomers (constitutional isomers and diastereomers of leucine and threonine) of the same configuration overlapped to various degrees. For this reason, drift tube ion mobility-mass spectrometry was added (i.e., LC-IM-MS) as an additional selectivity filter without extending run time. The IM separation dimension in combination with high-resolution demultiplexing enabled confirmation of threonine isomers (threonine, allo-threonine, homoserine), while leucine, isoleucine, and allo-isoleucine have almost identical collisional cross-section (DTCCSN2) values and added no selectivity to the partial LC separation. Density functional theory (DFT) calculations show that IM separation of threonine isomers was possible due to conformational stabilization by hydrogen bond formation between the hydroxyl side chain and the urea group. Generally, the CCSN2 of protonated ions increased uniformly with addition of the AQC label, while outliers could be explained by consideration of intramolecular interactions and additional structural analysis. Preliminary validation of the enantioselective LC-IM-MS method for quantitative analysis showed compliance of accuracy and precision with common limits in bioanalytical methods, and applicability to a natural lipopeptide and a therapeutic synthetic peptide could be demonstrated.

Trend Decomposition for Temperature Compensation in a Radar-Based Structural Health Monitoring System of Wind Turbine Blades.

The compensation of temperature is critical in every structural health monitoring (SHM) system for achieving maximum damage detection performance. This paper analyses a novel approach based on seasonal trend decomposition to eliminate the temperature effect in a radar-based SHM system for wind turbine blades that operates in the frequency band from 58 to 63.5 GHz. While the original seasonal trend decomposition searches for the trend of a periodic signal in its entirety, the new method uses a moving average to determine trends for each point of a periodic signal. The points of the seasonal signal no longer need to have the same trend. Based on the determined trends, the measurement signal can be corrected by temperature effects, providing accurate damage detection results under changing temperature conditions. The performance of the trend decomposition is demonstrated with experimental data obtained during a full-scale fatigue test of a 31 m long wind turbine blade subjected to ambient temperature variations. For comparison, the well-known optimal baseline selection (OBS) approach is used, which is based on multiple baseline measurements at different temperature conditions. The use of metrics, such as the contrast in damage indicators, enables the performance assessment of both methods.

Towards Tailored Dialdehyde Cellulose Derivatives: A Strategy for Tuning the Glass Transition Temperature.

The derivatization of dialdehyde cellulose (DAC) has received increasing attention in the development of sustainable thermoplastics. In this study, a series of dialcohol celluloses were generated by borohydride reduction, which exhibited glass transition temperature (Tg ) values ranging from 23 to 109 °C, depending on the initial degree of oxidation (DO) of the DAC intermediate. However, the DAC derivatives did not exhibit thermoplastic behavior when the DO of the modified DAC was below 26 %. The influence of introduced side chains was highlighted by comparing DAC-based thermoplastic materials obtained by either oximation or borohydride reduction. Our results provide insights into the generation of DAC-based thermoplastics and highlight a strategy for tailoring the Tg by adjusting the DO during the periodate oxidation step and selecting appropriate substituents in subsequent modifications.

Direct ink writing of multifunctional nanocellulose and allyl-modified gelatin biomaterial inks for the fabrication of mechanically and functionally graded constructs.

Recreating the intricate mechanical and functional gradients found in natural tissues through additive manufacturing poses significant challenges, including the need for precise control over time and space and the availability of versatile biomaterial inks. In this proof-of-concept study, we developed a new biomaterial ink for direct ink writing, allowing the creation of 3D structures with tailorable functional and mechanical gradients. Our ink formulation combined multifunctional cellulose nanofibrils (CNFs), allyl-functionalized gelatin (0.8-2.0 wt%), and polyethylene glycol dithiol (3.0-7.5 wt%). The CNF served as a rheology modifier, whereas a concentration of 1.8 w/v % in the inks was chosen for optimal printability and shape fidelity. In addition, CNFs were functionalized with azido groups, enabling the spatial distribution of functional moieties within a 3D structure. These functional groups were further modified using a spontaneous click chemistry reaction. Through additive manufacturing and a readily available static mixer, we successfully demonstrated the fabrication of mechanical gradients - ranging from 3 to 6 kPa in indentation strength - and functional gradients. Additionally, we introduced dual gradients by combining gradient printing with an anisotropic photocrosslinking step. The developed biomaterial ink opens up possibilities for printing intricate multigradient structures, resembling the complex hierarchical organization seen in living tissues.

Debugging periodate oxidation of cellulose: Why following the common protocol of quenching excess periodate with glycol is a bad idea.

Periodate oxidation of cellulose to produce "dialdehyde cellulose" (DAC) has lately received increasing attention in sustainable materials development. Despite the longstanding research interest and numerous reported studies, there is still an enormous variation in the proposed preparation and work-up protocols. This apparently reduces comparability and causes reproducibility problems in DAC research. Two simple but prevalent work-up protocols, namely glycol quenching and filtration/washing, were critically examined and compared, resulting in this cautionary note. Various analytical techniques were applied to quantify residual iodine species and organic contaminations from quenching side reactions. The commonly practiced glycol addition cannot remove all oxidising iodine compounds. Both glycol and the formed formaldehyde are incorporated into DAC's polymeric structure. Quenching of excess periodate with glycol can thus clearly be discouraged. Instead, simple washing protocols are recommended which do not bear the risk of side reactions with organic contaminants. While simple washing was sufficient for mildly oxidised celluloses, higher oxidised samples were more likely to trap residual (per)iodate, as determined by thiosulfate titration. For work-up, simple washing with water is proposed while determining potential iodine contaminations after washing with a simple colorimetric test and, if needed, removal of residual periodate by washing with an aqueous sodium thiosulfate solution.

Reductive Amination of Dialdehyde Cellulose: Access to Renewable Thermoplastics.

The reductive amination of dialdehyde cellulose (DAC) with 2-picoline borane was investigated for its applicability in the generation of bioderived thermoplastics. Five primary amines, both aliphatic and aromatic, were introduced to the cellulose backbone. The influences of the side chains on the course of the reaction were examined by various analytical techniques with microcrystalline cellulose as a model compound. The obtained insights were transferred to a 39%-oxidized softwood kraft pulp to study the thermal properties of thereby generated high-molecular-weight thermoplastics. The number-average molecular weights (Mn) of the diamine celluloses, ranging from 60 to 82 kD, were investigated by gel permeation chromatography. The diamine celluloses exhibited glass transition temperatures (Tg) from 71 to 112 °C and were stable at high temperatures. Diamine cellulose generated from aniline and DAC showed the highest conversion, the highest Tg (112 °C), and a narrow molecular weight distribution (D̵ of 1.30).

[Thoracopagus conjoined twins: case study conducted in Libreville and literature review]. / Jumeaux conjoints thoracopages: à propos d'un cas à Libreville et revue de la littérature.

Conjoined twins are a rare form of monozygotic and monoamniotic twins. Fetal prognosis is very poor and, if the diagnosis is made early, it most often requires therapeutic abortion. We here report a case of three-hour old thoracopagus conjoined twins who were born vaginally, at term, at 40 weeks + 3 days. They were born to non-consanguineous parents, without any significant pathological history. Their mother was young and primiparous. She received 5 antenatal visits and 3 obstetric ultrasounds were performed by an inexperienced physician. The diagnosis of thoracopages twins was suspected based on clinical examination and computerized tomography (CT) results. This test showed cardiovascular abnormalities incompatible with life. The twins died after 23 hours of age due to acute respiratory distress. Conjoined twins are a rare congenital abnormality. Early diagnosis based on ultrasound would help to determine common anatomical structures, investigate associated congenital abnormalities, schedule delivery in a suitable structure and multidisciplinary neonatal management.

Fourier transform and near infrared dataset of dialdehyde celluloses used to determine the degree of oxidation with chemometric analysis.

This dataset is related to the research article entitled ``A fast method to measure the degree of oxidation of dialdehyde celluloses using multivariate calibration and infrared spectroscopy''. In this article, 74 dialdehyde cellulose samples with different degrees of oxidation were prepared by periodate oxidation and analysed by Fourier-transform infrared (FTIR) and near-infrared spectroscopy (NIR). The corresponding degrees of oxidation were determined indirectly by periodate consumption using UV spectroscopy at 222 nm and by the quantitative reaction with hydroxylamine hydrochloride followed by potentiometric titration. Partial least squares regression (PLSR) was used to correlate the infrared data with the corresponding degree of oxidation (DO). The developed NIR/PLSR and FTIR/PLSR models can easily be implemented in other laboratories to quickly and reliably predict the degree of oxidation of dialdehyde celluloses.

A fast method to measure the degree of oxidation of dialdehyde celluloses using multivariate calibration and infrared spectroscopy.

The properties of dialdehyde celluloses, which are usually generated by periodate oxidation, are highly dependent on the aldehyde content, i.e. the degree of oxidation (DO). Thus far, the established methods for determining the DO in dialdehyde celluloses lack simplicity or sufficient speed. More than 60 dialdehyde cellulose samples with varying aldehyde content were analysed by near-infrared and Fourier-transform infrared spectroscopy. This was found to be a reliable method for quickly predicting the DO if combined with partial least squares regression (PLSR). The proposed PLSR models can predict the DO with a high determination coefficient (R2) of 99% when applied to a single pulp type and 94% when applied to multiple types. This new approach quickly and reliably determines the DO of dialdehyde celluloses. It can be easily implemented in everyday research to save money, time and resources, especially because the raw datasets and measured DO values are provided.

Neural activity in the human anterior thalamus during natural vision.

In natural vision humans and other primates explore environment by active sensing, using saccadic eye movements to relocate the fovea and sample different bits of information multiple times per second. Saccades induce a phase reset of ongoing neuronal oscillations in primary and higher-order visual cortices and in the medial temporal lobe. As a result, neuron ensembles are shifted to a common state at the time visual input propagates through the system (i.e., just after fixation). The extent of the brain's circuitry that is modulated by saccades is not yet known. Here, we evaluate the possibility that saccadic phase reset impacts the anterior nuclei of the thalamus (ANT). Using recordings in the human thalamus of three surgical patients during natural vision, we found that saccades and visual stimulus onset both modulate neural activity, but with distinct field potential morphologies. Specifically, we found that fixation-locked field potentials had a component that preceded saccade onset. It was followed by an early negativity around 50 ms after fixation onset which is significantly faster than any response to visual stimulus presentation. The timing of these events suggests that the ANT is predictively modulated before the saccadic eye movement. We also found oscillatory phase concentration, peaking at 3-4 Hz, coincident with suppression of Broadband High-frequency Activity (BHA; 80-180 Hz), both locked to fixation onset supporting the idea that neural oscillations in these nuclei are reorganized to a low excitability state right after fixation onset. These findings show that during real-world natural visual exploration neural dynamics in the human ANT is influenced by visual and oculomotor events, which supports the idea that ANT, apart from their contribution to episodic memory, also play a role in natural vision.

Endovascular Treatment for Acute Stroke in Cerebral Amyloid Angiopathy.

Background and Purpose: We aimed to compare outcome of endovascular thrombectomy in acute ischemic stroke in patients with and without cerebral amyloid angiopathy (CAA). Methods: We included patients with and without possible or probable CAA based on the modified Boston criteria from an observational multicenter cohort of patients with acute ischemic stroke and endovascular thrombectomy, the German Stroke Registry Endovascular Treatment trial. We analyzed baseline characteristics, procedural parameters, and functional outcome after 90 days. Results: Twenty-eight (17.3%) of 162 acute ischemic stroke patients were diagnosed with CAA based on iron-sensitive magnetic resonance imaging performed before endovascular thrombectomy. CAA patients were less likely to have a good 90-day outcome (14.3 versus 37.8%). National Institutes of Health Stroke Scale score (adjusted odds ratio, 0.88; P<0.001), successful recanalization (adjusted odds ratio 6.82; P=0.005), and CAA (adjusted odds ratio 0.28; P=0.049) were independent outcome predictors. Intravenous thrombolysis was associated with an increased rate of good outcome (36.3% versus 0%, P=0.031) in CAA. Conclusions: Endovascular thrombectomy with or without thrombolysis appears beneficial in acute ischemic stroke patients with possible or probable CAA, but is associated with a worse functional outcome. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.

Diagnostic Accuracy of Quantitative Imaging Biomarkers in the Differentiation of Benign and Malignant Vertebral Lesions : Combination of Diffusion-Weighted and Proton Density Fat Fraction Spine MRI.

PURPOSE: To compare and combine the diagnostic performance of the apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging (DWI) and proton density fat fraction (PDFF) derived from chemical-shift encoding (CSE)-based water-fat magnetic resonance imaging (MRI) for distinguishing benign and malignant vertebral bone marrow lesions (VBML). METHODS: A total of 55 consecutive patients with 53 benign (traumatic, inflammatory and primary) and 36 malignant (metastatic and hematologic) previously untreated VBMLs were prospectively enrolled in this IRB-approved study and underwent sagittal DWI (single-shot spin-echo echo-planar with multi-slice short TI inversion recovery fat suppression) and CSE-based MRI (gradient-echo 6­point modified Dixon) in addition to routine clinical spine MRI at 1.5 T or 3.0 T. Diagnostic reference standard was established according to histopathology or imaging follow-up. The ADC = ADC (0, 800) and PDFF = fat / (water + fat) were calculated voxel-wise and examined for differences between benign and malignant lesions. RESULTS: The ADC and PDFF values of malignant lesions were significantly lower compared to benign lesions (mean ADC 861â€¯× 10-6 mm2/s vs. 1323â€¯× 10-6 mm2/s, p < 0.001; mean PDFF 3.1% vs. 28.2%, p < 0.001). The areas under the curve (AUC) and diagnostic accuracies were 0.847 (p < 0.001) and 85.4% (cut-off at 1084.4â€¯× 10-6 mm2/s) for ADC and 0.940 (p < 0.001) and 89.9% for PDFF (cut-off at 7.8%), respectively. The combined use of ADC and PDFF improved the diagnostic accuracy to 96.6% (malignancy if ADC ≤ 1118.2â€¯× 10-6 mm2/s and PDFF ≤ 20.0%, otherwise benign). CONCLUSION: Quantitative evaluation of both ADC and PDFF was useful in differentiating benign VBMLs from malignancy. The combination of ADC and PDFF improved the diagnostic performance and yielded high diagnostic accuracy for the differentiation of benign and malignant VBMLs.

DeepCLIP: predicting the effect of mutations on protein-RNA binding with deep learning.

Nucleotide variants can cause functional changes by altering protein-RNA binding in various ways that are not easy to predict. This can affect processes such as splicing, nuclear shuttling, and stability of the transcript. Therefore, correct modeling of protein-RNA binding is critical when predicting the effects of sequence variations. Many RNA-binding proteins recognize a diverse set of motifs and binding is typically also dependent on the genomic context, making this task particularly challenging. Here, we present DeepCLIP, the first method for context-aware modeling and predicting protein binding to RNA nucleic acids using exclusively sequence data as input. We show that DeepCLIP outperforms existing methods for modeling RNA-protein binding. Importantly, we demonstrate that DeepCLIP predictions correlate with the functional outcomes of nucleotide variants in independent wet lab experiments. Furthermore, we show how DeepCLIP binding profiles can be used in the design of therapeutically relevant antisense oligonucleotides, and to uncover possible position-dependent regulation in a tissue-specific manner. DeepCLIP is freely available as a stand-alone application and as a webtool at http://deepclip.compbio.sdu.dk.

CNS Infections in Immunoincompetent Patients : Neuroradiological and Clinical Features.

In patients with immunodeficiency the pathogen spectrum of central nervous system (CNS) infections is broader and different from that of immunocompetent patients. Numerous opportunistic infections are characterized by a high prevalence of viral, bacterial and parasitic pathogens, and depend on the type of impaired immune defense, for example impaired T­cell or monocyte function, monoclonal antibody treatment, and impaired granulocyte function. Neuroradiological features as well as laboratory findings are often different and versatile in comparison to immunocompetent individuals and pathognomonic imaging findings do not exist; however, knowledge of possible pathways of pathogens in the CNS and preferred tissue affection may help in narrowing down differential diagnoses. Therefore, knowledge of the type of patient and the performed immunomodulatory therapy is essential for the neuroradiological assessment and the differential diagnostic considerations. Moreover, parenchymal reactions in the sense of an immune reconstitution inflammatory syndrome (IRIS) can occur when immunocompetence is restored. This review focus on the most common pathologies in immunocompromised patients, and an overview of imaging features but also of pathology and clinical aspects is given. The synopsis of anamnestic information, clinical findings and structured analysis of the lesion pattern, its spread and short-term follow-up may increase the correct diagnostic classification; however, the gold standard is still determination of the pathogen in the cerebrospinal fluid (CSF), blood cultures or biopsies.

Impact of knowledge, attitudes, and sociocultural factors on school enrollment of children with epilepsy in Gabon.

PURPOSE: Perceptions, beliefs and culture influence attitude towards epilepsy in sub-Saharan Africa. Misconceptions on epilepsy contribute to the persistence of negative attitudes in children with epilepsy particularly on their school enrollment. The aim of the study was to assess knowledge, attitudes, and sociocultural factors affecting schooling of children with epilepsy in Gabon. METHODS: Teachers and health workers from two urban and four rural localities of Gabon were assessed using a self-administered questionnaire. RESULTS: Overall 1310 subjects filled the survey questionnaire, including 813 teachers and 497 health workers. Knowledge on risk factors and suggestive signs of childhood epilepsy were globally poor. Misconceptions on etiology of epilepsy were significant with contagiousness (27.5%) and demonic possession (16.0%) representing the major prevalent idea about the origin of epilepsy in children. Attitudes of teachers and health workers towards schooling of children with epilepsy were positive (85.0%). However, more than half recommended enrollment of these children in specialized school programs. In multivariate analysis, education level (OR = 1.40; 95% confidence interval 1.01-1.81) and marital status (OR = 1.62; 95% confidence interval 1.18-2.22) were sociocultural factors likely to affect chances of school enrollment of children with epilepsy. CONCLUSION: Understanding the influence of socio-cultural factors surrounding school enrollment of children with epilepsy could enhance public awareness campaigns about epilepsy and to improve school integration of these children.

Genomic profiling in ovarian cancer retreated with platinum based chemotherapy presented homologous recombination deficiency and copy number imbalances of CCNE1 and RB1 genes.

BACKGROUND: Ovarian carcinomas presenting homologous recombination deficiency (HRD), which is observed in about 50% of cases, are more sensitive to platinum and PARP inhibitor therapies. Although platinum resistant disease has a low chance to be responsive to platinum-based chemotherapy, a set of patients is retreated with platinum and some of them are responsive. In this study, we evaluated copy number alterations, HR gene mutations and HR deficiency scores in ovarian cancer patients with prolonged platinum sensitivity. METHODS: In this retrospective study (2005 to 2014), we selected 31 patients with platinum resistant ovarian cancer retreated with platinum therapy. Copy number alterations and HR scores were evaluated using the OncoScan® FFPE platform in 15 cases. The mutational profile of 24 genes was investigated by targeted-NGS. RESULTS: The median values of the four HRD scores were higher in responders (LOH = 15, LST = 28, tAI = 33, CS = 84) compared with non-responders (LOH = 7.5, LST = 17.5, tAI = 23, CS = 47). Patients with high LOH, LST, tAI and CS scores had better response rates, although these differences were not statistically significant. Response rate to platinum retreatment was 22% in patients with CCNE1 gains and 83.5% in patients with no CCNE1 gains (p = 0.041). Furthermore, response rate was 54.5% in patients with RB1 loss and 25% in patients without RB1 loss (p = 0.569). Patients with CCNE1 gains showed a worse progression free survival (PFS = 11.1 months vs 3.7 months; p = 0.008) and a shorter overall survival (OS = 39.3 months vs 7.1 months; p = 0.007) in comparison with patients with no CCNE1 gains. Patients with RB1 loss had better PFS (9.0 months vs 2.6 months; p = 0.093) and OS (27.4 months vs 3.6 months; p = 0.025) compared with cases with no RB1 loss. Four tumor samples were BRCA mutated and tumor mutations were not associated with response to treatment. CONCLUSIONS: HR deficiency was found in 60% of our cases and HRD medium values were higher in responders than in non-responders. Despite the small number of patients tested, CCNE1 gain and RB1 loss discriminate patients with tumors extremely sensitive to platinum retreatment.

Proton density fat fraction MRI of vertebral bone marrow: Accuracy, repeatability, and reproducibility among readers, field strengths, and imaging platforms.

BACKGROUND: Chemical shift-encoding based water-fat MRI is an emerging method to noninvasively assess proton density fat fraction (PDFF), a promising quantitative imaging biomarker for estimating tissue fat concentration. However, in vivo validation of PDFF is still lacking for bone marrow applications. PURPOSE: To determine the accuracy and precision of MRI-determined vertebral bone marrow PDFF among different readers and across different field strengths and imager manufacturers. STUDY TYPE: Repeatability/reproducibility. SUBJECTS: Twenty-four adult volunteers underwent lumbar spine MRI with one 1.5T and two different 3.0T MR scanners from two vendors on the same day. FIELD STRENGTH/SEQUENCE: 1.5T and 3.0T/3D spoiled-gradient echo multipoint Dixon sequences. ASSESSMENT: Two independent readers measured intravertebral PDFF for the three most central slices of the L1-5 vertebral bodies. Single-voxel MR spectroscopy (MRS)-determined PDFF served as the reference standard for PDFF estimation. STATISTICAL TESTS: Accuracy and bias were assessed by Pearson correlation, linear regression analysis, and Bland-Altman plots. Repeatability and reproducibility were evaluated by Wilcoxon signed rank test, Friedman test, and coefficients of variation. Intraclass correlation coefficients were used to validate intra- and interreader as well as intraimager agreements. RESULTS: MRI-based PDFF estimates of lumbar bone marrow were highly correlated (r2 = 0.899) and accurate (mean bias, -0.6%) against the MRS-determined PDFF reference standard. PDFF showed high linearity (r2 = 0.972-0.978) and small mean bias (0.6-1.5%) with 95% limits of agreement within ±3.4% across field strengths, imaging platforms, and readers. Repeatability and reproducibility of PDFF were high, with the mean overall coefficient of variation being 0.86% and 2.77%, respectively. The overall intraclass correlation coefficient was 0.986 as a measure for an excellent interreader agreement. DATA CONCLUSION: MRI-based quantification of vertebral bone marrow PDFF is highly accurate, repeatable, and reproducible among readers, field strengths, and MRI platforms, indicating its robustness as a quantitative imaging biomarker for multicentric studies. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1762-1772.

Comprehensive Genomic Profiling of Androgen-Receptor-Negative Canine Prostate Cancer.

Canine carcinomas have been considered natural models for human diseases; however, the genomic profile of canine prostate cancers (PCs) has not been explored. In this study, 14 PC androgen-receptor-negative cases, 4 proliferative inflammatory atrophies (PIA), and 5 normal prostate tissues were investigated by array-based comparative genomic hybridization (aCGH). Copy number alterations (CNAs) were assessed using the Canine Genome CGH Microarray 4 × 44K (Agilent Technologies). Genes covered by recurrent CNAs were submitted to enrichment and cross-validation analysis. In addition, the expression levels of TP53, MDM2 and ZBTB4 were evaluated in an independent set of cases by qPCR. PC cases presented genomic complexity, while PIA samples had a small number of CNAs. Recurrent losses covering well-known tumor suppressor genes, such as ATM, BRCA1, CDH1, MEN1 and TP53, were found in PC. The in silico functional analysis showed several cancer-related genes associated with canonical pathways and interaction networks previously described in human PC. The MDM2, TP53, and ZBTB4 copy number alterations were translated into altered expression levels. A cross-validation analysis using The Cancer Genome Atlas (TCGA) database for human PC uncovered similarities between canine and human PCs. Androgen-receptor-negative canine PC is a complex disease characterized by high genomic instability, showing a set of genes with similar alterations to human cancer.

Quantitative evaluation of T2* relaxation times for the differentiation of acute benign and malignant vertebral body fractures.

OBJECTIVES: The aim of this prospective study was to evaluate the diagnostic performance of T2*-weighted magnetic resonance imaging (MRI) to differentiate between acute benign and neoplastic vertebral compression fractures (VCFs). MATERIALS AND METHODS: Thirty-seven consecutive patients with a total of 52 VCFs were prospectively enrolled in this IRB approved study. All VCFs were categorized as either benign or malignant according to direct bone biopsy and histopathologic confirmation. In addition to routine clinical spine MRI including at least sagittal T1-weighted, T2-weighted and T2 spectral attenuated inversion recovery (SPAIR)-weighted sequences, all patients underwent an additional sagittal six-echo modified Dixon gradient-echo sequence of the spine at 3.0-T. Intravertebral T2* and T2*ratio (fracture T2*/normal vertebrae T2*) for acute benign and malignant VCFs were calculated using region-of-interest analysis and compared between both groups. Additional receiver operating characteristic analyses were performed. Five healthy subjects were scanned three times to determine the short-term reproducibility of vertebral T2* measurements. RESULTS: There were 27 acute benign and 25 malignant VCFs. Both T2* and T2*ratio of malignant VCFs were significantly higher compared to acute benign VCFs (T2*, 30 ± 11 vs. 19 ± 11 ms [p = 0.001]; T2*ratio, 2.9 ± 1.6 vs. 1.2 ± 0.7 [p < 0.001]). The areas under the curve were 0.77 for T2* and 0.88 for T2*ratio, yielding an accuracy of 73% and 89% for distinguishing acute benign from malignant VCFs. The root mean square absolute precision error was 0.44 ms as a measure for the T2* short-term reproducibility. CONCLUSION: Quantitative assessment of vertebral bone marrow T2* relaxation times provides good diagnostic accuracy for the differentiation of acute benign and malignant VCFs.

Proton density fat fraction (PDFF) MR imaging for differentiation of acute benign and neoplastic compression fractures of the spine.

OBJECTIVES: To evaluate the diagnostic performance of proton density fat fraction (PDFF) magnetic resonance imaging (MRI) to differentiate between acute benign and neoplastic vertebral compression fractures (VCFs). METHODS: Fifty-seven consecutive patients with 46 acute benign and 41 malignant VCFs were prospectively enrolled in this institutional review board approved study and underwent routine clinical MRI with an additional six-echo modified Dixon sequence of the spine at a clinical 3.0-T scanner. All fractures were categorised as benign or malignant according to either direct bone biopsy or 6-month follow-up MRI. Intravertebral PDFF and PDFFratio (fracture PDFF/normal vertebrae PDFF) for benign and malignant VCFs were calculated using region-of-interest analysis and compared between both groups. Additional receiver operating characteristic and binary logistic regression analyses were performed. RESULTS: Both PDFF and PDFFratio of malignant VCFs were significantly lower compared to acute benign VCFs [PDFF, 3.48 ± 3.30% vs 23.99 ± 11.86% (p < 0.001); PDFFratio, 0.09 ± 0.09 vs 0.49 ± 0.24 (p < 0.001)]. The areas under the curve were 0.98 for PDFF and 0.97 for PDFFratio, yielding an accuracy of 96% and 95% for differentiating between acute benign and malignant VCFs. PDFF remained as the only imaging-based variable to independently differentiate between acute benign and malignant VCFs on multivariate analysis (odds ratio, 0.454; p = 0.005). CONCLUSIONS: Quantitative assessment of PDFF derived from modified Dixon water-fat MRI has high diagnostic accuracy for the differentiation of acute benign and malignant vertebral compression fractures. KEY POINTS: • Chemical-shift-encoding based water-fat MRI can reliably assess vertebral bone marrow PDFF • PDFF is significantly higher in acute benign than in malignant VCFs • PDFF provides high accuracy for differentiating acute benign from malignant VCFs.