Accelerated free-breathing liver fat and R 2 * quantification using multi-echo stack-of-radial MRI with motion-resolved multidimensional regularized reconstruction: Initial retrospective evaluation.

PURPOSE: To improve image quality, mitigate quantification biases and variations for free-breathing liver proton density fat fraction (PDFF) and R 2 * $$ {\mathrm{R}}_2^{\ast } $$ quantification accelerated by radial k-space undersampling. METHODS: A free-breathing multi-echo stack-of-radial MRI method was developed with compressed sensing with multidimensional regularization. It was validated in motion phantoms with reference acquisitions without motion and in 11 subjects (6 patients with nonalcoholic fatty liver disease) with reference breath-hold Cartesian acquisitions. Images, PDFF, and R 2 * $$ {\mathrm{R}}_2^{\ast } $$ maps were reconstructed using different radial view k-space sampling factors and reconstruction settings. Results were compared with reference-standard results using Bland-Altman analysis. Using linear mixed-effects model fitting (p < 0.05 considered significant), mean and SD were evaluated for biases and variations of PDFF and R 2 * $$ {\mathrm{R}}_2^{\ast } $$ , respectively, and coefficient of variation on the first echo image was evaluated as a surrogate for image quality. RESULTS: Using the empirically determined optimal sampling factor of 0.25 in the accelerated in vivo protocols, mean differences and limits of agreement for the proposed method were [-0.5; -33.6, 32.7] s-1 for R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and [-1.0%; -5.8%, 3.8%] for PDFF, close to those of a previous self-gating method using fully sampled radial views: [-0.1; -27.1, 27.0] s-1 for R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and [-0.4%; -4.5%, 3.7%] for PDFF. The proposed method had significantly lower coefficient of variation than other methods (p < 0.001). Effective acquisition time of 64 s or 59 s was achieved, compared with 171 s or 153 s for two baseline protocols with different radial views corresponding to sampling factor of 1.0. CONCLUSION: This proposed method may allow accelerated free-breathing liver PDFF and R 2 * $$ {\mathrm{R}}_2^{\ast } $$ mapping with reduced biases and variations.

Ferumoxytol-Enhanced Cardiac Cine MRI Reconstruction Using a Variable-Splitting Spatiotemporal Network.

BACKGROUND: Balanced steady-state free precession (bSSFP) imaging is commonly used in cardiac cine MRI but prone to image artifacts. Ferumoxytol-enhanced (FE) gradient echo (GRE) has been proposed as an alternative. Utilizing the abundance of bSSFP images to develop a computationally efficient network that is applicable to FE GRE cine would benefit future network development. PURPOSE: To develop a variable-splitting spatiotemporal network (VSNet) for image reconstruction, trained on bSSFP cine images and applicable to FE GRE cine images. STUDY TYPE: Retrospective and prospective. SUBJECTS: 41 patients (26 female, 53 ± 19 y/o) for network training, 31 patients (19 female, 49 ± 17 y/o) and 5 healthy subjects (5 female, 30 ± 7 y/o) for testing. FIELD STRENGTH/SEQUENCE: 1.5T and 3T, bSSFP and GRE. ASSESSMENT: VSNet was compared to VSNet with total variation loss, compressed sensing and low rank methods for 14× accelerated data. The GRAPPA×2/×3 images served as the reference. Peak signal-to-noise-ratio (PSNR), structural similarity index (SSIM), left ventricular (LV) and right ventricular (RV) end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were measured. Qualitative image ranking and scoring were independently performed by three readers. Latent scores were calculated based on scores of each method relative to the reference. STATISTICS: Linear mixed-effects regression, Tukey method, Fleiss' Kappa, Bland-Altman analysis, and Bayesian categorical cumulative probit model. A P-value <0.05 was considered statistically significant. RESULTS: VSNet achieved significantly higher PSNR (32.7 ± 0.2), SSIM (0.880 ± 0.004), rank (2.14 ± 0.06), and latent scores (-1.72 ± 0.22) compared to other methods (rank >2.90, latent score < -2.63). Fleiss' Kappa was 0.52 for scoring and 0.61 for ranking. VSNet showed no significantly different LV and RV ESV (P = 0.938) and EF (P = 0.143) measurements, but statistically significant different (2.62 mL) EDV measurements compared to the reference. CONCLUSION: VSNet produced the highest image quality and the most accurate functional measurements for FE GRE cine images among the tested 14× accelerated reconstruction methods. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Has the concept of polyspermy prevention been invented in the laboratory?

There is no evidence, nor need, for a fast block to polyspermy in animal oocytes. The idea that oocytes have evolved a mechanism to allow the entry of one spermatozoon and repel all others has, however, gained consensus over the last century. The main culprit is the sea urchin, which has been used for over a century in in vitro studies of the fertilization process. Images of sea urchin oocytes with thousands of sperm attached to the surface are commonplace in textbooks and appeal to the nature of the reader implying an intriguing surface mechanism of sperm selection despite these oocytes being fixed for photography (Figure ). The abundance of gametes in this marine invertebrate and the ease of experimentation have given us the possibility to elucidate many aspects of the mechanism of fertilization, but has also led to ongoing controversies in reproductive biology, one being polyspermy prevention. Kinetic experiments by Rothschild and colleagues in the 1950s led to the hypothesis of a fast partial block to polyspermy in sea urchin oocytes that reduced the probability of a second spermatozoon from entering the oocyte by 1/20th. In the 1970s, Jaffe and colleagues suggested, with circumstantial evidence, that this partial block was due to the sperm-induced depolarization of the oocyte plasma membrane. However, the fate of supernumerary spermatozoa is determined well before the plasma membrane of the oocyte depolarizes. Transmembrane voltage does not serve to regulate sperm entry. Scholastic texts have inadvertently promulgated this concept across the animal kingdom with no logical correlation or experimentation and, as of today, a molecular mechanism to regulate sperm entry in oocytes has not been identified.

Accelerated k-space shift calibration for free-breathing stack-of-radial MRI quantification of liver fat and R2∗.

PURPOSE: To develop an accelerated k-space shift calibration method for free-breathing 3D stack-of-radial MRI quantification of liver proton-density fat fraction (PDFF) and R2∗ . METHODS: Accelerated k-space shift calibration was developed to partially skip acquisition of k-space shift data in the through-plane direction then interpolate in processing, as well as to reduce the in-plane averages. A multi-echo stack-of-radial sequence with the baseline calibration was evaluated on a phantom versus vendor-provided reference-standard PDFF and R2∗ values at 1.5T, and in 13 healthy subjects and 5 clinical subjects at 3T with respect to reference-standard breath-hold Cartesian acquisitions. PDFF and R2∗ maps were calculated with different calibration acceleration factors offline and compared to reference-standard values using Bland-Altman analysis. Bias and uncertainty were evaluated using normal distribution and Bayesian probability of difference (P < .05 considered significant). RESULTS: Bland-Altman plots of phantom and in vivo data showed that substantial acceleration was highly feasible in both through-plane and in-plane directions. Compared to the baseline calibration without acceleration, Bayesian analysis revealed no significant differences on biases and uncertainties of PDFF and R2∗ measurements with all acceleration methods in this study, except the method with through-plane acceleration equaling slices and averages equaling 20 for PDFF and R2∗ (both P < .001) for the phantom. A six-fold reduction in equivalent calibration acquisition time (time saving ≥25 s and ≥80.7%) was achieved using recommended acceleration factors for the in vivo protocols in this study. CONCLUSION: This proposed method may allow accelerated calibration for free-breathing stack-of-radial MRI PDFF and R2∗ mapping.

Modulating oxidative stress and epigenetic homeostasis in preimplantation IVF embryos.

Assisted reproductive technology is today considered a safe and reliable medical intervention, with healthy live births a reality for many IVF and ICSI treatment cycles. However, there are increasing numbers of published reports describing epigenetic/imprinting anomalies in children born as a result of these procedures. These anomalies have been attributed to methylation errors in embryo chromatin remodelling during in vitro culture. Here we re-visit three concepts: (1) the so-called 'in vitro toxicity' of 'essential amino acids' before the maternal to zygotic transition period; (2) the effect of hyperstimulation (controlled ovarian hyperstimulation) on homocysteine in the oocyte environment and the effect on methylation in the absence of essential amino acids; and (3) the fact/postulate that during the early stages of development the embryo undergoes a 'global' demethylation. Methylation processes require efficient protection against oxidative stress, which jeopardizes the correct acquisition of methylation marks as well as subsequent methylation maintenance. The universal precursor of methylation [by S-adenosyl methionine (SAM)], methionine, 'an essential amino acid', should be present in the culture. Polyamines, regulators of methylation, require SAM and arginine for their syntheses. Cystine, another 'semi-essential amino acid', is the precursor of the universal protective antioxidant molecule: glutathione. It protects methylation marks against some undue DNA demethylation processes through ten-eleven translocation (TET), after formation of hydroxymethyl cytosine. Early embryos are unable to convert homocysteine to cysteine as the cystathionine ß-synthase pathway is not active. In this way, cysteine is a 'real essential amino acid'. Most IVF culture medium do not maintain methylation/epigenetic processes, even in mouse assays. Essential amino acids should be present in human IVF medium to maintain adequate epigenetic marking in preimplantation embryos. Furthermore, morphological and morphometric data need to be re-evaluated, taking into account the basic biochemical processes involved in early life.

Can sperm quality influence embryo development and its ploidy? Analysis of 811 blastocysts obtained from different sperm sources.

The aim of our study was to evaluate the correlation between sperm quality and ploidy status of the derived blastocysts. We performed a retrospective analysis on a restricted pool of patients enrolling only those who had no female factors. Male patients with genetic factors affecting spermatogenesis were also excluded. We chose a maternal age ≤38 years to decrease the female factor, therefore the male factor was the main component of sterility. We divided the patients in four groups based on semen quality and comparing fertilization, pregnancy and euploidy rates above all. In total, 201 intracytoplasmic sperm injection (ICSI) cycles were enrolled in the study. Cycles were divided into four groups, according to semen source: normal semen, oligoasthenoteratozoospermia (OAT), cryptospermia or non-obstructive azoospermia (NOA). An extremely statistically lower fertilization rate was found in NOA patients. Unexpectedly, no differences were detected in blastocyst formation, euploidy, aneuploidy and mosaicism rates among the four groups. Interestingly, we also found a higher abortion rate comparing NOA to normal semen with an odds ratio of 4.67. In our study no statistically significant differences among the analyzed groups were found, showing little or no effect at all using spermatozoa from different semen sources or quality. This may be linked to the oocyte competence of fixing sperm DNA damage and it could be hypothesized that only sperm with a good rate of DNA integrity are able to fertilize the oocyte, explaining why poor quality semen is reflected in a low fertilization rate without effect on ploidy.

Comparison of sperm preparation methods to improve the recovery of mature spermatozoa in sub-fertile males.

The integrity of chromatin in the spermatozoon is essential for reproductive outcome. The aim of this study was to evaluate the most effective and cost-effective method to reduce the percentage of spermatozoa with defects in chromatin decondensation for use in assisted reproductive technologies (ART) procedures. Sperm samples from 15 sub-fertile males were examined at CFA Naples to determine the sperm decondensation index (SDI), using the aniline blue test, before and after preparation, comparing density gradients with two different swim-up approaches. All three techniques led to a reduction in decondensed spermatozoa with no statistical difference (P > 0.05) between the control and the treated sperm. In contrast, we found a highly significant decrease in SDI (P < 0.01) after the two swim-up methods in all the samples, confirming the efficacy of these methods in lowering the percentage of chromatin compaction damage. There was no statistical difference between the two swim-up methods, however swim-up from the pellet led to improved count, motility and the percentage of normal condensed spermatozoa. We suggest that swim-up from the pellet be used in ART on sub-fertile males, both to reduce cell stress by multiple centrifugation and improve the recovery rate of mature spermatozoa.

CD36 promotes vasculogenic mimicry in melanoma by mediating adhesion to the extracellular matrix.

BACKGROUND: The formation of blood vessels within solid tumors directly contributes to cancer growth and metastasis. Until recently, tumor vasculature was thought to occur exclusively via endothelial cell (EC) lined structures (i.e. angiogenesis), but a second source of tumor vasculature arises from the cancer cells themselves, a process known as vasculogenic mimicry (VM). While it is generally understood that the function of VM vessels is the same as that of EC-lined vessels (i.e. to supply oxygen and nutrients to the proliferating cancer cells), the molecular mechanisms underpinning VM are yet to be fully elucidated. METHODS: Human VM-competent melanoma cell lines were examined for their VM potential using the in vitro angiogenesis assays (Matrigel), together with inhibition studies using small interfering RNA and blocking monoclonal antibodies. Invasion assays and adhesion assays were used to examine cancer cell function. RESULTS: Herein we demonstrate that CD36, a cell surface glycoprotein known to promote angiogenesis by ECs, also supports VM formation by human melanoma cancer cells. In silico analysis of CD36 expression within the melanoma cohort of The Cancer Genome Atlas suggests that melanoma patients with high expression of CD36 have a poorer clinical outcome. Using in vitro 'angiogenesis' assays and CD36-knockdown approaches, we reveal that CD36 supports VM formation by human melanoma cells as well as adhesion to, and invasion through, a cancer derived extracellular matrix substrate. Interestingly, thrombospondin-1 (TSP-1), a ligand for CD36 on ECs that inhibits angiogenesis, has no effect on VM formation. Further investigation revealed a role for laminin, but not collagen or fibronectin, as ligands for CD36 expressing melanoma cells. CONCLUSIONS: Taken together, this study suggests that CD36 is a novel regulator of VM by melanoma cancer cells that is facilitated, at least in part, via integrin-α3 and laminin. Unlike angiogenesis, VM is not perturbed by the presence of TSP-1, thus providing new information on differences between these two processes of tumor vascularization which may be exploited to combat cancer progression.

Free-Breathing Volumetric Liver R2* and Proton Density Fat Fraction Quantification in Pediatric Patients Using Stack-of-Radial MRI With Self-Gating Motion Compensation.

BACKGROUND: Stack-of-radial multiecho gradient-echo MRI is promising for free-breathing liver R2* quantification and may benefit children. PURPOSE: To validate stack-of-radial MRI with self-gating motion compensation in phantoms, and to evaluate it in children. STUDY TYPE: Prospective. PHANTOMS: Four vials with different R2* driven by a motion stage. SUBJECTS: Sixteen pediatric patients with suspected nonalcoholic fatty liver disease or steatohepatitis (five females, 13 ± 4 years, body mass index 29.2 ± 8.6 kg/m2 ). FIELD STRENGTH/SEQUENCES: Stack-of-radial, and 2D and 3D Cartesian multiecho gradient-echo sequences at 3T. ASSESSMENT: Ungated and gated stack-of-radial proton density fat fraction (PDFF) and R2* maps were reconstructed without and with self-gating motion compensation. Stack-of-radial R2* measurements of phantoms without and with motion were validated against reference 2D Cartesian results of phantoms without motion. In subjects, free-breathing stack-of-radial and reference breath-hold 3D Cartesian were acquired. Subject inclusion for statistical analysis and region of interest placement were determined independently by two observers. STATISTICAL TESTS: Phantom results were fitted with a weighted linear model. Demographic differences between excluded and included subjects were tested by multivariate analysis of variance. PDFF and R2* measurements were compared using Bland-Altman analysis. Interobserver agreement was assessed by the intraclass correlation coefficient (ICC). RESULTS: Ungated stack-of-radial R2* inside moving phantom vials showed a significant positive bias of 64.3 s-1 (P < 0.00001), unlike gated results (P > 0.31). Subject inclusion decisions for statistical analysis from two observers were consistent. No significant differences were found between four excluded and 12 included subjects (P = 0.14). Compared to breath-hold Cartesian, ungated and gated free-breathing stack-of-radial exhibited mean R2* differences of 18.5 s-1 and 3.6 s-1 . Mean PDFF differences were 1.1% and 1.0% for ungated and gated measurements, respectively. Interobserver agreement was excellent (ICC for PDFF = 0.99, ICC for R2* = 0.90; P < 0.0003). DATA CONCLUSION: Stack-of-radial MRI with self-gating motion compensation seems to allow free-breathing liver R2* and PDFF quantification in children. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

MTHFR (methylenetetrahydrofolate reductase: EC 1.5.1.20) SNPs (single-nucleotide polymorphisms) and homocysteine in patients referred for investigation of fertility.

PURPOSE: MTHFR, one of the major enzymes in the folate cycle, is known to acquire single-nucleotide polymorphisms that significantly reduce its activity, resulting in an increase in circulating homocysteine. Methylation processes are of crucial importance in gametogenesis, involved in the regulation of imprinting and epigenetic tags on DNA and histones. We have retrospectively assessed the prevalence of MTHFR SNPs in a population consulting for infertility according to gender and studied the impact of the mutations on circulating homocysteine levels. METHODS: More than 2900 patients having suffered at least two miscarriages (2 to 9) or two failed IVF/ICSI (2 to 10) attempts were included for analysis of MTHFR SNPs C677T and A1298C. Serum homocysteine levels were measured simultaneously. RESULTS: We observed no difference in the prevalence of different genetic backgrounds between men and women; only 15% of the patients were found to be wild type. More than 40% of the patients are either homozygous for one SNP or compound heterozygous carriers. As expected, the C677T SNP shows the greatest adverse effect on homocysteine accumulation. The impact of MTHFR SNPs on circulating homocysteine is different in men than in women. CONCLUSIONS: Determination of MTHFR SNPs in both men and women must be seriously advocated in the presence of long-standing infertility; male gametes, from MTHFR SNPs carriers, are not exempted from exerting a hazardous impact on fertility. Patients should be informed of the pleiotropic medical implications of these SNPs for their own health, as well as for the health of future children.

Effect of respiratory motion on free-breathing 3D stack-of-radial liver R2∗ relaxometry and improved quantification accuracy using self-gating.

PURPOSE: To develop an accurate free-breathing 3D liver R2∗ mapping approach and to evaluate it in vivo. METHODS: A free-breathing multi-echo stack-of-radial sequence was applied in 5 normal subjects and 6 patients at 3 Tesla. Respiratory motion compensation was implemented using the inherent self-gating signal. A breath-hold Cartesian acquisition was the reference standard. Proton density fat fraction and R2∗ were measured and compared between radial and Cartesian methods using Bland-Altman plots. The normal subject results were fitted to a linear mixed model (P < .05 considered significant). RESULTS: Free-breathing stack-of-radial without self-gating exhibited signal attenuation in echo images and artifactually elevated apparent R2∗ values. In the Bland-Altman plots of normal subjects, compared to breath-hold Cartesian, free-breathing stack-of-radial acquisitions of 22, 30, 36, and 44 slices, had mean R2∗ differences of 27.4, 19.4, 10.9, and 14.7 s-1 with 800 radial views, and they had 18.4, 11.9, 9.7, and 27.7 s-1 with 404 views, which were reduced to 0.4, 0.9, -0.2, and -0.7 s-1 and to -1.7, -1.9, -2.1, and 0.5 s-1 with self-gating, respectively. No substantial proton density fat fraction differences were found. The linear mixed model showed free-breathing radial R2∗ results without self-gating were significantly biased by 17.2 s-1 averagely (P = .002), which was eliminated with self-gating (P = .930). Proton density fat fraction results were not different (P > .234). For patients, Bland-Altman plots exhibited mean R2∗ differences of 14.4 and 0.1 s-1 for free-breathing stack-of-radial without self-gating and with self-gating, respectively, but no substantial proton density fat fraction differences. CONCLUSION: The proposed self-gating method corrects the respiratory motion bias and enables accurate free-breathing stack-of-radial quantification of liver R2∗ .

DAAM1 and PREP are involved in human spermatogenesis.

During differentiation of the male gamete, there is a massive remodelling in the shape and architecture of all the cells in the seminiferous epithelium. The cytoskeleton, as well as many associated proteins, plays a pivotal role in this process. To better characterise the factors involved, we analysed two proteins: the formin, dishevelled-associated activator of morphogenesis 1 (DAAM1), which participates in the regulation of actin polymerisation, and the protease, prolyl endopeptidase (PREP), engaged in microtubule-associated processes. In our previous studies we demonstrated their involvement in cytoskeletal dynamics necessary for correct postnatal development of the rat testis. Here, we used samples of testicular tissue obtained from infertile men by testicular sperm extraction and the spermatozoa of asthenoteratozoospermic patients. By western blot and immunofluorescent analysis, we found that DAAM1 and PREP expression and localisation were impaired in both the testis and spermatozoa, and in particular in the midpiece as well as in the principal and end-pieces of the flagella, as compared with spermatozoa of normospermic men. Our results provide new knowledge of the dynamics of spermatogenesis, raising the possibility of using DAAM1 and PREP as new markers of normal fertility.

Accurate fatty acid composition estimation of adipose tissue in the abdomen based on bipolar multi-echo MRI.

PURPOSE: To develop a bipolar multi-echo MRI method for the accurate estimation of the adipose tissue fatty acid composition (FAC) using clinically relevant protocols at clinical field strength. METHODS: The proposed technique jointly estimates confounding factors (field map, R2* , eddy-current phase) and triglyceride saturation state parameters by fitting multi-echo gradient echo acquisitions to a complex signal model. The noise propagation behavior was improved by applying a low-rank enforcing denoising technique and by addressing eddy-current-induced phase discrepancies analytically. The impact of the total echo train duration on the FAC parameter map accuracy was analyzed in an oil phantom at 3T. Accuracy and reproducibility assessment was based on in vitro oil phantom measurements at two field strengths (3T and 1.5T) and with two different protocols. Repeatability was assessed in vivo in patients (n = 8) with suspected fatty liver disease using test-retest acquisitions in the abdominal subcutaneous, perirenal and mesenteric fat depots. RESULTS: Echo train readout durations of at least five times the conventional in-phase time were required for accurate FAC estimation in areas of high fat content. In vitro, linear regression and Bland-Altman analyses demonstrated strong (r > 0.94) and significant (P â‰ª 0.01) correlations between measured and reference FACs for all acquisitions, with smaller overall intercepts and biases at 3T compared to 1.5T. In vivo, reported mean absolute differences between test and retest were 1.54%, 3.31%, and 2.63% for the saturated, mono-unsaturated, and poly-unsaturated fat component, respectively. CONCLUSIONS: Accurate and reproducible MRI-based FAC quantification within a breath-hold is possible at clinical field strengths.

The negative impact of the environment on methylation/epigenetic marking in gametes and embryos: A plea for action to protect the fertility of future generations.

Life expectancy has increased since World War II, and this may be attributed to several aspects of modern lifestyles. However, now we are faced with a downturn, which seems to be the result of environmental issues. This paradigm is paralleled with reduced human fertility, decreased sperm quality, increased premature ovarian failure, and diminished ovarian reserve syndromes. Endocrine disruptor chemicals and other toxic chemicals, herbicides, pesticides, plasticizers, to mention a few, are a rising concern in today's environment. Some of these are commonly used in the domestic setting: cleaning material and cosmetics and they have a known impact on epigenesis and imprinting via perturbation of methylation processes. Pollution from polyaromatic hydrocarbons, particulate matter <10 and <2.5 µm, and ozone released into the air, all affect fertility. Poor food processing management is a source of DNA adduct formation, which impairs the quality of gametes. An important concern is the nanoparticles that are present in food and are thought to induce oxidative stress. Now is the time to take a step backward. Global management of the environment and food production is required urgently to protect the fertility of future generations.

DNA Methylation Patterns in the Early Human Embryo and the Epigenetic/Imprinting Problems: A Plea for a More Careful Approach to Human Assisted Reproductive Technology (ART).

An increasing number of publications indicate that babies born after IVF (in vitro fertilization) procedures have higher rates of anomalies related to imprinting/epigenetic changes, which may be attributed to suboptimal culture conditions. Appropriate maintenance of DNA methylation during the first few days of an in vitro culture requires a supply of methyl donors, which are lacking in current in vitro culture systems. The absence of protection against oxidative stress in the culture increases the risks for errors in methylation. A decrease in the methylation processes is sometimes observed immediately post fertilization, due to delays that occur during the maternal⁻zygotic transition period. Care should be exercised in ART (assisted reproductive technology) procedures in order to avoid the risk of generating errors in methylation during the in vitro culture period immediately post fertilization, which has an impact on imprinting/epigenetics. Formulation of IVF culture media needs to be re-assessed in the perspective of current knowledge regarding embryo physiology.

Rotating single-shot acquisition (RoSA) with composite reconstruction for fast high-resolution diffusion imaging.

PURPOSE: To accelerate high-resolution diffusion imaging, rotating single-shot acquisition (RoSA) with composite reconstruction is proposed. Acceleration was achieved by acquiring only one rotating single-shot blade per diffusion direction, and high-resolution diffusion-weighted (DW) images were reconstructed by using similarities of neighboring DW images. A parallel imaging technique was implemented in RoSA to further improve the image quality and acquisition speed. RoSA performance was evaluated by simulation and human experiments. METHODS: A brain tensor phantom was developed to determine an optimal blade size and rotation angle by considering similarity in DW images, off-resonance effects, and k-space coverage. With the optimal parameters, RoSA MR pulse sequence and reconstruction algorithm were developed to acquire human brain data. For comparison, multishot echo planar imaging (EPI) and conventional single-shot EPI sequences were performed with matched scan time, resolution, field of view, and diffusion directions. RESULTS: The simulation indicated an optimal blade size of 48 × 256 and a 30 ° rotation angle. For 1 × 1 mm2 in-plane resolution, RoSA was 12 times faster than the multishot acquisition with comparable image quality. With the same acquisition time as SS-EPI, RoSA provided superior image quality and minimum geometric distortion. CONCLUSION: RoSA offers fast, high-quality, high-resolution diffusion images. The composite image reconstruction is model-free and compatible with various diffusion computation approaches including parametric and nonparametric analyses. Magn Reson Med 79:264-275, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Quantifying immature platelets as markers of increased platelet production after coronary artery bypass grafting surgery.

OBJECTIVES: An increased rate of platelet production is a possible cause of reduced antithrombotic response to once-daily aspirin. Markers of immature platelets (IPs), such as immature platelet count (IPC), immature platelet fraction (IPF), and mean platelet volume (MPV) might be useful for identifying patients who have an increase in their rate of platelet production. However, their potential as markers of platelet production has not been rigorously evaluated. We aimed to investigate the utility of the IPC, IPF, and MPV as surrogates for increased platelet production using coronary artery bypass grafting (CABG) as a model of enhanced thrombopoiesis. METHODS: Daily changes in platelet count, IPC, IPF, and MPV were followed in 45 patients undergoing CABG. RESULTS: The rise in IP markers preceded that in the platelet count. IPC (16% per day increase from nadir) but not IPF or MPV showed a significant and sustained rise, which paralleled the pattern observed with platelet count (18% per day increase from nadir). CONCLUSIONS: Of the 3 markers, IPC was the most promising as surrogates for platelet production. Future studies should evaluate the utility of the IPC to identify patients with cardiovascular disease with reduced response to aspirin who might benefit from twice-daily aspirin.

A novel framework for evaluating the image accuracy of dynamic MRI and the application on accelerated breast DCE MRI.

OBJECTIVE: To develop a novel framework for evaluating the accuracy of quantitative analysis on dynamic contrast-enhanced (DCE) MRI with a specific combination of imaging technique, scanning parameters, and scanner and software performance and to test this framework with breast DCE MRI with Time-resolved angiography WIth Stochastic Trajectories (TWIST). MATERIALS AND METHODS: Realistic breast tumor phantoms were 3D printed as cavities and filled with solutions of MR contrast agent. Full k-space raw data of individual tumor phantoms and a uniform background phantom were acquired. DCE raw data were simulated by sorting the raw data according to TWIST view order and scaling the raw data according to the enhancement based on pharmaco-kinetic (PK) models. The measured spatial and temporal characteristics from the images reconstructed using the scanner software were compared with the original PK model (ground truth). RESULTS: Images could be reconstructed using the manufacturer's platform with the modified 'raw data.' Compared with the 'ground truth,' the RMS error in all images was <10% in most cases. With increasing view-sharing acceleration, the error of the initial uptake slope decreased while the error of peak enhancement increased. Deviations of PK parameters varied with the type of enhancement. CONCLUSION: A new framework has been developed and tested to more realistically evaluate the quantitative measurement errors caused by a combination of the imaging technique, parameters and scanner and software performance in DCE-MRI.

Effect of a Low-Rank Denoising Algorithm on Quantitative Magnetic Resonance Imaging-Based Measures of Liver Fat and Iron.

PURPOSE: This study aimed to assess the effect of a low-rank denoising algorithm on quantitative magnetic resonance imaging-based measures of liver fat and iron. MATERIALS AND METHODS: This was an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, retrospective analysis of 42 consecutive subjects who were imaged at 3T using a multiecho gradient echo sequence that was reconstructed using the multistep adaptive fitting algorithm to obtain quantitative proton density fat fraction (PDFF) and R2* maps (original maps). A patch-wise low-rank denoising algorithm was then applied, and PDFF and R2* maps were created (denoised maps). Three readers independently rated the PDFF maps in terms of vessel and liver edge sharpness and image noise using a 5-point scale. Two other readers independently measured mean and standard deviation of PDFF and R2* values for the original and denoised maps; values were compared using intraclass correlation coefficients (ICCs) and mean difference analyses. RESULTS: Qualitatively, the denoised maps were preferred by all 3 readers based on image noise (P < 0.001) and by 2 of 3 readers based on vessel edge sharpness (P < 0.001-0.99). No reader had a significant preference regarding liver edge sharpness (P = 0.16-0.48). Quantitatively, agreement was near perfect between the original and denoised maps for PDFF (ICC = 0.995) and R2* (ICC = 0.995) values. Mean quantitative values obtained from the original and denoised maps were similar for liver PDFF (7.6 ± 7.7% vs 7.7 ± 7.8%; P = 0.63) and R2* (52.9 ± 40.3s vs 52.8 ± 41.1 s, P = 0.74). CONCLUSIONS: Applying the low-rank denoising algorithm to liver fat and iron quantification reduces image noise in PDFF and R2* maps without adversely affecting mean quantitative values or subjective image quality.

Laboratory measurement of the direct oral anticoagulants.

Direct oral anticoagulants (DOACs), including the direct thrombin inhibitor, dabigatran, and the direct factor Xa (FXa) inhibitors, rivaroxaban, apixaban and edoxaban, are approved for thromboembolism prevention and treatment. These drugs do not require routine coagulation monitoring but, in some circumstances, measurement of drug level or anticoagulant effect may be necessary. Although traditional coagulation tests lack analytical sensitivity and specificity, they are widely available and inexpensive, and can provide useful information regarding the residual anticoagulant effect of DOACs. Hemoclot® and ecarin-based assays can be used to quantify dabigatran level and calibrated chromogenic anti-FXa assays are suitable for measuring rivaroxaban, apixaban and edoxaban levels, but these tests are not yet widely available.