MR Approach Research Articles

Fasting Insulin and Risk of Overall and 14 Site-Specific Cancers: Evidence From Genetic Data.

ObjectiveWhether fasting insulin (FI) plays a role in cancer risk remains unclear. This study aimed to investigate the association between FI and cancer risk and to explore its potential mediator role in the association between type 2 diabetes mellitus (T2DM) and cancer.MethodsTwo-sample Mendelian randomization (TSMR) analysis was performed to evaluate the effect of FI on overall and 14 site-specific cancers using genome-wide association study (GWAS) summary-level data from Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) and consortia of 14 site-specific cancers. The primary MR approach was conducted by using the random-effect inverse-variance weighted (IVW) method, and sensitivity analyses were implemented by adopting weighted-median, weighted-mode, MR-Egger, and MR-PRESSO tests. Polygenic risk score analysis was executed by using individual-level data from UK Biobank to validate the findings from TSMR analyses. Multivariable Mendelian randomization (MVMR) was carried out to estimate the mediation effect of FI on the association between T2DM and cancer.ResultsTSMR study suggested that genetically determined high FI levels were associated with increased risk of colorectal cancer (odds ratio (OR) = 1.87, 95% CI: 1.23–2.84, p = 0.003) and endometrial cancer (OR = 1.89, 95% CI: 1.08–3.01, p = 0.008), but not associated with overall cancer risk or the other 12 studied cancer sites. Polygenic risk score analysis successfully replicated the association between genetic liability to high FI levels and the increased risk of colorectal and endometrial cancers. MVMR and MR mediation analyses detected an intermediary effect of FI and quantified that FI mediated 21.3% of the association between T2DM and endometrial cancer.ConclusionsThis study demonstrated that FI levels are associated with the risk of colorectal and endometrial cancers, and FI was found to play an intermediary role in the association between T2DM and endometrial cancer. The associations between FI and other cancers need to be further studied.

Assessment of bidirectional relationships between 98 genera of the human gut microbiota and amyotrophic lateral sclerosis: a 2-sample Mendelian randomization study

BackgroundGrowing evidence suggests a mutual interaction between gut microbiome alterations and ALS pathogenesis. However, previous studies were susceptible to potential confounding factors and reverse causation bias, likely leading to inconsistent and biased results.ObjectivesTo decipher the potentially mutual relationship between gut microbiota and ALS, we used a bidirectional two-sample MR approach to examine the associations between the gut microbiome and ALS.ResultsUsing the inverse variance-weighted method, OTU10032 unclassified Enterobacteriaceae species-level OTU and unclassified Acidaminococcaceae were associated with a higher risk of ALS (per relative abundance: OR, 1.04; 95% CI, 1.01–1.07; P = 0.011 and OR, 1.02; 95% CI, 1.01–1.04; P = 0.009, respectively). Importantly, Gamma-Glu-Phe was showed potential deleterious effects on the risk of ALS (genetically predicted per a 1-standard deviation increase in the level of Gamma-Glu-Phe: OR, 1.96; 95% CI, 1.50–2.55; P = 0.012). Sensitivity analysis of the two candidate genera and metabolites using the MR-Egger and weighted-median methods produced similar estimates, and no horizontal pleiotropy or outliers were observed. Intriguingly, genetically predicted ALS was associated with an increase in the relative abundance of OTU4607_Sutterella (per 1-unit higher log odds: β, 2.23; 95% CI, 1.27–3.18; P = 0.020) and Lactobacillales_ORDER (per 1-unit higher log odds: β, 0.51; 95% CI, 0.09–0.94; P = 0.019).ConclusionsOur findings provide novel evidence supporting the bidirectional relationship between the gut microbiota and ALS. These results may contribute to designing microbiome- and microbiome-dependent metabolite interventions in future ALS clinical trials.

Genetically determined risk of mood swings and cardiometabolic diseases: mendelian randomization study

Abstract Background Mood swings is believed to associated with increased risk of Cardiometabolic Diseases (CMD). However, the roles of mood swings on CMD are controversial because of the bias of reverse causation and/or confounding in epidemiological studies. Hence, we use a two-sample MR approach to identify the causal association between genetically determined mood swings and CMD. Methods We obtained 33 independent single-nucleotide polymorphisms (SNPs) with genome-wide significant (P<5×10–8) associated with mood swings as instrumental variable in UK Biobank. Summary data of outcomes were extracted from the Coronary Artery Disease Genome-wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics consortium, the Diabetes Genetics Replication and Meta-analysis consortium, the CKDGen consortium, and the International Stroke Genetics Consortium. Results The genetic instrument of 33 SNPs explained 4.8% of the variance in mood swings. Genetically determined mood swings was associated with an increased risk of coronary artery disease (CAD) (odds ratio 3.12, 95% confidence interval 1.92 to 5.08; P=4.32×10–6). However, mood swings had no effect on the other cardiometabolic outcomes. The above estimates were consistent across all three MR methods without significant heterogeneity. Also, there was no evidence of directional pleiotropy for each outcome except for large artery stroke. Conclusions Using MR approaches that are able draw causal inference, our results suggest that interventions aimed at improving mood swings in the population would lead to a reduction risk of CAD, which highlights the importance of mood management in high-risk CAD population. Funding Acknowledgement Type of funding sources: None.

MRCIP: a robust Mendelian randomization method accounting for correlated and idiosyncratic pleiotropy.

Mendelian randomization (MR) is a powerful instrumental variable (IV) method for estimating the causal effect of an exposure on an outcome of interest even in the presence of unmeasured confounding by using genetic variants as IVs. However, the correlated and idiosyncratic pleiotropy phenomena in the human genome will lead to biased estimation of causal effects if they are not properly accounted for. In this article, we develop a novel MR approach named MRCIP to account for correlated and idiosyncratic pleiotropy simultaneously. We first propose a random-effect model to explicitly model the correlated pleiotropy and then propose a novel weighting scheme to handle the presence of idiosyncratic pleiotropy. The model parameters are estimated by maximizing a weighted likelihood function with our proposed PRW-EM algorithm. Moreover, we can also estimate the degree of the correlated pleiotropy and perform a likelihood ratio test for its presence. Extensive simulation studies show that the proposed MRCIP has improved performance over competing methods. We also illustrate the usefulness of MRCIP on two real datasets. The R package for MRCIP is publicly available at https://github.com/siqixu/MRCIP.

Experimental assessment of a linear actuator driven by magnetorheological clutches for automotive active suspensions.

The main functions of automotive suspensions are to improve passenger comfort as well as vehicle dynamic performance. Simultaneously satisfying these functions is not possible because they require opposing suspension adjustments. This fundamental design trade-off can be solved with an active suspension system providing real-time modifications of the suspension behavior and vehicle attitude corrections. However, current active suspension actuator technologies have yet to reach a wide-spread commercial adoption due to excessive costs and performance limitations. This paper presents a design study assessing the potential of magnetorheological clutch actuators for automotive active suspension applications. An experimentally validated dynamic model is used to derive meaningful design requirements. An actuator design is proposed and built using a motor to feed counter-rotating MR clutches to provide upward and downward forces. Experimental characterization shows that all intended design requirements are met, and that the actuator can output a peak force of ±5300 N, a peak linear speed of ±1.9 m/s and a blocked-output force bandwidth of 92 Hz. When compared to other relevant technologies, the MR approach simultaneously shows both better force density and speeds (bandwidth) while adding minimal costs and weight. Results from this experimental assessment suggest that MR slippage actuation is promising for automotive active suspensions.

Impact of Prematurity on the Tissue Properties of the Neonatal Brain Stem: A Quantitative MR Approach.

Preterm birth interferes with regular brain development. The aim of this study was to investigate the impact of prematurity on the physical tissue properties of the neonatal brain stem using a quantitative MR imaging approach. A total of 55 neonates (extremely preterm [n = 30]: <28 + 0 weeks gestational age; preterm [n = 10]: 28 + 0-36 + 6 weeks gestational age; term [n = 15]: ≥37 + 0 weeks gestational age) were included in this retrospective study. In most cases, imaging was performed at approximately term-equivalent age using a standard MR protocol. MR data postprocessing software SyMRI was used to perform multidynamic multiecho sequence (acquisition time: 5 minutes, 24 seconds)-based MR postprocessing to determine T1 relaxation time, T2 relaxation time, and proton density. Mixed-model ANCOVA (covariate: gestational age at MR imaging) and the post hoc Bonferroni test were used to compare the groups. There were significant differences between premature and term infants for T1 relaxation time (midbrain: P < .001; pons: P < .001; basis pontis: P = .005; tegmentum pontis: P < .001; medulla oblongata: P < .001), T2 relaxation time (midbrain: P < .001; tegmentum pontis: P < .001), and proton density (tegmentum pontis: P = .004). The post hoc Bonferroni test revealed that T1 relaxation time/T2 relaxation time in the midbrain differed significantly between extremely preterm and preterm (T1 relaxation time: P < .001/T2 relaxation time: P = .02), extremely preterm and term (T1 relaxation time/T2 relaxation time: P < .001), and preterm and term infants (T1 relaxation time: P < .001/T2 relaxation time: P = .006). Quantitative MR parameters allow preterm and term neonates to be differentiated. T1 and T2 relaxation time metrics of the midbrain allow differentiation between the different stages of prematurity. SyMRI allows for a quantitative assessment of incomplete brain maturation by providing tissue-specific properties while not exceeding a clinically acceptable imaging time.

Fusion of registered medical images using deep learning convolutional neural network with statistics based steered image filter

Medical image fusion technique plays an increasingly critical role in many clinical applications by deriving the complementary information from medical images with different modalities. In this, a novel MR and CT image fusion approach is proposed which utilises the deep learning convolutional neural networks (CNNs) with statistics based steered image filter (SSIF). In our method, a deep learning convolutional network is adopted to generate a weight map which integrates the pixel activity information from MR and CT images. The fusion process is conducted via SSIF fusion rule which computes the weights of obtained detail layers using image statistics. In addition, weighted average method is utilised to obtain the fused image. Further, proposed fusion algorithm is extended to applicable for RGB image fusion. Experimental results demonstrate that the proposed method can achieve promising results in terms of both visual quality and objective assessment.

Fusion of registered medical images using deep learning convolutional neural network with statistics based steered image filter

Medical image fusion technique plays an increasingly critical role in many clinical applications by deriving the complementary information from medical images with different modalities. In this, a novel MR and CT image fusion approach is proposed which utilises the deep learning convolutional neural networks (CNNs) with statistics based steered image filter (SSIF). In our method, a deep learning convolutional network is adopted to generate a weight map which integrates the pixel activity information from MR and CT images. The fusion process is conducted via SSIF fusion rule which computes the weights of obtained detail layers using image statistics. In addition, weighted average method is utilised to obtain the fused image. Further, proposed fusion algorithm is extended to applicable for RGB image fusion. Experimental results demonstrate that the proposed method can achieve promising results in terms of both visual quality and objective assessment.

Early-Life Factors and Risk of Multiple Sclerosis: An MR-EWAS

Background: Although several risk factors are associated with multiple sclerosis (MS) in adulthood, evidence for risk factors acting from birth to adolescence is scarce. Methods: We conceived a 2-step study design, where signals from an Environment-Wide Association Study are prioritized for follow-up in a Mendelian Randomization study (MR-EWAS), to examine the association of early-life factors with risk of MS. The EWAS was conducted in UK Biobank, where we agnostically selected all the available risk factors acting from the perinatal period until the adolescence, including perinatal factors, anthropometric characteristics during childhood, male and female sexual factors, and skin phenotypic characteristics. We prioritized statistically significant risk factors to perform a 2-sample MR study using publicly available summary-level genetic data. We also calculated the power of the 2-step MR-EWAS approach under several scenarios and compared it against a 1-step hypothesis-free MR approach to detect risk factors of MS. Results: In the EWAS, an increase per 1 year in age at menarche was associated with a lower risk of MS (OR = 0.93; 95% CI: 0.90–0.96) and a plumper than average body size at the age of 10 was associated with a higher risk of MS (OR = 1.42; 95% CI: 1.24–1.61). Individuals getting very tanned or moderately tanned were at higher risk of MS compared with individuals that never tan or get mildly to occasionally tanned (OR = 0.86; 95% CI: 0.79–0.94). The MR analysis supported the association of age at menarche and childhood body mass index (BMI) without presence of pleiotropic effects. In the multivariable MR analysis, the association of age at menarche was not statistically significant after adjusting for childhood BMI. The MR analysis for ease of tanning did not reveal a statistically significant association. In multiple scenarios, the power of MR-EWAS approach was larger than the power of a hypothesis-free MR approach. Conclusions: We introduced the MR-EWAS, a 2-step approach that is more powerful compared with the hypothesis-free MR approach under certain scenarios, to test potential causal signals. Our comprehensive assessment of early-life risk factors of MS highlighted a potential causal role of early menarche and elevated childhood BMI for risk of MS.

Pseudoprogression in Gliomas: the Use of Advanced MRI for Treatment Decisions

The definitions of pseudoprogression (PsP) have greatly varied with time, with a reported incidence ranging from 10 to 30%. PsP is mainly a radiological definition, as a new or enlarging area of contrast agent enhancement, without argument of true tumor progression (TP), which will resolve or stabilize without any change in treatment. Because anatomical magnetic resonance imaging (MRI) is unsatisfactory in differentiating PsP from TP, advanced MR techniques are needed, adding sensitivity and specificity to obtain a more solid diagnosis. Because of its high reported diagnostic accuracy, perfusion MR seems to be the most reliable technique to better identify PsP, the lack of standardization of MR spectroscopy compromising its availability in daily practice. A multi-modal and dynamic MR approach is recommended, after harmonization of image acquisition and post-processing. Due to the recent interest of immunotherapies, identifying PsP will continue to be an issue, particularly in better including true progressing patients in clinical trials.

P5505Inflammation implicated in the aetiology of major vascular and non-vascular diseases in East Asians

Abstract Background Mendelian randomisation (MR) studies using genetic variants in the IL6R gene encoding the interleukin-6 (IL-6) receptor have demonstrated that IL-6 plays a causal role in the aetiology of coronary heart disease (CHD) in European populations, with implications for the development of drugs targeting inflammation-related pathways. It is less clear whether IL-6 signalling plays a causal role in vascular disease or major non-vascular diseases in East Asians. Purpose Using an MR approach, we investigated associations of altered IL-6 signalling with subtypes of CHD, stroke, cancer and respiratory disease in a large East Asian cohort. Methods In approximately 150,000 Chinese adults from the China Kadoorie Biobank, we investigated associations of rs7529229 (in strong linkage disequilibrium, r2=0.99, with the IL6R Asp358Ala variant rs2228145) with blood biomarkers and selected disease events in which inflammation has previously been implicated. First, we used linear regression to quantify the per-allele association of rs7529229 with levels in plasma of log-transformed C-reactive protein (CRP) (n=17,866), fibrinogen (n=9,255), and IL-6 protein (n=633). Second, we used logistic regression to evaluate the association of rs7529229 with incidence of CHD, stroke, cancer, and respiratory disease events. All models were adjusted for age, age-squared, sex (except breast cancer), and case ascertainment (for CRP and fibrinogen), and stratified by recruitment region. We assessed significance at a 5% false discovery rate. Results IL6R rs7529229 C-allele was associated with lower log CRP (–0.11 SDs per C-allele; p=4.9x10–25) and log fibrinogen (–0.07 SDs; p=2.2x10–7), and higher log IL-6 (0.15 SDs; p=0.011) (Figure 1), mimicking therapeutic blockade of IL6R. IL6R rs7529229 was associated with a lower risk of acute myocardial infarction (n=4,047 cases; OR: 0.92 [95% CI 0.88–0.96] per C-allele; p=2.8x10–4), with the association similar for fatal and non-fatal cases (Figure 2). There was no evidence of association with ischaemic stroke (n=18,315; OR: 1.00 [0.98–1.03]; p=0.90) or intracerebral haemorrhage (n=7,372; OR: 1.03 [0.99–1.07]; p=0.10). For non-cardiovascular diseases, the IL6R rs7529229 was associated with a lower risk of oesophageal (n=824; OR: 0.88 [0.79–0.97] per C-allele; p=0.013) and colorectal (n=1,151; OR: 0.89 [0.82–0.97]; p=8.3x10–3) cancers, but a higher risk of tuberculosis (n=1,017; OR: 1.15 [1.05–1.26]; p=2.4x10–3). Conclusion The results of the present study are consistent with a causal role for the IL-6 signalling pathway in the aetiology of myocardial infarction and some cancers, but not of stroke. These findings provide further genetic support for drug development targeting inflammation in the prevention and treatment of coronary and selected cancer outcomes. Acknowledgement/Funding Kadoorie Charitable Foundation, UK Wellcome Trust, Chinese Ministry of Science and Technology, BHF, CRUK, NIHR

Modification of Classical Hydraulic damper into Semi active damper using MR Approach

Modification of Classical Hydraulic damper into Semi active damper using MR Approach

Investigation of chemotherapy-induced brain structural alterations in breast cancer patients with generalized q-sampling MRI and graph theoretical analysis

BackgroundBreast neoplasms are the most common cancer among women in Taiwan. Cognitive deficits are common complications of breast cancer survivors treated with chemotherapy. The most frequently observed disorders involve executive function and memory impairment. With improvements in tumor intervention and the consequent increase in the number of cancer survivors, the quality of life of patients has become an important issue. We are interested in the early effects of chemotherapy on the brain structures of patients. In addition, generalized q-sampling imaging (GQI), a wide range of q-space datasets for a more accurate and sophisticated diffusion MR approach, was first used in this topic.MethodsAs diffusion tensor imaging (DTI) is associated with restrictions in the resolution of crossing fibers, we attempted to use GQI, which can overcome these difficulties and is advantageous over DTI for tractography of the crossing fibers. This cross-sectional study included two groups: breast cancer survivors who had completed their chemotherapy (n = 19) and healthy controls (n = 20). All participants underwent diffusion MRI exams and neuropsychological assessments. We included four parts in our image analysis, i.e., voxel-based statistical analysis, multiple regression analysis, graph theoretical analysis and network-based statistical analysis.ResultsThe results from the voxel-based statistical analysis showed significantly lower GFA and NQA values in the breast cancer group than those in the control group. We found significant positive correlations between the FACT-Cog and GQI indices. In the graph theoretical analysis, the breast cancer group demonstrated significantly longer characteristic path length. Adjuvant chemotherapy affected the integrity of white matter and resulted in poor cognitive performance, as indicated by the correlations between the neuropsychological assessment scales and the GQI indices. In addition, it was found that the characteristic path lengths in the breast cancer group increased, indicating that the brain network integration became worse.ConclusionsOur study demonstrated alterations in structural brain networks and associated neuropsychological deficits among breast cancer survivors.

In vivo myocardial tissue characterization of all four chambers using high-resolution quantitative MRI

Abstract Quantitative native T1 Mapping of the myocardium without the application of contrast agents can be used to detect fibrosis in the left ventricle. Spatial resolution of standard native T1 mapping is limited by cardiac motion and hence is not sufficient to resolve small myocardial structures, such as the right ventricle and the atria. Here, we present a novel MR approach which provides cardiac motion information and native T1 maps from the same data. Motion information is utilized to optimize data selection for T1 mapping and a model-based iterative reconstruction scheme ensures high-resolution T1 maps for the entire heart. Feasibility of the approach was demonstrated in three healthy volunteers. In the T1 maps, the myocardium of all four chambers can be visualized and T1 values of the left atrium and right chambers were comparable to left ventricular T1 values.

Does education protect against depression? Evidence from the Young Finns Study using Mendelian randomization

Using participants (N = 1733) drawn from the nationally representative longitudinal Young Finns Study (YFS) we estimate the effect of education on depressive symptoms. In 2007, when the participants were between 30 and 45 years old, they reported their depressive symptoms using a revised version of Beck's Depression Inventory. Education was measured using register information on the highest completed level of education in 2007, which was converted to years of education. To identify a causal relationship between education and depressive symptoms we use an instrumental variables approach (Mendelian randomization, MR) with a genetic risk score as an instrument for years of education. The genetic risk score was based on 74 genetic variants, which were associated with years of education in a genome-wide association study (GWAS). Because the genetic variants are randomly assigned at conception, they induce exogenous variation in years of education and thus identify a causal effect if the assumptions of the MR approach are met. In Ordinary Least Squares (OLS) estimation years of education in 2007 were negatively associated with depressive symptoms in 2007 (b = −0.027, 95% Confidence Interval (CI) = −0.040, −0.015). However, the results based on Mendelian randomization suggested that the effect is not causal (b = 0.017; 95% CI = −0.144, 0.178). This indicates that omitted variables correlated with education and depression may bias the linear regression coefficients and exogenous variation in education caused by differences in genetic make-up does not seem to protect against depressive symptoms.

Diagnostic accuracy of biparametric vs multiparametric MRI in clinically significant prostate cancer: Comparison between readers with different experience

BackgroundMRI plays a crucial role to identify men with a high likelihood of clinically significant prostate cancer who require immediate biopsy. The added value of DCE MRI in combination with T2-weighted imaging and DWI is controversial (risks related to gadolinium administration, duration of MR exam, financial burden, effects on diagnostic performance). A comparison of a biparametric and a standard multiparametric MR imaging protocol, taking into account the different experience of the readers, may help to choose the best MR approach regarding diagnostic performance. PurposeTo determine the added value of dynamic contrasted-enhanced imaging (DCE) over T2-weighted imaging (T2-WI) and diffusion weighted imaging (DWI) for the detection of clinically significant prostate cancer, and to evaluate how it affects the diagnostic performance of three readers with different grade of experience in prostate imaging. Materials and methodsEighty-five patients underwent prostate MR examination at 1.5 T MR scanner performed because of elevated prostate-specific antigen level and/or suspicion of prostate cancer at digital rectal examination.Two MR images sets (Set 1 = biparametric, Set 2 = multiparametric) were retrospectively and independently scored by three radiologists with 7, 3 and 1 years of experience in prostate MR imaging respectively, according to PI-RADS v2. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated by dichotomizing reader scores. Receiver operating characteristic (ROC) analysis was performed and areas under the curve (AUCs) were calculated for each reader and image set. A comparison of ROC curves was performed to test the difference between the areas under the ROC curves among the three readers. ResultsThere was no significant difference regarding the detection of clinically significant tumor among the three readers between the two image sets. The AUC for the bi-parametric and multi-parametric MR imaging protocol was respectively 0.68–0.72 (Reader 1), 0.72–0.70 (Reader 2) and 0.60–0.54 (Reader 3). ROC curve comparison revealed no statistically significant differences for each protocol among the most experienced (Reader 1) and the other readers (Readers 2–3). ConclusionThe diagnostic accuracy of a bi-parametric MR imaging protocol consisting of T2-weighted imaging and DWI is comparable with that of a standard multi-parametric imaging protocol for the detection of clinically significant prostate cancer. The experience of the reader does not significantly modify the diagnostic performance of both MR protocols.

Multicomponent Assessment of the Geometrical Uncertainty and Consequent Margins in Prostate Cancer Radiotherapy Treatment Using Fiducial Markers

The aim is to compute all sources of geometrical uncertainty in prostate radiotherapy using fiducial markers and determine the safety treatment margins. Based on the markers position, correlations between prostate rotation/deformation and rectal and bladder fillings as well as changes in prostate volume during the treatment course are analyzed. The study includes 375 pre-treatment CBCT images from 15 prostate cancer patients treated with hypofractionated radiotherapy. The position coordinates of the markers were obtained from each image acquisition. In addition, rectum and bladder were outlined on CBCTs. The intrafractional error was estimated by an additional post-treatment CBCT acquired on alternate days. Tau-Kendall analysis was performed to correlate organ fillings with prostate rotation/deformation. Delineation uncertainty was assessed from contours of 10 patients performed by two radiation oncologists and repeated twice. The CT contouring was assisted by a multiparametric MR approach combining a T2-weighted with diffusion-weighted imaging, and a gradient recalled echo for fiducial marker identification. Uncertainty associated to treatment unit was estimated from phantom measurements. The obtained clinical margins were 4.4, 7.3, 5.1 mm in the Left-Right, Superior-Inferior, and Anterior-Posterior directions, respectively, being the contouring the most important contribution. The mechanical limitations of the beam delivery system and the associated imaging device entailed errors of the same order as prostate motion, rotation or deformation. Weak correlations between variation of the rectal volume and the presence of rotations/deformations were found (correlation coefficient 0.182, p = 0.001 for rotations around lateral axis; correlation coefficients 0.1, p < 0.05 for deformations). The distance between markers decreased with session number, becoming more pronounced from fraction 13 and reaching 1 - 1.8 mm at the end of the treatment. In summary we have determined the optimal treatment margins based on geometrical uncertainty assessment using van Herk formalism. An appropriate preparation of rectum and bladder involves minimizing the effect of prostate rotations/deformations. The prostate tends to decrease in size during the treatment which could influence treatment re-planning strategies.

Time-Dependent Changes in T1 during Fracture Healing in Juvenile Rats: A Quantitative MR Approach.

Quantitative magnetic resonance imaging (qMRI) offers several advantages in imaging and determination of soft tissue alterations when compared to qualitative imaging techniques. Although applications in brain and muscle tissues are well studied, its suitability to quantify relaxation times of intact and injured bone tissue, especially in children, is widely unknown. The objective observation of a fracture including its age determination can become of legal interest in cases of child abuse or maltreatment. Therefore, the aim of this study is the determination of time dependent changes in intact and corresponding injured bones in immature rats via qMRI, to provide the basis for an objective and radiation-free approach for fracture dating. Thirty-five MR scans of 7 Sprague-Dawley rats (male, 4 weeks old, 100 ± 5 g) were acquired on a 3T MRI scanner (TimTrio, Siemens AG, Erlangen, Germany) after the surgical infliction of an epiphyseal fracture in the tibia. The images were taken at days 1, 3, 7, 14, 28, 42 and 82 post-surgery. A proton density-weighted and a T1-weighted 3D FLASH sequence were acquired to calculate the longitudinal relaxation time T1 of the fractured region and the surrounding tissues. The calculation of T1 in intact and injured bone resulted in a quantitative observation of bone development in intact juvenile tibiae as well as the bone healing process in the injured tibiae. In both areas, T1 decreased over time. To evaluate the differences in T1 behaviour between the intact and injured bone, the relative T1 values (bone-fracture) were calculated, showing clear detectable alterations of T1 after fracture occurrence. These results indicate that qMRI has a high potential not only for clinically relevant applications to detect growth defects or developmental alterations in juvenile bones, but also for forensically relevant applications such as the dating of fractures in cases of child abuse or maltreatment.

Methodology to Improve the AASHTO Subgrade Resilient Modulus Equation for Network-Level Use

AbstractFalling weight deflectometer (FWD) testing is commonly used to estimate subgrade resilient modulus (MR) by using back calculation and/or the AASHTO MR equation. Considering the availability of limited information in the pavement management information system (PMIS) database, the AASHTO MR approach is suitable for subgrade assessment at a network level because of its simplicity. An adjustment factor is commonly applied to the AASHTO MR equation because of the difference between laboratory-measured MR and estimated MR. However, large variations in the adjustment factor have been observed with different geographical locations and climate conditions. Thus, using a fixed value of the adjustment factor has led to inaccurate assessment of subgrade soil MR. This paper presents a methodology to improve the accuracy of the existing AASHTO MR equation by constructing an MR adjustment factor based on the correlation of back-calculated ER and AASHTO MR. This study also investigated the effects of subgrade soil...

DANTE-prepared three-dimensional FLASH: A fast isotropic-resolution MR approach to morphological evaluation of the peripheral arterial wall at 3 Tesla.

To develop and assess a sequence using DANTE dark-blood preparation combined with FLASH readout (DANTE-FLASH) for rapid isotropic-resolution three-dimensional (3D) peripheral vessel wall imaging at 3 Tesla (T). Numerical simulations were first conducted to optimize imaging parameters for maximizing the wall-lumen contrast. The sequence, implemented at 3T, was then assessed in the bilateral superficial femoral arteries of eight healthy volunteers and three patients who were undergoing non-contrast-enhanced MRA due to known peripheral artery disease. Conventional 2D dark-blood turbo spin echo (DB-TSE) was performed as a reference in all subjects. Image quality on a 5-point scale, apparent wall signal-to-noise ratio, apparent wall-lumen contrast-to-noise ratio, wall thickness, wall area and lumen area were assessed or measured in all healthy subjects. Additionally, the agreement in the depiction of wall thickening or luminal stenosis between DANTE-FLASH and DB-TSE, or MRA was assessed using a 4-point scale in the patient study. DANTE-FLASH allowed for a 30-cm-long coverage within 4 min, whereas DB-TSE took approximately 7 min for a 9-cm-long coverage. Good image quality was obtained by DANTE-FLASH (score > 3). The wall thickness, wall area, and lumen area were all comparable (t-test; P = 0.334, 0.224 and 0.136) and showed excellent agreement between DANTE-FLASH and DB-TSE (intra-class correlation = 0.81, 0.85, and 0.98). The atherosclerotic plaques and luminal stenosis identified by DANTE-FLASH were in accordance with the findings by 2D DB-TSE or MRA. DANTE-FLASH is a 3D dark-blood MR sequence allowing for rapid isotropic-resolution imaging of the peripheral vessel wall at 3T.