Radiomics and visual analysis for predicting success of transplantation of heterotopic glioblastoma in mice with MRI.

BACKGROUND: Quantifying tumor growth and treatment response noninvasively poses a challenge to all experimental tumor models. The aim of our study was, to assess the value of quantitative and visual examination and radiomic feature analysis of high-resolution MR images of heterotopic glioblastoma xenografts in mice to determine tumor cell proliferation (TCP). METHODS: Human glioblastoma cells were injected subcutaneously into both flanks of immunodeficient mice and followed up on a 3 T MR scanner. Volumes and signal intensities were calculated. Visual assessment of the internal tumor structure was based on a scoring system. Radiomic feature analysis was performed using MaZda software. The results were correlated with histopathology and immunochemistry. RESULTS: 21 tumors in 14 animals were analyzed. The volumes of xenografts with high TCP (H-TCP) increased, whereas those with low TCP (L-TCP) or no TCP (N-TCP) continued to decrease over time (p < 0.05). A low intensity rim (rim sign) on unenhanced T1-weighted images provided the highest diagnostic accuracy at visual analysis for assessing H-TCP (p < 0.05). Applying radiomic feature analysis, wavelet transform parameters were best for distinguishing between H-TCP and L-TCP / N-TCP (p < 0.05). CONCLUSION: Visual and radiomic feature analysis of the internal structure of heterotopically implanted glioblastomas provide reproducible and quantifiable results to predict the success of transplantation.

Bayesian modelling of time series data (BayModTS)-a FAIR workflow to process sparse and highly variable data.

MOTIVATION: Systems biology aims to better understand living systems through mathematical modelling of experimental and clinical data. A pervasive challenge in quantitative dynamical modelling is the integration of time series measurements, which often have high variability and low sampling resolution. Approaches are required to utilize such information while consistently handling uncertainties. RESULTS: We present BayModTS (Bayesian modelling of time series data), a new FAIR (findable, accessible, interoperable, and reusable) workflow for processing and analysing sparse and highly variable time series data. BayModTS consistently transfers uncertainties from data to model predictions, including process knowledge via parameterized models. Further, credible differences in the dynamics of different conditions can be identified by filtering noise. To demonstrate the power and versatility of BayModTS, we applied it to three hepatic datasets gathered from three different species and with different measurement techniques: (i) blood perfusion measurements by magnetic resonance imaging in rat livers after portal vein ligation, (ii) pharmacokinetic time series of different drugs in normal and steatotic mice, and (iii) CT-based volumetric assessment of human liver remnants after clinical liver resection. AVAILABILITY AND IMPLEMENTATION: The BayModTS codebase is available on GitHub at https://github.com/Systems-Theory-in-Systems-Biology/BayModTS. The repository contains a Python script for the executable BayModTS workflow and a widely applicable SBML (systems biology markup language) model for retarded transient functions. In addition, all examples from the paper are included in the repository. Data and code of the application examples are stored on DaRUS: https://doi.org/10.18419/darus-3876. The raw MRI ROI voxel data were uploaded to DaRUS: https://doi.org/10.18419/darus-3878. The steatosis metabolite data are published on FairdomHub: 10.15490/fairdomhub.1.study.1070.1.

Effects of Tetrahydrolipstatin on Glioblastoma in Mice: MRI-Based Morphologic and Texture Analysis Correlated with Histopathology and Immunochemistry Findings-A Pilot Study.

BACKGROUND: This study aimed to investigate the effects of tetrahydrolipstatin (orlistat) on heterotopic glioblastoma in mice by applying MRI and correlating the results with histopathology and immunochemistry. METHODS: Human glioblastoma cells were injected subcutaneously into the groins of immunodeficient mice. After tumor growth of >150 mm3, the animals were assigned into a treatment group (n = 6), which received daily intraperitoneal injections of orlistat, and a control group (n = 7). MRI was performed at the time of randomization and before euthanizing the animals. Tumor volumes were calculated, and signal intensities were analyzed. The internal tumor structure was evaluated visually and with texture analysis. Western blotting and protein expression analysis were performed. RESULTS: At histology, all tumors showed high mitotic and proliferative activity (Ki67 ≥ 10%). Reduced fatty acid synthetase expression was measured in the orlistat group (p < 0.05). Based on the results of morphologic MRI-based analysis, tumor growth remained concentric in the control group and changed to eccentric in the treatment group (p < 0.05). The largest area under the receiver operating curve of the predictors derived from the texture analysis of T2w images was for wavelet transform parameters WavEnHL_s3 and WavEnLH_s4 at 0.96 and 1.00, respectively. CONCLUSIONS: Orlistat showed effects on heterotopically implanted glioblastoma multiforme in MRI studies of mice based on morphologic and texture analysis.

Targeted Disruption of the MORG1 Gene in Mice Causes Embryonic Resorption in Early Phase of Development.

The mitogen-activated protein kinase organizer 1 (MORG1) is a scaffold molecule for the ERK signaling pathway, but also binds to prolyl-hydroxylase 3 and modulates HIFα expression. To obtain further insight into the role of MORG1, knockout-mice were generated by homologous recombination. While Morg1+/- mice developed normally without any apparent phenotype, there were no live-born Morg1-/- knockout offspring, indicating embryonic lethality. The intrauterine death of Morg1-/- embryos is caused by a severe failure to develop brain and other neuronal structures such as the spinal cord and a failure of chorioallantoic fusion. On E8.5, Morg1-/- embryos showed severe underdevelopment and proliferative arrest as indicated by absence of Ki67 expression, impaired placental vascularization and altered phenotype of trophoblast giant cells. On E9.5, the malformed Morg1-/- embryos showed defective turning into the final fetal position and widespread apoptosis in many structures. In the subsequent days, apoptosis and decomposition of embryonic tissue progressed, accompanied by a massive infiltration of inflammatory cells. Developmental aberrancies were accompanied by altered expression of HIF-1/2α and VEGF-A and caspase-3 activation in embryos and extraembryonic tissues. In conclusion, the results suggest a multifactorial process that causes embryonic death in homozygous Morg1 mutant mice, described here, to the best of our knowledge, for the first time.

Perfusion and T2 Relaxation Time as Predictors of Severity and Outcome in Sepsis-Associated Acute Kidney Injury: A Preclinical MRI Study.

BACKGROUND: Preventing sepsis-associated acute kidney injury (S-AKI) can be challenging because it develops rapidly and is often asymptomatic. Probability assessment of disease progression for therapeutic follow-up and outcome are important to intervene and prevent further damage. PURPOSE: To establish a noninvasive multiparametric MRI (mpMRI) tool, including T1 , T2 , and perfusion mapping, for probability assessment of the outcome of S-AKI. STUDY TYPE: Preclinical randomized prospective study. ANIMAL MODEL: One hundred and forty adult female SD rats (65 control and 75 sepsis). FIELD STRENGTH/SEQUENCE: 9.4T; T1 and perfusion map (FAIR-EPI) and T2 map (multiecho RARE). ASSESSMENT: Experiment 1: To identify renal injury in relation to sepsis severity, serum creatinine levels were determined (31 control and 35 sepsis). Experiment 2: Animals underwent mpMRI (T1 , T2 , perfusion) 18 hours postsepsis. A subgroup of animals was immediately sacrificed for histology examination (nine control and seven sepsis). Result of mpMRI in follow-up subgroup (25 control and 33 sepsis) was used to predict survival outcomes at 96 hours. STATISTICAL TESTS: Mann-Whitney U test, Spearman/Pearson correlation (r), P < 0.05 was considered statistically significant. RESULTS: Severely ill septic animals exhibited significantly increased serum creatinine levels compared to controls (70 ± 30 vs. 34 ± 9 µmol/L, P < 0.0001). Cortical perfusion (480 ± 80 vs. 330 ± 140 mL/100 g tissue/min, P < 0.005), and cortical and medullary T2 relaxation time constants were significantly reduced compared to controls (41 ± 4 vs. 37 ± 5 msec in cortex, P < 0.05, 52 ± 7 vs. 45 ± 6 msec in medulla, P < 0.05). The combination of cortical T2 relaxation time constants and perfusion results at 18 hours could predict survival outcomes at 96 hours with high sensitivity (80%) and specificity (73%) (area under curve of ROC = 0.8, Jmax = 0.52). DATA CONCLUSION: This preclinical study suggests combined T2 relaxation time and perfusion mapping as first line diagnostic tool for treatment planning. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Brain Macro-Structural Alterations in Aging Rats: A Longitudinal Lifetime Approach.

Aging is accompanied by macro-structural alterations in the brain that may relate to age-associated cognitive decline. Animal studies could allow us to study this relationship, but so far it remains unclear whether their structural aging patterns correspond to those in humans. Therefore, by applying magnetic resonance imaging (MRI) and deformation-based morphometry (DBM), we longitudinally screened the brains of male RccHan:WIST rats for structural changes across their average lifespan. By combining dedicated region of interest (ROI) and voxel-wise approaches, we observed an increase in their global brain volume that was superimposed by divergent local morphologic alterations, with the largest aging effects in early and middle life. We detected a modality-dependent vulnerability to shrinkage across the visual, auditory, and somato-sensory cortical areas, whereas the piriform cortex showed partial resistance. Furthermore, shrinkage emerged in the amygdala, subiculum, and flocculus as well as in frontal, parietal, and motor cortical areas. Strikingly, we noticed the preservation of ectorhinal, entorhinal, retrosplenial, and cingulate cortical regions, which all represent higher-order brain areas and extraordinarily grew with increasing age. We think that the findings of this study will further advance aging research and may contribute to the establishment of interventional approaches to preserve cognitive health in advanced age.

Characterization of microparticles of iron oxide for magnetic resonance imaging.

Microparticles of iron oxide (MPIOs) are increasingly used for contrast generation in magnetic resonance imaging (MRI). In particular, Dynabeads® MyOne™ Tosylactivated MPIOs have enabled sensitive and targeted molecular imaging, e.g., to detect vascular inflammation. For the first time we measured the relaxivities as well as the molar susceptibility χM of these MPIOs at 7 T in agarose gels. They are r1 = 0.69 ± 0.03 s-1/mM, r2 = 220 ± 6 s-1/mM, r2* = 679 ± 14 s-1/mM, and χM = 0.66 ± 0.05 ppm/mM, when expressed with respect to the iron concentration. These material parameters are essential to optimize MRI protocols and progress toward quantitative imaging. To address the heterogeneous nature of the MPIO distributions over the size of a typical MRI voxel, we coupled the MPIOs to a fluorophore to create a bimodal phantom that can be imaged by both Light Sheet microscopy and MRI. In this phantom, the MPIOs produced contrast similar to that found in vivo . The submicron resolution of Light Sheet microscopy images provided a precise measurement of the MPIO spatial distribution in phantoms also imaged by MRI. MPIO aggregates occupying less than one MRI voxel were responsible for alterations in R2* and magnetic susceptibility χ across several MRI voxels. In these cases, the sum of R2* or χ over the affected MRI volume correlated better with the microscopically determined number of MPIOs. These findings were confirmed with simulations performed in the static dephasing regime. The microscopically determined MPIO distribution was also entered directly into the simulation framework, indicating that the bimodal phantom is a useful tool to test theoretical models against experimental measurements.

High-resolution MRI of the human palatine tonsil and its schematic anatomic 3D reconstruction.

The palatine tonsils form an important part of the human immune system. Together with the other lymphoid tonsils of Waldeyer's tonsillar ring, they act as the first line of defense against ingested or inhaled pathogens. Although histologically stained sections of the palatine tonsil are widely available, they represent the tissue only in two dimensions and do not provide reference to three-dimensional space. Such a representation of a tonsillar specimen based on imaging data as a 3D anatomical reconstruction is lacking both in scientific publications and especially in textbooks. As a first step in this direction, the objective of the present work was to image a resected tonsil specimen with high spatial resolution in a 9.4 T small-bore pre-clinical MRI and to combine these data with data from the completely sectioned and H&E stained same palatine tonsil. Based on the information from both image modalities, a 3D anatomical sketch was drawn by a scientific graphic artist. In perspective, such studies could help to overcome the difficulty of capturing the spatial extent and arrangement of anatomical structures from 2D images and to establish a link between three-dimensional anatomical preparations and two-dimensional sections or illustrations, as they have been found so far in common textbooks and anatomical atlases.

Ultrashort echo time MRI of the lung in children and adolescents: comparison with non-enhanced computed tomography and standard post-contrast T1w MRI sequences.

OBJECTIVES: To compare the diagnostic value of ultrashort echo time (UTE) magnetic resonance imaging (MRI) for the lung versus the gold standard computed tomography (CT) and two T1-weighted MRI sequences in children. METHODS: Twenty-three patients with proven oncologic disease (14 male, 9 female; mean age 9.0 + / - 5.4 years) received 35 low-dose CT and MRI examinations of the lung. The MRI protocol (1.5-T) included the following post-contrast sequences: two-dimensional (2D) incoherent gradient echo (GRE; acquisition with breath-hold), 3D volume interpolated GRE (breath-hold), and 3D high-resolution radial UTE sequences (performed during free-breathing). Images were evaluated by considering image quality as well as distinct diagnosis of pulmonary nodules and parenchymal areal opacities with consideration of sizes and characterisations. RESULTS: The UTE technique showed significantly higher overall image quality, better sharpness, and fewer artefacts than both other sequences. On CT, 110 pulmonary nodules with a mean diameter of 4.9 + / - 2.9 mm were detected. UTE imaging resulted in a significantly higher detection rate compared to both other sequences (p < 0.01): 76.4% (84 of 110 nodules) for UTE versus 60.9% (67 of 110) for incoherent GRE and 62.7% (69 of 110) for volume interpolated GRE sequences. The detection of parenchymal areal opacities by the UTE technique was also significantly higher with a rate of 93.3% (42 of 45 opacities) versus 77.8% (35 of 45) for 2D GRE and 80.0% (36 of 45) for 3D GRE sequences (p < 0.05). CONCLUSION: The UTE technique for lung MRI is favourable in children with generally high diagnostic performance compared to standard T1-weighted sequences as well as CT. Key Points • Due to the possible acquisition during free-breathing of the patients, the UTE MRI sequence for the lung is favourable in children. • The UTE technique reaches higher overall image quality, better sharpness, and lower artefacts, but not higher contrast compared to standard post-contrast T1-weighted sequences. • In comparison to the gold standard chest CT, the detection rate of small pulmonary nodules small nodules ≤ 4 mm and subtle parenchymal areal opacities is higher with the UTE imaging than standard T1-weighted sequences.

Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function.

Liver resection causes marked perfusion alterations in the liver remnant both on the organ scale (vascular anatomy) and on the microscale (sinusoidal blood flow on tissue level). These changes in perfusion affect hepatic functions via direct alterations in blood supply and drainage, followed by indirect changes of biomechanical tissue properties and cellular function. Changes in blood flow impose compression, tension and shear forces on the liver tissue. These forces are perceived by mechanosensors on parenchymal and non-parenchymal cells of the liver and regulate cell-cell and cell-matrix interactions as well as cellular signaling and metabolism. These interactions are key players in tissue growth and remodeling, a prerequisite to restore tissue function after PHx. Their dysregulation is associated with metabolic impairment of the liver eventually leading to liver failure, a serious post-hepatectomy complication with high morbidity and mortality. Though certain links are known, the overall functional change after liver surgery is not understood due to complex feedback loops, non-linearities, spatial heterogeneities and different time-scales of events. Computational modeling is a unique approach to gain a better understanding of complex biomedical systems. This approach allows (i) integration of heterogeneous data and knowledge on multiple scales into a consistent view of how perfusion is related to hepatic function; (ii) testing and generating hypotheses based on predictive models, which must be validated experimentally and clinically. In the long term, computational modeling will (iii) support surgical planning by predicting surgery-induced perfusion perturbations and their functional (metabolic) consequences; and thereby (iv) allow minimizing surgical risks for the individual patient. Here, we review the alterations of hepatic perfusion, biomechanical properties and function associated with hepatectomy. Specifically, we provide an overview over the clinical problem, preoperative diagnostics, functional imaging approaches, experimental approaches in animal models, mechanoperception in the liver and impact on cellular metabolism, omics approaches with a focus on transcriptomics, data integration and uncertainty analysis, and computational modeling on multiple scales. Finally, we provide a perspective on how multi-scale computational models, which couple perfusion changes to hepatic function, could become part of clinical workflows to predict and optimize patient outcome after complex liver surgery.

Pulmonary Arteriovenous Pressure Gradient and Time-Averaged Mean Velocity of Small Pulmonary Arteries Can Serve as Sensitive Biomarkers in the Diagnosis of Pulmonary Arterial Hypertension: A Preclinical Study by 4D-Flow MRI.

(1) Background: Pulmonary arterial hypertension (PAH) is a serious condition that is associated with many cardiopulmonary diseases. Invasive right heart catheterization (RHC) is currently the only method for the definitive diagnosis and follow-up of PAH. In this study, we sought a non-invasive hemodynamic biomarker for the diagnosis of PAH. (2) Methods: We applied prospectively respiratory and cardiac gated 4D-flow MRI at a 9.4T preclinical scanner on three different groups of Sprague Dawley rats: baseline (n = 11), moderate PAH (n = 8), and severe PAH (n = 8). The pressure gradients as well as the velocity values were analyzed from 4D-flow data and correlated with lung histology. (3) Results: The pressure gradient between the pulmonary artery and vein on the unilateral side as well as the time-averaged mean velocity values of the small pulmonary arteries were capable of distinguishing not only between baseline and severe PAH, but also between the moderate and severe stages of the disease. (4) Conclusions: The current preclinical study suggests the pulmonary arteriovenous pressure gradient and the time-averaged mean velocity as potential biomarkers to diagnose PAH.

Experience-dependent structural plasticity in the adult brain: How the learning brain grows.

Volumetric magnetic resonance imaging studies have shown that intense learning can be associated with grey matter volume increases in the adult brain. The underlying mechanisms are poorly understood. Here we used monocular deprivation in rats to analyze the mechanisms underlying use-dependent grey matter increases. Optometry for quantification of visual acuity was combined with volumetric magnetic resonance imaging and microscopic techniques in longitudinal and cross-sectional studies. We found an increased spatial vision of the open eye which was associated with a transient increase in the volumes of the contralateral visual and lateral entorhinal cortex. In these brain areas dendrites of neurons elongated, and there was a strong increase in the number of spines, the targets of synapses, which was followed by spine maturation and partial pruning. Astrocytes displayed a transient pronounced swelling and underwent a reorganization of their processes. The use-dependent increase in grey matter corresponded predominantly to the swelling of the astrocytes. Experience-dependent increase in brain grey matter volume indicates a gain of structure plasticity with both synaptic and astrocyte remodeling.

Comparison of image quality in brain MRI with and without MR compatible incubator and predictive value of brain MRI at expected delivery date in preterm babies.

Objectives MR compatible incubators (MRcI) offer the examination of preterm and critically ill infants in controlled environment. The aim of the study was to compare objective and subjective image quality as well as diagnostic value of MRI brain examinations with and without using the MRcI. Thus, predictive value of brain MRI at expected delivery date in general was investigated. Methods This retrospective study included MRI brain examinations conducted at patients' corrected age ≤6 months and presence of four standard sequences (PD TSE transversal, T2 TSE transversal, T2 TSE sagittal and T1 SE transversal). Signal-to-Noise Ratio (SNR) and Contrast-to-Noise Ratio (CNR) was calculated. Subjective image quality was estimated using a 5-point Likert scale. Findings of MRI were compared with those of previous transfontanellar ultrasound because of additional diagnostic information. Severe brain abnormality scaled by score of Kidokoro was related to results of Munich Functional Developmental Diagnostics (MFDD) within first year. Results One hundred MRI brain examinations (76 with MRcI, 24 without MRcI) were performed in 79 patients. Using the MRcI SNR and CNR were significantly higher in PD- and in T2-weighted sequences (p<0.05). TSE PD transversal demonstrated a higher risk of non-diagnostic quality using MRcI (OR 5.23; 95%-CI 1.86-14.72). MRcI revealed additional diagnostic information (OR 5.69; 95%-CI 1.15-28.24). Severe brain abnormality was associated with walking deficits (r=0.570; p=0.021). Conclusions The MRcI increased objective image quality and revealed additional diagnostic information to transfontanellar ultrasound. Nevertheless, prediction of infants' future development remains limited.

MRI as an alternative to serum ferritin for diagnosis of iron overload in children in the context of immune response after stem cell transplantation.

Multiple blood cell transfusions may cause iron overload or even liver fibrosis, requiring early diagnosis and intervention. SF is the standard for estimating iron levels in the body, but it also increases with inflammation. We hypothesized that T2 * magnetic resonance (MR) relaxometry is a more accurate alternative for follow-up in pediatric patients before and after allogenic SCT. Twenty-three children (mean age 10.2 years, 10 female, 13 male) were evaluated prospectively before SCT as well as at least 1 year after SCT with T2 * relaxometry on a 1.5 T MR-scanner to estimate liver iron concentrations from the T2 * values ("MR-Fe"). The results were compared with SF, while also considering CRP, and correlated with the number of transfusions. Overall, 24.3 transfusions were administered in average, mainly within 100 days of SCT (mean 10.5 units). Both MR-Fe and SF increased after SCT and decreased in the absence of new transfusions 1 year later without chelate therapy. This suggests regeneration of LP and iron loss, although the original states were not reached. Additionally, simultaneous peaks of CRP and SF were observed directly after SCT. MR-Fe did neither reveal these peaks nor was it associated with CRP (P = .39). We postulate that these early CRP and SF peaks after SCT are probably related to inflammatory reactions and not to iron overload. Thus, SF is not reliable for iron overload diagnosis after SCT in every condition. Beside this interaction, SF and MR-Fe revealed similar accuracy. MRI, however, has practical and economical disadvantages in routine estimation of iron.

Propentdyopents as Heme Degradation Intermediates Constrict Mouse Cerebral Arterioles and Are Present in the Cerebrospinal Fluid of Patients With Subarachnoid Hemorrhage.

RATIONALE: Delayed ischemic neurological deficit is the most common cause of neurological impairment and unfavorable prognosis in patients with subarachnoid hemorrhage (SAH). Despite the existence of neuroimaging modalities that depict the onset of the accompanying cerebral vasospasm, preventive and therapeutic options are limited and fail to improve outcome owing to an insufficient pathomechanistic understanding of the delayed perfusion deficit. Previous studies have suggested that BOXes (bilirubin oxidation end products), originating from released heme surrounding ruptured blood vessels, are involved in arterial vasoconstriction. Recently, isolated intermediates of oxidative bilirubin degradation, known as PDPs (propentdyopents), have been considered as potential additional effectors in the development of arterial vasoconstriction. OBJECTIVE: To investigate whether PDPs and BOXes are present in hemorrhagic cerebrospinal fluid and involved in the vasoconstriction of cerebral arterioles. METHODS AND RESULTS: Via liquid chromatography/mass spectrometry, we measured increased PDP and BOX concentrations in cerebrospinal fluid of SAH patients compared with control subjects. Using differential interference contrast microscopy, we analyzed the vasoactivity of PDP isomers in vitro by monitoring the arteriolar diameter in mouse acute brain slices. We found an arteriolar constriction on application of PDPs in the concentration range that occurs in the cerebrospinal fluid of patients with SAH. By imaging arteriolar diameter changes using 2-photon microscopy in vivo, we demonstrated a short-onset vasoconstriction after intrathecal injection of either PDPs or BOXes. Using magnetic resonance imaging, we observed a long-term PDP-induced delay in cerebral perfusion. For all conditions, the arteriolar narrowing was dependent on functional big conductance potassium channels and was absent in big conductance potassium channels knockout mice. CONCLUSIONS: For the first time, we have quantified significantly higher concentrations of PDP and BOX isomers in the cerebrospinal fluid of patients with SAH compared to controls. The vasoconstrictive effect caused by PDPs in vitro and in vivo suggests a hitherto unrecognized pathway contributing to the pathogenesis of delayed ischemic deficit in patients with SAH.

Evaluation of liver tissue by ultrasound elastography and clinical parameters in children with multiple blood cell transfusions.

BACKGROUND: Children receiving multiple blood cell transfusions are prone to iron overload and successive tissue damage in liver parenchyma, making noninvasive screening options desirable. Ultrasound (US) elastography using acoustic radiation force impulse (ARFI) imaging enables evaluation of liver parenchyma stiffness, and MRI allows for quantification of liver iron concentration. OBJECTIVE: The objective was to correlate US elastography with MRI in children who had undergone bone marrow transplantation and to evaluate the modification of liver tissue with US in combination with clinical parameters at follow-up. MATERIALS AND METHODS: ARFI, T2*-weighted MRI and a clinical score (HepScore, based on parameters of liver function) were performed in 45 patients (24 male; mean age 9.7 years) before and 100 days and 365 days after transplantation. All received multiple blood transfusions (mean number 22.2 up until 1 year after transplantation). We correlated US findings and HepScore with MRI findings. RESULTS: We observed signs of iron accumulation in 29/45 (64.4%) patients on MRI (T2*<10 ms) and 15/45 (33.3%) showed increased tissue stiffness (ARFI>5.5 kPa). Correlation of elastography and MRI was not significant (P=0.57; n=51 matched measurements). Comparing US elastography with HepScore in receiver operating characteristic (ROC) curve analysis indicated a cut-off for affected parenchyma if HepScore was >5 points (sensitivity 67%, specificity 68%). Simultaneous increases of both indicated tissue alteration. CONCLUSION: Combining US and HepScore enabled detection of liver tissue alteration through iron overload, but we found no direct significant effect of estimated iron from MRI on ARFI imaging.

Computational Modeling in Liver Surgery.

The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery.

Luminomagnetic Eu3+- and Dy3+-doped hydroxyapatite for multimodal imaging.

Multimodal imaging has recently attracted much attention due to the advantageous combination of different imaging modalities, like photoluminescence (PL) and magnetic resonance imaging (MRI). In the present study, luminescent and magnetic hydroxyapatites (HAp) were prepared via doping with europium (Eu3+) and dysprosium (Dy3+), respectively. Co-doping of Eu3+ and Dy3+ was used to combine the desired physical properties. Both lanthanide ions were successfully incorporated in the HAp crystal lattice, where they preferentially occupied calcium(I) sites. While Eu-doped HAp (Eu:HAp) exhibits dopant concentration dependent persistent PL properties, Dy-doped HAp (Dy:HAp) shows paramagnetic behavior due to the high magnetic moment of Dy3+. Co-doped HAp (Eu:Dy:HAp) nanoparticles combine both properties in one single crystal. Remarkably, multimodal co-doped HAp features enhanced PL properties due to an energy transfer from Dy3+ sensitizer to Eu3+ activator ions. Eu:Dy:HAp exhibits strong transverse relaxation effects with a maximum transverse relaxivity of 83.3L/(mmol·s). Due to their tunable PL, magnetic properties and cytocompatibility Eu:-, Dy:- and Eu:Dy:HAp represent promising biocompatible ceramic materials for luminescence imaging that simultaneously may serve as a contrast agent for MRI in permanent implants or functional coatings.

GlucoCEST magnetic resonance imaging in vivo may be diagnostic of acute renal allograft rejection.

Acute cellular renal allograft rejection (AR) frequently occurs after kidney transplantations. It is a sterile T-cell mediated inflammation leading to increased local glucose metabolism. Here we demonstrate in an allogeneic model of Brown Norway rat kidneys transplanted into uninephrectomized Lewis rats the successful implementation of the recently developed glucose chemical exchange saturation transfer (glucoCEST) magnetic resonance imaging. This technique is a novel method to assess and differentiate AR. Renal allografts undergoing AR showed significantly increased glucoCEST contrast ratios of cortex to medulla of 1.61 compared to healthy controls (1.02), syngeneic Lewis kidney to Lewis rat transplants without rejection (0.92), kidneys with ischemia reperfusion injury (0.99) and kidneys affected by cyclosporine A toxicity (1.10). Receiver operating characteristic curve analysis showed an area under the curve value of 0.92, and the glucoCEST contrast ratio predicted AR with a sensitivity of 100% and a specificity of 69% at a threshold level over 1.08. In defined animal models of kidney injuries, the glucoCEST contrast ratios of cortex to medulla correlated positively with mRNA expression levels of T-cell markers (CD3, CD4, CD8a/b), but did not correlate to impaired renal perfusion. Thus, the glucoCEST parameter may be valuable for the assessment and follow up treatment of AR.

Time Efficient 3D Radial UTE Sampling with Fully Automatic Delay Compensation on a Clinical 3T MR Scanner.

This work's aim was to minimize the acquisition time of a radial 3D ultra-short echo-time (UTE) sequence and to provide fully automated, gradient delay compensated, and therefore artifact free, reconstruction. The radial 3D UTE sequence (echo time 60 µs) was implemented as single echo acquisition with center-out readouts and improved time efficient spoiling on a clinical 3T scanner without hardware modifications. To assess the sequence parameter dependent gradient delays each acquisition contained a quick calibration scan and utilized the phase of the readouts to detect the actual k-space center. This calibration scan does not require any user interaction. To evaluate the robustness of this automatic delay estimation phantom experiments were performed and 19 in vivo imaging data of the head, tibial cortical bone, feet and lung were acquired from 6 volunteers. As clinical application of this fast 3D UTE acquisition single breath-hold lung imaging is demonstrated. The proposed sequence allowed very short repetition times (TR~1ms), thus reducing total acquisition time. The proposed, fully automated k-phase based gradient delay calibration resulted in accurate delay estimations (difference to manually determined optimal delay -0.13 ± 0.45 µs) and allowed unsupervised reconstruction of high quality images for both phantom and in vivo data. The employed fast spoiling scheme efficiently suppressed artifacts caused by incorrectly refocused echoes. The sequence proved to be quite insensitive to motion, flow and susceptibility artifacts and provides oversampling protection against aliasing foldovers in all directions. Due to the short TR, acquisition times are attractive for a wide range of clinical applications. For short T2* mapping this sequence provides free choice of the second TE, usually within less scan time as a comparable dual echo UTE sequence.