Does serous tubal intraepithelial carcinoma (STIC) metastasize? The clonal relationship between STIC and subsequent high-grade serous carcinoma in BRCA1/2 mutation carriers several years after risk-reducing salpingo-oophorectomy.

OBJECTIVE: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood. METHODS: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing. RESULTS: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months). CONCLUSION: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.

[Effects of a smoke-free policy on healthcare staff attitudes and aggression in psychiatry]. / Effecten van een rookvrijbeleid op attitudes zorgpersoneel en agressie in de psychiatrie.

Background The prevalence of smoking among patients with psychiatric disorders is 3-4 times higher than the general population. However, smoking is still permitted in many psychiatric clinics. The National Prevention Agreement (2018) mandates that all psychiatric wards be smoke-free by 2025. The UMC Utrecht clinics have been smoke-free since November 2020. Aim To examine healthcare workers’ attitudes before and after implementing the smoke-free policy. Method In an observational study with quantitative data analysis, data were collected in one center from healthcare workers in psychiatry departments with surveys. We collected demographic information, smoking status, attitudes towards the smoke-free policy, and its impact on patients and care. Incidents of aggression were prospectively recorded and reported in the MAP (aggression incidents in patient care). Results Out of 172 healthcare workers invited to participate, 30% (n = 52) completed the pre-implementation survey, and 20% (n = 34) completed the post-implementation survey. Prior to implementation, 62% (n = 32/52) of healthcare workers had a positive attitude towards the smoke-free policy, which increased to 77% (n = 26/34) post-implementation. Expectations of increased aggression incidents were reported by 62% (n = 32/52) during the pre-implementation phase. The number of aggression incidents was 46 in the one-year period before implementation (November 2019 – February 2020) and 45 incidents after implementation (November 2020 – February 2021). Conclusion This study supports the implementation of a smoke-free policy in psychiatric clinics due to the lack of a significant increase in aggression incidents. Healthcare workers perceived this outcome and observed quicker granting of ‘green’ freedoms.

A database for MR-based electrical properties tomography with in silico brain data-ADEPT.

PURPOSE: Several reconstruction methods for MR-based electrical properties tomography (EPT) have been developed. However, the lack of common data makes it difficult to objectively compare their performances. This is, however, a necessary precursor for standardizing and introducing this technique in the clinical setting. To enable objective comparison of the performances of reconstruction methods and provide common data for their training and testing, we created ADEPT, a database of simulated data for brain MR-EPT reconstructions. METHODS: ADEPT is a database containing in silico data for brain EPT reconstructions. This database was created from 25 different brain models, with and without tumors. Rigid geometric augmentations were applied, and different electrical properties were assigned to white matter, gray matter, CSF, and tumors to generate 120 different brain models. These models were used as input for finite-difference time-domain simulations in Sim4Life, used to compute the electromagnetic fields needed for MR-EPT reconstructions. RESULTS: Electromagnetic fields from 84 healthy and 36 tumor brain models were simulated. The simulated fields relevant for MR-EPT reconstructions (transmit and receive RF fields and transceive phase) and their ground-truth electrical properties are made publicly available through ADEPT. Additionally, nonattainable fields such as the total magnetic field and the electric field are available upon request. CONCLUSION: ADEPT will serve as reference database for objective comparisons of reconstruction methods and will be a first step toward standardization of MR-EPT reconstructions. Furthermore, it provides a large amount of data that can be exploited to train data-driven methods. It can be accessed from  https://doi.org/10.34894/V0HBJ8.

Ultrastructural characterization of maturing iPSC-derived nephron structures upon transplantation.

Pluripotent stem cell-derived kidney organoids hold great promise as a potential auxiliary transplant tissue for individuals with end-stage renal disease and as a platform for studying kidney diseases and drug discovery. To establish accurate models, it is crucial to thoroughly characterize the morphological features and maturation stages of the cellular components within these organoids. Nephrons, the functional units of the kidney, possess distinct morphological structures that directly correlate with their specific functions. High spatial resolution imaging emerges as a powerful technique for capturing ultrastructural details that may go unnoticed with other methods such as immunofluorescent imaging and scRNA sequencing. In our study, we have applied software capable of seamlessly stitching virtual slides generated from electron microscopy, resulting in high-definition overviews of tissue slides. With this technology, we can comprehensively characterize the development and maturation of kidney organoids when transplanted under the renal capsule of mice. These organoids exhibit advanced ultrastructural developments upon transplantation, including the formation of the filtration barrier in the renal corpuscle, the presence of microvilli in the proximal tubule, and various types of cell sub-segmentation in the connecting tubule similarly to those seen in the adult kidney. Such ultrastructural characterization provides invaluable insights into the structural development and functional morphology of nephron segments within kidney organoids and how to advance them by interventions such as a transplantation. Research Highlights High-resolution imaging is crucial to determine morphological maturation of hiPSC-derived kidney organoids. Upon transplantation, refined ultrastructural development of nephron segments was observed, such as the development of the glomerular filtration barrier.

An Overview of the Protein Binding of Cephalosporins in Human Body Fluids: A Systematic Review.

Introduction: Protein binding can diminish the pharmacological effect of beta-lactam antibiotics. Only the free fraction has an antibacterial effect. The aim of this systematic literature review was to give an overview of the current knowledge of protein binding of cephalosporins in human body fluids as well as to describe patient characteristics influencing the level of protein binding. Method: A systematic literature search was performed in Embase, Medline ALL, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials with the following search terms: "protein binding," "beta-lactam antibiotic," and "body fluid." Only studies were included where protein binding was measured in humans in vivo. Results: The majority of studies reporting protein binding were performed in serum or plasma. Other fluids included pericardial fluid, blister fluid, bronchial secretion, pleural exudate, wound exudate, cerebrospinal fluid, dialysate, and peritoneal fluid. Protein binding differs between diverse cephalosporins and between different patient categories. For cefazolin, ceftriaxone, cefpiramide, and cefonicid a non-linear pattern in protein binding in serum or plasma was described. Several patient characteristics were associated with low serum albumin concentrations and were found to have lower protein binding compared to healthy volunteers. This was for critically ill patients, dialysis patients, and patients undergoing cardiopulmonary bypass during surgery. While mean/median percentages of protein binding are lower in these patient groups, individual values may vary considerably. Age is not likely to influence protein binding by itself, however limited data suggest that lower protein binding in newborns. Obesity was not correlated with altered protein binding. Discussion/Conclusion: Conclusions on protein binding in other body fluids than blood cannot be drawn due to the scarcity of data. In serum and plasma, there is a large variability in protein binding per cephalosporin and between different categories of patients. Several characteristics were identified which lead to a lower protein binding. The finding that some of the cephalosporins display a non-linear pattern of protein binding makes it even more difficult to predict the unbound concentrations in individual patients. Taken all these factors, it is recommended to measure unbound concentrations to optimize antibiotic exposure in individual patients. Systematic Review Registration: PROSPERO, identifier (CRD42021252776).

Technical feasibility of magnetic resonance fingerprinting on a 1.5T MRI-linac.

Hybrid MRI-linac (MRL) systems enable daily multiparametric quantitative MRI to assess tumor response to radiotherapy. Magnetic resonance fingerprinting (MRF) may provide time efficient means of rapid multiparametric quantitative MRI. The accuracy of MRF, however, relies on adequate control over system imperfections, such as eddy currents and [Formula: see text], which are different and not as well established on MRL systems compared to diagnostic systems. In this study we investigate the technical feasibility of gradient spoiled 2D MRF on a 1.5T MRL. We show with phantom experiments that the MRL generates reliable MRF signals that are temporally stable during the day and have good agreement with spin-echo reference measurements. Subsequent in-vivo MRF scans in healthy volunteers and a patient with a colorectal liver metastasis showed good image quality, where the quantitative values of selected organs corresponded with the values reported in literature. Therefore we conclude that gradient spoiled 2D MRF is feasible on a 1.5T MRL with similar performance as on a diagnostic system. The precision and accuracy of the parametric maps are sufficient for further investigation of the clinical utility of MRF for online quantitatively MRI-guided radiotherapy.

The noise navigator for MRI-guided radiotherapy: an independent method to detect physiological motion.

Motion is problematic during radiotherapy as it could lead to potential underdosage of the tumor, and/or overdosage in organs-at-risk. A solution is adaptive radiotherapy guided by magnetic resonance imaging (MRI). MRI allows for imaging of target volumes and organs-at-risk before and during treatment delivery with superb soft tissue contrast in any desired orientation, enabling motion management by means of (real-time) adaptive radiotherapy. The noise navigator, which is independent of the MR signal, could serve as a secondary motion detection method in synergy with MR imaging. The feasibility of respiratory motion detection by means of the noise navigator was demonstrated previously. Furthermore, from electromagnetic simulations we know that the noise navigator is sensitive to tissue displacement and thus could in principle be used for the detection of various types of motion. In this study we demonstrate the detection of various types of motion for three anatomical use cases of MRI-guided radiotherapy, i.e. torso (bulk movement and variable breathing), head-and-neck (swallowing) and cardiac. Furthermore, it is shown that the noise navigator can detect bulk movement, variable breathing and swallowing on a hybrid 1.5 T MRI-linac system. Cardiac activity detection through the noise navigator seems feasible in an MRI-guided radiotherapy setting, but needs further optimization. The noise navigator is a versatile and fast (millisecond temporal resolution) motion detection method independent of MR signal that could serve as an independent verification method to detect the occurrence of motion in synergy with real-time MRI-guided radiotherapy.

A deep learning method for image-based subject-specific local SAR assessment.

PURPOSE: Local specific absorption rate (SAR) cannot be measured and is usually evaluated by offline numerical simulations using generic body models that of course will differ from the patient's anatomy. An additional safety margin is needed to include this intersubject variability. In this work, we present a deep learning-based method for image-based subject-specific local SAR assessment. We propose to train a convolutional neural network to learn a "surrogate SAR model" to map the relation between subject-specific B1+ maps and the corresponding local SAR. METHOD: Our database of 23 subject-specific models with an 8-transmit channel body array for prostate imaging at 7 T was used to build 5750 training samples. These synthetic complex B1+ maps and local SAR distributions were used to train a conditional generative adversarial network. Extra penalization for local SAR underestimation errors was included in the loss function. In silico and in vivo validation were performed. RESULTS: In silico cross-validation shows a good qualitative and quantitative match between predicted and ground-truth local SAR distributions. The peak local SAR estimation error distribution shows a mean overestimation error of 15% with 13% probability of underestimation. The higher accuracy of the proposed method allows the use of less conservative safety factors compared with standard procedures. In vivo validation shows that the method is applicable with realistic measurement data with impressively good qualitative and quantitative agreement to simulations. CONCLUSION: The proposed deep learning method allows online image-based subject-specific local SAR assessment. It greatly reduces the uncertainty in current state-of-the-art SAR assessment methods, reducing the time in the examination protocol by almost 25%.

The noise navigator: a surrogate for respiratory-correlated 4D-MRI for motion characterization in radiotherapy.

Respiratory-correlated 4D-MRI can characterize respiratory-induced motion of tumors and organs-at-risk for radiotherapy treatment planning and is a necessity for image guidance of moving tumors treated on an MRI-linac. Essential for 4D-MRI generation is a robust respiratory surrogate signal. We investigated the feasibility of the noise navigator as respiratory surrogate signal for 4D-MRI generation. The noise navigator is based on the respiratory-induced modulation of the thermal noise variance measured by the receive coils during MR acquisition and thus is inherently present and synchronized with MRI data acquisition. Additionally, the noise navigator can be combined with any rectilinear readout strategy (e.g. radial and cartesian) and is independent of MR image contrast and imaging orientation. For radiotherapy applications, the noise navigator provides a robust respiratory signal for patients scanned with an elevated coil setup. This is particularly attractive for widely used cartesian sequences where currently a non-interfering self-navigation means is lacking for MRI-based simulation and MRI-guided radiotherapy. The feasibility of 4D-MRI generation with the noise navigator as respiratory surrogate signal was demonstrated for both cartesian and radial readout strategies in radiotherapy setup on four healthy volunteers and two radiotherapy patients on a dedicated 1.5 T MRI scanner and two radiotherapy patients on a 1.5 T MRI-linac system. Moreover, the respiratory-correlated 4D-MR images showed liver motion comparable to a reference 2D cine MRI series for the volunteers. For 2D cartesian cine MRI acquisitions, both the noise navigator and respiratory bellows were benchmarked against an image navigator. Respiratory phase detection based on the noise navigator agreed 1.4 times better with the image navigator than the respiratory bellows did. For a 3D Stack-of-Stars acquisitions, the noise navigator was compared to radial self-navigation and a 1.7 times higher respiratory phase detection agreement was observed than for the respiratory bellows compared to radial self-navigation.

Dosimetric impact of soft-tissue based intrafraction motion from 3D cine-MR in prostate SBRT.

To investigate the dosimetric impact of intrafraction translation and rotation motion of the prostate, as extracted from daily acquired post-treatment 3D cine-MR based on soft-tissue contrast, in extremely hypofractionated (SBRT) prostate patients. Accurate dose reconstruction is performed by using a prostate intrafraction motion trace which is obtained with a soft-tissue based rigid registration method on 3D cine-MR dynamics with a temporal resolution of 11 s. The recorded motion of each time-point was applied to the planning CT, resulting in the respective dynamic volume used for dose calculation. For each treatment fraction, the treatment delivery record was generated by proportionally splitting the plan into 11 s intervals based on the delivered monitor units. For each fraction the doses of all partial plan/dynamic volume combinations were calculated and were summed to lead to the motion-affected fraction dose. Finally, for each patient the five fraction doses were summed, yielding the total treatment dose. Both daily and total doses were compared to the original reference dose of the respective patient to assess the impact of the intrafraction motion. Depending on the underlying motion of the prostate, different types of motion-affected dose distributions were observed. The planning target volumes (PTVs) ensured CTV_30 (seminal vesicles) D99% coverage for all patients, CTV_35 (prostate corpus) coverage for 97% of the patients and GTV_50 (local boost) for 83% of the patients when compared against the strict planning target D99% value. The dosimetric impact due to prostate intrafraction motion in extremely hypofractionated treatments was determined. The presented study is an essential step towards establishing the actual delivered dose to the patient during radiotherapy fractions.

Fast contour propagation for MR-guided prostate radiotherapy using convolutional neural networks.

PURPOSE: To quickly and automatically propagate organ contours from pretreatment to fraction images in magnetic resonance (MR)-guided prostate external-beam radiotherapy. METHODS: Five prostate cancer patients underwent 20 fractions of image-guided external-beam radiotherapy on a 1.5 T MR-Linac system. For each patient, a pretreatment T2-weighted three-dimensional (3D) MR imaging (MRI) scan was used to delineate the clinical target volume (CTV) contours. The same scan was repeated during each fraction, with the CTV contour being manually adapted if necessary. A convolutional neural network (CNN) was trained for combined image registration and contour propagation. The network estimated the propagated contour and a deformation field between the two input images. The training set consisted of a synthetically generated ground truth of randomly deformed images and prostate segmentations. We performed a leave-one-out cross-validation on the five patients and propagated the prostate segmentations from the pretreatment to the fraction scans. Three variants of the CNN, aimed at investigating supervision based on optimizing segmentation overlap, optimizing the registration, and a combination of the two were compared to results of the open-source deformable registration software package Elastix. RESULTS: The neural networks trained on segmentation overlap or the combined objective achieved significantly better Hausdorff distances between predicted and ground truth contours than Elastix, at the much faster registration speed of 0.5 s. The CNN variant trained to optimize both the prostate overlap and deformation field, and the variant trained to only maximize the prostate overlap, produced the best propagation results. CONCLUSIONS: A CNN trained on maximizing prostate overlap and minimizing registration errors provides a fast and accurate method for deformable contour propagation for prostate MR-guided radiotherapy.

Soft-tissue prostate intrafraction motion tracking in 3D cine-MR for MR-guided radiotherapy.

To develop a method to automatically determine intrafraction motion of the prostate based on soft tissue contrast on 3D cine-magnetic resonance (MR) images with high spatial and temporal resolution. Twenty-nine patients who underwent prostate stereotactic body radiotherapy (SBRT), with four implanted cylindrical gold fiducial markers (FMs), had cine-MR imaging sessions after each of five weekly fractions. Each cine-MR session consisted of 55 sequentially obtained 3D data sets ('dynamics') and was acquired over an 11 s period, covering a total of 10 min. The prostate was delineated on the first dynamic of every dataset and this delineation was used as the starting position for the soft tissue tracking (SST). Each subsequent dynamic was rigidly aligned to the first dynamic, based on the contrast of the prostate. The obtained translation and rotation describes the intrafraction motion of the prostate. The algorithm was applied to 6270 dynamics over 114 scans of 29 patients and the results were validated by comparing to previously obtained fiducial marker tracking data of the same dataset. Our proposed tracking method was also retro-perspectively applied to cine-MR images acquired during MR-guided radiotherapy of our first prostate patient treated on the MR-Linac. The difference in the 3D translation results between the soft tissue and marker tracking was below 1 mm for 98.2% of the time. The mean translation at 10 min were X: 0.0 [Formula: see text] 0.8 mm, Y: 1.0 [Formula: see text] 1.8 mm and Z: [Formula: see text] mm. The mean rotation results at 10 min were X: [Formula: see text], Y: 0.1 [Formula: see text] 0.6° and Z: 0.0 [Formula: see text] 0.7°. A fast, robust and accurate SST algorithm was developed which obviates the need for FMs during MR-guided prostate radiotherapy. To our knowledge, this is the first data using full 3D cine-MR images for real-time soft tissue prostate tracking, which is validated against previously obtained marker tracking data.

Understanding the physical relations governing the noise navigator.

PURPOSE: The noise navigator is a passive way to detect physiological motion occurring in a patient through thermal noise modulations measured by standard clinical radiofrequency receive coils. The aim is to gain a deeper understanding of the potential and applications of physiologically induced thermal noise modulations. METHODS: Numerical electromagnetic simulations and MR measurements were performed to investigate the relative contribution of tissue displacement versus modulation of the dielectric lung properties over the respiratory cycle, the impact of coil diameter and position with respect to the body. Furthermore, the spatial motion sensitivity of specific noise covariance matrix elements of a receive array was investigated. RESULTS: The influence of dielectric lung property variations on the noise variance is negligible compared to tissue displacement. Coil size affected the thermal noise variance modulation, but the location of the coil with respect to the body had a larger impact. The modulation depth of a 15 cm diameter stationary coil approximately 3 cm away from the chest (i.e. radiotherapy setup) was 39.7% compared to 4.2% for a coil of the same size on the chest, moving along with respiratory motion. A combination of particular noise covariance matrix elements creates a specific spatial sensitivity for motion. CONCLUSIONS: The insight gained on the physical relations governing the noise navigator will allow for optimized use and development of new applications. An optimized combination of elements from the noise covariance matrix offer new ways of performing, e.g. motion tracking.

Fiducial marker based intra-fraction motion assessment on cine-MR for MR-linac treatment of prostate cancer.

We have developed a method to determine intrafraction motion of the prostate through automatic fiducial marker (FM) tracking on 3D cine-magnetic resonance (MR) images with high spatial and temporal resolution. Twenty-nine patients undergoing prostate stereotactic body radiotherapy (SBRT), with four implanted cylindrical gold FMs, had cine-MR imaging sessions after each of five weekly fractions. Each cine-MR examination consisted of 55 sequentially obtained 3D datasets ('dynamics'), acquired over a 11 s period, covering a total of 10 min. FM locations in the first dynamic were manually identified by a clinician, FM centers in subsequent dynamics were automatically determined. Center of mass (COM) translations and rotations were determined by calculating the rigid transformations between the FM template of the first and subsequent dynamics. The algorithm was applied to 7315 dynamics over 133 scans of 29 patients and the obtained results were validated by comparing the COM locations recorded by the clinician at the halfway-dynamic (after 5 min) and end dynamic (after 10 min). The mean COM translations at 10 min were X: 0.0 [Formula: see text] 0.8 mm, Y: 1.0 [Formula: see text] 1.9 mm and Z: 0.9 [Formula: see text] 2.0 mm. The mean rotation results at 10 min were X: 0.1 [Formula: see text] 3.9°, Y: 0.0 [Formula: see text] 1.3° and Z: 0.1 [Formula: see text] 1.2°. The tracking success rate was 97.7% with a mean 3D COM error of 1.1 mm. We have developed a robust, fast and accurate FM tracking algorithm for cine-MR data, which allows for continuous monitoring of prostate motion during MR-guided radiotherapy (MRgRT). These results will be used to validate automatic prostate tracking based on soft-tissue contrast.

Magnetic Resonance Imaging only Workflow for Radiotherapy Simulation and Planning in Prostate Cancer.

Magnetic resonance imaging (MRI) is often combined with computed tomography (CT) in prostate radiotherapy to optimise delineation of the target and organs-at-risk (OAR) while maintaining accurate dose calculation. Such a dual-modality workflow requires two separate imaging sessions, and it has some fundamental and logistical drawbacks. Due to the availability of new MRI hardware and software solutions, CT examinations can be omitted for prostate radiotherapy simulations. All information for treatment planning, including electron density maps and bony anatomy, can nowadays be obtained with MRI. Such an MRI-only simulation workflow reduces delineation ambiguities, eases planning logistics, and improves patient comfort; however, careful validation of the complete MRI-only workflow is warranted. The first institutes are now adopting this MRI-only workflow for prostate radiotherapy. In this article, we will review technology and workflow requirements for an MRI-only prostate simulation workflow.

Recommendations for MRI-based contouring of gross tumor volume and organs at risk for radiation therapy of pancreatic cancer.

PURPOSE: Local recurrence is a common and morbid event in patients with unresectable pancreatic adenocarcinoma. A more conformal and targeted radiation dose to the macroscopic tumor in nonmetastatic pancreatic cancer is likely to reduce acute toxicity and improve local control. Optimal soft tissue contrast is required to facilitate delineation of a target and creation of a planning target volume with margin reduction and motion management. Magnetic resonance imaging (MRI) offers considerable advantages in optimizing soft tissue delineation and is an ideal modality for imaging and delineating a gross tumor volume (GTV) within the pancreas, particularly as it relates to conformal radiation planning. Currently, no guidelines have been defined for the delineation of pancreatic tumors for radiation therapy treatment planning. Moreover, abdominal MRI sequences are complex and the anatomy relevant to the radiation oncologist can be challenging. The purpose of this study is to provide recommendations for delineation of GTV and organs at risk (OARs) using MRI and incorporating multiple MRI sequences. METHODS AND MATERIALS: Five patients with pancreatic cancer and 1 healthy subject were imaged with MRI scans either on 1.5T or on 3T magnets in 2 separate institutes. The GTV and OARs were contoured for all patients in a consensus meeting. RESULTS: An overview of MRI-based anatomy of the GTV and OARs is provided. Practical contouring instructions for the GTV and the OARs with the aid of MRI were developed and included in these recommendations. In addition, practical suggestions for implementation of MRI in pancreatic radiation treatment planning are provided. CONCLUSIONS: With this report, we attempt to provide recommendations for MRI-based contouring of pancreatic tumors and OARs. This could lead to better uniformity in defining the GTV and OARs for clinical trials and in radiation therapy treatment planning, with the ultimate goal of improving local control while minimizing morbidity.

(1) H MRS in the human spinal cord at 7 T using a dielectric waveguide transmitter, RF shimming and a high density receive array.

Multimodal MRI is the state of the art method for clinical diagnostics and therapy monitoring of the spinal cord, with MRS being an emerging modality that has the potential to detect relevant changes of the spinal cord tissue at an earlier stage and to enhance specificity. Methodological challenges related to the small dimensions and deep location of the human spinal cord inside the human body, field fluctuations due to respiratory motion, susceptibility differences to adjacent tissue such as vertebras and pulsatile flow of the cerebrospinal fluid hinder the clinical application of (1) H MRS to the human spinal cord. Complementary to previous studies that partly addressed these problems, this work aims at enhancing the signal-to-noise ratio (SNR) of (1) H MRS in the human spinal cord. To this end a flexible tight fit high density receiver array and ultra-high field strength (7 T) were combined. A dielectric waveguide and dipole antenna transmission coil allowed for dual channel RF shimming, focusing the RF field in the spinal cord, and an inner-volume saturated semi-LASER sequence was used for robust localization in the presence of B1 (+) inhomogeneity. Herein we report the first 7 T spinal cord (1) H MR spectra, which were obtained in seven independent measurements of 128 averages each in three healthy volunteers. The spectra exhibit high quality (full width at half maximum 0.09 ppm, SNR 7.6) and absence of artifacts and allow for reliable quantification of N-acetyl aspartate (NAA) (NAA/Cr (creatine) 1.31 ± 0.20; Cramér-Rao lower bound (CRLB) 5), total choline containing compounds (Cho) (Cho/Cr 0.32 ± 0.07; CRLB 7), Cr (CRLB 5) and myo-inositol (mI) (mI/Cr 1.08 ± 0.22; CRLB 6) in 7.5 min in the human cervical spinal cord. Thus metabolic information from the spinal cord can be obtained in clinically feasible scan times at 7 T, and its benefit for clinical decision making in spinal cord disorders will be investigated in the future using the presented methodology. Copyright © 2016 John Wiley & Sons, Ltd.

In vivo electric conductivity of cervical cancer patients based on B1⁺ maps at 3T MRI.

The in vivo electric conductivity (σ) values of tissue are essential for accurate electromagnetic simulations and specific absorption rate (SAR) assessment for applications such as thermal dose computations in hyperthermia. Currently used σ-values are mostly based on ex vivo measurements. In this study the conductivity of human muscle, bladder content and cervical tumors is acquired non-invasively in vivo using MRI. The conductivity of 20 cervical cancer patients was measured with the MR-based electric properties tomography method on a standard 3T MRI system. The average in vivo σ-value of muscle is 14% higher than currently used in human simulation models. The σ-value of bladder content is an order of magnitude higher than the value for bladder wall tissue that is used for the complete bladder in many models. Our findings are confirmed by various in vivo animal studies from the literature. In cervical tumors, the observed average conductivity was 13% higher than the literature value reported for cervical tissue. Considerable deviations were found for the electrical conductivity observed in this study and the commonly used values for SAR assessment, emphasizing the importance of acquiring in vivo conductivity for more accurate SAR assessment in various applications.

Fast thermal simulations and temperature optimization for hyperthermia treatment planning, including realistic 3D vessel networks.

PURPOSE: Accurate thermal simulations in hyperthermia treatment planning require discrete modeling of large blood vessels. The very long computation time of the finite difference based DIscrete VAsculature model (DIVA) developed for this purpose is impractical for clinical applications. In this work, a fast steady-state thermal solver was developed for simulations with realistic 3D vessel networks. Additionally, an efficient temperature-based optimization method including the thermal effect of discrete vasculature was developed. METHODS: The steady-state energy balance for vasculature and tissue was described by a linear system, which was solved with an iterative method on the graphical processing unit. Temperature calculations during optimization were performed by superposition of several precomputed temperature distributions, calculated with the developed thermal solver. The thermal solver and optimization were applied to a human anatomy, with the prostate being the target region, heated with the eight waveguide 70 MHz AMC-8 system. Realistic 3D pelvic vasculature was obtained from angiography. Both the arterial and venous vessel networks consisted of 174 segments and 93 endpoints with a diameter of 1.2 mm. RESULTS: Calculation of the steady-state temperature distribution lasted about 3.3 h with the original DIVA model, while the newly developed method took only ≈ 1-1.5 min. Temperature-based optimization with and without taking the vasculature into account showed differences in optimized waveguide power of more than a factor 2 and optimized tumor T90 differed up to ≈ 0.5°C. This shows the necessity to take discrete vasculature into account during optimization. CONCLUSIONS: A very fast method was developed for thermal simulations with realistic 3D vessel networks. The short simulation time allows online calculations and makes temperature optimization with realistic vasculature feasible, which is an important step forward in hyperthermia treatment planning.

SU-E-J-57: MRI-Linac (MRL) Guided Treatment for Esophageal Cancer.

For radiotherapy, oesophageal cancer is located in a difficult area. Spatial control of the dose distribution is difficult to achieve with current CT-based radiation techniques, as on CT, soft-tissue contrast is too low. Furthermore, the oesophagus moves and organs at risk (e.g. lung, heart, liver, spinal cord) are in close proximity. An 1.5 T MRI-accelerator (MRL) has sufficient soft-tissue tumour visualization possibilities to allow for precise real-time, online, position verification and for dose escalation without organ at riskoverdose. Our research consists of the preparatory work for the first clinical study on the MRL for patients with oesophageal cancer. To improve image quality and reduce the motion artefacts, the benefit of cardiac triggering and breath holds is evaluated on fifteen oesophageal patients. Results show the superb image quality of these MRI sequences. The use of this high quality MRI gives the possibility for non-invasive real-time visualization andtracking of the tumour. We quantify oesophageal tumour motion on cineMRI. The tumour is tracked on sequential mixed T1/T2w images (acquisition time: 60s, temporal resolution: 0.5s, slice thickness: 7mm) of a single coronal and sagittal slice using a Minimum Output Sum of Squared Error (MOSSE) adaptive correlation filter. Tumour registration within the individual images can typically be done at a millisecond time scale. Motion of oesophageal tumours can well be tracked and is highly variable between patients. The greatest mobility is seen in cranio-caudal direction, with amaximum peak-to-peak amplitude of tumour movement of 24.5mm followed by the dorso-ventral and the medio-lateral direction. Movement seems greatest in tumours located in the lower part of the oesophagus. This study shows both the superb image quality for GTV localisation and the possibility for on-line and real time tumour tracking. The study opens thepossibility for tracked radiation delivery with a 1.5T MRI accelerator. Partial funding has been obtained by Elekta and Philips.