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Nuclear magnetic resonance (NMR) in combination with pulsed magnetic field gradients has proven very successful for measuring molecular diffusion, where the correlation time of the motion is much shorter than the timescale of the experiment. In this article, it is demonstrated that a single-scan NMR technique to measure molecular diffusion can be employed to also study incoherent random motions over macroscopic length scales that show correlation times similar to the timescale of the experiment. Such motions are observed, for example, after the mixing of two components or after transferring a sample from one container into another. To measure the fluid settling, a series of magnetization helices were encoded onto a sample. Stimulated gradient echo trains were then generated after different mixing times, which enabled the determination of an effective dispersion coefficient for the fluid. This technique was used to optimize the timing of NMR experiments combined with dissolution dynamic nuclear polarization, where a sample was shuttled between two magnets. In addition to the decay of fluid turbulences, the presence of microbubbles in the sample tube at the end of the shuttling step was identified as another contribution to the NMR linewidth. Microbubbles could be indirectly observed through the line broadening effect on the NMR signal due to their different susceptibility compared to the solvent, which induced field gradients near the interfaces. Using these data, the signal attenuation caused by sample motion in single-scan two-dimensional correlation spectroscopy NMR experiments could be predicted with reasonable accuracy. [ABSTRACT FROM AUTHOR]

Objective To assess the optimal timing and predictive value of early intra-treatment changes in multimodality functional and molecular imaging (FMI) parameters as biomarkers for clinical remission in patients receiving chemoradiation for head and neck squamous cell carcinoma (HNSCC). Methods Thirty-five patients with stage III-IVb (AJCC 7th edition) HNSCC prospectively underwent 18F-FDG-PET/CT, and diffusion-weighted (DW), dynamic contrast-enhanced (DCE) and susceptibility-weighted MRI at baseline, week 1 and week 2 of chemoradiation. Patients with evidence of persistent or recurrent disease during follow-up were classed as non-responders. Changes in FMI parameters at week 1 and week 2 were compared between responders and non-responders with the Mann-Whitney U test. The significance threshold was set at a p value of <0.05. Results There were 27 responders and 8 non-responders. Responders showed a greater reduction in PET-derived tumor total lesion glycolysis (TLG40%; p = 0.007) and maximum standardized uptake value (SUVmax; p = 0.034) after week 1 than nonresponders but these differences were absent by week 2. In contrast, it was not until week 2 that MRI-derived parameters were able to discriminate between the two groups: larger fractional increases in primary tumor apparent diffusion coefficient (ADC; p < 0.001), volume transfer constant (Ktrans; p = 0.012) and interstitial space volume fraction (Ve; p = 0.047) were observed in responders versus non-responders. ADC was the most powerful predictor (Δ >17%, AUC 0.937). Conclusion Early intra-treatment changes in FDG-PET, DW and DCE MRI-derived parameters are predictive of ultimate response to chemoradiation in HNSCC. However, the optimal timing for assessment with FDG-PET parameters (week 1) differed from MRI parameters (week 2). This highlighted the importance of scanning time points for the design of FMI risk-stratified interventional studies. [ABSTRACT FROM AUTHOR]

Background: The use of clinical MRI scanners to conduct pre-clinical research facilitates comparisons with clinical studies. Here the utility and sensitivity of anatomical and functional MRI data/biomarkers acquired from transgenic mouse models of neuroblastoma using a dedicated radiofrequency (RF) coil on a clinical 3T scanner was evaluated.Methods: Multiparametric MRI of transgenic mice bearing abdominal neuroblastomas was performed at 3T, and data cross-referenced to that acquired from the same mice on a pre-clinical 7T MRI system. T2-weighted imaging, quantitation of the native longitudinal relaxation time (T1) and the transverse relaxation rate (R2*), and dynamic contrast-enhanced (DCE)-MRI, was used to assess tumour volume, phenotype and response to cyclophosphamide or cabozantinib.Results: Excellent T2-weighted image contrast enabled clear tumour delineation at 3T. Significant correlations of tumour volume (R=0.98, P<0.0001) and R2* (R=0.87, P<0.002) measured at 3 and 7T were established. Mice with neuroblastomas harbouring the anaplastic lymphoma kinase mutation exhibited a significantly slower R2* (P<0.001), consistent with impaired tumour perfusion. DCE-MRI was performed simultaneously on three transgenic mice, yielding estimates of Ktrans for each tumour (median Ktrans values of 0.202, 0.168 and 0.114 min-1). Cyclophosphamide elicited a significant reduction in both tumour burden (P<0.002) and native T1 (P<0.01), whereas cabozantinib induced significant (P<0.01) tumour growth delay.Conclusions: Simultaneous multiparametric MRI of multiple tumour-bearing animals using this coil arrangement at 3T can provide high efficiency/throughput for both phenotypic characterisation and evaluation of novel therapeutics, and facilitate the introduction of functional MRI biomarkers into aligned imaging-embedded clinical trials. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is a challenging tumour site for radiotherapy delivery owing to its complex anatomy and proximity to organs at risk (OARs) such as the spinal cord and optic apparatus. Despite significant advances in radiotherapy planning techniques, radiation-induced morbidities remain substantial. Further improvement would require high-quality imaging and tailored radiotherapy based on intratreatment response. For these reasons, the use of MRI in radiotherapy planning for HNC is rapidly gaining popularity. MRI provides superior soft-tissue contrast in comparison with CT, allowing better definition of the tumour and OARs. The lack of additional radiation exposure is another attractive feature for intratreatment monitoring. In addition, advanced MRI techniques such as diffusion-weighted, dynamic contrast-enhanced and intrinsic susceptibility-weighted MRI techniques are capable of characterizing tumour biology further by providing quantitative functional parameters such as tissue cellularity, vascular permeability/perfusion and hypoxia. These functional parameters are known to have radiobiological relevance, which potentially could guide treatment adaptation based on their changes prior to or during radiotherapy. In this article, we first present an overview of the applications of anatomical MRI sequences in head and neck radiotherapy, followed by the potentials and limitations of functional MRI sequences in personalizing therapy. [ABSTRACT FROM AUTHOR]

Background: Patients with head and neck squamous cell carcinoma (HNSCC) undergoing radical chemo-radiation (CRT) frequently receive transfusion with packed red cells (PRCT) during radiotherapy on the basis that PRCT increases tumour oxygenation and overcomes hypoxia-induced radio-resistance. This is likely to be a significant oversimplification given the fact that tumour hypoxia is the result of several intrinsic and extrinsic factors, including many that are not directly related to serum haemoglobin (Hb). Therefore, we have studied the effect of PRCT on tumour oxygenation in a prospective cohort of patients who developed low Hb during radical CRT for HNSCC.Methods: This was a prospective study of 20 patients with HNSCC receiving radical CRT undergoing PRCT for Hb<11.5 g dl-1. Patients underwent pretransfusion and posttransfusion intrinsic susceptibility-weighted (SWI) MRI and dynamic contrast-enhanced (DCE) MRI. Blood samples were obtained at the time of MRI scanning and two further time points for measuring Hb and a panel of serum cytokine markers of tumour hypoxia. 3D T2* and Ktrans maps were calculated from the MRI data for primary tumours and cervical lymph node metastases.Results: PRCT produced no change (11 patients) or reduced (1 patient) T2* (tumour oxygenation) in 12 of the 16 (75%) evaluable primary tumours. Three of the four patients with improved tumour oxygenation progressed or had partial response following treatment completion. There were variable changes in Ktrans (tumour perfusion or vessel permeability) following PRCT that were of small magnitude for most tumours. Pre- and Post-PRCT levels of measured cytokines were not significantly different.Conclusions: This study suggests that PRCT during radical CRT for HNSCC does not improve tumour oxygenation. Therefore, oncologists should consider changing practice according to NICE and American Association of Blood Banks guidelines on PRCT for anaemia. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of different time-resolved angiography with stochastic trajectories (TWIST) k-space undersampling schemes on calculated pharmacokinetic dynamic contrast-enhanced (DCE) vascular parameters. Methods: A digital perfusion phantom was employed to simulate effects of TWIST on characteristics of signal changes in DCE. Furthermore, DCE-MRI was acquired without undersampling in a group of patients with head and neck squamous cell carcinoma and used to simulate a range of TWIST schemes. Errors were calculated as differences between reference and TWIST-simulated DCE parameters. Parametrical error maps were used to display the averaged results from all tumors. Results: For a relatively wide range of undersampling schemes, errors in pharmacokinetic parameters due to TWIST were under 10% for the volume transfer constant, Ktrans, and total extracellular extravascular space volume, Ve. TWIST induced errors in the total blood plasma volume, Vp, were the largest observed, and these were inversely dependent on the area of the fully sampled k-space. The magnitudes of errors were not correlated with Ktrans, Vp and weakly correlated with Ve. Conclusions: The authors demonstrated methods to validate and optimize k-space view-sharing techniques for pharmacokinetic DCE studies using a range of clinically relevant spatial and temporal patient derived data. The authors found a range of undersampling patterns for which the TWIST sequence can be reliably used in pharmacokinetic DCE-MRI. The parameter maps created in the study can help to make a decision between temporal and spatial resolution demands and the quality of enhancement curve characterization. [ABSTRACT FROM AUTHOR]

Background and purpose Magnetic resonance (MR) and computed tomography (CT) images are degraded in the presence of metallic implants. We investigate whether SEMAC (Slice Encoding for Metal Artifact Correction) MR is advantageous for radiotherapy (RT) planning. Methods Conventional and SEMAC MR protocols were compared (1.5 T). A spine fixation device suspended in gelatine, two patients with spine fixation devices and six patients with bilateral hip replacements were scanned with both conventional and SEMAC protocols. In spine patients the visibility of the spinal canal and spinal cord was assessed; in prostate patients, the visibility of the prostate, pelvic structures and the pelvic girdle. Results The signal loss volume surrounding the spine fixation device was reduced by approximately 20% when the SEMAC protocol was employed, and registration errors were reduced. For spine patients, the spinal canal was completely visible only using the SEMAC protocol. In hip replacement patients, metal artifacts were local; the signal loss extended to the internal surface of the acetabulum in eight implants with conventional protocols, but only in four using SEMAC. Conclusions SEMAC MR contributes towards correct co-registration of MR and CT images for RT planning, and is particularly relevant when the TV or OARs are close to implants. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to investigate whether the microvascular pseudodiffusion effects resulting with non-monoexponential behavior are present in breast cancer, taking into account tumor spatial heterogeneity. Additionally, methodological factors affecting the signal in low and high diffusion-sensitizing gradient ranges were explored in phantom studies. Methods: The effect of eddy currents and accuracy of b-value determination using a multiple b-value diffusion-weighted MR imaging sequence were investigated in test objects. Diffusion model selection and noise were then investigated in volunteers (n = 5) and breast tumor patients (n = 21) using the Bayesian information criterion. Results: 54.3% of lesion voxels were best fitted by a monoexponential, 26.2% by a stretchedexponential, and 19.5% by a biexponential intravoxel incoherent motion (IVIM) model. High correlation (0.92) was observed between diffusion coefficients calculated using mono- and stretched-exponential models and moderate (0.59) between monoexponential and IVIM (medians: 0.96/0.84/0.72×10-3 mm²/s, respectively). Distortion due to eddy currents depended on the direction of the diffusion gradient and displacement varied between 1 and 6 mm for high b-value images. Shift in the apparent diffusion coefficient due to intrinsic field gradients was compensated for by averaging diffusion data obtained from opposite directions. Conclusions: Pseudodiffusion and intravoxel heterogeneity effects were not observed in approximately half of breast cancer and normal tissue voxels. This result indicates that stretched and IVIM models should be utilized in regional analysis rather than global tumor assessment. Cross terms between diffusion-sensitization gradients and other imaging or susceptibility-related gradients are relevant in clinical protocols, supporting the use of geometric averaging of diffusion-weighted images acquired with diffusion-sensitization gradients in opposite directions. [ABSTRACT FROM AUTHOR]

Background/Objectives: Ataxia telangiectasia (A‐T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A‐T. We aimed to understand the current international practice regarding cancer surveillance in A‐T and agreed‐upon approaches to develop cancer surveillance in A‐T. Design/Methods: We used a consensus development method, the e‐Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents' professional background, experience, and current practice of cancer surveillance in A‐T. Rounds 2 and 3 were designed based on previous rounds and modified according to the comments made by the panellists. The pre‐specified consensus threshold was ≥75% agreement. Results: Thirty‐five expert panellists from 13 countries completed the study. The survey indicated that the current practice of cancer surveillance varies widely between experts and centres'. Consensus was reached that evidence‐based guidelines are needed for cancer surveillance in people with A‐T, with separate recommendations for adults and children. Statements relating to the tests that should be included, the age for starting and stopping cancer surveillance and the optimal surveillance interval were also agreed upon, although in some areas, the consensus was that further research is needed. Conclusion: The international expert consensus statement confirms the need for evidence‐based cancer surveillance guidelines in A‐T, highlights key features that the guidelines should include, and identifies areas of uncertainty in the expert community. This elucidates current knowledge gaps and will inform the design of future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Radical chemo-radiotherapy (CRT) is an effective organ-sparing treatment option for patients with locally advanced head and neck cancer (LAHNC). Despite advances in treatment for LAHNC, a significant minority of these patients continue to fail to achieve complete response with standard CRT. By constructing a multi-modality functional imaging (FI) predictive biomarker for CRT outcome for patients with LAHNC we hope to be able to reliably identify those patients at high risk of failing standard CRT. Such a biomarker would in future enable CRT to be tailored to the specific biological characteristics of each patients' tumour, potentially leading to improved treatment outcomes. Methods/design: The INSIGHT study is a single-centre, prospective, longitudinal multi-modality imaging study using functional MRI and FDG-PET/CT for patients with LAHNC squamous cell carcinomas receiving radical CRT. Two cohorts of patients are being recruited: one treated with, and another treated without, induction chemotherapy. All patients receive radical intensity modulated radiotherapy with concurrent chemotherapy. Patients undergo functional imaging before, during and 3 months after completion of radiotherapy, as well as at the time of relapse, should that occur within the first two years after treatment. Serum samples are collected from patients at the same time points as the FI scans for analysis of a panel of serum markers of tumour hypoxia. Discussion: The primary aim of the INSIGHT study is to acquire a prospective multi-parametric longitudinal data set comprising functional MRI, FDG PET/CT, and serum biomarker data from patients with LAHNC undergoing primary radical CRT. This data set will be used to construct a predictive imaging biomarker for outcome after CRT for LAHNC. This predictive imaging biomarker will be used in future studies of functional imaging based treatment stratification for patients with LAHNC. Additional objectives are: defining the reproducibility of FI parameters; determining robust methods for defining FI based biological target volumes for IMRT planning; creation of a searchable database of functional imaging data for data mining. The INSIGHT study will help to establish the role of FI in the clinical management of LAHNC. [ABSTRACT FROM AUTHOR]

Background/Objectives: Ataxia–telangiectasia (A‐T) is a complex inherited disease associated with an increased risk of malignancy. Surveillance guidelines have demonstrated significant health benefits in other cancer predisposition syndromes. However, evidence‐based guidelines for cancer screening are not currently used in the United Kingdom for people affected by A‐T. This study aims to understand how people with A‐T and their parents feel about cancer surveillance using whole‐body magnetic resonance imaging (MRI) to inform the future development of cancer surveillance guidelines. Design/Methods: We conducted semistructured interviews with people affected by A‐T. Data were analysed inductively using thematic analysis. Results: Nine parents of children with A‐T and four adults with A‐T were interviewed. Five main themes emerged from the data, including (1) cancer screening was considered invaluable with the perceived value of early detection highlighted; (2) the cancer fear can increase anxiety; (3) the perceived limitations around current practice, with the responsibility for monitoring falling too strongly on parents and patients; (4) the need for effective preparation for cancer screening, including clear communication and (5) the challenges associated with MRI screening, where specific recommendations were made for improving the child's experience. Conclusion: This study suggests that stakeholders are positive about the perceived advantages of a cancer screening programme. Ongoing support and preparation techniques should be adopted to maximise adherence and minimise adverse psychosocial outcomes. Patient or Public Contribution: People with A‐T and parents of people with A‐T were actively involved in this study by giving their consent to be interviewed. An independent parent representative contributed to the study, supporting the research team in interpreting and commenting on the appropriateness of the language used in this report. [ABSTRACT FROM AUTHOR]

Background: Radical chemo-radiotherapy (CRT) is an effective organ-sparing treatment option for patients with locally advanced head and neck cancer (LAHNC). Despite advances in treatment for LAHNC, a significant minority of these patients continue to fail to achieve complete response with standard CRT. By constructing a multi-modality functional imaging (FI) predictive biomarker for CRT outcome for patients with LAHNC we hope to be able to reliably identify those patients at high risk of failing standard CRT. Such a biomarker would in future enable CRT to be tailored to the specific biological characteristics of each patients' tumour, potentially leading to improved treatment outcomes.Methods/design: The INSIGHT study is a single-centre, prospective, longitudinal multi-modality imaging study using functional MRI and FDG-PET/CT for patients with LAHNC squamous cell carcinomas receiving radical CRT. Two cohorts of patients are being recruited: one treated with, and another treated without, induction chemotherapy. All patients receive radical intensity modulated radiotherapy with concurrent chemotherapy. Patients undergo functional imaging before, during and 3 months after completion of radiotherapy, as well as at the time of relapse, should that occur within the first two years after treatment. Serum samples are collected from patients at the same time points as the FI scans for analysis of a panel of serum markers of tumour hypoxia.Discussion: The primary aim of the INSIGHT study is to acquire a prospective multi-parametric longitudinal data set comprising functional MRI, FDG PET/CT, and serum biomarker data from patients with LAHNC undergoing primary radical CRT. This data set will be used to construct a predictive imaging biomarker for outcome after CRT for LAHNC. This predictive imaging biomarker will be used in future studies of functional imaging based treatment stratification for patients with LAHNC. Additional objectives are: defining the reproducibility of FI parameters; determining robust methods for defining FI based biological target volumes for IMRT planning; creation of a searchable database of functional imaging data for data mining. The INSIGHT study will help to establish the role of FI in the clinical management of LAHNC.Trial Registration: NCRI H&N CSG ID 13860. [ABSTRACT FROM AUTHOR]

Highlights: [•] Na-P1 and Na-X were derived from coal fly ash and after silver impregnation tested for Hg uptake. [•] Na-X/Ag achieved higher breakthrough capacities than commercially available activated carbon. [•] Material is thermally stable and can be regenerated. [Copyright &y& Elsevier]

The possibility and effectiveness of removal of phosphate from aqueous solutions with the use of new low-cost synthetic zeolites obtained from fly ash and modified with lanthanum, was studied. Physicochemical properties of the zeolites were characterized by different techniques such as X-ray diffraction, low-temperature nitrogen sorption and scanning electron microscopy. It has been established that lanthanum is preferentially located in the zeolites channels and cages, which is related to the ion-exchange method of modification. Introduction of lanthanum cations leads to a reduction in BET surface area, mainly due to a decrease in the area of micropores and reduction in the pore volume. The key element of the study was a series of tests of phosphate adsorption from aqueous solutions. The efficiency of adsorption process was found to depend on the concentration of adsorbate, pH of its solution and temperature. The sorption capacity of zeolites obtained from fly ashes (La-P1, La-A) towards phosphate was compared with that of a natural zeolite – clinoptilolite, modified with lanthanum (La-CLP). The sorption capacities of the particular samples were as follows: La-P1 – 58.2 mg/g, La-A – 44.0 mg/g and La-CLP – 24.6 mg/g. The experimental data were well fitted by the Langmuir isotherm model. The sorption capacities of all samples towards phosphate increased with temperature increasing from 25 to 60 °C. The values of the thermodynamic parameters ΔH 0 and ΔG 0 revealed that the adsorption was spontaneous and endothermic. [ABSTRACT FROM AUTHOR]

Purpose: To determine the 3-dimensional (3D) intrafractional motion of head and neck squamous cell carcinoma (HNSCC).Methods and Materials: Dynamic contrast-enhanced magnetic resonance images from 56 patients with HNSCC in the treatment position were analyzed. Dynamic contrast-enhanced magnetic resonance imaging consisted of 3D images acquired every 2.9 seconds for 4 minutes 50 seconds. Intrafractional tumor motion was studied in the 3 minutes 43 seconds of images obtained after initial contrast enhancement. To assess tumor motion, rigid registration (translations only) was performed using a region of interest (ROI) mask around the tumor. The results were compared with bulk body motion from registration to all voxels. Motion was split into systematic motion and random motion. Correlations between the tumor site and random motion were tested. The within-subject coefficient of variation was determined from 8 patients with repeated baseline measures. Random motion was also assessed at the end of the first week (38 patients) and second week (25 patients) of radiation therapy to investigate trends of motion.Results: Tumors showed irregular occasional rapid motion (eg, swallowing or coughing), periodic intermediate motion (respiration), and slower systematic drifts throughout treatment. For 95% of the patients, displacements due to systematic and random motion were <1.4 mm and <2.1 mm, respectively, 95% of the time. The motion without an ROI mask was significantly (P<.0001, Wilcoxon signed rank test) less than the motion with an ROI mask, indicating that tumors can move independently from the bony anatomy. Tumor motion was significantly (P=.005, Mann-Whitney U test) larger in the hypopharynx and larynx than in the oropharynx. The within-subject coefficient of variation for random motion was 0.33. The average random tumor motion did not increase notably during the first 2 weeks of treatment.Conclusions: The 3D intrafractional tumor motion of HNSCC is small, with systematic motion <1.4 mm and random motion <2.1 mm 95% of the time. [ABSTRACT FROM AUTHOR]

Real-time detection of the rates of metabolic flux, or exchange rates of endogenous enzymatic reactions, is now feasible in biological systems using Dynamic Nuclear Polarization Magnetic Resonance. Derivation of reaction rate kinetics from this technique typically requires multi-compartmental modeling of dynamic data, and results are therefore model-dependent and prone to misinterpretation. We present a model-free formulism based on the ratio of total areas under the curve (AUC) of the injected and product metabolite, for example pyruvate and lactate. A theoretical framework to support this novel analysis approach is described, and demonstrates that the AUC ratio is proportional to the forward rate constant k. We show that the model-free approach strongly correlates with k for whole cell in vitro experiments across a range of cancer cell lines, and detects response in cells treated with the pan-class I PI3K inhibitor GDC-0941 with comparable or greater sensitivity. The same result is seen in vivo with tumor xenograft-bearing mice, in control tumors and following drug treatment with dichloroacetate. An important finding is that the area under the curve is independent of both the input function and of any other metabolic pathways arising from the injected metabolite. This model-free approach provides a robust and clinically relevant alternative to kinetic model-based rate measurements in the clinical translation of hyperpolarized 13C metabolic imaging in humans, where measurement of the input function can be problematic. [ABSTRACT FROM AUTHOR]