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Rationale and Objectives: Intratumoral heterogeneity means single site tumor biopsy might not be representative. Here we develop and optimize an MRI-informed robotic multiregional 'smart' biopsy technique in retroperitoneal and pelvic sarcomas (RPS). We also explore the relationship between imaging and histological biomarkers., Materials and Methods: Participants with suspected RPS underwent multiparametric (mp)MRI within a week prior to biopsy. Three target regions with differing MRI characteristics were contoured. Robotic or freehand multiregional biopsy was performed, collecting samples from each target region in separate specimen pots. CT/MRI fusion extracted quantitative imaging biomarkers for correlation with histological biomarkers at precise biopsy sites. The primary endpoint was feasibility and safety. Spearman's correlation explored the relationship between imaging and histological biomarkers., Results: Twelve participants (7 women), median age 58.6 years interquartile range [IQR]: 52 - 75 years underwent biopsy. All procedures were technically successful with same-day discharge. The within-tumor range of Apparent Diffusion Coefficeint correlated very strongly with the within-tumor range of Ki-67 proliferation index; Spearman's ρ = 0.91 (95% CI 0.68 to 0.98). Ranges represent intratumoral heterogeneity uniquely obtained by multiregional biopsy., Conclusion: Multiregional robotic MRI-informed, CT-guided biopsy is feasible and safe in RPS. Sampling three distinct regions within tumors provides a more comprehensive and accurate representation of tumor biology than standard biopsy. The close relationship between imaging and histological heterogeneity biomarkers has broader implications for pancancer biopsy techniques, imaging characterization, and personalized treatment selection., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Edward W Johnston reports financial support was provided by Royal College of Radiologists. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The apparent diffusion coefficient (ADC) provides a quantitative measure of water mobility that can be used to probe alterations in tissue microstructure due to disease or treatment. Establishment of the accepted level of variance in ADC measurements for each clinical application is critical for its successful implementation. The Diffusion-Weighted Imaging Biomarker Committee of the Quantitative Imaging Biomarkers Alliance (QIBA) has recently advanced the ADC Profile from the consensus to clinically feasible stage for the brain, liver, prostate, and breast. This profile distills multiple studies on ADC repeatability and describes detailed procedures to achieve stated performance claims on an observed ADC change within acceptable confidence limits. In addition to reviewing the current ADC Profile claims, this report has used recent literature to develop proposed updates for establishing metrology benchmarks for mean lesion ADC change that account for measurement variance. Specifically, changes in mean ADC exceeding 8% for brain lesions, 27% for liver lesions, 27% for prostate lesions, and 15% for breast lesions are claimed to represent true changes with 95% confidence. This report also discusses the development of the ADC Profile, highlighting its various stages, and describes the workflow essential to achieving a standardized implementation of advanced quantitative diffusion-weighted MRI in the clinic. The presented QIBA ADC Profile guidelines should enable successful clinical application of ADC as a quantitative imaging biomarker and ensure reproducible ADC measurements that can be used to confidently evaluate longitudinal changes and treatment response for individual patients., (© RSNA, 2024 See also the editorial by Haider in this issue.)

Objective. Image quality in whole-body MRI (WB-MRI) may be degraded by faulty radiofrequency (RF) coil elements or mispositioning of the coil arrays. Phantom-based quality control (QC) is used to identify broken RF coil elements but the frequency of these acquisitions is limited by scanner and staff availability. This work aimed to develop a scan-specific QC acquisition and processing pipeline to detect broken RF coil elements, which is sufficiently rapid to be added to the clinical WB-MRI protocol. The purpose of this is to improve the quality of WB-MRI by reducing the number of patient examinations conducted with suboptimal equipment. Approach. A rapid acquisition (14 s additional acquisition time per imaging station) was developed that identifies broken RF coil elements by acquiring images from each individual coil element and using the integral body coil. This acquisition was added to one centre's clinical WB-MRI protocol for one year (892 examinations) to evaluate the effect of this scan-specific QC. To demonstrate applicability in multi-centre imaging trials, the technique was also implemented on scanners from three manufacturers. Main results . Over the course of the study RF coil elements were flagged as potentially broken on five occasions, with the faults confirmed in four of those cases. The method had a precision of 80% and a recall of 100% for detecting faulty RF coil elements. The coil array positioning measurements were consistent across scanners and have been used to define the expected variation in signal. Significance . The technique demonstrated here can identify faulty RF coil elements and positioning errors and is a practical addition to the clinical WB-MRI protocol. This approach was fully implemented on systems from two manufacturers and partially implemented on a third. It has potential to reduce the number of clinical examinations conducted with suboptimal hardware and improve image quality across multi-centre studies., (Creative Commons Attribution license.)

Objectives: Diffusion-weighted imaging (DWI) with simultaneous multi-slice (SMS) acquisition and advanced processing can accelerate acquisition time and improve MR image quality. This study evaluated the image quality and apparent diffusion coefficient (ADC) measurements of free-breathing DWI acquired from patients with liver metastases using a prototype SMS-DWI acquisition (with/without an advanced processing option) and conventional DWI., Methods: Four DWI schemes were compared in a pilot 5-patient cohort; three DWI schemes were further assessed in a 24-patient cohort. Two readers scored image quality of all b-value images and ADC maps across the three methods. ADC measurements were performed, for all three methods, in left and right liver parenchyma, spleen, and liver metastases. The Friedman non-parametric test (post-hoc Wilcoxon test with Bonferroni correction) was used to compare image quality scoring; t-test was used for ADC comparisons., Results: SMS-DWI was faster (by 24%) than conventional DWI. Both readers scored the SMS-DWI with advanced processing as having the best image quality for highest b-value images (b750) and ADC maps; Cohen's kappa inter-reader agreement was 0.6 for b750 image and 0.56 for ADC maps. The prototype SMS-DWI sequence with advanced processing allowed a better visualization of the left lobe of the liver. ADC measured in liver parenchyma, spleen, and liver metastases using the SMS-DWI with advanced processing option showed lower values than those derived from the SMS-DWI method alone (t-test, p < 0.0001; p < 0.0001; p = 0.002)., Conclusions: Free-breathing SMS-DWI with advanced processing was faster and demonstrated better image quality versus a conventional DWI protocol in liver patients., Clinical Relevance Statement: Free-breathing simultaneous multi-slice- diffusion-weighted imaging (DWI) with advanced processing was faster and demonstrated better image quality versus a conventional DWI protocol in liver patients., Key Points: • Diffusion-weighted imaging (DWI) with simultaneous multi-slice (SMS) can accelerate acquisition time and improve image quality. • Apparent diffusion coefficients (ADC) measured in liver parenchyma, spleen, and liver metastases using the simultaneous multi-slice DWI with advanced processing were significantly lower than those derived from the simultaneous multi-slice DWI method alone. • Simultaneous multi-slice DWI sequence with inline advanced processing was faster and demonstrated better image quality in liver patients., (© 2023. The Author(s).)

Objectives: MAchine Learning In MyelomA Response (MALIMAR) is an observational clinical study combining "real-world" and clinical trial data, both retrospective and prospective. Images were acquired on three MRI scanners over a 10-year window at two institutions, leading to a need for extensive curation., Methods: Curation involved image aggregation, pseudonymisation, allocation between project phases, data cleaning, upload to an XNAT repository visible from multiple sites, annotation, incorporation of machine learning research outputs and quality assurance using programmatic methods., Results: A total of 796 whole-body MR imaging sessions from 462 subjects were curated. A major change in scan protocol part way through the retrospective window meant that approximately 30% of available imaging sessions had properties that differed significantly from the remainder of the data. Issues were found with a vendor-supplied clinical algorithm for "composing" whole-body images from multiple imaging stations. Historic weaknesses in a digital video disk (DVD) research archive (already addressed by the mid-2010s) were highlighted by incomplete datasets, some of which could not be completely recovered. The final dataset contained 736 imaging sessions for 432 subjects. Software was written to clean and harmonise data. Implications for the subsequent machine learning activity are considered., Conclusions: MALIMAR exemplifies the vital role that curation plays in machine learning studies that use real-world data. A research repository such as XNAT facilitates day-to-day management, ensures robustness and consistency and enhances the value of the final dataset. The types of process described here will be vital for future large-scale multi-institutional and multi-national imaging projects., Critical Relevance Statement: This article showcases innovative data curation methods using a state-of-the-art image repository platform; such tools will be vital for managing the large multi-institutional datasets required to train and validate generalisable ML algorithms and future foundation models in medical imaging., Key Points: • Heterogeneous data in the MALIMAR study required the development of novel curation strategies. • Correction of multiple problems affecting the real-world data was successful, but implications for machine learning are still being evaluated. • Modern image repositories have rich application programming interfaces enabling data enrichment and programmatic QA, making them much more than simple "image marts"., (© 2024. The Author(s).)

T 2 -weighted magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) are essential components of cervical cancer diagnosis. However, combining these channels for the training of deep learning models is challenging due to image misalignment. Here, we propose a novel multi-head framework that uses dilated convolutions and shared residual connections for the separate encoding of multiparametric MRI images. We employ a residual U-Net model as a baseline, and perform a series of architectural experiments to evaluate the tumor segmentation performance based on multiparametric input channels and different feature encoding configurations. All experiments were performed on a cohort of 207 patients with locally advanced cervical cancer. Our proposed multi-head model using separate dilated encoding for T 2 W MRI and combined b1000 DWI and apparent diffusion coefficient (ADC) maps achieved the best median Dice similarity coefficient (DSC) score, 0.823 (confidence interval (CI), 0.595-0.797), outperforming the conventional multi-channel model, DSC 0.788 (95% CI, 0.568-0.776), although the difference was not statistically significant ( p > 0.05). We investigated channel sensitivity using 3D GRAD-CAM and channel dropout, and highlighted the critical importance of T 2 W and ADC channels for accurate tumor segmentation. However, our results showed that b1000 DWI had a minor impact on the overall segmentation performance. We demonstrated that the use of separate dilated feature extractors and independent contextual learning improved the model's ability to reduce the boundary effects and distortion of DWI, leading to improved segmentation performance. Our findings could have significant implications for the development of robust and generalizable models that can extend to other multi-modal segmentation applications.

Background: The Myeloma Response Assessment and Diagnosis System (MY-RADS) guidelines establish a standardised acquisition and analysis pipeline for whole-body MRI (WB-MRI) in patients with myeloma. This is the first study to assess image quality in a multi-centre prospective trial using MY-RADS., Methods: The cohort consisted of 121 examinations acquired across ten sites with a range of prior WB-MRI experience, three scanner manufacturers and two field strengths. Image quality was evaluated qualitatively by a radiologist and quantitatively using a semi-automated pipeline to quantify common artefacts and image quality issues. The intra- and inter-rater repeatability of qualitative and quantitative scoring was also assessed., Results: Qualitative radiological scoring found that the image quality was generally good, with 94% of examinations rated as good or excellent and only one examination rated as non-diagnostic. There was a significant correlation between radiological and quantitative scoring for most measures, and intra- and inter-rater repeatability were generally good. When the quality of an overall examination was low, this was often due to low quality diffusion-weighted imaging (DWI), where signal to noise ratio (SNR), anterior thoracic signal loss and brain geometric distortion were found as significant predictors of examination quality., Conclusions: It is possible to successfully deliver a multi-centre WB-MRI study using the MY-RADS protocol involving scanners with a range of manufacturers, models and field strengths. Quantitative measures of image quality were developed and shown to be significantly correlated with radiological assessment. The SNR of DW images was identified as a significant factor affecting overall examination quality., Trial Registration: ClinicalTrials.gov, NCT03188172 , Registered on 15 June 2017., Critical Relevance Statement: Good overall image quality, assessed both qualitatively and quantitatively, can be achieved in a multi-centre whole-body MRI study using the MY-RADS guidelines., Key Points: • A prospective multi-centre WB-MRI study using MY-RADS can be successfully delivered. • Quantitative image quality metrics were developed and correlated with radiological assessment. • SNR in DWI was identified as a significant predictor of quality, allowing for rapid quality adjustment., (© 2023. European Society of Radiology (ESR).)

Objective: To establish optimised diffusion weightings ('b-values') for acquisition of whole-body diffusion-weighted MRI (WB-DWI) for estimation of the apparent diffusion coefficient (ADC) in patients with metastatic melanoma (MM). Existing recommendations for WB-DWI have not been optimised for the tumour properties in MM; therefore, evaluation of acquisition parameters is essential before embarking on larger studies., Methods: Retrospective clinical data and phantom experiments were used. Clinical data comprised 125 lesions from 14 examinations in 11 patients with multifocal MM, imaged before and/or after treatment with immunotherapy at a single institution. ADC estimates from these data were applied to a model to estimate the optimum b-value. A large non-diffusing phantom was used to assess eddy current-induced geometric distortion., Results: Considering all tumour sites from pre- and post-treatment examinations together, metastases exhibited a large range of mean ADC values, [0.67-1.49] × 10 -3 mm 2 /s, and the optimum high b-value (b high ) for ADC estimation was 1100 (10th-90th percentile: 740-1790) s/mm 2 . At higher b-values, geometric distortion increased, and longer echo times were required, leading to reduced signal., Conclusions: Theoretical optimisation gave an optimum b high of 1100 (10th-90th percentile: 740-1790) s/mm 2 for ADC estimation in MM, with the large range of optimum b-values reflecting the wide range of ADC values in these tumours. Geometric distortion and minimum echo time increase at higher b-values and are not included in the theoretical optimisation; b high in the range 750-1100 s/mm 2 should be adopted to maintain acceptable image quality but performance should be evaluated for a specific scanner., Key Points: • Theoretical optimisation gave an optimum high b-value of 1100 (10th-90th percentile: 740-1790) s/mm 2 for ADC estimation in metastatic melanoma. • Considering geometric distortion and minimum echo time (TE), a b-value in the range 750-1100 s/mm 2 is recommended. • Sites should evaluate the performance of specific scanners to assess the effect of geometric distortion and minimum TE., (© 2022. The Author(s).)

Background: Magnetic resonance imaging (MRI) can be used to target tumour components in biopsy procedures, while the ability to precisely correlate histology and MRI signal is crucial for imaging biomarker validation. Robotic MRI/computed tomography (CT) fusion biopsy offers the potential for this without in-gantry biopsy, although requires development., Methods: Test-retest T1 and T2 relaxation times, attenuation (Hounsfield units, HU), and biopsy core quality were prospectively assessed (January-December 2021) in a range of gelatin, agar, and mixed gelatin/agar solutions of differing concentrations on days 1 and 8 after manufacture. Suitable materials were chosen, and four biopsy phantoms were constructed with twelve spherical 1-3-cm diameter targets visible on MRI, but not on CT. A technical pipeline was developed, and intraoperator and interoperator reliability was tested in four operators performing a total of 96 biopsies. Statistical analysis included T1, T2, and HU repeatability using Bland-Altman analysis, Dice similarity coefficient (DSC), and intraoperator and interoperator reliability., Results: T1, T2, and HU repeatability had 95% limits-of-agreement of 8.3%, 3.4%, and 17.9%, respectively. The phantom was highly reproducible, with DSC of 0.93 versus 0.92 for scanning the same or two different phantoms, respectively. Hit rate was 100% (96/96 targets), and all operators performed robotic biopsies using a single volumetric acquisition. The fastest procedure time was 32 min for all 12 targets., Conclusions: A reproducible biopsy phantom was developed, validated, and used to test robotic MRI/CT-fusion biopsy. The technique was highly accurate, reliable, and achievable in clinically acceptable timescales meaning it is suitable for clinical application., (© 2022. The Author(s) under exclusive licence to European Society of Radiology.)

Purpose: This overview of the current landscape of quantitative magnetic resonance imaging biomarkers (qMR IBs) aims to support the standardisation of academic IBs to assist their translation to clinical practice., Methods: We used three complementary approaches to investigate qMR IB use and quality management practices within the UK: 1) a literature search of qMR and quality management terms during 2011-2015 and 2016-2020; 2) a database search for clinical research studies using qMR IBs during 2016-2020; and 3) a survey to ascertain the current availability and quality management practices for clinical MRI scanners and associated equipment at research institutions across the UK., Results: The analysis showed increased use of all qMR methods between the periods 2011-2015 and 2016-2020 and diffusion-tensor MRI and volumetry to be popular methods. However, the "translation ratio" of journal articles to clinical research studies was higher for qMR methods that have evidence of clinical translation via a commercial route, such as fat fraction and T 2 mapping. The number of journal articles citing quality management terms doubled between the periods 2011-2015 and 2016-2020; although, its proportion relative to all journal articles only increased by 3.0%. The survey suggested that quality assurance (QA) and quality control (QC) of data acquisition procedures are under-reported in the literature and that QA/QC of acquired data/data analysis are under-developed and lack consistency between institutions., Conclusions: We summarise current attempts to standardise and translate qMR IBs, and conclude by outlining the ideal quality management practices and providing a gap analysis between current practice and a metrological standard., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Size-based assessments are inaccurate indicators of tumor response in soft-tissue sarcoma (STS), motivating the requirement for new response imaging biomarkers for this rare and heterogeneous disease. In this study, we assess the test-retest repeatability of radiomic features from MR diffusion-weighted imaging (DWI) and derived maps of apparent diffusion coefficient (ADC) in retroperitoneal STS and compare baseline repeatability with changes in radiomic features following radiotherapy (RT)., Materials and Methods: Thirty patients with retroperitoneal STS received an MR examination prior to treatment, of whom 23/30 were investigated in our repeatability analysis having received repeat baseline examinations and 14/30 patients were investigated in our post-treatment analysis having received an MR examination after completing pre-operative RT. One hundred and seven radiomic features were extracted from the full manually delineated tumor region using PyRadiomics. Test-retest repeatability was assessed using an intraclass correlation coefficient (baseline ICC), and post-radiotherapy variance analysis (post-RT-IMS) was used to compare the change in radiomic feature value to baseline repeatability., Results: For the ADC maps and DWI images, 101 and 102 features demonstrated good baseline repeatability (baseline ICC > 0.85), respectively. Forty-three and 2 features demonstrated both good baseline repeatability and a high post-RT-IMS (>0.85), respectively. Pearson correlation between the baseline ICC and post-RT-IMS was weak (0.432 and 0.133, respectively)., Conclusions: The ADC-based radiomic analysis shows better test-retest repeatability compared with features derived from DWI images in STS, and some of these features are sensitive to post-treatment change. However, good repeatability at baseline does not imply sensitivity to post-treatment change., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Thrussell, Winfield, Orton, Miah, Zaidi, Arthur, Thway, Strauss, Collins, Koh, Oelfke, Huang, O’Connor, Messiou and Blackledge.)

A shift in radiology to a data-driven specialty has been unlocked by synergistic developments in imaging biomarkers (IB) and computational science. This is advancing the capability to deliver "virtual biopsies" within oncology. The ability to non-invasively probe tumour biology both spatially and temporally would fulfil the potential of imaging to inform management of complex tumours; improving diagnostic accuracy, providing new insights into inter- and intra-tumoral heterogeneity and individualised treatment planning and monitoring. Soft tissue sarcomas (STS) are rare tumours of mesenchymal origin with over 150 histological subtypes and notorious heterogeneity. The combination of inter- and intra-tumoural heterogeneity and the rarity of the disease remain major barriers to effective treatments. We provide an overview of the process of successful IB development, the key imaging and computational advancements in STS including quantitative magnetic resonance imaging, radiomics and artificial intelligence, and the studies to date that have explored the potential biological surrogates to imaging metrics. We discuss the promising future directions of IBs in STS and illustrate how the routine clinical implementation of a virtual biopsy has the potential to revolutionise the management of this group of complex cancers and improve clinical outcomes., Competing Interests: RJ is the recipient of grants/research support from Merck Sharp & Dohme and GlaxoSmithKline. RJ is the recipient of consultation fees from Adaptimmune, Athenex, Blueprint Medicines, Clinigen, Eisai, Epizyme, Daichii, Deciphera, Immune Design, Lilly, Merck, PharmaMar and UpToDate. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Arthur, Johnston, Winfield, Blackledge, Jones, Huang and Messiou.)

As part of a program to investigate aspects of surface chemistry relevant to methyl chloride synthesis catalysis, the interaction of methanol with η-alumina doped with either CsCl or KCl in the range 0.01-1.0 mmol g (cat) -1 is investigated by a combination of diffuse reflectance infrared Fourier transform spectroscopy and temperature-programed desorption (TPD). Infrared spectra (IR) recorded at 293 K show that increasing the concentration of the group 1 metal chloride progressively decreases the surface concentration of associatively chemisorbed methanol and changes the environment in which the adsorbed methanol resides. For CsCl concentrations of ≥0.6 mmol g (cat) -1 , chemisorbed methoxy species dominate the IR spectrum, while TPD studies show that the amount of methanol adsorbed onto the surface, and subsequently desorbed unchanged, changes relatively little. In the TPD experiments, some of the adsorbed methanol reacts to give dimethyl ether (DME) which then desorbs; for dopant concentrations of 1.0 mmol g (cat) -1 , DME formation is suppressed to below the limit of detection. Unexpectedly, the presence of formate species generated at 293 K is also observed spectroscopically, characterized by a ν asym (COO) mode which exhibits a hypsochromic shift relative to potassium formate; surface concentrations of formate are higher at higher loadings of group 1 metal chloride. Temperature-programed IR spectroscopy shows that the room-temperature formate species desorbs, decomposes, or migrates on warming to 653 K. Thermal ramping of the methanol-saturated surface also results in formate production but one that exhibits an IR profile in agreement with earlier observations and literature values. Increasing the concentrations of the group 1 metal chloride progressively decreases the presence of the thermally induced formate moiety. The study not only reinforces the concept of group 1 metal chloride additives progressively rendering ineffective those Lewis acid sites present at the η-alumina surface which convey discrete reaction characteristics [ e.g. , (i) dimerization of methanol to form DME and (ii) an activated methoxy → formate transition] but also suggests the generation of reactive sites not present in the undoped alumina., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Diffusion weighted imaging (DWI) with intravoxel incoherent motion (IVIM) modelling can inform on tissue perfusion without exogenous contrast administration. Dynamic-contrast-enhanced (DCE) MRI can also characterise tissue perfusion, but requires a bolus injection of a Gadolinium-based contrast agent. This study compares the use of DCE-MRI and IVIM-DWI methods in assessing response to anti-angiogenic treatment in patients with colorectal liver metastases in a cohort with confirmed treatment response., Methods: This prospective imaging study enrolled 25 participants with colorectal liver metastases to receive Regorafenib treatment. A target metastasis > 2 cm in each patient was imaged before and at 15 days after treatment on a 1.5T MR scanner using slice-matched IVIM-DWI and DCE-MRI protocols. MRI data were motion-corrected and tumour volumes of interest drawn on b=900 s/mm 2 diffusion-weighted images were transferred to DCE-MRI data for further analysis. The median value of four IVIM-DWI parameters [diffusion coefficient D (10 -3 mm 2 /s), perfusion fraction f (ml/ml), pseudodiffusion coefficient D* (10 -3 mm 2 /s), and their product fD* (mm 2 /s)] and three DCE-MRI parameters [volume transfer constant K trans (min -1 ), enhancement fraction EF (%), and their product KEF (min -1 )] were recorded at each visit, before and after treatment. Changes in pre- and post-treatment measurements of all MR parameters were assessed using Wilcoxon signed-rank tests (P<0.05 was considered significant). DCE-MRI and IVIM-DWI parameter correlations were evaluated with Spearman rank tests. Functional MR parameters were also compared against Response Evaluation Criteria In Solid Tumours v.1.1 (RECIST) evaluations., Results: Significant treatment-induced reductions of DCE-MRI parameters across the cohort were observed for EF (91.2 to 50.8%, P<0.001), KEF (0.095 to 0.045 min -1 , P<0.001) and K trans (0.109 to 0.078 min -1 , P=0.002). For IVIM-DWI, only D (a non-perfusion parameter) increased significantly post treatment (0.83 to 0.97 × 10 -3 mm 2 /s, P<0.001), while perfusion-related parameters showed no change. No strong correlations were found between DCE-MRI and IVIM-DWI parameters. A moderate correlation was found, after treatment, between K trans and D* (r=0.60; P=0.002) and fD* (r=0.67; P<0.001). When compared to RECIST v.1.1 evaluations, KEF and D correctly identified most clinical responders, whilst non-responders were incorrectly identified., Conclusion: IVIM-DWI perfusion-related parameters showed limited sensitivity to the anti-angiogenic effects of Regorafenib treatment in colorectal liver metastases and showed low correlation with DCE-MRI parameters, despite profound and significant post-treatment reductions in DCE-MRI measurements., Trial Registration: NCT03010722 clinicaltrials.gov; registration date 6 th January 2015., (© 2021. The Author(s).)

The recent rise of deep learning (DL) and its promising capabilities in capturing non-explicit detail from large datasets have attracted substantial research attention in the field of medical image processing. DL provides grounds for technological development of computer-aided diagnosis and segmentation in radiology and radiation oncology. Amongst the anatomical locations where recent auto-segmentation algorithms have been employed, the pelvis remains one of the most challenging due to large intra- and inter-patient soft-tissue variabilities. This review provides a comprehensive, non-systematic and clinically-oriented overview of 74 DL-based segmentation studies, published between January 2016 and December 2020, for bladder, prostate, cervical and rectal cancers on computed tomography (CT) and magnetic resonance imaging (MRI), highlighting the key findings, challenges and limitations.

Whole-body magnetic resonance imaging (MRI) is now a crucial tool for the assessment of the extent of systemic malignant bone disease and response to treatment, and forms part of national and international recommendations for imaging patients with myeloma or metastatic prostate cancer. Recent developments in scanners have enabled acquisition of good-quality whole-body MRI data within 45 minutes on modern MRI systems from all main manufacturers. This provides complimentary morphological and functional whole-body imaging; however, lack of prior experience and acquisition times required can act as a barrier to adoption in busy radiology departments. This article aims to tackle the former by reviewing the indications and providing guidance for technical delivery and clinical interpretation of whole-body MRI for patients with malignant bone disease., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To compare integrated slice-specific dynamic shim (iShim) with distortion correction post-processing to conventional 3D volume shim for the reduction of artefacts and signal loss in 1.5 T whole-body diffusion-weighted imaging (WB-DWI)., Methods: Ten volunteers underwent WB-DWI using conventional 3D volume shim and iShim. Forty-eight consecutive patients underwent WB-DWI with either volume shim (n = 24) or iShim (n = 24) only. For all subjects, displacement of the spinal cord at imaging station interfaces was measured on composed b = 900 s/mm 2 images. The signal intensity ratios, computed as the average signal intensity in a region of high susceptibility gradient (sternum) divided by the average signal intensity in a region of low susceptibility gradient (vertebral body), were compared in volunteers. For patients, image quality was graded from 1 to 5 (1 = Poor, 5 = Excellent). Signal intensity discontinuity scores were recorded from 1 to 4 (1 = 2 + steps, 4 = 0 steps). A p value of < 0.05 was considered significant., Results: Spinal cord displacement artefacts were lower with iShim (p < 0.05) at the thoracic junction in volunteers and at the cervical and thoracic junctions in patients (p < 0.05). The sternum/vertebra signal intensity ratio in healthy volunteers was higher with iShim compared with the volume shim sequence (p < 0.05). There were no significant differences between the volume shim and iShim patient groups in terms of image quality and signal intensity discontinuity scores., Conclusion: iShim reduced the degree of spinal cord displacement artefact between imaging stations and susceptibility-gradient-induced signal loss., (© 2020. The Author(s).)

Background: Computed tomography (CT) and magnetic resonance imaging (MRI) are the mainstay imaging modalities in radiotherapy planning. In MR-Linac treatment, manual annotation of organs-at-risk (OARs) and clinical volumes requires a significant clinician interaction and is a major challenge. Currently, there is a lack of available pre-annotated MRI data for training supervised segmentation algorithms. This study aimed to develop a deep learning (DL)-based framework to synthesize pelvic T 1 -weighted MRI from a pre-existing repository of clinical planning CTs., Methods: MRI synthesis was performed using UNet++ and cycle-consistent generative adversarial network (Cycle-GAN), and the predictions were compared qualitatively and quantitatively against a baseline UNet model using pixel-wise and perceptual loss functions. Additionally, the Cycle-GAN predictions were evaluated through qualitative expert testing (4 radiologists), and a pelvic bone segmentation routine based on a UNet architecture was trained on synthetic MRI using CT-propagated contours and subsequently tested on real pelvic T 1 weighted MRI scans., Results: In our experiments, Cycle-GAN generated sharp images for all pelvic slices whilst UNet and UNet++ predictions suffered from poorer spatial resolution within deformable soft-tissues (e.g. bladder, bowel). Qualitative radiologist assessment showed inter-expert variabilities in the test scores; each of the four radiologists correctly identified images as acquired/synthetic with 67%, 100%, 86% and 94% accuracy. Unsupervised segmentation of pelvic bone on T1-weighted images was successful in a number of test cases., Conclusion: Pelvic MRI synthesis is a challenging task due to the absence of soft-tissue contrast on CT. Our study showed the potential of deep learning models for synthesizing realistic MR images from CT, and transferring cross-domain knowledge which may help to expand training datasets for 21 development of MR-only segmentation models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kalantar, Messiou, Winfield, Renn, Latifoltojar, Downey, Sohaib, Lalondrelle, Koh and Blackledge.)

The interaction of CO with an attapulgite-supported, KCl modified CuCl 2 catalyst has previously been examined using a combination of XANES, EXAFS and DFT calculations. Exposing the catalyst to CO at elevated temperatures leads to the formation of CO 2 as the only identifiable product. However, phosgene production can be induced by a catalyst pre-treatment stage, where the supported CuCl 2 sample is exposed to a diluted stream of dichlorine; subsequent CO exposure at ∼643 K then leads to phosgene production. This communication describes a series of FTIR based micro-reactor measurements, coupled with characterisation measurements utilising TEM, XRD and XPS to define the nature of the catalyst at different stages of the reaction coordinate. The CuCl 2 catalyst is able to support Deacon activity , establishing this work with the possibility of utilising the oxy-chlorination of CO to produce phosgene. Continuous dosing of CO at elevated temperatures over the chlorine pre-dosed CuCl 2 catalyst shows diminishing phosgene production as a function of time-on-stream, indicating surface chlorine supply to be rate-limiting under the reaction conditions studied. A pictorial reaction scheme is proposed to account for the surface chemistry observed.

The effect of relatively low concentrations of Br 2(g) in the Cl 2(g) feedstock for phosgene synthesis catalysis via the reaction of CO (g) and Cl 2(g) over activated carbon (Donau Supersorbon K40) is explored. Under the stated reaction conditions and in the absence of a catalyst, BrCl (g) forms from the reaction of Cl 2(g) and Br 2(g) . Phosgene synthesis over the catalyst at 323 K is investigated for Br 2(g) :Cl 2(g) molar flow ratios in the range 0-1.52% (0-15,190 ppm) and shows enhanced rates of phosgene production. Maximum phosgene production is observed at a Br 2(g) :Cl 2(g) molar flow ratio of 1.52% (15,190 ppm), which corresponds to an enhancement in the rate of phosgene production of ∼227% with respect to the phosgene flow rate observed in the absence of an incident bromine co-feed. A reaction model is proposed to account for the experimental observables, where BrCl (g) is highlighted as a significant intermediate. Specifically, enhanced rates of phosgene production are associated with the dissociative adsorption of BrCl (g) that indirectly increases the pool of Cl (ad) available for reaction., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Diffusion-weighted magnetic resonance imaging (DW-MRI) potentially interrogates site-specific response to neoadjuvant chemotherapy (NAC) in epithelial ovarian cancer (EOC)., Methods: Participants with newly diagnosed EOC due for platinum-based chemotherapy and interval debulking surgery were recruited prospectively in a multicentre study (n = 47 participants). Apparent diffusion coefficient (ADC) and solid tumour volume (up to 10 lesions per participant) were obtained from DW-MRI before and after NAC (including double-baseline for repeatability assessment in n = 19). Anatomically matched lesions were analysed after surgical excision (65 lesions obtained from 25 participants). A trained algorithm determined tumour cell fraction, percentage tumour and percentage necrosis on histology. Whole-lesion post-NAC ADC and pre/post-NAC ADC changes were compared with histological metrics (residual tumour/necrosis) for each tumour site (ovarian, omental, peritoneal, lymph node)., Results: Tumour volume reduced at all sites after NAC. ADC increased between pre- and post-NAC measurements. Post-NAC ADC correlated negatively with tumour cell fraction. Pre/post-NAC changes in ADC correlated positively with percentage necrosis. Significant correlations were driven by peritoneal lesions., Conclusions: Following NAC in EOC, the ADC (measured using DW-MRI) increases differentially at disease sites despite similar tumour shrinkage, making its utility site-specific. After NAC, ADC correlates negatively with tumour cell fraction; change in ADC correlates positively with percentage necrosis., Clinical Trial Registration: ClinicalTrials.gov NCT01505829.

Background Treatment of advanced epithelial ovarian cancer results in a relapse rate of 75%. Early markers of response would enable optimization of management and improved outcome in both primary and recurrent disease. Purpose To assess the apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI, as an indicator of response, progression-free survival (PFS), and overall survival. Materials and Methods This prospective multicenter trial (from 2012-2016) recruited participants with stage III or IV ovarian, primary peritoneal, or fallopian tube cancer (newly diagnosed, cohort one; relapsed, cohort two) scheduled for platinum-based chemotherapy, with interval debulking surgery in cohort one. Cohort one underwent two baseline MRI examinations separated by 0-7 days to assess ADC repeatability; an additional MRI was performed after three treatment cycles. Cohort two underwent imaging at baseline and after one and three treatment cycles. ADC changes in responders and nonresponders were compared (Wilcoxon rank sum tests). PFS and overall survival were assessed by using a multivariable Cox model. Results A total of 125 participants (median age, 63.3 years [interquartile range, 57.0-70.7 years]; 125 women; cohort one, n = 47; cohort two, n = 78) were included. Baseline ADC (range, 77-258 × 10 -5 mm 2 s -1 ) was repeatable (upper and lower 95% limits of agreement of 12 × 10 -5 mm 2 s -1 [95% confidence interval {CI}: 6 × 10 -5 mm 2 s -1 to 18 × 10 -5 mm 2 s -1 ] and -15 × 10 -5 mm 2 s -1 [95% CI: -21 × 10 -5 mm 2 s -1 to -9 × 10 -5 mm 2 s -1 ]). ADC increased in 47% of cohort two after one treatment cycle, and in 58% and 53% of cohorts one and two, respectively, after three cycles. Percentage change from baseline differed between responders and nonresponders after three cycles (16.6% vs 3.9%; P = .02 [biochemical response definition]; 19.0% vs 6.2%; P = .04 [radiologic definition]). ADC increase after one cycle was associated with longer PFS in cohort two (adjusted hazard ratio, 0.86; 95% CI: 0.75, 0.98; P = .03). ADC change was not indicative of overall survival for either cohort. Conclusion After three cycles of platinum-based chemotherapy, apparent diffusion coefficient (ADC) changes are indicative of response. After one treatment cycle, increased ADC is indicative of improved progression-free survival in relapsed disease. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Background: Multi-parametric MRI provides non-invasive methods for response assessment of soft-tissue sarcoma (STS) from non-surgical treatments. However, evaluation of MRI parameters over the whole tumor volume may not reveal the full extent of post-treatment changes as STS tumors are often highly heterogeneous, including cellular tumor, fat, necrosis, and cystic tissue compartments. In this pilot study, we investigate the use of machine-learning approaches to automatically delineate tissue compartments in STS, and use this approach to monitor post-radiotherapy changes. Methods: Eighteen patients with retroperitoneal sarcoma were imaged using multi-parametric MRI; 8/18 received a follow-up imaging study 2-4 weeks after pre-operative radiotherapy. Eight commonly-used supervised machine-learning techniques were optimized for classifying pixels into one of five tissue sub-types using an exhaustive cross-validation approach and expert-defined regions of interest as a gold standard. Final pixel classification was smoothed using a Markov Random Field (MRF) prior distribution on the final machine-learning models. Findings: 5/8 machine-learning techniques demonstrated high median cross-validation accuracies (82.2%, range 80.5-82.5%) with no significant difference between these five methods. One technique was selected (Naïve-Bayes) due to its relatively short training and class-prediction times (median 0.73 and 0.69 ms, respectively on a 3.5 GHz personal machine). When combined with the MRF-prior, this approach was successfully applied in all eight post-radiotherapy imaging studies and provided visualization and quantification of changes to independent STS sub-regions following radiotherapy for heterogeneous response assessment. Interpretation: Supervised machine-learning approaches to tissue classification in multi-parametric MRI of soft-tissue sarcomas provide quantitative evaluation of heterogeneous tissue changes following radiotherapy., (Copyright © 2019 Blackledge, Winfield, Miah, Strauss, Thway, Morgan, Collins, Koh, Leach and Messiou.)

The effect of modifying an η-alumina methyl chloride synthesis catalyst by doping with CsCl and KCl over the concentration range of 0.1-1.0 mmol g (cat) -1 is investigated by a combination of pyridine chemisorption coupled with infrared spectroscopy and mass-selective temperature-programmed desorption measurements. The loading of group 1 metal chloride is equivalent to a titrant that enables selective neutralization of Lewis acid sites present at the surface of the reference η-alumina catalyst. Specifically, a loading of 0.1 mmol g (cat) -1 is sufficient to neutralize the strong Lewis acid sites; a loading of 0.6 mmol g (cat) -1 is sufficient to neutralize the strong and medium-strong Lewis acid sites; a loading of 1.0 mmol g (cat) -1 neutralizes all of the strong and medium-strong Lewis acid sites and partially neutralizes the medium-weak Lewis acid site. These deductions connect with a catalyst design program to develop a methyl chloride synthesis catalyst that exhibits minimal formation of the byproduct dimethyl ether., Competing Interests: The authors declare no competing financial interest.

Purpose: To evaluate repeatability of quantitative multi-parametric MRI in retroperitoneal sarcomas, assess parameter changes with radiotherapy, and correlate pre-operative values with histopathological findings in the surgical specimens. Materials and Methods: Thirty patients with retroperitoneal sarcoma were imaged at baseline, of whom 27 also underwent a second baseline examination for repeatability assessment. 14/30 patients were treated with pre-operative radiotherapy and were imaged again after completing radiotherapy (50.4 Gy in 28 daily fractions, over 5.5 weeks). The following parameter estimates were assessed in the whole tumor volume at baseline and following radiotherapy: apparent diffusion coefficient (ADC), parameters of the intra-voxel incoherent motion model of diffusion-weighted MRI (D, f , D * ), transverse relaxation rate, fat fraction, and enhancing fraction after gadolinium-based contrast injection. Correlation was evaluated between pre-operative quantitative parameters and histopathological assessments of cellularity and fat fraction in post-surgical specimens (ClinicalTrials.gov, registration number NCT01902667). Results: Upper and lower 95% limits of agreement were 7.1 and -6.6%, respectively for median ADC at baseline. Median ADC increased significantly post-radiotherapy. Pre-operative ADC and D were negatively correlated with cellularity ( r = -0.42, p = 0.01, 95% confidence interval (CI) -0.22 to -0.59 for ADC; r = -0.45, p = 0.005, 95% CI -0.25 to -0.62 for D), and fat fraction from Dixon MRI showed strong correlation with histopathological assessment of fat fraction ( r = 0.79, p = 10 -7 , 95% CI 0.69-0.86). Conclusion: Fat fraction on MRI corresponded to fat content on histology and therefore contributes to lesion characterization. Measurement repeatability was excellent for ADC; this parameter increased significantly post-radiotherapy even in disease categorized as stable by size criteria, and corresponded to cellularity on histology. ADC can be utilized for characterizing and assessing response in heterogeneous retroperitoneal sarcomas.

Quantitative radiomics features, extracted from medical images, characterize tumour-phenotypes and have been shown to provide prognostic value in predicting clinical outcomes. Stability of radiomics features extracted from apparent diffusion coefficient (ADC)-maps is essential for reliable correlation with the underlying pathology and its clinical applications. Within a multicentre, multi-vendor trial we established a method to analyse radiomics features from ADC-maps of ovarian (n = 12), lung (n = 19), and colorectal liver metastasis (n = 30) cancer patients who underwent repeated (<7 days) diffusion-weighted imaging at 1.5 T and 3 T. From these ADC-maps, 1322 features describing tumour shape, texture and intensity were retrospectively extracted and stable features were selected using the concordance correlation coefficient (CCC > 0.85). Although some features were tissue- and/or respiratory motion-specific, 122 features were stable for all tumour-entities. A large proportion of features were stable across different vendors and field strengths. By extracting stable phenotypic features, fitting-dimensionality is reduced and reliable prognostic models can be created, paving the way for clinical implementation of ADC-based radiomics.

Background: Whole body magnetic resonance imaging (WBMRI) is currently recommended by guidelines for the assessment of myeloma. This will inevitably result in incidental findings. We aimed to assess the frequency of extraskeletal incidental findings and the added value of contrast-enhanced (CE) T1-weighted (T1-W) and diffusion-weighted (DWI) sequences for their characterization in a single WBMRI examination., Patients and Methods: We performed 1.5 T WBMRI in 100 patients (53 female; median age, 65 years) with plasma-cell disorders from January 2014 to July 2017. T2-weighted sequences were reviewed initially for incidental findings, followed by sequential review of T1-W, CE T1-W, and DWI sequences for lesion characterization. Descriptive statistics were undertaken., Results: A total of 348 incidental findings were detected in 97 (97%) of 100 patients; only 38 (10.9%) of 348 findings were indeterminate. T1-W sequences increased diagnostic confidence in the characterization of 12 (31.6%) of 38; CE T1-W sequences in the characterization of 16 (50%) of 32; and DWI increased diagnostic confidence in 21 (55.3%) of 38 compared to the T2-weighted sequence alone., Conclusion: Incidental findings are common, but the majority are of no clinical consequence. No additional cancers were noted in our series. DWI and CE T1-W sequences increased diagnostic confidence in 50% of indeterminate findings and may reduce the need for further investigation., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The interaction of CO with an attapulgite-supported Cu(ii)Cl2 catalyst has been examined in a micro-reactor arrangement. CO exposure to the dried, as-received catalyst at elevated temperatures leads to the formation of CO2 as the only identifiable product. However, phosgene production can be induced by using a catalyst pre-treatment where the supported Cu(ii)Cl2 sample is exposed to a diluted stream of chlorine. Subsequent CO exposure at ∼370 °C then leads to phosgene production. In order to investigate the origins of this atypical set of reaction characteristics, a series of X-ray absorption experiments were performed that were supplemented by DFT calculations. XANES measurements establish that at the elevated temperatures connected with phosgene formation, the catalyst is comprised of Cu+ and a small amount of Cu2+. Moreover, the data show that unique to the chlorine pre-treated sample, CO exposure at elevated temperature results in a short-lived oxidation of the copper. On the basis of calculated CO adsorption energies, DFT calculations indicate that a mixed Cu+/Cu2+ catalyst is required to support CO chemisorption.

Objectives: The aim of this study was to identify apparent diffusion coefficient (ADC) values for typical haemangiomas in the spine and to compare them with active malignant focal deposits., Methods: This was a retrospective single-institution study. Whole-body magnetic resonance imaging (MRI) scans of 106 successive patients with active multiple myeloma, metastatic prostate or breast cancer were analysed. ADC values of typical vertebral haemangiomas and malignant focal deposits were recorded., Results: The ADC of haemangiomas (72 ROIs, median ADC 1,085×10 -6 mm 2 s -1 , interquartile range 927-1,295×10 -6 mm 2 s -1 ) was significantly higher than the ADC of malignant focal deposits (97 ROIs, median ADC 682×10 -6 mm 2 s -1 , interquartile range 583-781×10 -6 mm 2 s -1 ) with a p-value < 10 -6 . Receiver operating characteristic (ROC) analysis produced an area under the curve of 0.93. An ADC threshold of 872×10 -6 mm 2 s -1 separated haemangiomas from malignant focal deposits with a sensitivity of 84.7 % and specificity of 91.8 %., Conclusions: ADC values of classical vertebral haemangiomas are significantly higher than malignant focal deposits. The high ADC of vertebral haemangiomas allows them to be distinguished visually and quantitatively from active sites of disease, which show restricted diffusion., Key Points: • Whole-body diffusion-weighted MRI is becoming widely used in myeloma and bone metastases. • ADC values of vertebral haemangiomas are significantly higher than malignant focal deposits. • High ADCs of haemangiomas allows them to be distinguished from active disease.

For body imaging, diffusion-weighted MRI may be used for tumour detection, staging, prognostic information, assessing response and follow-up. Disease detection and staging involve qualitative, subjective assessment of images, whereas for prognosis, progression or response, quantitative evaluation of the apparent diffusion coefficient (ADC) is required. Validation and qualification of ADC in multicentre trials involves examination of i) technical performance to determine biomarker bias and reproducibility and ii) biological performance to interrogate a specific aspect of biology or to forecast outcome. Unfortunately, the variety of acquisition and analysis methodologies employed at different centres make ADC values non-comparable between them. This invalidates implementation in multicentre trials and limits utility of ADC as a biomarker. This article reviews the factors contributing to ADC variability in terms of data acquisition and analysis. Hardware and software considerations are discussed when implementing standardised protocols across multi-vendor platforms together with methods for quality assurance and quality control. Processes of data collection, archiving, curation, analysis, central reading and handling incidental findings are considered in the conduct of multicentre trials. Data protection and good clinical practice are essential prerequisites. Developing international consensus of procedures is critical to successful validation if ADC is to become a useful biomarker in oncology., Key Points: • Standardised acquisition/analysis allows quantification of imaging biomarkers in multicentre trials. • Establishing "precision" of the measurement in the multicentre context is essential. • A repository with traceable data of known provenance promotes further research.

Background: Magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) can palliate metastatic bone pain by periosteal neurolysis. We investigated the value of diffusion-weighted imaging (DWI) for monitoring soft tissue changes adjacent to bone during MR-guided HIFU. We evaluated the repeatability of the apparent diffusion coefficient (ADC) measurement, the temporal evolution of ADC change after sonication, and its relationship with thermal parameters., Methods: Ex-vivo experiments in lamb legs ( n = 8) were performed on a Sonalleve MR-guided HIFU system. Baseline proton resonance frequency shift (PRFS) thermometry evaluated the accuracy of temperature measurements and tissue cooling times after exposure. PRFS acquired during sonication ( n = 27) was used to estimate thermal dose volume and temperature. After repeat baseline measurements, DWI was assessed longitudinally and relative ADC changes were derived for heated regions., Results: Baseline PRFS was accurate to 1 °C and showed that tissues regained baseline temperatures within 5 min. Before sonication, coefficient of variation for repeat ADC measurements was 0.8%. After sonication, ADC increased in the muscle adjacent to the exposed periosteum, it was maximal 1-5 min after sonication, and it significantly differed between samples with persistent versus non-persistent ADC changes beyond 20 min. ADC increases at 20 min were stable for 2 h and correlated significantly with thermal parameters (ADC versus applied acoustic energy at 16-20 min: r = 0.77, p < 0.001). A 20% ADC increase resulted in clear macroscopic tissue damage., Conclusions: Our preliminary results suggest that DWI can detect intra-procedural changes in ex-vivo muscle overlying the periosteum. This could be useful for studying the safety and efficacy of clinical MR-guided HIFU bone treatments., Competing Interests: Institutional hygiene requirements for handling ex-vivo specimens in a clinical environment were adhered to. There were no ethical requirements for this study.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Purpose To assess the repeatability of apparent diffusion coefficient (ADC) estimates in extracranial soft-tissue diffusion-weighted magnetic resonance imaging across a wide range of imaging protocols and patient populations. Materials and Methods Nine prospective patient studies and one prospective volunteer study, performed between 2006 and 2016 with research ethics committee approval and written informed consent from each subject, were included in this single-institution study. A total of 141 tumors and healthy organs were imaged twice (interval between repeated examinations, 45 minutes to 10 days, depending the on study) to assess the repeatability of median and mean ADC estimates. The Levene test was used to determine whether ADC repeatability differed between studies. The Pearson linear correlation coefficient was used to assess correlation between coefficient of variation (CoV) and the year the study started, study size, and volumes of tumors and healthy organs. The repeatability of ADC estimates from small, medium, and large tumors and healthy organs was assessed irrespective of study, and the Levene test was used to determine whether ADC repeatability differed between these groups. Results CoV aggregated across all studies was 4.1% (range for each study, 1.7%-6.5%). No correlation was observed between CoV and the year the study started or study size. CoV was weakly correlated with volume (r = -0.5, P = .1). Repeatability was significantly different between small, medium, and large tumors (P < .05), with the lowest CoV (2.6%) for large tumors. There was a significant difference in repeatability between studies-a difference that did not persist after the study with the largest tumors was excluded. Conclusion ADC is a robust imaging metric with excellent repeatability in extracranial soft tissues across a wide range of tumor sites, sizes, patient populations, and imaging protocol variations. Online supplemental material is available for this article.

Objectives: Assessment of empirical diffusion-weighted MRI (DW-MRI) models in cervical tumours to investigate whether fitted parameters distinguish between types and grades of tumours., Methods: Forty-two patients (24 squamous cell carcinomas, 14 well/moderately differentiated, 10 poorly differentiated; 15 adenocarcinomas, 13 well/moderately differentiated, two poorly differentiated; three rare types) were imaged at 3 T using nine b-values (0 to 800 s mm -2 ). Mono-exponential, stretched exponential, kurtosis, statistical, and bi-exponential models were fitted. Model preference was assessed using Bayesian Information Criterion analysis. Differences in fitted parameters between tumour types/grades and correlation between fitted parameters were assessed using two-way analysis of variance and Pearson's linear correlation coefficient, respectively., Results: Non-mono-exponential models were preferred by 83 % of tumours with bi-exponential and stretched exponential models preferred by the largest numbers of tumours. Apparent diffusion coefficient (ADC) and diffusion coefficients from non-mono-exponential models were significantly lower in poorly differentiated tumours than well/moderately differentiated tumours. α (stretched exponential), K (kurtosis), f and D* (bi-exponential) were significantly different between tumour types. Strong correlation was observed between ADC and diffusion coefficients from other models., Conclusions: Non-mono-exponential models were preferred to the mono-exponential model in DW-MRI data from cervical tumours. Parameters of non-mono-exponential models showed significant differences between types and grades of tumours., Key Points: • Non-mono-exponential DW-MRI models are preferred in the majority of cervical tumours. • Poorly differentiated cervical tumours exhibit lower diffusion coefficients than well/moderately differentiated tumours. • Non-mono-exponential model parameters α, K, f, and D* differ between tumour types. • Micro-structural features are likely to affect parameters in non-mono-exponential models differently.

Aspects of the chemistry of selected metal fluorides, which are pertinent to their real or potential use as Lewis acidic, heterogeneous catalysts, are reviewed. Particular attention is paid to β-aluminum trifluoride, aluminum chlorofluoride and aluminas γ and η, whose surfaces become partially fluorinated or chlorinated, through pre-treatment with halogenating reagents or during a catalytic reaction. In these cases, direct comparisons with nanostructured metal fluorides are possible. In the second part of the review, attention is directed to iron(III) and copper(II) metal chlorides, whose Lewis acidity and potential redox function have had important catalytic implications in large-scale chlorohydrocarbons chemistry. Recent work, which highlights the complexity of reactions that can occur in the presence of supported copper(II) chloride as an oxychlorination catalyst, is featured. Although direct comparisons with nanostructured fluorides are not currently possible, the work could be relevant to possible future catalytic developments in nanostructured materials.

Multi-parametric magnetic resonance imaging (mpMRI) offers a unique insight into tumor biology by combining functional MRI techniques that inform on cellularity (diffusion-weighted MRI), vascular properties (dynamic contrast-enhanced MRI), and metabolites (magnetic resonance spectroscopy) and has scope to provide valuable information for prognostication and response assessment. Challenges in the application of mpMRI in the clinic include the technical considerations in acquiring good quality functional MRI data, development of robust techniques for analysis, and clinical interpretation of the results. This article summarizes the technical challenges in acquisition and analysis of multi-parametric MRI data before reviewing the key applications of multi-parametric MRI in clinical research and practice., Competing Interests: The authors report no conflicts of interest.

In previous work by the authors, aspects of the surface chemistry connected with methyl chloride synthesis over an η-alumina catalyst have been examined. This communication considers a role for Group 1 metal salts to modify the catalytic performance of the well characterised η-alumina catalyst. Firstly, based on a previously postulated mechanism for the reaction of methanol on η-alumina, a mechanism for methyl chloride synthesis over the η-alumina catalyst is proposed. Secondly, the validity of the new mechanism is tested by observing how the (i) type and (ii) loading of the Group 1 metal salt may perturb methyl chloride selectivity. The outcomes of these measurements are rationalised with reference to the postulated mechanism. Overall, this study represents an example of how a proposed reaction mechanism has been used to inform and guide a catalyst development strategy for a large-scale industrial process.

A modern industrial route for the manufacture of methyl methacrylate involves the reaction of methyl propanoate and formaldehyde over a silica-supported Cs catalyst. Although the process has been successfully commercialised, little is known about the surface interactions responsible for the forward chemistry. This work concentrates upon the interaction of methyl propanoate over a representative silica. A combination of infrared spectroscopy, inelastic neutron scattering, DFT calculations, X-ray diffraction and temperature-programmed desorption is used to deduce how the ester interacts with the silica surface.

Purpose: Diffusion-weighted (DW) and dynamic contrast-enhanced magnetic resonance imaging (MRI) are increasingly applied for the assessment of functional tissue biomarkers for diagnosis, lesion characterization, or for monitoring of treatment response. However, these techniques are vulnerable to the influence of various factors, so there is a necessity for a standardized MR quality assurance procedure utilizing a phantom to facilitate the reliable estimation of repeatability of these quantitative biomarkers arising from technical factors (e.g., B1 variation) affecting acquisition on scanners of different vendors and field strengths. The purpose of this study is to present a novel phantom designed for use in quality assurance for multicenter trials, and the associated repeatability measurements of functional and quantitative imaging protocols across different MR vendors and field strengths., Methods: A cylindrical acrylic phantom was manufactured containing 7 vials of polyvinylpyrrolidone (PVP) solutions of different concentrations, ranging from 0% (distilled water) to 25% w/w, to create a range of different MR contrast parameters. Temperature control was achieved by equilibration with ice-water. Repeated MR imaging measurements of the phantom were performed on four clinical scanners (two at 1.5 T, two at 3.0 T; two vendors) using the same scanning protocol to assess the long-term and short-term repeatability. The scanning protocol consisted of DW measurements, inversion recovery (IR) T1 measurements, multiecho T2 measurement, and dynamic T1-weighted sequence allowing multiple variable flip angle (VFA) estimation of T1 values over time. For each measurement, the corresponding calculated parameter maps were produced. On each calculated map, regions of interest (ROIs) were drawn within each vial and the median value of these voxels was assessed. For the dynamic data, the autocorrelation function and their variance were calculated; for the assessment of the repeatability, the coefficients of variation (CoV) were calculated., Results: For both field strengths across the available vendors, the apparent diffusion coefficient (ADC) at 0 °C ranged from (1.12 ± 0.01) × 10(-3) mm(2)/s for pure water to (0.48 ± 0.02) × 10(-3) mm(2)/s for the 25% w/w PVP concentration, presenting a minor variability between the vendors and the field strengths. T2 and IR-T1 relaxation time results demonstrated variability between the field strengths and the vendors across the different acquisitions. Moreover, the T1 values derived from the VFA method exhibited a large variation compared with the IR-T1 values across all the scanners for all repeated measurements, although the calculation of the standard deviation of the VFA-T1 estimate across each ROI and the autocorrelation showed a stability of the signal for three scanners, with autocorrelation of the signal over the dynamic series revealing a periodic variation in one scanner. Finally, the ADC, the T2, and the IR-T1 values exhibited an excellent repeatability across the scanners, whereas for the dynamic data, the CoVs were higher., Conclusions: The combination of a novel PVP phantom, with multiple compartments to give a physiologically relevant range of ADC and T1 values, together with ice-water as a temperature-controlled medium, allows reliable quality assurance measurements that can be used to measure agreement between MRI scanners, critical in multicenter functional and quantitative imaging studies.

At present, there is no standardised approach for the radiological evaluation of soft tissue sarcomas following radiotherapy (RT). This manuscript, produced by a European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) and Imaging Group endorsed task force, aims to propose standardisation of magnetic resonance imaging techniques and interpretation after neoadjuvant RT for routine use and within clinical trials., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To develop methods for optimization of diffusion-weighted MRI (DW-MRI) in the abdomen and pelvis on 1.5 T MR scanners from three manufacturers and assess repeatability of apparent diffusion coefficient (ADC) estimates in a temperature-controlled phantom and abdominal and pelvic organs in healthy volunteers., Methods: Geometric distortion, ghosting, fat suppression, and repeatability and homogeneity of ADC estimates were assessed using phantoms and volunteers. Healthy volunteers (ten per scanner) were each scanned twice on the same scanner. One volunteer traveled to all three institutions in order to provide images for qualitative comparison. The common volunteer was excluded from quantitative analysis of the data from scanners 2 and 3 in order to ensure statistical independence, giving n = 10 on scanner 1 and n = 9 on scanners 2 and 3 for quantitative analysis. Repeatability and interscanner variation of ADC estimates in kidneys, liver, spleen, and uterus were assessed using within-patient coefficient of variation (wCV) and Kruskal-Wallis tests, respectively., Results: The coefficient of variation of ADC estimates in the temperature-controlled phantom was 1%-4% for all scanners. Images of healthy volunteers from all scanners showed homogeneous fat suppression and no marked ghosting or geometric distortion. The wCV of ADC estimates was 2%-4% for kidneys, 3%-7% for liver, 6%-9% for spleen, and 7%-10% for uterus. ADC estimates in kidneys, spleen, and uterus showed no significant difference between scanners but a significant difference was observed in liver (p < 0.05)., Conclusions: DW-MRI protocols can be optimized using simple phantom measurements to produce good quality images in the abdomen and pelvis at 1.5 T with repeatable quantitative measurements in a multicenter study.

Objectives: To assess goodness-of-fit and repeatability of mono-exponential, stretched exponential and bi-exponential models of diffusion-weighted MRI (DW-MRI) data in primary and metastatic ovarian cancer., Methods: Thirty-nine primary and metastatic lesions from thirty-one patients with stage III or IV ovarian cancer were examined before and after chemotherapy using DW-MRI with ten diffusion-weightings. The data were fitted with (a) a mono-exponential model to give the apparent diffusion coefficient (ADC), (b) a stretched exponential model to give the distributed diffusion coefficient (DDC) and stretching parameter (α), and (c) a bi-exponential model to give the diffusion coefficient (D), perfusion fraction (f) and pseudodiffusion coefficient (D*)., Results: Coefficients of variation, established from repeated baseline measurements, were: ADC 3.1%, DDC 4.3%, α 7.0%, D 13.2%, f 44.0%, D* 165.1%. The bi-exponential model was unsuitable in these data owing to poor repeatability. After excluding the bi-exponential model, analysis using Akaike Information Criteria showed that the stretched exponential model provided the better fit to the majority of pixels in 64% of lesions., Conclusions: The stretched exponential model provides the optimal fit to DW-MRI data from ovarian, omental and peritoneal lesions and lymph nodes in pre-treatment and post-treatment measurements with good repeatability., Key Points: • DW-MRI data in ovarian cancer show deviation from mono-exponential behaviour • Parameters derived from the stretched exponential model showed good repeatability (CV 7%) • The bi-exponential model was unsuitable because of poor parameter repeatability • The stretched exponential model showed comparable repeatability to the mono-exponential model • The extra parameter (α) provides scope for investigation of heterogeneity or response.

Objective: To assess the effect of fasting and eating on estimates of apparent diffusion coefficient (ADC) in the livers of healthy volunteers using a diffusion-weighted MRI protocol with b-values of 100, 500 and 900 s mm(-2) in a multicentre study at 1.5 T., Methods: 20 volunteers were scanned using 4 clinical 1.5-T MR scanners. Volunteers were scanned after fasting for at least 4 h and after eating a meal; the scans were repeated on a subsequent day. Median ADC estimates were calculated from all pixels in three slices near the centre of the liver. Analysis of variance (ANOVA) was used to assess the difference between ADC estimates in fasted and non-fasted states and between ADC estimates on different days., Results: ANOVA showed no difference between ADC estimates in fasted and non-fasted states (p = 0.8) nor between ADC estimates on different days (p = 0.8). The repeatability of the measurements was good, with coefficients of variation of 5.1% and 4.6% in fasted and non-fasted states, respectively., Conclusion: There was no significant difference in ADC estimates between fasted and non-fasted measurements, indicating that the perfusion sensitivity of ADC estimates obtained from b-values of 100, 500 and 900 s mm(-2) is sufficiently low that changes in blood flow in the liver after eating are undetectable beyond the variability in the measurements., Advances in Knowledge: Assessment of the effect of prandial state on ADC estimates is critical, in order to determine the appropriate patient preparation for biological validation in clinical trials.

Imaging biomarkers derived from MRI or CT describe functional properties of tumours and normal tissues. They are finding increasing numbers of applications in diagnosis, monitoring of response to treatment and assessment of progression or recurrence. Imaging biomarkers also provide scope for assessment of heterogeneity within and between lesions. A wide variety of functional parameters have been investigated for use as biomarkers in oncology. Some imaging techniques are used routinely in clinical applications while others are currently restricted to clinical trials or preclinical studies. Apparent diffusion coefficient, magnetization transfer ratio and native T1 relaxation time provide information about structure and organization of tissues. Vascular properties may be described using parameters derived from dynamic contrast-enhanced MRI, dynamic contrast-enhanced CT, transverse relaxation rate (R2*), vessel size index and relative blood volume, while magnetic resonance spectroscopy may be used to probe the metabolic profile of tumours. This review describes the mechanisms of contrast underpinning each technique and the technical requirements for robust and reproducible imaging. The current status of each biomarker is described in terms of its validation, qualification and clinical applications, followed by a discussion of the current limitations and future perspectives.

We present the development and application of a phantom for assessment and optimization of fat suppression over a large field-of-view in diffusion-weighted magnetic resonance imaging at 1.5 T and 3 T. A Perspex cylinder (inner diameter 185 mm, height 300 mm) which contains a second cylinder (inner diameter 140 mm) was constructed. The inner cylinder was filled with water doped with copper sulphate and sodium chloride and the annulus was filled with corn oil, which closely matches the spectrum and longitudinal relaxation times of subcutaneous abdominal fat. Placement of the phantom on the couch at 45° to the z-axis presented an elliptical cross-section, which was of a similar size and shape to axial abdominal images. The use of a phantom for optimization of fat suppression allowed quantitative comparison between studies without the differences introduced by variability between human subjects. We have demonstrated that the phantom is suitable for selection of inversion delay times, spectral adiabatic inversion recovery delays and assessment of combinatorial methods of fat suppression. The phantom is valuable in protocol development and the assessment of new techniques, particularly in multi-centre trials.

The hydrochlorination of 4,4'-methylenedianiline, NH(2)C(6)H(4)CH(2)C(6)H(4)NH(2) (MDA), in chlorobenzene to produce 4,4'-methylenedianiline dihydrochloride, [H(3)NC(6)H(4)CH(2)C(6)H(4)NH(3)]Cl(2) (MDA x 2 HCl) is an important reaction for the production of isocyanates, which are used to manufacture polyurethanes. This reaction is examined here. MDA is moderately soluble in chlorobenzene, whereas MDA x 2 HCl is effectively insoluble. Controlled addition of anhydrous HCl to MDA in chlorobenzene led to the isolation of a solid whose stoichiometry is MDA x HCl. Crystals obtained from solutions of MDA x HCl in methanol were found by X-ray analysis to consist of the basic hydrochloride salt, [MDAH(2)][Cl](2)[MDA](2)H(2)O, which is stabilised by complex hydrogen-bonding. The starting material MDA has an H-bonded structure in which the molecules are linked in a one-dimensional chain. Hydrogen-bonding is extensive in MDA x 2 HCl which contains ladders of [H(3)NC(6)H(4)CH(2)C(6)H(4)NH(3)](2+) dications stabilised by N-H...Cl linkages. Energy calculations on the crystalline systems allow an identification of the main factors in intermolecular cohesion; these are related to melting temperature and solubility data. Such improvements in understanding of solute-solute interactions are prerequisites for improving the atom economy of this important stage within the polyurethane manufacture process chain. The solid phase IR spectrum of MDA x 2 HCl is diagnostic, principally as a result of a Fermi resonance process.

Quantum-chemical calculations performed on poly[2,7-(9,9-di-n-octylfluorene)(1-x)-co-4,7-(2,1,3-benzothiadiazole)(x)] copolymers (0 < or = x < or = 0.5) show that the lowest unoccupied molecular orbital is always highly localized on the benzothiadiazole (BT) units while the highest occupied molecular orbital is delocalized over the whole chain. Chains with a low BT content are characterized by a reduced oscillator strength of the lowest optical transition and by an increased charge-transfer character of the exciton. These results are supported experimentally by a blueshift of the lowest energy absorption band upon reduction in the BT ratio, lower photoluminescence efficiency, longer excited state lifetimes, and greater solvent dependence of the emission properties.

The combination of several probe molecules has enabled the construction of a detailed picture of the surface of aluminium hydroxyl fluoride, AlF(2.6)(OH)(0.4), which has the hexagonal tungsten bronze (HTB) structure. Using pyridine as a probe leads to features at 1628 cm(-1), ascribed to very strong Lewis acid sites, and at 1620-1623 cm(-1), which is the result of several different types of Lewis sites. This heterogeneity is indicated also from CO adsorption at 100 K; the presence of five different types of Lewis site is deduced and is suggested to arise from the hydroxylated environment. Brønsted acid sites of medium strength are indicated by adsorption of lutidine and CO. Adsorption of lutidine occurs at OH groups, which are exposed at the surface and CO reveals that these OH groups have a single environment that can be correlated with their specific location inside the bulk, assuming that the surface OH group may reflect the bulk OH periodicity. A correlation between the data obtained from CO and pyridine molecules has been established using co-adsorption experiments, which also highlight the inductive effect produced by pyridine. Adsorption of the strong Brønsted acid, anhydrous hydrogen chloride, detected by monitoring the beta(-) emission of [(36)Cl]-HCl at the surface, indicates that surface hydroxyl groups can behave also as a Brønsted base and that H(2)O-HCl interactions, either within the hexagonal channels or at the surface are possible. Finally, the formation of strongly bound H(36)Cl as a result of the room temperature dehydrochlorination of [(36)Cl]-labelled tert-butyl chloride provides additional evidence that HTB-AlF(2.6)(OH)(0.4) can behave as a Lewis acid.

The hydrochlorination of 4-benzylaniline in chlorobenzene to produce 4-benzylaniline hydrochloride has been examined. This has required spectroscopic and computational analysis of the solvation of gaseous HCl in the process solvent. The characterisation of the reagent and product of the hydrochlorination reaction by various techniques, including FTIR and (1)H NMR spectroscopy and X-ray diffraction, is described. The infrared spectrum of the hydrochloride salt contains a strong Fermi resonance interaction, readily distinguishing it from that of the starting material. Using the structural results as a basis, the lattice energies of reagent and product have been evaluated by the recently developed PIXEL method. This method allows the contributions of specific intermolecular interactions to the total lattice energy to be assessed and, in this case, tentatively correlated with solubility measurements.

A non-aqueous sol-gel Al-based fluoride has been subjected to the microwave solvothermal process. The final material depends on the temperature heat treatment used. Three types of material have been prepared: 1) for low temperature heat treatment (90 degrees C) X-ray amorphous alkoxy fluoride was obtained; 2) for the highest temperature used (200 degrees C) the metastable form beta-AlF3 was obtained with a very large surface area of 125 m2 g(-1). The mechanism of the amorphous=crystalline transformation has been rationalised by the occurrence of a decomposition reaction of the gel fluoride induced by the microwave irradiation. 3) Finally, at intermediate temperature (180 degrees C) a multi-component material mixture exhibiting a huge surface area of 525 m2 g(-1) has been obtained and further investigated after mild post-treatment fluorination using F2 gas. The resulting aluminium-based fluoride still possesses a high-surface-area of 330 m2 g(-1). HRTEM revealed that the solid is built from large particles (50 nm) identified as alpha-AlF3, and small ones (10 nm), relative to an unidentified phase. This new high-surface-area material exhibits strong Lewis acidity as revealed by pyridine adsorption and catalytic tests. By comparison with other materials, it has been shown that whatever the composition/structure of the Al-based fluoride materials, the number of strong Lewis acid sites is related to the surface area, highlighting the role of surface reconstruction occurring on a nanoscopic scale on the formation of the strongest Lewis acid sites.