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Quantitative BOLD (qBOLD) imaging of oxygen metabolism and blood oxygenation in the human body: A scoping reviewPurpose: There are many approaches to the quantitative BOLD (qBOLD) technique described in the literature, differing in pulse sequences, MRI parameters and data processing. Thus, in this review, we summarized the acquisition methods, approaches used for oxygenation quantification and clinical populations investigated. Method(s): Three databases were systematically searched (Medline, Embase, and Web of Science) for published research that used qBOLD methods for quantification of oxygen metabolism. Data extraction and synthesis were performed by one author and reviewed by a second author. Result(s): A total of 93 relevant papers were identified. Acquisition strategies were summarized, and oxygenation parameters were found to have been investigated in many pathologies such as steno-occlusive diseases, stroke, glioma, and multiple sclerosis disease. Conclusion(s): A summary of qBOLD approaches for oxygenation measurements and applications could help researchers to identify good practice and provide objective information to inform the development of future consensus recommendations.Copyright © 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.
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Oxygen-enhanced MRI assessment of tumour hypoxia in head and neck cancer is feasible and well tolerated in the clinical settingBackground: Tumour hypoxia is a recognised cause of radiotherapy treatment resistance in head and neck squamous cell carcinoma (HNSCC). Current positron emission tomography-based hypoxia imaging techniques are not routinely available in many centres. We investigated if an alternative technique called oxygen-enhanced magnetic resonance imaging (OE-MRI) could be performed in HNSCC. Method(s): A volumetric OE-MRI protocol for dynamic T1 relaxation time mapping was implemented on 1.5-T clinical scanners. Participants were scanned breathing room air and during high-flow oxygen administration. Oxygen-induced changes in T1 times (DELTAT1) and R2* rates (DELTAR2*) were measured in malignant tissue and healthy organs. Unequal variance t-test was used. Patients were surveyed on their experience of the OE-MRI protocol. Result(s): Fifteen patients with HNSCC (median age 59 years, range 38 to 76) and 10 non-HNSCC subjects (median age 46.5 years, range 32 to 62) were scanned; the OE-MRI acquisition took less than 10 min and was well tolerated. Fifteen histologically confirmed primary tumours and 41 malignant nodal masses were identified. Median (range) of DELTAT1 times and hypoxic fraction estimates for primary tumours were -3.5% (-7.0 to -0.3%) and 30.7% (6.5 to 78.6%) respectively. Radiotherapy-responsive and radiotherapy-resistant primary tumours had mean estimated hypoxic fractions of 36.8% (95% confidence interval CI] 17.4 to 56.2%) and 59.0% (95% CI 44.6 to 73.3%), respectively (p = 0.111). Conclusion(s): We present a well-tolerated implementation of dynamic, volumetric OE-MRI of the head and neck region allowing discernment of differing oxygen responses within biopsy-confirmed HNSCC. Trial registration: ClinicalTrials.gov, NCT04724096. Registered on 26 January 2021. Relevance statement: MRI of tumour hypoxia in head and neck cancer using routine clinical equipment is feasible and well tolerated and allows estimates of tumour hypoxic fractions in less than ten minutes. Key points: * Oxygen-enhanced MRI (OE-MRI) can estimate tumour hypoxic fractions in ten-minute scanning. * OE-MRI may be incorporable into routine clinical tumour imaging. * OE-MRI has the potential to predict outcomes after radiotherapy treatment. Graphical Abstract: (Figure presented.)Copyright © The Author(s) 2024.
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T1 based oxygen-enhanced MRI in tumours; A scoping review of current researchOBJECTIVE: Oxygen-enhanced MRI (OE-MRI) or tissue oxygen-level dependent (TOLD) MRI is an imaging technique under investigation for its ability to quantify and map oxygen distributions within tumours. The aim of this study was to identify and characterise the research into OE-MRI for characterising hypoxia in solid tumours., METHODS: A scoping review of published literature was performed on the PubMed and Web of Science databases for articles published before 27 May 2022. Studies imaging solid tumours using proton-MRI to measure oxygen-induced T1/R1 relaxation time/rate changes were included. Grey literature was searched from conference abstracts and active clinical trials., RESULTS: 49 unique records met the inclusion criteria consisting of 34 journal articles and 15 conference abstracts. The majority of articles were pre-clinical studies (31 articles) with 15 human only studies. Pre-clinical studies in a range of tumour types demonstrated consistent correlation of OE-MRI with alternative hypoxia measurements. No clear consensus on optimal acquisition technique or analysis methodology was found. No prospective, adequately powered, multicentre clinical studies relating OE-MRI hypoxia markers to patient outcomes were identified., CONCLUSION: There is good pre-clinical evidence of the utility of OE-MRI in tumour hypoxia assessment; however, there are significant gaps in clinical research that need to be addressed to develop OE-MRI into a clinically applicable tumour hypoxia imaging technique., ADVANCES IN KNOWLEDGE: The evidence base of OE-MRI in tumour hypoxia assessment is presented along with a summary of the research gaps to be addressed to transform OE-MRI derived parameters into tumour hypoxia biomarkers.
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Mapping the human genetic architecture of COVID-19The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3-7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.Copyright © 2021, The Author(s).
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Synthesis of the European ALARA network 20th workshop 'ALARA for interventional radiology and nuclear medicine'The European as low as reasonably achievable(ALARA) network regularly organises workshops on topical issues in radiation protection (RP). The topic of the 20th workshop was: 'ALARA for interventional radiology (IR) and nuclear medicine (NM)'. The objective was to examine the challenges faced when applying the optimisation principle (ALARA) in IR and NM and to consider how ALARA could be better implemented for patient and staff exposures. This memorandum provides a synthesis of the workshop sessions, and recommendations coming from the working groups discussion. Parallels are drawn with the recommendations arising from the 13th EAN workshop on 'ALARA and the medical sector (2011)' to consider how the optimisation challenges in IR and NM have evolved over the past decade. Current levels of exposure are presented along with operational practice and the challenges and opportunities for improvement, both in monitoring and practice. Whilst RP challenges remain, the application of ALARA appears more established in IR compared with experiences reported in 2011. The application of ALARA to emerging technologies in the NM setting is in need of further development to ensure that RP is considered at all stages in the development process of new radiopharmaceuticals. Besides the obvious technical and operational aspects, the importance of education and training, human factors and broadly the RP 'culture' were deemed fundamental to the success of the application of ALARA and where further emphasis is needed. All concerned parties, medical physics experts (MPEs), radiation protection experts, clinical staff, manufacturers and regulators have a role to play in the application of ALARA and this is discussed in the memorandum. Many of the recommendations from the 13th EAN workshop remain applicable today and overlap with the recommendations arising from the 20th workshop. This should prompt attention given that the use of IR and the development of novel radiopharmaceuticals for NM is only anticipated to increase with time.Copyright © 2024 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.
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Assessing empirical thresholds for investigation in people referred on a symptomatic colorectal cancer pathway: A cohort study utilising faecal immunochemical and blood tests in EnglandObjective To quantify risk of colorectal cancer (CRC) at empirical FIT cut offs, across age, haemoglobin and platelet strata in current diagnostic pathways. Design Cohort study of all people who were referred on a symptomatic CRC diagnosis pathway from primary care with a FIT test in Nottingham, UK between November 2017 and 2021 with 1-year follow-up for cancer and death. Heat maps showed the cumulative 1-year CRC risk using Kaplan-Meier estimates. We estimated the number of investigations that could potentially be re-purposed if a threshold of >=3% 1-year risk of CRC was instigated. Results During the study period 514 (1.5%) colorectal cancers were diagnosed following 33694 index FIT tests with available blood tests. Individuals with a FIT >=10 microg Hb/g faeces had a greater than 3% risk of CRC, except patients under the age of 40 years (CRC risk 1.45% (95% CI 0.03-2.86%)). Non-anaemic patients with a FIT =3% CRC threshold in patients < 55 years calculated using FIT, age and anaemia would allow 160-220 colonoscopies per 10000 FIT tests to be used for other pathways, at the cost of missing 1-2 CRCs. Conclusions CRC risk varies by FIT, age and anaemia status when fHb levels are below 100 microg Hb/g faeces. Tailored cut offs for investigation on a CRC pathway could reduce the number of investigations needed at a 3% CRC risk threshold.Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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National UK survey of radiation doses during endovascular aortic interventionsPurpose: Endovascular aortic repair (EAR) interventions, endovascular abdominal aortic repair (EVAR) and thoracic endovascular aortic repair (TEVAR), are associated with significant radiation exposures. We aimed to investigate the radiation doses from real-world practice and propose diagnostic reference level (DRL) for the UK. Material(s) and Method(s): Radiation data and essential demographics were retrospectively collected from 24 vascular and interventional radiology centres in the UK for all patients undergoing EAR-standard EVAR or complex, branched/fenestrated (BEVAR/FEVAR), and TEVAR-between 2018 and 2021. The data set was further categorised according to X-ray unit type, either fixed or mobile. The proposed national DRL is the 75th percentile of the collective medians for procedure KAP (kerma area product), cumulative air kerma (CAK), fluoroscopy KAP and CAK. Result(s): Data from 3712 endovascular aortic procedures were collected, including 2062 cases were standard EVAR, 906 cases of BEVAR/FEVAR and 509 cases of TEVAR. The majority of endovascular procedures (3477/3712) were performed on fixed X-ray units. The proposed DRL for KAP was 162 Gy cm2, 175 Gy cm2 and 266 Gy cm2 for standard EVAR, TEVAR and BEVAR/FEVAR, respectively. Conclusion(s): The development of DRLs is pertinent to EAR procedures as the first step to optimise the radiation risks to patients and staff while maintaining the highest patient care and paving the way for steps to reduce radiation exposures.Copyright © 2023, The Author(s).
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A comparison of two peak skin dose metrics calculated by patient dose management systems: Implications for clinical managementObjective: The patient dose monitoring systems DoseWatch and DoseWise were compared to evaluate their reported patient Peak Skin Dose. Method(s): 20 patients with the highest Peak Skin Dose on DoseWise were obtained; the values were converted to a Reference Point Air Kerma (RPAK) value and used for comparison. These patients were accessed in DoseWatch to obtain the recorded Worst Case RPAK. The co-ordinates for the position were obtained for each patient to find a primary and secondary angular position for the peak skin dose. The two positions produced by the two softwares were compared. Result(s): There is a mean deviation of over 0.5 Gy between the two software packages when comparing the calculated maximum skin air kerma Peak skin dose from DoseWise and the Worst Case RPAK from DoseWatch. Conclusion(s): We have shown mean deviations between these two systems. This difference is enough, for higher peak skin absorbed dose patients, to change the management of patients, so local services must understand their models to properly implement patient management. Advances in knowledge: Neither system is incorrect, but these differences show that a deeper understanding of the analysis limitations is required to properly inform post-procedural high-skin dose follow-up procedures.Copyright © 2021 The Authors. Published by the British Institute of Radiology
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Expression of Cathepsin D in early-stage breast cancer and its prognostic and predictive valuePurpose: Cathepsin D is a proteolytic enzyme that is normally localized in the lysosomes and is involved in the malignant progression of breast cancer. There are conflicting results regarding Cathepsin D significance as prognostic and predictor marker in breast cancer. This study aimed to evaluate the expression and prognostic significance of Cathepsin D in early-stage breast cancer. Method(s): Expression of Cathepsin D was assessed by immunohistochemical staining of tissue microarrays, in a large well-characterized series of early-stage operable breast cancer (n = 954) from Nottingham Primary Breast Carcinoma Series between the period of 1988 and 1998 who underwent primary surgery. Correlation of Cathepsin D expression with clinicopathological parameters and prognosis was evaluated. Result(s): Cathepsin D expression was positive in 71.2% (679/954) of breast cancer tumours. Positive expression of Cathepsin D was significantly associated with high histological grade (p = 0.007), pleomorphism (p = 0.002), poor Nottingham Prognostic Index (NPI) score (p < 0.002), recurrence (p = 0.005) and distant metastasis (p < 0.0001). Kaplan-Meier analysis showed that Cathepsin D expression was significantly associated with shorter breast cancer-specific survival (p = 0.001), higher risk of recurrence (p = 0.001) and distant metastasis (p < 0.0001). ER-positive tumours expressing Cathepsin D and treated with tamoxifen demonstrated a significantly higher risk of distant metastasis. Conclusion(s): Cathepsin D expression significantly predicts poor prognosis in breast cancer and is associated with variables of poor prognosis and shorter outcome. The strong association of Cathepsin D with aggressive tumour characteristics and poor outcomes warrants further research of its potential as a therapeutic target The results also suggest a possible interaction between Cathepsin D and tamoxifen therapy in ER-positive breast cancer which needs further investigation to elucidate the underlying mechanisms.Copyright © The Author(s) 2024.
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A new defense of brain death as the death of the human organismThis paper provides a new rationale for equating brain death with the death of the human organism, in light of well-known criticisms made by Alan D Shewmon, Franklin Miller and Robert Truog and a number of other writers. We claim that these criticisms can be answered, but only if we accept that we have slightly redefined the concept of death when equating brain death with death simpliciter. Accordingly, much of the paper defends the legitimacy of redefining death against objections, before turning to the specific task of defending a new rationale for equating brain death with death as slightly redefined. Copyright © The Author(s) 2023. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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The use of cerebral computed tomographic angiography as an ancillary investigation to support a clinical diagnosis of death using neurological criteria: A consensus guidelineThis multidisciplinary consensus statement was produced following a recommendation by the Faculty of Intensive Care Medicine to develop a UK guideline for ancillary investigation, when one is required, to support the diagnosis of death using neurological criteria. A multidisciplinary panel reviewed the literature and UK practice in the diagnosis of death using neurological criteria and recommended cerebral CT angiography as the ancillary investigation of choice when death cannot be confirmed by clinical criteria alone. Cerebral CT angiography has been shown to have 100% specificity in supporting a diagnosis of death using neurological criteria and is an investigation available in all acute hospitals in the UK. A standardised technique for performing the investigation is described alongside a reporting template. The panel were unable to make recommendations for ancillary testing in children or patients receiving extracorporeal membrane oxygenation. Copyright © 2023 Association of Anaesthetists.
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Digitally-enabled remote critical care: The challenges of geography and history?The COVID-19 pandemic has rejuvenated interest in the possibility of using telemedicine as an approach to providing critical care services to patients in remote areas. Conceptual and governance considerations remain unaddressed. We summarise the first steps in a recent collaborative effort between key organisations in Australia, India, New Zealand, and the UK, and call for an international consensus on standards with due considerations to governance and regulation of this emerging clinical practice. Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
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Noise suppression of proton magnetic resonance spectroscopy improves paediatric brain tumour classificationProton magnetic resonance spectroscopy (1H-MRS) is increasingly used for clinical brain tumour diagnosis, but suffers from limited spectral quality. This retrospective and comparative study aims at improving paediatric brain tumour classification by performing noise suppression on clinical 1H-MRS. Eighty-three/forty-two children with either an ependymoma (ages 4.6 5.3/9.3 5.4), a medulloblastoma (ages 6.9 3.5/6.5 4.4), or a pilocytic astrocytoma (8.0 3.6/6.3 5.0), recruited from four centres across England, were scanned with 1.5T/3T short-echo-time point-resolved spectroscopy. The acquired raw 1H-MRS was quantified by using Totally Automatic Robust Quantitation in NMR (TARQUIN), assessed by experienced spectroscopists, and processed with adaptive wavelet noise suppression (AWNS). Metabolite concentrations were extracted as features, selected based on multiclass receiver operating characteristics, and finally used for identifying brain tumour types with supervised machine learning. The minority class was oversampled through the synthetic minority oversampling technique for comparison purposes. Post-noise-suppression 1H-MRS showed significantly elevated signal-to-noise ratios (P < .05, Wilcoxon signed-rank test), stable full width at half-maximum (P > .05, Wilcoxon signed-rank test), and significantly higher classification accuracy (P < .05, Wilcoxon signed-rank test). Specifically, the cross-validated overall and balanced classification accuracies can be improved from 81% to 88% overall and 76% to 86% balanced for the 1.5T cohort, whilst for the 3T cohort they can be improved from 62% to 76% overall and 46% to 56%, by applying Naïve Bayes on the oversampled 1H-MRS. The study shows that fitting-based signal-to-noise ratios of clinical 1H-MRS can be significantly improved by using AWNS with insignificantly altered line width, and the post-noise-suppression 1H-MRS may have better diagnostic performance for paediatric brain tumours.
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Comparison of echo planar and turbo spin echo diffusion-weighted imaging in intraoperative MRIBACKGROUND: Diffusion-weighted imaging (DWI) is routinely used in brain tumor surgery guided by intraoperative MRI (IoMRI). However, conventional echo planar imaging DWI (EPI-DWI) is susceptible to distortion and artifacts that affect image quality. Turbo spin echo DWI (TSE-DWI) is an alternative technique with minimal spatial distortions that has the potential to be the radiologically preferred sequence., PURPOSE: To compare via single- and multisequence assessment EPI-DWI and TSE-DWI in the IoMRI setting to determine whether there is a radiological preference for either sequence., STUDY TYPE: Retrospective., POPULATION: Thirty-four patients (22 female) aged 2-61 years (24 under 18 years) undergoing IoMRI during surgical resection of intracranial tumors., FIELD STRENGTH/SEQUENCE: 3-T, EPI-DWI, and TSE-DWI., ASSESSMENT: Patients were scanned with EPI- and TSE-DWI as part of the standard IoMRI scanning protocol. A single-sequence assessment of spatial distortion and image artifact was performed by three neuroradiologists blinded to the sequence type. Images were scored regarding distortion and artifacts, around and remote to the resection cavity. A multisequence radiological assessment was performed by three neuroradiologists in full radiological context including all other IoMRI sequences from each case. The DWI images were directly compared with scorings of the radiologists on which they preferred with respect to anatomy, abnormality, artifact, and overall preference., STATISTICAL TESTS: Wilcoxon signed-rank tests for single-sequence assessment, weighted kappa for single and multisequence assessment. A P-value : Wilcoxon signed-rank tests for single-sequence assessment, weighted kappa for single and multisequence assessment. A P-value RESULTS: For the blinded single-sequence assessment, the TSE-DWI sequence was scored equal to or superior to the EPI-DWI sequence for distortion and artifacts, around and remote to the resection cavity for every case. In the multisequence assessment, all radiologists independently expressed a preference for TSE-DWI over EPI-DWI sequences on viewing brain anatomy, abnormalities, and artifacts., DATA CONCLUSION: The TSE-DWI sequences may be favored over EPI-DWI for IoMRI in patients with intracranial tumors., LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 5. Copyright © 2024 The Author(s). Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.
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Predictors of long-term disability in multiple sclerosis patients using routine magnetic resonance imaging data: A 15-year retrospective studyINTRODUCTION: Early identification of patients at high risk of progression could help with a personalised treatment strategy. Magnetic resonance imaging (MRI) measures have been proposed to predict long-term disability in multiple sclerosis (MS), but a reliable predictor that can be easily implemented clinically is still needed., AIM: Assess MRI measures during the first 5 years of the MS disease course for the ability to predict progression at 10+ years., METHODS: Eighty-two MS patients (53 females), with >=10 years of clinical follow-up and having two MRI scans, were included. Clinical data were obtained at baseline, follow-up and at >=10 years. White matter lesion (WML) counts and volumes, and four linear brain sizes were measured on T2/FLAIR 'Fluid-Attenuated-Inversion-Recovery' and T1-weighted images., RESULTS: Baseline and follow-up inter-caudate diameter (ICD) and third ventricular width (TVW) measures correlated positively with Expanded Disability Status Scale, >=10 or more of WMLs showed a high sensitivity in predicting progression, at >=10 years. A steeper rate of lesion volume increase was observed in subjects converting to secondary progressive MS. The sensitivity and specificity of both ICD and TVW, to predict disability at >=10 years were 60% and 64%, respectively., CONCLUSION: Despite advances in brain imaging and computerised volumetric analysis, ICD and TVW remain relevant as they are simple, fast and have the potential in predicting long-term disability. However, in this study, despite the statistical significance of these measures, the clinical utility is still not reliable.
