Imaging breast cancer using hyperpolarized carbon-13 MRI.

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

Quantifying normal human brain metabolism using hyperpolarized [1-13C]pyruvate and magnetic resonance imaging.

Hyperpolarized 13C Magnetic Resonance Imaging (13C-MRI) provides a highly sensitive tool to probe tissue metabolism in vivo and has recently been translated into clinical studies. We report the cerebral metabolism of intravenously injected hyperpolarized [1-13C]pyruvate in the brain of healthy human volunteers for the first time. Dynamic acquisition of 13C images demonstrated 13C-labeling of both lactate and bicarbonate, catalyzed by cytosolic lactate dehydrogenase and mitochondrial pyruvate dehydrogenase respectively. This demonstrates that both enzymes can be probed in vivo in the presence of an intact blood-brain barrier: the measured apparent exchange rate constant (kPL) for exchange of the hyperpolarized 13C label between [1-13C]pyruvate and the endogenous lactate pool was 0.012 ±â€¯0.006 s-1 and the apparent rate constant (kPB) for the irreversible flux of [1-13C]pyruvate to [13C]bicarbonate was 0.002 ±â€¯0.002 s-1. Imaging also revealed that [1-13C]pyruvate, [1-13C]lactate and [13C]bicarbonate were significantly higher in gray matter compared to white matter. Imaging normal brain metabolism with hyperpolarized [1-13C]pyruvate and subsequent quantification, have important implications for interpreting pathological cerebral metabolism in future studies.

Electroreception in marine fishes: chondrichthyans.

Electroreception in marine fishes occurs across a variety of taxa and is best understood in the chondrichthyans (sharks, skates, rays, and chimaeras). Here, we present an up-to-date review of what is known about the biology of passive electroreception and we consider how electroreceptive fishes might respond to electric and magnetic stimuli in a changing marine environment. We briefly describe the history and discovery of electroreception in marine Chondrichthyes, the current understanding of the passive mode, the morphological adaptations of receptors across phylogeny and habitat, the physiological function of the peripheral and central nervous system components, and the behaviours mediated by electroreception. Additionally, whole genome sequencing, genetic screening and molecular studies promise to yield new insights into the evolution, distribution, and function of electroreceptors across different environments. This review complements that of electroreception in freshwater fishes in this special issue, which provides a comprehensive state of knowledge regarding the evolution of electroreception. We conclude that despite our improved understanding of passive electroreception, several outstanding gaps remain which limits our full comprehension of this sensory modality. Of particular concern is how electroreceptive fishes will respond and adapt to a marine environment that is being increasingly altered by anthropogenic electric and magnetic fields.

The longitudinal effect of ejaculation on seminal vesicle fluid volume and whole-prostate ADC as measured on prostate MRI.

OBJECTIVE: To prospectively investigate the longitudinal effect of ejaculatory abstinence on MRI-measured seminal vesicle (SV) volume and whole-prostate ADC over consecutive days. METHODS: 15 healthy male volunteers (mean 35.9 years, range 27-53) underwent 3-T MRI at baseline and 1, 2 and 3 days post-ejaculation. Prostate and SV volumes were derived by volume segmentation and whole-gland apparent diffusion coefficient (ADC) values calculated. A mixed-effects linear regression compared ADC values and prostate/seminal vesicle volumes in each volunteer between studies in a pairwise manner. RESULTS: All subjects completed the four MRIs. Mean prostate volume was 22.45 cm3 (range 13.04-31.21 cm3), with no change between the four studies (p = 0.89-0.99). 13/15 subjects showed SV volume reduction from baseline to day 1, with group-mean decreasing from 6.45 to 4.80 cm3 (-25.6%, p < 0.001), and a significant reduction from baseline to day 2 (-18.1%, p = 0.002). There was a significant volume increase from both day 1 (+21.3%, p = 0.006) and day 2 (+10.2%, p = 0.022) to day 3 post-ejaculation. There was a significant reduction in ADC from 1.105 at baseline to 1.056 × 10-3 mm2/s at day 1 (mean -4.3%, p = 0.009). CONCLUSION: The longitudinal effect of ejaculation on SV volume was demonstrated. Significant reductions in SV volume and whole-gland ADC were observed post-ejaculation, supporting a 3-day period of abstinence before prostate MRI. KEY POINTS: • Seminal vesicle volume significantly reduced 24 h post-ejaculation remaining reduced at day 2 • Seminal vesicle fluid volume significantly increased from day 1 to day 3 post-ejaculation • There was a significant reduction in whole-gland prostate ADC values day 1 post-ejaculation • 3-day abstinence from ejaculation is required to ensure maximal seminal vesicle distension.

Assessment of early treatment response to neoadjuvant chemotherapy in breast cancer using non-mono-exponential diffusion models: a feasibility study comparing the baseline and mid-treatment MRI examinations.

OBJECTIVES: To assess the feasibility of the mono-exponential, bi-exponential and stretched-exponential models in evaluating response of breast tumours to neoadjuvant chemotherapy (NACT) at 3 T. METHODS: Thirty-six female patients (median age 53, range 32-75 years) with invasive breast cancer undergoing NACT were enrolled for diffusion-weighted MRI (DW-MRI) prior to the start of treatment. For assessment of early response, changes in parameters were evaluated on mid-treatment MRI in 22 patients. DW-MRI was performed using eight b values (0, 30, 60, 90, 120, 300, 600, 900 s/mm2). Apparent diffusion coefficient (ADC), tissue diffusion coefficient (D t), vascular fraction (ƒ), distributed diffusion coefficient (DDC) and alpha (α) parameters were derived. Then t tests compared the baseline and changes in parameters between response groups. Repeatability was assessed at inter- and intraobserver levels. RESULTS: All patients underwent baseline MRI whereas 22 lesions were available at mid-treatment. At pretreatment, mean diffusion coefficients demonstrated significant differences between groups (p < 0.05). At mid-treatment, percentage increase in ADC and DDC showed significant differences between responders (49 % and 43 %) and non-responders (21 % and 32 %) (p = 0.03, p = 0.04). Overall, stretched-exponential parameters showed excellent repeatability. CONCLUSION: DW-MRI is sensitive to baseline and early treatment changes in breast cancer using non-mono-exponential models, and the stretched-exponential model can potentially monitor such changes. KEY POINTS: • Baseline diffusion coefficients demonstrated significant differences between complete pathological responders and non-responders. • Increase in ADC and DDC at mid-treatment can discriminate responders and non-responders. • The ƒ fraction at mid-treatment decreased in responders whereas increased in non-responders. • The mono- and stretched-exponential models showed excellent inter- and intrarater repeatability. • Treatment effects can potentially be assessed by non-mono-exponential diffusion models.

A comparison of quantitative methods for clinical imaging with hyperpolarized (13)C-pyruvate.

Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized (13)C-labelled molecules, such as the conversion of [1-(13)C]pyruvate to [1-(13)C]lactate, to be dynamically and non-invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model-free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two-way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time-to-peak and the lactate-to-pyruvate area under the curve ratio were simple model-free approaches that accurately represented the full reaction, with the time-to-peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized (13)C data.

Elasmobranch cognitive ability: using electroreceptive foraging behaviour to demonstrate learning, habituation and memory in a benthic shark.

Top predators inhabiting a dynamic environment, such as coastal waters, should theoretically possess sufficient cognitive ability to allow successful foraging despite unpredictable sensory stimuli. The cognition-related hunting abilities of marine mammals have been widely demonstrated. Having been historically underestimated, teleost cognitive abilities have also now been significantly demonstrated. Conversely, the abilities of elasmobranchs have received little attention, despite many species possessing relatively large brains comparable to some mammals. The need to determine what, if any, cognitive ability these globally distributed, apex predators are endowed with has been highlighted recently by questions arising from environmental assessments, specifically whether they are able to learn to distinguish between anthropogenic electric fields and prey bioelectric fields. We therefore used electroreceptive foraging behaviour in a model species, Scyliorhinus canicula (small-spotted catshark), to determine cognitive ability by analysing whether elasmobranchs are able to learn to improve foraging efficiency and remember learned behavioural adaptations. Positive reinforcement, operant conditioning was used to study catshark foraging behaviour towards artificial, prey-type electric fields (Efields). Catsharks rewarded with food for responding to Efields throughout experimental weeks were compared with catsharks that were not rewarded for responding in order to assess behavioural adaptation via learning ability. Experiments were repeated after a 3-week interval with previously rewarded catsharks this time receiving no reward and vice versa to assess memory ability. Positive reinforcement markedly and rapidly altered catshark foraging behaviour. Rewarded catsharks exhibited significantly more interest in the electrical stimulus than unrewarded catsharks. Furthermore, they improved their foraging efficiency over time by learning to locate and bite the electrodes to gain food more quickly. In contrast, unrewarded catsharks showed some habituation, whereby their responses to the electrodes abated and eventually entirely ceased, though they generally showed no changes in most foraging parameters. Behavioural adaptations were not retained after the interval suggesting learned behaviour was not memorised beyond the interval. Sequences of individual catshark search paths clearly illustrated learning and habituation behavioural adaptation. This study demonstrated learning and habituation occurring after few foraging events and a memory window of between 12 h and 3 weeks. These cognitive abilities are discussed in relation to diet, habitat, ecology and anthropogenic Efield sources.

Do electromagnetic fields from subsea power cables effect benthic elasmobranch behaviour? A risk-based approach for the Dutch Continental Shelf.

Subsea power cables cause electromagnetic fields (EMFs) into the marine environment. Elasmobranchs (rays, skates, sharks) are particularly sensitive to EMFs as they use electromagnetic-receptive sensory systems for orientation, navigation, and locating conspecifics or buried prey. Cables may intersect with egg laying sites, mating, pupping, and nursery grounds, foraging habitat and migration routes of elasmobranchs and the effects of encountering EMFs on species of elasmobranchs are largely unknown. Demonstrated behavioural effects are attraction, disturbance and indifference, depending on EMF characteristics, exposed life stage, exposure level and duration. We estimated exposure levels of elasmobranchs to subsea power cable EMFs, based on modelled magnetic fields in the Dutch Continental Shelf and compared these to reported elasmobranch sensory sensitivity ranges and experimental effect levels. We conclude that the risk from subsea power cables has a large uncertainty and varies per life stage and species ecology. Based on estimated no-observed effect levels (from 10-3 to 10-1 µT) we discuss what will probably be the most affected species and life stage for six common benthic elasmobranchs in the Southern North Sea. We then identify critical knowledge gaps for reducing the uncertainty in the risk assessments for EMFs effects on benthic elasmobranchs.

23Na MRI: inter-reader reproducibility of normal fibroglandular sodium concentration measurements at 3 T.

BACKGROUND: To study the reproducibility of 23Na magnetic resonance imaging (MRI) measurements from breast tissue in healthy volunteers. METHODS: Using a dual-tuned bilateral 23Na/1H breast coil at 3-T MRI, high-resolution 23Na MRI three-dimensional cones sequences were used to quantify total sodium concentration (TSC) and fluid-attenuated sodium concentration (FASC). B1-corrected TSC and FASC maps were created. Two readers manually measured mean, minimum and maximum TSC and mean FASC values using two sampling methods: large regions of interest (LROIs) and small regions of interest (SROIs) encompassing fibroglandular tissue (FGT) and the highest signal area at the level of the nipple, respectively. The reproducibility of the measurements and correlations between density, age and FGT apparent diffusion coefficient (ADC) values were evaluatedss. RESULTS: Nine healthy volunteers were included. The inter-reader reproducibility of TSC and FASC using SROIs and LROIs was excellent (intraclass coefficient range 0.945-0.979, p < 0.001), except for the minimum TSC LROI measurements (p = 0.369). The mean/minimum LROI TSC and mean LROI FASC values were lower than the respective SROI values (p < 0.001); the maximum LROI TSC values were higher than the SROI TSC values (p = 0.009). TSC correlated inversely with age but not with FGT ADCs. The mean and maximum FGT TSC and FASC values were higher in dense breasts in comparison to non-dense breasts (p < 0.020). CONCLUSIONS: The chosen sampling method and the selected descriptive value affect the measured TSC and FASC values, although the inter-reader reproducibility of the measurements is in general excellent. RELEVANCE STATEMENT: 23Na MRI at 3 T allows the quantification of TSC and FASC sodium concentrations. The sodium measurements should be obtained consistently in a uniform manner. KEY POINTS: • 23Na MRI allows the quantification of total and fluid-attenuated sodium concentrations (TSC/FASC). • Sampling method (large/small region of interest) affects the TSC and FASC values. • Dense breasts have higher TSC and FASC values than non-dense breasts. • The inter-reader reproducibility of TSC and FASC measurements was, in general, excellent. • The results suggest the importance of stratifying the sodium measurements protocol.

High-resolution and highly accelerated MRI T2 mapping as a tool to characterise renal tumour subtypes and grades.

BACKGROUND: Clinical imaging tools to probe aggressiveness of renal masses are lacking, and T2-weighted imaging as an integral part of magnetic resonance imaging protocol only provides qualitative information. We developed high-resolution and accelerated T2 mapping methods based on echo merging and using k-t undersampling and reduced flip angles (TEMPURA) and tested their potential to quantify differences between renal tumour subtypes and grades. METHODS: Twenty-four patients with treatment-naïve renal tumours were imaged: seven renal oncocytomas (RO); one eosinophilic/oncocytic renal cell carcinoma; two chromophobe RCCs (chRCC); three papillary RCCs (pRCC); and twelve clear cell RCCs (ccRCC). Median, kurtosis, and skewness of T2 were quantified in tumours and in the normal-adjacent kidney cortex and were compared across renal tumour subtypes and between ccRCC grades. RESULTS: High-resolution TEMPURA depicted the tumour structure at improved resolution compared to conventional T2-weighted imaging. The lowest median T2 values were present in pRCC (high-resolution, 51 ms; accelerated, 45 ms), which was significantly lower than RO (high-resolution; accelerated, p = 0.012) and ccRCC (high-resolution, p = 0.019; accelerated, p = 0.008). ROs showed the lowest kurtosis (high-resolution, 3.4; accelerated, 4.0), suggestive of low intratumoural heterogeneity. Lower T2 values were observed in higher compared to lower grade ccRCCs (grades 2, 3 and 4 on high-resolution, 209 ms, 151 ms, and 106 ms; on accelerated, 172 ms, 160 ms, and 102 ms, respectively), with accelerated TEMPURA showing statistical significance in comparison (p = 0.037). CONCLUSIONS: Both high-resolution and accelerated TEMPURA showed marked potential to quantify differences across renal tumour subtypes and between ccRCC grades. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03741426 . Registered on 13 November 2018. RELEVANCE STATEMENT: The newly developed T2 mapping methods have improved resolution, shorter acquisition times, and promising quantifiable readouts to characterise incidental renal masses.

Open source code for the generation of digital reference objects for dynamic contrast-enhanced MRI analysis software validation.

OBJECTIVES: Dynamic contrast-enhanced MR images can be analyzed through the application of a wide range of kinetic models. This process is prone to variability and a lack of standardization that can affect the measured metrics. There is a need for customized digital reference objects (DROs) for the validation of DCE-MRI software packages that undertake kinetic model analysis. DROs are currently available only for a small subset of the kinetic models commonly applied to DCE-MRI data. This work aimed to address this gap. METHODS: Code was written in the MATLAB programming environment to generate customizable DROs. This modular code allows the insertion of a plug-in to describe the kinetic model to be tested. We input our generated DROs into three commercial and open-source analysis packages and assessed the agreement of kinetic model parameter values output with the 'ground-truth' values used in the DRO generation. RESULTS: For the five kinetic models tested, the concordance correlation coefficient values were >98%, indicating excellent agreement of the results with 'ground-truth'. CONCLUSIONS: Testing our DROs on three independent software packages produced concordant results, strongly suggesting our DRO generation code is correct. This implies that our DROs can be used to validate other third party software for the kinetic model analysis of DCE-MRI data. ADVANCES IN KNOWLEDGE: This work extends published work of others to allow customized generation of test objects for any applied kinetic model and allows the incorporation of B1 mapping into the DRO for application at higher field strengths.

'Scaling up' our understanding of environmental effects of marine renewable energy development from single devices to large-scale commercial arrays.

Global expansion of marine renewable energy (MRE) technologies is needed to help address the impacts of climate change, to ensure a sustainable transition from carbon-based energy sources, and to meet national energy security needs using locally-generated electricity. However, the MRE sector has yet to realize its full potential due to the limited scale of device deployments (i.e., single devices or small demonstration-scale arrays), and is hampered by various factors including uncertainty about environmental effects and how the magnitude of these effects scale with an increasing number of devices. This paper seeks to expand our understanding of the environmental effects of MRE arrays using existing frameworks and through the adaptation and application of cumulative environmental effects terminology to key stressor-receptor interactions. This approach facilitates the development of generalized concepts for the scaling of environmental effects for key stressor-receptor interactions, identifying high priority risks and revealing knowledge gaps that require investigation to aid expansion of the MRE sector. Results suggest that effects of collision risk for an array may be additive, antagonistic, or synergistic, but are likely dependent on array location and configuration. Effects of underwater noise are likely additive as additional devices are deployed in an array, while the effects of electromagnetic fields may be dominant, additive, or antagonistic. Changes to benthic habitats are likely additive, but may be dependent on array configuration and could be antagonistic or synergistic at the ecosystem scale. Effects of displacement, entanglement, and changes to oceanographic systems for arrays are less certain because little information is available about effects at the current scale of MRE development.

Lesion-specific 3D-printed moulds for image-guided tissue multi-sampling of ovarian tumours: A prospective pilot study.

Background: High-Grade Serous Ovarian Carcinoma (HGSOC) is the most prevalent and lethal subtype of ovarian cancer, but has a paucity of clinically-actionable biomarkers due to high degrees of multi-level heterogeneity. Radiogenomics markers have the potential to improve prediction of patient outcome and treatment response, but require accurate multimodal spatial registration between radiological imaging and histopathological tissue samples. Previously published co-registration work has not taken into account the anatomical, biological and clinical diversity of ovarian tumours. Methods: In this work, we developed a research pathway and an automated computational pipeline to produce lesion-specific three-dimensional (3D) printed moulds based on preoperative cross-sectional CT or MRI of pelvic lesions. Moulds were designed to allow tumour slicing in the anatomical axial plane to facilitate detailed spatial correlation of imaging and tissue-derived data. Code and design adaptations were made following each pilot case through an iterative refinement process. Results: Five patients with confirmed or suspected HGSOC who underwent debulking surgery between April and December 2021 were included in this prospective study. Tumour moulds were designed and 3D-printed for seven pelvic lesions, covering a range of tumour volumes (7 to 133 cm3) and compositions (cystic and solid proportions). The pilot cases informed innovations to improve specimen and subsequent slice orientation, through the use of 3D-printed tumour replicas and incorporation of a slice orientation slit in the mould design, respectively. The overall research pathway was compatible with implementation within the clinically determined timeframe and treatment pathway for each case, involving multidisciplinary clinical professionals from Radiology, Surgery, Oncology and Histopathology Departments. Conclusions: We developed and refined a computational pipeline that can model lesion-specific 3D-printed moulds from preoperative imaging for a variety of pelvic tumours. This framework can be used to guide comprehensive multi-sampling of tumour resection specimens.

Advanced ovarian cancer: multiparametric MR imaging demonstrates response- and metastasis-specific effects.

PURPOSE: To investigate the role of multiparametric magnetic resonance (MR) imaging in the evaluation of response to platinum-based neoadjuvant chemotherapy in advanced ovarian cancer and to compare imaging parameters between primary ovarian mass and metastatic disease. MATERIALS AND METHODS: Evaluable patients suspected of having advanced ovarian carcinoma were enrolled in a prospective protocol-driven study. Research ethics committee approval and written informed consent were obtained. Multiparametric MR imaging (diffusion-weighted MR imaging, dynamic contrast material-enhanced [DCE] MR imaging, and hydrogen 1 MR spectroscopy) was performed with a 3.0-T wholebody MR imaging system. Three marker lesions-primary ovarian mass, omental cake, and peritoneal deposit-were outlined by a radiologist on apparent diffusion coefficient (ADC) and vascular signal fraction (VSF) maps and on DCE MR images. Comparisons of mean ADC, mean VSF, DCE MR imaging parameters, and choline concentration between responders and nonresponders were based on Response Evaluation Criteria in Solid Tumors and CA-125 criteria. RESULTS: Twenty-two patients were evaluable. The mean ADC for peritoneal metastases was lower than that for ovarian (P = .015) and omental (P = .006) sites. There were no differences in pretreatment DCE MR imaging parameters between tumor sites. After treatment, responders showed a significantly larger increase in ADC (P = .021) and fractional volume of the extravascular extracellular space (v(e)) (P = .025) of ovarian lesions compared with nonresponders, but there was no change in ADC at other sites. Pre- and posttreatment values of choline concentration of ovarian lesions were lower in responders (P = .025) than in nonresponders (P = .010). CONCLUSION: The significant differences in baseline ADCs among primary ovarian cancer, omental cake, and peritoneal deposits indicate that diffusivity profiles may be tumor-site dependent, suggesting biologic heterogeneity of disease. ADC and v(e) parameters correlated with the cytotoxic effects of platinum-based therapy and may be useful response markers, while choline concentration predicted but did not reflect response.

Standalone portable xenon-129 hyperpolariser for multicentre clinical magnetic resonance imaging of the lungs.

OBJECTIVES: Design and build a portable xenon-129 (129Xe) hyperpolariser for clinically accessible 129Xe lung MRI. METHODS: The polariser system consists of six main functional components: (i) a laser diode array and optics; (ii) a B0 coil assembly; (iii) an oven containing an optical cell; (iv) NMR and optical spectrometers; (v) a gas-handling manifold; and (vi) a cryostat within a permanent magnet. All components run without external utilities such as compressed air or three-phase electricity, and require just three mains sockets for operation. The system can be manually transported in a lightweight van and rapidly installed on a small estates footprint in a hospital setting. RESULTS: The polariser routinely provides polarised 129Xe for routine clinical lung MRI. To test the concept of portability and rapid deployment, it was transported 200 km, installed at a hospital with no previous experience with the technology and 129Xe MR images of a diagnostic quality were acquired the day after system transport and installation. CONCLUSION: This portable 129Xe hyperpolariser system could form the basis of a cost-effective platform for wider clinical dissemination and multicentre evaluation of 129Xe lung MR imaging. ADVANCES IN KNOWLEDGE: Our work successfully demonstrates the feasibility of multicentre clinical 129Xe MRI with a portable hyperpolariser system.

Particle motion observed during offshore wind turbine piling operation.

Measurement of particle motion from an offshore piling event in the North was conducted to determine noise levels. For this purpose, a bespoken sensor was developed that was both autonomous and sensitive up to 2 kHz. The measurement was undertaken both for unmitigated and mitigated piling. Three different types of mitigation techniques were employed. The acceleration zero-to-peak values and the acceleration exposure levels were determined. The results show that inferred mitigation techniques reduce the levels significantly as well as decreases the power content of higher frequencies. These results suggest that mitigation has an effect and will reduce the effect ranges of impact on marine species.

Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.

Hyperpolarised magnetic resonance imaging (HP 13C-MRI) is an emerging clinical technique to detect [1-13C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-13C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-13C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, we show that HP 13C-MRI predominantly measures metabolism in the epithelial compartment of the tumour, rather than the stroma. MRI-derived tumour [1-13C]lactate labelling correlated with epithelial mRNA expression of the enzyme lactate dehydrogenase (LDHA and LDHB combined), and the ratio of lactate transporter expression between the epithelial and stromal compartments (epithelium-to-stroma MCT4). We observe similar changes in MCT4, LDHA, and LDHB between tumours with primary Gleason patterns 3 and 4 in an independent TCGA cohort. Therefore, HP 13C-MRI can metabolically phenotype clinically significant disease based on underlying metabolic differences in the epithelial and stromal tumour compartments.

Magnetization transfer imaging of ovarian cancer: initial experiences of correlation with tissue cellularity and changes following neoadjuvant chemotherapy.

Objectives: To investigate the relationship between magnetization transfer (MT) imaging and tissue macromolecules in high-grade serous ovarian cancer (HGSOC) and whether MT ratio (MTR) changes following neoadjuvant chemotherapy (NACT). Methods: This was a prospective observational study. 12 HGSOC patients were imaged before treatment. MTR was compared to quantified tissue histology and immunohistochemistry. For a subset of patients (n = 5), MT imaging was repeated after NACT. The Shapiro-Wilk test was used to assess for normality of data and Spearman's rank-order or Pearson's correlation tests were then used to compare MTR with tissue quantifications. The Wilcoxon signed-rank test was used to assess for changes in MTR after treatment. Results: Treatment-naïve tumour MTR was 21.9 ± 3.1% (mean ± S.D.). MTR had a positive correlation with cellularity, rho = 0.56 (p < 0.05) and a negative correlation with tumour volume, ρ = -0.72 (p = 0.01). MTR did not correlate with the extracellular proteins, collagen IV or laminin (p = 0.40 and p = 0.90). For those patients imaged before and after NACT, an increase in MTR was observed in each case with mean MTR 20.6 ± 3.1% (median 21.1) pre-treatment and 25.6 ± 3.4% (median 26.5) post-treatment (p = 0.06). Conclusion: In treatment-naïve HGSOC, MTR is associated with cellularity, possibly reflecting intracellular macromolecular concentration. MT may also detect the HGSOC response to NACT, however larger studies are required to validate this finding. Advances in knowledge: MTR in HGSOC is influenced by cellularity. This may be applied to assess for cell changes following treatment.