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Hyperpolarized carbon-13 ( 13 C) magnetic resonance imaging (MRI) has shown promise for non-invasive assessment of the cerebral metabolism of [1- 13 C]pyruvate in both healthy volunteers and patients. The exchange of pyruvate to lactate catalysed by lactate dehydrogenase (LDH) and that of pyruvate flux to bicarbonate through pyruvate dehydrogenase (PDH) are the most widely studied reactions in vivo. Here we show the potential of the technique to probe additional enzymatic activity within the brain. Approximately 50 s after intravenous injection of hyperpolarized pyruvate, high-flip-angle pulses were used to detect cerebral 13 C-labelled carbon dioxide ( 13 CO 2 ), in addition to the 13 C-bicarbonate (H 13 CO 3 - ) subsequently formed by carbonic anhydrase (CA). Brain pH measurements, which were weighted towards the extracellular compartment, were calculated from the ratio of H 13 CO 3 - to 13 CO 2 in seven volunteers using the Henderson-Hasselbalch equation, demonstrating an average pH ± SD of 7.40 ± 0.02, with inter-observer reproducibility of 0.04. In addition, hyperpolarized [1- 13 C]aspartate was also detected, demonstrating irreversible pyruvate carboxylation to oxaloacetate by pyruvate carboxylase (PC) and subsequent transamination by aspartate aminotransferase (AST), with the average flux being on average 11% ± 3% of that through PDH. A hyperpolarized [1- 13 C]alanine signal was also detected, but this was localized to extracranial muscle tissue in keeping with skeletal alanine aminotransferase (ALT) activity. The results demonstrate the potential of hyperpolarized 13 C-MRI to assess cerebral and extracerebral [1- 13 C]pyruvate metabolism in addition to LDH and PDH activity. Non-invasive measurements of brain pH could be particularly important in assessing cerebral pathology given the wide range of disease processes that alter acid-base balance., (© 2024 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.)

Introduction: Localised renal masses are an increasing burden on healthcare due to the rising number of cases. However, conventional imaging cannot reliably distinguish between benign and malignant renal masses, and renal mass biopsies are unable to characterise the entirety of the tumour due to sampling error, which may lead to delayed treatment or overtreatment. There is an unmet clinical need to develop novel imaging techniques to characterise renal masses more accurately. Renal tumours demonstrate characteristic metabolic reprogramming, and novel MRI methods have the potential to detect these metabolic perturbations, which may therefore aid accurate characterisation. Here, we present our study protocol for the investigation of the differential biology of benign and malignant renal masses using advanced MRI techniques (IBM-Renal)., Methods and Analysis: IBM-Renal is a multiarm, single-centre, non-randomised, feasibility study with the aim to provide preliminary evidence for the potential role of the novel MRI techniques to phenotype localised renal lesions. 30 patients with localised renal masses will be recruited to three imaging arms, with 10 patients in each: (1) hyperpolarised [1- 13 C]-pyruvate MRI, (2) deuterium metabolic imaging (DMI) and (3) sodium MRI. The diagnosis will be made on samples acquired at biopsy or at surgery. The primary objective is the technical development of the novel MRI techniques, with the ultimate aim to understand whether these can identify differences between benign and malignant tumours, while the secondary objectives aim to assess how complementary the techniques are, and if they provide additional information. The exploratory objective is to link imaging findings with clinical data and molecular analyses for the biological validation of the novel MRI techniques., Ethics and Dissemination: This study was ethically approved (UK REC HRA: 22/EE/0136; current protocol version 2.1 dated 11 August 2022). The plans for dissemination include presentations at conferences, publications in scientific journals, a doctoral thesis and patient and public involvement., Trial Registration Number: NCT06016075., Competing Interests: Competing interests: GDS has received educational grants from Pfizer, AstraZeneca and Intuitive Surgical; consultancy fees from Pfizer, MSD, EUSA Pharma and CMR Surgical; Travel expenses from MSD and Pfizer; Speaker fees from Pfizer; Clinical lead (urology) National Kidney Cancer Audit and Topic Advisor for the NICE kidney cancer guideline. SJW is a founder and director of Pinto Medical Consultancy. FAG has research grants from GlaxoSmithKline and AstraZeneca, research support from GE Healthcare and has consulted for AstraZeneca on behalf of the University of Cambridge. All other authors have no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Purpose: To develop a highly accelerated multi-echo spin-echo method, TEMPURA, for reducing the acquisition time and/or increasing spatial resolution for kidney T 2 mapping., Methods: TEMPURA merges several adjacent echoes into one k-space by either combining independent echoes or sharing one echo between k-spaces. The combined k-space is reconstructed based on compressed sensing theory. Reduced flip angles are used for the refocusing pulses, and the extended phase graph algorithm is used to correct the effects of indirect echoes. Two sequences were developed: a fast breath-hold sequence; and a high-resolution sequence. The performance was evaluated prospectively on a phantom, 16 healthy subjects, and two patients with different types of renal tumors., Results: The fast TEMPURA method reduced the acquisition time from 3-5 min to one breath-hold (18 s). Phantom measurements showed that fast TEMPURA had a mean absolute percentage error (MAPE) of 8.2%, which was comparable to a standardized respiratory-triggered sequence (7.4%), but much lower than a sequence accelerated by purely k-t undersampling (21.8%). High-resolution TEMPURA reduced the in-plane voxel size from 3 × 3 to 1 × 1 mm 2 , resulting in improved visualization of the detailed anatomical structure. In vivo T 2 measurements demonstrated good agreement (fast: MAPE = 1.3%-2.5%; high-resolution: MAPE = 2.8%-3.3%) and high correlation coefficients (fast: R = 0.85-0.98; high-resolution: 0.82-0.96) with the standardized method, outperforming k-t undersampling alone (MAPE = 3.3-4.5%, R = 0.57-0.59)., Conclusion: TEMPURA provides fast and high-resolution renal T 2 measurements. It has the potential to improve clinical throughput and delineate intratumoral heterogeneity and tissue habitats at unprecedented spatial resolution., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objectives: To assess the feasibility of sodium-23 MRI for performing quantitative and non-invasive measurements of total sodium concentration (TSC) and relaxation in a variety of abdominal organs., Materials and Methods: Proton and sodium imaging of the abdomen was performed in 19 healthy volunteers using a 3D cones sequence and a sodium-tuned 4-rung transmit/receive body coil on a clinical 3 T system. The effects of B 1 non-uniformity on TSC measurements were corrected using the double-angle method. The long-component of 23 Na T 2 * relaxation time was measured using a series of variable echo-times., Results: The mean and standard deviation of TSC and long-component 23 Na T 2 * values were calculated across the healthy volunteer group in the kidneys, cerebrospinal fluid (CSF), liver, gallbladder, spleen, aorta, and inferior vena cava., Discussion: Mean TSC values in the kidneys, liver, and spleen were similar to those reported using 23 Na-MRI previously in the literature. Measurements in the CSF and gallbladder were lower, potentially due to the reduced spatial resolution achievable in a clinically acceptable scan time. Mean long-component 23 Na T 2 * values were consistent with previous reports from the kidneys and CSF. Intra-population standard error was larger in smaller, fluid-filled structures due to fluid motion and partial volume effects., (© 2024. The Author(s).)

Hyperpolarised magnetic resonance imaging (HP- 13 C-MRI) has shown promise as a clinical tool for detecting and characterising prostate cancer. Here we use a range of spatially resolved histological techniques to identify the biological mechanisms underpinning differential [1- 13 C]lactate labelling between benign and malignant prostate, as well as in tumours containing cribriform and non-cribriform Gleason pattern 4 disease. Here we show that elevated hyperpolarised [1- 13 C]lactate signal in prostate cancer compared to the benign prostate is primarily driven by increased tumour epithelial cell density and vascularity, rather than differences in epithelial lactate concentration between tumour and normal. We also demonstrate that some tumours of the cribriform subtype may lack [1- 13 C]lactate labelling, which is explained by lower epithelial lactate dehydrogenase expression, higher mitochondrial pyruvate carrier density, and increased lipid abundance compared to lactate-rich non-cribriform lesions. These findings highlight the potential of combining spatial metabolic imaging tools across scales to identify clinically significant metabolic phenotypes in prostate cancer., (© 2024. The Author(s).)

Objective. A model-based alternating reconstruction coupling fitting, termed Model-based Alternating Reconstruction COupling fitting (MARCO), is proposed for accurate and fast magnetic resonance parameter mapping. Approach. MARCO utilizes the signal model as a regularization by minimizing the bias between the image series and the signal produced by the suitable signal model based on iteratively updated parameter maps when reconstructing. The technique can incorporate prior knowledge of both image series and parameters by adding sparsity constraints. The optimization problem is decomposed into three subproblems and solved through three alternating steps involving reconstruction and nonlinear least-square fitting, which can produce both contrast-weighted images and parameter maps simultaneously. Main results. The algorithm is applied to T 2 mapping with extended phase graph algorithm integrated and validated on undersampled multi-echo spin-echo data from both phantom and in vivo sources. Compared with traditional compressed sensing and model-based methods, the proposed approach yields more accurate T 2 maps with more details at high acceleration factors. Significance. The proposed method provides a basic framework for quantitative MR relaxometry, theoretically applicable to all quantitative MR relaxometry. It has the potential to improve the diagnostic utility of quantitative imaging techniques., (© 2024 Institute of Physics and Engineering in Medicine.)

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 T 2 mapping methods have improved resolution, shorter acquisition times, and promising quantifiable readouts to characterise incidental renal masses., (© 2024. The Author(s).)

Objectives: The aim of this study was to investigate the load and composition of cerebral microemboli in adult patients undergoing venoarterial extracorporeal life support (ECLS)., Methods: Adult ECLS patients were investigated for the presence of cerebral microemboli and compared to critically ill, pressure-controlled ventilated controls and healthy volunteers. Cerebral microemboli were detected in both middle cerebral arteries for 30 min using transcranial Doppler ultrasound. Neurological outcome (ischaemic stroke, global brain ischaemia, intracerebral haemorrhage, seizure, metabolic encephalopathy, sensorimotor sequelae and neuropsychiatric disorders) was additionally evaluated., Results: Twenty ECLS patients (cannulations: 15 femoro-femoral, 4 femoro-subclavian, 1 femoro-aortic), 20 critically ill controls and 20 healthy volunteers were analysed. ECLS patients had statistically significantly more cerebral microemboli than critically ill controls {123 (43-547) [median (interquartile range)] vs 35 (16-74), difference: 88 [95% confidence interval (CI) 19-320], P = 0.023} and healthy volunteers [11 (5-12), difference: 112 (95% CI 45-351), P < 0.0001]. In ECLS patients, 96.5% (7346/7613) of cerebral microemboli were of gaseous composition, while solid cerebral microemboli [1 (0-5)] were detected in 12 out of 20 patients. ECLS patients had more neurological complications than critically ill controls (12/20 vs 3/20, P = 0.003). In ECLS patients, a high microembolic rate (>100/30 min) tended to be associated with neurological complications including ischaemic stroke, neuropsychiatric disorders, sensorimotor sequelae and non-convulsive status epilepticus (odds ratio 4.5, 95% CI 0.46-66.62; P = 0.559)., Conclusions: Our results indicate that adult ECLS patients are continuously exposed to many gaseous and, frequently, to few solid cerebral microemboli. Prolonged cerebral microemboli formation may contribute to neurological morbidity related to ECLS treatment., Clinical Trial Registration: ClinicalTrials.gov, NCT02020759, https://clinicaltrials.gov/ct2/show/NCT02020759?term=erdoes&rank=1., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)