Metabolic imaging across scales reveals distinct prostate cancer phenotypes.

Hyperpolarised magnetic resonance imaging (HP-13C-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 [1-13C]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 [1-13C]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 [1-13C]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.

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.

Highly accelerated parameter mapping using model-based alternating reconstruction coupling fitting.

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 toT2mapping 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 accurateT2maps 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.

Quantitative 23Na magnetic resonance imaging in the abdomen at 3 T.

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 B1 non-uniformity on TSC measurements were corrected using the double-angle method. The long-component of 23Na T2* relaxation time was measured using a series of variable echo-times. RESULTS: The mean and standard deviation of TSC and long-component 23Na T2* 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 23Na-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 23Na T2* 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.

Fast and High-Resolution T2 Mapping Based on Echo Merging Plus k-t Undersampling with Reduced Refocusing Flip Angles (TEMPURA) as Methods for Human Renal MRI.

PURPOSE: To develop a highly accelerated multi-echo spin-echo method, TEMPURA, for reducing the acquisition time and/or increasing spatial resolution for kidney T2 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 mm2, resulting in improved visualization of the detailed anatomical structure. In vivo T2 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 T2 measurements. It has the potential to improve clinical throughput and delineate intratumoral heterogeneity and tissue habitats at unprecedented spatial resolution.

Cerebral microemboli during extracorporeal life support: a single-centre cohort study.

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.