Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-13C]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study.

Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (13C) MRI to monitor the exchange of the hyperpolarized 13C label between injected [1-13C]pyruvate and tumor lactate and bicarbonate. Materials and Methods In this prospective study, seven treatment-naive patients (age [mean ± SD], 60 years ± 11; five men) with GBM were imaged at 3 T by using a dual-tuned 13C-hydrogen 1 head coil. Hyperpolarized [1-13C]pyruvate was injected, and signal was acquired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP), and in healthy volunteers by using paired or unpaired t tests and a Wilcoxon signed rank test. The Spearman ρ correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. Results The bicarbonate-to-pyruvate (BP) ratio was lower in the tumor than in the contralateral NABP (P < .01). The tumor lactate-to-pyruvate (LP) ratio was not different from that in the NABP (P = .38). The LP and BP ratios in the NABP were higher than those observed previously in healthy volunteers (P < .05). Tumor lactate and bicarbonate signal intensities were strongly correlated with the pyruvate signal intensity (ρ = 0.92, P < .001, and ρ = 0.66, P < .001, respectively), and the LP ratio was weakly correlated with LDH-A expression in biopsy samples (ρ = 0.43, P = .04). Conclusion Hyperpolarized 13C MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors than in the surrounding NABP. Keywords: Hyperpolarized 13C MRI, Glioblastoma, Metabolism, Cancer, MRI, Neuro-oncology Supplemental material is available for this article. Published under a CC BY 4.0 license.

Evaluation of Dynamic Contrast-Enhanced MRI Measures of Lung Congestion and Endothelial Permeability in Heart Failure: A Prospective Method Validation Study.

BACKGROUND: Methods for accurate quantification of lung fluid in heart failure (HF) are needed. Dynamic contrast-enhanced (DCE)-MRI may be an appropriate modality. PURPOSE: DCE-MRI evaluation of fraction of fluid volume in the interstitial lung space (ve ) and vascular permeability (Ktrans ). STUDY TYPE: Prospective, single-center method validation. POPULATION: Seventeen evaluable healthy volunteers (HVs), 12 participants with HF, and 3 with acute decompensated HF (ADHF). FIELD STRENGTH/SEQUENCE: T1 mapping (spoiled gradient echo variable flip angle acquisition) followed by dynamic series (three-dimensional spoiled gradient-recalled echo acquisitions [constant echo time, repetition time, and flip angle at 1.5 T]). ASSESSMENT: Three whole-chest scans were acquired: baseline (Session 1), 1-week later (Session 2), following exercise (Session 3). Extended Tofts model quantified ve and Ktrans (voxel-wise basis); total lung median measures were extracted and fitted via repeat measure analysis of variance (ANOVA) model. Patient tolerability of the scanning protocol was assessed. STATISTICAL TESTS: This was constructed as an experimental medicine study. PRIMARY ENDPOINTS: Ktrans and ve at baseline (HV vs. HF), change in Ktrans and ve following exercise, and following lung congestion resolution (ADHF). Ktrans and ve were fitted separately using ANOVA. Secondary endpoint: repeatability, that is, within-participant variability in ve and Ktrans between sessions (coefficient of variation estimated via mixed effects model). RESULTS: There was no significant difference in mean Ktrans between HF and HV (P ≤ 0.17): 0.2216 minutes-1 and 0.2353 minutes-1 (Session 1), 0.2044 minutes-1 and 0.2567 minutes-1 (Session 2), 0.1841 minutes-1 and 0.2108 minutes-1 (Session 3), respectively. ve was greater in the HF group (all scans, P ≤ 0.02). Results were repeatable between Sessions 1 and 2; mean values for HF and HV were 0.4946 and 0.3346 (Session 1), 0.4353 and 0.3205 (Session 2), respectively. There was minimal difference in Ktrans or ve between scans for participants with ADHF (small population precluded significance testing). Scanning was well tolerated. DATA CONCLUSION: While no differences were detected in Ktrans , ve was greater in chronic HF patients vs. HV, augmented beyond plasma and intracellular volume. DCE-MRI is a valuable diagnostic and physiologic tool to evaluate changes in fluid volume in the interstitial lung space associated with symptomatic HF. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

T2-PROPELLER Compared to T2-FRFSE for Image Quality and Lesion Detection at Prostate MRI.

PURPOSE: The primary objective was to compare T2-FRFSE and T2-PROPELLER sequences for image quality. The secondary objective was to compare the ability to detect prostate lesions at MRI in the presence and absence of motion artefact using the 2 sequences. METHODS: 99 patients underwent 3 T MRI examination of the prostate, including T2-FRFSE and T2-PROPELLER sequences. All patients underwent prostate biopsy. Two independent readers rated overall image quality, presence of motion artefact, and blurring for both sequences using a 5-point Likert scale. Scores were compared for the whole group and for subgroups with and without significant motion artefact. Outcome for lesion detection at an MRI threshold of PI-RADS score ≥3 was compared between T2-FRFSE and T2-PROPELLER. RESULTS: The overall image quality was not significantly different between T2-FRFSE and T2-PROPELLER sequences (3.74 vs. 3.93, p = 0.275). T2-PROPELLER recorded a lesser degree of motion artefact (score 4.53 vs. 3.78, p <0.0001), but demonstrated greater image blurring (score 3.29 vs. 3.73, p <0.001). However, in a subgroup of patients with significant motion artefact on T2-FRFSE, the T2-PROPELLER sequence demonstrated significantly higher image quality (3.46 vs. 2.49, p <0.001). T2-FRFSE and T2-PROPELLER showed comparable positive predictive values for lesion detection at 93.2% and 97.7%, respectively. CONCLUSIONS: T2-PROPELLER provides higher quality imaging in the presence of motion artefact, but T2-FRFSE is preferred in the absence of motion. T2-PROPELLER is therefore recommended as a secondary T2 sequence when imaging requires repeat acquisition due to motion artefact.

Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients.

Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1-13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7-11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5-6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. SIGNIFICANCE: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7-11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.

Reproducibility of magnetic resonance fingerprinting-based T1 mapping of the healthy prostate at 1.5 and 3.0 T: A proof-of-concept study.

Facilitating clinical translation of quantitative imaging techniques has been suggested as means of improving interobserver agreement and diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) of the prostate. One such technique, magnetic resonance fingerprinting (MRF), has significant competitive advantages over conventional mapping techniques in terms of its multi-site reproducibility, short scanning time and inherent robustness to motion. It has also been shown to improve the detection of clinically significant prostate cancer when added to standard mpMRI sequences, however, the existing studies have all been conducted on 3.0 T MRI systems, limiting the technique's use on 1.5 T MRI scanners that are still more widely used for prostate imaging across the globe. The aim of this proof-of-concept study was, therefore, to evaluate the cross-system reproducibility of prostate MRF T1 in healthy volunteers (HVs) using 1.5 and 3.0 T MRI systems. The initial validation of MRF T1 against gold standard inversion recovery fast spin echo (IR-FSE) T1 in the ISMRM/NIST MRI system revealed a strong linear correlation between phantom-derived MRF and IR-FSE T1 values was observed at both field strengths (R2 = 0.998 at 1.5T and R2 = 0.993 at 3T; p = < 0.0001 for both). In young HVs, inter-scanner CVs demonstrated marginal differences across all tissues with the highest difference of 3% observed in fat (2% at 1.5T vs 5% at 3T). At both field strengths, MRF T1 could confidently differentiate prostate peripheral zone from transition zone, which highlights the high quantitative potential of the technique given the known difficulty of tissue differentiation in this age group. The high cross-system reproducibility of MRF T1 relaxometry of the healthy prostate observed in this preliminary study, therefore, supports the technique's prospective clinical validation as part of larger trials employing 1.5 T MRI systems, which are still widely used clinically for routine mpMRI of the prostate.

Hyperpolarized 13C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer.

Purpose: To compare hyperpolarized carbon 13 (13C) MRI with dynamic contrast material-enhanced (DCE) MRI in the detection of early treatment response in breast cancer. Materials and Methods: In this institutional review board-approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent 13C MRI after injection of hyperpolarized [1-carbon 13 {13C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The 13C-labeled lactate-to-pyruvate ratio derived from hyperpolarized 13C MRI and the pharmacokinetic parameters transfer constant (K trans) and washout parameter (k ep) derived from DCE MRI were compared before and after treatment. Results: Exchange of the 13C label between injected hyperpolarized [1-13C]-pyruvate and the endogenous lactate pool was observed, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the 13C-labeled lactate-to-pyruvate ratio resulted in correct identification of the patient as a responder to therapy, which was subsequently confirmed via a complete pathologic response. However, DCE MRI showed an increase in mean K trans (132%) and mean k ep (31%), which could be incorrectly interpreted as a poor response to treatment. Conclusion: Hyperpolarized 13C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI.Published under a CC BY 4.0 license.

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.

The effect of capped biparametric magnetic resonance imaging slots on weekly prostate cancer imaging workload.

OBJECTIVE: To introduce capped biparametric (bp) MRI slots for follow-up imaging of prostate cancer patients enrolled in active surveillance (AS) and evaluate the effect on weekly variation in the number of AS cases and total MRI workload. METHODS: Three 20 min bpMRI AS slots on two separate days were introduced at Addenbrooke's Hospital, Cambridge. The weekly numbers of total prostate MRIs and AS cases recorded 15 months before and after the change (Groups 1 and 2, respectively). An intergroup variation in the weekly scan numbers was assessed using the coefficient of variance (CV) and mean absolute deviation; the Mann-Whitney U test was used for an intergroup comparison of the latter. RESULTS: In AS patients, a shift from considerable to moderate variation in weekly scan numbers was observed between the two groups (CV, 51.7 and 26.8%, respectively); mean absolute deviation of AS scans also demonstrated a significant decrease in Group 2 (1.28 vs 2.58 in Group 1; p < 0.001). No significant changes in the variation in total prostate MRIs were observed, despite a 10% increased workload in Group 2. CONCLUSION: A significant reduction in weekly variation of AS cases was demonstrated following the introduction of capped bpMRI slots, which can be used for more accurate long-term planning of MRI workload. ADVANCES IN KNOWLEDGE: The paper illustrates the potential of introducing capped AS MRI slots using a bp protocol to reduce weekly variation in demand and allow for optimising workflow, which will be increasingly important as the demands on radiology departments increase worldwide.

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.

Role of PROPELLER-DWI of the prostate in reducing distortion and artefact from total hip replacement metalwork.

OBJECTIVE: To compare image quality, artefact, and distortion in standard echo-planar imaging (EPI) with periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) for prostate magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) in patients with previous total hip replacement (THR). METHODS: 21 male subjects with a clinical suspicion for, or known prostate cancer and previous THR were scanned at 1.5 T using a phased-array body coil. DWI was obtained using single-shot EPI and PROPELLER techniques using fat saturation (PROPELLER-DWI-FS), and without (PROPELLER-DWI-NFS). Image quality (the overall impression of diagnostic quality) was compared to T2-weighted (T2WI) imaging using a 5-point Likert scale, with diffusion sequences additionally scored for artefact and distortion according to a 4-point scale, with artefact defined as the amount of prostate affected and distortion as the degree of warping of the organ. The T2W and DW image volumes were compared to produce quantitative distortion maps. A two-sample Wilcoxon test compared the qualitative scores, with inter-reader variability calculated using Cohen's kappa. RESULTS: 21 patients were included in the study, with an average age of 70.4 years and PSA 9.2 ng/ml. Hip metalwork was present bilaterally in 3 patients, left-sided in 9, and right-sided in 9. PROPELLER-DWI-FS significantly improved image quality (p < 0.01) and reduced distortion (p < 0.01) when compared to standard EP-DWI. Artefact was not shown to be significantly improved. The last 5 patients in the study were additionally imaged with PROPELLER-DWI-NFS, which resulted in a significant reduction in artefact compared to EP-DWI (p < 0.05). Quantitative distortion was significantly lower compared to EP-DWI for both PROPELLER with fat saturation (p < 0.01) and without fat saturation (p < 0.01). CONCLUSION: PROPELLER-DWI demonstrates better image quality and decreases both artefact and distortion compared to conventional echo planar sequences in patients with hip metalwork.

Imaging intralesional heterogeneity of sodium concentration in multiple sclerosis: Initial evidence from 23Na-MRI.

Sodium MRI (23Na-MRI) has been used to non-invasively quantify tissue sodium but has been limited by low spatial resolution. Here we demonstrate for the first time that high resolution 23Na-MRI reveals the spatial heterogeneity of sodium concentration within a multiple sclerosis (MS) lesion. A patient with treatment-naïve relapsing-remitting MS and a ring-enhancing lesion was imaged using 23Na-MRI. The periphery of the lesion demonstrated an elevated total sodium content compared to the normal appearing white and grey matter (p<0.01), as well as a heterogeneous distribution of both the total tissue sodium concentration and the intracellular-weighted sodium concentration.

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.

Evaluating the effect of rectal distension on prostate multiparametric MRI image quality.

PURPOSE: To evaluate the effect of rectal distension on the quality of anatomical and functional prostate multiparametric (mp) MRI. MATERIALS AND METHODS: Multiparametric (mp) 3T-MRI images of 173 patients were independently evaluated by two radiologists in this retrospective study. Planimetry rectal volumes were derived and a subjective assessment of rectal distension was made using a 5-point Likert scale (1=no stool/gas, 5=large amount of stool/gas). Image quality of diffusion-weighted imaging (DWI) was evaluated using a 5-point Likert scale. DWI was further scored for distortion and artefact. T2W images were evaluated for image sharpness and the presence of motion artefact. The stability of the dynamic contrast-enhancement acquisition was assessed by recording the number of corrupt data points during the wash-out phase. RESULTS: There was a strong correlation between subjective scoring of rectal loading and objectively measured rectal volume (r=0.82), p<0.001. A significant correlation was shown between increased rectal distension and both reduced DW image quality (r=-0.628, p<0.001), and increased DW image distortion (r=0.814, p<0.001). There was also a significant trend for rectal distension to increase artefact at DWI (r=0.154, p=0.042). Increased rectal distension led to increased motion artefact on T2 (p=0.0096), but did not have a significant effect on T2-sharpness (p=0.0638). There was no relationship between rectal distension and DCE image quality (p=0.693). 63 patients underwent lesion-targeted biopsy post MRI, there was a trend to higher positive predictive values in patients with minor rectal distension (34/38, 89.5%) compared to those with moderate/marked distension (18/25, 72%), p=0.09. CONCLUSION: Rectal distension has a significant negative effect on the quality of both T2W and DW images. Consideration should therefore be given to bowel preparation prior to prostate mpMRI to optimise image quality.