Sex, Genotype, and Liver Volume Progression as Risk of Hospitalization Determinants in Autosomal Dominant Polycystic Liver Disease.

BACKGROUND & AIMS: Autosomal dominant polycystic liver disease is a rare condition with a female preponderance, based mainly on pathogenic variants in 2 genes, PRKCSH and SEC63. Clinically, autosomal dominant polycystic liver disease is characterized by vast heterogeneity, ranging from asymptomatic to highly symptomatic hepatomegaly. To date, little is known about the prediction of disease progression at early stages, hindering clinical management, genetic counseling, and the design of randomized controlled trials. To improve disease prognostication, we built a consortium of European and US centers to recruit the largest cohort of patients with PRKCSH and SEC63 liver disease. METHODS: We analyzed an international multicenter cohort of 265 patients with autosomal dominant polycystic liver disease harboring pathogenic variants in PRKCSH or SEC63 for genotype-phenotype correlations, including normalized age-adjusted total liver volumes and polycystic liver disease-related hospitalization (liver event) as primary clinical end points. RESULTS: Classifying individual total liver volumes into predefined progression groups yielded predictive risk discrimination for future liver events independent of sex and underlying genetic defects. In addition, disease severity, defined by age at first liver event, was considerably more pronounced in female patients and patients with PRKCSH variants than in those with SEC63 variants. A newly developed sex-gene score was effective in distinguishing mild, moderate, and severe disease, in addition to imaging-based prognostication. CONCLUSIONS: Both imaging and clinical genetic scoring have the potential to inform patients about the risk of developing symptomatic disease throughout their lives. The combination of female sex, germline PRKCSH alteration, and rapid total liver volume progression is associated with the greatest odds of polycystic liver disease-related hospitalization.

Magnetic Resonance Liver Iron Concentration Can Guide Venesection Decision-Making in Hyperferritinemia.

BACKGROUND: The clinical benefit of venesection in suspected iron overload can be unclear and serum ferritin may overestimate the degree of iron overload. AIMS: To help inform practice, we examined magnetic resonance liver iron concentration (MRLIC) in a cohort investigated for haemochromatosis. METHODS: One hundred and six subjects with suspected haemochromatosis underwent HFE genotyping and MRLIC with time-matched serum ferritin and transferrin saturation values. For those treated with venesection, volume of blood removed was calculated as a measure of iron overload. RESULTS: Forty-seven C282Y homozygotes had median ferritin 937 µg/l and MRLIC 4.83 mg/g; MRLIC was significantly higher vs non-homozygotes for any given ferritin concentration. No significant difference in MRLIC was observed between homozygotes with and without additional risk factors for hyperferritinemia. Thirty-three compound heterozygotes (C282Y/H63D) had median ferritin 767 µg/l and MRLIC 2.58 mg/g; ferritin < 750 µg/l showed 100% specificity for lack of significant iron overload (< 3.2 mg/g). 79% of C282Y/H63D had additional risk factors-mean MRLIC was significantly lower in this sub-group (2.4 mg/g vs 3.23 mg/g). 26 C282Y heterozygous or wild-type had median ferritin 1226 µg/l and MRLIC 2.13 mg/g; 69% with additional risk factors had significantly higher ferritin concentrations (with comparable MRLIC) and ferritin < 1000 µg/l showed 100% specificity for lack of significant iron overload. In 31 patients (26 homozygotes, 5 C282Y/H63D) venesected to ferritin < 100 µg/l, MRLIC and total venesection volume correlated strongly (r = 0.749), unlike MRLIC and serum ferritin. CONCLUSION: MRLIC is an accurate marker of iron overload in haemochromatosis. We propose serum ferritin thresholds in non-homozygotes which, if validated, could tailor cost-effective use of MRLIC in venesection decision-making.

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.

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.

Removing rician bias in diffusional kurtosis of the prostate using real-data reconstruction.

PURPOSE: To compare prostate diffusional kurtosis imaging (DKI) metrics generated using phase-corrected real data with those generated using magnitude data with and without noise compensation (NC). METHODS: Diffusion-weighted images were acquired at 3T in 16 prostate cancer patients, measuring 6 b-values (0-1500 s/mm2 ), each acquired with 6 signal averages along 3 diffusion directions, with noise-only images acquired to allow NC. In addition to conventional magnitude averaging, phase-corrected real data were averaged in an attempt to reduce rician noise-bias, with a range of phase-correction low-pass filter (LPF) sizes (8-128 pixels) tested. Each method was also tested using simulations. Pixelwise maps of apparent diffusion (D) and apparent kurtosis (K) were calculated for magnitude data with and without NC and phase-corrected real data. Average values were compared in tumor, normal transition zone (NTZ), and normal peripheral zone (NPZ). RESULTS: Simulations indicated LPF size can strongly affect K metrics, where 64-pixel LPFs produced accurate metrics. Relative to metrics estimated from magnitude data without NC, median NC K were lower (P < 0.0001) by 6/11/8% in tumor/NPZ/NTZ, 64-LPF real-data K were lower (P < 0.0001) by 4/10/7%, respectively. CONCLUSION: Compared with magnitude data with NC, phase-corrected real data can produce similar K, although the choice of phase-correction LPF should be chosen carefully.

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.

Subtractive non-contrast-enhanced MRI of lower limb veins using multiple flow-dependent preparation strategies.

PURPOSE: To evaluate the performance of acceleration-dependent vascular anatomy for non-contrast-enhanced MR venography (ADVANCE-MRV) in femoral veins and to investigate whether venous signal uniformity can be improved by applying multiple acquisitions with different flow suppressions or multiple flow suppressions in 1 acquisition. METHODS: The ADVANCE-MRV method uses flow-sensitized modules to acquire a dark-artery image set and a dark-artery vein set, which are subsequently subtracted. Ten healthy volunteers were imaged using the ADVANCE-MRV sequence with improved venous suppression uniformity in the dark-artery vein images achieved by applying multiple flow suppressions in the same acquisition or by combining multiple images acquired with different flow suppressions. The performance of the improved technique was also evaluated in 13 patients with lower-limb deep venous thrombosis. RESULTS: Multiple-preparation and multiple-acquisition approaches all improved venous signal uniformity and reduced the signal void artifacts observed in the original ADVANCE-MRV images. The multiple-acquisition approaches achieved excellent blood signal uniformity and intensity, albeit at the cost of an increase in the total acquisition time. The double-preparation approach demonstrated good performance in all measurements, providing a good compromise between signal uniformity and acquisition time. The blood signal spatial variation and its variation using different gradient amplitudes were reduced by 20% and 29%. All patient images showed uniform and bright venous signal in nonoccluded sections of vein. CONCLUSION: The enhanced ADVANCE-MRV methods substantially improved signal uniformity in healthy volunteers and patients with known deep venous thrombosis. The double-preparation approach gave good-quality femoral vein images, providing improved venous signal uniformity without increasing acquisition time in comparison to the original sequence.

Diagnostic evaluation of magnetization transfer and diffusion kurtosis imaging for prostate cancer detection in a re-biopsy population.

OBJECTIVE: To evaluate diffusion kurtosis imaging (DKI) and magnetisation transfer imaging (MTI) compared to standard MRI for prostate cancer assessment in a re-biopsy population. METHODS: Thirty-patients were imaged at 3 T including DKI (Kapp and Dapp) with b-values 150/450/800/1150/1500 s/mm2 and MTI performed with and without MT saturation. Patients underwent transperineal biopsy based on prospectively defined MRI targets. Receiver-operating characteristic (ROC) analyses assessed the parameters and Wilcoxon-signed ranked test assessed relationships between metrics. RESULTS: Twenty patients had ≥ 1 core positive for cancer in a total of 26 MRI targets (Gleason 3+3 in 8, 3+4 in 12, ≥ 4+3 in 6): 13 peripheral (PZ) and 13 transition zone (TZ). The apparent diffusion coefficient (ADC) and Dapp were significantly lower and the Kapp and MT ratio (MTR) significantly higher in tumour versus benign tissue (all p ≤ 0.005); ROC values 0.767-1.000. Normal TZ had: lower ADC and Dapp and higher Kapp and MTR compared to normal PZ. MTR showed a moderate correlation to Kapp (r = 0.570) and Dapp (r = -0.537) in normal tissue but a poor correlation in tumours. No parameter separated low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease for either PZ (p = 0.414-0.825) or TZ (p = 0.148-0.825). CONCLUSION: ADC, Dapp, Kapp and MTR all distinguished benign tissue from tumour, but none reliably differentiated low- from high-grade disease. KEY POINTS: • MTR was significantly higher in PZ and TZ tumours versus normal tissue • K app was significantly lower and D app higher for PZ and TZ tumours • There was no incremental value for DKI/MTI over mono-exponential ADC parameters • No parameter could consistently differentiate low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease • Divergent MTR/DKI values in TZ tumours suggests they offer different functional information.

Gadofosveset-enhanced thoracic MR venography: a comparative study evaluating steady state imaging versus conventional first-pass time-resolved dynamic imaging.

Background Dedicated blood-pool contrast agents combined with optimal angiographic protocols could improve the diagnostic accuracy of thoracic magnetic resonance angiography (MRA). Purpose To assess the clinical utility of Gadofesveset-enhanced imaging and compare an optimized steady-state (SS) sequence against conventional first-pass dynamic multi-phase (DMP) imaging. Material and Methods Twenty-nine patients (17 men, 12 women; mean age = 42.7, age range = 18-72 years) referred for MR thoracic venography were recruited. Imaging was performed on a 1.5T MRI system. A blood-pool contrast agent (Gadofesveset) was administered intravenously. Thirty temporal phases were acquired using DMP. This was immediately followed by a high-resolution SS sequence. Three radiologists in consensus reviewed seven thoracic vascular segments after randomizing the acquisition order. Image quality, stenoses, thromboses, and artifacts were graded using a categorical scoring system. The image quality for both approaches was compared using Wilcoxon's signed-rank test. McNemar's test was used to compare the proportions of stenosis grades, thrombus and artifacts. Results SS had significantly better image quality than DMP (3.14 ± 0.73 and 2.92 ± 0.60, respectively; P < 0.001). SS identified fewer stenoses (>50%) than DMP; the differences in stenosis categorizations was statistically significant ( P = 0.013). There was no significant difference in the proportions of vessels with thromboses ( P = 0.617). DMP produced more artifacts than SS (101 versus 85); however, the difference was not statistically significant ( P = 0.073). Conclusion Gadofesveset-enhanced thoracic angiography is clinically feasible. SS imaging produces better image quality and fewer artifacts than conventional DMP imaging.

Quantitative BOLD imaging at 3T: Temporal changes in hepatocellular carcinoma and fibrosis following oxygen challenge.

PURPOSE: To evaluate the utility of oxygen challenge and report on temporal changes in blood oxygenation level-dependent (BOLD) contrast in normal liver, hepatocellular carcinoma (HCC) and background fibrosis. MATERIALS AND METHODS: Eleven volunteers (nine male and two female, mean age 33.5, range 27-41 years) and 10 patients (nine male and one female, mean age 68.9, range 56-87 years) with hepatocellular carcinoma on a background of diffuse liver disease were recruited. Imaging was performed on a 3T system using a multiphase, multiecho, fast gradient echo sequence. Oxygen was administered via a Hudson mask after 2 minutes of free-breathing. Paired t-tests were performed to determine if the mean pre- and post-O2 differences were statistically significant. RESULTS: In patients with liver fibrosis (n = 8) the change in T2* following O2 administration was elevated (0.88 ± 0.582 msec, range 0.03-1.69 msec) and the difference was significant (P = 0.004). The magnitude of the BOLD response in patients with HCC (n = 10) was larger, however the response was more variable (1.07 ± 1.458 msec, range -0.93-3.26 msec), and the difference was borderline significant (P = 0.046). The BOLD response in the volunteer cohort was not significant (P = 0.121, 0.59 ± 1.162 msec, range -0.81-2.44 msec). CONCLUSION: This work demonstrates that the BOLD response following oxygen challenge within cirrhotic liver is consistent with a breakdown in vascular autoregulatory mechanisms. Similarly, the elevated BOLD response within HCC is consistent with the abnormal capillary vasculature within tumors and the arterialization of the blood supply. Our results suggest that oxygen challenge may prove a viable BOLD contrast mechanism in the liver. J. Magn. Reson. Imaging 2016;44:739-744.

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.

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.

Multiparametric MRI of early tumor response to immune checkpoint blockade in metastatic melanoma.

BACKGROUND: Immune checkpoint inhibitors are now standard of care treatment for many cancers. Treatment failure in metastatic melanoma is often due to tumor heterogeneity, which is not easily captured by conventional CT or tumor biopsy. The aim of this prospective study was to investigate early microstructural and functional changes within melanoma metastases following immune checkpoint blockade using multiparametric MRI. METHODS: Fifteen treatment-naïve metastatic melanoma patients (total 27 measurable target lesions) were imaged at baseline and following 3 and 12 weeks of treatment on immune checkpoint inhibitors using: T2-weighted imaging, diffusion kurtosis imaging, and dynamic contrast-enhanced MRI. Treatment timepoint changes in tumor cellularity, vascularity, and heterogeneity within individual metastases were evaluated and correlated to the clinical outcome in each patient based on Response Evaluation Criteria in Solid Tumors V.1.1 at 1 year. RESULTS: Differential tumor growth kinetics in response to immune checkpoint blockade were measured in individual metastases within the same patient, demonstrating significant intertumoral heterogeneity in some patients. Early detection of tumor cell death or cell loss measured by a significant increase in the apparent diffusivity (Dapp) (p<0.05) was observed in both responding and pseudoprogressive lesions after 3 weeks of treatment. Tumor heterogeneity, as measured by apparent diffusional kurtosis (Kapp), was consistently higher in the pseudoprogressive and true progressive lesions, compared with the responding lesions throughout the first 12 weeks of treatment. These preceded tumor regression and significant tumor vascularity changes (Ktrans, ve, and vp) detected after 12 weeks of immunotherapy (p<0.05). CONCLUSIONS: Multiparametric MRI demonstrated potential for early detection of successful response to immune checkpoint inhibitors in metastatic melanoma.

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.

Ferumoxytol-enhanced three-dimensional magnetic resonance imaging of carotid atheroma- a feasibility and temporal dependence study.

Ferumoxytol is an ultrasmall super paramagnetic particles of iron oxide (USPIO) agent recently used for magnetic resonance (MR) vascular imaging. Other USPIOs have been previously used for assessing inflammation within atheroma. We aim to assess feasibility of ferumoxytol in imaging carotid atheroma (with histological assessment); and the optimum MR imaging time to detect maximum quantitative signal change post-ferumoxytol infusion. Ten patients with carotid artery disease underwent high-resolution MR imaging of their carotid arteries on a 1.5 T MR system. MR imaging was performed before and at 24, 48, 72 and 96 hrs post ferumoxytol infusion. Optimal ferumoxytol uptake time was evaluated by quantitative relaxometry maps indicating the difference in T2* (ΔT2*) and T2 (ΔT2) between baseline and post-Ferumoxytol MR imaging using 3D DANTE MEFGRE qT2*w and iMSDE black-blood qT2w sequences respectively. 20 patients in total (10 symptomatic and 10 with asymptomatic carotid artery disease) had ferumoxytol-enhanced MR imaging at the optimal imaging window. 69 carotid MR imaging studies were completed. Ferumoxytol uptake (determined by a decrease in ΔT2* and ΔT2) was identified in all carotid plaques (symptomatic and asymptomatic). Maximum quantitative decrease in ΔT2* (10.4 [3.5-16.2] ms, p < 0.001) and ΔT2 (13.4 [6.2-18.9] ms; p = 0.001) was found on carotid MR imaging at 48 hrs following the ferumoxytol infusion. Ferumoxytol uptake by carotid plaques was assessed by histopathological analysis of excised atheroma. Ferumoxytol-enhanced MR imaging using quantitative 3D MR pulse sequences allows assessment of inflammation within carotid atheroma in symptomatic and asymptomatic patients. The optimum MR imaging time for carotid atheroma is 48 hrs after its administration.

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.

Assessment of a Novel 3T MRI Compatible Cochlear Implant Magnet: Torque, Forces, Demagnetization, and Imaging.

HYPOTHESIS: A novel cochlea implant (CI) device magnet providing alignment to the static field of a magnetic resonance imaging (MRI) will lead to reduced torque, longitudinal forces, and demagnetization effects. The image void and distortion will be comparable to those obtained with standard CI magnets. BACKGROUND: MRI investigations of CI users pose several challenges such as magnet dislocation, demagnetization, and may cause pain. The presence of a CI magnet within MRI field causes image distortions and may diminish the diagnostic value of an MRI procedure. Objective of this work is to evaluate magnetic forces and imaging properties of the novel CI magnet within 1.5 and 3T MRI. METHODS: Forces and torque of the novel CI magnet were measured in both 1.5 and 3T MRI and compared with the standard magnet in 1.5T. One cadaver head was implanted with the CI devices containing the novel and standard magnets in different configurations reflecting clinical scenarios and imaging properties were assessed and compared. RESULTS: In particular the torque has been reduced with the novel CI magnet in comparison to the standard one. Both CI magnets have not shown any signs of demagnetization. The image void and distortion was comparable between the two magnets for the main MRI clinical scanning protocols in 1.5T MRI. CONCLUSIONS: The novel CI magnet is safe to use for MRI investigations of CI users in 3T MRI without a need for bandaging and has acceptable level of image artefacts.

Diffusion kurtosis MRI as a predictive biomarker of response to neoadjuvant chemotherapy in high grade serous ovarian cancer.

This study assessed the feasibility of using diffusion kurtosis imaging (DKI) as a measure of tissue heterogeneity and proliferation to predict the response of high grade serous ovarian cancer (HGSOC) to neoadjuvant chemotherapy (NACT). Seventeen patients with HGSOC were imaged at 3 T and had biopsy samples taken prior to any treatment. The patients were divided into two groups: responders and non-responders based on Response Evaluation Criteria In Solid Tumours (RECIST) criteria. The following imaging metrics were calculated: apparent diffusion coefficient (ADC), apparent diffusion (Dapp) and apparent kurtosis (Kapp). Tumour cellularity and proliferation were quantified using histology and Ki-67 immunohistochemistry. Mean Kapp before therapy was higher in responders compared to non-responders: 0.69 ± 0.13 versus 0.51 ± 0.11 respectively, P = 0.02. Tumour cellularity correlated positively with Kapp (rho = 0.50, P = 0.04) and negatively with both ADC (rho = -0.72, P = 0.001) and Dapp (rho = -0.80, P < 0.001). Ki-67 expression correlated with Kapp (rho = 0.53, P = 0.03) but not with ADC or Dapp. In conclusion, Kapp was found to be a potential predictive biomarker of NACT response in HGSOC, which suggests that DKI is a promising clinical tool for use oncology and radiology that should be evaluated further in future larger studies.

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.

Comparison of breath-hold, respiratory navigated and free-breathing MR elastography of the liver.

PURPOSE: Hepatic magnetic resonance elastography (MRE) is currently a breath-hold imaging technique. Patients with chronic liver disease can have comorbidities that limit their ability to breath-hold (BH) for the required acquisition time. Our aim was to evaluate whether stiffness measurements obtained from a navigator-triggered MRE acquisition are comparable to standard expiratory breath-hold, inspiratory breath-hold or free-breathing in healthy participants. MATERIALS AND METHODS: Twelve healthy participants were imaged using the four methods on a clinical 1.5T MR system equipped with a product MRE system. Mean liver stiffness, and measurable area of stiffness (with a confidence threshold >95%) were compared between sequences using the concordance correlation coefficient. Repeatability of each sequence between two acquisitions was also assessed. RESULTS: The standard BH expiratory technique had high concordance with the navigated technique (r=0.716), and low concordance with the BH inspiration (r=0.165) and free-breathing (r=0.105) techniques. The navigator-triggered technique showed no statistical difference in measurable area of liver or in repeatability compared with the standard expiratory acquisition (p=0.997 and p=0.407 respectively). The free-breathing technique produced less measurable liver area and was less repeatable than the alternative techniques. The increase in acquisition time for navigator techniques was 3min 6s compared to standard expiratory breath-hold. CONCLUSION: Navigator-based hepatic MRE measurements are comparable to the reference standard expiratory breath-hold acquisition in healthy participants.