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.

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.

Deuterium metabolic imaging and hyperpolarized 13C-MRI of the normal human brain at clinical field strength reveals differential cerebral metabolism.

Deuterium metabolic imaging (DMI) and hyperpolarized 13C-pyruvate MRI (13C-HPMRI) are two emerging methods for non-invasive and non-ionizing imaging of tissue metabolism. Imaging cerebral metabolism has potential applications in cancer, neurodegeneration, multiple sclerosis, traumatic brain injury, stroke, and inborn errors of metabolism. Here we directly compare these two non-invasive methods at 3 T for the first time in humans and show how they simultaneously probe both oxidative and non-oxidative metabolism. DMI was undertaken 1-2 h after oral administration of [6,6'-2H2]glucose, and 13C-MRI was performed immediately following intravenous injection of hyperpolarized [1-13C]pyruvate in ten and nine normal volunteers within each arm respectively. DMI was used to generate maps of deuterium-labelled water, glucose, lactate, and glutamate/glutamine (Glx) and the spectral separation demonstrated that DMI is feasible at 3 T. 13C-HPMRI generated maps of hyperpolarized carbon-13 labelled pyruvate, lactate, and bicarbonate. The ratio of 13C-lactate/13C-bicarbonate (mean 3.7 ± 1.2) acquired with 13C-HPMRI was higher than the equivalent 2H-lactate/2H-Glx ratio (mean 0.18 ± 0.09) acquired using DMI. These differences can be explained by the route of administering each probe, the timing of imaging after ingestion or injection, as well as the biological differences in cerebral uptake and cellular physiology between the two molecules. The results demonstrate these two metabolic imaging methods provide different yet complementary readouts of oxidative and reductive metabolism within a clinically feasible timescale. Furthermore, as DMI was undertaken at a clinical field strength within a ten-minute scan time, it demonstrates its potential as a routine clinical tool in the future.

Sodium accumulation in breast cancer predicts malignancy and treatment response.

BACKGROUND: Breast cancer remains a leading cause of death in women and novel imaging biomarkers are urgently required. Here, we demonstrate the diagnostic and treatment-monitoring potential of non-invasive sodium (23Na) MRI in preclinical models of breast cancer. METHODS: Female Rag2-/- Il2rg-/- and Balb/c mice bearing orthotopic breast tumours (MDA-MB-231, EMT6 and 4T1) underwent MRI as part of a randomised, controlled, interventional study. Tumour biology was probed using ex vivo fluorescence microscopy and electrophysiology. RESULTS: 23Na MRI revealed elevated sodium concentration ([Na+]) in tumours vs non-tumour regions. Complementary proton-based diffusion-weighted imaging (DWI) linked elevated tumour [Na+] to increased cellularity. Combining 23Na MRI and DWI measurements enabled superior classification accuracy of tumour vs non-tumour regions compared with either parameter alone. Ex vivo assessment of isolated tumour slices confirmed elevated intracellular [Na+] ([Na+]i); extracellular [Na+] ([Na+]e) remained unchanged. Treatment with specific inward Na+ conductance inhibitors (cariporide, eslicarbazepine acetate) did not affect tumour [Na+]. Nonetheless, effective treatment with docetaxel reduced tumour [Na+], whereas DWI measures were unchanged. CONCLUSIONS: Orthotopic breast cancer models exhibit elevated tumour [Na+] that is driven by aberrantly elevated [Na+]i. Moreover, 23Na MRI enhances the diagnostic capability of DWI and represents a novel, non-invasive biomarker of treatment response with superior sensitivity compared to DWI alone.

Three dimensional MRF obtains highly repeatable and reproducible multi-parametric estimations in the healthy human brain at 1.5T and 3T.

Magnetic resonance fingerprinting (MRF) is highly promising as a quantitative MRI technique due to its accuracy, robustness, and efficiency. Previous studies have found high repeatability and reproducibility of 2D MRF acquisitions in the brain. Here, we have extended our investigations to 3D MRF acquisitions covering the whole brain using spiral projection k-space trajectories. Our travelling head study acquired test/retest data from the brains of 12 healthy volunteers and 8 MRI systems (3 systems at 3 T and 5 at 1.5 T, all from a single vendor), using a study design not requiring all subjects to be scanned at all sites. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived PD T1 and T2 maps to an anatomical atlas, coefficients of variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site. Our analysis demonstrated a high repeatability (CVs 0.7-1.3% for T1, 2.0-7.8% for T2, 1.4-2.5% for normalized PD) and reproducibility (CVs of 2.0-5.8% for T1, 7.4-10.2% for T2, 5.2-9.2% for normalized PD) in gray and white matter. Both repeatability and reproducibility improved when compared to similar experiments using 2D acquisitions. Three-dimensional MRF obtains highly repeatable and reproducible estimations of T1 and T2, supporting the translation of MRF-based fast quantitative imaging into clinical applications.

Combined 23 Na and 13 C imaging at 3.0 Tesla using a single-tuned large FOV birdcage coil.

PURPOSE: An unmet need in carbon-13 (13 C)-MRI is a transmit system that provides uniform excitation across a large FOV and can accommodate patients of wide-ranging body habitus. Due to the small difference between the resonant frequencies, sodium-23 (23 Na) coil developments can inform 13 C coil design while being simpler to assess due to the higher naturally abundant 23 Na signal. Here we present a removable 23 Na birdcage, which also allows operation as a 13 C abdominal coil. METHODS: We demonstrate a quadrature-driven 4-rung 23 Na birdcage coil of 50 cm in length for both 23 Na and 13 C abdominal imaging. The coil transmit efficiencies and B1+ maps were compared to a linearly driven 13 C Helmholtz-based (clamshell) coil. SNR was investigated with 23 Na and 13 C data using an 8-channel 13 C receive array within the 23 Na birdcage. RESULTS: The 23 Na birdcage longitudinal FOV was > 40 cm, whereas the 13 C clamshell was < 32 cm. The transmit efficiency of the birdcage at the 23 Na frequency was 0.65 µT/sqrt(W), similar to the clamshell for 13 C. However, the coefficient of variation of 23 Na- B1+ was 16%, nearly half that with the 13 C clamshell. The 8-channel 13 C receive array combined with the 23 Na birdcage coil generated a greater than twofold increase in 23 Na-SNR from the central abdomen compared with the birdcage alone. DISCUSSION: This 23 Na birdcage coil has a larger FOV and improved B1+ uniformity when compared to the widely used clamshell coil design while also providing similar transmit efficiency. The coil has the potential to be used for both 23 Na and 13 C imaging.

Characterization and correction of center-frequency effects in X-nuclear eddy current compensations on a clinical MR system.

PURPOSE: The aim of the study was to investigate whether incorrectly compensated eddy currents are the source of persistent X-nuclear spectroscopy and imaging artifacts, as well as methods to correct this. METHODS: Pulse-acquire spectra were collected for 1 H and X-nuclei (23 Na or 31 P) using the minimum TR permitted on a 3T clinical MRI system. Data were collected in 3 orientations (axial, sagittal, and coronal) with the spoiler gradient at the end of the TR applied along the slice direction for each. Modifications to system calibration files to tailor eddy current compensation for each X-nucleus were developed and applied, and data were compared with and without these corrections for: slice-selective MRS (for 23 Na and 31 P), 2D spiral trajectories (for 13 C), and 3D cones trajectories (for 23 Na). RESULTS: Line-shape distortions characteristic of eddy currents were demonstrated for X-nuclei, which were not seen for 1 H. The severity of these correlated with the amplitude of the eddy current frequency compensation term applied by the system along the axis of the applied spoiler gradient. A proposed correction to eddy current compensation, taking account of the gyromagnetic ratio, was shown to dramatically reduce these distortions. The same correction was also shown to improve data quality of non-Cartesian imaging (2D spiral and 3D cones trajectories). CONCLUSION: A simple adaptation of the default compensation for eddy currents was shown to eliminate a range of artifacts detected on X-nuclear spectroscopy and imaging.

Dynamic contrast-enhanced MRI of synovitis in knee osteoarthritis: repeatability, discrimination and sensitivity to change in a prospective experimental study.

OBJECTIVES: Evaluate test-retest repeatability, ability to discriminate between osteoarthritic and healthy participants, and sensitivity to change over 6 months, of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarkers in knee OA. METHODS: Fourteen individuals aged 40-60 with mild-moderate knee OA and 6 age-matched healthy volunteers (HV) underwent DCE-MRI at 3 T at baseline, 1 month and 6 months. Voxelwise pharmacokinetic modelling of dynamic data was used to calculate DCE-MRI biomarkers including Ktrans and IAUC60. Median DCE-MRI biomarker values were extracted for each participant at each study visit. Synovial segmentation was performed using both manual and semiautomatic methods with calculation of an additional biomarker, the volume of enhancing pannus (VEP). Test-retest repeatability was assessed using intraclass correlation coefficients (ICC). Smallest detectable differences (SDDs) were calculated from test-retest data. Discrimination between OA and HV was assessed via calculation of between-group standardised mean differences (SMD). Responsiveness was assessed via the number of OA participants with changes greater than the SDD at 6 months. RESULTS: Ktrans demonstrated the best test-retest repeatability (Ktrans/IAUC60/VEP ICCs 0.90/0.84/0.40, SDDs as % of OA mean 33/71/76%), discrimination between OA and HV (SMDs 0.94/0.54/0.50) and responsiveness (5/1/1 out of 12 OA participants with 6-month change > SDD) when compared to IAUC60 and VEP. Biomarkers derived from semiautomatic segmentation outperformed those derived from manual segmentation across all domains. CONCLUSIONS: Ktrans demonstrated the best repeatability, discrimination and sensitivity to change suggesting that it is the optimal DCE-MRI biomarker for use in experimental medicine studies. KEY POINTS: • Dynamic contrast-enhanced MRI (DCE-MRI) provides quantitative measures of synovitis in knee osteoarthritis which may permit early assessment of efficacy in experimental medicine studies. • This prospective observational study compared DCE-MRI biomarkers across domains relevant to experimental medicine: test-retest repeatability, discriminative validity and sensitivity to change. • The DCE-MRI biomarker Ktrans demonstrated the best performance across all three domains, suggesting that it is the optimal biomarker for use in future interventional studies.

Quantitative analysis of the ACL and PCL using T1rho and T2 relaxation time mapping: an exploratory, cross-sectional comparison between OA and healthy control knees.

BACKGROUND: Quantitative magnetic resonance imaging (MRI) methods such as T1rho and T2 mapping are sensitive to changes in tissue composition, however their use in cruciate ligament assessment has been limited to studies of asymptomatic populations or patients with posterior cruciate ligament tears only. The aim of this preliminary study was to compare T1rho and T2 relaxation times of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) between subjects with mild-to-moderate knee osteoarthritis (OA) and healthy controls. METHODS: A single knee of 15 patients with mild-to-moderate knee OA (Kellgren-Lawrence grades 2-3) and of 6 age-matched controls was imaged using a 3.0 T MRI. Three-dimensional (3D) fat-saturated spoiled gradient recalled-echo images were acquired for morphological assessment and T1ρ- and T2-prepared pseudo-steady-state 3D fast spin echo images for compositional assessment of the cruciate ligaments. Manual segmentation of whole ACL and PCL, as well as proximal / middle / distal thirds of both ligaments was carried out by two readers using ITK-SNAP and mean relaxation times were recorded. Variation between thirds of the ligament were assessed using repeated measures ANOVAs and differences in these variations between groups using a Kruskal-Wallis test. Inter- and intra-rater reliability were assessed using intraclass correlation coefficients (ICCs). RESULTS: In OA knees, both T1rho and T2 values were significantly higher in the distal ACL when compared to the rest of the ligament with the greatest differences in T1rho (e.g. distal mean = 54.5 ms, proximal = 47.0 ms, p < 0.001). The variation of T2 values within the PCL was lower in OA knees (OA: distal vs middle vs proximal mean = 28.5 ms vs 29.1 ms vs 28.7 ms, p = 0.748; Control: distal vs middle vs proximal mean = 26.4 ms vs 32.7 ms vs 33.3 ms, p = 0.009). ICCs were excellent for the majority of variables. CONCLUSION: T1rho and T2 mapping of the cruciate ligaments is feasible and reliable. Changes within ligaments associated with OA may not be homogeneous. This study is an important step forward in developing a non-invasive, radiological biomarker to assess the ligaments in diseased human populations in-vivo.

Improving the quantitative classification of Erlenmeyer flask deformities.

The Erlenmeyer flask deformity is a common skeletal modeling deformity, but current classification systems are binary and may restrict its utility as a predictor of associated skeletal conditions. A quantifiable 3-point system of severity classification could improve its predictive potential in disease. Ratios were derived from volumes of regions of interests drawn in 50 Gaucher's disease patients. ROIs were drawn from the distal physis to 2 cm proximal, 2 cm to 4 cm, and 4 cm to 6 cm. Width was also measured at each of these boundaries. Two readers rated these 100 femurs using a 3-point scale of severity classification. Weighted kappa indicated reliability and one-way analysis of variance characterized ratio differences across the severity scale. Accuracy analyses allowed determination of clinical cutoffs for each ratio. Pearson's correlations assessed the associations of volume and width with a shape-based concavity metric of the femur. The volume ratio incorporating the metaphyseal region from 0 to 2 cm and the diametaphyseal region at 4-6 cm was most accurate at distinguishing femurs on the 3-point scale. Receiver operating characteristic curves for this ratio indicated areas of 0.95 to distinguish normal and mild femurs and 0.93 to distinguish mild and severe femurs. Volume was moderately associated with the degree of femur concavity. The proposed volume ratio method is an objective, proficient method at distinguishing severities of the Erlenmeyer flask deformity with the potential for automation. This may have application across diseases associated with the deformity and deficient osteoclast-mediated modeling of growing bone.

Enhancing Distraction Osteogenesis With Carbon Fiber Reinforced Polyether Ether Ketone Bone Pins and a Three-Dimensional Printed Transfer Device to Permit Artifact-Free Three-Dimensional Magnetic Resonance Imaging.

OBJECTIVES: To: (1) design an artifact-free 3D-printed MR-safe temporary transfer device, (2) engineer bone-pins from carbon fiber reinforced polyether ether ketone (CFR-PEEK), (3) evaluate the imaging artifacts of CFR-PEEK, and (4) confirm the osteointegration potential of CFR-PEEK, thus enhancing 3D-planning of bony advancements in hemifacial microsomia using sequential magnetic resonance imaging (MRI). STUDY DESIGN: Engineered CRF-PEEK bone pins and a 3D printed ex-fix device were implanted into a sheep head and imaged with MRI and computed tomography . The osseointegration and bony compatibility potential of CFR-PEEK was assessed with scanning electron microscopy images of MC3T3 preosteoblast cells on the surface of the material. RESULTS: The CFR-PEEK pins resulted in a signal void equivalent to the dimension of the pin, with no adjacent areas of MR-signal loss or computed tomography artifact. MCT3 cells adhered and proliferated on the surface of the discs by forming a monolayer of cells, confirming compatibility and osseointegration potential. CONCLUSION: A 3D printed transfer device could be utilized temporarily during MRI to permit artifact-free 3D planning. CFR-PEEK pins eliminate imaging artifact permitting sequential MRI examination. In combination, this has the potential to enhance distraction osteogenesis, by permitting accurate three-dimensional planning without ionizing radiation.

Visualization of sodium dynamics in the kidney by magnetic resonance imaging in a multi-site study.

Sodium magnetic resonance imaging (MRI) is a powerful, non-invasive technique to assess sodium distribution within the kidney. Here we undertook pre-clinical and clinical studies to quantify the corticomedullary sodium gradient in healthy individuals and in a porcine model of diuresis. The results demonstrated that sodium MRI could detect spatial differences in sodium biodistribution across the kidney. The sodium gradient of the kidney changed significantly after diuresis in the pig model and was independent of blood electrolyte measurements. Thus, rapid sodium MRI can be used to dynamically quantify sodium biodistribution in the porcine and human kidney.

Creating a clinical platform for carbon-13 studies using the sodium-23 and proton resonances.

PURPOSE: Calibration of hyperpolarized 13 C-MRI is limited by the low signal from endogenous carbon-containing molecules and consequently requires 13 C-enriched external phantoms. This study investigated the feasibility of using either 23 Na-MRI or 1 H-MRI to calibrate the 13 C excitation. METHODS: Commercial 13 C-coils were used to estimate the transmit gain and center frequency for 13 C and 23 Na resonances. Simulations of the transmit B1 profile of a Helmholtz loop were performed. Noise correlation was measured for both nuclei. A retrospective analysis of human data assessing the use of the 1 H resonance to predict [1-13 C]pyruvate center frequency was also performed. In vivo experiments were undertaken in the lower limbs of 6 pigs following injection of hyperpolarized 13 C-pyruvate. RESULTS: The difference in center frequencies and transmit gain between tissue 23 Na and [1-13 C]pyruvate was reproducible, with a mean scale factor of 1.05179 ± 0.00001 and 10.4 ± 0.2 dB, respectively. Utilizing the 1 H water peak, it was possible to retrospectively predict the 13 C-pyruvate center frequency with a standard deviation of only 11 Hz sufficient for spectral-spatial excitation-based studies. CONCLUSION: We demonstrate the feasibility of using the 23 Na and 1 H resonances to calibrate the 13 C transmit B1 using commercially available 13 C-coils. The method provides a simple approach for in vivo calibration and could improve clinical workflow.

Molecular imaging of the prostate: Comparing total sodium concentration quantification in prostate cancer and normal tissue using dedicated 13 C and 23 Na endorectal coils.

BACKGROUND: There has been recent interest in nonproton MRI including hyperpolarized carbon-13 (13 C) imaging. Prostate cancer has been shown to have a higher tissue sodium concentration (TSC) than normal tissue. Sodium (23 Na) and 13 C nuclei have a frequency difference of only 1.66 MHz at 3T, potentially enabling 23 Na imaging with a 13 C-tuned coil and maximizing the metabolic information obtained from a single study. PURPOSE: To compare TSC measurements from a 13 C-tuned endorectal coil to those quantified with a dedicated 23 Na-tuned coil. STUDY TYPE: Prospective. POPULATION: Eight patients with biopsy-proven, intermediate/high risk prostate cancer imaged prior to prostatectomy. SEQUENCE: 3T MRI with separate dual-tuned 1 H/23 Na and 1 H/13 C endorectal receive coils to quantify TSC. ASSESSMENT: Regions-of-interest for TSC quantification were defined for normal peripheral zone (PZ), normal transition zone (TZ), and tumor, with reference to histopathology maps. STATISTICAL TESTS: Two-sided Wilcoxon rank sum with additional measures of correlation, coefficient of variation, and Bland-Altman plots to assess for between-test differences. RESULTS: Mean TSC for normal PZ and TZ were 39.2 and 33.9 mM, respectively, with the 23 Na coil and 40.1 and 36.3 mM, respectively, with the 13 C coil (P = 0.22 and P = 0.11 for the intercoil comparison, respectively). For tumor tissue, there was no statistical difference between the overall mean tumor TSC measured with the 23 Na coil (41.8 mM) and with the 13 C coil (46.6 mM; P = 0.38). Bland-Altman plots showed good repeatability for tumor TSC measurements between coils, with a reproducibility coefficient of 9 mM; the coefficient of variation between the coils was 12%. The Pearson correlation coefficient for TSC between coils for all measurements was r = 0.71 (r2 = 0.51), indicating a strong positive linear relationship. The mean TSC within PZ tumors was significantly higher compared with normal PZ for both the 23 Na coil (45.4 mM; P = 0.02) and the 13 C coil (49.4 mM; P = 0.002). DATA CONCLUSION: We demonstrated the feasibility of using a carbon-tuned coil to quantify TSC, enabling dual metabolic information from a single coil. This approach could make the acquisition of both 23 Na-MRI and 13 C-MRI feasible in a single clinical imaging session. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:90-97.

Effectively Measuring Exercise-Related Variations in T1ρ and T2 Relaxation Times of Healthy Articular Cartilage.

BACKGROUND: Determining the compositional response of articular cartilage to dynamic joint-loading using MRI may be a more sensitive assessment of cartilage status than conventional static imaging. However, distinguishing the effects of joint-loading vs. inherent measurement variability remains difficult, as the repeatability of these quantitative methods is often not assessed or reported. PURPOSE: To assess exercise-induced changes in femoral, tibial, and patellar articular cartilage composition and compare these against measurement repeatability. STUDY TYPE: Prospective observational study. POPULATION: Phantom and 19 healthy participants. FIELD STRENGTH/SEQUENCE: 3T; 3D fat-saturated spoiled gradient recalled-echo; T1ρ - and T2 -prepared pseudosteady-state 3D fast spin echo. ASSESSMENT: The intrasessional repeatability of T1ρ and T2 relaxation mapping, with and without knee repositioning between two successive measurements, was determined in 10 knees. T1ρ and T2 relaxation mapping of nine knees was performed before and at multiple timepoints after a 5-minute repeated, joint-loading stepping activity. 3D surface models were created from patellar, femoral, and tibial articular cartilage. STATISTICAL TESTS: Repeatability was assessed using root-mean-squared-CV (RMS-CV). Using Bland-Altman analysis, thresholds defined as the smallest detectable difference (SDD) were determined from the repeatability data with knee repositioning. RESULTS: Without knee repositioning, both surface-averaged T1ρ and T2 were very repeatable on all cartilage surfaces, with RMS-CV <1.1%. Repositioning of the knee had the greatest effect on T1ρ of patellar cartilage with the surface-averaged RMS-CV = 4.8%. While T1ρ showed the greatest response to exercise at the patellofemoral cartilage region, the largest changes in T2 were determined in the lateral femorotibial region. Following thresholding, significant (>SDD) average exercise-induced in T1ρ and T2 of femoral (-8.0% and -5.3%), lateral tibial (-6.9% and -5.9%), medial tibial (+5.8% and +2.9%), and patellar (-7.9% and +2.8%) cartilage were observed. DATA CONCLUSION: Joint-loading with a stepping activity resulted in T1ρ and T2 changes above background measurement error. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1 J. MAGN. RESON. IMAGING 2020;52:1753-1764.

Three-Dimensional Surface-Based Analysis of Cartilage MRI Data in Knee Osteoarthritis: Validation and Initial Clinical Application.

BACKGROUND: Traditional quantitative analysis of cartilage with MRI averages measurements (eg, thickness) across regions-of-interest (ROIs) which may reduce responsiveness. PURPOSE: To validate and describe clinical application of a semiautomated surface-based method for analyzing cartilage relaxation times ("composition") and morphology on MRI, 3D cartilage surface mapping (3D-CaSM). STUDY TYPE: Validation study in cadaveric knees and prospective observational (cohort) study in human participants. POPULATION: Four cadaveric knees and 14 participants aged 40-60 with mild-moderate knee osteoarthritis (OA) and 6 age-matched healthy volunteers, imaged at baseline, 1, and 6 months. FIELD STRENGTH/SEQUENCE: 3D spoiled gradient echo, T1 rho/T2 magnetization-prepared 3D fast spin echo for mapping of T1 rho/T2 relaxation times and delayed gadolinium enhanced MRI of cartilage (dGEMRIC) using variable flip angle T1 relaxation time mapping at 3T. ASSESSMENT: 3D-CaSM was validated against high-resolution peripheral quantitative computed tomography (HRpQCT) in cadaveric knees, with comparison to expert manual segmentation. The clinical study assessed test-retest repeatability and sensitivity to change over 6 months for cartilage thickness and relaxation times. STATISTICAL TESTS: Bland-Altman analysis was performed for the validation study and evaluation of test-retest repeatability. Six-month changes were assessed via calculation of the percentage of each cartilage surface affected by areas of significant change (%SC), defined using thresholds based on area and smallest detectable difference (SDD). RESULTS: Bias and precision (0.06 ± 0.25 mm) of 3D-CaSM against reference HRpQCT data were comparable to expert manual segmentation (-0.13 ± 0.26 mm). 3D-CaSM demonstrated significant (>SDD) 6-month changes in cartilage thickness and relaxation times in both OA participants and healthy controls. The parameter demonstrating the greatest 6-month change was T2 relaxation time (OA median %SC [IQR] = 8.8% [5.5 to 12.6]). DATA CONCLUSION: This study demonstrates the construct validity and potential clinical utility of 3D-CaSM, which may offer advantages to conventional ROI-based methods. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2. J. Magn. Reson. Imaging 2020;52:1139-1151.

Multi-site repeatability and reproducibility of MR fingerprinting of the healthy brain at 1.5 and 3.0 T.

Fully-quantitative MR imaging methods are useful for longitudinal characterization of disease and assessment of treatment efficacy. However, current quantitative MRI protocols have not been widely adopted in the clinic, mostly due to lengthy scan times. Magnetic Resonance Fingerprinting (MRF) is a new technique that can reconstruct multiple parametric maps from a single fast acquisition in the transient state of the MR signal. Due to the relative novelty of this technique, the repeatability and reproducibility of quantitative measurements obtained using MRF has not been extensively studied. Our study acquired test/retest data from the brains of nine healthy volunteers, each scanned on five MRI systems (two at 3.0 T and three at 1.5 T, all from a single vendor) located at two different centers. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived M0, T1 and T2 maps to an anatomical atlas, coefficients-of-variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site. Our analysis demonstrated an excellent repeatability (CVs of 2-3% for T1, 5-8% for T2, 3% for normalized-M0) and a good reproducibility (CVs of 3-8% for T1, 8-14% for T2, 5% for normalized-M0) in grey and white matter.

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.

Magnetic resonance fingerprinting with dictionary-based fat and water separation (DBFW MRF): A multi-component approach.

PURPOSE: To obtain a fast and robust fat-water separation with simultaneous estimation of water T1 , fat T1 , and fat fraction maps. METHODS: We modified an MR fingerprinting (MRF) framework to use a single dictionary combination of a water and fat dictionary. A variable TE acquisition pattern with maximum TE = 4.8 ms was used to increase the fat-water separability. Radiofrequency (RF) spoiling was used to reduce the size of the dictionary by reducing T2 sensitivity. The technique was compared both in vitro and in vivo to an MRF method that incorporated 3-point Dixon (DIXON MRF), as well as Cartesian IDEAL with different acquisition parameters. RESULTS: The proposed dictionary-based fat-water separation technique (DBFW MRF) successfully provided fat fraction, water, and fat T1 , B0 , and B1+ maps both in vitro and in vivo. The fat fraction and water T1 values obtained with DBFW MRF show excellent agreement with DIXON MRF as well as with the reference values obtained using a Cartesian IDEAL with a long TR (concordance correlation coefficient: 0.97/0.99 for fat fraction-water T1 ). Whereas fat fraction values with Cartesian IDEAL were degraded in the presence of T1 saturation, MRF methods successfully estimated and accounted for T1 in the fat fraction estimates. CONCLUSION: The DBFW MRF technique can successfully provide T1 and fat fraction quantification in under 20 s per slice, intrinsically correcting T1 biases typical of fast Dixon techniques. These features could improve the diagnostic quality and use of images in presence of fat.

T2* Measurement bias due to concomitant gradient fields.

PURPOSE: To demonstrate that concomitant magnetic fields can cause significant spatially dependent biases in T2* relaxometry measurements with implications for clinical applications such as BOLD and dynamic susceptibility contrast-enhanced MRI. THEORY AND METHODS: After developing a theoretical framework for intravoxel dephasing and signal loss from concomitant magnetic fields, this framework and the effect of concomitant fields on T2* are validated with phantom experiments and numerical simulation. In lower leg and renal T2* mapping, we quantify measurement bias for imaging protocols with high gradient amplitude multiecho readouts, comparable to those used in clinical applications. RESULTS: Concordance between phantom experiment and numerical simulation validate the theoretical framework. Changes in T2* measured in the lower leg and kidney varied by up to 15% and 35%, respectively, as a result of concomitant gradient effects when compared with the control measurements. CONCLUSION: Concomitant magnetic fields produced by imaging gradient coils can cause clinically significant T2* mapping errors when high amplitude, long duration gradient waveforms are used. While we have shown that measurement biases can be quite large, modification of imaging parameters can potentially reduce concomitant field-induced measurement errors to acceptable levels. Magn Reson Med 77:1562-1572, 2017. © 2016 International Society for Magnetic Resonance in Medicine.