Imaging of osteoarthritis from the ankle through the midfoot.

Ankle, hindfoot, and midfoot osteoarthritis (OA) is most commonly posttraumatic and tends to become symptomatic in younger patients. It often results from instability due to insufficiency of supportive soft tissue structures, such as ligaments and tendons. Diagnostic imaging can be helpful to detect and characterize the distribution of OA, and to assess the integrity of these supportive structures, which helps determine prognosis and guide treatment. However, the imaging findings associated with OA and instability may be subtle and unrecognized until the process is advanced, which may ultimately limit therapeutic options to salvage procedures. It is important to understand the abilities and limitations of various imaging modalities used to assess ankle, hindfoot, and midfoot OA, and to be familiar with the imaging findings of OA and instability patterns.

Cancellation of streak artifacts in radial abdominal imaging using interference null space projection.

PURPOSE: In radial abdominal imaging, it has been commonly observed that signal from the arms cause streaks due to system imperfections. We previously introduced a streak removal technique (B-STAR), which is inherently spatially variant and limited to work in image space. In this work, we propose a spatially invariant streak cancellation technique (CACTUS), which can be applied in either image space or k-space and is compatible with iterative reconstructions. THEORY AND METHODS: Streak sources are typically spatially localized and can be represented using a low-dimensional subspace. CACTUS identifies the streak subspace by leveraging the spatial redundancy of receiver coils and projects the data onto the streak null space to eliminate the streaks. When applied in k-space, CACTUS can be combined with iterative reconstructions. CACTUS was tested in phantoms and in vivo abdominal imaging using a radial turbo spin-echo pulse sequence. RESULTS: In phantoms, CACTUS improved T2 estimation in comparison to previous de-streaking methods. In vivo experiments showed that CACTUS reduced streaks and yielded T2 estimation, in regions affected by streaks, closer to a streak-free reference. Evaluation using a clinical abdominal dataset (n = 20) showed that CACTUS is comparable to B-STAR and yields significantly better signal preservation and streak cancellation than coil removal and suppression methods. CONCLUSION: CACTUS provides superior signal preservation and streak reduction performance compared to coil removal and suppression methods. As a clear advantage over B-STAR, CACTUS can be integrated with iterative reconstruction methods. In abdominal T2 mapping, CACTUS improves the accuracy of parameter estimation in areas affected by streaks.

Abdominal T2-Weighted Imaging and T2 Mapping Using a Variable Flip Angle Radial Turbo Spin-Echo Technique.

BACKGROUND: T2 mapping is of great interest in abdominal imaging but current methods are limited by low resolution, slice coverage, motion sensitivity, or lengthy acquisitions. PURPOSE: Develop a radial turbo spin-echo technique with refocusing variable flip angles (RADTSE-VFA) for high spatiotemporal T2 mapping and efficient slice coverage within a breath-hold and compare to the constant flip angle counterpart (RADTSE-CFA). STUDY TYPE: Prospective technical efficacy. SUBJECTS: Testing performed on agarose phantoms and 12 patients. Focal liver lesion classification tested on malignant (N = 24) and benign (N = 11) lesions. FIELD STRENGTH/SEQUENCE: 1.5 T/RADTSE-VFA, RADTSE-CFA. ASSESSMENT: A constrained objective function was used to optimize the refocusing flip angles. Phantom and/or in vivo data were used to assess relative contrast, T2 estimation, specific absorption rate (SAR), and focal liver lesion classification. STATISTICAL TESTS: t-Tests or Mann-Whitney Rank Sum tests were used. RESULTS: Phantom data did not show significant differences in mean relative contrast (P = 0.10) and T2 accuracy (P = 0.99) between RADTSE-VFA and RADTSE-CFA. Adding noise caused T2 overestimation predominantly for RADTSE-CFA and low T2 values. In vivo results did not show significant differences in mean spleen-to-liver (P = 0.62) and kidney-to-liver (P = 0.49) relative contrast between RADTSE-VFA and RADTSE-CFA. Mean T2 values were not significantly different between the two techniques for spleen (T2VFA  = 109.2 ± 12.3 msec; T2CFA  = 110.7 ± 11.1 msec; P = 0.78) and kidney-medulla (T2VFA  = 113.0 ± 8.7 msec; T2CFA  = 114.0 ± 8.6 msec; P = 0.79). Liver T2 was significantly higher for RADTSE-CFA (T2VFA  = 52.6 ± 6.6 msec; T2CFA  = 60.4 ± 8.0 msec) consistent with T2 overestimation in the phantom study. Focal liver lesion classification had comparable T2 distributions for RADTSE-VFA and RADTSE-CFA for malignancies (P = 1.0) and benign lesions (P = 0.39). RADTSE-VFA had significantly lower SAR than RADTSE-CFA increasing slice coverage by 1.5. DATA CONCLUSION: RADTSE-VFA provided noise-robust T2 estimation compared to the constant flip angle counterpart while generating T2-weighted images with comparable contrast. The VFA scheme minimized SAR improving slice efficiency for breath-hold imaging. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density.

PURPOSE: Obesity is a known risk factor for post-menopausal breast cancer and may increase risk for triple negative breast cancer in premenopausal women. Intervention strategies are clearly needed to reduce obesity-associated breast cancer risk. METHODS: We conducted a Phase II double-blind, randomized, placebo-controlled trial of metformin in overweight/obese premenopausal women with components of metabolic syndrome to assess the potential of metformin for primary breast cancer prevention. Eligible participants were randomized to receive metformin (850 mg BID, n = 76) or placebo (n = 75) for 12 months. Outcomes included breast density, assessed by fat/water MRI with change in percent breast density as the primary endpoint, anthropometric measures, and intervention feasibility. RESULTS: Seventy-six percent in the metformin arm and 83% in the placebo arm (p = 0.182) completed the 12-month intervention. Adherence to study agent was high with more than 80% of participants taking ≥ 80% assigned pills. The most common adverse events reported in the metformin arm were gastrointestinal in nature and subsided over time. Compared to placebo, metformin intervention led to a significant reduction in waist circumference (p < 0.001) and waist-to-hip ratio (p = 0.019). Compared to placebo, metformin did not change percent breast density and dense breast volume but led to a numerical but not significant decrease in non-dense breast volume (p = 0.070). CONCLUSION: We conclude that metformin intervention resulted in favorable changes in anthropometric measures of adiposity and a borderline decrease in non-dense breast volume in women with metabolic dysregulation. More research is needed to understand the impact of metformin on breast cancer risk reduction. TRIAL REGISTRATION: ClinicalTrials.gov NCT02028221. Registered January 7, 2014, https://clinicaltrials.gov/ct2/show/NCT02028221.

Radial streak artifact reduction using phased array beamforming.

PURPOSE: A new method for streak artifact reduction in radial MRI based on phased array filtering. THEORY: Radial imaging in applications that require large fields-of-view can be susceptible to streaking artifacts due to gradient nonlinearities. Coil removal methods prune the coils contributing the most to streaking artifacts at the expense of signal loss. Phased array beamforming is a form of spatial filtering used to suppress unwanted signals. The proposed method uses interference covariance generated from the streaking artifact samples which are manually extracted with phased array beamforming to suppress streaking in the images. METHODS: The performance of the proposed method was evaluated on abdomen radial fast spin echo images acquired on a 1.5T Siemens scanner and compared with previously proposed methods. RESULTS: Our results demonstrate that the proposed method can effectively suppress streaking artifacts without any noticeable loss in signal levels. Coil removal methods can suppress streaks as well but they may incur significant signal loss due to coil pruning. Quantitative metrics also demonstrate the superiority of the proposed method over earlier methods. CONCLUSION: The use of interference covariance with phased array beamforming can help reduce streaking artifacts.

An efficient 3D stack-of-stars turbo spin echo pulse sequence for simultaneous T2-weighted imaging and T2 mapping.

PURPOSE: To design a pulse sequence for efficient 3D T2-weighted imaging and T2 mapping. METHODS: A stack-of-stars turbo spin echo pulse sequence with variable refocusing flip angles and a flexible pseudorandom view ordering is proposed for simultaneous T2-weighted imaging and T2 mapping. An analytical framework is introduced for the selection of refocusing flip angles to maximize relative tissue contrast while minimizing T2 estimation errors and maintaining low specific absorption rate. Images at different echo times are generated using a subspace constrained iterative reconstruction algorithm. T2 maps are obtained by modeling the signal evolution using the extended phase graph model. The technique is evaluated using phantoms and demonstrated in vivo for brain, knee, and carotid imaging. RESULTS: Numerical simulations demonstrate an improved point spread function with the proposed pseudorandom view ordering compared to golden angle view ordering. Phantom experiments show that T2 values estimated from the stack-of-stars turbo spin echo pulse sequence with variable refocusing flip angles have good concordance with spin echo reference values. In vivo results show the proposed pulse sequence can generate qualitatively comparable T2-weighted images as conventional Cartesian 3D SPACE in addition to simultaneously generating 3D T2 maps. CONCLUSION: The proposed stack-of-stars turbo spin echo pulse sequence with pseudorandom view ordering and variable refocusing flip angles allows high resolution isotropic T2 mapping in clinically acceptable scan times. The optimization framework for the selection of refocusing flip angles improves T2 estimation accuracy while generating T2-weighted contrast comparable to conventional Cartesian imaging.

Rapid high-resolution T1 mapping using a highly accelerated radial steady-state free-precession technique.

BACKGROUND: T1 mapping is often used in some clinical protocols. Existing techniques are limited in slice coverage, and/or spatial-temporal resolution, or require long acquisitions. Here we present a multi-slice inversion-recovery (IR) radial steady-state free precession (radSSFP) pulse sequence combined with a principal component (PC) based reconstruction that overcomes these limitations. PURPOSE: To develop a fast technique for multi-slice high-resolution T1 mapping. STUDY TYPE: Technical efficacy study done prospectively. PHANTOM/SUBJECTS: IR-radSSFP was tested in phantoms, five healthy volunteers, and four patients with abdominal lesions. FIELD STRENGTH/SEQUENCE: IR-radSSFP was implemented at 3T. ASSESSMENT: Computer simulations were performed to optimize the flip angle for T1 estimation; testing was done in phantoms using as reference an IR spin-echo pulse sequence. T1 mapping with IR-radSSFP was also assessed in vivo (brain and abdomen) and T1 values were compared with literature. T1 maps were also compared with a radial IR-FLASH technique. STATISTICAL TESTS: A two-tailed t-test was used to compare T1 values in phantoms. A repeatability study was carried out in vivo using Bland-Altman analysis. RESULTS: Simulations and phantom experiments showed that a flip angle of 20˚ was optimal for T1 mapping. When comparing single to multi-slice experiments in phantoms there were no significant differences between the means T1 values (P = 0.0475). In vivo results show that T1 maps with spatial resolution as high as 0.69 mm × 0.69 mm × 2.00 mm (brain) and 0.83 mm × 0.83 mm × 3.00 mm (abdomen) can be generated for 84 brain slices in 3 min and 10 abdominal slices in a breath-hold; T1 values were comparable to those reported in literature. The coefficients of variation from the repeatability study were 1.7% for brain and 2.5-2.7% in the abdomen. DATA CONCLUSION: A multi-slice IR-radSSFP technique combined with a PC-based reconstruction was demonstrated for higher resolution T1 mapping. This technique is fast, motion-insensitive and yields repeatable T1 values comparable to those in literature. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:239-252.

Accelerated MR parameter mapping with a union of local subspaces constraint.

PURPOSE: A new reconstruction method for multi-contrast imaging and parameter mapping based on a union of local subspaces constraint is presented. THEORY: Subspace constrained reconstructions use a predetermined subspace to explicitly constrain the relaxation signals. The choice of subspace size ( K ) impacts the approximation error vs noise-amplification tradeoff associated with these methods. A different approach is used in the model consistency constraint (MOCCO) framework to leverage the subspace model to enforce a softer penalty. Our proposed method, MOCCO-LS, augments the MOCCO model with a union of local subspaces (LS) approach. The union of local subspaces model is coupled with spatial support constraints and incorporated into the MOCCO framework to regularize the contrast signals in the scene. METHODS: The performance of the MOCCO-LS method was evaluated in vivo on T1 and T2 mapping of the human brain and with Monte-Carlo simulations and compared against MOCCO and the explicit subspace constrained models. RESULTS: The results demonstrate a clear improvement in the multi-contrast images and parameter maps. We sweep across the model order space ( K ) to compare the different reconstructions and demonstrate that the reconstructions have different preferential operating points. Experiments on T2 mapping show that the proposed method yields substantial improvements in performance even when operating at very high acceleration rates. CONCLUSIONS: The use of a union of local subspace constraints coupled with a sparsity promoting penalty leads to improved reconstruction quality of multi-contrast images and parameter maps.

Reproducible automated breast density measure with no ionizing radiation using fat-water decomposition MRI.

BACKGROUND: Increased breast density is a significant independent risk factor for breast cancer, and recent studies show that this risk is modifiable. Hence, breast density measures sensitive to small changes are desired. PURPOSE: Utilizing fat-water decomposition MRI, we propose an automated, reproducible breast density measurement, which is nonionizing and directly comparable to mammographic density (MD). STUDY TYPE: Retrospective study. POPULATION: The study included two sample sets of breast cancer patients enrolled in a clinical trial, for concordance analysis with MD (40 patients) and reproducibility analysis (10 patients). FIELD STRENGTH/SEQUENCE: The majority of MRI scans (59 scans) were performed with a 1.5T GE Signa scanner using radial IDEAL-GRASE sequence, while the remaining (seven scans) were performed with a 3T Siemens Skyra using 3D Cartesian 6-echo GRE sequence with a similar fat-water separation technique. ASSESSMENT: After automated breast segmentation, breast density was calculated using FraGW, a new measure developed to reliably reflect the amount of fibroglandular tissue and total water content in the entire breast. Based on its concordance with MD, FraGW was calibrated to MR-based breast density (MRD) to be comparable to MD. A previous breast density measurement, Fra80-the ratio of breast voxels with <80% fat fraction-was also calculated for comparison with FraGW. STATISTICAL TESTS: Pearson correlation was performed between MD (reference standard) and FraGW (and Fra80). Test-retest reproducibility of MRD was evaluated using the difference between test-retest measures (Δ1-2 ) and intraclass correlation coefficient (ICC). RESULTS: Both FraGW and Fra80 were strongly correlated with MD (Pearson ρ: 0.96 vs. 0.90, both P < 0.0001). MRD converted from FraGW showed higher test-retest reproducibility (Δ1-2 variation: 1.1% ± 1.2%; ICC: 0.99) compared to MD itself (literature intrareader ICC ≤0.96) and Fra80. DATA CONCLUSION: The proposed MRD is directly comparable with MD and highly reproducible, which enables the early detection of small breast density changes and treatment response. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;48:971-981.

A multi-band double-inversion radial fast spin-echo technique for T2 cardiovascular magnetic resonance mapping of the heart.

BACKGROUND: Double inversion recovery (DIR) fast spin-echo (FSE) cardiovascular magnetic resonance (CMR) sequences are used clinically for black-blood T2-weighted imaging. However, these sequences suffer from slice inefficiency due to the non-selective inversion pulses. We propose a multi-band (MB) encoded DIR radial FSE (MB-DIR-RADFSE) technique to simultaneously excite two slices. This sequence has improved signal-to-noise ratio per unit time compared to a single slice excitation. It is also motion robust and enables the reconstruction of high-resolution black-blood T2-weighted images and T2 maps for the excited slices. METHODS: Hadamard encoded MB pulses were used in MB-DIR-RADFSE to simultaneously excite two slices. A principal component based iterative reconstruction was used to jointly reconstruct black-blood T2-weighted images and T2 maps. Phantom and in vivo experiments were performed to evaluate T2 mapping performance and results were compared to a T2-prepared balanced steady state free precession (bSSFP) method. The inter-segment variability of the T2 maps were assessed using data acquired on healthy subjects. A reproducibility study was performed to evaluate reproducibility of the proposed technique. RESULTS: Phantom experiments show that the T2 values estimated from MB-DIR-RADFSE are comparable to the spin-echo based reference, while T2-prepared bSSFP over-estimated T2 values. The relative contrast of the black-blood images from the multi-band scheme was comparable to those from a single slice acquisition. The myocardial segment analysis on 8 healthy subjects indicated a significant difference (p-value < 0.01) in the T2 estimates from the apical slice when compared to the mid-ventricular slice. The mean T2 estimate from 12 subjects obtained using T2-prepared bSSFP was significantly higher (p-value = 0.012) compared to MB-DIR-RADFSE, consistent with the phantom results. The Bland-Altman analysis showed excellent reproducibility between the MB-DIR-RADFSE measurements, with a mean T2 difference of 0.12 ms and coefficient of reproducibility of 2.07 in 15 clinical subjects. The utility of this technique is demonstrated in two subjects where the T2 maps show elevated values in regions of pathology. CONCLUSIONS: The use of multi-band pulses for excitation improves the slice efficiency of the double inversion fast spin-echo pulse sequence. The use of a radial trajectory and a joint reconstruction framework allows reconstruction of TE images and T2 maps for the excited slices.

Validation of Peripheral Quantitative Computed Tomography-Derived Thigh Adipose Tissue Subcompartments in Young Girls Using a 3 T MRI Scanner.

The ability to assess skeletal muscle adipose tissue is important given the negative clinical implications associated with greater fat infiltration of the muscle. Computed tomography and magnetic resonance imaging (MRI) are highly accurate for measuring appendicular soft tissue and muscle composition, but have limitations. Peripheral quantitative computed tomography (pQCT) is an alternative that investigators find valuable because of its low radiation, fast scan time, and comparatively lower costs. The present investigation sought to assess the accuracy of pQCT-derived estimates of total, subcutaneous, skeletal muscle, intermuscular, and calculated intramuscular adipose tissue areas, and muscle density in the midthigh of young girls using the gold standard, 3 T MRI, as the criterion. Cross-sectional data were analyzed for 26 healthy girls aged 9-12 years. Midthigh soft tissue composition was assessed by both pQCT and 3 T MRI. Mean tissue area for corresponding adipose compartments by pQCT and MRI was compared using t tests, regression analysis, and Bland-Altman plots. Muscle density was regressed on MRI skeletal muscle adipose tissue, intermuscular adipose tissue, and intramuscular adipose tissue, each expressed as a percentage of total muscle area. Correlations were high between MRI and pQCT for total adipose tissue (r2 = 0.98), subcutaneous adipose tissue (r2 = 0.95), skeletal muscle adipose tissue (r2 = 0.83), and intermuscular adipose tissue (r2 = 0.82), and pQCT muscle density correlated well with both MRI skeletal muscle adipose tissue (r2 = 0.70) and MRI intermuscular adipose tissue (r2 = 0.70). There was a slight, but statistically significant underestimation by pQCT for total and subcutaneous adipose tissue, whereas no significant difference was observed for skeletal muscle adipose tissue. Both pQCT-estimated intramuscular adipose tissue and muscle density were weakly correlated with MRI-intramuscular adipose tissue. We conclude that pQCT is a valid measurement technique for estimating all adipose subcompartments, except for intramuscular adipose tissue, for the midthigh region in young/adolescent girls.

A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen.

PURPOSE: Diindolylmethane (DIM), a bioactive metabolite of indole-3-carbinol found in cruciferous vegetables, has proposed cancer chemoprevention activity in the breast. There is limited evidence of clinically relevant activity of DIM or long-term safety data of its regular use. A randomized, double-blind, placebo-controlled trial was conducted to determine the activity and safety of combined use of BioResponse DIM® (BR-DIM) with tamoxifen. METHODS: Women prescribed tamoxifen (n = 130) were randomly assigned oral BR-DIM at 150 mg twice daily or placebo, for 12 months. The primary study endpoint was change in urinary 2/16α-hydroxyestrone (2/16α-OHE1) ratio. Changes in 4-hydroxyestrone (4-OHE1), serum estrogens, sex hormone-binding globulin (SHBG), breast density, and tamoxifen metabolites were assessed. RESULTS: Ninety-eight women (51 placebo, 47 DIM) completed intervention; compliance with treatment was >91%. BR-DIM increased the 2/16α-OHE1 ratio (+3.2 [0.8, 8.4]) compared to placebo (-0.7 [-1.7, 0.8], P < 0.001). Serum SHBG increased with BR-DIM compared to placebo (+25 ± 22 and +1.1 ± 19 nmol/L, respectively). No change in breast density measured by mammography or by MRI was observed. Plasma tamoxifen metabolites (endoxifen, 4-OH tamoxifen, and N-desmethyl-tamoxifen) were reduced in women receiving BR-DIM versus placebo (P < 0.001). Minimal adverse events were reported and did not differ by treatment arm. CONCLUSION: In patients taking tamoxifen for breast cancer, daily BR-DIM promoted favorable changes in estrogen metabolism and circulating levels of SHBG. Further research is warranted to determine whether BR-DIM associated decreases in tamoxifen metabolites, including effects on endoxifen levels, attenuates the clinical benefit of tamoxifen. TRIAL REGISTRATION: ClinicalTrials.gov NCT01391689.

Multiresolution imaging using golden angle stack-of-stars and compressed sensing for dynamic MR urography.

PURPOSE: To develop a novel multiresolution MRI methodology for accurate estimation of glomerular filtration rate (GFR) in vivo. MATERIALS AND METHODS: A three-dimensional golden-angle radial stack-of-stars (SoS) trajectory was used for data acquisition on a 3 Tesla MRI scanner. Multiresolution reconstruction and analysis was performed using arterial input function reconstructed at 1-s. temporal resolution and renal dynamic data reconstructed using compressed sensing (CS) with 4-s temporal resolution. The method was first validated using simulations and the clinical utility of the technique was evaluated by comparing the GFR estimates from the proposed method to the estimated GFR (eGFR) obtained from serum creatinine for 10 subjects. RESULTS: The 4-s temporal resolution CS images minimized streaking artifacts and noise while the 1-s temporal resolution AIF minimized errors in GFR estimates. A paired t-test showed that there was no statistically significant difference between MRI based total GFR values and serum creatinine based eGFR estimates (P = 0.92). CONCLUSION: We have demonstrated the feasibility of multiresolution MRI using a golden angle radial stack-of-stars scheme to accurately estimate GFR as well as produce diagnostic quality dynamic images in vivo. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;46:303-311.

Volumetric MRI of the lungs during forced expiration.

PURPOSE: Lung function is typically characterized by spirometer measurements, which do not offer spatially specific information. Imaging during exhalation provides spatial information but is challenging due to large movement over a short time. The purpose of this work is to provide a solution to lung imaging during forced expiration using accelerated magnetic resonance imaging. The method uses radial golden angle stack-of-stars gradient echo acquisition and compressed sensing reconstruction. METHODS: A technique for dynamic three-dimensional imaging of the lungs from highly undersampled data is developed and tested on six subjects. This method takes advantage of image sparsity, both spatially and temporally, including the use of reference frames called bookends. Sparsity, with respect to total variation, and residual from the bookends, enables reconstruction from an extremely limited amount of data. RESULTS: Dynamic three-dimensional images can be captured at sub-150 ms temporal resolution, using only three (or less) acquired radial lines per slice per timepoint. The images have a spatial resolution of 4.6×4.6×10 mm. Lung volume calculations based on image segmentation are compared to those from simultaneously acquired spirometer measurements. CONCLUSION: Dynamic lung imaging during forced expiration is made possible by compressed sensing accelerated dynamic three-dimensional radial magnetic resonance imaging. Magn Reson Med 75:2295-2302, 2016. © 2015 Wiley Periodicals, Inc.

Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol.

BACKGROUND: Two-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk. METHODS/DESIGN: This is a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have elements of metabolic syndrome. Eligible participants will be randomized to receive metformin 850 mg BID (n = 75) or placebo (n = 75) for 12 months. The primary endpoint is change in breast density, based on magnetic resonance imaging (MRI) acquired fat-water features. Secondary outcomes include changes in serum insulin levels, serum insulin-like growth factor (IGF)-1 to insulin-like growth factor binding protein (IGFBP)-3 ratio, serum IGF-2 levels, serum testosterone levels, serum leptin to adiponectin ratio, body weight, and waist circumference. Exploratory outcomes include changes in metabolomic profiles in plasma and nipple aspirate fluid. Changes in tissue architecture as well as cellular and molecular targets in breast tissue collected in a subgroup of participants will also be explored. DISCUSSION: The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition. The study should help determine the potential breast cancer preventive activity of metformin in a growing population at risk for multiple diseases. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02028221 . Registered on January 2, 2014. Grant #: 1R01CA172444-01A1 awarded on Sept 11, 2013.

Correcting partial volume effects in biexponential T2 estimation of small lesions.

PURPOSE: T2 mapping provides a quantitative approach for focal liver lesion characterization. For small lesions, a biexponential model should be used to account for partial volume effects (PVE). However, conventional biexponential fitting suffers from large uncertainty of the fitted parameters when noise is present. The purpose of this work is to develop a more robust method to correct for PVE affecting small lesions. METHODS: We developed a region of interest-based joint biexponential fitting (JBF) algorithm to estimate the T2 of lesions affected by PVE. JBF takes advantage of the lesion fraction variation among voxels within a region of interest. JBF is compared to conventional approaches using Cramér-Rao lower bound analysis, numerical simulations, phantom, and in vivo data. RESULTS: JBF provides more accurate and precise T2 estimates in the presence of PVE. Furthermore, JBF is less sensitive to region of interest drawing. Phantom and in vivo results show that JBF can be combined with a reconstruction method for highly undersampled data, enabling the characterization of small abdominal lesions from data acquired in a single breath hold. CONCLUSION: The JBF algorithm provides more accurate and stable T2 estimates for small structures than conventional techniques when PVE is present. It should be particularly useful for the characterization of small abdominal lesions.

T2 mapping of the heart with a double-inversion radial fast spin-echo method with indirect echo compensation.

BACKGROUND: The abnormal signal intensity in cardiac T2-weighted images is associated with various pathologies including myocardial edema. However, the assessment of pathologies based on signal intensity is affected by the acquisition parameters and the sensitivities of the receiver coils. T2 mapping has been proposed to overcome limitations of T2-weighted imaging, but most methods are limited in spatial and/or temporal resolution. Here we present and evaluate a double inversion recovery radial fast spin-echo (DIR-RADFSE) technique that yields data with high spatiotemporal resolution for cardiac T2 mapping. METHODS: DIR-RADFSE data were collected at 1.5 T on phantoms and subjects with echo train length (ETL) = 16, receiver bandwidth (BW) = ±32 kHz, TR = 1RR, matrix size = 256 × 256. Since only 16 views per echo time (TE) are collected, two algorithms designed to reconstruct highly undersampled radial data were used to generate images for 16 time points: the Echo-Sharing (ES) and the CUrve Reconstruction via pca-based Linearization with Indirect Echo compensation (CURLIE) algorithm. T2 maps were generated via least-squares fitting or the Slice-resolved Extended Phase Graph (SEPG) model fitting. The CURLIE-SEPG algorithm accounts for the effect of indirect echoes. The algorithms were compared based on reproducibility, using Bland-Altman analysis on data from 7 healthy volunteers, and T2 accuracy (against a single-echo spin-echo technique) using phantoms. RESULTS: Both reconstruction algorithms generated in vivo images with high spatiotemporal resolution and showed good reproducibility. Mean T2 difference between repeated measures and the coefficient of repeatability were 0.58 ms and 2.97 for ES and 0.09 ms and 4.85 for CURLIE-SEPG. In vivo T2 estimates from ES were higher than those from CURLIE-SEPG. In phantoms, CURLIE-SEPG yielded more accurate T2s compared to reference values (error was 7.5-13.9% for ES and 0.6-2.1% for CURLIE-SEPG), consistent with the fact that CURLIE-SEPG compensates for the effects of indirect echoes. The potential of T2 mapping with CURLIE-SEPG is demonstrated in two subjects with known heart disease. Elevated T2 values were observed in areas of suspected pathology. CONCLUSIONS: DIR-RADFSE yielded TE images with high spatiotemporal resolution. Two algorithms for generating T2 maps from highly undersampled data were evaluated in terms of accuracy and reproducibility. Results showed that CURLIE-SEPG yields T2 estimates that are reproducible and more accurate than ES.

Reducing annotation burden in MR: A novel MR-contrast guided contrastive learning approach for image segmentation.

BACKGROUND: Contrastive learning, a successful form of representational learning, has shown promising results in pretraining deep learning (DL) models for downstream tasks. When working with limited annotation data, as in medical image segmentation tasks, learning domain-specific local representations can further improve the performance of DL models. PURPOSE: In this work, we extend the contrastive learning framework to utilize domain-specific contrast information from unlabeled Magnetic Resonance (MR) images to improve the performance of downstream MR image segmentation tasks in the presence of limited labeled data. METHODS: The contrast in MR images is controlled by underlying tissue properties (e.g., T1 or T2) and image acquisition parameters. We hypothesize that learning to discriminate local representations based on underlying tissue properties should improve subsequent segmentation tasks on MR images. We propose a novel constrained contrastive learning (CCL) strategy that uses tissue-specific information via a constraint map to define positive and negative local neighborhoods for contrastive learning, embedding this information in the representational space during pretraining. For a given MR contrast image, the proposed strategy uses local signal characteristics (constraint map) across a set of related multi-contrast MR images as a surrogate for underlying tissue information. We demonstrate the utility of the approach for downstream: (1) multi-organ segmentation tasks in T2-weighted images where a DL model learns T2 information with constraint maps from a set of 2D multi-echo T2-weighted images (n = 101) and (2) tumor segmentation tasks in multi-parametric images from the public brain tumor segmentation (BraTS) (n = 80) dataset where DL models learn T1 and T2 information from multi-parametric BraTS images. Performance is evaluated on downstream multi-label segmentation tasks with limited data in (1) T2-weighted images of the abdomen from an in-house Radial-T2 (Train/Test = 30/20), (2) public Cartesian-T2 (Train/Test = 6/12) dataset, and (3) multi-parametric MR images from the public brain tumor segmentation dataset (BraTS) (Train/Test = 40/50). The performance of the proposed CCL strategy is compared to state-of-the-art self-supervised contrastive learning techniques. In each task, a model is also trained using all available labeled data for supervised baseline performance. RESULTS: The proposed CCL strategy consistently yielded improved Dice scores, Precision, and Recall metrics, and reduced HD95 values across all segmentation tasks. We also observed performance comparable to the baseline with reduced annotation effort. The t-SNE visualization of features for T2-weighted images demonstrates its ability to embed T2 information in the representational space. On the BraTS dataset, we also observed that using an appropriate multi-contrast space to learn T1+T2, T1, or T2 information during pretraining further improved the performance of tumor segmentation tasks. CONCLUSIONS: Learning to embed tissue-specific information that controls MR image contrast with the proposed constrained contrastive learning improved the performance of DL models on subsequent segmentation tasks compared to conventional self-supervised contrastive learning techniques. The use of such domain-specific local representations could help understand, improve performance, and mitigate the scarcity of labeled data in MR image segmentation tasks.

T2 relaxometry with indirect echo compensation from highly undersampled data.

PURPOSE: To develop an algorithm for fast and accurate T2 estimation from highly undersampled multi-echo spin-echo data. METHODS: The algorithm combines a model-based reconstruction with a signal decay based on the slice-resolved extended phase graph (SEPG) model with the goal of reconstructing T2 maps from highly undersampled radial multi-echo spin-echo data with indirect echo compensation. To avoid problems associated with the nonlinearity of the SEPG model, principal component decomposition is used to linearize the signal model. The proposed CUrve Reconstruction via principal component-based Linearization with Indirect Echo compensation (CURLIE) algorithm is used to estimate T2 curves from highly undersampled data. T2 maps are obtained by fitting the curves to the SEPG model. RESULTS: Results on phantoms showed T2 biases (1.9% to 18.4%) when indirect echoes are not taken into account. The T2 biases were reduced (< 3.2%) when the CURLIE reconstruction was performed along with SEPG fitting even for high degrees of undersampling (4% sampled). Experiments in vivo for brain, liver, and heart followed the same trend as the phantoms. CONCLUSION: The CURLIE reconstruction combined with SEPG fitting enables accurate T2 estimation from highly undersampled multi-echo spin-echo radial data thus, yielding a fast T2 mapping method without errors caused by indirect echoes.

T2 mapping from highly undersampled data by reconstruction of principal component coefficient maps using compressed sensing.

Recently, there has been an increased interest in quantitative MR parameters to improve diagnosis and treatment. Parameter mapping requires multiple images acquired with different timings usually resulting in long acquisition times. While acquisition time can be reduced by acquiring undersampled data, obtaining accurate estimates of parameters from undersampled data is a challenging problem, in particular for structures with high spatial frequency content. In this work, principal component analysis is combined with a model-based algorithm to reconstruct maps of selected principal component coefficients from highly undersampled radial MRI data. This novel approach linearizes the cost function of the optimization problem yielding a more accurate and reliable estimation of MR parameter maps. The proposed algorithm--reconstruction of principal component coefficient maps using compressed sensing--is demonstrated in phantoms and in vivo and compared with two other algorithms previously developed for undersampled data.