Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk.

In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we performed secondary and exploratory analysis of blood samples from a randomized clinical trial (NCT02158897) and show that 3 FMD cycles in adult study participants are associated with reduced insulin resistance and other pre-diabetes markers, lower hepatic fat (as determined by magnetic resonance imaging) and increased lymphoid to myeloid ratio: an indicator of immune system age. Based on a validated measure of biological age predictive of morbidity and mortality, 3 FMD cycles were associated with a decrease of 2.5 years in median biological age, independent of weight loss. Nearly identical findings resulted from  a second clinical study (NCT04150159). Together these results provide initial support for beneficial effects of the FMD on multiple cardiometabolic risk factors and biomarkers of biological age.

Effects of Dietary Sugar Reduction on Biomarkers of Cardiometabolic Health in Latino Youth: Secondary Analyses from a Randomized Controlled Trial.

Pediatric obesity and cardiometabolic disease disproportionately impact minority communities. Sugar reduction is a promising prevention strategy with consistent cross-sectional associations of increased sugar consumption with unfavorable biomarkers of cardiometabolic disease. Few trials have tested the efficacy of pediatric sugar reduction interventions. Therefore, in a parallel-design trial, we randomized Latino youth with obesity (BMI ≥ 95th percentile) [n = 105; 14.8 years] to control (standard diet advice) or sugar reduction (clinical intervention with a goal of ≤10% of calories from free sugar) for 12-weeks. Outcomes included changes in glucose tolerance and its determinants as assessed by a 2-h frequently sample oral glucose tolerance test, fasting serum lipid profile (total cholesterol, HDL, LDL, triglycerides, cholesterol:HDL), and inflammatory markers (CRP, IL-6, TNF-α). Free sugar intake decreased in the intervention group compared to the control group [11.5% to 7.3% vs. 13.9% to 10.7% (% Energy), respectively, p = 0.02], but there were no effects on any outcome of interest (pall > 0.07). However, an exploratory analysis revealed that sugar reduction, independent of randomization, was associated with an improved Oral-disposition index (p < 0.001), triglycerides (p = 0.049), and TNF-α (p = 0.02). Dietary sugar reduction may have the potential to reduce chronic disease risks through improvements in beta-cell function, serum triglycerides, and inflammatory markers in Latino adolescents with obesity.

Submillimeter lung MRI at 0.55 T using balanced steady-state free precession with half-radial dual-echo readout (bSTAR).

PURPOSE: To demonstrate the feasibility of high-resolution morphologic lung MRI at 0.55 T using a free-breathing balanced steady-state free precession half-radial dual-echo imaging technique (bSTAR). METHODS: Self-gated free-breathing bSTAR (TE1 /TE2 /TR of 0.13/1.93/2.14 ms) lung imaging in five healthy volunteers and a patient with granulomatous lung disease was performed using a 0.55 T MR-scanner. A wobbling Archimedean spiral pole (WASP) trajectory was used to ensure a homogenous coverage of k-space over multiple breathing cycles. WASP uses short-duration interleaves randomly tilted by a small polar angle and rotated by a golden angle about the polar axis. Data were acquired continuously over 12:50 min. Respiratory-resolved images were reconstructed off-line using compressed sensing and retrospective self-gating. Reconstructions were performed with a nominal resolution of 0.9 mm and a reduced isotropic resolution of 1.75 mm corresponding to shorter simulated scan times of 8:34 and 4:17 min, respectively. Analysis of apparent SNR was performed in all volunteers and reconstruction settings. RESULTS: The technique provided artifact-free morphologic lung images in all subjects. The short TR of bSTAR in conjunction with a field strength of 0.55 T resulted in a complete mitigation of off-resonance artifacts in the chest. Mean SNR values in healthy lung parenchyma for the 12:50 min scan were 3.6 ± 0.8 and 24.9 ± 6.2 for 0.9 mm and 1.75 mm reconstructions, respectively. CONCLUSION: This study demonstrates the feasibility of morphologic lung MRI with a submillimeter isotropic spatial resolution in human subjects with bSTAR at 0.55 T.

Effects of B1+ Heterogeneity on Spin Echo-Based Liver Iron Estimates.

BACKGROUND: Liver iron concentration (LIC) measured by MRI has become the clinical reference standard for managing iron overload in chronically transfused patients. Transverse relaxivity (R2 or R2* ) measurements are converted to LIC units using empirically derived calibration curves. HYPOTHESIS: That flip angle (FA) error due to B1+ spatial heterogeneity causes significant LIC quantitation error. B1+ scale (b1 , [FAactual /FAspecified ]) variation is a major problem at 3 T which could reduce the accuracy of transverse relaxivity measurements. STUDY TYPE: Prospective. POPULATION: Forty-seven subjects with chronic transfusional iron overload undergoing clinically indicated LIC assessment. FIELD STRENGTH/SEQUENCE: 5 T/3 T dual-repetition time B1+ mapping sequence ASSESSMENT: We quantified the average/standard deviation b1 in the right and left lobes of the liver from B1+ maps acquired at 1.5 T and 3 T. The impact of b1 variation on spin echo LIC estimates was determined using a Monte Carlo model. STATISTICAL TESTS: Mean, median, and standard deviation in whole liver and right and left lobes; two-sided t-test between whole-liver b1 means. RESULTS: Average b1 within the liver was 99.3% ± 12.3% at 1.5 T versus 69.6% ± 14.6% at 3 T and was independent of iron burden (P < 0.05). Monte Carlo simulations demonstrated that b1 systematically increased R2 estimates at lower LIC (<~25 mg/g at 1.5 T, <~15 mg/g at 3 T) but flattened or even inverted the R2 -LIC relationship at higher LIC (≥~25 mg/g to 1.5 T, ≥~15 mg/g to 3 T); changes in the R2 -LIC relationship were symmetric with respect to over and under excitation and were similar at 1.5 T and 3 T (for the same R2 value). The R2* -LIC relationship was independent of b1 . CONCLUSION: Spin echo R2 measurement of LIC at 3 T is error-prone without correction for b1 errors. The impact of b1 error on current 1.5 T spin echo-based techniques for LIC quantification is large enough to introduce measurable intersubject variability but the in vivo effect size needs a dedicated validation study. TECHNICAL EFFICACY STAGE: 2.

Pseudo Test-Retest Evaluation of Millimeter-Resolution Whole-Brain Dynamic Contrast-enhanced MRI in Patients with High-Grade Glioma.

Background Advances in sub-Nyquist-sampled dynamic contrast-enhanced (DCE) MRI enable monitoring of brain tumors with millimeter resolution and whole-brain coverage. Such undersampled quantitative methods need careful characterization regarding achievable test-retest reproducibility. Purpose To demonstrate a fully automated high-resolution whole-brain DCE MRI pipeline with 30-fold sparse undersampling and estimate its reproducibility on the basis of reference regions of stable tissue types during multiple posttreatment time points by using longitudinal clinical images of high-grade glioma. Materials and Methods Two methods for sub-Nyquist-sampled DCE MRI were extended with automatic estimation of vascular input functions. Continuously acquired three-dimensional k-space data with ramped-up flip angles were partitioned to yield high-resolution, whole-brain tracer kinetic parameter maps with matched precontrast-agent T1 and M0 maps. Reproducibility was estimated in a retrospective study in participants with high-grade glioma, who underwent three consecutive standard-of-care examinations between December 2016 and April 2019. Coefficients of variation and reproducibility coefficients were reported for histogram statistics of the tracer kinetic parameters plasma volume fraction and volume transfer constant (Ktrans) on five healthy tissue types. Results The images from 13 participants (mean age ± standard deviation, 61 years ± 10; nine women) with high-grade glioma were evaluated. In healthy tissues, the protocol achieved a coefficient of variation less than 57% for median Ktrans, if Ktrans was estimated consecutively. The maximum reproducibility coefficient for median Ktrans was estimated to be at 0.06 min-1 for large or low-enhancing tissues and to be as high as 0.48 min-1 in smaller or strongly enhancing tissues. Conclusion A fully automated, sparsely sampled DCE MRI reconstruction with patient-specific vascular input function offered high spatial and temporal resolution and whole-brain coverage; in healthy tissues, the protocol estimated median volume transfer constant with maximum reproducibility coefficient of 0.06 min-1 in large, low-enhancing tissue regions and maximum reproducibility coefficient of less than 0.48 min-1 in smaller or more strongly enhancing tissue regions. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Lenkinski in this issue.

Sparse precontrast T1 mapping for high-resolution whole-brain DCE-MRI.

PURPOSE: To develop and evaluate an efficient precontrast T1 mapping technique suitable for quantitative high-resolution whole-brain dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI). METHODS: Variable flip angle (VFA) T1 mapping was considered that provides 1 × 1 × 2 mm3 resolution to match a recent high-resolution whole-brain DCE-MRI protocol. Seven FAs were logarithmically spaced from 1.5° to 15°. T1 and M0 maps were estimated using model-based reconstruction. This approach was evaluated using an anatomically realistic brain tumor digital reference object (DRO) with noise-mimicking 3T neuroimaging and fully sampled data acquired from one healthy volunteer. Methods were also applied on fourfold prospectively undersampled VFA data from 13 patients with high-grade gliomas. RESULTS: T1 -mapping precision decreased with undersampling factor R, althoughwhereas bias remained small before a critical R. In the noiseless DRO, T1 bias was <25 ms in white matter (WM) and <11 ms in brain tumor (BT). T1 standard deviation (SD) was <119.5 ms in WM (coefficient of variation [COV] ~11.0%) and <253.2 ms in BT (COV ~12.7%). In the noisy DRO, T1 bias was <50 ms in WM and <30 ms in BT. For R ≤ 10, T1 SD was <107.1 ms in WM (COV ~9.9%) and <240.9 ms in BT (COV ~12.1%). In the healthy subject, T1 bias was <30 ms for R ≤ 16. At R = 4, T1 SD was 171.4 ms (COV ~13.0%). In the prospective brain tumor study, T1 values were consistent with literature values in WM and BT. CONCLUSION: High-resolution whole-brain VFA T1 mapping is feasible with sparse sampling, supporting its use for quantitative DCE-MRI.

Liver Fat Reduction After Gastric Banding and Associations with Changes in Insulin Sensitivity and ß-Cell Function.

OBJECTIVE: The aim of this study was to examine the relationship between changes in liver fat and changes in insulin sensitivity and ß-cell function 2 years after gastric banding surgery. METHODS: Data included 23 adults with the surgery who had prediabetes or type 2 diabetes for less than 1 year and BMI 30 to 40 kg/m2 at baseline. Body adiposity measures including liver fat content (LFC), insulin sensitivity (M/I), and ß-cell responses (acute, steady-state, and arginine-stimulated maximum C-peptide) were assessed at baseline and 2 years after surgery. Regression models were used to assess associations adjusted for age and sex. RESULTS: Two years after surgery, all measures of body adiposity, LFC, fasting and 2-hour glucose, and hemoglobin A1c significantly decreased; M/I significantly increased; and ß-cell responses adjusted for M/I did not change significantly. Among adiposity measures, reduction in LFC had the strongest association with M/I increase (r = -0.61, P = 0.003). Among ß-cell measures, change in LFC was associated with change in acute C-peptide response to arginine at maximal glycemic potentiation adjusted for M/I (r = 0.66, P = 0.007). Significant reductions in glycemic measures and increase in M/I were observed in individuals with LFC loss >2.5%. CONCLUSIONS: Reduction in LFC after gastric banding surgery appears to be an important factor associated with long-term improvements in insulin sensitivity and glycemic profiles in adults with obesity and prediabetes or early type 2 diabetes.

Impact of (k,t) sampling on DCE MRI tracer kinetic parameter estimation in digital reference objects.

PURPOSE: To evaluate the impact of (k,t) data sampling on the variance of tracer-kinetic parameter (TK) estimation in high-resolution whole-brain dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) using digital reference objects. We study this in the context of TK model constraints, and in the absence of other constraints. METHODS: Three anatomically and physiologically realistic brain-tumor digital reference objects were generated. Data sampling strategies included uniform and variable density; zone-based, lattice, pseudo-random, and pseudo-radial; with 50-time frames and 4-fold to 25-fold undersampling. In all cases, we assume a fully sampled first time frame, and prior knowledge of the arterial input function. TK parameters were estimated by indirect estimation (i.e., image-time-series reconstruction followed by model fitting), and direct estimation from the under-sampled data. We evaluated methods based on the Cramér-Rao bound and Monte-Carlo simulations, over the range of signal-to-noise ratio (SNR) seen in clinical brain DCE-MRI. RESULTS: Lattice-based sampling provided the lowest SDs, followed by pseudo-random, pseudo-radial, and zone-based. This ranking was consistent for the Patlak and extended Tofts model. Pseudo-random sampling resulted in 19% higher averaged SD compared to lattice-based sampling. Zone-based sampling resulted in substantially higher SD at undersampling factors above 10. CRB analysis showed only a small difference between uniform and variable density for both lattice-based and pseudo-random sampling up to undersampling factors of 25. CONCLUSION: Lattice sampling provided the lowest SDs, although the differences between sampling schemes were not substantial at low undersampling factors. The differences between lattice-based and pseudo-random sampling strategies with both uniform and variable density were within the range of error induced by other sources, at up to 25-fold undersampling.

Efficient DCE-MRI Parameter and Uncertainty Estimation Using a Neural Network.

Quantitative DCE-MRI provides voxel-wise estimates of tracer-kinetic parameters that are valuable in the assessment of health and disease. These maps suffer from many known sources of variability. This variability is expensive to compute using current methods, and is typically not reported. Here, we demonstrate a novel approach for simultaneous estimation of tracer-kinetic parameters and their uncertainty due to intrinsic characteristics of the tracer-kinetic model, with very low computation time. We train and use a neural network to estimate the approximate joint posterior distribution of tracer-kinetic parameters. Uncertainties are estimated for each voxel and are specific to the patient, exam, and lesion. We demonstrate the methods' ability to produce accurate tracer-kinetic maps. We compare predicted parameter ranges with uncertainties introduced by noise and by differences in post-processing in a digital reference object. The predicted parameter ranges correlate well with tracer-kinetic parameter ranges observed across different noise realizations and regression algorithms. We also demonstrate the value of this approach to differentiate significant from insignificant changes in brain tumor pharmacokinetics over time. This is achieved by enforcing consistency in resolving model singularities in the applied tracer-kinetic model.

Tracer kinetic models as temporal constraints during brain tumor DCE-MRI reconstruction.

PURPOSE: To apply tracer kinetic models as temporal constraints during reconstruction of under-sampled brain tumor dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI). METHODS: A library of concentration vs time profiles is simulated for a range of physiological kinetic parameters. The library is reduced to a dictionary of temporal bases, where each profile is approximated by a sparse linear combination of the bases. Image reconstruction is formulated as estimation of concentration profiles and sparse model coefficients with a fixed sparsity level. Simulations are performed to evaluate modeling error, and error statistics in kinetic parameter estimation in presence of noise. Retrospective under-sampling experiments are performed on a brain tumor DCE digital reference object (DRO), and 12 brain tumor in-vivo 3T datasets. The performances of the proposed under-sampled reconstruction scheme and an existing compressed sensing-based temporal finite-difference (tFD) under-sampled reconstruction were compared against the fully sampled inverse Fourier Transform-based reconstruction. RESULTS: Simulations demonstrate that sparsity levels of 2 and 3 model the library profiles from the Patlak and extended Tofts-Kety (ETK) models, respectively. Noise sensitivity analysis showed equivalent kinetic parameter estimation error statistics from noisy concentration profiles, and model approximated profiles. DRO-based experiments showed good fidelity in recovery of kinetic maps from 20-fold under-sampled data. In-vivo experiments demonstrated reduced bias and uncertainty in kinetic mapping with the proposed approach compared to tFD at under-sampled reduction factors >= 20. CONCLUSIONS: Tracer kinetic models can be applied as temporal constraints during brain tumor DCE-MRI reconstruction. The proposed under-sampled scheme resulted in model parameter estimates less biased with respect to conventional fully sampled DCE MRI reconstructions and parameter estimation. The approach is flexible, can use nonlinear kinetic models, and does not require tuning of regularization parameters.

Non-contrast assessment of microvascular integrity using arterial spin labeled cardiovascular magnetic resonance in a porcine model of acute myocardial infarction.

BACKGROUND: Following acute myocardial infarction (AMI), microvascular integrity and function may be compromised as a result of microvascular obstruction (MVO) and vasodilator dysfunction. It has been observed that both infarcted and remote myocardial territories may exhibit impaired myocardial blood flow (MBF) patterns associated with an abnormal vasodilator response. Arterial spin labeled (ASL) CMR is a novel non-contrast technique that can quantitatively measure MBF. This study investigates the feasibility of ASL-CMR to assess MVO and vasodilator response in swine. METHODS: Thirty-one swine were included in this study. Resting ASL-CMR was performed on 24 healthy swine (baseline group). A subset of 13 swine from the baseline group underwent stress ASL-CMR to assess vasodilator response. Fifteen swine were subjected to a 90-min left anterior descending (LAD) coronary artery occlusion followed by reperfusion. Resting ASL-CMR was performed post-AMI at 1-2 days (N = 9, of which 6 were from the baseline group), 1-2 weeks (N = 8, of which 4 were from the day 1-2 group), and 4 weeks (N = 4, of which 2 were from the week 1-2 group). Resting first-pass CMR and late gadolinium enhancement (LGE) were performed post-AMI for reference. RESULTS: At rest, regional MBF and physiological noise measured from ASL-CMR were 1.08 ± 0.62 and 0.15 ± 0.10 ml/g/min, respectively. Regional MBF increased to 1.47 ± 0.62 ml/g/min with dipyridamole vasodilation (P < 0.001). Significant reduction in MBF was found in the infarcted region 1-2 days, 1-2 weeks, and 4 weeks post-AMI compared to baseline (P < 0.03). This was consistent with perfusion deficit seen on first-pass CMR and with MVO seen on LGE. There were no significant differences between measured MBF in the remote regions pre and post-AMI (P > 0.60). CONCLUSIONS: ASL-CMR can assess vasodilator response in healthy swine and detect significant reduction in regional MBF at rest following AMI. ASL-CMR is an alternative to gadolinium-based techniques for assessment of MVO and microvascular integrity within infarcted, as well as salvageable and remote myocardium. This has the potential to provide early indications of adverse remodeling processes post-ischemia.

Joint arterial input function and tracer kinetic parameter estimation from undersampled dynamic contrast-enhanced MRI using a model consistency constraint.

PURPOSE: To develop and evaluate a model-based reconstruction framework for joint arterial input function (AIF) and kinetic parameter estimation from undersampled brain tumor dynamic contrast-enhanced MRI (DCE-MRI) data. METHODS: The proposed method poses the tracer-kinetic (TK) model as a model consistency constraint, enabling the flexible inclusion of different TK models and TK solvers, and the joint estimation of the AIF. The proposed method is evaluated using an anatomic realistic digital reference object (DRO), and nine retrospectively down-sampled brain tumor DCE-MRI datasets. We also demonstrate application to 30-fold prospectively undersampled brain tumor DCE-MRI. RESULTS: In DRO studies with up to 60-fold undersampling, the proposed method provided TK maps with low error that were comparable to fully sampled data and were demonstrated to be compatible with a third-party TK solver. In retrospective undersampling studies, this method provided patient-specific AIF with normalized root mean-squared-error (normalized by the 90th percentile value) less than 8% at up to 100-fold undersampling. In the 30-fold undersampled prospective study, the proposed method provided high-resolution whole-brain TK maps and patient-specific AIF. CONCLUSION: The proposed model-based DCE-MRI reconstruction enables the use of different TK solvers with a model consistency constraint and enables joint estimation of patient-specific AIF. TK maps and patient-specific AIF with high fidelity can be reconstructed at up to 100-fold undersampling in k,t-space. Magn Reson Med 79:2804-2815, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Assessment of segmental myocardial blood flow and myocardial perfusion reserve by adenosine-stress myocardial arterial spin labeling perfusion imaging.

PURPOSE: To determine the feasibility of measuring increases in myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) on a per-segment basis using arterial spin labeled (ASL) magnetic resonance imaging (MRI) with adenosine vasodilator stress in normal human myocardium. MATERIALS AND METHODS: Myocardial ASL scans at rest and during adenosine infusion were incorporated into a routine 3T MR adenosine-induced vasodilator stress protocol and were performed in 10 healthy human volunteers. Myocardial ASL was performed using single-gated flow-sensitive alternating inversion recovery (FAIR) tagging and balanced steady-state free precession (bSSFP) imaging at 3T. A T2 -prep blood oxygen level-dependent (BOLD) SSFP sequence was used to concurrently assess segmental myocardial oxygenation with BOLD signal intensity (SI) percent change in the same subjects. RESULTS: There was a statistically significant difference between MBF measured by ASL at rest (1.75 ± 0.86 ml/g/min) compared to adenosine stress (4.58 ± 2.14 ml/g/min) for all wall segments (P < 0.0001), yielding a per-segment MPR of 3.02 ± 1.51. When wall segments were divided into specific segmental myocardial perfusion territories (ie, anteroseptal, anterior, anterolateral, inferolateral, inferior, and inferoseptal), the differences between rest and stress regional MBF for each territory remained consistently statistically significant (P < 0.001) after correcting for multiple comparisons. CONCLUSION: This study demonstrates the feasibility of measuring MBF and MPR on a segmental basis by single-gated cardiac ASL in normal volunteers. Second, this study demonstrates the feasibility of performing the ASL sequence and T2 -prepared SSFP BOLD imaging during a single adenosine infusion. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:413-420.

A fast and flexible MRI system for the study of dynamic vocal tract shaping.

PURPOSE: The aim of this work was to develop and evaluate an MRI-based system for study of dynamic vocal tract shaping during speech production, which provides high spatial and temporal resolution. METHODS: The proposed system utilizes (a) custom eight-channel upper airway coils that have high sensitivity to upper airway regions of interest, (b) two-dimensional golden angle spiral gradient echo acquisition, (c) on-the-fly view-sharing reconstruction, and (d) off-line temporal finite difference constrained reconstruction. The system also provides simultaneous noise-cancelled and temporally aligned audio. The system is evaluated in 3 healthy volunteers, and 1 tongue cancer patient, with a broad range of speech tasks. RESULTS: We report spatiotemporal resolutions of 2.4 × 2.4 mm2 every 12 ms for single-slice imaging, and 2.4 × 2.4 mm2 every 36 ms for three-slice imaging, which reflects roughly 7-fold acceleration over Nyquist sampling. This system demonstrates improved temporal fidelity in capturing rapid vocal tract shaping for tasks, such as producing consonant clusters in speech, and beat-boxing sounds. Novel acoustic-articulatory analysis was also demonstrated. CONCLUSION: A synergistic combination of custom coils, spiral acquisitions, and constrained reconstruction enables visualization of rapid speech with high spatiotemporal resolution in multiple planes. Magn Reson Med 77:112-125, 2017. © 2016 Wiley Periodicals, Inc.

Direct estimation of tracer-kinetic parameter maps from highly undersampled brain dynamic contrast enhanced MRI.

PURPOSE: The purpose of this work was to develop and evaluate a T1 -weighted dynamic contrast enhanced (DCE) MRI methodology where tracer-kinetic (TK) parameter maps are directly estimated from undersampled (k,t)-space data. THEORY AND METHODS: The proposed reconstruction involves solving a nonlinear least squares optimization problem that includes explicit use of a full forward model to convert parameter maps to (k,t)-space, utilizing the Patlak TK model. The proposed scheme is compared against an indirect method that creates intermediate images by parallel imaging and compressed sensing before to TK modeling. Thirteen fully sampled brain tumor DCE-MRI scans with 5-second temporal resolution are retrospectively undersampled at rates R = 20, 40, 60, 80, and 100 for each dynamic frame. TK maps are quantitatively compared based on root mean-squared-error (rMSE) and Bland-Altman analysis. The approach is also applied to four prospectively R = 30 undersampled whole-brain DCE-MRI data sets. RESULTS: In the retrospective study, the proposed method performed statistically better than indirect method at R ≥ 80 for all 13 cases. This approach provided restoration of TK parameter values with less errors in tumor regions of interest, an improvement compared to a state-of-the-art indirect method. Applied prospectively, the proposed method provided whole-brain, high-resolution TK maps with good image quality. CONCLUSION: Model-based direct estimation of TK maps from k,t-space DCE-MRI data is feasible and is compatible up to 100-fold undersampling. Magn Reson Med 78:1566-1578, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

GOCART: GOlden-angle CArtesian randomized time-resolved 3D MRI.

PURPOSE: To develop and evaluate a novel 3D Cartesian sampling scheme which is well suited for time-resolved 3D MRI using parallel imaging and compressed sensing. METHODS: The proposed sampling scheme, termed GOlden-angle CArtesian Randomized Time-resolved (GOCART) 3D MRI, is based on golden angle (GA) Cartesian sampling, with random sampling of the ky-kz phase encode locations along each Cartesian radial spoke. This method was evaluated in conjunction with constrained reconstruction of retrospectively and prospectively undersampled in-vivo dynamic contrast enhanced (DCE) MRI data and simulated phantom data. RESULTS: In in-vivo retrospective studies and phantom simulations, images reconstructed from phase encodes defined by GOCART were equal to or superior to those with Poisson disc or GA sampling schemes. Typical GOCART sampling tables were generated in <100ms. GOCART has also been successfully utilized prospectively to produce clinically valuable whole-brain DCE-MRI images. CONCLUSION: GOCART is a practical and efficient sampling scheme for time-resolved 3D MRI. It shows great potential for highly accelerated DCE-MRI and is well suited to modern reconstruction methods such as parallel imaging and compressed sensing.

Highly accelerated dynamic contrast enhanced imaging.

PURPOSE: Dynamic contrast-enhanced imaging provides unique physiological information, notably the endothelial permeability (K(trans)), and may improve the diagnosis and management of multiple pathologies. Current acquisition methods provide limited spatial-temporal resolution and field-of-view, often preventing characterization of the entire pathology and precluding measurement of the arterial input function. We present a method for highly accelerated dynamic imaging and demonstrate its utility for dynamic contrast-enhanced modeling. METHODS: We propose a novel Poisson ellipsoid sampling scheme and enforce multiple spatial and temporal l1-norm constraints during image reconstruction. Retrospective and prospective analyses were performed to validate the approach. RESULTS: Retrospectively, no mean bias or diverging trend was observed as the acceleration rate was increased from 3× to 18×; less than 10% error was measured in K(trans) at any individual rates in this range. Prospectively accelerated images at a rate of 36× enabled full brain coverage with 0.94 × 0.94 × 1.9 mm(3) spatial and 4.1 s temporal resolutions. Images showed no visible degradation and provided accurate K(trans) values when compared to a clinical population. CONCLUSION: Highly accelerated dynamic MRI using compressed sensing and parallel imaging provides accurate permeability modeling and enables full brain, high resolution acquisitions.

Arterial spin labeled CMR detects clinically relevant increase in myocardial blood flow with vasodilation.

OBJECTIVES: This study sought to determine whether arterial spin labeled (ASL) cardiac magnetic resonance (CMR) is capable of detecting clinically relevant increases in regional myocardial blood flow (MBF) with vasodilator stress testing in human myocardium. BACKGROUND: Measurements of regional myocardial perfusion at rest and during vasodilatation are used to determine perfusion reserve, which indicates the presence and distribution of myocardial ischemia. ASL CMR is a perfusion imaging technique that does not require any contrast agents, and is therefore safe for use in patients with end-stage renal disease, and capable of repeated or continuous measurement. METHODS: Myocardial ASL scans at rest and during adenosine infusion were incorporated into a routine CMR adenosine induced vasodilator stress protocol and was performed in 29 patients. Patients who were suspected of having ischemic heart disease based on first-pass imaging also underwent x-ray angiography. Myocardial ASL was performed using double-gated flow-sensitive alternating inversion recovery tagging and balanced steady-state free precession imaging at 3-T. RESULTS: Sixteen patients were found to be normal and 13 patients were found to have visible perfusion defect based on first-pass CMR using intravenous gadolinium chelate. In the normal subjects, there was a statistically significant difference between MBF measured by ASL during adenosine infusion (3.67 ± 1.36 ml/g/min), compared to at rest (0.97 ± 0.64 ml/g/min), with p < 0.0001. There was also a statistically significant difference in perfusion reserve (MBF(stress)/MBF(rest)) between normal myocardial segments (3.18 ± 1.54) and the most ischemic segments in the patients with coronary artery disease identified by x-ray angiography (1.44 ± 0.97), with p = 0.0011. CONCLUSIONS: This study indicates that myocardial ASL is capable of detecting clinically relevant increases in MBF with vasodilatation and has the potential to identify myocardial ischemia.

Differential computed tomographic attenuation of metabolically active and inactive adipose tissues: preliminary findings.

This study investigates differences in computed tomography Hounsfield units between metabolically active (brown fat) and inactive adipose tissues (white fat) due to variations in their densities. Positron emission and computed tomographic data from 101 pediatric and adolescent patients were analyzed. Regions of metabolically active and inactive adipose tissues were identified, and standard uptake values and Hounsfield units were measured. Hounsfield units of active brown fat were more positive (P < 0.001) than inactive fat (-62.4 ± 5.3 vs -86.7 ± 7.0) and the difference was observed in both males and females.

High-resolution real-time spiral MRI for guiding vascular interventions in a rabbit model at 1.5 T.

PURPOSE: To study the feasibility of a combined high spatial and temporal resolution real-time spiral MRI sequence for guiding coronary-sized vascular interventions. MATERIALS AND METHODS: Eight New Zealand White rabbits (four normal and four with a surgically-created stenosis in the abdominal aorta) were studied. A real-time interactive spiral MRI sequence combining 1.1 x 1.1 mm(2) in-plane resolution and 189-msec total image acquisition time was used to image all phases of an interventional procedure (i.e., guidewire placement, balloon angioplasty, and stenting) in the rabbit aorta using coronary-sized devices on a 1.5 T MRI system. RESULTS: Real-time spiral MRI identified all rabbit aortic stenoses and provided high-temporal-resolution visualization of guide-wires crossing the stenoses in all animals. Angioplasty balloon dilatation and deployment of coronary-sized copper stents in the rabbit aorta were also successfully imaged by real-time spiral MRI. CONCLUSION: Combining high spatial and temporal resolution with spiral MRI allows real-time MR-guided vascular intervention using coronary-sized devices in a rabbit model. This is a promising approach for guiding coronary interventions.