Intravoxel incoherent motion (IVIM)-derived perfusion fraction mapping for the visual evaluation of MR-guided high intensity focused ultrasound (MR-HIFU) ablation of uterine fibroids.

BACKGROUND: A method for periprocedural contrast agent-free visualization of uterine fibroid perfusion could potentially shorten magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) treatment times and improve outcomes. Our goal was to test feasibility of perfusion fraction mapping by intravoxel incoherent motion (IVIM) modeling using diffusion-weighted MRI as method for visual evaluation of MR-HIFU treatment progression. METHODS: Conventional and T2-corrected IVIM-derived perfusion fraction maps were retrospectively calculated by applying two fitting methods to diffusion-weighted MRI data (b = 0, 50, 100, 200, 400, 600 and 800 s/mm2 at 1.5 T) from forty-four premenopausal women who underwent MR-HIFU ablation treatment of uterine fibroids. Contrast in perfusion fraction maps between areas with low perfusion fraction and surrounding tissue in the target uterine fibroid immediately following MR-HIFU treatment was evaluated. Additionally, the Dice similarity coefficient (DSC) was calculated between delineated areas with low IVIM-derived perfusion fraction and hypoperfusion based on CE-T1w. RESULTS: Average perfusion fraction ranged between 0.068 and 0.083 in areas with low perfusion fraction based on visual assessment, and between 0.256 and 0.335 in surrounding tissues (all p < 0.001). DSCs ranged from 0.714 to 0.734 between areas with low perfusion fraction and the CE-T1w derived non-perfused areas, with excellent intraobserver reliability of the delineated areas (ICC 0.97). CONCLUSION: The MR-HIFU treatment effect in uterine fibroids can be visualized using IVIM perfusion fraction mapping, in moderate concordance with contrast enhanced MRI. IVIM perfusion fraction mapping has therefore the potential to serve as a contrast agent-free imaging method to visualize the MR-HIFU treatment progression in uterine fibroids.

Evaluation of Neuromuscular Diseases and Complaints by Quantitative Muscle MRI.

Background: Quantitative muscle MRI (qMRI) is a promising tool for evaluating and monitoring neuromuscular disorders (NMD). However, the application of different imaging protocols and processing pipelines restricts comparison between patient cohorts and disorders. In this qMRI study, we aim to compare dystrophic (limb-girdle muscular dystrophy), inflammatory (inclusion body myositis), and metabolic myopathy (Pompe disease) as well as patients with post-COVID-19 conditions suffering from myalgia to healthy controls. Methods: Ten subjects of each group underwent a 3T lower extremity muscle MRI, including a multi-echo, gradient-echo, Dixon-based sequence, a multi-echo, spin-echo (MESE) T2 mapping sequence, and a spin-echo EPI diffusion-weighted sequence. Furthermore, the following clinical assessments were performed: Quick Motor Function Measure, patient questionnaires for daily life activities, and 6-min walking distance. Results: Different involvement patterns of conspicuous qMRI parameters for different NMDs were observed. qMRI metrics correlated significantly with clinical assessments. Conclusions: qMRI metrics are suitable for evaluating patients with NMD since they show differences in muscular involvement in different NMDs and correlate with clinical assessments. Still, standardisation of acquisition and processing is needed for broad clinical use.

31 P MR Spectroscopy in the Pancreas: Repeatability, Comparison With Liver, and Pilot Pancreatic Cancer Data.

BACKGROUND: Non-invasive evaluation of phosphomonoesters (PMEs) and phosphodiesters (PDEs) by 31-phosphorus MR spectroscopy (31 P MRS) may have potential for early therapy (non-)response assessment in cancer. However, 31 P MRS has not yet been applied to investigate the human pancreas in vivo. PURPOSE: To assess the technical feasibility and repeatability of 31 P MR spectroscopic imaging (MRSI) of the pancreas, compare 31 P metabolite levels between pancreas and liver, and determine the feasibility of 31 P MRSI in pancreatic cancer. STUDY TYPE: Prospective cohort study. POPULATION: 10 healthy subjects (age 34 ± 12 years, four females) and one patient (73-year-old female) with pancreatic ductal adenocarcinoma. FIELD STRENGTH/SEQUENCE: 7-T, 31 P FID-MRSI, 1 H gradient-echo MRI. ASSESSMENT: 31 P FID-MRSI of the abdomen (including the pancreas and liver) was performed with a nominal voxel size of 20 mm (isotropic). For repeatability measurements, healthy subjects were scanned twice on the same day. The patient was only scanned once. Test-retest 31 P MRSI data of pancreas and liver voxels (segmented on 1 H MRI) of healthy subjects were quantified by fitting in the time domain and signal amplitudes were normalized to γ-adenosine triphosphate. In addition, the PME/PDE ratio was calculated. Metabolite levels were averaged over all voxels within the pancreas, right liver lobe and left liver lobe, respectively. STATISTICAL TESTS: Repeatability of test-retest data from healthy pancreas was assessed by paired t-tests, Bland-Altman analyses, and calculation of the intrasubject coefficients of variation (CoVs). Significant differences between healthy pancreas and right and left liver lobes were assessed with a two-way analysis of variance (ANOVA) for repeated measures. A P-value <0.05 was considered statistically significant. RESULTS: The intrasubject CoVs for PME, PDE, and PME/PDE in healthy pancreas were below 20%. Furthermore, PME and PME/PDE were significantly higher in pancreas compared to liver. In the patient with pancreatic cancer, qualitatively, elevated relative PME signals were observed in comparison with healthy pancreas. DATA CONCLUSION: In vivo 31 P MRSI of the human healthy pancreas and in pancreatic cancer may be feasible at 7 T. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Leisure time physical activity is associated with improved diastolic heart function and is partly mediated by unsupervised quantified metabolic health.

Objectives: To investigate the association between leisure time physical activity (LTPA) and MRI-based diastolic function and the mediating role of metabolic health. Methods: This cross-sectional analysis comprised 901 participants (46% women, mean age (SD): 56 (6) years (The Netherlands, 2008-2012)). LTPA was assessed via questionnaire, quantified in metabolic equivalent of tasks (METs)-minutes per week and participants underwent abdominal and cardiovascular MRI. Confirmatory factor analysis was used to construct the metabolic load factor. Piecewise structural equation model with adjustments for confounders was used to determine associations between LTPA and diastolic function and the mediating effect of metabolic load. Results: Significant differences in mitral early/late peak filling rate (E/A) ratio per SD of LTPA (men=1999, women=1870 MET-min/week) of 0.18, (95% CI= 0.03 to 0.33, p=0.021) were observed in men, but not in women: -0.01 (-0.01 to 0.34, p=0.058). Difference in deceleration time of mitral early filling (E-DT) was 0.13 (0.01 to 0.24, p=0.030) in men and 0.17 (0.05 to 0.28, p=0.005) in women. Metabolic load, including MRI-based visceral and subcutaneous adipose tissue, fasting glucose, high-density lipoprotein cholesterol and triglycerides, mediated these associations as follows: E/A-ratio of 0.030 (0.000 to 0.067, 19% mediated, p=0.047) in men but not in women: 0.058 (0.027 to 0.089, p<0.001) and E-DT not in men 0.004 (-0.012 to 0.021, p=0.602) but did in women 0.044 (0.013 to 0.057, 27% mediated, p=0.006). Conclusions: A larger amount of LTPA was associated with improved diastolic function where confirmatory factor analysis-based metabolic load partly mediated this effect. Future studies should assess whether improving indicators of metabolic load alongside LTPA will benefit healthy diastolic function even more.

Pre-participation screenings frequently miss occult cardiovascular conditions in apparently healthy male middle-aged first-time marathon runners.

INTRODUCTION: The optimal pre-participation screening strategy to identify athletes at risk for exercise-induced cardiovascular events is unknown. We therefore aimed to compare the American College of Sports Medicine (ACSM) and European Society of Cardiology (ESC) pre-participation screening strategies against extensive cardiovascular evaluations in identifying high-risk individuals among 35-50-year-old apparently healthy men. METHODS: We applied ACSM and ESC pre-participation screenings to 25 men participating in a study on first-time marathon running. We compared screening outcomes against medical history, physical examination, electrocardiography, blood tests, echocardiography, cardiopulmonary exercise testing, and magnetic resonance imaging. RESULTS: ACSM screening classified all participants as 'medical clearance not necessary'. ESC screening classified two participants as 'high-risk'. Extensive cardiovascular evaluations revealed ≥1 minor abnormality and/or cardiovascular condition in 17 participants, including three subjects with mitral regurgitation and one with a small atrial septal defect. Eleven participants had dyslipidaemia, six had hypertension, and two had premature atherosclerosis. Ultimately, three (12%) subjects had a serious cardiovascular condition warranting sports restrictions: aortic aneurysm, hypertrophic cardiomyopathy (HCM), and myocardial fibrosis post-myocarditis. Of these three participants, only one had been identified as 'high-risk' by the ESC screening (for dyslipidaemia, not HCM) and none by the ACSM screening. CONCLUSION: Numerous occult cardiovascular conditions are missed when applying current ACSM/ESC screening strategies to apparently healthy middle-aged men engaging in their first high-intensity endurance sports event.

A three-dimensional Magnetic Resonance Spin Tomography in Time-domain protocol for high-resolution multiparametric quantitative magnetic resonance imaging.

Magnetic Resonance Spin TomogrAphy in Time-domain (MR-STAT) is a multiparametric quantitative MR framework, which allows for simultaneously acquiring quantitative tissue parameters such as T1, T2, and proton density from one single short scan. A typical two-dimensional (2D) MR-STAT acquisition uses a gradient-spoiled, gradient-echo sequence with a slowly varying RF flip-angle train and Cartesian readouts, and the quantitative tissue maps are reconstructed by an iterative, model-based optimization algorithm. In this work, we design a three-dimensional (3D) MR-STAT framework based on previous 2D work, in order to achieve better image signal-to-noise ratio, higher though-plane resolution, and better tissue characterization. Specifically, we design a 7-min, high-resolution 3D MR-STAT sequence, and the corresponding two-step reconstruction algorithm for the large-scale dataset. To reduce the long acquisition time, Cartesian undersampling strategies such as SENSE are adopted in our transient-state quantitative framework. To reduce the computational burden, a data-splitting scheme is designed for decoupling the 3D reconstruction problem into independent 2D reconstructions. The proposed 3D framework is validated by numerical simulations, phantom experiments, and in vivo experiments. High-quality knee quantitative maps with 0.8 × 0.8 × 1.5 mm3 resolution and bilateral lower leg maps with 1.6 mm isotropic resolution can be acquired using the proposed 7-min acquisition sequence and the 3-min-per-slice decoupled reconstruction algorithm. The proposed 3D MR-STAT framework could have wide clinical applications in the future.

A 3-slice cardiac quantitative native and post-contrast T1 and T2 MRI protocol requiring only four BHs using a 72-channel receive array coil.

Introduction: Current practice to obtain left ventricular (LV) native and post-contrast T1 and T2 comprises single-slice readouts with multiple breath-holds (BHs). We propose a multi-slice parallel-imaging approach with a 72-channel receive-array to reduce BHs and demonstrate this in healthy subjects and hypertrophic cardiomyopathy (HCM) patients. Methods: A T1/T2 phantom was scanned at 3 T using a 16-channel and a novel 72-channel coil to assess the impact of different coils and acceleration factors on relaxation times. 16-18 healthy participants (8 female, age 28.4 ± 5.1 years) and 3 HCM patients (3 male, age 55.3 ± 4.2 years) underwent cardiac-MRI with the 72-channel coil, using a Modified Look-Locker scan with a shared inversion pulse across 3 slices and a Gradient-Spin-Echo scan. Acceleration was done by sensitivity encoding (SENSE) with accelerations 2, 4, and 6. LV T1 and T2 values were analyzed globally, per slice, and in 16 segments, with SENSE = 2 as the reference. Results: The phantom scans revealed no bias between coils and acceleration factors for T1 or T2, except for T2 with SENSE = 2, which resulted in a bias of 8.0 ± 6.7 ms (p < 0.001) between coils. SENSE = 4 and 6 enabled T1 mapping of three slices in a single BH, and T2 mapping of three slices within two BHs. In healthy subjects, T1 and T2 values varied. We found an average overestimation of T1 in 3 slices of 25 ± 87 ms for SENSE = 4 and 30 ± 103 ms using SENSE = 6, as compared to SENSE = 2. Acceleration resulted in decreased signal-to-noise; however, visually insignificant and without increased incidence of SENSE-artifacts. T2 was overestimated by 2.1 ± 5.0 ms for SENSE = 4 and 6.4 ± 9.7 ms using SENSE = 6, as compared to SENSE = 2. Native and post-contrast T1 measurements with SENSE = 4 and ECV quantification in HCM patients was successful. Conclusion: The 72-channel receiver-array coil with SENSE = 4 and 6, enabled LV-tissue characterization in three slices. Pre- and post-contrast T1 maps were obtained in a single BH, while T2 required two BHs.

Muscle diffusion MRI reveals autophagic buildup in a mouse model for Pompe disease.

Quantitative muscle MRI is increasingly important in the non-invasive evaluation of neuromuscular disorders and their progression. Underlying histopathotological alterations, leading to changes in qMRI parameters are incompletely unraveled. Early microstructural differences of unknown origin reflected by Diffusion MRI in non-fat infiltrated muscles were detected in Pompe patients. This study employed a longitudinal approach with a Pompe disease mouse model to investigate the histopathological basis of these changes. Monthly scans of Pompe (Gaa6neo/6neo) and wildtype mice (age 1-8 months) were conducted using diffusion MRI, T2-mapping, and Dixon-based water-fat imaging on a 7 T scanner. Immunofluorescence studies on quadriceps muscles were analyzed for lysosomal accumulations and autophagic buildup and correlated with MRI outcome measures. Fat fraction and water-T2 did not differ between groups and remained stable over time. In Pompe mice, fractional anisotropy increased, while mean diffusivity (MD) and radial diffusivity (RD) decreased in all observed muscles. Autophagic marker and muscle fibre diameter revealed significant negative correlations with reduced RD and MD, while lysosomal marker did not show any change or correlation. Using qMRI, we showed diffusion changes in muscles of presymptomatic Pompe mice without fat-infiltrated muscles and correlated them to autophagic markers and fibre diameter, indicating diffusion MRI reveals autophagic buildup.

Diffusion tensor imaging and quantitative T2 mapping to monitor muscle recovery following hamstring injury.

MRI examinations are accurate for diagnosing sports-related acute hamstring injuries. However, sensitive imaging methods for assessing recovery of these injuries are lacking. Diffusion tensor imaging (DTI) and quantitative T2 (qT2) mapping have both shown promise for assessing recovery of muscle micro trauma and exercise effects. The purpose of this study was to explore the potential of DTI and qT2 mapping for monitoring the muscle recovery processes after acute hamstring injury. In this prospective study, athletes with an acute hamstring injury underwent a 3-T MRI examination of the injured and contralateral hamstrings including DTI and qT2 measurements at three time points: (1) within 1 week after sustaining the injury, (2) 2 weeks after time point 1, and (3) return to play (RTP). A linear mixed model was used for time-effect analysis and paired t-tests for the detection of differences between injured and uninjured muscles. Forty-one athletes (age 27.8 ± 7 years; two females and 39 males) were included. Mean RTP time was 50 (range 12-169) days. A significant time effect was found for mean diffusivity, radial diffusivity, and the second and third eigenvalues (p ≤ 0.001) in the injured muscles. Fractional anisotropy (p = 0.40), first eigenvalue (p = 0.02), and qT2 (p = 0.61) showed no significant time effect. All DTI indices, except for fractional anisotropy, were significantly elevated compared with control muscles right after the injury (p < 0.001). Values normalized during the recovery period, with no significant differences between control and injured muscles at RTP (p values ranged from 0.08 to 0.51). Mean qT2 relaxation times in injured muscles were not significantly elevated compared with control muscles at any time point (p > 0.04). In conclusion, DTI can be used to monitor recovery after an acute hamstring injury. Future work should explore the potential of DTI indices to predict RTP and recovery times in athletes after an acute strain injury.

Effect of two eccentric hamstring exercises on muscle architectural characteristics assessed with diffusion tensor MRI.

OBJECTIVES: To evaluate the effect of a Nordic hamstring exercise or Diver hamstring exercise intervention on biceps femoris long head, semitendinosus and semimembranosus muscle's fascicle length and orientation through diffusion tensor imaging (DTI) with magnetic resonance imaging. METHODS: In this three-arm, single-center, randomized controlled trial, injury-free male basketball players were randomly assigned to a Nordic, Diver hamstring exercise intervention or control group. The primary outcome was the DTI-derived fascicle length and orientation of muscles over 12 weeks. RESULTS: Fifty-three participants were included for analysis (mean age 22 ± 7 years). Fascicle length in the semitendinosus over 12 weeks significantly increased in the Nordic-group (mean [M]: 20.8 mm, 95% confidence interval [95% CI]: 7.8 to 33.8) compared with the Control-group (M: 0.9 mm, 95% CI: -7.1 to 8.9), mean between-groups difference: 19.9 mm, 95% CI: 1.9 to 37.9, p = 0.026. Fascicle orientation in the biceps femoris long head over 12 weeks significantly decreased in the Diver-group (mean: -2.6°, 95% CI: -4.1 to -1.0) compared with the Control-group (mean: -0.2°, 95% CI: -1.4 to 1.0), mean between-groups difference: -2.4°, 95% CI: -4.7 to -0.1, p = 0.039. CONCLUSION: The Nordic hamstring exercise intervention did significantly increase the fascicle length of the semitendinosus and the Diver hamstring exercise intervention did significantly change the orientation of fascicles of the biceps femoris long head. As both exercises are complementary to each other, the combination is relevant for preventing hamstring injuries.

In vivo phosphorus magnetic resonance spectroscopic imaging of the whole human liver at 7 T using a phosphorus whole-body transmit coil and 16-channel receive array: Repeatability and effects of principal component analysis-based denoising.

Quantitative three-dimensional (3D) imaging of phosphorus (31 P) metabolites is potentially a promising technique with which to assess the progression of liver disease and monitor therapy response. However, 31 P magnetic resonance spectroscopy has a low sensitivity and commonly used 31 P surface coils do not provide full coverage of the liver. This study aimed to overcome these limitations by using a 31 P whole-body transmit coil in combination with a 16-channel 31 P receive array at 7 T. Using this setup, we determined the repeatability of whole-liver 31 P magnetic resonance spectroscopic imaging (31 P MRSI) in healthy subjects and assessed the effects of principal component analysis (PCA)-based denoising on the repeatability parameters. In addition, spatial variations of 31 P metabolites within the liver were analyzed. 3D 31 P MRSI data of the liver were acquired with a nominal voxel size of 20 mm isotropic in 10 healthy volunteers twice on the same day. Data were reconstructed without denoising, and with PCA-based denoising before or after channel combination. From the test-retest data, repeatability parameters for metabolite level quantification were determined for 12 31 P metabolite signals. On average, 31 P MR spectra from 100 ± 25 voxels in the liver were analyzed. Only voxels with contamination from skeletal muscle or the gall bladder were excluded and no voxels were discarded based on (low) signal-to-noise ratio (SNR). Repeatability for most quantified 31 P metabolite levels in the liver was good to excellent, with an intrasubject variability below 10%. PCA-based denoising increased the SNR ~ 3-fold, but did not improve the repeatability for mean liver 31 P metabolite quantification with the fitting constraints used. Significant spatial heterogeneity of various 31 P metabolite levels within the liver was observed, with marked differences for the phosphomonoester and phosphodiester metabolites between the left and right lobe. In conclusion, using a 31 P whole-body transmit coil in combination with a 16-channel 31 P receive array at 7 T allowed 31 P MRSI acquisitions with full liver coverage and good to excellent repeatability.

Diffusion-weighted MRI with deep learning for visualizing treatment results of MR-guided HIFU ablation of uterine fibroids.

OBJECTIVES: No method is available to determine the non-perfused volume (NPV) repeatedly during magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablations of uterine fibroids, as repeated acquisition of contrast-enhanced T1-weighted (CE-T1w) scans is inhibited by safety concerns. The objective of this study was to develop and test a deep learning-based method for translation of diffusion-weighted imaging (DWI) into synthetic CE-T1w scans, for monitoring MR-HIFU treatment progression. METHODS: The algorithm was retrospectively trained and validated on data from 33 and 20 patients respectively who underwent an MR-HIFU treatment of uterine fibroids between June 2017 and January 2019. Postablation synthetic CE-T1w images were generated by a deep learning network trained on paired DWI and reference CE-T1w scans acquired during the treatment procedure. Quantitative analysis included calculation of the Dice coefficient of NPVs delineated on synthetic and reference CE-T1w scans. Four MR-HIFU radiologists assessed the outcome of MR-HIFU treatments and NPV ratio based on the synthetic and reference CE-T1w scans. RESULTS: Dice coefficient of NPVs was 71% (± 22%). The mean difference in NPV ratio was 1.4% (± 22%) and not statistically significant (p = 0.79). Absolute agreement of the radiologists on technical treatment success on synthetic and reference CE-T1w scans was 83%. NPV ratio estimations on synthetic and reference CE-T1w scans were not significantly different (p = 0.27). CONCLUSIONS: Deep learning-based synthetic CE-T1w scans derived from intraprocedural DWI allow gadolinium-free visualization of the predicted NPV, and can potentially be used for repeated gadolinium-free monitoring of treatment progression during MR-HIFU therapy for uterine fibroids. KEY POINTS: • Synthetic CE-T1w scans can be derived from diffusion-weighted imaging using deep learning. • Synthetic CE-T1w scans may be used for visualization of the NPV without using a contrast agent directly after MR-HIFU ablations of uterine fibroids.

A 72-channel receive array coil allows whole-heart cine MRI in two breath holds.

BACKGROUND: A new 72-channel receive array coil and sensitivity encoding, compressed (C-SENSE) and noncompressed (SENSE), were investigated to decrease the number of breath-holds (BHs) for cardiac magnetic resonance (CMR). METHODS: Three-T CMRs were performed using the 72-channel coil with SENSE-2/4/6 and C-SENSE-2/4/6 accelerated short-axis cine two-dimensional balanced steady-state free precession sequences. A 16-channel coil with SENSE-2 served as reference. Ten healthy subjects were included. BH-time was kept under 15 s. Data were compared in terms of image quality, biventricular function, number of BHs, and scan times. RESULTS: BHs decreased from 7 with C-SENSE-2 (scan time 70 s, 2 slices/BH) to 3 with C-SENSE-4 (scan time 42 s, 4-5 slices/BH) and 2 with C-SENSE-6 (scan time 28 s, 7 slices/BH). Compared to reference, image sharpness was similar for SENSE-2/4/6, slightly inferior for C-SENSE-2/4/6. Blood-to-myocardium contrast was unaffected. C-SENSE-4/6 was given lower qualitative median scores, but images were considered diagnostically adequate to excellent, with C-SENSE-6 suboptimal. Biventricular end-diastolic (EDV), end-systolic (ESV) and stroke volumes, ejection fractions (EF), cardiac outputs, and left ventricle (LV)-mass were similar for SENSE-2/4/6 with no systematic bias and clinically appropriate limits of agreements. C-SENSE slightly underestimated LV-EDV (-6.38 ± 6.0 mL, p < 0.047), LV-ESV (-7.94 ± 6.0 mL, p < 0.030) and overestimated LV-EF (3.16 ± 3.10%; p < 0.047) with C-SENSE-4. Bland-Altman analyses revealed minor systematic biases in these variables with C-SENSE-2/4/6 and for LV-mass with C-SENSE-6. CONCLUSIONS: Using the 72-channel coil, short-axis CMR for quantifying biventricular function was feasible in two BHs where SENSE slightly outperformed C-SENSE.

Quantitative muscle MRI captures early muscle degeneration in calpainopathy.

To evaluate differences in qMRI parameters of muscle diffusion tensor imaging (mDTI), fat-fraction (FF) and water T2 time in leg muscles of calpainopathy patients (LGMD R1/D4) compared to healthy controls, to correlate those findings to clinical parameters and to evaluate if qMRI parameters show muscle degeneration in not-yet fatty infiltrated muscles. We evaluated eight thigh and seven calf muscles of 19 calpainopathy patients and 19 healthy matched controls. MRI scans were performed on a 3T MRI including a mDTI, T2 mapping and mDixonquant sequence. Clinical assessment was done with manual muscle testing, patient questionnaires (ACTIVLIM, NSS) as well as gait analysis. Average FF was significantly different in all muscles compared to controls (p < 0.001). In muscles with less than 8% FF a significant increase of FA (p < 0.005) and decrease of RD (p < 0.004) was found in high-risk muscles of calpainopathy patients. Water T2 times were increased within the low- and intermediate-risk muscles (p ≤ 0.045) but not in high-risk muscles (p = 0.062). Clinical assessments correlated significantly with qMRI values: QMFM vs. FF: r = - 0.881, p < 0.001; QMFM versus FA: r = - 0.747, p < 0.001; QMFM versus MD: r = 0.942, p < 0.001. A good correlation of FF and diffusion metrics to clinical assessments was found. Diffusion metrics and T2 values are promising candidates to serve as sensitive early and non-invasive methods to capture early muscle degeneration in non-fat-infiltrated muscles in calpainopathies.

Confirmatory factor analysis including MRI-derived adipose tissues quantification improves associations of metabolic dysregulation to diastolic dysfunction.

AIMS: To quantify metabolic impairment via a one-factor approach with confirmatory factor analysis (CFA) including MRI-derived visceral and subcutaneous adipose tissues and to associate it with diastolic dysfunction. METHODS: In this cross-sectional analysis, 916 participants (53% female, mean age (SD): 56 (6)) underwent abdominal and cardiovascular MRI. With CFA a metabolic-load factor of metabolic-syndrome variables and visceral and subcutaneous adipose tissues was constructed. A piecewise structural equation model approach with adjustment for confounding factors was used to determine associations with left-ventricular diastolic function, cardiac morphology and hemodynamics. RESULTS: Model fitting excluding blood pressure and waist circumference but including visceral and subcutaneous adipose tissues, fasting glucose, HDL-c and triglycerides was used to construct the metabolic-load factor. Evaluating measurement invariance demonstrated sex-specificity. Change in mitral early/late peak filling rate ratio was -0.12 for both males [-0.20; -0.05, p > 0.05] and females [-0.17; -0.07, p > 0.001] per SD of metabolic-load factor. Change in deceleration time of mitral early filling was -11.83 ms in females [-17.38; -6.27] per SD of metabolic-load factor. CONCLUSION: A single latent metabolic-load factor via CFA including MRI-derived adipose tissues increased sensitivity for metabolic impairment obsoleting waist circumference and is associated with a decreased left-ventricular diastolic function, more apparent in females than in males.

Dynamic Contrast-enhanced and Diffusion-weighted Magnetic Resonance Imaging for Response Evaluation After Single-Dose Ablative Neoadjuvant Partial Breast Irradiation.

Purpose: We aimed to evaluate changes in dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) scans acquired before and after single-dose ablative neoadjuvant partial breast irradiation (NA-PBI), and explore the relation between semiquantitative MRI parameters and radiologic and pathologic responses. Methods and Materials: We analyzed 3.0T DCE and DW-MRI of 36 patients with low-risk breast cancer who were treated with single-dose NA-PBI, followed by breast-conserving surgery 6 or 8 months later. MRI was acquired before NA-PBI and 1 week, 2, 4, and 6 months after NA-PBI. Breast radiologists assessed the radiologic response and breast pathologists scored the pathologic response after surgery. Patients were grouped as either pathologic responders or nonresponders (<10% vs ≥10% residual tumor cells). The semiquantitative MRI parameters evaluated were time to enhancement (TTE), 1-minute relative enhancement (RE1min), percentage of enhancing voxels (%EV), distribution of washout curve types, and apparent diffusion coefficient (ADC). Results: In general, the enhancement increased 1 week after NA-PBI (baseline vs 1 week median - TTE: 15s vs 10s; RE1min: 161% vs 197%; %EV: 47% vs 67%) and decreased from 2 months onward (6 months median - TTE: 25s; RE1min: 86%; %EV: 12%). Median ADC increased from 0.83 × 10-3 mm2/s at baseline to 1.28 × 10-3 mm2/s at 6 months. TTE, RE1min, and %EV showed the most potential to differentiate between radiologic responses, and TTE, RE1min, and ADC between pathologic responses. Conclusions: Semiquantitative analyses of DCE and DW-MRI showed changes in relative enhancement and ADC 1 week after NA-PBI, indicating acute inflammation, followed by changes indicating tumor regression from 2 to 6 months after radiation therapy. A relation between the MRI parameters and radiologic and pathologic responses could not be proven in this exploratory study.

Dynamic brain ADC variations over the cardiac cycle and their relation to tissue strain assessed with DENSE at high-field MRI.

PURPOSE: The ADC of brain tissue slightly varies over the cardiac cycle. This variation could reflect physiology, including mixing of the interstitial fluid, relevant for brain waste clearance. However, it is known from cardiac diffusion imaging that tissue deformation by itself affects the magnitude of the MRI signal, leading to artificial ADC variations as well. This study investigates to what extent tissue deformation causes artificial ADC variations in the brain. THEORY AND METHODS: We implemented a high-field MRI sequence with stimulated echo acquisition mode that simultaneously measures brain tissue deformation and ADC. Based on the measured tissue deformation, we simulated the artificial ADC variation by combining established theoretical frameworks and compared the results with the measured ADC variation. We acquired data in 8 healthy volunteers with diffusion weighting b = 300 and b = 1000 s/mm2 . RESULTS: Apparent diffusion coefficient variation was largest in the feet-to-head direction and showed the largest deviation from the mean ADC at peak systole. Artificial ADC variation estimated from tissue deformation was 1.3 ± 0.37·10-5  mm2 /s in the feet-to-head direction for gray matter, and 0.75 ± 0.29·10-5  mm2 /s for white matter. The measured ADC variation in the feet-to-head direction was 5.6·10-5 ± 1.5·10-5  mm2 /s for gray matter and 3.2·10-5 ± 1.0·10-5  mm2 /s for white matter, which was a factor of 3.5 ± 0.82 and 3.4 ± 0.57 larger than the artificial diffusion variations. The measured diffusion variations in the right-to-left/anterior-to-posterior direction were a factor of 1.5 ± 1.0/1.7 ± 1.4 and 2.0 ± 0.91/2.5 ± 0.94 larger than the artificial diffusion variations for gray matter and white matter, respectively. CONCLUSION: Apparent diffusion coefficient variations in the brain likely largely reflect physiology.

Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis.

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.

Robustness and stability of volume-based tractography in a multicenter setting.

Muscle diffusion tensor imaging (mDTI)-based tractography is a promising tool with which to detect subclinical changes in muscle injuries and to evaluate pathophysiology in neuromuscular diseases. Classic region of interest (ROI)-based tractography is very time-consuming and requires an examiner with extensive experience. (Semi)automatic approaches such as volume-based tractography (VBT) can diminish this problem but its robustness and stability are unknown. The aim of the current study was to assess the performance of VBT in a multicenter setting and to evaluate semiautomatic segmentation approaches in the analysis of VBT-derived data in terms of the comparability of the outcome measures. Five traveling volunteers underwent 3-T mDTI of seven calf muscles of both legs at six different MR sites. Tract properties and diffusion metrics were calculated using VBT. Within-subject coefficients of variance (wsCVs) and intraclass correlation coefficients (ICCs) were calculated to assess the multicenter reproducibility of tract properties such as tract density (TD), mean tract length, volume and tract propagation angle, and diffusion metrics such as fractional anisotropy, mean diffusivity, axial diffusivity (λ1 ) and radial diffusivity in traveling subjects. Furthermore, 50 individual datasets from five different centers (10 datasets per center) were pooled to assess the feasibility of VBT with manual and semiautomatic segmentation. To assess the differences of tract properties and diffusion metrics between segmentation approaches an ANOVA was performed, and ICC and Bland-Altman plots were analyzed. wsCVs and ICCs showed good reproducibility of the tract properties TD and volume, as well as diffusion metrics. ANOVA showed no significant differences between manual and semiautomatic approaches. ICCs were excellent (≥ 0.992) and Bland-Altman analysis did not reveal any systemic bias between the methods. Tract properties and diffusion metrics derived from VBT showed good comparability among centers. Semiautomatic approaches revealed excellent agreement with gold standard of manual segmentation. These findings suggest that pooling data from different centers to construct a reference database for tractography results is feasible using semiautomatic segmentation approaches.