Contrast-free dynamic susceptibility contrast using sinusoidal and bolus oxygenation challenges.

Deoxygenation-based dynamic susceptibility contrast (dDSC) MRI uses respiratory challenges as a source of endogenous contrast as an alternative to gadolinium injection. These gas challenges induce T2*-weighted MRI signal losses, after which tracer kinetics modeling was applied to calculate cerebral perfusion. This work compares three gas challenges, desaturation (transient hypoxia), resaturation (transient normoxia), and SineO2 (sinusoidal modulation of end-tidal oxygen pressures) in a cohort of 10 healthy volunteers (age 37 ± 11 years; 60% female). Perfusion estimates consisted of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Calculations were computed using a traditional tracer kinetics model in the time domain for desaturation and resaturation and in the frequency domain for SineO2. High correlations and limits of agreement were observed among the three deoxygenation-based paradigms for CBV, although MTT and CBF estimates varied with the hypoxic stimulus. Cross-modality correlation with gadolinium DSC was lower, particularly for MTT, but on a par with agreement between the other perfusion references. Overall, this work demonstrated the feasibility and reliability of oxygen respiratory challenges to measure brain perfusion. Additional work is needed to assess the utility of dDSC in the diagnostic evaluation of various pathologies such as ischemic strokes, brain tumors, and neurodegenerative diseases.

Muscle fiber strain rates in the lower leg during ankle dorsi-/plantarflexion exercise.

Static quantitative magnetic resonance imaging (MRI) provides readouts of structural changes in diseased muscle, but current approaches lack the ability to fully explain the loss of contractile function. Muscle contractile function can be assessed using various techniques including phase-contrast MRI (PC-MRI), where strain rates are quantified. However, current two-dimensional implementations are limited in capturing the complex motion of contracting muscle in the context of its three-dimensional (3D) fiber architecture. The MR acquisitions (chemical shift-encoded water-fat separation scan, spin echo-echoplanar imaging with diffusion weighting, and two time-resolved 3D PC-MRI) wereperformed at 3 T. PC-MRI acquisitions and performed with and without load at 7.5% of the maximum voluntary dorsiflexion contraction force. Acquisitions (3 T, chemical shift-encoded water-fat separation scan, spin echo-echo planar imaging with diffusion weighting, and two time-resolved 3D PC-MRI) were performed with and without load at 7.5% of the maximum voluntary dorsiflexion contraction force. Strain rates and diffusion tensors were calculated and combined to obtain strain rates along and perpendicular to the muscle fibers in seven lower leg muscles during the dynamic dorsi-/plantarflexion movement cycle. To evaluate strain rates along the proximodistal muscle axis, muscles were divided into five equal segments. t-tests were used to test if cyclic strain rate patterns (amplitude > 0) were present along and perpendicular to the muscle fibers. The effects of proximal-distal location and load were evaluated using repeated measures ANOVAs. Cyclic temporal strain rate patterns along and perpendicular to the fiber were found in all muscles involved in dorsi-/plantarflexion movement (p < 0.0017). Strain rates along and perpendicular to the fiber were heterogeneously distributed over the length of most muscles (p < 0.003). Additional loading reduced strain rates of the extensor digitorum longus and gastrocnemius lateralis muscle (p < 0.001). In conclusion, the lower leg muscles involved in cyclic dorsi-/plantarflexion exercise showed cyclic fiber strain rate patterns with amplitudes that varied between muscles and between the proximodistal segments within the majority of muscles.

Single Breath-Hold MR Elastography for Fast Biomechanical Probing of Pancreatic Stiffness.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) stromal disposition is thought to influence chemotherapy efficacy and increase tissue stiffness, which could be quantified noninvasively via MR elastography (MRE). Current methods cause position-based errors in pancreas location over time, hampering accuracy. It would be beneficial to have a single breath-hold acquisition. PURPOSE: To develop and test a single breath-hold three-dimensional MRE technique utilizing prospective undersampling and a compressed sensing reconstruction (CS-MRE). STUDY TYPE: Prospective. POPULATION: A total of 30 healthy volunteers (HV) (31 ± 9 years; 33% male) and five patients with PDAC (69 ± 5 years; 80% male). FIELD STRENGTH/SEQUENCE: 3-T, GRE Ristretto MRE. ASSESSMENT: First, optimization of multi breath-hold MRE was done in 10 HV using four combinations of vibration frequency, number of measured wave-phase offsets, and TE and looking at MRE quality measures in the pancreas head. Second, viscoelastic parameters delineated in the pancreas head or tumor of CS-MRE were compared against (I) 2D and (II) 3D four breath-hold acquisitions in HV (N = 20) and PDAC patients. Intrasession repeatability was assessed for CS-MRE in a subgroup of healthy volunteers (N = 15). STATISTICAL TESTS: Tests include repeated measures analysis of variance (ANOVA), Bland-Altman analysis, and coefficients of variation (CoVs). A P-value <.05 was considered statistically significant. RESULTS: Optimization of the four breath-hold acquisitions resulted in 40 Hz vibration frequency, five wave-phases, and echo time (TE) = 6.9 msec as the preferred method (4BH-MRE). CS-MRE quantitative results did not differ from 4BH-MRE. Shear wave speed (SWS) and phase angle differed significantly between HV and PDAC patients using 4BH-MRE or CS-MRE. The limits of agreement for SWS were [-0.09, 0.10] m/second and the within-subject CoV was 4.8% for CS-MRE. DATA CONCLUSION: CS-MRE might allow a single breath-hold MRE acquisition with comparable SWS and phase angle as 4BH-MRE, and it may still enable to differentiate between HV and PDAC. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2.

MR Elastography of the Pancreas: Bowel Preparation and Repeatability Assessment in Pancreatic Cancer Patients and Healthy Controls.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) stromal viscoelasticity can be measured using MR elastography (MRE). Bowel preparation regimens could affect MRE quality and knowledge on repeatability is crucial for clinical implementation. PURPOSE: To assess effects of four bowel preparation regimens on MRE quality and to evaluate repeatability and differentiate patients from healthy controls. STUDY TYPE: Prospective. POPULATION: 15 controls (41 ± 16 years; 47% female), 16 PDAC patients (one excluded, 66 ± 12 years; 40% female) with 15 age-/sex-matched controls (65 ± 11 years; 40% female). Final sample size was 25 controls and 15 PDAC. FIELD STRENGTH/SEQUENCE: 3-T, spin-echo echo-planar-imaging, turbo spin-echo, and fast field echo gradient-echo. ASSESSMENT: Four different regimens were used: fasting; scopolaminebutyl; drinking 0.5 L water; combination of 0.5 L water and scopolaminebutyl. MRE signal-to-noise ratio (SNR) was compared between all regimens. MRE repeatability (test-retest) and differences in shear wave speed (SWS) and phase angle (ϕ) were assessed in PDAC and controls. Regions-of-interest were defined for tumor, nontumorous (n = 8) tissue in PDAC, and whole pancreas in controls. Two radiologists delineated tumors twice for evaluation of intraobserver and interobserver variability. STATISTICAL TESTS: Repeated measures analysis of variance, coefficients of variation (CoVs), Bland-Altman analysis, (un)paired t-test, Mann-Whitney U-test, and Wilcoxon signed-rank test. P-value<0.05 was considered statistically significant. RESULTS: Preparation regimens did not significantly influence MRE-SNR. Therefore, the least burdensome preparation (fasting only) was continued. CoVs for tumor SWS were: intrasession (12.8%) and intersession (21.7%), and intraobserver (7.9%) and interobserver (10.3%) comparisons. For controls, CoVs were intrasession (4.6%) and intersession (6.4%). Average SWS for tumor, nontumor, and healthy tissue were: 1.74 ± 0.58, 1.38 ± 0.27, and 1.18 ± 0.16 m/sec (ϕ: 1.02 ± 0.17, 0.91 ± 0.07, and 0.85 ± 0.08 rad), respectively. Significant differences were found between all groups, except for ϕ between healthy-nontumor (P = 0.094). DATA CONCLUSION: The proposed bowel preparation regimens may not influence MRE quality. MRE may be able to differentiate between healthy tissue-tumor and tumor-nontumor. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Cerebral hemodynamics and oxygenation in adult patients with sickle cell disease after stem cell transplantation.

Sickle cell disease (SCD) is characterized by chronic hemolytic anemia associated with impaired cerebral hemodynamics and oxygen metabolism. Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for patients with SCD. Whereas normalization of hemoglobin levels and hemolysis markers has been reported after HSCT, its effects on cerebral perfusion and oxygenation in adult SCD patients remain largely unexplored. This study investigated the effects of HSCT on cerebral blood flow (CBF), oxygen delivery, cerebrovascular reserve (CVR), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2 ) in 17 adult SCD patients (mean age: 25.0 ± 8.0, 6 females) before and after HSCT and 10 healthy ethnicity-matched controls (mean age: 28.0 ± 8.8, 6 females) using MRI. For the CVR assessment, perfusion scans were performed before and after acetazolamide as a vasodilatory stimulus. Following HSCT, gray and white matter (GM and WM) CBF decreased (p < .01), while GM and WM CVR increased (p < .01) compared with the baseline measures. OEF and CMRO2 also increased towards levels in healthy controls (p < .01). The normalization of cerebral perfusion and oxygen metabolism corresponded with a significant increase in hemoglobin levels and decreases in reticulocytes, total bilirubin, and LDH as markers of hemolysis (p < .01). This study shows that HSCT results in the normalization of cerebral perfusion and oxygen metabolism, even in adult patients with SCD. Future follow-up MRI scans will determine whether the observed normalization of cerebral hemodynamics and oxygen metabolism prevents new silent cerebral infarcts.

The role of gadolinium-based contrast agents in magnetic resonance imaging structured reporting and data systems (RADS).

Among the 28 reporting and data systems (RADS) available in the literature, we identified 15 RADS that can be used in Magnetic Resonance Imaging (MRI). Performing examinations without using gadolinium-based contrast agents (GBCA) has benefits, but GBCA administration is often required to achieve an early and accurate diagnosis. The aim of the present review is to summarize the current role of GBCA in MRI RADS. This overview suggests that GBCA are today required in most of the current RADS and are expected to be used in most MRIs performed in patients with cancer. Dynamic contrast enhancement is required for correct scores calculation in PI-RADS and VI-RADS, although scientific evidence may lead in the future to avoid the GBCA administration in these two RADS. In Bone-RADS, contrast enhancement can be required to classify an aggressive lesion. In RADS scoring on whole body-MRI datasets (MET-RADS-P, MY-RADS and ONCO-RADS), in NS-RADS and in Node-RADS, GBCA administration is optional thanks to the intrinsic high contrast resolution of MRI. Future studies are needed to evaluate the impact of the high T1 relaxivity GBCA on the assignment of RADS scores.

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.

Model-based reconstructions for intravoxel incoherent motion and diffusion tensor imaging parameter map estimations.

Intravoxel incoherent motion (IVIM) imaging and diffusion tensor imaging (DTI) facilitate noninvasive quantification of tissue perfusion and diffusion. Both are promising biomarkers in various diseases and a combined acquisition is therefore desirable. This comes with challenges, including noisy parameter maps and long scan times, especially for the perfusion fraction f and pseudo-diffusion coefficient D*. A model-based reconstruction has the potential to overcome these challenges. As a first step, our goal was to develop a model-based reconstruction framework for IVIM and combined IVIM-DTI parameter estimation. The IVIM and IVIM-DTI models were implemented in the PyQMRI model-based reconstruction framework and validated with simulations and in vivo data. Commonly used voxel-wise nonlinear least-squares fitting was used as the reference. Simulations with the IVIM and IVIM-DTI models were performed with 100 noise realizations to assess accuracy and precision. Diffusion-weighted data were acquired for IVIM reconstruction in the liver (n = 5), as well as for IVIM-DTI in the kidneys (n = 5) and lower-leg muscles (n = 6) of healthy volunteers. The median and interquartile range (IQR) values of the IVIM and IVIM-DTI parameters were compared to assess bias and precision. With model-based reconstruction, the parameter maps exhibited less noise, which was most pronounced in the f and D* maps, both in the simulations and in vivo. The bias values in the simulations were comparable between model-based reconstruction and the reference method. The IQR was lower with model-based reconstruction compared with the reference for all parameters. In conclusion, model-based reconstruction is feasible for IVIM and IVIM-DTI and improves the precision of the parameter estimates, particularly for f and D* maps.

Venous Blood Oxygenation Measurements Using TRUST and T2-TRIR MRI During Hypoxic and Hypercapnic Gas Challenges.

BACKGROUND: Oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2 ) may serve as biomarkers in several diseases. OEF and CMRO2 can be estimated from venous blood oxygenation (Yv ) levels, which in turn can be calculated from venous blood T2 values (T2b ). T2b can be measured using different MRI sequences, including T2-relaxation-under-spin-tagging (TRUST) and T2-prepared-blood-relaxation-imaging-with-inversion-recovery (T2-TRIR). The latter measures both T2b and T1 (T1b ) but was found previously to overestimate T2b compared to TRUST. It remained unclear, however, if this bias is constant across higher and lower oxygen saturations. PURPOSE: To compare TRUST and T2-TRIR across a range of O2 saturations using hypoxic and hypercapnic gas challenges. STUDY TYPE: Prospective. POPULATION: Twelve healthy volunteers (four female, age 36 ± 10 years). FIELD STRENGTH/SEQUENCE: A 3T; turbo-field echo-planar-imaging (TFEPI), echo-planar-imaging (EPI), and fast-field-echo (FFE). ASSESSMENT: TRUST- and T2-TRIR-derived T2b , Yv , OEF, and CMRO2 were compared across different respiratory challenges. T1b from T2-TRIR was used to estimate Hct (HctTRIR ) and compared with venipuncture (HctVP ). STATISTICAL TESTS: Shapiro-Wilk, one-sample and paired-sample t-test, repeated measures ANOVA, Friedman test, Bland-Altman, and correlation analysis. Bonferroni multiple-comparison correction was performed. Significance level was 0.05. RESULTS: A significant bias was observed between TRUST- and T2-TRIR-derived T2b , Yv , and OEF values (-13 ± 11 msec, -5.3% ± 3.5% and 5.9 ± 4.1%, respectively). For Yv and OEF, this bias was constant across the range of measured values. T1b was significantly lower during severe hypoxia and hypercapnia compared to baseline (1712 ± 86 msec and 1634 ± 79 msec compared to 1757 ± 90 msec). While no significant bias was found between HctVP and HctTRIR (0.02% ± 0.06%, P = 0.20), the correlation between these Hct values was significant but weak (r = 0.19). DATA CONCLUSION: Given the constant bias, TRUST- and T2-TRIR-derived venous T2b values can be used interchangeably to estimate Yv , OEF, and CMRO2 across a broad range of oxygen saturations. Hct from T2-TRIR-derived T1-values only weakly correlated with Hct from venipuncture. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Four-Dimensional Flow MRI-Derived Hemodynamics in Abdominal Aortic Aneurysms: Reproducibility and Associations With Diameter, Intraluminal Thrombus Volume, and Vorticity.

BACKGROUND: Maximum diameter measurements are used to assess the rupture risk of abdominal aortic aneurysms (AAAs); however, these are not precise enough to predict all ruptures. Four-dimensional (4D) flow MRI-derived parameters provide additional information by visualizing hemodynamics in AAAs but merit further investigation before they are clinically applicable. PURPOSE: To assess the reproducibility of 4D flow MRI-derived hemodynamics, to investigate possible correlations with lumen and maximum diameter, and to explore potential relationships with vorticity and aneurysm growth. STUDY TYPE: Prospective single-arm study. POPULATION: A total of 22 (71.5 ± 6.1 years, 20 male) asymptomatic AAA patients with a maximum diameter of at least 30 mm. FIELD STRENGTH/SEQUENCE: A 3.0 T/Free-breathing 4D flow MRI phase-contrast acquisition with retrospective ECG-gating. ASSESSMENT: Patients underwent two consecutive 4D flow MRI scans 1-week apart. Aortic volumes were segmented from time-averaged phase contrast magnetic resonance angiographies. Reproducibility was assessed by voxelwise analysis after registration. Mean flow velocity, mean wall shear stress (WSS), mean lumen diameter, and qualitative vorticity scores were assessed. In addition, Dixon MRI and retrospective surveillance data were used to study maximum diameter (including thrombus), intraluminal thrombus volume (ILT), and growth rate. STATISTICAL TESTS: For reproducibility assessment, Bland-Altman analyses, Pearson correlation, Spearman's correlation, and orthogonal regression were conducted. Potential correlations between hemodynamics and vorticity scores were assessed using linear regression. P < 0.05 was considered statistically significant. RESULTS: Test-retest median Pearson correlation coefficients for flow velocity and WSS were 0.85 (IQR = 0.08) m/sec and 0.82 (IQR = 0.10) Pa, respectively. Mean WSS significantly correlated with mean flow velocity (R = 0.75) and inversely correlated with mean lumen diameter (R = -0.73). No significant associations were found between 4D flow MRI-derived hemodynamic parameters and maximum diameter (flow velocity: P = 0.98, WSS: P = 0.22). DATA CONCLUSION: A 4D flow MRI is robust for assessing the hemodynamics within AAAs. No correlations were found between hemodynamic parameters and maximum diameter, ILT volume and growth rate. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Quantitative Magnetic Resonance Imaging to Assess Progression and Rupture Risk of Aortic Aneurysms: A Scoping Review.

PURPOSE: In current practice, the diameter of an aortic aneurysm is utilized to estimate the rupture risk and decide upon timing of elective repair, although it is known to be imprecise and not patient-specific. Quantitative magnetic resonance imaging (MRI) enables the visualization of several biomarkers that provide information about processes within the aneurysm and may therefore facilitate patient-specific risk stratification. We performed a scoping review of the literature on quantitative MRI techniques to assess aortic aneurysm progression and rupture risk, summarized these findings, and identified knowledge gaps. METHODS: Literature concerning primary research was of interest and the medical databases PubMed, Scopus, Embase, and Cochrane were systematically searched. This study used the PRISMA protocol extension for scoping reviews. Articles published between January 2010 and February 2023 involving animals and/or humans were included. Data were extracted by 2 authors using a predefined charting method. RESULTS: A total of 1641 articles were identified, of which 21 were included in the scoping review. Quantitative MRI-derived biomarkers were categorized into hemodynamic (8 studies), wall (5 studies) and molecular biomarkers (8 studies). Fifteen studies included patients and/or healthy human subjects. Animal models were investigated in the other 6 studies. A cross-sectional study design was the most common, whereas 5 animal studies had a longitudinal component and 2 studies including patients had a prospective design. A promising hemodynamic biomarker is wall shear stress (WSS), which is estimated based on 4D-flow MRI. Molecular biomarkers enable the assessment of inflammatory and wall deterioration processes. The ADAMTS4-specific molecular magnetic resonance (MR) probe showed potential to predict abdominal aortic aneurysm (AAA) formation and rupture in a murine model. Wall biomarkers assessed using dynamic contrast-enhanced (DCE) MRI showed great potential for assessing AAA progression independent of the maximum diameter. CONCLUSION: This scoping review provides an overview of quantitative MRI techniques studied and the biomarkers derived from them to assess aortic aneurysm progression and rupture risk. Longitudinal studies are needed to validate the causal relationships between the identified biomarkers and aneurysm growth, rupture, or repair. In the future, quantitative MRI could play an important role in the personalized risk assessment of aortic aneurysm rupture. CLINICAL IMPACT: The currently used maximum aneurysm diameter fails to accurately assess the multifactorial pathology of an aortic aneurysm and precisely predicts rupture in a patient-specific manner. Quantitative magnetic resonance imaging (MRI) enables the detection of various quantitative parameters involved in aneurysm progression and subsequent rupture. This scoping review provides an overview of the studied quantitative MRI techniques, the biomarkers derived from them, and recommendations for future research needed for the implementation of these biomarkers. Ultimately, quantitative MRI could facilitate personalized risk assessment for patients with aortic aneurysms, thereby reducing untimely repairs and improving rupture prevention.

Magnetic resonance reveals mitochondrial dysfunction and muscle remodelling in spinal muscular atrophy.

Genetic therapy has changed the prognosis of hereditary proximal spinal muscular atrophy, although treatment efficacy has been variable. There is a clear need for deeper understanding of underlying causes of muscle weakness and exercise intolerance in patients with this disease to further optimize treatment strategies. Animal models suggest that in addition to motor neuron and associated musculature degeneration, intrinsic abnormalities of muscle itself including mitochondrial dysfunction contribute to the disease aetiology. To test this hypothesis in patients, we conducted the first in vivo clinical investigation of muscle bioenergetics. We recruited 15 patients and 15 healthy age and gender-matched control subjects in this cross-sectional clinico-radiological study. MRI and 31P magnetic resonance spectroscopy, the modality of choice to interrogate muscle energetics and phenotypic fibre-type makeup, was performed of the proximal arm musculature in combination with fatiguing arm-cycling exercise and blood lactate testing. We derived bioenergetic parameter estimates including: blood lactate, intramuscular pH and inorganic phosphate accumulation during exercise, and muscle dynamic recovery constants. A linear correlation was used to test for associations between muscle morphological and bioenergetic parameters and clinico-functional measures of muscle weakness. MRI showed significant atrophy of triceps but not biceps muscles in patients. Maximal voluntary contraction force normalized to muscle cross-sectional area for both arm muscles was 1.4-fold lower in patients than in controls, indicating altered intrinsic muscle properties other than atrophy contributed to muscle weakness in this cohort. In vivo31P magnetic resonance spectroscopy identified white-to-red remodelling of residual proximal arm musculature in patients on the basis of altered intramuscular inorganic phosphate accumulation during arm-cycling in red versus white and intermediate myofibres. Blood lactate rise during arm-cycling was blunted in patients and correlated with muscle weakness and phenotypic muscle makeup. Post-exercise metabolic recovery was slower in residual intramuscular white myofibres in patients demonstrating mitochondrial ATP synthetic dysfunction in this particular fibre type. This study provides the first in vivo evidence in patients that degeneration of motor neurons and associated musculature causing atrophy and muscle weakness in 5q spinal muscular atrophy type 3 and 4 is aggravated by disproportionate depletion of myofibres that contract fastest and strongest. Our finding of decreased mitochondrial ATP synthetic function selectively in residual white myofibres provides both a possible clue to understanding the apparent vulnerability of this particular fibre type in 5q spinal muscular atrophy types 3 and 4 as well as a new biomarker and target for therapy.

A comparison of myocardial magnetic resonance extracellular volume mapping at 3 T against histology of tissue collagen in severe aortic valve stenosis and obstructive hypertrophic cardiomyopathy.

OBJECTIVE: Quantitative extracellular volume fraction (ECV) mapping with MRI is commonly used to investigate in vivo diffuse myocardial fibrosis. This study aimed to validate ECV measurements against ex vivo histology of myocardial tissue samples from patients with aortic valve stenosis or hypertrophic cardiomyopathy. MATERIALS AND METHODS: Sixteen patients underwent MRI examination at 3 T to acquire native T1 maps and post-contrast T1 maps after gadobutrol administration, from which hematocrit-corrected ECV maps were estimated. Intra-operatively obtained myocardial tissue samples from the same patients were stained with picrosirius red for quantitative histology of myocardial interstitial fibrosis. Correlations between in vivo ECV and ex vivo myocardial collagen content were evaluated with regression analyses. RESULTS: Septal ECV was 30.3% ± 4.6% and correlated strongly (n = 16, r = 0.70; p = 0.003) with myocardial collagen content. Myocardial native T1 values (1206 ± 36 ms) did not correlate with septal ECV (r = 0.41; p = 0.111) or with myocardial collagen content (r = 0.32; p = 0.227). DISCUSSION: We compared myocardial ECV mapping at 3 T against ex vivo histology of myocardial collagen content, adding evidence to the notion that ECV mapping is a surrogate marker for in vivo diffuse myocardial fibrosis.

A vision of 14 T MR for fundamental and clinical science.

OBJECTIVE: We outline our vision for a 14 Tesla MR system. This comprises a novel whole-body magnet design utilizing high temperature superconductor; a console and associated electronic equipment; an optimized radiofrequency coil setup for proton measurement in the brain, which also has a local shim capability; and a high-performance gradient set. RESEARCH FIELDS: The 14 Tesla system can be considered a 'mesocope': a device capable of measuring on biologically relevant scales. In neuroscience the increased spatial resolution will anatomically resolve all layers of the cortex, cerebellum, subcortical structures, and inner nuclei. Spectroscopic imaging will simultaneously measure excitatory and inhibitory activity, characterizing the excitation/inhibition balance of neural circuits. In medical research (including brain disorders) we will visualize fine-grained patterns of structural abnormalities and relate these changes to functional and molecular changes. The significantly increased spectral resolution will make it possible to detect (dynamic changes in) individual metabolites associated with pathological pathways including molecular interactions and dynamic disease processes. CONCLUSIONS: The 14 Tesla system will offer new perspectives in neuroscience and fundamental research. We anticipate that this initiative will usher in a new era of ultra-high-field MR.

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.

Dynamic MR imaging of cerebral perfusion during bicycling exercise.

Habitual physical activity is beneficial for cerebrovascular health and cognitive function. Physical exercise therefore constitutes a clinically relevant cerebrovascular stimulus. This study demonstrates the feasibility of quantitative cerebral blood flow (CBF) measurements during supine bicycling exercise with pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI) at 3 Tesla. Twelve healthy volunteers performed a steady-state exercise-recovery protocol on an MR-compatible bicycle ergometer, while dynamic pCASL data were acquired at rest, during moderate (60% of the age-predicted supine maximal heart rate (HRmax)) and vigorous (80% of supine HRmax) exercise, and subsequent recovery. These CBF measurements were compared with 2D phase-contrast MRI measurements of blood flow through the carotid arteries. Procedures were repeated on a separate day for an assessment of measurement repeatability. Whole-brain (WB) CBF was 41.2 ± 6.9 mL/100 g/min at rest (heart rate 63 [57-71] beats/min), remained similar at moderate exercise (102 [97-107] beats/min), decreased by 10% to 37.1 ± 5.7 mL/100 g/min (p = 0.001) during vigorous exercise (139 [136-142] beats/min) and decreased further to 34.2 ± 6.0 mL/100 g/min (p < 0.001) during recovery. Hippocampus CBF decreased by 12% (p = 0.001) during moderate exercise, decreased further during vigorous exercise (-21%; p < 0.001) and was even lower during recovery (-31%; p < 0.001). In contrast, motor cortex CBF increased by 12% (p = 0.027) during moderate exercise, returned to resting-state values during vigorous exercise, and decreased by 17% (p = 0.006) during recovery. The inter-session repeatability coefficients for WB CBF were approximately 20% for all stages of the exercise-recovery protocol. Phase-contrast blood flow measurements through the common carotid arteries overestimated the WB CBF because of flow directed to the face and scalp. This bias increased with exercise. We have demonstrated the feasibility of dynamic pCASL-MRI of the human brain for a quantitative evaluation of cerebral perfusion during bicycling exercise. Our spatially resolved measurements revealed a differential response of CBF in the motor cortex as well as the hippocampus compared with the brain as a whole. Caution is warranted when using flow through the common carotid arteries as a surrogate measure for cerebral perfusion.

Multi-parametric quantitative magnetic resonance imaging of the upper arm muscles of patients with spinal muscular atrophy.

Quantitative magnetic resonance imaging (qMRI) is frequently used to map the disease state and disease progression in the lower extremity muscles of patients with spinal muscular atrophy (SMA). This is in stark contrast to the almost complete lack of data on the upper extremity muscles, which are essential for carrying out daily activities. The aim of this study was therefore to assess the disease state in the upper arm muscles of patients with SMA in comparison with healthy controls by quantitative assessment of fat fraction, diffusion indices, and water T2 relaxation times, and to relate these measures to muscle force. We evaluated 13 patients with SMA and 15 healthy controls with a 3-T MRI protocol consisting of DIXON, diffusion tensor imaging, and T2 sequences. qMRI measures were compared between groups and related to muscle force measured with quantitative myometry. Fat fraction was significantly increased in all upper arm muscles of the patients with SMA compared with healthy controls and correlated negatively with muscle force. Additionally, fat fraction was heterogeneously distributed within the triceps brachii (TB) and brachialis muscle, but not in the biceps brachii muscle. Diffusion indices and water T2 relaxation times were similar between patients with SMA and healthy controls, but we did find a slightly reduced mean diffusivity (MD), λ1, and λ3 in the TB of patients with SMA. Furthermore, MD was positively correlated with muscle force in the TB of patients with SMA. The variation in fat fraction further substantiates the selective vulnerability of muscles. The reduced diffusion tensor imaging indices, along with the positive correlation of MD with muscle force, point to myofiber atrophy. Our results show the feasibility of qMRI to map the disease state in the upper arm muscles of patients with SMA. Longitudinal data in a larger cohort are needed to further explore qMRI to map disease progression and to capture the possible effects of therapeutic interventions.

Assessment of functional shunting in patients with sickle cell disease.

Silent cerebral infarcts (SCI) are common in patients with sickle cell disease (SCD) and are thought to be caused by a mismatch between oxygen delivery and consumption. Functional cerebrovascular shunting is defined as reduced oxygen offloading due to the rapid transit of blood through the capillaries caused by increased flow and has been suggested as a potential mechanism underlying reduced oxygenation and SCI. We investigated the venous arterial spin labeling signal (VS) in the sagittal sinus as a proxy biomarker of cerebral functional shunting, and its association with hemodynamic imaging and hematological laboratory parameters. We included 28 children and 38 adults with SCD, and ten healthy racematched adult controls. VS, cerebral blood flow (CBF), velocity in the brain feeding arteries, oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) were measured before and after acetazolamide administration. VS was higher in patients with SCD compared to controls (P<0.01) and was increased after acetazolamide administration in all groups (P<0.01). VS was primarily predicted by CBF (P<0.01), but CBF-corrected VS was also associated with decreased CMRO2 (P<0.01). Additionally, higher disease severity defined by low hemoglobin and increased hemolysis was associated with higher CBF-corrected VS. Finally, CMRO2 was negatively correlated with fetal hemoglobin, and positively correlated with lactate dehydrogenase, which could be explained by changes in oxygen affinity. These findings provide evidence for cerebral functional shunting and encourage future studies investigating the potential link to aberrant capillary exchange in SCD.

Comparative Analysis of Blood T2 Values Measured by T2 -TRIR and TRUST.

BACKGROUND: Venous blood oxygenation (Yv), which can be derived from venous blood T2 (T2 b), combined with oxygen-extraction fraction (OEF) and cerebral metabolic rate of oxygen, is considered indicative for tissue viability and brain functioning and frequently assessed in patients with sickle cell disease. Recently, T2 -Prepared-Blood-Relaxation-Imaging-with-Inversion-Recovery (T2 -TRIR) was introduced allowing for simultaneous measurements of blood T2 and T1 (T1 b), potentially improving Yv estimation by overcoming the need to estimate hematocrit. PURPOSE: To optimize and compare T2 -TRIR with T2 -relaxation-under-spin-tagging (TRUST) sequence. STUDY TYPE: Prospective. POPULATION: A total of 12 healthy volunteers (six female, 27 ± 3 years old) and 7 patients with sickle cell disease (five female, 32 ± 12 years old). FIELD STRENGTH/SEQUENCE: 3 T; turbo field echo planar imaging (TFEPI), echo planar imaging (EPI), and fast field echo (FFE). ASSESSMENT: T2 b, Yv, and OEF from TRUST and T2 -TRIR were compared and T2 -TRIR-derived T1 b was assessed. Within- and between-session repeatability was quantified in the controls, whereas sensitivity to hemodynamic changes after acetazolamide (ACZ) administration was assessed in the patients. STATISTICAL TESTS: Shapiro-Wilk, one-sample and paired-sample t-test, repeated measures ANOVA, mixed linear model, Bland-Altman analysis and correlation analysis. Sidak multiple-comparison correction was performed. Significance level was 0.05. RESULTS: In controls, T2 b from T2 -TRIR (70 ± 11 msec) was higher compared to TRUST (60 ± 8 msec). In patients, T2 b values were lower pre- compared to post-ACZ administration (TRUST: 80 ± 15 msec and 106 ± 23 msec and T2 -TRIR: 95 ± 21 msec and 125 ± 36 msec). Consequently, Yv and OEF were lower and higher pre- compared to post-ACZ administration (TRUST Yv: 68% ± 7% and 77% ± 8%, T2 -TRIR Yv: 74% ± 8% and 80% ± 6%, TRUST OEF: 30% ± 7% and 21% ± 8%, and T2 -TRIR OEF: 25% ± 8% and 18% ± 6%). DATA CONCLUSION: TRUST and T2 -TRIR are reproducible, but T2 -TRIR-derived T2 b values are significantly higher compared to TRUST, resulting in higher Yv and lower OEF estimates. This bias might be considered when evaluating cerebral oxygen homeostasis. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Whole-Heart 4D Flow MRI for Evaluation of Normal and Regurgitant Valvular Flow: A Quantitative Comparison Between Pseudo-Spiral Sampling and EPI Readout.

BACKGROUND: Pseudo-spiral Cartesian sampling with compressed sensing reconstruction has facilitated highly accelerated 4D flow magnetic resonance imaging (MRI) in various cardiovascular structures. However, unlike echo planar imaging (EPI)-accelerated 4D flow MRI, it has not been validated in whole-heart applications. HYPOTHESIS: Pseudo-spiral 4D flow MRI (PROUD [PROspective Undersampling in multiple Dimensions]) is comparable to EPI in robustness of valvular flow measurements and remains comparable as the undersampling factor is increased and scan time reduced. STUDY TYPE: Prospective. POPULATION: Twelve healthy subjects and eight patients with valvular regurgitation. FIELD STRENGTH/SEQUENCE: 3.0 T; PROUD and EPI 4D flow sequences, 2D flow and balanced steady-state free precession sequences. ASSESSMENT: Valvular blood flow was quantified using valve tracking. PROUD- and EPI-based measurements of aortic (AV) and pulmonary (PV) flow volumes and left and right ventricular stroke volumes were tested for agreement with 2D MRI-based measurements. PROUD reconstructions with undersampling factors (R) of 9, 14, 28, and 56 were tested for intervalve consistency (per valve, compared to the other valves) and preservation of peak velocities and E/A ratios. STATISTICAL TESTS: We used repeated measures ANOVA, Bland-Altman, Wilcoxon signed rank, and intraclass correlation coefficients. P < 0.05 was considered statistically significant. RESULTS: PROUD and EPI intervalve consistencies were not significantly different both in healthy subjects (valve-averaged mean difference [limits of agreement width]: 3.2 ± 0.8 [8.7 ± 1.1] mL/beat for PROUD, 5.5 ± 2.9 [13.7 ± 2.3] mL/beat for EPI, P = 0.07) and in patients with valvular regurgitation (2.3 ± 1.2 [15.3 ± 5.9] mL/beat for PROUD, 0.6 ± 0.6 [19.3 ± 2.9] mL/beat for EPI, P = 0.47). Agreement between EPI and PROUD was higher than between 4D flow (EPI or PROUD) and 2D MRI for forward flow, stroke volumes, and regurgitant volumes. Up to R = 28 in healthy subjects and R = 14 in patients with valvular regurgitation, PROUD intervalve consistency remained comparable to that of EPI. Peak velocities and E/A ratios were preserved up to R = 9. CONCLUSION: PROUD is comparable to EPI in terms of intervalve consistency and may be used with higher undersampling factors to shorten scan times further. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.