Publications by authors named "Martijn Froeling"

93 Publications

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

J Diabetes Complications 2022 Jun 21;36(6):108202. Epub 2022 Apr 21.

Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.

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.
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http://dx.doi.org/10.1016/j.jdiacomp.2022.108202DOI Listing
June 2022

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

Adv Radiat Oncol 2022 Mar-Apr;7(2):100854. Epub 2021 Nov 20.

Department of Radiation Oncology, UMC Utrecht, Utrecht, the Netherlands.

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 (RE), 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; RE: 161% vs 197%; %EV: 47% vs 67%) and decreased from 2 months onward (6 months median - TTE: 25s; RE: 86%; %EV: 12%). Median ADC increased from 0.83 × 10 mm/s at baseline to 1.28 × 10 mm/s at 6 months. TTE, RE, and %EV showed the most potential to differentiate between radiologic responses, and TTE, RE, 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.
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http://dx.doi.org/10.1016/j.adro.2021.100854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977856PMC
November 2021

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

Magn Reson Med 2022 07 28;88(1):266-279. Epub 2022 Mar 28.

Center for Image Sciences, University Medical Center Utrecht, Utrecht, The Netherlands.

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/mm .

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  mm /s in the feet-to-head direction for gray matter, and 0.75 ± 0.29·10  mm /s for white matter. The measured ADC variation in the feet-to-head direction was 5.6·10  ± 1.5·10  mm /s for gray matter and 3.2·10  ± 1.0·10  mm /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.
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http://dx.doi.org/10.1002/mrm.29209DOI Listing
July 2022

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

Nat Med 2022 02 7;28(2):260-271. Epub 2022 Feb 7.

Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.

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.
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http://dx.doi.org/10.1038/s41591-021-01663-5DOI Listing
February 2022

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

NMR Biomed 2022 Jul 18;35(7):e4707. Epub 2022 Feb 18.

Department of Neurology, BG-University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany.

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 (λ ) 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.
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http://dx.doi.org/10.1002/nbm.4707DOI Listing
July 2022

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

NMR Biomed 2022 Jul 14;35(7):e4696. Epub 2022 Feb 14.

UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

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.
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http://dx.doi.org/10.1002/nbm.4696DOI Listing
July 2022

MRI of the intraspinal nerve roots in patients with chronic inflammatory neuropathies: abnormalities correlate with clinical phenotypes.

J Neurol 2022 Jun 6;269(6):3159-3166. Epub 2022 Jan 6.

Department of Neurology and Neurosurgery, University Medical Center Utrecht, Heidelberglaan 100, 3508GA, Utrecht, The Netherlands.

Objective: Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) are caused by inflammatory changes of peripheral nerves. It is unknown if the intra-spinal roots are also affected. This MRI study systematically visualized intra-spinal nerve roots, i.e., the ventral and dorsal roots, in patients with CIDP, MMN and motor neuron disease (MND).

Methods: We performed a cross-sectional study in 40 patients with CIDP, 27 with MMN and 34 with MND. All patients underwent an MRI scan of the cervical intra-spinal roots. We systematically measured intra-spinal nerve root sizes bilaterally in the transversal plane at C5, C6 and C7 level. We calculated mean nerve root sizes and compared them between study groups and between different clinical phenotypes using a univariate general linear model.

Results: Patients with MMN and CIDP with a motor phenotype had thicker ventral roots compared to patients with CIDP with a sensorimotor phenotype (p = 0.012), while patients with CIDP with a sensory phenotype had thicker dorsal roots compared to patients with a sensorimotor phenotype (p = 0.001) and with MND (p = 0.004).

Conclusion: We here show changes in the morphology of intra-spinal nerve roots in patients with chronic inflammatory neuropathies, compatible with their clinical phenotype.
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http://dx.doi.org/10.1007/s00415-021-10864-4DOI Listing
June 2022

3D Automated Segmentation of Lower Leg Muscles Using Machine Learning on a Heterogeneous Dataset.

Diagnostics (Basel) 2021 Sep 23;11(10). Epub 2021 Sep 23.

Department of Neurology, BG-University Hospital Bergmannsheil gGmbH, Ruhr-University Bochum, 44789 Bochum, Germany.

Quantitative MRI combines non-invasive imaging techniques to reveal alterations in muscle pathophysiology. Creating muscle-specific labels manually is time consuming and requires an experienced examiner. Semi-automatic and fully automatic methods reduce segmentation time significantly. Current machine learning solutions are commonly trained on data from healthy subjects using homogeneous databases with the same image contrast. While yielding high Dice scores (DS), those solutions are not applicable to different image contrasts and acquisitions. Therefore, the aim of our study was to evaluate the feasibility of automatic segmentation of a heterogeneous database. To create a heterogeneous dataset, we pooled lower leg muscle images from different studies with different contrasts and fields-of-view, containing healthy controls and diagnosed patients with various neuromuscular diseases. A second homogenous database with uniform contrasts was created as a subset of the first database. We trained three 3D-convolutional neuronal networks (CNN) on those databases to test performance as compared to manual segmentation. All networks, training on heterogeneous data, were able to predict seven muscles with a minimum average DS of 0.75. U-Net performed best when trained on the heterogeneous dataset (DS: 0.80 ± 0.10, AHD: 0.39 ± 0.35). ResNet and DenseNet yielded higher DS, when trained on a heterogeneous dataset (both DS: 0.86), as compared to a homogeneous dataset (ResNet DS: 0.83, DenseNet DS: 0.76). In conclusion, a CNN trained on a heterogeneous dataset achieves more accurate labels for predicting a heterogeneous database of lower leg muscles than a CNN trained on a homogenous dataset. We propose that a large heterogeneous database is needed, to make automated segmentation feasible for different kinds of image acquisitions.
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http://dx.doi.org/10.3390/diagnostics11101747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534967PMC
September 2021

Residual quadrupolar couplings observed in 7 Tesla deuterium MR spectra of skeletal muscle.

Magn Reson Med 2022 03 17;87(3):1165-1173. Epub 2021 Oct 17.

Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.

Purpose: Deuterium metabolic imaging could potentially be used to investigate metabolism in skeletal muscle noninvasively. However, skeletal muscle is a tissue with a high degree of spatial organization. In this study, we investigated the effect of incomplete motional averaging on the naturally abundant deuterated water signal in 7 Tesla deuterium spectra of the lower leg muscles and the dependence on the angle between the muscle fibers and the main magnetic field B , as determined by DTI.

Methods: Natural abundance deuterium MRSI measurements of the right lower leg muscles were performed at 7 Tesla. Three subjects were scanned in a supine position, with the right leg parallel with the B field. One subject was scanned twice; during the second scan, the subject was laying on his right side and the right knee was bent such that the angle between the right lower leg and B was approximately 45°. DTI was performed in the same subjects in the same positions at 3 Tesla to determine muscle fiber angles.

Results: We observed splittings in the natural abundance deuterated water signal. The size of the splittings varied between different muscles in the lower leg but were mostly similar among subjects for each muscle. The splittings depended on the orientation of the muscle fibers with respect to the main magnetic field B .

Conclusion: Partial molecular alignment in skeletal muscle leads to residual deuteron quadrupolar couplings in deuterated water, the size of which depends on the angle between the muscle fibers and B .
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http://dx.doi.org/10.1002/mrm.29053DOI Listing
March 2022

High Inter-Rater Reliability of Manual Segmentation and Volume-Based Tractography in Healthy and Dystrophic Human Calf Muscle.

Diagnostics (Basel) 2021 Aug 24;11(9). Epub 2021 Aug 24.

Department of Neurology, BG-University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, Germany.

Background: Muscle diffusion tensor imaging (mDTI) is a promising surrogate biomarker in the evaluation of muscular injuries and neuromuscular diseases. Since mDTI metrics are known to vary between different muscles, separation of different muscles is essential to achieve muscle-specific diffusion parameters. The commonly used technique to assess DTI metrics is parameter maps based on manual segmentation (MSB). Other techniques comprise tract-based approaches, which can be performed in a previously defined volume. This so-called volume-based tractography (VBT) may offer a more robust assessment of diffusion metrics and additional information about muscle architecture through tract properties. The purpose of this study was to assess DTI metrics of human calf muscles calculated with two segmentation techniques-MSB and VBT-regarding their inter-rater reliability in healthy and dystrophic calf muscles.

Methods: 20 healthy controls and 18 individuals with different neuromuscular diseases underwent an MRI examination in a 3T scanner using a 16-channel Torso XL coil. DTI metrics were assessed in seven calf muscles using MSB and VBT. Coefficients of variation (CV) were calculated for both techniques. MSB and VBT were performed by two independent raters to assess inter-rater reliability by ICC analysis and Bland-Altman plots. Next to analysis of DTI metrics, the same assessments were also performed for tract properties extracted with VBT.

Results: For both techniques, low CV were found for healthy controls (≤13%) and neuromuscular diseases (≤17%). Significant differences between methods were found for all diffusion metrics except for λ. High inter-rater reliability was found for both MSB and VBT (ICC ≥ 0.972). Assessment of tract properties revealed high inter-rater reliability (ICC ≥ 0.974).

Conclusions: Both segmentation techniques can be used in the evaluation of DTI metrics in healthy controls and different NMD with low rater dependency and high precision but differ significantly from each other. Our findings underline that the same segmentation protocol must be used to ensure comparability of mDTI data.
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http://dx.doi.org/10.3390/diagnostics11091521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466691PMC
August 2021

On the generalizability of diffusion MRI signal representations across acquisition parameters, sequences and tissue types: Chronicles of the MEMENTO challenge.

Neuroimage 2021 10 6;240:118367. Epub 2021 Jul 6.

National Institute of Health, Bethesda, USA.

Diffusion MRI (dMRI) has become an invaluable tool to assess the microstructural organization of brain tissue. Depending on the specific acquisition settings, the dMRI signal encodes specific properties of the underlying diffusion process. In the last two decades, several signal representations have been proposed to fit the dMRI signal and decode such properties. Most methods, however, are tested and developed on a limited amount of data, and their applicability to other acquisition schemes remains unknown. With this work, we aimed to shed light on the generalizability of existing dMRI signal representations to different diffusion encoding parameters and brain tissue types. To this end, we organized a community challenge - named MEMENTO, making available the same datasets for fair comparisons across algorithms and techniques. We considered two state-of-the-art diffusion datasets, including single-diffusion-encoding (SDE) spin-echo data from a human brain with over 3820 unique diffusion weightings (the MASSIVE dataset), and double (oscillating) diffusion encoding data (DDE/DODE) of a mouse brain including over 2520 unique data points. A subset of the data sampled in 5 different voxels was openly distributed, and the challenge participants were asked to predict the remaining part of the data. After one year, eight participant teams submitted a total of 80 signal fits. For each submission, we evaluated the mean squared error, the variance of the prediction error and the Bayesian information criteria. The received submissions predicted either multi-shell SDE data (37%) or DODE data (22%), followed by cartesian SDE data (19%) and DDE (18%). Most submissions predicted the signals measured with SDE remarkably well, with the exception of low and very strong diffusion weightings. The prediction of DDE and DODE data seemed more challenging, likely because none of the submissions explicitly accounted for diffusion time and frequency. Next to the choice of the model, decisions on fit procedure and hyperparameters play a major role in the prediction performance, highlighting the importance of optimizing and reporting such choices. This work is a community effort to highlight strength and limitations of the field at representing dMRI acquired with trending encoding schemes, gaining insights into how different models generalize to different tissue types and fiber configurations over a large range of diffusion encodings.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118367DOI Listing
October 2021

Quantitative magnetic resonance imaging of the brachial plexus shows specific changes in nerve architecture in chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy and motor neuron disease.

Eur J Neurol 2021 08 27;28(8):2716-2726. Epub 2021 May 27.

Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.

Background: The immunological pathophysiologies of chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) differ considerably, but neither has been elucidated completely. Quantitative magnetic resonance imaging (MRI) techniques such as diffusion tensor imaging, T2 mapping, and fat fraction analysis may indicate in vivo pathophysiological changes in nerve architecture. Our study aimed to systematically study nerve architecture of the brachial plexus in patients with CIDP, MMN, motor neuron disease (MND) and healthy controls using these quantitative MRI techniques.

Methods: We enrolled patients with CIDP (n = 47), MMN (n = 29), MND (n = 40) and healthy controls (n = 10). All patients underwent MRI of the brachial plexus and we obtained diffusion parameters, T2 relaxation times and fat fraction using an automated processing pipeline. We compared these parameters between groups using a univariate general linear model.

Results: Fractional anisotropy was lower in patients with CIDP compared to healthy controls (p < 0.001), patients with MND (p = 0.010) and MMN (p < 0.001). Radial diffusivity was higher in patients with CIDP compared to healthy controls (p = 0.015) and patients with MND (p = 0.001) and MMN (p < 0.001). T2 relaxation time was elevated in patients with CIDP compared to patients with MND (p = 0.023). Fat fraction was lower in patients with CIDP and MMN compared to patients with MND (both p < 0.001).

Conclusion: Our results show that quantitative MRI parameters differ between CIDP, MMN and MND, which may reflect differences in underlying pathophysiological mechanisms.
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http://dx.doi.org/10.1111/ene.14896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362016PMC
August 2021

Quantitative Muscle-MRI Correlates with Histopathology in Skeletal Muscle Biopsies.

J Neuromuscul Dis 2021 ;8(4):669-678

Department of Neurology, Heimer Institute for Muscle Research, University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.

Background: Skeletal muscle biopsy is one of the gold standards in the diagnostic workup of muscle disorders. By histopathologic analysis, characteristic features like inflammatory cellular infiltrations, fat and collagen replacement of muscle tissue or structural defects of the myofibers can be detected. In the past years, novel quantitative MRI (qMRI) techniques have been developed to quantify tissue parameters, thus providing a non-invasive diagnostic tool in several myopathies.

Objective: This proof-of-principle study was performed to validate the qMRI-techniques to skeletal muscle biopsy results.

Methods: Ten patients who underwent skeletal muscle biopsy for diagnostic purposes were examined by qMRI. Fat fraction, water T2-time and diffusion parameters were measured in the muscle from which the biopsy was taken. The proportion of fat tissue, the severity of degenerative and inflammatory parameters and the amount of type 1- and type 2- muscle fibers were determined in all biopsy samples. The qMRI-data were then correlated to the histopathological findings.

Results: The amount of fat tissue in skeletal muscle biopsy correlated significantly with the fat fraction derived from the Dixon sequence. The water T2-time, a parameter for tissue edema, correlated with the amount of vacuolar changes of myofibers and endomysial macrophages in the histopathologic analysis. No significant correlations were found for diffusion parameters.

Conclusion: In this proof-of-principle study, qMRI techniques were related to characteristic histopathologic features in neuromuscular disorders. The study provides the basis for further development of qMRI methods in the follow-up of patients with neuromuscular disorders, especially in the context of emerging treatment strategies.
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http://dx.doi.org/10.3233/JND-210641DOI Listing
December 2021

No need to detune transmitters in 32-channel receiver arrays at 7 T.

NMR Biomed 2021 06 10;34(6):e4491. Epub 2021 Feb 10.

Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands.

Ultrahigh field magnetic resonance imaging facilitates high spatiotemporal resolution that benefits from increasing the number of receiver elements. Because high-density receiver arrays have a relatively small element size compared with the transmitter, a side effect is that such setups cause low flux coupling between the transmitter and receiver. Moreover, when transmitters are designed in a multitransmit configuration, their relative size is much smaller than the sample, reducing coupling to the sample and thereby potentially also the coupling to the receivers. Transmitters are traditionally detuned during reception. In this study, we investigate, for a 32-channel receiver head array at 7 T, if transmitter detuning of a quadrature birdcage or of an eight-channel transmit coil can be omitted without substantially sacrificing signal-to-noise ratio (SNR). The transmit elements are operated once with and once without detuning and, in the latter, the received signals are either merged with the array or excluded for image reconstruction. For each of the three measurements, SNR and 1/g-factor maps are investigated. The tuning of the quadrature and eight-channel transmit coils during signal reception introduced a 10.1% and 6.5% penalty in SNR, respectively, relative to the SNR received with detuned transmitters. When also incorporating the signal of the transmit coils, the SNR was regained to 98.5% or 101.4% for the quadrature and eight-channel coil, respectively, relative to the detuned transmitters, while the 1/g-factor maps improved slightly. For the 32-channel receive coil used the SNR penalty can become negligible when omitting detuning of the transmit coils. This not only simplifies transmit coil designs, potentially increasing their efficiency, but also enables the transmitters to be used as receivers in parallel to the receiver array, thus increasing parallel imaging performance.
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http://dx.doi.org/10.1002/nbm.4491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244117PMC
June 2021

PCA denoising and Wiener deconvolution of P 3D CSI data to enhance effective SNR and improve point spread function.

Magn Reson Med 2021 06 1;85(6):2992-3009. Epub 2021 Feb 1.

Department of Radiology, Imaging Division, University Medical Center Utrecht, Utrecht, The Netherlands.

Purpose: This study evaluates the performance of 2 processing methods, that is, principal component analysis-based denoising and Wiener deconvolution, to enhance the quality of phosphorus 3D chemical shift imaging data.

Methods: Principal component analysis-based denoising increases the SNR while maintaining spectral information. Wiener deconvolution reduces the FWHM of the voxel point spread function, which is increased by Hamming filtering or Hamming-weighted acquisition. The proposed methods are evaluated using simulated and in vivo 3D phosphorus chemical shift imaging data by 1) visual inspection of the spatial signal distribution; 2) SNR calculation of the PCr peak; and 3) fitting of metabolite basis functions.

Results: With the optimal order of processing steps, we show that the effective SNR of in vivo phosphorus 3D chemical shift imaging data can be increased. In simulations, we show we can preserve phosphorus-containing metabolite peaks that had an SNR < 1 before denoising. Furthermore, using Wiener deconvolution, we were able to reduce the FWHM of the voxel point spread function with only partially reintroducing Gibb-ringing artifacts while maintaining the SNR. After data processing, fitting of the phosphorus-containing metabolite signals improved.

Conclusion: In this study, we have shown that principal component analysis-based denoising in combination with regularized Wiener deconvolution allows increasing the effective spectral SNR of in vivo phosphorus 3D chemical shift imaging data, with reduction of the FWHM of the voxel point spread function. Processing increased the effective SNR by at least threefold compared to Hamming weighted acquired data and minimized voxel bleeding. With these methods, fitting of metabolite amplitudes became more robust with decreased fitting residuals.
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http://dx.doi.org/10.1002/mrm.28654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986807PMC
June 2021

Quantification of disease progression in spinal muscular atrophy with muscle MRI-a pilot study.

NMR Biomed 2021 04 22;34(4):e4473. Epub 2021 Jan 22.

Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Objectives: Quantitative MRI (qMRI) of muscles is a promising tool to measure disease progression or to assess therapeutic effects in neuromuscular diseases. Longitudinal imaging studies are needed to show sensitivity of qMRI in detecting disease progression in spinal muscular atrophy (SMA). In this pilot study we therefore studied one-year changes in quantitative MR parameters in relation to clinical scores.

Methods: We repeated quantitative 3 T MR analysis of thigh muscles and clinical testing one year after baseline in 10 treatment-naïve patients with SMA, 5 with Type 2 (21.6 ± 7.0 years) and 5 with Type 3 (33.4 ± 11.9 years). MR protocol consisted of Dixon, T mapping and diffusion tensor imaging (DTI). The temporal relation of parameters was examined with a mixed model.

Results: We detected a significant increase in fat fraction (baseline, 38.2% SE 0.6; follow-up, 39.5% SE 0.6; +1.3%, p = 0.001) in all muscles. Muscles with moderate to high fat infiltration at baseline show a larger increase over time (+1.6%, p < 0.001). We did not find any changes in DTI parameters except for low fat-infiltration muscles (m. adductor longus and m. biceps femoris (short head)). The T of muscles decreased from 28.2 ms to 28.0 ms (p = 0.07). Muscle strength and motor function scores were not significantly different between follow-up and baseline.

Conclusion: Longitudinal imaging data show slow disease progression in skeletal muscle of the thigh of (young-) adult patients with SMA despite stable strength and motor function scores. Quantitative muscle imaging demonstrates potential as a biomarker for disease activity and monitoring of therapy response.
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http://dx.doi.org/10.1002/nbm.4473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988555PMC
April 2021

Post-exercise intramuscular O supply is tightly coupled with a higher proximal-to-distal ATP synthesis rate in human tibialis anterior.

J Physiol 2021 03 13;599(5):1533-1550. Epub 2021 Jan 13.

Department of Medical Imaging/Radiology, Radboud university medical center, Nijmegen, The Netherlands.

Key Points: The post-exercise recovery of phosphocreatine, a measure of the oxidative capacity of muscles, as assessed by P MR spectroscopy, shows a striking increase from distal to proximal along the human tibialis anterior muscle. To investigate why this muscle exhibits a greater oxidative capacity proximally, we tested whether the spatial variation in phosphocreatine recovery rate is related to oxygen supply, muscle fibre type or type of exercise. We revealed that oxygen supply also increases from distal to proximal along the tibialis anterior, and that it strongly correlated with phosphocreatine recovery. Carnosine level, a surrogate measure for muscle fibre type was not different between proximal and distal, and type of exercise did not affect the gradient in phosphocreatine recovery rate. Taken together, the findings of this study suggest that the post-exercise spatial gradients in oxygen supply and phosphocreatine recovery are driven by a higher intrinsic mitochondrial oxidative capacity proximally.

Abstract: Phosphorus magnetic resonance spectroscopy ( P MRS) of human tibialis anterior (TA) revealed a strong proximo-distal gradient in the post-exercise phosphocreatine (PCr) recovery rate constant (k ), a measure of muscle oxidative capacity. The aim of this study was to investigate whether this k gradient is related to O supply, resting phosphorylation potential, muscle fibre type, or type of exercise. Fifteen male volunteers performed continuous isometric ankle dorsiflexion at 30% maximum force until exhaustion. At multiple locations along the TA, we measured the oxidative PCr resynthesis rate (V = k × PCr depletion) by P MRS, the oxyhaemoglobin recovery rate constant (k ) by near infrared spectroscopy, and muscle perfusion with MR intravoxel incoherent motion imaging. The k , k , V and muscle perfusion depended on measurement location (P < 0.001, P < 0.001, P = 0.032 and P = 0.003, respectively), all being greater proximally. The k and muscle perfusion correlated with k (r = 0.956 and r = 0.852, respectively) and V (r = 0.932 and r = 0.985, respectively), the latter reflecting metabolic O consumption. Resting phosphorylation potential (PCr/inorganic phosphate) was also higher proximally (P < 0.001). The surrogate for fibre type, carnosine content measured by H MRS, did not differ between distal and proximal TA (P = 0.884). Performing intermittent exercise to avoid exercise ischaemia, still led to larger k proximally than distally (P = 0.013). In conclusion, the spatial k gradient is strongly associated with the spatial variation in O supply. It cannot be explained by exercise-induced ischaemia nor by fibre type. Our findings suggest it is driven by a higher proximal intrinsic mitochondrial oxidative capacity, apparently to support contractile performance of the TA.
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http://dx.doi.org/10.1113/JP280771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986184PMC
March 2021

Evaluation of interrater reliability of different muscle segmentation techniques in diffusion tensor imaging.

NMR Biomed 2021 02 20;34(2):e4430. Epub 2020 Nov 20.

Department of Neurology, BG-University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany.

Introduction: Muscle diffusion tensor imaging (mDTI) is a quantitative MRI technique that can provide information about muscular microstructure and integrity. Ultrasound and DTI studies have shown intramuscular differences, and therefore separation of different muscles for analysis is essential. The commonly used methods to assess DTI metrics in muscles are manual segmentation and tract-based analysis. Recently methods such as volume-based tractography have been applied to optimize muscle architecture estimation, but can also be used to assess DTI metrics.

Purpose: To evaluate diffusion metrics obtained using three different methods-volume-based tractography, manual segmentation-based analysis and tract-based analysis-with respect to their interrater reliability and their ability to detect intramuscular variance.

Materials And Methods: 30 volunteers underwent an MRI examination in a 3 T scanner using a 16-channel Torso XL coil. Diffusion-weighted images were acquired to obtain DTI metrics. These metrics were evaluated in six thigh muscles using volume-based tractography, manual segmentation and standard tractography. All three methods were performed by two independent raters to assess interrater reliability by ICC analysis and Bland-Altman plots. Ability to assess intramuscular variance was compared using an ANOVA with muscle as a between-subjects factor.

Results: Interrater reliability for all methods was found to be excellent. The highest interrater reliability was found for volume-based tractography (ICC ≥ 0.967). Significant differences for the factor muscle in all examined diffusion parameters were shown in muscles using all methods (main effect p < 0.001).

Conclusions: Diffusion data can be assessed by volume tractography, standard tractography and manual segmentation with high interrater reliability. Each method produces different results for the investigated DTI parameters. Volume-based tractography was superior to conventional manual segmentation and tractography regarding interrater reliability and detection of intramuscular variance, while tract-based analysis showed the lowest coefficients of variation.
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http://dx.doi.org/10.1002/nbm.4430DOI Listing
February 2021

Can sodium MRI be used as a method for mapping of cartilage stiffness?

MAGMA 2021 Jun 12;34(3):327-336. Epub 2020 Nov 12.

Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.

Objective: Sodium concentration is responsible for (at least part of) the stiffness of articular cartilage due to the osmotic pressure it generates. Therefore, we hypothesized that we could use sodium MRI to approximate the stiffness of cartilage to assess early cartilage degeneration.

Methods: Four human tibial plateaus were retrieved from patients undergoing total knee replacement (TKR), and their cartilage stiffness mapped with indentation testing, after which samples were scanned in a 7 T MRI to determine sodium concentration. The relation of biomechanical parameters to MRI sodium and glycosaminoglycan (GAG) concentration was explored by a linear mixed model.

Results: Weak correlations of GAG concentration with apparent peak modulus (p = 0.0057) and apparent equilibrium modulus (p = 0.0181) were observed and lack of correlation of GAG concentration versus MRI sodium concentration was observed. MRI sodium concentration was not correlated with apparent peak modulus, though a moderate correlation of MRI sodium concentration with permeability was shown (p = 0.0014).

Discussion And Conclusion: Although there was correlation between GAG concentration and cartilage stiffness, this was not similar with sodium concentration as measured by MRI. Thus, if the correlation between MRI sodium imaging and GAG concentration could be resolved, this strategy for assessing cartilage functional quality still holds promise.
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http://dx.doi.org/10.1007/s10334-020-00893-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154796PMC
June 2021

MRI of Skeletal Muscles in Participants with Type 2 Diabetes with or without Diabetic Polyneuropathy.

Radiology 2020 12 13;297(3):608-619. Epub 2020 Oct 13.

From the Departments of Neurology and International Diabetic Neuropathy Consortium (A.S., K.S.K., H.A.), Clinical Neurophysiology and International Diabetic Neuropathy Consortium (A.G.K.), Clinical Neurophysiology (H.T.), and Neurology (M.V.), Neurologisk Afdeling, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus, Denmark; Image Division, Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands (L.S., M.F.); and Department of Neurology, BG-University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany (L.S.).

BackgroundDiabetic polyneuropathy (DPN) is associated with loss of muscle strength. MRI including diffusion-tensor imaging (DTI) may enable detection of muscle abnormalities related to type 2 diabetes mellitus (DM2) and DPN.PurposeTo assess skeletal muscle abnormalities in participants with DM2 with or without DPN by using MRI.Materials and MethodsThis prospective cross-sectional study included participants with DM2 and DPN (DPN positive), participants with DM2 without DPN (DPN negative), and healthy control (HC) participants enrolled between August 2017 and June 2018. Muscle strength at the knee and ankle was determined with isokinetic dynamometry. MRI of the lower extremities included the Dixon sequence, multicomponent T2 mapping, and DTI calculated fat fractions (FFs), T2 relaxation of muscle (T2), fractional anisotropy (FA), and diffusivity (mean, axial, and radial). One-way analysis of variance and Tukey honestly significant difference were applied for comparison between groups, and multivariate regression models were used for association between MRI parameters, nerve conduction, strength, and body mass index (BMI).ResultsTwenty participants with DPN (mean age, 65 years ± 9 [standard deviation]; 70% men; mean BMI, 34 kg/m ± 5), 20 participants without DPN (mean age, 64 years ± 9; 55% men; mean BMI, 30 kg/m ± 6), and 20 HC participants (mean age, 61 years ± 10; 55% men; mean BMI, 27 kg/m ± 5) were enrolled in this study. Muscle strength adjusted for age, sex, and BMI was lower in participants with DPN than in DPN-negative and HC participants in the upper and lower leg (plantar flexors [PF], 62% vs 78% vs 89%; < .001; knee extensors [KE], 73% vs 95% vs 93%; < .001). FF was higher in leg muscle groups of participants with DPN than in DPN-negative and HC participants (PF, 20% vs 10% vs 8%; < .001; KE, 13% vs 8% vs 6%; < .001). T2 was prolonged in leg muscle groups of participants with DPN when compared with HC participants (PF, 33 msec vs 31 msec; < .001; KE, 32 msec vs 31 msec; = .002) and in the lower leg when compared with participants without DPN (PF, 33 msec vs 32 msec; = .03). In multivariate regression models, strength was associated with FA ( = -0.0004), T2 ( = -0.03 msec), and FF ( = -0.1%) at thigh level ( < .001). Furthermore, FA ( = -0.007), T2 ( = -0.53 msec), and FF ( = -4.0%) were associated with nerve conduction at calf level ( < .001).ConclusionMRI of leg muscle groups revealed fat accumulation, differences in water composition, and structural changes in participants with type 2 diabetes mellitus and neuropathy. Abnormalities were most pronounced in the plantar flexors.© RSNA, 2020See also the editorial by Sneag and Tan in this issue.
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http://dx.doi.org/10.1148/radiol.2020192647DOI Listing
December 2020

The YOUth cohort study: MRI protocol and test-retest reliability in adults.

Dev Cogn Neurosci 2020 10 8;45:100816. Epub 2020 Jul 8.

UMCU Brain Center, University Medical Center Utrecht, University Utrecht, Utrecht, the Netherlands. Electronic address:

The YOUth cohort study is a unique longitudinal study on brain development in the general population. As part of the YOUth study, 2000 children will be included at 8, 9 or 10 years of age and planned to return every three years during adolescence. Magnetic resonance imaging (MRI) brain scans are collected, including structural T1-weighted imaging, diffusion-weighted imaging (DWI), resting-state functional MRI and task-based functional MRI. Here, we provide a comprehensive report of the MR acquisition in YOUth Child & Adolescent including the test-retest reliability of brain measures derived from each type of scan. To measure test-retest reliability, 17 adults were scanned twice with a week between sessions using the full YOUth MRI protocol. Intraclass correlation coefficients were calculated to quantify reliability. Global brain measures derived from structural T1-weighted and DWI scans were reliable. Resting-state functional connectivity was moderately reliable, as well as functional brain measures for both the inhibition task (stop versus go) and the emotion task (face versus house). Our results complement previous studies by presenting reliability results of regional brain measures collected with different MRI modalities. YOUth facilitates data sharing and aims for reliable and high-quality data. Here we show that using the state-of-the art YOUth MRI protocol brain measures can be estimated reliably.
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http://dx.doi.org/10.1016/j.dcn.2020.100816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365929PMC
October 2020

Proton nuclear magnetic resonance J-spectroscopy of phantoms containing brain metabolites on a portable 0.05 T MRI scanner.

J Magn Reson 2020 11 24;320:106834. Epub 2020 Sep 24.

C. J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.

We examined approaches for obtaining H NMR spectra of brain metabolites on a low-field (B = 0.05 T) portable MRI scanner, which was developed in our laboratory with the aim of bringing cost-effective radiological services to populations in underserved, remote regions. The low static magnetic field B dictates low signal to noise ratio for metabolites in the mM concentration range, and results in an overall spectral region for the H resonances of these metabolites narrower than the linewidth obtainable in our scanner. The narrow spectral range also precludes the possibility of suppressing the large contribution of the water resonance at the acquisition stage. We used a spectroscopic Carr-Purcell-Meiboom-Gill (CPMG) sequence to acquire multiecho data from solutions of J-coupled brain metabolites, focusing on lactic acid, a metabolite whose concentration is negligible in the healthy brain and increases significantly in several disease conditions. The J spectra we obtained for lactate from the Fourier transformation of the multiecho data are spectrally well-resolved for a range of echo spacing values. We show that the J spectra at different echo spacings fit well with simulations of the evolution of echo train signal of the lactate under the same conditions. Applying a J-refocused variant of the CPMG sequence, the J modulation of the echo decay is removed, providing a way for subtracting the large contribution of the non-modulated component in the J spectrum in conditions where notching it using post-processing methods is impossible. We also demonstrate by means of experimental data and simulations that in our experimental conditions, J-spectra of other prominent brain metabolites, such as the neurotransmitter glutamate, do not yield discernible peaks and only contribute to a broad peak at zero frequency.
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http://dx.doi.org/10.1016/j.jmr.2020.106834DOI Listing
November 2020

Quantitative assessment of brachial plexus MRI for the diagnosis of chronic inflammatory neuropathies.

J Neurol 2021 Mar 23;268(3):978-988. Epub 2020 Sep 23.

Department of Neurology and Neurosurgery, University Medical Center Utrecht Brain Center, Utrecht, The Netherlands.

Objective: This study aimed at developing a quantitative approach to assess abnormalities on MRI of the brachial plexus and the cervical roots in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) and to evaluate interrater reliability and its diagnostic value.

Methods: We performed a cross-sectional study in 50 patients with CIDP, 31 with MMN and 42 disease controls. We systematically measured cervical nerve root sizes on MRI bilaterally (C5, C6, C7) in the coronal [diameter (mm)] and sagittal planes [area (mm)], next to the ganglion (G) and 1 cm distal from the ganglion (G). We determined their diagnostic value using a multivariate binary logistic model and ROC analysis. In addition, we evaluated intra- and interrater reliability.

Results: Nerve root size was larger in patients with CIDP and MMN compared to controls at all predetermined anatomical sites. We found that nerve root diameters in the coronal plane had optimal reliability (intrarater ICC 0.55-0.87; interrater ICC 0.65-0.90). AUC was 0.78 (95% CI 0.69-0.87) for measurements at G and 0.81 (95% CI 0.72-0.91) for measurements at G. Importantly, our quantitative assessment of brachial plexus MRI identified an additional 10% of patients that showed response to treatment, but were missed by nerve conduction (NCS) and nerve ultrasound studies.

Conclusion: Our study showed that a quantitative assessment of brachial plexus MRI is reliable. MRI can serve as an important additional diagnostic tool to identify treatment-responsive patients, complementary to NCS and nerve ultrasound.
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http://dx.doi.org/10.1007/s00415-020-10232-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914242PMC
March 2021

Validation of multiparametric MRI by histopathology after nephrectomy: a case study.

MAGMA 2021 Jun 20;34(3):377-387. Epub 2020 Sep 20.

Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Objectives: Renal multiparametric MRI (mpMRI) is a promising tool to monitor renal allograft health to enable timely treatment of chronic allograft nephropathy. This study aims to validate mpMRI by whole-kidney histology following transplantectomy.

Materials And Methods: A patient with kidney transplant failure underwent mpMRI prior to transplantectomy. The mpMRI included blood oxygenation level-dependent (BOLD) MRI, T and T mapping, diffusion-weighted imaging (DWI), 2D phase contrast (2DPC) and arterial spin labeling (ASL). Parenchymal mpMRI measures were compared to normative values obtained in 19 healthy controls. Differences were expressed in standard deviations (SD) of normative values. The mpMRI measures were compared qualitatively to histology.

Results: The mpMRI showed a heterogeneous parenchyma consistent with extensive interstitial hemorrhage on histology. A global increase in T (+ 3.0 SD) and restricted diffusivity (- 3.6 SD) were consistent with inflammation and fibrosis. Decreased T (- 1.8 SD) indicated fibrosis or hemorrhage. ASL showed diminished cortical perfusion (- 2.9 SD) with patent proximal arteries. 2DPC revealed a 69% decrease in renal perfusion. Histological evaluation showed a dense inflammatory infiltrate and fibrotic changes, consistent with mpMRI results. Most interlobular arteries were obliterated while proximal arteries were patent, consistent with ASL findings.

Discussion: mpMRI findings correlated well with histology both globally as well as locally.
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http://dx.doi.org/10.1007/s10334-020-00887-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154819PMC
June 2021

Marathon running transiently depletes the myocardial lipid pool.

Physiol Rep 2020 09;8(17):e14543

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

Lipids, stored as intracellular triacylglycerol droplets within the myocardium, serve as an important source of energy, particularly in times of prolonged increased energy expenditure. In only a few studies, the acute effects of exercise on such ectopic myocardial lipid storage were investigated. We studied the dynamic behavior of the myocardial lipid pool in response to completing the 2017 Amsterdam Marathon using proton magnetic resonance (MR) spectroscopy ( H-MRS). We hypothesized that the prolonged increased myocardial energy demand of running a marathon could shift the balance of myocardial triacylglycerol turnover from triacylglycerol synthesis toward lipolysis and mitochondrial fatty acid β-oxidation, and decrease the myocardial lipid pool. We employed two 3 Tesla MR systems in parallel to noninvasively examine endurance-trained healthy men (n = 8; age 50.7 [50.1-52.7] y) at 1 week prior (baseline), <6 hr after finishing the marathon (post-marathon), and 2 weeks thereafter (recovery). Exercise intensity was 89 ± 6% of the age-predicted maximal heart rate, with a finish time of 3:56 [3:37-4:42] h:min. Myocardial lipid content was 0.66 [0.58-0.87]% of the total myocardial water signal at baseline, was lower post-marathon (0.47 [0.41-0.63]% of the total myocardial water signal), and had restored to 0.55 [0.49-0.83]% of the total myocardial water signal at recovery, representing a transient marathon running-induced depletion of 29 ± 24% (p = .04). The magnitude of this myocardial lipid pool depletion did not correlate with exercise intensity (r = -0.39; p = .39), nor with marathon finishing time (ρ = 0.57; p = .15). Our data show that prolonged high-intensity exercise can induce a transient depletion of the myocardial lipid pool, reinforcing the dynamic nature of ectopic triacylglycerol storage under real-life conditions of extreme endurance exercise.
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http://dx.doi.org/10.14814/phy2.14543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460059PMC
September 2020

Multi-parametric MR in Becker muscular dystrophy patients.

NMR Biomed 2020 11 5;33(11):e4385. Epub 2020 Aug 5.

C.J. Gorter Center, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.

Quantitative MRI and MRS of muscle are increasingly being used to measure individual pathophysiological processes in Becker muscular dystrophy (BMD). In particular, muscle fat fraction was shown to be highly associated with functional tests in BMD. However, the muscle strength per unit of contractile cross-sectional area is lower in patients with BMD compared with healthy controls. This suggests that the quality of the non-fat-replaced (NFR) muscle tissue is lower than in healthy controls. Consequently, a measure that reflects changes in muscle tissue itself is needed. Here, we explore the potential of water T relaxation times, diffusion parameters and phosphorus metabolic indices as early disease markers in patients with BMD. For this purpose, we examined these measures in fat-replaced (FR) and NFR lower leg muscles in patients with BMD and compared these values with those in healthy controls. Quantitative proton MRI (three-point Dixon, multi-spin-echo and diffusion-weighted spin-echo echo planar imaging) and 2D chemical shift imaging P MRS data were acquired in 24 patients with BMD (age 18.8-66.2 years) and 13 healthy controls (age 21.3-63.6 years). Muscle fat fractions, phosphorus metabolic indices, and averages and standard deviations (SDs) of the water T relaxation times and diffusion tensor imaging (DTI) parameters were assessed in six individual leg muscles. Phosphodiester levels were increased in the NFR and FR tibialis anterior, FR peroneus and FR gastrocnemius lateralis muscles. No clear pattern was visible for the other metabolic indices. Increased T SD was found in the majority of FR muscles compared with NFR and healthy control muscles. No differences in average water T relaxation times or DTI indices were found between groups. Overall, our results indicate that primarily muscles that are further along in the disease process showed increases in T heterogeneity and changes in some metabolic indices. No clear differences were found for the DTI indices between groups.
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http://dx.doi.org/10.1002/nbm.4385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687231PMC
November 2020

Spherical deconvolution with tissue-specific response functions and multi-shell diffusion MRI to estimate multiple fiber orientation distributions (mFODs).

Neuroimage 2020 11 1;222:117206. Epub 2020 Aug 1.

PROVIDI Lab, Image Sciences Institute, UMC Utrecht, Heidelberglaan 100, 3584CX, Utrecht, the Netherlands.

In diffusion MRI, spherical deconvolution approaches can estimate local white matter (WM) fiber orientation distributions (FOD) which can be used to produce fiber tractography reconstructions. The applicability of spherical deconvolution to gray matter (GM), however, is still limited, despite its critical role as start/endpoint of WM fiber pathways. The advent of multi-shell diffusion MRI data offers additional contrast to model the GM signal but, to date, only isotropic models have been applied to GM. Evidence from both histology and high-resolution diffusion MRI studies suggests a marked anisotropic character of the diffusion process in GM, which could be exploited to improve the description of the cortical organization. In this study, we investigated whether performing spherical deconvolution with tissue specific models of both WM and GM can improve the characterization of the latter while retaining state-of-the-art performances in WM. To this end, we developed a framework able to simultaneously accommodate multiple anisotropic response functions to estimate multiple, tissue-specific, fiber orientation distributions (mFODs). As proof of principle, we used the diffusion kurtosis imaging model to represent the WM signal, and the neurite orientation dispersion and density imaging (NODDI) model to represent the GM signal. The feasibility of the proposed approach is shown with numerical simulations and with data from the Human Connectome Project (HCP). The performance of our method is compared to the current state of the art, multi-shell constrained spherical deconvolution (MSCSD). The simulations show that with our new method we can accurately estimate a mixture of two FODs at SNR≥50. With HCP data, the proposed method was able to reconstruct both tangentially and radially oriented FODs in GM, and performed comparably well to MSCSD in computing FODs in WM. When performing fiber tractography, the trajectories reconstructed with mFODs reached the cortex with more spatial continuity and for a longer distance as compared to MSCSD and allowed to reconstruct short trajectories tangential to the cortical folding. In conclusion, we demonstrated that our proposed method allows to perform spherical deconvolution of multiple anisotropic response functions, specifically improving the performances of spherical deconvolution in GM tissue.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117206DOI Listing
November 2020

Untangling the diffusion signal using the phasor transform.

NMR Biomed 2020 12 23;33(12):e4372. Epub 2020 Jul 23.

Center for Image Sciences, UMC Utrecht, Utrecht, the Netherlands.

Separating the decay signal from diffusion-weighted scans into two or more components can be challenging. The phasor technique is well established in the field of optical microscopy for visualization and separation of fluorescent dyes with different lifetimes. The use of the phasor technique for separation of diffusion-weighted decay signals was recently proposed. In this study, we investigate the added value of this technique for fitting decay models and visualization of decay rates. Phasor visualization was performed in five glioblastoma patients. Using simulations, the influence of incorrect diffusivity values and of the number of b-values on fitting a three-component model with fixed diffusivities (dubbed "unmixing") was investigated for both a phasor-based fit and a linear least squares (LLS) fit. Phasor-based intravoxel incoherent motion (IVIM) fitting was compared with nonlinear least squares (NLLS) and segmented fitting (SF) methods in terms of accuracy and precision. The distributions of the parameter estimates of simulated data were compared with those obtained in a healthy volunteer. In the phasor visualizations of two glioblastoma patients, a cluster of points was observed that was not seen in healthy volunteers. The identified cluster roughly corresponded to the enhanced edge region of the tumor of two glioblastoma patients visible on fluid-attenuated inversion recovery (FLAIR) images. For fitting decay models the usefulness of the phasor transform is less pronounced, but the additional knowledge gained from the geometrical configuration of phasor space can aid fitting routines. This has led to slightly improved fitting results for the IVIM model: phasor-based fitting yielded parameter maps with higher precision than the NLLS and SF methods for parameters f and D (interquartile range [IQR] for f: NLLS 27, SF 12, phasor 5.7%; IQR for D: NLLS 0.28, SF 0.18, phasor 0.10 μm /s). For unmixing, LLS fitting slightly but consistently outperformed phasor-based fitting in all of the tested scenarios.
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http://dx.doi.org/10.1002/nbm.4372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685171PMC
December 2020
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