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1.	Ahlgren, André, et al. (author) Quantification of microcirculatory parameters by joint analysis of flow-compensated and non-flow-compensated intravoxel incoherent motion (IVIM) data. 2016 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 29:5, s. 640-649 Journal article (peer-reviewed)abstract The aim of this study was to improve the accuracy and precision of perfusion fraction and blood velocity dispersion estimates in intravoxel incoherent motion (IVIM) imaging, using joint analysis of flow-compensated and non-flow-compensated motion-encoded MRI data. A double diffusion encoding sequence capable of switching between flow-compensated and non-flow-compensated encoding modes was implemented. In vivo brain data were collected in eight healthy volunteers and processed using the joint analysis. Simulations were used to compare the performance of the proposed analysis method with conventional IVIM analysis. With flow compensation, strong rephasing was observed for the in vivo data, approximately cancelling the IVIM effect. The joint analysis yielded physiologically reasonable perfusion fraction maps. Estimated perfusion fractions were 2.43 ± 0.81% in gray matter, 1.81 ± 0.90% in deep gray matter, and 1.64 ± 0.72% in white matter (mean ± SD, n = 8). Simulations showed improved accuracy and precision when using joint analysis of flow-compensated and non-flow-compensated data, compared with conventional IVIM analysis. Double diffusion encoding with flow compensation was feasible for in vivo imaging of the perfusion fraction in the brain. The strong rephasing implied that blood flowing through the cerebral microvascular system was closer to the ballistic limit than the diffusive limit. © 2016 The Authors NMR in Biomedicine published by John Wiley & Sons Ltd.
2.	Aksoy, M, et al. (author) Effects of motion and b-matrix correction for high resolution DTI with short-axis PROPELLER-EPI 2010 In: NMR in biomedicine. - : Wiley. - 1099-1492 .- 0952-3480. ; 23:7, s. 794-802 Journal article (peer-reviewed)
3.	Alexander, Daniel C., et al. (author) Imaging brain microstructure with diffusion MRI : Practicality and applications 2019 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 32:4, s. 3841-3841 Research review (peer-reviewed)abstract This article gives an overview of microstructure imaging of the brain with diffusion MRI and reviews the state of the art. The microstructure-imaging paradigm aims to estimate and map microscopic properties of tissue using a model that links these properties to the voxel scale MR signal. Imaging techniques of this type are just starting to make the transition from the technical research domain to wide application in biomedical studies. We focus here on the practicalities of both implementing such techniques and using them in applications. Specifically, the article summarizes the relevant aspects of brain microanatomy and the range of diffusion-weighted MR measurements that provide sensitivity to them. It then reviews the evolution of mathematical and computational models that relate the diffusion MR signal to brain tissue microstructure, as well as the expanding areas of application. Next we focus on practicalities of designing a working microstructure imaging technique: model selection, experiment design, parameter estimation, validation, and the pipeline of development of this class of technique. The article concludes with some future perspectives on opportunities in this topic and expectations on how the field will evolve in the short-to-medium term.
4.	Borga, Magnus, et al. (author) Validation of a Fast Method for Quantification of Intra-abdominal and Subcutaneous Adipose Tissue for Large Scale Human Studies 2015 In: NMR in Biomedicine. - : John Wiley & Sons. - 1099-1492 .- 0952-3480. ; 28:12, s. 1747-1753 Journal article (peer-reviewed)abstract Central obesity is the hallmark of a number of non-inheritable disorders. The advent of imaging techniques such as magnetic resonance imaging (MRI) has allowed for a fast and accurate assessment of body fat content and distribution. However, image analysis continues to be one of the major obstacles for the use of MRI in large scale studies. In this study we assess the validity of the recently proposed fat-muscle-quantitation-system (AMRATM Profiler) for the quantification of intra-abdominal adipose tissue (IAAT) and abdominal subcutaneous adipose tissue (ASAT) from abdominal MR images. Abdominal MR images were acquired from 23 volunteers with a broad range of BMIs and analysed using SliceOmatic, the current gold-standard, and the AMRATM Profiler based on a non-rigid image registration of a library of segmented atlases. The results show that there was a highly significant correlation between the fat volumes generated by both analysis methods, (Pearson correlation r = 0.97 p<0.001), with the AMRATM Profiler analysis being significantly faster (~3 mins) than the conventional SliceOmatic approach (~40 mins). There was also excellent agreement between the methods for the quantification of IAAT (AMRA 4.73 ± 1.99 vs SliceOmatic 4.73 ± 1.75 litres, p=0.97). For the AMRATM Profiler analysis, the intra-observer coefficient of variation was 1.6 % for IAAT and 1.1 % for ASAT, the inter-observer coefficient of variation was 1.4 % for IAAT and 1.2 % for ASAT, the intra-observer correlation was 0.998 for IAAT and 0.999 for ASAT, and the inter-observer correlation was 0.999 for both IAAT and ASAT. These results indicate that precise and accurate measures of body fat content and distribution can be obtained in a fast and reliable form by the AMRATM Profiler, opening up the possibility of large-scale human phenotypic studies.
5.	Brabec, Jan, et al. (author) Time-dependent diffusion in undulating thin fibers : Impact on axon diameter estimation 2020 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:3 Journal article (peer-reviewed)abstract Diffusion MRI may enable non-invasive mapping of axonal microstructure. Most approaches infer axon diameters from effects of time-dependent diffusion on the diffusion-weighted MR signal by modeling axons as straight cylinders. Axons do not, however, propagate in straight trajectories, and so far the impact of the axonal trajectory on diameter estimation has been insufficiently investigated. Here, we employ a toy model of axons, which we refer to as the undulating thin fiber model, to analyze the impact of undulating trajectories on the time dependence of diffusion. We study time-dependent diffusion in the frequency domain and characterize the diffusion spectrum by its height, width, and low-frequency behavior (power law exponent). Results show that microscopic orientation dispersion of the thin fibers is the main parameter that determines the characteristics of the diffusion spectra. At lower frequencies (longer diffusion times), straight cylinders and undulating thin fibers can have virtually identical spectra. If the straight-cylinder assumption is used to interpret data from undulating thin axons, the diameter is overestimated by an amount proportional to the undulation amplitude and microscopic orientation dispersion of the fibers. At higher frequencies (shorter diffusion times), spectra from cylinders and undulating thin fibers differ. The low-frequency behavior of the spectra from the undulating thin fibers may also differ from that of cylinders, because the power law exponent of undulating fibers can reach values below 2 for experimentally relevant frequency ranges. In conclusion, we argue that the non-straight nature of axonal trajectories should not be overlooked when analyzing and interpreting diffusion MRI data.
6.	Brinkhof, S., et al. (author) Uncompromised MRI of knee cartilage while incorporating sensitive sodium MRI 2019 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. Journal article (peer-reviewed)abstract Sodium imaging is able to assess changes in ion content, linked to glycosaminoglycan content, which is important to guide orthopeadic procedures such as articular cartilage repair. Sodium imaging is ideally performed using double tuned RF coils, to combine high resolution morphological imaging with biochemical information from sodium imaging to assess ion content. The proton image quality of such coils is often harshly degraded, with up to 50% of SNR or severe acceleration loss as compared to single tuned coils. Reasons are that the number of proton receive channels often severely reduced and double tuning will degrade the intrinsic sensitivity of the RF coil on at least one of the nuclei. However, the aim of this work was to implement a double-tuned sodium/proton knee coil setup without deterioration of the proton signal whilst being able to achieve acquisition of high SNR sodium images. A double-tuned knee coil was constructed as a shielded birdcage optimized for sodium and compromised for proton. To exclude any compromise, the proton part of the birdcage is used for transmit only and interfaced to RF amplifiers that can fully mitigate the reduced efficiency. In addition, a 15 channel single tuned proton receiver coil was embedded within the double-resonant birdcage to maintain optimal SNR and acceleration for proton imaging. To validate the efficiency of our coil, the designed coil was compared with the state-of-the-art single-tuned alternative at 7 T. B1+ corrected SNR maps were used to compare both coils on proton performance and g-factor maps were used to compare both coils on acceleration possibilities. The newly constructed double-tuned coil was shown to have comparable proton quality and acceleration possibilities to the single-tuned alternative while also being able to acquire high SNR sodium images.
7.	Chakwizira, Arthur, et al. (author) Diffusion MRI with pulsed and free gradient waveforms : effects of restricted diffusion and exchange 2023 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 36:1 Journal article (peer-reviewed)abstract Monitoring time-dependence with diffusion MRI yields observables sensitive to compartment sizes (restricted diffusion) and membrane permeability (water exchange). However, restricted diffusion and exchange have opposite effects on the diffusion-weighted signal, which can lead to errors in parameter estimates. In this work, we propose a signal representation that incorporates the effects of both restricted diffusion and exchange up to second order in b-value and is compatible with gradient waveforms of arbitrary shape. The representation features mappings from a gradient waveform to two scalars that separately control the sensitivity to restriction and exchange. We demonstrate that these scalars span a two-dimensional space that can be used to choose waveforms that selectively probe restricted diffusion or exchange, eliminating the correlation between the two phenomena. We found that waveforms with specific but unconventional shapes provide an advantage over conventional pulsed and oscillating gradient acquisitions. We also show that parametrisation of waveforms into a two-dimensional space can be used to understand protocols from other approaches that probe restricted diffusion and exchange. For example, we found that the variation of mixing time in filter-exchange imaging corresponds to variation of our exchange-weighting scalar at a fixed value of the restriction-weighting scalar. The proposed signal representation was evaluated using Monte Carlo simulations in identical parallel cylinders with hexagonal and random packing as well as parallel cylinders with gamma-distributed radii. Results showed that the approach is sensitive to sizes in the interval 4 - 12 μm and exchange rates in the simulated range of 0 to 20 s -1 , but also that there is a sensitivity to the extracellular geometry. The presented theory constitutes a simple and intuitive description of how restricted diffusion and exchange influence the signal as well as a guide to protocol design capable of separating the two effects.
8.	Eigentler, Thomas Wilhelm, et al. (author) Wideband Self-Grounded Bow-Tie Antenna for Thermal MR 2020 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:5 Journal article (peer-reviewed)abstract The objective of this study was the design, implementation, evaluation and application of a compact wideband self-grounded bow-tie (SGBT) radiofrequency (RF) antenna building block that supports anatomical proton (H-1) MRI, fluorine (F-19) MRI, MR thermometry and broadband thermal intervention integrated in a whole-body 7.0 T system. Design considerations and optimizations were conducted with numerical electromagnetic field (EMF) simulations to facilitate a broadband thermal intervention frequency of the RF antenna building block. RF transmission (B-1(+)) field efficiency and specific absorption rate (SAR) were obtained in a phantom, and the thigh of human voxel models (Ella, Duke) for H-1 and F-19 MRI at 7.0 T. B-1(+) efficiency simulations were validated with actual flip-angle imaging measurements. The feasibility of thermal intervention was examined by temperature simulations (f = 300, 400 and 500 MHz) in a phantom. The RF heating intervention (P-in = 100 W, t = 120 seconds) was validated experimentally using the proton resonance shift method and fiberoptic probes for temperature monitoring. The applicability of the SGBT RF antenna building block for in vivo H-1 and F-19 MRI was demonstrated for the thigh and forearm of a healthy volunteer. The SGBT RF antenna building block facilitated F-19 and H-1 MRI at 7.0 T as well as broadband thermal intervention (234-561 MHz). For the thigh of the human voxel models, a B-1(+) efficiency >= 11.8 mu T/root kW was achieved at a depth of 50 mm. Temperature simulations and heating experiments in a phantom demonstrated a temperature increase Delta T >7 K at a depth of 10 mm. The compact SGBT antenna building block provides technology for the design of integrated high-density RF applicators and for the study of the role of temperature in (patho-) physiological processes by adding a thermal intervention dimension to an MRI device (Thermal MR).
9.	Einarsson, Emma, et al. (author) The role of cartilage glycosaminoglycan structure in gagCEST 2020 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:5 Journal article (peer-reviewed)abstract Glycosaminoglycan (GAG) chemical exchange saturation transfer (gagCEST) is a potential method for cartilage quality assessment. The aim of this study was to investigate how the gagCEST effect depends on the types and molecular organization of GAG typically found in articular cartilage. gagCEST was performed on different concentrations of GAG in various forms: free chains of chondroitin sulfate (CS) of different types (-A and -C) and GAG bound to protein in aggregated and nonaggregated aggrecan extracted from calf articular cartilage. The measured magnetization transfer ratio asymmetry (MTRasym ) was compared with known GAG concentrations or GAG concentrations determined through biochemical analysis. The gagCEST effect was assessed through the linear regression coefficient with 95% confidence interval of MTRasym per GAG concentration. We observed a lower gagCEST effect in phantoms containing a mixture of CS-A and CS-C compared with phantoms containing mainly CS-A. The difference in response corresponds well to the difference in CS-A concentration. GAG bound in aggrecan from calf articular cartilage, where CS-A is assumed to be the major type of GAG, produed a similar gagCEST effect as that observed for free CS-A. The effect was also similar for aggregated (ie, bound to hyaluronic acid) and nonaggregated aggrecan. In conclusion, our results indicate that the aggrecan structure in itself does not impact the gagCEST effect, but that the effect is strongly dependent on GAG type. In phantoms, the current implementation of gagCEST is sensitive to CS-A while for CS-C, the main GAG component in mature human articular cartilage, the sensitivity is limited. This difference in gagCEST sensitivity between GAG types detected in phantoms is a strong motivation to also explore the possibility of a similar effect in vivo.
10.	Ferizi, U., et al. (author) Diffusion MRI microstructure models with in vivo human brain Connectome data: results from a multi-group comparison 2017 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 30:9, s. Article no e3734 - Journal article (peer-reviewed)abstract A large number of mathematical models have been proposed to describe the measured signal in diffusion-weighted (DW) magnetic resonance imaging (MRI). However, model comparison to date focuses only on specific subclasses, e.g. compartment models or signal models, and little or no information is available in the literature on how performance varies among the different types of models. To address this deficiency, we organized the White Matter Modeling Challenge' during the International Symposium on Biomedical Imaging (ISBI) 2015 conference. This competition aimed to compare a range of different kinds of models in their ability to explain a large range of measurable in vivo DW human brain data. Specifically, we assessed the ability of models to predict the DW signal accurately for new diffusion gradients and b values. We did not evaluate the accuracy of estimated model parameters, as a ground truth is hard to obtain. We used the Connectome scanner at the Massachusetts General Hospital, using gradient strengths of up to 300mT/m and a broad set of diffusion times. We focused on assessing the DW signal prediction in two regions: the genu in the corpus callosum, where the fibres are relatively straight and parallel, and the fornix, where the configuration of fibres is more complex. The challenge participants had access to three-quarters of the dataset and their models were ranked on their ability to predict the remaining unseen quarter of the data. The challenge provided a unique opportunity for a quantitative comparison of diverse methods from multiple groups worldwide. The comparison of the challenge entries reveals interesting trends that could potentially influence the next generation of diffusion-based quantitative MRI techniques. The first is that signal models do not necessarily outperform tissue models; in fact, of those tested, tissue models rank highest on average. The second is that assuming a non-Gaussian (rather than purely Gaussian) noise model provides little improvement in prediction of unseen data, although it is possible that this may still have a beneficial effect on estimated parameter values. The third is that preprocessing the training data, here by omitting signal outliers, and using signal-predicting strategies, such as bootstrapping or cross-validation, could benefit the model fitting. The analysis in this study provides a benchmark for other models and the data remain available to build up a more complete comparison in the future.
11.	Gillies, P., et al. (author) Quantification of MRS data in the frequency domain using a wavelet filter, an approximated Voigt lineshape model and prior knowledge 2006 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 19:5, s. 617-626 Journal article (peer-reviewed)abstract Quantification of MRS spectra is a challenging problem when a large baseline is present along with a low signal to noise ratio. This work investigates a robust fitting technique that yields accurate peak areas under these conditions. Using simulated long echo time 1H MRS spectra with low signal to noise ratio and a large baseline component, both the accuracy and reliability of the fit in the frequency domain were greatly improved by reducing the number of fitted parameters and making full use of all the known information concerning the Voigt lineshape. Using an appropriate first order approximation to a popular approximation of the Voigt lineshape, a significant improvement in the estimate of the area of a known spectral peak was obtained with a corresponding reduction in the residual. Furthermore, this improved parameter choice resulted in a large reduction in the number of iterations of the least-squares fitting routine. On the other hand, making use of the known centre frequency differences of the component resonances gave negligible improvement. A wavelet filter was used to remove the baseline component. In addition to performing a Monte Carlo study, these fitting techniques were also applied to a set of 10 spectra acquired from healthy human volunteers.Again, the same reduced parameter model gave the lowest value for X2 in each case.
12.	Gottschalk, Michael (author) Look-Locker FAIR TrueFISP for arterial spin labelling on mouse at 9.4 T 2020 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:3, s. 1-11 Journal article (peer-reviewed)abstract Pulsed arterial spin labelling remains a non-invasive and highly used method for the study of rodent cerebral blood flow (CBF). Flow-sensitive alternating inversion recovery (FAIR) is one of the most commonly used MR-sequences for this purpose and exists with many different strategies to record the images. This study investigates Look-Locker (LL) TrueFISP readout for FAIR as an alternative to the standard EPI readout, which is provided by the manufacturer. The aim was to show the improved image quality using TrueFISP and to verify the reproducibility of the determination of the cerebral blood flow values. The measurement of many inversion points also allowed to investigate the influence of the correct blood relaxation rate on the fit of the CBF data. For the LL-FAIR TrueFISP an in-house written method was created. The method was tested on a group of C57BL/6 mice at the field strength of 9.4 T. The results show CBF maps with less distortion than for EPI and the values found are in good agreement with the literature. A comparison of the CBF values found with EPI and LL-TrueFISP shows very small differences, most being not significant. In conclusion, the method presented gives equivalent CBF maps in comparison to standard FAIR-EPI. Both methods have the same measurement time. TrueFISP has the advantage to EPI of producing undistorted images over larger areas of the mouse brain. It is advisable to check the value of the blood relaxation rate by measurement or to estimate it as a fitting parameter.
13.	Han, Zheng, et al. (author) Dynamic contrast-enhanced CEST MRI using a low molecular weight dextran 2022 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 35:3 Journal article (peer-reviewed)abstract Natural and synthetic sugars have great potential for developing highly biocompatible and translatable chemical exchange saturation transfer (CEST) MRI contrast agents. In this study, we aimed to develop the smallest clinically available form of dextran, Dex1 (molecular weight, MW ~ 1 kDa), as a new CEST agent. We first characterized the CEST properties of Dex1 in vitro at 11.7 T and showed that the Dex1 had a detectable CEST signal at ~1.2 ppm, attributed to hydroxyl protons. In vivo CEST MRI studies were then carried out on C57BL6 mice bearing orthotopic GL261 brain tumors (n = 5) using a Bruker BioSpec 11.7 T MRI scanner. Both steady-state full Z-spectral images and single offset (1.2 ppm) dynamic dextran-enhanced (DDE) images were acquired before and after the intravenous injection of Dex1 (2 g/kg). The steady-state Z-spectral analysis showed a significantly higher CEST contrast enhancement in the tumor than in contralateral brain (∆MTRasym 1.2 ppm = 0.010 ± 0.006 versus 0.002 ± 0.008, P = 0.0069) at 20 min after the injection of Dex1. Pharmacokinetic analyses of DDE were performed using the area under the curve (AUC) in the first 10 min after Dex1 injection, revealing a significantly higher uptake of Dex1 in the tumor than in brain tissue for tumor-bearing mice (AUC[0-10 min] = 21.9 ± 4.2 versus 5.3 ± 6.4%·min, P = 0.0294). In contrast, no Dex1 uptake was foundling in the brains of non-tumor-bearing mice (AUC[0-10 min] = -1.59 ± 2.43%·min). Importantly, the CEST MRI findings were consistent with the measurements obtained using DCE MRI and fluorescence microscopy, demonstrating the potential of Dex1 as a highly translatable CEST MRI contrast agent for assessing tumor hemodynamics.
14.	Helms, Gunther, et al. (author) Simultaneous measurement of saturation and relaxation in human brain by repetitive magnetization transfer pulses 2005 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 18, s. 44-50 Journal article (peer-reviewed)
15.	Henneke, Marco, et al. (author) In vivo proton MR spectroscopy findings specific for adenylosuccinate lyase deficiency 2010 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 23:5, s. 441-445 Journal article (peer-reviewed)
16.	Henningsson, Markus, et al. (author) Myocardial arterial spin labeling in systole and diastole using flow-sensitive alternating inversion recovery with parallel imaging and compressed sensing 2021 In: NMR in Biomedicine. - : WILEY. - 0952-3480 .- 1099-1492. ; 34:2 Journal article (peer-reviewed)abstract Quantitative myocardial perfusion can be achieved without contrast agents using flow-sensitive alternating inversion recovery (FAIR) arterial spin labeling. However, FAIR has an intrinsically low sensitivity, which may be improved by mitigating the effects of physiological noise or by increasing the area of artifact-free myocardium. The aim of this study was to investigate if systolic FAIR may increase the amount of analyzable myocardium compared with diastolic FAIR and its effect on physiological noise. Furthermore, we compare parallel imaging acceleration with a factor of 2 with compressed sensing acceleration with a factor of 3 for systolic FAIR. Twelve healthy subjects were scanned during rest on a 3 T scanner using diastolic FAIR with parallel imaging factor 2 (FAIR-PI2(D)), systolic FAIR with the same acceleration (FAIR-PI2(S)) and systolic FAIR with compressed sensing factor 3 (FAIR-CS3(S)). The number of analyzable pixels in the myocardium, temporal signal-to-noise ratio (TSNR) and mean myocardial blood flow (MBF) were calculated for all methods. The number of analyzable pixels using FAIR-CS3(S) (663 +/- 55) and FAIR-PI2(S) (671 +/- 58) was significantly higher than for FAIR-PI2(D) (507 +/- 82; P = .001 for both), while there was no significant difference between FAIR-PI2(S) and FAIR-CS3(S). The mean TSNR of the midventricular slice for FAIR-PI2(D) was 11.4 +/- 3.9, similar to that of FAIR-CS3(S,) which was 11.0 +/- 3.3, both considerably higher than for FAIR-PI2(S,) which was 8.4 +/- 3.1 (P < .05 for both). Mean MBF was similar for all three methods. The use of compressed sensing accelerated systolic FAIR benefits from an increased number of analyzable myocardial pixels compared with diastolic FAIR without suffering from a TSNR penalty, unlike systolic FAIR with parallel imaging acceleration.
17.	Ijare, OB, et al. (author) Absence of glycochenodeoxycholic acid (GCDCA) in human bile is an indication of cholestasis: a 1H MRS study 2009 In: NMR in biomedicine. - : Wiley. - 1099-1492 .- 0952-3480. ; 22:5, s. 471-479 Journal article (peer-reviewed)
18.	Karlsson, Anette, 1986-, et al. (author) The effect on precision and T1 bias comparing two flip angles when estimating muscle fat infiltration using fat-referenced chemical shift-encoded imaging 2021 In: NMR in Biomedicine. - : John Wiley & Sons. - 0952-3480 .- 1099-1492. ; 34:11 Journal article (peer-reviewed)abstract Investigation of the effect on accuracy and precision of different parameter settings is important for quantitative Magnetic Resonance Imaging. The purpose of this study was to investigate T1-bias and precision for muscle fat infiltration (MFI) using fat-referenced chemical shift magnetic resonance imaging at 5° and 10° flip angle. This [MB1] experimental study was done on forty postmenopausal women using 3T MRI test and retest images using 4-point 3D spoiled gradient multi-echo acquisition including real and imaginary images for reconstruction acquired at Flip angles 5° and 10°. Post-processing included T2* correction and fat-referenced calibration of the fat signal. The mean MFI was calculated in six different automatically segmented muscle regions using both the fat-referenced fat signal and the fat fraction calculated from the fat and water image pair for each acquisition. The variance of the difference between mean MFI from test and retest was used as measure of precision. The SNR characteristics were analyzed by measuring difference of the full width half maximum of the fat signal distribution using Student’s t-test.There was no difference in the mean fat-referenced MFI at different flip angles with the fat-referenced technique, which was the case using the fat fraction. No significant difference in the precision was found in any of the muscles analyzed. However, the full width half maximum of the fat signal distribution was significantly lower at 10° flip angle compared to 5°. Fat-referenced MFI is insensitive to T1 bias in chemical shift magnetic resonance imaging enabling usage of a higher and more SNR effective flip angle. The lower full-width-at half-maximum in fat-referenced MFI at 10° indicates that high flip angle acquisition is advantageous although no significant differences in precision was observed comparing 5° and 10°.
19.	Knutsson, Linda, et al. (author) Imaging of sugar-based contrast agents using their hydroxyl proton exchange properties 2023 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 36:6 Journal article (peer-reviewed)abstract The ability of CEST MRI to detect the presence of millimolar concentrations of non-metallic contrast agents has made it possible to study, noninvasively, important biological molecules such as proteins and sugars, as well as drugs already approved for clinical use. Here, we review efforts to use sugar and sugar polymers as exogenous contrast agents, which is possible based on the exchange of their hydroxyl protons with water protons. While this capability has raised early enthusiasm, for instance about the possibility to image D-glucose metabolism with MRI in a way analogous to PET, experience over the past decade has shown that this is not trivial. On the other hand, many studies have confirmed the possibility to image a large variety of sugar analogues, each with potentially interesting applications to assess tissue physiology. Some promising applications are the study of (i) sugar delivery and transport to assess blood brain barrier integrity, (ii) sugar uptake by cells for their characterization (e.g. cancer vs healthy), as well as (iii) clearance of sugars to assess tissue drainage for instance through the glymphatic system. To judge these opportunities and their challenges, especially in the clinic, it is needed to understand the technical aspects of detecting the presence of rapidly exchanging protons through the water signal in MRI, especially as a function of magnetic field strength. We expect that novel approaches in terms of MRI detection (both saturation transfer and relaxation based), MRI data analysis, and sugar design will push this young field forward in the next decade.
20.	Lasič, Samo, et al. (author) Apparent exchange rate for breast cancer characterization. 2016 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 29:5, s. 631-639 Journal article (peer-reviewed)abstract Although diffusion MRI has shown promise for the characterization of breast cancer, it has low specificity to malignant subtypes. Higher specificity might be achieved if the effects of cell morphology and molecular exchange across cell membranes could be disentangled. The quantification of exchange might thus allow the differentiation of different types of breast cancer cells. Based on differences in diffusion rates between the intra- and extracellular compartments, filter exchange spectroscopy/imaging (FEXSY/FEXI) provides non-invasive quantification of the apparent exchange rate (AXR) of water between the two compartments. To test the feasibility of FEXSY for the differentiation of different breast cancer cells, we performed experiments on several breast epithelial cell lines in vitro. Furthermore, we performed the first in vivo FEXI measurement of water exchange in human breast. In cell suspensions, pulsed gradient spin-echo experiments with large b values and variable pulse duration allow the characterization of the intracellular compartment, whereas FEXSY provides a quantification of AXR. These experiments are very sensitive to the physiological state of cells and can be used to establish reliable protocols for the culture and harvesting of cells. Our results suggest that different breast cancer subtypes can be distinguished on the basis of their AXR values in cell suspensions. Time-resolved measurements allow the monitoring of the physiological state of cells in suspensions over the time-scale of hours, and reveal an abrupt disintegration of the intracellular compartment. In vivo, exchange can be detected in a tumor, whereas, in normal tissue, the exchange rate is outside the range experimentally accessible for FEXI. At present, low signal-to-noise ratio and limited scan time allows the quantification of AXR only in a region of interest of relatively large tumors. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.
21.	Lasič, Samo, et al. (author) Motion-compensated b-tensor encoding for in vivo cardiac diffusion-weighted imaging 2020 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:2 Journal article (peer-reviewed)abstract Motion is a major confound in diffusion-weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac applications, due to the nonrigid cyclical deformation of the myocardium. Spin echo-based DWI commonly employs gradient moment-nulling techniques to desensitise the acquisition to velocity and acceleration, ie, nulling gradient moments up to the 2nd order (M2-nulled). However, current M2-nulled DWI scans are limited to encode diffusion along a single direction at a time. We propose a method for designing b-tensors of arbitrary shapes, including planar, spherical, prolate and oblate tensors, while nulling gradient moments up to the 2nd order and beyond. The design strategy comprises initialising the diffusion encoding gradients in two encoding blocks about the refocusing pulse, followed by appropriate scaling and rotation, which further enables nulling undesired effects of concomitant gradients. Proof-of-concept assessment of in vivo mean diffusivity (MD) was performed using linear and spherical tensor encoding (LTE and STE, respectively) in the hearts of five healthy volunteers. The results of the M2-nulled STE showed that (a) the sequence was robust to cardiac motion, and (b) MD was higher than that acquired using standard M2-nulled LTE, where diffusion-weighting was applied in three orthogonal directions, which may be attributed to the presence of restricted diffusion and microscopic diffusion anisotropy. Provided adequate signal-to-noise ratio, STE could significantly shorten estimation of MD compared with the conventional LTE approach. Importantly, our theoretical analysis and the proposed gradient waveform design may be useful in microstructure imaging beyond diffusion tensor imaging where the effects of motion must be suppressed.
22.	Li, Jing-Rebecca, et al. (author) Practical computation of the diffusion MRI signal of realistic neurons based on Laplace eigenfunctions 2020 In: NMR in Biomedicine. - : John Wiley and Sons Ltd. - 0952-3480 .- 1099-1492. ; 33:10 Journal article (peer-reviewed)abstract The complex transverse water proton magnetization subject to diffusion-encoding magnetic field gradient pulses in a heterogeneous medium such as brain tissue can be modeled by the Bloch-Torrey partial differential equation. The spatial integral of the solution of this equation in realistic geometry provides a gold-standard reference model for the diffusion MRI signal arising from different tissue micro-structures of interest. A closed form representation of this reference diffusion MRI signal called matrix formalism, which makes explicit the link between the Laplace eigenvalues and eigenfunctions of the biological cell and its diffusion MRI signal, was derived 20 years ago. In addition, once the Laplace eigendecomposition has been computed and saved, the diffusion MRI signal can be calculated for arbitrary diffusion-encoding sequences and b-values at negligible additional cost. Up to now, this representation, though mathematically elegant, has not been often used as a practical model of the diffusion MRI signal, due to the difficulties of calculating the Laplace eigendecomposition in complicated geometries. In this paper, we present a simulation framework that we have implemented inside the MATLAB-based diffusion MRI simulator SpinDoctor that efficiently computes the matrix formalism representation for realistic neurons using the finite element method. We show that the matrix formalism representation requires a few hundred eigenmodes to match the reference signal computed by solving the Bloch-Torrey equation when the cell geometry originates from realistic neurons. As expected, the number of eigenmodes required to match the reference signal increases with smaller diffusion time and higher b-values. We also convert the eigenvalues to a length scale and illustrate the link between the length scale and the oscillation frequency of the eigenmode in the cell geometry. We give the transformation that links the Laplace eigenfunctions to the eigenfunctions of the Bloch-Torrey operator and compute the Bloch-Torrey eigenfunctions and eigenvalues. This work is another step in bringing advanced mathematical tools and numerical method development to the simulation and modeling of diffusion MRI.
23.	Liu, Chunlei, et al. (author) Multimodal integration of diffusion MRI for better characterization of tissue biology 2019 In: NMR in Biomedicine. - : John Wiley & Sons. - 0952-3480 .- 1099-1492. ; 32:4 Research review (peer-reviewed)abstract The contrast in diffusion-weighted MR images is due to variations of diffusion properties within the examined specimen. Certain microstructural information on the underlying tissues can be inferred through quantitative analyses of the diffusion-sensitized MR signals. In the first part of the paper, we review two types of approach for characterizing diffusion MRI signals: Blochs equations with diffusion terms, and statistical descriptions. Specifically, we discuss expansions in terms of cumulants and orthogonal basis functions, the confinement tensor formalism and tensor distribution models. Further insights into the tissue properties may be obtained by integrating diffusion MRI with other techniques, which is the subject of the second part of the paper. We review examples involving magnetic susceptibility, structural tensors, internal field gradients, transverse relaxation and functional MRI. Integrating information provided by other imaging modalities (MR based or otherwise) could be a key to improve our understanding of how diffusion MRI relates to physiology and biology.
24.	Lundholm, Lukas, et al. (author) VERDICT MRI for radiation treatment response assessment in neuroendocrine tumors. 2022 In: NMR in biomedicine. - : Wiley. - 1099-1492 .- 0952-3480. ; 35:6 Journal article (peer-reviewed)abstract Non-invasive methods to study changes in the tumor microstructure would enable early assessment of treatment response and thus facilitate personalized treatment. The aim of this study was to evaluate the diffusion MRI model Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors (VERDICT) for early response assessment to external radiation treatment and to compare the results to those of more studied sets of parameters derived from diffusion-weighted MRI data. Mice xenografted with human small intestine tumors were treated with external radiation treatment, and diffusion MRI experiments were performed on the day before and up to two weeks after treatment. The diffusion models VERDICT, ADC, IVIM, and DKI were fitted to MRI data, and the treatment response of each tumor was calculated based on pre-treatment tumor growth and post-treatment tumor volume regression. Linear regression and correlation analysis were used to evaluate each model and their respective parameters for explaining the treatment response. VERDICT analysis showed significant changes from day -1 to day 3 for the intracellular and extracellular volume fraction, as well as the cell radius index (P < 0.05; Wilcoxon signed-rank test). The strongest correlation between the diffusion model parameters and the tumor treatment response was seen for the ADC, kurtosis-corrected diffusion coefficient, and intracellular volume fraction on day 3 (τ = 0.47, 0.52, and -0.49 respectively, P < 0.05; Kendall rank correlation coefficient). Of all tested models, VERDICT held the strongest explanatory value for the tumor treatment response on day 3 (R2 = 0.75, P < 0.01; linear regression). In conclusion, VERDICT holds potential for early assessment of external radiation treatment and may provide further insight into the underlying biological effects of radiation on tumor tissue. In addition, the results suggested that the time window for assessment of treatment response using dMRI may be narrow.
25.	Lätt, Jimmy, et al. (author) Diffusion-weighted MRI measurements on stroke patients reveal water-exchange mechanisms in sub-acute ischaemic lesions. 2009 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 22:6, s. 619-628 Journal article (peer-reviewed)abstract The aim of this study was to investigate the diffusion time dependence of signal-versus-b curves obtained from diffusion-weighted magnetic resonance imaging (DW-MRI) of sub-acute ischaemic lesions in stroke patients. In this case series study, 16 patients with sub-acute ischaemic stroke were examined with DW-MRI using two different diffusion times (60 and 260 ms). Nine of these patients showed sufficiently large lesions without artefacts to merit further analysis. The signal-versus-b curves from the lesions were plotted and analysed using a two-compartment model including compartmental exchange. To validate the model and to aid the interpretation of the estimated model parameters, Monte Carlo simulations were performed. In eight cases, the plotted signal-versus-b curves, obtained from the lesions, showed a signal-curve split-up when data for the two diffusion times were compared, revealing effects of compartmental water exchange. For one of the patients, parametric maps were generated based on the extracted model parameters. These novel observations suggest that water exchange between different water pools is measurable and thus potentially useful for clinical assessment. The information can improve the understanding of the relationship between the DW-MRI signal intensity and the microstructural properties of the lesions. Copyright (c) 2009 John Wiley & Sons, Ltd.
26.	Michaelis, Thomas, et al. (author) Identification of scyllo-inositol in proton NMR-spectra of human brain invivo 1993 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 6, s. 105-109 Journal article (peer-reviewed)
27.	Moazzami, Ali, et al. (author) Changes in the metabolic profile of rat liver after α-tocopherol deficiency as revealed by metabolomic analysis 2011 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 24, s. 499-505 Journal article (peer-reviewed)
28.	Montelius, Mikael, 1979, et al. (author) Multiparametric MR for non-invasive evaluation of tumour tissue histological characteristics after radionuclide therapy. 2019 In: NMR in biomedicine. - : Wiley. - 1099-1492 .- 0952-3480. ; 31:3 Journal article (peer-reviewed)abstract Early non-invasive tumour therapy response assessment requires methods sensitive to biological and physiological tumour characteristics. The aim of this study was to find and evaluate magnetic resonance imaging (MRI) derived tumour tissue parameters that correlate with histological parameters and that reflect effects of radionuclide therapy. Mice bearing a subcutaneous human small-intestine neuroendocrine tumour were i.v. injected with 177 Lu-octreotate. MRI was performed (7T Bruker Biospec) on different post-therapy intervals (1 and 13days) using T2-weighted imaging, mapping of T2* and T1 relaxation time constants, as well as diffusion and dynamic contrast enhancement (DCE-MRI) techniques. After MRI, animals were killed and tumours excised. Four differently stained histological sections of the most central imaged tumour plane were digitized, and segmentation techniques were used to produce maps reflecting fibrotic and vascular density, apoptosis, and proliferation. Histological maps were aligned with MRI-derived parametric maps using landmark-based registration. Correlations and predictive power were evaluated using linear mixed-effects models and cross-validation, respectively. Several MR parameters showed statistically significant correlations with histological parameters. In particular, three DCE-MRI-derived parameters reflecting capillary function additionally showed high predictive power regarding apoptosis (2/3) and proliferation (1/3). T1 could be used to predict vascular density, and perfusion fraction derived from diffusion MRI could predict fibrotic density, although with lower predictive power. This work demonstrates the potential to use multiparametric MRI to retrieve important information on the tumour microenvironment after radiotherapy. The non-invasiveness of the method also allows longitudinal tumour tissue characterization. Further investigation is warranted to evaluate the parameters highlighted in this study longitudinally, in larger studies, and with additional histological methods.
29.	Müller, Christoph A., et al. (author) Dynamic 2D and 3D mapping of hyperpolarized pyruvate to lactate conversion in vivo with efficient multi-echo balanced steady-state free precession at 3 T 2020 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:6 Journal article (peer-reviewed)abstract The aim of this study was to acquire the transient MRI signal of hyperpolarized tracers and their metabolites efficiently, for which specialized imaging sequences are required. In this work, a multi-echo balanced steady-state free precession (me-bSSFP) sequence with Iterative Decomposition with Echo Asymmetry and Least squares estimation (IDEAL) reconstruction was implemented on a clinical 3 T positron-emission tomography/MRI system for fast 2D and 3D metabolic imaging. Simulations were conducted to obtain signal-efficient sequence protocols for the metabolic imaging of hyperpolarized biomolecules. The sequence was applied in vitro and in vivo for probing the enzymatic exchange of hyperpolarized [1–13C]pyruvate and [1–13C]lactate. Chemical shift resolution was achieved using a least-square, iterative chemical species separation algorithm in the reconstruction. In vitro, metabolic conversion rate measurements from me-bSSFP were compared with NMR spectroscopy and free induction decay-chemical shift imaging (FID-CSI). In vivo, a rat MAT-B-III tumor model was imaged with me-bSSFP and FID-CSI. 2D metabolite maps of [1–13C]pyruvate and [1–13C]lactate acquired with me-bSSFP showed the same spatial distributions as FID-CSI. The pyruvate-lactate conversion kinetics measured with me-bSSFP and NMR corresponded well. Dynamic 2D metabolite mapping with me-bSSFP enabled the acquisition of up to 420 time frames (scan time: 180-350 ms/frame) before the hyperpolarized [1–13C]pyruvate was relaxed below noise level. 3D metabolite mapping with a large field of view (180 × 180 × 48 mm3) and high spatial resolution (5.6 × 5.6 × 2 mm3) was conducted with me-bSSFP in a scan time of 8.2 seconds. It was concluded that Me-bSSFP improves the spatial and temporal resolution for metabolic imaging of hyperpolarized [1–13C]pyruvate and [1–13C]lactate compared with either of the FID-CSI or EPSI methods reported at 3 T, providing new possibilities for clinical and preclinical applications.
30.	Nilsson, Markus, et al. (author) Resolution limit of cylinder diameter estimation by diffusion MRI : The impact of gradient waveform and orientation dispersion 2017 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 30:7 Journal article (peer-reviewed)abstract Diffusion MRI has been proposed as a non-invasive technique for axonal diameter mapping. However, accurate estimation of small diameters requires strong gradients, which is a challenge for the transition of the technique from preclinical to clinical MRI scanners, since these have weaker gradients. In this work, we develop a framework to estimate the lower bound for accurate diameter estimation, which we refer to as the resolution limit. We analyse only the contribution from the intra-axonal space and assume that axons can be represented by impermeable cylinders. To address the growing interest in using techniques for diffusion encoding that go beyond the conventional single diffusion encoding (SDE) sequence, we present a generalised analysis capable of predicting the resolution limit regardless of the gradient waveform. Using this framework, waveforms were optimised to minimise the resolution limit. The results show that, for parallel cylinders, the SDE experiment is optimal in terms of yielding the lowest possible resolution limit. In the presence of orientation dispersion, diffusion encoding sequences with square-wave oscillating gradients were optimal. The resolution limit for standard clinical MRI scanners (maximum gradient strength 60-80mT/m) was found to be between 4 and 8μm, depending on the noise levels and the level of orientation dispersion. For scanners with a maximum gradient strength of 300mT/m, the limit was reduced to between 2 and 5μm.
31.	Nyblom, Hanna K., et al. (author) Glucose-induced de novo synthesis of fatty acyls causes proportional increases in INS-1E cellular lipids 2008 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 21:4, s. 357-365 Journal article (peer-reviewed)abstract Raised concentrations of glucose for extended periods of time have detrimental effects on the insulin-producing P-cell. As de novo synthesis of lipids has been observed under such conditions, it was hypothesized that newly formed lipids may preferentially contain saturated fatty acids, which in particular have been associated with impaired beta-cell function. Glucose-induced de novo synthesis of fatty acids in INS-1E cells cultured in 5.5, 11, 20 or 27 mM glucose for 5 days was assessed by high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy and gas chromatography-mass spectrometry (GC-MS). The glucose origin of the increase in fatty acyls was verified by replacing glucose with [1-C-13]glucose during culture followed by analysis with two-dimensional H-1-C-13 NMR spectroscopy. The composition of the fatty acyls was determined by GC-MS. Fatty acyls determined by HR-MAS H-1 NMR spectroscopy were increased fivefold in INS-1E cells cultured in 20 or 27mM glucose compared with cells cultured in 5.5mM glucose. The five most abundant fatty acids with their relative percentages in INS-1E cells cultured in 5.5 mM glucose were oleate (33%), palmitate (25%), stearate (19%), octadecenoate (13%) and palmitoleate (4.4%). These proportions were not affected by glucose-induced de novo synthesis in INS-1E cells cultured in 11, 20 or 27 mM glucose. It is concluded that glucose-induced de novo lipid synthesis results in accumulation of both saturated and unsaturated fatty acids in specific proportions that are identical with those present under control conditions.
32.	Reymbaut, Alexis, et al. (author) Accuracy and precision of statistical descriptors obtained from multidimensional diffusion signal inversion algorithms 2020 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:12 Journal article (peer-reviewed)abstract In biological tissues, typical MRI voxels comprise multiple microscopic environments, the local organization of which can be captured by microscopic diffusion tensors. The measured diffusion MRI signal can, therefore, be written as the multidimensional Laplace transform of an intravoxel diffusion tensor distribution (DTD). Tensor-valued diffusion encoding schemes have been designed to probe specific features of the DTD, and several algorithms have been introduced to invert such data and estimate statistical descriptors of the DTD, such as the mean diffusivity, the variance of isotropic diffusivities, and the mean squared diffusion anisotropy. However, the accuracy and precision of these estimations have not been assessed systematically and compared across methods. In this article, we perform and compare such estimations in silico for a one-dimensional Gamma fit, a generalized two-term cumulant approach, and two-dimensional and four-dimensional Monte-Carlo-based inversion techniques, using a clinically feasible tensor-valued acquisition scheme. In particular, we compare their performance at different signal-to-noise ratios (SNRs) for voxel contents varying in terms of the aforementioned statistical descriptors, orientational order, and fractions of isotropic and anisotropic components. We find that all inversion techniques share similar precision (except for a lower precision of the two-dimensional Monte Carlo inversion) but differ in terms of accuracy. While the Gamma fit exhibits infinite-SNR biases when the signal deviates strongly from monoexponentiality and is unaffected by orientational order, the generalized cumulant approach shows infinite-SNR biases when this deviation originates from the variance in isotropic diffusivities or from the low orientational order of anisotropic diffusion components. The two-dimensional Monte Carlo inversion shows remarkable accuracy in all systems studied, given that the acquisition scheme possesses enough directions to yield a rotationally invariant powder average. The four-dimensional Monte Carlo inversion presents no infinite-SNR bias, but suffers significantly from noise in the data, while preserving good contrast in most systems investigated.
33.	Risse, Frank, et al. (author) A texture analysis approach to quantify ventilation changes in hyperpolarised (3) He MRI of the rat lung in an asthma model. 2012 In: NMR in biomedicine. - : Wiley. - 1099-1492 .- 0952-3480. ; 25:1, s. 131-141 Journal article (peer-reviewed)abstract In preclinical research, allergic asthma is investigated in rats sensitised with the antigen ovalbumin (OVA), followed by a challenge with aerosolised OVA to induce an inflammatory reaction of the lower airways. This causes diffuse, nonfocal ventilation defects that lead to heterogeneously distributed signal intensities in hyperpolarised (HP) (3) He MR images, which are difficult to assess directly by diagnostic grading or volumetry. Texture analysis can characterise these changes and does not require segmentation of the lung structures prior to the analysis. The aim of this work was to evaluate a texture analysis approach to quantify changes in lung ventilation in HP (3) He MRI of OVA-challenged rats. OVA-challenged animals were treated with two different compound doses to evaluate the sensitivity of the texture analysis. Four groups were investigated using HP (3) He MRI at 4.7T: controls, vehicle-treated, and low- and high-dose budesonide-treated rats. In addition, broncho-alveolar lavage was performed and the eosinophil cell count was used as a biological reference marker. First-order texture, geometrical features and features based on second-order statistics using run-length and grey-level co-occurrence matrices were calculated. In addition, wavelet transforms were applied to compute first-order statistics on multiple scales. The texture analysis was able to show significant differences between the control and untreated vehicle groups as well as between the vehicle and treatment groups. This is in agreement with the findings of the eosinophil cell counts, which were used as a marker for the severity of inflammation. However, not all features used in the different texture analysis methods could differentiate between the treatment groups. In conclusion, texture analysis can be used to quantify changes in lung ventilation as measured with HP (3) He MRI after therapeutic intervention with budesonide. Copyright © 2011 John Wiley & Sons, Ltd.
34.	Rivera-Rivera, Leonardo A., et al. (author) Four-dimensional flow MRI for quantitative assessment of cerebrospinal fluid dynamics : Status and opportunities 2024 In: NMR in Biomedicine. - : John Wiley & Sons. - 0952-3480 .- 1099-1492. ; 37:7 Journal article (peer-reviewed)abstract Neurological disorders can manifest with altered neurofluid dynamics in different compartments of the central nervous system. These include alterations in cerebral blood flow, cerebrospinal fluid (CSF) flow, and tissue biomechanics. Noninvasive quantitative assessment of neurofluid flow and tissue motion is feasible with phase contrast magnetic resonance imaging (PC MRI). While two-dimensional (2D) PC MRI is routinely utilized in research and clinical settings to assess flow dynamics through a single imaging slice, comprehensive neurofluid dynamic assessment can be limited or impractical. Recently, four-dimensional (4D) flow MRI (or time-resolved three-dimensional PC with three-directional velocity encoding) has emerged as a powerful extension of 2D PC, allowing for large volumetric coverage of fluid velocities at high spatiotemporal resolution within clinically reasonable scan times. Yet, most 4D flow studies have focused on blood flow imaging. Characterizing CSF flow dynamics with 4D flow (i.e., 4D CSF flow) is of high interest to understand normal brain and spine physiology, but also to study neurological disorders such as dysfunctional brain metabolite waste clearance, where CSF dynamics appear to play an important role. However, 4D CSF flow imaging is challenged by the long T1 time of CSF and slower velocities compared with blood flow, which can result in longer scan times from low flip angles and extended motion-sensitive gradients, hindering clinical adoption. In this work, we review the state of 4D CSF flow MRI including challenges, novel solutions from current research and ongoing needs, examples of clinical and research applications, and discuss an outlook on the future of 4D CSF flow.
35.	Sandvig, Ioanna, et al. (author) In vivo MRI of olfactory ensheathing cell grafts and regenerating axons in transplant mediated repair of the adult rat optic nerve 2012 In: NMR in Biomedicine. - Malden, MA, USA : John Wiley & Sons. - 0952-3480 .- 1099-1492. ; 25:4, s. 620-631 Journal article (peer-reviewed)abstract The purpose of the present study was to use magnetic resonance imaging (MRI) as a tool for monitoring transplant-mediated repair of the adult rat visual pathway. We labelled rat olfactory ensheathing cells (OECs) using micron-sized particles of iron oxide (MPIO) and transplanted them by: i) intravitreal injection (ivit) and ii) intra-optic nerve (ON) injection (iON) in adult rats with ON crush (ONC) injury. We applied T2-weighted MRI and manganese-enhanced MRI (MEMRI) to visualise transplanted cells and ON axons at specific times after injury and cell engraftment. Our findings demonstrate that ivit MPIO-labelled OECs are unequivocally detected by T2-weighted MRI in vivo and that the T1-weighted 3D FLASH sequence applied for MEMRI facilitates simultaneous visualisation of Mn2+-enhanced regenerating retinal ganglion cell (RGC) axons and MPIO-labelled OEC grafts. Furthermore, analysis of MRI data and ultrastructural findings supports the hypothesis that iON OEC transplants mediate regeneration and remyelination of RGC axons post injury.
36.	Seidemo, Anina, et al. (author) Tissue response curve shape analysis of dynamic glucose enhanced (DGE) and dynamic contrast enhanced (DCE) MRI in patients with brain tumor 2023 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 36:6 Journal article (peer-reviewed)abstract Dynamic glucose enhanced (DGE) MRI is used to study the signal intensity time course (tissue response curve) after D-glucose injection. D-glucose has potential as a biodegradable alternative or complement to gadolinium-based contrast agents, with DGE being comparable to dynamic contrast enhanced (DCE) MRI. However, the tissue uptake kinetics as well as the detection methods of DGE differ from DCE, and it is relevant to compare these techniques in terms of spatiotemporal enhancement patterns. This study aims to develop a DGE analysis method based on tissue response curve shapes, and to investigate whether DGE MRI provides similar or complementary information to DCE MRI. Eleven patients with suspected gliomas were studied. Tissue response curves were measured for DGE and DCE MRI at 7 tesla and the area under curve (AUC) was assessed. Seven types of response curve shapes were postulated and subsequently identified by deep learning to create color-coded “curve maps” showing the spatial distribution of different curve types. DGE AUC values were significantly higher in lesions than in normal tissue (p
37.	Seidemo, Anina, et al. (author) Towards robust glucose chemical exchange saturation transfer imaging in humans at 3 T: Arterial input function measurements and the effects of infusion time 2022 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 35:2, s. 4624-4624 Journal article (peer-reviewed)abstract Dynamic glucose-enhanced (DGE) magnetic resonance imaging (MRI) has shown potential for tumor imaging using D-glucose as a biodegradable contrast agent. The DGE signal change is small at 3 T (around 1 and accurate detection is hampered by motion. The intravenous D-glucose injection is associated with transient side effects that can indirectly generate subject movements. In this study, the aim was to study DGE arterial input functions (AIFs) in healthy volunteers at 3 T for different scanning protocols, as a step towards making the glucose chemical exchange saturation transfer (glucoCEST) protocol more robust. Two different infusion durations (1.5 and 4.0 min) and saturation frequency offsets (1.2 and 2.0 ppm) were used. The effect of subject motion on the DGE signal was studied by using motion estimates retrieved from standard retrospective motion correction to create pseudo-DGE maps, where the apparent DGE signal changes were entirely caused by motion. Furthermore, the DGE AIFs were compared with venous blood glucose levels. A significant difference (p = 0.03) between arterial baseline and postinfusion DGE signal was found after D-glucose infusion. The results indicate that the measured DGE AIF signal change depends on both motion and blood glucose concentration change, emphasizing the need for sufficient motion correction in glucoCEST imaging. Finally, we conclude that a longer infusion duration (e.g. 3–4 min) should preferably be used in glucoCEST experiments, because it can minimize the glucose infusion side effects without negatively affecting the DGE signal change.
38.	Starck, Göran, et al. (author) k-space analysis of point-resolved spectroscopy (PRESS) with regard to spurious echoes in in vivo (1)H MRS. 2009 In: NMR in biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 22:2, s. 137-47 Journal article (peer-reviewed)abstract The spurious echo artefact, not uncommon in (1)H MRS in the brain, comes from refocusing outer volume signal. Application of MRS in small volumes in susceptibility-affected regions often results in large shim gradients. The artefact problem is accentuated when the global effect of the shim gradient shifts the water resonance outside the water suppression band in the outer volume. This scenario brings the issue of spurious echoes once again to the fore. In this paper, spurious signals of the point-resolved spectroscopy (PRESS) sequence are analysed using the concept of k-space. This new approach facilitates a more geometrical view of the problem, well suited for studying the effect of gradient spoiling and refocusing of signal. Several spoiling options are shown, and the probability of the global effects of shimming being a primary cause of the artefact is discussed. Fourier transform analysis of realistic slice profiles, combined with the k-space description of spurious echoes, shows that unsuppressed water signal in outer regions greatly increases the demands on spoiling. Gradient spoiling adequate for artefact suppression at a given size of MRS volume may not be sufficient at a smaller size. Several ways to improve PRESS measurements with regard to suppression of spurious signal are discussed.
39.	Stephenson, M C, et al. (author) Variability in fasting lipid and glycogen contents in hepatic and skeletal muscle tissue in subjects with and without type 2 diabetes : a 1H and 13C MRS study 2013 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 26:11, s. 1518-1526 Journal article (peer-reviewed)abstract The measurement of tissue lipid and glycogen contents and the establishment of normal levels of variability are important when assessing changes caused by pathology or treatment. We measured hepatic and skeletal muscle lipid and glycogen levels using 1H and 13C MRS at 3 T in groups of subjects with and without type 2 diabetes. Within-visit reproducibility, due to repositioning and instrument errors was determined from repeat measurements made over 1 h. Natural variability was assessed from separate measurements made on three occasions over 1 month. Hepatic lipid content was greater in subjects with diabetes relative to healthy subjects (p = 0.03), whereas levels of hepatic and skeletal muscle glycogen, and of intra- and extra-myocellular lipid, were similar. The single-session reproducibility values (coefficient of variation, CV) for hepatic lipid content were 12% and 7% in groups of subjects with and without diabetes, respectively. The variability of hepatic lipid content over 1 month was greater than the reproducibility, with CV = 22% (p = 0.08) and CV = 44% (p = 0.004) in subjects with and without diabetes, respectively. Similarly, levels of variation in basal hepatic glycogen concentrations (subjects with diabetes, CV = 38%; healthy volunteers, CV = 35%) were significantly larger than single-session reproducibility values (CV = 17%, p = 0.02 and CV = 13%, p = 0.05, respectively), indicating substantial biological changes in basal concentrations over 1 month. There was a decreasing correlation in measurements of both hepatic lipid and glycogen content with increasing time between scans. Levels of variability in intra- and extra-myocellular lipid in the soleus muscle, and glycogen concentrations in the gastrocnemius muscle, tended to be larger than expected from single-session reproducibility, although these did not reach significance.
40.	Tobisch, Alexandra, et al. (author) Comparison of basis functions and q-space sampling schemes for robust compressed sensing reconstruction accelerating diffusion spectrum imaging 2019 In: NMR in Biomedicine. - : WILEY. - 0952-3480 .- 1099-1492. ; 32:3 Journal article (peer-reviewed)abstract Time constraints placed on magnetic resonance imaging often restrict the application of advanced diffusion MRI (dMRI) protocols in clinical practice and in high throughput research studies. Therefore, acquisition strategies for accelerated dMRI have been investigated to allow for the collection of versatile and high quality imaging data, even if stringent scan time limits are imposed. Diffusion spectrum imaging (DSI), an advanced acquisition strategy that allows for a high resolution of intra-voxel microstructure, can be sufficiently accelerated by means of compressed sensing (CS) theory. CS theory describes a framework for the efficient collection of fewer samples of a data set than conventionally required followed by robust reconstruction to recover the full data set from sparse measurements. For an accurate recovery of DSI data, a suitable acquisition scheme for sparse q-space sampling and the sensing and sparsifying bases for CS reconstruction need to be selected. In this work we explore three different types of q-space undersampling schemes and two frameworks for CS reconstruction based on either Fourier or SHORE basis functions. After CS recovery, diffusion and microstructural parameters and orientational information are estimated from the reconstructed data by means of state-of-the-art processing techniques for dMRI analysis. By means of simulation, diffusion phantom and in vivo DSI data, an isotropic distribution of q-space samples was found to be optimal for sparse DSI. The CS reconstruction results indicate superior performance of Fourier-based CS-DSI compared to the SHORE-based approach. Based on these findings we outline an experimental design for accelerated DSI and robust CS reconstruction of the sparse measurements that is suitable for the application within time-limited studies.
41.	Topgaard, Daniel (author) Diffusion tensor distribution imaging 2019 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 32:5 Journal article (peer-reviewed)abstract Conventional diffusion MRI yields voxel-averaged parameters that suffer from ambiguities for heterogeneous anisotropic materials such as brain tissue. Using principles from solid-state NMR spectroscopy, we have previously introduced the shape of the diffusion encoding tensor as a separate acquisition dimension that disentangles isotropic and anisotropic contributions to the observed diffusivities, thereby allowing for unconstrained data inversion into diffusion tensor distributions with “size,” “shape,” and orientation dimensions. Here we combine our recent non-parametric data inversion algorithm and data acquisition protocol with an imaging pulse sequence to demonstrate spatial mapping of diffusion tensor distributions using a previously developed composite phantom with multiple isotropic and anisotropic components. We propose a compact format for visualizing two-dimensional arrays of the distributions, new scalar parameters quantifying intra-voxel heterogeneity, and a binning procedure giving maps of all relevant parameters for each of the components resolved in the multidimensional distribution space.
42.	Torres, Alejandra N, et al. (author) Positional and compositional analysis of saturated, monounsaturated, and polyunsaturated fatty acids in human adipose tissue triglyceride by 13 C nuclear magnetic resonance 2023 In: NMR in Biomedicine. - : John Wiley & Sons. - 0952-3480 .- 1099-1492. ; 36:4 Journal article (peer-reviewed)abstract The synthesis and turnover of triglyceride in adipose tissue involves enzymes with preferences for specific fatty acid classes and/or regioselectivity regarding the fatty acid position within the glycerol moiety. The focus of the current study was to characterize both the composition of fatty acids and their positional distribution in triglycerides of biopsied human subcutaneous adipose tissue, from subjects with wide ranges of body mass index (BMI) and insulin sensitivity, using 13 C nuclear magnetic resonance (NMR) spectroscopy. The triglyceride sn2 position was significantly more enriched with monounsaturated fatty acids compared with that of sn1,3, while the abundance of saturated fatty acids was significantly lower in the sn2 position compared with that of sn1,3. Furthermore, the analysis revealed significant positive correlations between the total fraction of palmitoleic acid with both BMI and insulin sensitivity scores (homeostatic model assessment of insulin resistance index). Additionally, we established that 13 C NMR chemical shifts for ω-3 signals, centered at 31.9 ppm, provided superior resolution of the most abundant fatty acid species, including palmitoleate, compared with the ω-2 signals that were used previously. 13 C NMR spectroscopy reveals for the first time a highly nonhomogenous distribution of fatty acids in the glycerol sites of human adipose tissue triglyceride, and that these distributions are correlated with different phenotypes, such as BMI and insulin sensitivity.
43.	Ulloa, Jose L, et al. (author) Assessment of gadoxetate DCE-MRI as a biomarker of hepatobiliary transporter inhibition 2013 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 26:10, s. 1258-1270 Journal article (peer-reviewed)abstract Drug-induced liver injury (DILI) is a clinically important adverse drug reaction, which prevents the development of many otherwise safe and effective new drugs. Currently, there is a lack of sensitive and specific biomarkers that can be used to predict, assess and manage this toxicity. The aim of this work was to evaluate gadoxetate-enhanced MRI as a potential novel biomarker of hepatobiliary transporter inhibition in the rat. Initially, the volume fraction of extracellular space in the liver was determined using gadopentetate to enable an estimation of the gadoxetate concentration in hepatocytes. Using this information, a compartmental model was developed to characterise the pharmacokinetics of hepatic uptake and biliary excretion of gadoxetate. Subsequently, we explored the impact of an investigational hepatobiliary transporter inhibitor on the parameters of the model in vivo in rats. The investigational hepatobiliary transporter inhibitor reduced both the rate of uptake of gadoxetate into the hepatocyte, k 1 , and the Michaelis-Menten constant, V max , characterising its excretion into bile, whereas K M values for biliary efflux were increased. These effects were dose dependent and correlated with effects on plasma chemistry markers of liver dysfunction, in particular bilirubin and bile acids. These results indicate that gadoxetate-enhanced MRI provides a novel functional biomarker of inhibition of transporter-mediated hepatic uptake and clearance in the rat. Since gadoxetate is used clinically, the technology has the potential to provide a translatable biomarker of drug-induced perturbation of hepatic transporters that may also be useful in humans to explore deleterious functional alterations caused by transporter inhibition. © 2013 John Wiley & Sons, Ltd.
44.	van Osch, Matthias J. P., et al. (author) Human brain clearance imaging : pathways taken by magnetic resonance imaging contrast agents after administration in cerebrospinal fluid and blood 2024 In: NMR in Biomedicine. - : John Wiley & Sons. - 0952-3480 .- 1099-1492. ; 37:9 Research review (peer-reviewed)abstract Over the last decade, it has become evident that cerebrospinal fluid (CSF) plays a pivotal role in brain solute clearance through perivascular pathways and interactions between the brain and meningeal lymphatic vessels. Whereas most of this fundamental knowledge was gained from rodent models, human brain clearance imaging has provided important insights into the human system and highlighted the existence of important interspecies differences. Current gold standard techniques for human brain clearance imaging involve the injection of gadolinium-based contrast agents and monitoring their distribution and clearance over a period from a few hours up to 2 days. With both intrathecal and intravenous injections being used, which each have their own specific routes of distribution and thus clearance of contrast agent, a clear understanding of the kinetics associated with both approaches, and especially the differences between them, is needed to properly interpret the results. Because it is known that intrathecally injected contrast agent reaches the blood, albeit in small concentrations, and that similarly some of the intravenously injected agent can be detected in CSF, both pathways are connected and will, in theory, reach the same compartments. However, because of clear differences in relative enhancement patterns, both injection approaches will result in varying sensitivities for assessment of different subparts of the brain clearance system. In this opinion review article, the "EU Joint Programme – Neurodegenerative Disease Research (JPND)" consortium on human brain clearance imaging provides an overview of contrast agent pharmacokinetics in vivo following intrathecal and intravenous injections and what typical concentrations and concentration–time curves should be expected. This can be the basis for optimizing and interpreting contrast-enhanced MRI for brain clearance imaging. Furthermore, this can shed light on how molecules may exchange between blood, brain, and CSF.
45.	Weis, Jan, 1956-, et al. (author) Phosphorus MRS of healthy human spleen. 2022 In: NMR in Biomedicine. - : John Wiley & Sons. - 0952-3480 .- 1099-1492. ; 35:10 Journal article (peer-reviewed)abstract Phosphorus (31 P-) MRS in vivo enables detection and quantification of important phosphorus-containing metabolites in biological tissues. 31 P-MRS of the normal spleen is challenging due to the relatively small volume and the larger distance between the spleen and surface coil. However, reference spectra of the healthy spleen are invaluable in studies of splenic malignancies and benign causes of splenomegaly, as well as in the study of its physiology. The purpose of this work was to investigate the feasibility of localized 31 P-MRS of healthy spleen in situ in a clinically acceptable measurement time using a clinical 3 T MR scanner. In this work, 31 P spectra of five healthy volunteers were measured using single-voxel image-selected in vivo spectroscopy (ISIS). The measurement sequence was augmented by broadband proton decoupling and nuclear Overhauser effect enhancement. It is demonstrated that localized 31 P-MRS of the spleen in situ using single-voxel ISIS is feasible on a clinical 3 T scanner in a clinically acceptable acquisition time. However, results have to be corrected for the transmitter excitation profile, and chemical shift displacement errors need to be taken into consideration during placement of the volume of interest. Results presented here could be used as a reference in future studies of splenomegaly caused by haematological malignancies.
46.	Wennerberg, ABA, et al. (author) A comparative fMRI study: T2-weighted imaging versus R2 mapping 2001 In: NMR in biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 14:1, s. 41-47 Journal article (peer-reviewed)
47.	Wiggermann, Vanessa, et al. (author) In vivo investigation of the multi‐exponential T2 decay in human white matter at 7 T: Implications for myelin water imaging at UHF 2021 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 34:2 Journal article (peer-reviewed)abstract IntroductionMulti‐component T2 mapping using a gradient‐ and spin‐echo (GraSE) acquisition has become standard for myelin water imaging at 3 T. Higher magnetic field strengths promise signal‐to‐noise ratio benefits but face specific absorption rate limits and shortened T2 times. This study investigates compartmental T2 times in vivo and addresses advantages and challenges of multi‐component T2 mapping at 7 T.MethodsWe acquired 3D multi‐echo GraSE data in seven healthy adults at 7 T, with three subjects also scanned at 3 T. Stimulated echoes arising from B1+ inhomogeneities were accounted for by the extended phase graph (EPG) algorithm. We used the computed T2 distributions to determine T2 times that identify different water pools and assessed signal‐to‐noise and fit‐to‐noise characteristics of the signal estimation. We compared short T2 fractions and T2 properties of the intermediate water pool at 3 T and 7 T.ResultsFlip angle mapping confirmed that EPG accurately determined the larger B1+ inhomogeneity at 7 T. Multi‐component T2 analysis demonstrated shortened T2 times at 7 T compared with 3 T. Fit‐to‐noise and signal‐to‐noise ratios were improved at 7 T but depended on B1+ homogeneity. Adjusting the shortest T2 to 8 ms and the T2 threshold that separates different water compartments to 20 ms yielded short T2 fractions at 7 T that conformed to 3 T data. Short T2 fractions in myelin‐rich white matter regions were lower at 7 T than at 3 T, and higher in iron‐rich structures.DiscussionAdjusting the T2 compartment boundaries was required due to the shorter T2 relaxation times at 7 T. Shorter echo spacing would better sample the fast decaying signal but would increase peripheral nerve stimulation. Multi‐channel transmission will improve T2 measurements at 7 T.ConclusionWe used a multi‐echo 3D GraSE sequence to characterize the multi‐exponential T2 decay at 7 T. We adapted T2 parameters for evaluation of the short T2 fraction. Obtained 7 T multi‐component T2 maps were in good agreement with 3 T data.
48.	Wiggermann, Vanessa, et al. (author) Non-negative least squares computation for in vivo myelin mapping using simulated multi-echo spin-echo T2 decay data 2020 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:12 Journal article (peer-reviewed)abstract Multi‐compartment T2 mapping has gained particular relevance for the study of myelin water in the brain. As a facilitator of rapid saltatory axonal signal transmission, myelin is a cornerstone indicator of white matter development and function. Regularized non‐negative least squares fitting of multi‐echo T2 data has been widely employed for the computation of the myelin water fraction (MWF), and the obtained MWF maps have been histopathologically validated. MWF measurements depend upon the quality of the data acquisition, B1+ homogeneity and a range of fitting parameters. In this special issue article, we discuss the relevance of these factors for the accurate computation of multi‐compartment T2 and MWF maps. We generated multi‐echo spin‐echo T2 decay curves following the Carr‐Purcell‐Meiboom‐Gill approach for various myelin concentrations and myelin T2 scenarios by simulating the evolution of the magnetization vector between echoes based on the Bloch equations. We demonstrated that noise and imperfect refocusing flip angles yield systematic underestimations in MWF and intra−/extracellular water geometric mean T2 (gmT2). MWF estimates were more stable than myelin water gmT2 time across different settings of the T2 analysis. We observed that the lower limit of the T2 distribution grid should be slightly shorter than TE1. Both TE1 and the acquisition echo spacing also have to be sufficiently short to capture the rapidly decaying myelin water T2 signal. Among all parameters of interest, the estimated MWF and intra−/extracellular water gmT2 differed by approximately 0.13–4 percentage points and 3–4 ms, respectively, from the true values, with larger deviations observed in the presence of greater B1+ inhomogeneities and at lower signal‐to‐noise ratio. Tailoring acquisition strategies may allow us to better characterize the T2 distribution, including the myelin water, in vivo.
49.	Yon, Maxime, et al. (author) Diffusion tensor distribution imaging of an in vivo mouse brain at ultrahigh magnetic field by spatiotemporal encoding 2020 In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:11 Journal article (peer-reviewed)abstract Diffusion tensor distribution (DTD) imaging builds on principles from diffusion, solid-state and low-field NMR spectroscopies, to quantify the contents of heterogeneous voxels as nonparametric distributions, with tensor “size”, “shape” and orientation having direct relations to corresponding microstructural properties of biological tissues. The approach requires the acquisition of multiple images as a function of the magnitude, shape and direction of the diffusion-encoding gradients, leading to long acquisition times unless fast image read-out techniques like EPI are employed. While in previous in vivo human brain studies performed at 3 T this proved a viable option, porting these measurements to very high magnetic fields and/or to heterogeneous organs induces B0- and B1-inhomogeneity artifacts that challenge the limits of EPI. To overcome such challenges, we demonstrate here that high spatial resolution DTD of mouse brain can be carried out at 15.2 T with a surface-cryoprobe, by relying on SPatiotemporal ENcoding (SPEN) imaging sequences. These new acquisition and data-processing protocols are demonstrated with measurements on in vivo mouse brain, and validated with synthetic phantoms designed to mimic the diffusion properties of white matter, gray matter and cerebrospinal fluid. While still in need of full extensions to 3D mappings and of scanning additional animals to extract more general physiological conclusions, this work represents another step towards the model-free, noninvasive in vivo characterization of tissue microstructure and heterogeneity in animal models, at ≈0.1 mm resolutions.
50.	Zufiria, Blanca, et al. (author) A feature-based convolutional neural network for reconstruction of interventional MRI 2019 In: NMR in Biomedicine. - : John Wiley and Sons Ltd. - 0952-3480 .- 1099-1492. Journal article (peer-reviewed)abstract Real-time interventional MRI (I-MRI) could help to visualize the position of the interventional feature, thus improving patient outcomes in MR-guided neurosurgery. In particular, in deep brain stimulation, real-time visualization of the intervention procedure using I-MRI could improve the accuracy of the electrode placement. However, the requirements of a high undersampling rate and fast reconstruction speed for real-time imaging pose a great challenge for reconstruction of the interventional images. Based on recent advances in deep learning (DL), we proposed a feature-based convolutional neural network (FbCNN) for reconstructing interventional images from golden-angle radially sampled data. The method was composed of two stages: (a) reconstruction of the interventional feature and (b) feature refinement and postprocessing. With only five radially sampled spokes, the interventional feature was reconstructed with a cascade CNN. The final interventional image was constructed with a refined feature and a fully sampled reference image. With a comparison of traditional reconstruction techniques and recent DL-based methods, it was shown that only FbCNN could reconstruct the interventional feature and the final interventional image. With a reconstruction time of ~ 500 ms per frame and an acceleration factor of ~ 80, it was demonstrated that FbCNN had the potential for application in real-time I-MRI.

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