Toll-like receptor 2 (TLR2) belongs to the TLR protein family that plays an important role in the immune and inflammation response system. While TLR2 is predominantly expressed in immune cells, its... Show moreToll-like receptor 2 (TLR2) belongs to the TLR protein family that plays an important role in the immune and inflammation response system. While TLR2 is predominantly expressed in immune cells, its expression has also been detected in the brain, specifically in microglia and astrocytes. Recent studies indicate that genomic deletion of TLR2 can result in impaired neurobehavioural function. It is currently not clear if the genomic deletion of TLR2 leads to any alterations in the microstructural features of the brain. In the current study, we noninvasively assess microstructural changes in the brain of TLR2-deficient (tlr2-/-) zebrafish using state-of-the art magnetic resonance imaging (MRI) methods at ultrahigh magnetic field strength (17.6 T). A significant increase in cortical thickness and an overall trend towards increased brain volumes were observed in young tlr2-/- zebrafish. An elevated T2 relaxation time and significantly reduced apparent diffusion coefficient (ADC) unveil brain-wide microstructural alterations, potentially indicative of cytotoxic oedema and astrogliosis in the tlr2-/- zebrafish. Multicomponent analysis of the ADC diffusivity signal by the phasor approach shows an increase in the slow ADC component associated with restricted diffusion. Diffusion tensor imaging and diffusion kurtosis imaging analysis revealed diminished diffusivity and enhanced kurtosis in various white matter tracks in tlr2-/- compared with control zebrafish, identifying the microstructural underpinnings associated with compromised white matter integrity and axonal degeneration. Taken together, our findings demonstrate that the genomic deletion of TLR2 results in severe alterations to the microstructural features of the zebrafish brain. This study also highlights the potential of ultrahigh field diffusion MRI techniques in discerning exceptionally fine microstructural details within the small zebrafish brain, offering potential for investigating microstructural changes in zebrafish models of various brain diseases. Show less
Metabolite-weighted chemical exchange saturation transfer MRI can be used to indirectly image metabolites such as creatine and glutamate. This study aims to further explore the contrast of CEST at... Show moreMetabolite-weighted chemical exchange saturation transfer MRI can be used to indirectly image metabolites such as creatine and glutamate. This study aims to further explore the contrast of CEST at 2 ppm in the human brain at 7T and investigate the metabolite correlates of CEST at 2 ppm via correlations with magnetic resonance spectroscopy (MRS). Simulations were performed to establish the optimal acquisition parameters, such as total saturation time (tsat) and B1 root mean squared (B1rms) for CEST at 2 ppm in the human brain. Parameters were validated via in vitro phantom studies at 7T using concentrations, pH and temperature comparable to what is found in the human brain. Finally, 10 healthy volunteers were scanned at 7T for comparison with MRS. Our results show that the optimal parameters to acquire CEST at 2 ppm images are: B1rms = 2.14 mu T & tsat = 1500 ms, respectively. Comparison with MRS showed no significant correlation between CEST at 2 ppm and total Creatine measured by MRS (R = 0.19; p-value = 0.273). However, a significant correlation was found between CEST at 2 ppm and Glu (R = 0.39; p-value = 0.033), indicating the broad Glutamate-weighted CEST as the main measurable contributor to CEST at 2 ppm. We identified and confirmed optimal CEST at 2 ppm sequence parameters and validated CEST at 2 ppm measurements in a controlled in vitro environment. Our findings suggest that glutamate is a substantial contributor to the CEST at 2 ppm contrast observed in the human brain, whereas the creatine contribution to CEST at 2 ppm in the brain did not show a measurable contribution.CEST can be used to indirectly image in vivo amine protons, such as those in creatine and glutamate. CEST at 2 ppm was measured in the human gray and white matter (A) and correlated with MRS concentrations of total creatine and glutamate of the same regions (B). A significant correlation was found between CEST at 2 ppm and glutamate (C), suggesting glutamate to substantially contribute to CEST contrast at 2 ppm in the human brainimage Show less
Static quantitative magnetic resonance imaging (MRI) provides readouts of structural changes in diseased muscle, but current approaches lack the ability to fully explain the loss of contractile... Show moreStatic quantitative magnetic resonance imaging (MRI) provides readouts of structural changes in diseased muscle, but current approaches lack the ability to fully explain the loss of contractile function. Muscle contractile function can be assessed using various techniques including phase-contrast MRI (PC-MRI), where strain rates are quantified. However, current two-dimensional implementations are limited in capturing the complex motion of contracting muscle in the context of its three-dimensional (3D) fiber architecture. The MR acquisitions (chemical shift-encoded water–fat separation scan, spin echo-echoplanar imaging with diffusion weighting, and two time-resolved 3D PC-MRI) wereperformed at 3 T. PC-MRI acquisitions and performed with and without load at 7.5% of the maximum voluntary dorsiflexion contraction force. Acquisitions (3 T, chemical shift-encoded water–fat separation scan, spin echo-echo planar imaging with diffusion weighting, and two time-resolved 3D PC-MRI) were performed with and without load at 7.5% of the maximum voluntary dorsiflexion contraction force. Strain rates and diffusion tensors were calculated and combined to obtain strain rates along and perpendicular to the muscle fibers in seven lower leg muscles during the dynamic dorsi-/plantarflexion movement cycle. To evaluate strain rates along the proximodistal muscle axis, muscles were divided into five equal segments. t-tests were used to test if cyclic strain rate patterns (amplitude > 0) were present along and perpendicular to the muscle fibers. The effects of proximal-distal location and load were evaluated using repeated measures ANOVAs. Cyclic temporal strain rate patterns along and perpendicular to the fiber were found in all muscles involved in dorsi-/plantarflexion movement (p < 0.0017). Strain rates along and perpendicular to the fiber were heterogeneously distributed over the length of most muscles (p < 0.003). Additional loading reduced strain rates of the extensor digitorum longus and gastrocnemius lateralis muscle (p < 0.001). In conclusion, the lower leg muscles involved in cyclic dorsi-/plantarflexion exercise showed cyclic fiber strain rate patterns with amplitudes that varied between muscles and between the proximodistal segments within the majority of muscles. Show less
Tseng, C.H.; Jaspers, J.; Romero, A.M.; Wielopolski, P.; Smits, M.; Osch, M.J.P. van; Vos, F. 2023
The arterial input function (AIF) plays a crucial role in estimating quantitative perfusion properties from dynamic susceptibility contrast (DSC) MRI. An important issue, however, is that... Show moreThe arterial input function (AIF) plays a crucial role in estimating quantitative perfusion properties from dynamic susceptibility contrast (DSC) MRI. An important issue, however, is that measuring the AIF in absolute contrast-agent concentrations is challenging, due to uncertainty in relation to the measured -weighted signal, signal depletion at high concentration, and partial-volume effects. A potential solution could be to derive the AIF from separately acquired dynamic contrast enhanced (DCE) MRI data. We aim to compare the AIF determined from DCE MRI with the AIF from DSC MRI, and estimated perfusion coefficients derived from DSC data using a DCE-driven AIF with perfusion coefficients determined using a DSC-based AIF. AIFs were manually selected in branches of the middle cerebral artery (MCA) in both DCE and DSC data in each patient. In addition, a semi-automatic AIF-selection algorithm was applied to the DSC data. The amplitude and full width at half-maximum of the AIFs were compared statistically using the Wilcoxon rank-sum test, applying a 0.05 significance level. Cerebral blood flow (CBF) was derived with different AIF approaches and compared further. The results showed that the AIFs extracted from DSC scans yielded highly variable peaks across arteries within the same patient. The semi-automatic DSC–AIF had significantly narrower width compared with the manual AIFs, and a significantly larger peak than the manual DSC–AIF. Additionally, the DCE-based AIF provided a more stable measurement of relative CBF and absolute CBF values estimated with DCE–AIFs that were compatible with previously reported values. In conclusion, DCE-based AIFs were reproduced significantly better across vessels, showed more realistic profiles, and delivered more stable and reasonable CBF measurements. The DCE–AIF can, therefore, be considered as an alternative AIF source for quantitative perfusion estimations in DSC MRI. Show less
PurposeTo describe the construction and testing of a portable point-of-care low-field MRI system on site in Africa. MethodsAll of the components to assemble a 50 mT Halbach magnet-based system,... Show morePurposeTo describe the construction and testing of a portable point-of-care low-field MRI system on site in Africa. MethodsAll of the components to assemble a 50 mT Halbach magnet-based system, together with the necessary tools, were air-freighted from the Netherlands to Uganda. The construction steps included individual magnet sorting, filling of each ring of the magnet assembly, fine-tuning the inter-ring separations of the 23-ring magnet assembly, gradient coil construction, integration of gradient coils and magnet assembly, construction of the portable aluminum trolley and finally testing of the entire system with an open source MR spectrometer. ResultsWith four instructors and six untrained personnel, the complete project from delivery to first image took approximately 11 days. ConclusionsAn important step in translating scientific developments in the western world from high-income industrialized countries to low- and middle-income countries (LMICs) is to produce technology that can be assembled and ultimately constructed locally. Local assembly and construction are associated with skill development, low costs and jobs. Point-of-care systems have a large potential to increase the accessibility and sustainability of MRI in LMICs, and this work demonstrates that technology and knowledge transfer can be performed relatively seamlessly. Show less
Harten, T.W. van; Rooden, S. van; Koemans, E.A.; Opstal, A.M. van; Greenberg, S.M.; Grond, J. van der; ... ; Osch, M.J.P. van 2023
Cerebral vascular reactivity quantified using blood oxygen level-dependent functional MRI in conjuncture with a visual stimulus has been proven to be a potent and early marker for cerebral amyloid... Show moreCerebral vascular reactivity quantified using blood oxygen level-dependent functional MRI in conjuncture with a visual stimulus has been proven to be a potent and early marker for cerebral amyloid angiopathy. This work investigates the influence of different postprocessing methods on the outcome of such vascular reactivity measurements. Three methods for defining the region of interest (ROI) over which the reactivity is measured are investigated: structural (transformed V1), functional (template based on the activation of a subset of subjects), and percentile (11.5 cm(3) most responding voxels). Evaluation is performed both in a test-retest experiment in healthy volunteers (N = 12), as well as in 27 Dutch-type cerebral amyloid angiopathy patients and 33 age- and sex-matched control subjects. The results show that the three methods select a different subset of voxels, although all three lead to similar outcome measures in healthy subjects. However, in (severe) pathology, the percentile method leads to higher reactivity measures than the other two, due to circular analysis or "double dipping" by defining a subject-specific ROI based on the strongest responses within each subject. Furthermore, while different voxels are included in the presence of lesions, this does not necessarily result in different outcome measures. In conclusion, to avoid bias created by the method, either a structural or a functional method is recommended. Both of these methods provide similar reactivity measures, although the functional ROI appears to be less reproducible between studies, because slightly different subsets of voxels were found to be included. On the other hand, the functional method did include fewer lesion voxels than the structural method. Show less
Anazodo, U.C.; Ng, J.J.; Ehiogu, B.; Obungoloch, J.; Fatade, A.; Mutsaerts, H.J.M.M.; ... ; Consortium Advanced MRI Education Research in Africa (CAMERA) 2022
Magnetic resonance imaging (MRI) technology has profoundly transformed current healthcare systems globally, owing to advances in hardware and software research innovations. Despite these advances,... Show moreMagnetic resonance imaging (MRI) technology has profoundly transformed current healthcare systems globally, owing to advances in hardware and software research innovations. Despite these advances, MRI remains largely inaccessible to clinicians, patients, and researchers in low-resource areas, such as Africa. The rapidly growing burden of noncommunicable diseases in Africa underscores the importance of improving access to MRI equipment as well as training and research opportunities on the continent. The Consortium for Advancement of MRI Education and Research in Africa (CAMERA) is a network of African biomedical imaging experts and global partners, implementing novel strategies to advance MRI access and research in Africa. Upon its inception in 2019, CAMERA sets out to identify challenges to MRI usage and provide a framework for addressing MRI needs in the region. To this end, CAMERA conducted a needs assessment survey (NAS) and a series of symposia at international MRI society meetings over a 2-year period. The 68-question NAS was distributed to MRI users in Africa and was completed by 157 clinicians and scientists from across Sub-Saharan Africa (SSA). On average, the number of MRI scanners per million people remained at less than one, of which 39% were obsolete low-field systems but still in use to meet daily clinical needs. The feasibility of coupling stable energy supplies from various sources has contributed to the growing number of higher-field (1.5 T) MRI scanners in the region. However, these systems are underutilized, with only 8% of facilities reporting clinical scans of 15 or more patients per day, per scanner. The most frequently reported MRI scans were neurological and musculoskeletal. The CAMERA NAS combined with the World Health Organization and International Atomic Energy Agency data provides the most up-to-date data on MRI density in Africa and offers a unique insight into Africa's MRI needs. Reported gaps in training, maintenance, and research capacity indicate ongoing challenges in providing sustainable high-value MRI access in SSA. Findings from the NAS and focused discussions at international MRI society meetings provided the basis for the framework presented here for advancing MRI capacity in SSA. While these findings pertain to SSA, the framework provides a model for advancing imaging needs in other low-resource settings. Show less
For better quantification of perfusion with arterial spin labeling (ASL), partial volume correction (PVC) is used to disentangle the signals from gray matter (GM) and white matter within any voxel... Show moreFor better quantification of perfusion with arterial spin labeling (ASL), partial volume correction (PVC) is used to disentangle the signals from gray matter (GM) and white matter within any voxel. Based on physiological considerations, PVC algorithms typically assume zero signal in the cerebrospinal fluid (CSF). Recent measurements, however, have shown that CSF-ASL signal can exceed 10% of GM signal, even when using recommended ASL labeling parameters. CSF signal is expected to particularly affect PVC results in the choroid plexus. This study aims to measure the impact of CSF signal on PVC perfusion measurements, and to investigate the potential use of PVC to retrieve pure CSF-ASL signal for blood–CSF barrier characterization. In vivo imaging included six pCASL sequences with variable label duration and post-labeling delay (PLD), and an eight-echo 3D-GRASE readout. A dataset was simulated to estimate the effect of CSF-PVC with known ground-truth parameters. Differences between the results of CSF-PVC and non-CSF-PVC were estimated for regions of interest (ROIs) based on GM probability, and a separate ROI isolating the choroid plexus. In vivo, the suitability of PVC-CSF signal as an estimate of pure CSF was investigated by comparing its time course with the long-TE CSF signal. Results from both simulation and in vivo data indicated that including the CSF signal in PVC improves quantification of GM CBF by approximately 10%. In simulated data, this improvement was greater for multi-PLD (model fitting) quantification than for single PLD (~1–5% difference). In the choroid plexus, the difference between CSF-PVC and non-CSF-PVC was much larger, averaging around 30%. Long-TE (pure) CSF signal could not be estimated from PVC CSF signal as it followed a different time course, indicating the presence of residual macrovascular signal in the PVC. The inclusion of CSF adds value to PVC for more accurate measurements of GM perfusion, and especially for quantification of perfusion in the choroid plexus and study of the glymphatic system. Show less
For better quantification of perfusion with arterial spin labeling (ASL), partial volume correction (PVC) is used to disentangle the signals from gray matter (GM) and white matter within any voxel.... Show moreFor better quantification of perfusion with arterial spin labeling (ASL), partial volume correction (PVC) is used to disentangle the signals from gray matter (GM) and white matter within any voxel. Based on physiological considerations, PVC algorithms typically assume zero signal in the cerebrospinal fluid (CSF). Recent measurements, however, have shown that CSF-ASL signal can exceed 10% of GM signal, even when using recommended ASL labeling parameters. CSF signal is expected to particularly affect PVC results in the choroid plexus. This study aims to measure the impact of CSF signal on PVC perfusion measurements, and to investigate the potential use of PVC to retrieve pure CSF-ASL signal for blood-CSF barrier characterization. In vivo imaging included six pCASL sequences with variable label duration and post-labeling delay (PLD), and an eight-echo 3D-GRASE readout. A dataset was simulated to estimate the effect of CSF-PVC with known ground-truth parameters. Differences between the results of CSF-PVC and non-CSF-PVC were estimated for regions of interest (ROls) based on GM probability, and a separate ROI isolating the choroid plexus. In vivo, the suitability of PVC-CSF signal as an estimate of pure CSF was investigated by comparing its time course with the long-TE CSF signal. Results from both simulation and in vivo data indicated that including the CSF signal in PVC improves quantification of GM CBF by approximately 10%. In simulated data, this improvement was greater for multi-PLD (model fitting) quantification than for single PLD (similar to 1-5% difference). In the choroid plexus, the difference between CSF-PVC and non-CSF-PVC was much larger, averaging around 30%. Long-TE (pure) CSF signal could not be estimated from PVC CSF signal as it followed a different time course, indicating the presence of residual macrovascular signal in the PVC. The inclusion of CSF adds value to PVC for more accurate measurements of GM perfusion, and especially for quantification of perfusion in the choroid plexus and study of the glymphatic system. Show less
Purpose: To describe the current properties and capabilities of an open-source hardware and software package that is being developed by many sites internationally with the aim of providing an... Show morePurpose: To describe the current properties and capabilities of an open-source hardware and software package that is being developed by many sites internationally with the aim of providing an inexpensive yet flexible platform for low-cost MRI. Methods: This article describes three different setups from 50 to 360 mT in different settings, all of which used the MaRCoS console for acquiring data, and different types of software interface (custom-built GUI or Pulseq overlay) to acquire it. Results: Images are presented both from phantoms and in vivo from healthy volunteers to demonstrate the image quality that can be obtained from the MaRCoS hardware/software interfaced to different low-field magnets. Conclusions: The results presented here show that a number of different sequences commonly used in the clinic can be programmed into an open-source system relatively quickly and easily, and can produce good quality images even at this early stage of development. Both the hardware and software will continue to develop, and it is an aim of this article to encourage other groups to join this international consortium. Show less
Dong, Y.M.; Riedel, M.; Koolstra, K.; Osch, M.J.P. van; Börnert, P. 2022
The purpose of this study was to develop a self-navigation strategy to improve scan efficiency and image quality of water/fat-separated, diffusion-weighted multishot echo-planar imaging (ms-EPI).... Show moreThe purpose of this study was to develop a self-navigation strategy to improve scan efficiency and image quality of water/fat-separated, diffusion-weighted multishot echo-planar imaging (ms-EPI). This is accomplished by acquiring chemical shift-encoded diffusion-weighted data and using an appropriate water-fat and diffusion-encoded signal model to enable reconstruction directly from k-space data. Multishot EPI provides reduced geometric distortion and improved signal-to-noise ratio in diffusion-weighted imaging compared with single-shot approaches. Multishot acquisitions require corrections for physiological motion-induced shot-to-shot phase errors using either extra navigators or self-navigation principles. In addition, proper fat suppression is important, especially in regions with large B0 inhomogeneity. This makes the use of chemical shift encoding attractive. However, when combined with ms-EPI, shot-to-shot phase navigation can be challenging because of the spatial displacement of fat signals along the phase-encoding direction. In this work, a new model-based, self-navigated water/fat separation reconstruction algorithm is proposed. Experiments in legs and in the head–neck region of 10 subjects were performed to validate the algorithm. The results are compared with an image-based, two-dimensional (2D) navigated water/fat separation approach for ms-EPI and with a conventional fat saturation approach. Compared with the 2D navigated method, the use of self-navigation reduced the shot duration time by 30%–35%. The proposed algorithm provided improved diffusion-weighted water images in both leg and head–neck regions compared with the 2D navigator-based approach. The proposed algorithm also produced better fat suppression compared with the conventional fat saturation technique in the B0 inhomogeneous regions. In conclusion, the proposed self-navigated reconstruction algorithm can produce superior water-only diffusion-weighted EPI images with less artefacts compared with the existing methods. Show less
In a standard spin echo, the time evolution due to homonuclear couplings is not reversed, leading to echo time (TE)-dependent modulation of the signal amplitude and signal loss in the case of... Show moreIn a standard spin echo, the time evolution due to homonuclear couplings is not reversed, leading to echo time (TE)-dependent modulation of the signal amplitude and signal loss in the case of overlapping multiplet resonances. This has an adverse effect on quantification of several important metabolites such as glutamate and glutamine. Here, we propose a J-refocused variant of the sLASER sequence (J-sLASER) to improve quantification of J-coupled metabolites at ultrahigh field (UHF). The use of the sLASER sequence is particularly advantageous at UHF as it minimizes chemical shift displacement error and results in relatively homogenous refocusing. We simulated the MRS signal from brain metabolites over a broad range of TE values with sLASER and J-sLASER, and showed that the signal of J-coupled metabolites was increased with J-sLASER with TE values up to similar to 80 ms. We further simulated "brain-like" spectra with both sequences at the shortest TE available on our scanner. We showed that, despite the slightly longer TE, the J-sLASER sequence results in significantly lower Cramer-Rao lower bounds (CRLBs) for J-coupled metabolites compared with those obtained with sLASER. Following phantom validation, we acquired spectra from two brain regions in 10 healthy volunteers (age 38 +/- 15 years) using both sequences. We showed that using J-sLASER results in a decrease of CRLBs for J-coupled metabolites. In particular, we measured a robust similar to 38% decrease in the mean CRLB (glutamine) in parietal white matter and posterior cingulate cortex (PCC). We further showed, in 10 additional healthy volunteers (age 34 +/- 15 years), that metabolite quantification following two separate acquisitions with J-sLASER in the PCC was repeatable. The improvement in quantification of glutamine may in turn improve the independent quantification of glutamate, the main excitatory neurotransmitter in the brain, and will simultaneously help to track possible modulations of glutamine, which is a key player in the glutamatergic cycle in astrocytes. Show less
Microvascular function is an important component in the physiology of muscle. One of the major parameters, blood perfusion, can be measured noninvasively and quantitatively by arterial spin... Show moreMicrovascular function is an important component in the physiology of muscle. One of the major parameters, blood perfusion, can be measured noninvasively and quantitatively by arterial spin labeling (ASL) MRI. Most studies using ASL in muscle have only reported data from a single slice, thereby assuming that muscle perfusion is homogeneous within muscle, whereas recent literature has reported proximodistal differences in oxidative capacity and perfusion. Here, we acquired pulsed ASL data in 12 healthy volunteers after dorsiflexion exercise in two slices separated distally by 7 cm. We combined this with a Look-Locker scheme to acquire images at multiple postlabeling delays (PLDs) and with a multiecho readout to measure T-2*. This enabled the simultaneous evaluation of quantitative muscle blood flow (MBF), arterial transit time (ATT), and T-2* relaxation time in the tibialis anterior muscle during recovery. Using repeated measures analyses of variance we tested the effect of time, slice location, and their interaction on MBF, ATT, and T-2*. Our results showed a significant difference as a function of time postexercise for all three parameters (MBF: F = 34.0, p < .0001; T-2*: F = 73.7, p < .0001; ATT: F = 13.6, p < .001) and no average differences between slices over the total time postexercise were observed. The interaction effect between time postexercise and slice location was significant for MBF and T-2* (F = 5.5, p = 0.02, F = 6.1, p = 0.02, respectively), but not for ATT (F = 2.2, p = .16). The proximal slice showed a higher MBF and a lower ATT than the distal slice during the first 2 min of recovery, and T-2* showed a delayed response in the distal slice. These results imply a higher perfusion and faster microvascular response to exercise in the proximal slice, in line with previous literature. Moreover, the differences in ATT indicate that it is difficult to correctly determine perfusion based on a single PLD as is commonly performed in the muscle literature. Show less
Koolstra, K.; Staring, M.; Bruin, P. de; Osch, M.J.P. van 2022
Background suppression (BGS) in arterial spin labeling (ASL) magnetic resonance imaging leads to a higher temporal signal-to-noise ratio (tSNR) of the perfusion images compared with ASL without BGS... Show moreBackground suppression (BGS) in arterial spin labeling (ASL) magnetic resonance imaging leads to a higher temporal signal-to-noise ratio (tSNR) of the perfusion images compared with ASL without BGS. The performance of the BGS, however, depends on the tissue relaxation times and on inhomogeneities of the scanner's magnetic fields, which differ between subjects and are unknown at the moment of scanning. Therefore, we developed a feedback loop (FBL) mechanism that optimizes the BGS for each subject in the scanner during acquisition. We implemented the FBL for 2D pseudo-continuous ASL scans with an echo-planar imaging readout. After each dynamic scan, the acquired ASL images were automatically sent to an external computer and processed with a Python processing tool. Inversion times were optimized on the fly using 80 iterations of the Nelder-Mead method, by minimizing the signal intensity in the label image while maximizing the signal intensity in the perfusion image. The performance of this method was first tested in a four-component phantom. The regularization parameter was then tuned in six healthy subjects (three males, three females, age 24-62 years) and set as lambda = 4 for all other experiments. The resulting ASL images, perfusion images, and tSNR maps obtained from the last 20 iterations of the FBL scan were compared with those obtained without BGS and with standard BGS in 12 healthy volunteers (five males, seven females, age 24-62 years) (including the six volunteers used for tuning of lambda). The FBL resulted in perfusion images with a statistically significantly higher tSNR (2.20) compared with standard BGS (1.96) ( p<5x10-3$$ p, two-sided paired t-test). Minimizing signal in the label image furthermore resulted in control images, from which approximate changes in perfusion signal can directly be appreciated. This could be relevant to ASL applications that require a high temporal resolution. Future work is needed to minimize the number of initial acquisitions during which the performance of BGS is reduced compared with standard BGS, and to extend the technique to 3D ASL. Show less
Forsting, J.; Rehmann, R.; Rohm, M.; Guttsches, A.K.; Froeling, M.; Kan, H.E.; ... ; Schlaffke, L. 2022
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.... Show moreMuscle 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 (lambda(1)) 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. Show less
In Becker muscular dystrophy (BMD), muscle weakness progresses relatively slowly, with a highly variable rate among patients. This complicates clinical trials, as clinically relevant changes are... Show moreIn Becker muscular dystrophy (BMD), muscle weakness progresses relatively slowly, with a highly variable rate among patients. This complicates clinical trials, as clinically relevant changes are difficult to capture within the typical duration of a trial. Therefore, predictors for disease progression are needed. We assessed if temporal increase of fat fraction (FF) in BMD follows a sigmoidal trajectory and whether fat fraction at baseline (FFbase) could therefore predict FF increase after 2 years (Delta FF). Thereafter, for two different MR-based parameters, we tested the additional predictive value to FFbase. We used 3-T Dixon data from the upper and lower leg, and multiecho spinecho MRI and 7-T P-31 MRS datasets from the lower leg, acquired in 24 BMD patients (age: 41.4 [SD 12.8] years). We assessed the pattern of increase in FF using mixed-effects modelling. Subsequently, we tested if indicators of muscle damage like standard deviation in water T-2 (stdT(2)) and the phosphodiester (PDE) over ATP ratio at baseline had additional value to FFbase for predicting Delta FF. The association between FFbase and Delta FF was described by the derivative of a sigmoid function and resulted in a peak Delta FF around 0.45 FFbase (fourth-order polynomial term: t = 3.7, p < .001). StdT(2) and PDE/ATP were not significantly associated with Delta FF if FFbase was included in the model. The relationship between FFbase and Delta FF suggests a sigmoidal trajectory of the increase in FF over time in BMD, similar to that described for Duchenne muscular dystrophy. Our results can be used to identify muscles (or patients) that are in the fast progressing stage of the disease, thereby facilitating the conduct of clinical trials. Show less
The article of Lopez et al describes the use of a multi-parametric MR approach to study muscle T-2 relaxation times and P-31-MRS indices of energetics and sarcolemma integrity in a mouse model of... Show moreThe article of Lopez et al describes the use of a multi-parametric MR approach to study muscle T-2 relaxation times and P-31-MRS indices of energetics and sarcolemma integrity in a mouse model of DMD, the mdx mouse. Muscular dystrophies have a multi-factorial disease cascade, and there are several MR methods used to assess these. Aspects that reflect disease progression are outlined on the left, while features that are more related to disease activity are outlined on the right. Show less
Increasingly, dynamic magnetic resonance imaging (MRI) has potential as a noninvasive and accessible tool for diagnosing and monitoring gastrointestinal motility in healthy and diseased bowel.... Show moreIncreasingly, dynamic magnetic resonance imaging (MRI) has potential as a noninvasive and accessible tool for diagnosing and monitoring gastrointestinal motility in healthy and diseased bowel. However, current MRI methods of measuring bowel motility have limitations: requiring bowel preparation or long acquisition times; providing mainly surrogate measures of motion; and estimating bowel-wall movement in just two dimensions. In this proof-of-concept study we apply a method that provides a quantitative measure of motion within the bowel, in both two and three dimensions, using existing, vendor-implemented MRI pulse sequences with minimal bowel preparation. This method uses a minimised cost function to fit linear vectors in the spatial and temporal domains. It is sensitised to the spatial scale of the bowel and aims to address issues relating to the low signal-to-noise in high-temporal resolution dynamic MRI scans, previously compensated for by performing thick-slice (10-mm) two-dimensional (2D) coronal scans. We applied both 2D and three-dimensional (3D) scanning protocols in two healthy volunteers. For 2D scanning, analysis yielded bi-modal velocity peaks, with a mean antegrade motion of 5.5 mm/s and an additional peak at similar to 9 mm/s corresponding to longitudinal peristalsis, as supported by intraoperative data from the literature. Furthermore, 3D scans indicated a mean forward motion of 4.7 mm/s, and degrees of antegrade and retrograde motion were also established. These measures show promise for the noninvasive assessment of bowel motility, and have the potential to be tuned to particular regions of interest and behaviours within the bowel. Show less
Dorth, D. van; Venugopal, K.; Poot, D.H.J.; Hirschler, L.; Bresser, J. de; Smits, M.; ... ; Osch, M.J.P. van 2021
Dynamic susceptibility contrast (DSC) MRI is clinically used to measure brain perfusion by monitoring the dynamic passage of a bolus of contrast agent through the brain. For quantitative analysis... Show moreDynamic susceptibility contrast (DSC) MRI is clinically used to measure brain perfusion by monitoring the dynamic passage of a bolus of contrast agent through the brain. For quantitative analysis of the DSC images, the arterial input function is required. It is known that the original assumption of a linear relation between the R-2((*)) relaxation and the arterial contrast agent concentration is invalid, although the exact relation is as of yet unknown. Studying this relation in vitro is time-consuming, because of the widespread variations in field strengths, MRI sequences, contrast agents, and physiological conditions. This study aims to simulate the R-2((*)) versus contrast concentration relation under varying physiological and technical conditions using an adapted version of an open-source simulation tool. The approach was validated with previously acquired data in human whole blood at 1.5 T by means of a gradient-echo sequence (proof-of-concept). Subsequently, the impact of hematocrit, field strength, and oxygen saturation on this relation was studied for both gradient-echo and spin-echo sequences. The results show that for both gradient-echo and spin-echo sequences, the relaxivity increases with hematocrit and field strength, while the hematocrit dependency was nonlinear for both types of MRI sequences. By contrast, oxygen saturation has only a minor effect. In conclusion, the simulation setup has proven to be an efficient method to rapidly calibrate and estimate the relation between R-2((*)) and gadolinium concentration in whole blood. This knowledge will be useful in future clinical work to more accurately retrieve quantitative information on brain perfusion. Show less
Alzheimer's disease (AD) is the leading cause of cognitive impairment and dementia in elderly individuals. According to the current biomarker framework for "unbiased descriptive classification",... Show moreAlzheimer's disease (AD) is the leading cause of cognitive impairment and dementia in elderly individuals. According to the current biomarker framework for "unbiased descriptive classification", biomarkers of neurodegeneration, "N", constitute a critical component in the tri-category "A/T/N" system. Current biomarkers of neurodegeneration suffer from potential drawbacks such as requiring invasive lumbar puncture, involving ionizing radiation, or representing a late, irreversible marker. Recent human studies have suggested that reduced brain oxygen metabolism may be a new functional marker of neurodegeneration in AD, but the heterogeneity and the presence of mixed pathology in human patients did not allow a full understanding of the role of oxygen extraction and metabolism in AD. In this report, global brain oxygen metabolism and related physiological parameters were studied in two AD mouse models with relatively pure pathology, using advanced MRI techniques including T-2-relaxation-under-spin-tagging (TRUST) and phase contrast (PC) MRI. Additionally, regional cerebral blood flow (CBF) was determined with pseudocontinuous arterial spin labeling. Reduced global oxygen extraction fraction (by -18.7%, p = 0.008), unit-mass cerebral metabolic rate of oxygen (CMRO2) (by -17.4%, p = 0.04) and total CMRO2 (by -30.8%, p < 0.001) were observed in Tau4R Delta K mice-referred to as the tau AD model-which manifested pronounced neurodegeneration, as measured by diminished brain volume (by -15.2%, p < 0.001). Global and regional CBF in these mice were not different from those of wild-type mice (p > 0.05), suggesting normal vascular function. By contrast, in B6;SJL-Tg [APPSWE]2576Kha (APP) mice-referred to as the amyloid AD model-no brain volume reduction, as well as relatively intact brain oxygen extraction and metabolism, were found (p > 0.05). Consistent with the imaging data, behavioral measures of walking distance were impaired in Tau4R Delta K mice (p = 0.004), but not in APP mice (p = 0.88). Collectively, these findings support the hypothesis that noninvasive MRI measurement of brain oxygen metabolism may be a promising biomarker of neurodegeneration in AD. Show less
