Diffusely appearing white matter in multiple sclerosis: Insights from sodium (23Na) MRI.

BACKGROUND: In multiple sclerosis (MS), magnetic resonance imaging (MRI) frequently shows ill-defined areas with intermediate signal intensity between the normal appearing white matter (NAWM) and focal T2-hyperintense lesions, termed "diffusely appearing white matter" (DAWM). Even though several advanced MRI techniques have shown the potential to detect and quantify subtle commonly not visible microscopic tissue changes, to date only a few advanced MRI studies investigated DAWM changes in a quantitative manner. The aim of this study was to detect and quantify tissue abnormalities in the DAWM in comparison to focal lesions and the NAWM in MS patients by sodium (23Na) MRI. METHODS: 23Na and conventional MRI were performed in 25 MS patients with DAWM (DAWM+) and in 25 sex- and age matched MS patients without DAWM (DAWM-), as well as in ten healthy controls (HC). Mean total sodium concentrations (TSC) were quantified in the DAWM, NAWM, normal appearing grey matter (NAGM) and in focal MS lesions. RESULTS: In MS DAWM+and DAWM-, TSC values were increased in the NAGM (DAWM+: 44.61 ± 4.09 mM; DAWM-: 45.37 ± 3.8 mM) and in the NAWM (DAWM+: 39.85 ± 3.89 mM; DAWM-: 39.82 ± 4.25 mM) compared to normal grey and white matter in HC (GM 40.87 ± 3.25 mM, WM 35.9 ± 1.81 mM; p < 0.05 for all comparisons). Interestingly, the DAWM showed similar sodium concentrations (39.32 ± 4.59 mM) to the NAWM (39.85 ± 3.89 mM), whereas TSC values in T1 hypointense (46.53 ± 7.87 mM) and T1 isointense (41.99 ± 6.10 mM) lesions were significantly higher than in the DAWM (p < 0.001 and 0.017 respectively). CONCLUSION: 23Na MRI is confirmed as a sensitive marker of even subtle tissue abnormalities. DAWM sodium levels are increased and comparable to the abnormalities in NAWM, suggesting pathological changes less severe than in focal lesions comparable to what is expected in the NAWM.

23 Na MRI in ischemic stroke: Acquisition time reduction using postprocessing with convolutional neural networks.

Quantitative 23 Na magnetic resonance imaging (MRI) provides tissue sodium concentration (TSC), which is connected to cell viability and vitality. Long acquisition times are one of the most challenging aspects for its clinical establishment. K-space undersampling is an approach for acquisition time reduction, but generates noise and artifacts. The use of convolutional neural networks (CNNs) is increasing in medical imaging and they are a useful tool for MRI postprocessing. The aim of this study is 23 Na MRI acquisition time reduction by k-space undersampling. CNNs were applied to reduce the resulting noise and artifacts. A retrospective analysis from a prospective study was conducted including image datasets from 46 patients (aged 72 ± 13 years; 25 women, 21 men) with ischemic stroke; the 23 Na MRI acquisition time was 10 min. The reconstructions were performed with full dataset (FI) and with a simulated dataset an image that was acquired in 2.5 min (RI). Eight different CNNs with either U-Net-based or ResNet-based architectures were implemented with RI as input and FI as label, using batch normalization and the number of filters as varying parameters. Training was performed with 9500 samples and testing included 400 samples. CNN outputs were evaluated based on signal-to-noise ratio (SNR) and structural similarity (SSIM). After quantification, TSC error was calculated. The image quality was subjectively rated by three neuroradiologists. Statistical significance was evaluated by Student's t-test. The average SNR was 21.72 ± 2.75 (FI) and 10.16 ± 0.96 (RI). U-Nets increased the SNR of RI to 43.99 and therefore performed better than ResNet. SSIM of RI to FI was improved by three CNNs to 0.91 ± 0.03. CNNs reduced TSC error by up to 15%. The subjective rating of CNN-generated images showed significantly better results than the subjective image rating of RI. The acquisition time of 23 Na MRI can be reduced by 75% due to postprocessing with a CNN on highly undersampled data.

Evaluation of Sodium (23Na) MR-imaging as a Biomarker and Predictor for Neurodegenerative Changes in Patients With Alzheimer's Disease.

BACKGROUND/AIM: Sodium (23Na) MR imaging is a noninvasive MRI technique that has been shown to be sensitive to visualize biochemical information about tissue viability, their cell integrity, and cell function in various studies. The aim of this study was to evaluate differences in regional brain 23Na signal intensity between Alzheimer's disease (AD) and healthy controls to preliminarily evaluate the capability of 23Na imaging as a biomarker for AD. PATIENTS AND METHODS: A total of 14 patients diagnosed with AD were included: 12 in the state of dementia and 2 with mild cognitive impairment (MCI), and 12 healthy controls (HC); they were all scanned on a 3T clinical scanner with a double tuned 1H/23Na birdcage head coil. After normalizing the signal intensity with that of the vitreous humor, relative tissue sodium concentration (rTSC) was measured after automated segmentation in the hippocampus, amygdala, basal ganglia, white matter (WM) and grey matter (GM) in both cerebral hemispheres. RESULTS: Patients with AD showed a significant increase in rTSC in comparison to healthy controls in the following brain regions: WM 13.6%; p=0.007, hippocampus 12.9%; p=0.003, amygdala 18.9%; p=0.0007. CONCLUSION: 23Na-MRI has the potential to be developed as a useful biomarker for the diagnosis of AD.

X-nuclei imaging: Current state, technical challenges, and future directions.

1 H imaging is concerned with contrast generation among anatomically distinct soft tissues. X-nuclei imaging, on the other hand, aims to reveal the underlying changes in the physiological processes on a cellular level. Advanced clinical MR hardware systems improved 1 H image quality and simultaneously enabled X-nuclei imaging. Adaptation of 1 H methods and optimization of both sequence design and postprocessing protocols launched X-nuclei imaging past feasibility studies and into clinical studies. This review outlines the current state of X-nuclei MRI, with the focus on 23 Na, 35 Cl, 39 K, and 17 O. Currently, various aspects of technical challenges limit the possibilities of clinical X-nuclei MRI applications. To address these challenges, quintessential physical and technical concepts behind different applications are presented, and the advantages and drawbacks are delineated. The working process for methods such as quantification and multiquantum imaging is shown step-by-step. Clinical examples are provided to underline the potential value of X-nuclei imaging in multifaceted areas of application. In conclusion, the scope of the latest technical advance is outlined, and suggestions to overcome the most fundamental hurdles on the way into clinical routine by leveraging the full potential of X-nuclei imaging are presented. Level of Evidence: 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:355-376.

Feasibility study of a double resonant 8-channel 1H/ 8-channel 23Na receive-only head coil at 3 Tesla.

Sodium (23Na) magnetic resonance imaging (MRI), especially brain applications are increasingly interesting since sodium MRI can provide additional information about tissue viability and vitality. In order to include sodium MRI in the clinical routine, a single RF setup is preferable which provides high sodium sensitivity and full proton performance in terms of signal-to-noise ratio (SNR) and parallel imaging performance. The aim of this work was to evaluate the feasibility of a double resonant receive (Rx) coil array for proton and sodium head MRI. The coil was designed to provide high sodium SNR and full proton performance comparable to commercial coils which are optimized for sodium MRI or for proton MRI, respectively. A measurement setup was built which comprised an 8-channel Rx degenerate Birdcage for sodium imaging and an 8-channel Rx array for proton imaging. The performance of the coil was evaluated against commercial sodium and proton coils using phantom and in-vivo measurements of two healthy volunteers.

Feasibility study of a double resonant (1H/23Na) abdominal RF setup at 3T.

Sodium magnetic resonance imaging (MRI) of the human abdomen is of increasing clinical interest for e.g. kidney, intervertebral disks, prostate and tumor monitoring examinations in the abdomen. To overcome the low MR sensitivity of sodium, optimal radio frequency (RF) structures should be used. A common approach is to combine a volumetric transmit coil for homogeneous excitation with an array of sensitive receive coils adapted to the human shape. Additionally, proton imaging is required to match the physiological sodium images to the morphological proton images. In this work, we demonstrated the feasibility of a double resonant proton/sodium RF setup for abdominal MRI at 3T, providing a high sodium sensitivity. After extensive simulations, a 16-channel sodium receive array was built and used in combination with a volumetric sodium transmit coil. Additionally, a local proton coil was included in the setup for anatomical localizations. The setup was investigated using electromagnetic field simulations, phantom measurements and final in-vivo measurements of a healthy volunteer. A 3 to 6-fold sensitivity improvement of the sodium receive array compared to the volumetric sodium coil was achieved using the phantom simulations and measurements. Safety assessments of the local proton transmit/receive coil were performed using specific absorption rate simulations. Finally, the feasibility of such a setup was proven by in-vivo measurements.

Temporal evolution of acute multiple sclerosis lesions on serial sodium (23Na) MRI.

BACKGROUND: Several studies have reported the characteristics of acute multiple sclerosis (MS) lesions on diffusion-weighted magnetic resonance imaging (DWI MRI). Current publications reported a transient reduction of the apparent diffusion coefficient (ADC) delineating an early phase of lesion evolution, before increased diffusion occurs in parallel to blood-brain-barrier (BBB) breakdown. Sodium MRI might provide another perspective on lesion development, but clinical applications have been limited to high field MR systems. The objective in this study was to investigate the temporal evolution of acute MS lesions using conventional (T2-fluid-attenuated inversion recovery (T2-FLAIR) images, post-contrast T1-weighted images), diffusion and sodium MRI. METHODS: Initial and follow-up MRI (23Na and 1H MRI) were performed on a 3T scanner. Quantitative assessment of total sodium concentration (TSC) and ADC was performed. The study was designed for frequent follow-up MRI examinations during 4 weeks after the initial presentation. RESULTS: Thirty-one acute MS lesions (7 lesions with reduced diffusion) in eleven MS patients were included. On initial MRI, TSC in contrast-enhancing lesions was increased when compared to the normal-appearing white matter (NAWM), while lesions with an initial reduced diffusion showed a TSC comparable to the NAWM. On follow-up MRI, in lesions with reduced diffusion subsequent increase of ADC and TSC values occurred along with signs of the development of vasogenic edema and contrast-enhancement. After four weeks, TSC values decreased along with regression of vasogenic edema and contrast-enhancement. CONCLUSIONS: In lesions with a reduction of the ADC sodium levels are near normal and precede signs of BBB breakdown. These findings suggest a relatively preserved tissue structure in this early phase of lesion evolution.

Influence of Gadolinium-Based Contrast Agents on Tissue Sodium Quantification in Sodium Magnetic Resonance Imaging.

OBJECTIVES: Sodium magnetic resonance (MR) imaging provides noninvasive insights to cellular processes by measuring tissue sodium concentration (TSC). Many clinical studies combine sodium MR imaging with clinical standard MR procedures, in which contrast media is frequently administered. This work investigates the influence of gadolinium-based contrast agents on quantification of TSC. Thus, either scan pauses between early and late contrast-enhanced acquisitions can be used efficiently or sodium imaging can be performed as the final scan after dynamic contrast-enhanced acquisition. MATERIALS AND METHODS: For this study, 2 gadolinium-based contrast agents, Dotarem and Gadovist, were diluted with saline solution covering contrast agent concentrations in a clinical range. In addition, agarose-based sample series were created to simulate tissue relaxation time behavior. In vivo, the influence of Dotarem on sodium acquisition and TSC quantification was investigated in 1 ischemic stroke patient. RESULTS: Proton relaxation times decreased for increasing contrast agent concentrations as hyperbolic functions. Sodium relaxation times displayed a negative slope in regression analysis in most cases. The largest influence (-1.52 milliseconds per mmol/L contrast agent) was measured for sodium T1. Worst case calculations in ultrashort echo time sequence signal analysis showed a signal drop of (1.21% ± 0.56%) on tissue sodium quantification. In vivo sodium brain acquisitions of a stroke patient before and after Dotarem injection resulted in statistically nonsignificant differences in TSC quantification of relevant tissues and stroke areas (P > 0.05). CONCLUSIONS: Our study showed a quantitative influence of Dotarem and Gadovist on sodium relaxation times. However, quantification of TSC was not impaired, which was proven by worst case calculations and nonsignificant differences in vivo in an ischemic stroke patient. We suggest performing sodium imaging in useful clinical positions in protocols regardless of included Dotarem or Gadovist administrations. Being flexible in the study protocol design will strengthen ongoing sodium imaging investigations for various pathologies.

Comparison of image-based and reconstruction-based respiratory motion correction for golden radial phase encoding coronary MR angiography.

PURPOSE: To evaluate two commonly used respiratory motion correction techniques for coronary magnetic resonance angiography (MRA) regarding their dependency on motion estimation accuracy and final image quality and to compare both methods to the respiratory gating approach used in clinical practice. MATERIALS AND METHODS: Ten healthy volunteers were scanned using a non-Cartesian radial phase encoding acquisition. Respiratory motion was corrected for coronary MRA according to two motion correction techniques, image-based (IMC) and reconstruction-based (RMC) respiratory motion correction. Both motion correction approaches were compared quantitatively and qualitatively against a reference standard navigator-based respiratory gating (RG) approach. Quantitative comparisons were performed regarding visible vessel length, vessel sharpness, and total acquisition time. Two experts carried out a visual scoring of image quality. Additionally, numerical simulations were performed to evaluate the effect of motion estimation inaccuracy on RMC and IMC. RESULTS: RMC led to significantly better image quality than IMC (P's paired Student's t-test were smaller than 0.001 for vessel sharpness and visual scoring). RMC did not show a statistically significant difference compared to reference standard RG (vessel length [99% confidence interval]: 86.913 [83.097-95.015], P = 0.107; vessel sharpness: 0.640 [0.605-0.802], P = 0.012; visual scoring: 2.583 [2.410-3.424], P = 0.018) in terms of vessel visualization and image quality while reducing scan times by 56%. Simulations showed higher dependencies for RMC than for IMC on motion estimation inaccuracies. CONCLUSION: RMC provides a similar image quality as the clinically used RG approach but almost halves the scan time and is independent of subjects' breathing patterns. Clinical validation of RMC is now desirable.