Simon Konstandin

Distribution of Brain Sodium Accumulation Correlates with Disability in Multiple Sclerosis: A Cross-sectional 23Na MR Imaging Study

PURPOSE To quantify brain sodium accumulations and characterize for the first time the spatial location of sodium abnormalities at different stages of relapsing-remitting (RR) multiple sclerosis (MS) by using sodium 23 ((23)Na) magnetic resonance (MR) imaging. MATERIALS AND METHODS This study was approved by the local committee on ethics, and written informed consent was obtained from all participants. Three-dimensional (23)Na MR imaging data were obtained with a 3.0-T unit in two groups of patients with RR MS-14 with early RR MS (disease duration <5 years) and 12 with advanced RR MS (disease duration >5 years)-and 15 control subjects. Quantitative assessment of total sodium concentration (TSC) levels within compartments (MS lesions, white matter [WM], and gray matter [GM]) as well as statistical mapping analyses of TSC abnormalities were performed. RESULTS TSC was increased inside demyelinating lesions in both groups of patients, whereas increased TSC was observed in normal-appearing WM and GM only in those with advanced RR MS. In patients, increased TSC inside GM was correlated with disability (as determined with the Expanded Disability Status Scale [EDSS] score; P = .046, corrected) and lesion load at T2-weighted imaging (P = .003, corrected) but not with disease duration (P = .089, corrected). Statistical mapping analysis showed confined TSC increases inside the brainstem, cerebellum, and temporal poles in early RR MS and widespread TSC increases that affected the entire brain in advanced RR MS. EDSS score correlated with TSC increases inside motor networks. CONCLUSION TSC accumulation dramatically increases in the advanced stage of RR MS, especially in the normal-appearing brain tissues, concomitant with disability. Brain sodium MR imaging may help monitor the occurrence of tissue injury and disability.

Quantitative and Qualitative 23Na MR Imaging of the Human Kidneys at 3 T: Before and after a Water Load

PURPOSE To qualitatively and quantitatively assess the corticomedullary sodium 23 ((23)Na) concentration in human kidneys before and after oral administration of a water load by using 3-T magnetic resonance (MR) imaging. MATERIALS AND METHODS Fourteen healthy volunteers (mean age, 28 years; range, 24-34 years) were included in this institutional review board-approved study between July and December 2009. For (23)Na MR imaging, a density-adapted three-dimensional radial gradient echo sequence (echo time, 0.55 msec; repetition time, 120 msec; spatial resolution, 5 × 5 × 5 mm) was used with a dedicated (23)Na-tuned coil. Beforehand, the coil profile was assessed by using phantom measurements, and the volunteer images were mathematically corrected accordingly. Images of the volunteers were obtained before and 30 minutes after oral ingestion of 1 L of water. As internal reference, (23)Na concentration of the cerebrospinal fluid (CSF) was calculated. Well-defined corticomedullary complexes in each kidney were assessed, with (23)Na concentrations in the cortex and medulla assessed at various standardized points. From these values, quantitative (23)Na concentrations were derived, and the slopes of the linear portion of the concentration gradient were calculated. Paired t tests were performed. RESULTS Mean calculated (23)Na concentrations of CSF before (135.2 mmol/L ± 10.4) and after water load (135.5 mmol/L ± 11.0) fell within physiologic ranges (P = .95). An increase in average (23)Na concentration from 63.5 mmol/L ± 9.3 in the cortex to 108.0 mmol/L ± 10.9 in the medulla was identified. After the water load, this gradient was preserved, although (23)Na concentrations decreased significantly (P < .0001) to 48.6 mmol/L ± 5.3 in the cortex and 81.9 mmol/L ± 10.1 in the medulla-declines of 23.4% and 24.7%, respectively. CONCLUSION This study demonstrates the physiologic evaluation of human kidneys with 3-T (23)Na MR imaging. The (23)Na imaging technique used allows the quantification of the corticomedullary (23)Na concentration and the assessment of its change with differing physiologic conditions.

Measurement techniques for magnetic resonance imaging of fast relaxing nuclei

In this review article, techniques for sodium (23Na) magnetic resonance imaging (MRI) are presented. These techniques can also be used to image other nuclei with short relaxation times (e.g., 39K, 35Cl, 17O). Twisted projection imaging, density-adapted 3D projection reconstruction, and 3D cones are preferred because of uniform k-space sampling and ultra-short echo times. Sampling density weighted apodization can be applied if intrinsic filtering is desired. This approach leads to an increased signal-to-noise ratio compared to postfiltered acquisition in cases of short readout durations relative to T2* relaxation time. Different MR approaches for anisotropic resolution are presented, which are important for imaging of thin structures such as myocardium, cartilage, and skin. The third part of this review article describes different methods to put more weighting either on the intracellular or the extracellular sodium signal by means of contrast agents, relaxation-weighted imaging, or multiple-quantum filtering.

Two‐dimensional radial acquisition technique with density adaption in sodium MRI

Conventional 2D radial projections suffer from losses in signal‐to‐noise ratio efficiency because of the nonuniform k‐space sampling. In this study, a 2D projection reconstruction method with variable gradient amplitudes is presented to cover the k‐space uniformly. The gradient is designed to keep the average sampling density constant. By this, signal‐to‐noise ratio is increased, and the linear form of the radial trajectory is kept. The simple gradient design and low hardware requirements in respect of slew rate allow an easy implementation at MR scanners. Measurements with the density‐adapted 2D radial trajectory were compared with the conventional projection reconstruction method. It is demonstrated that the density‐adapted 2D radial trajectory technique provides higher signal‐to‐noise ratio (up to 28% in brain tissue), less blurring, and fewer artifacts in the presence of magnetic field inhomogeneities than imaging with the conventional 2D radial trajectory scheme. The presented sequence is well‐suited for electrocardiographically gated sodium heart MRI and other applications with short relaxation times. Magn Reson Med, 2010.

Performance of sampling density-weighted and postfiltered density-adapted projection reconstruction in sodium magnetic resonance imaging.

Sampling density‐weighted apodization projection reconstruction sequences are evaluated for three‐dimensional radial imaging. The readout gradients of the sampling density‐weighted apodization sequence are designed such that the locally averaged sampling density matches a Hamming filter function. This technique is compared with density‐adapted projection reconstruction with nonfiltered and postfiltered image reconstruction. Sampling density‐weighted apodization theoretically allows for a 1.28‐fold higher signal‐to‐noise ratio compared with postfiltered density‐adapted projection reconstruction sequences, if T  2* decay is negligible compared with the readout duration TRO. Simulations of the point‐spread functions are performed for monoexponential and biexponential decay to investigate the effects of T  2* decay on the performance of the different sequences. Postfiltered density‐adapted projection reconstruction performs superior to sampling density‐weighted apodization for large TRO/T  2* ratios [>1.36 (monoexponential decay); >0.35 (biexponential decay with T  2s* /T  2f* = 10)], if signal‐to‐noise ratio of point‐like objects is considered. In conclusion, it depends on the readout parameters, the T  2* relaxation times, and the dimensions of the subject which of both sequences is most suitable. Magn Reson Med, 2013.

Whole body sodium MRI at 3T using an asymmetric birdcage resonator and short echo time sequence: first images of a male volunteer

Sodium magnetic resonance imaging (²³Na MRI) is a non-invasive technique which allows spatial resolution of the tissue sodium concentration (TSC) in the human body. TSC measurements could potentially serve to monitor early treatment success of chemotherapy on patients who suffer from whole body metastases. Yet, the acquisition of whole body sodium (²³Na) images has been hampered so far by the lack of large resonators and the extremely low signal-to-noise ratio (SNR) achieved with existing resonator systems. In this study, a ²³Na resonator was constructed for whole body ²³Na MRI at 3T comprising of a 16-leg, asymmetrical birdcage structure with 34 cm height, 47.5 cm width and 50 cm length. The resonator was driven in quadrature mode and could be used either as a transceiver resonator or, since active decoupling was included, as a transmit-only resonator in conjunction with a receive-only (RO) surface resonator. The relative B₁-field profile was simulated and measured on phantoms, and 3D whole body ²³Na MRI data of a healthy male volunteer were acquired in five segments with a nominal isotropic resolution of (6 × 6 × 6) mm³ and a 10 min acquisition time per scan. The measured SNR values in the ²³Na-MR images varied from 9 ± 2 in calf muscle, 15 ± 2 in brain tissue, 23 ± 2 in the prostate and up to 42 ± 5 in the vertebral discs. Arms, legs, knees and hands could also be resolved with applied resonator and short time-to-echo (TE) (0.5 ms) radial sequence. Up to fivefold SNR improvement was achieved through combining the birdcage with local RO surface coil. In conclusion, ²³Na MRI of the entire human body provides sub-cm spatial resolution, which allows resolution of all major human body parts with a scan time of less than 60 min.

Quantitative sodium MRI of kidney

One of the main tasks of the human kidneys is to maintain the homeostasis of the bodys fluid and electrolyte balance by filtration of the plasma and excretion of the end products. Herein, the regulation of extracellular sodium in the kidney is of particular importance. Sodium MRI (23Na MRI) allows for the absolute quantification of the tissue sodium concentration (TSC) and thereby provides a direct link between TSC and tissue viability. Renal 23Na MRI can provide new insights into physiological tissue function and viability thought to differ from the information obtained by standard 1H MRI. Sodium imaging has the potential to become an independent surrogate biomarker not only for renal imaging, but also for oncology indications. However, this technique is now on the threshold of clinical implementation. Numerous, initial pre‐clinical and clinical studies have already outlined the potential of this technique; however, future studies need to be extended to larger patient groups to show the diagnostic outcome. In conclusion, 23Na MRI is seen as a powerful technique with the option to establish a non‐invasive renal biomarker for tissue viability, but is still a long way from real clinical implementation. Copyright

Apparent diffusion coefficient and sodium concentration measurements in human prostate tissue via hydrogen-1 and sodium-23 magnetic resonance imaging in a clinical setting at 3T.

IntroductionMultiparametric magnetic resonance imaging (MRI) of the prostate involves morphologic and functional imaging techniques, which could potentially enable to distinguish between common benign prostate diseases, especially prostatitis and prostate cancer. The aim of this study was to determine the apparent diffusion coefficient (ADC) and the tissue sodium concentration (TSC) in 2 different regions of the human prostate, that is, the central gland (CG) and the peripheral gland (PG), by means of standard hydrogen-1 (1H) MRI and quantitative sodium-23 (23Na) MRI at 3 T to increase the spectrum of diagnostic parameters for prostate examinations. MethodsAll measurements were performed on a 3-T clinical whole-body magnetic resonance (MR) scanner. 23Na MR images were acquired with density-adapted 3-dimensional radial sequence and isotropic voxel resolution of 5 × 5 × 5 mm3. After approval by the institutional review board and informed consent were obtained, 8 healthy volunteers were included in this study. Diffusion-weighted imaging and T2-weighted images were also recorded and hence enabled the correlation of measured TSC values with current state-of-the-art 1H MRI techniques. ResultsThe ADC in both subregions was measured to be at normal levels (CG, 1.19 [0.09] ×10−3 mm2/s; PG, 1.54 [0.14] × 10−3 mm2/s) in all 8 volunteers. Good spatial resolution of the 23Na images allowed for an easy identification of the same subregions from the 23Na MR images. In healthy adult volunteers (age, 29 [2] years), the TSC was measured lower in central (55 [15] mmol/L) and higher in peripheral (69 [16] mmol/L) prostate tissue. A correlation between the TSC and the ADC in the 2 subregions was found in the same volunteer group (Pearson correlation coefficient = 0.87). DiscussionFor the first time, TSC was spatially resolved in human prostate tissue by means of 23Na MRI. Interestingly, the herein found TSC values of ∼60 mmol/L were half as high as in a previously reported 23Na MRI study where prostate TSC was measured in 5-month-old mice. Future studies are required to determine the prostate TSC in cancer patients as well as in older volunteers. In conclusion, TSC can be measured in humans with sufficiently high spatial and temporal resolution at 3 T and could hence provide an additional noninvasive marker for the diagnosis of various prostate pathologies.

Chemical shift sodium imaging in a mouse model of thromboembolic stroke at 9.4 T

To estimate changes in the 23Na density and in the 23Na relaxation time T2* in the anatomically small murine brain after stroke.

Imaging of tumor viability in lung cancer: initial results using 23Na-MRI.

PURPOSE 23Na-MRI has been proposed as a potential imaging biomarker for the assessment of tumor viability and the evaluation of therapy response but has not yet been evaluated in patients with lung cancer. We aimed to assess the feasibility of 23Na-MRI in patients with lung cancer. MATERIALS AND METHODS Three patients with stage IV adenocarcinoma of the lung were examined on a clinical 3 Tesla MRI system (Magnetom TimTrio, Siemens Healthcare, Erlangen, Germany). Feasibility of 23Na-MRI images was proven by comparison and fusion of 23Na-MRI with 1H-MR, CT and FDG-PET-CT images. 23Na signal intensities (SI) of tumor and cerebrospinal fluid (CSF) of the spinal canal were measured and the SI ratio in tumor and CSF was calculated. One chemonaive patient was examined before and after the initiation of combination therapy (Carboplatin, Gemcitabin, Cetuximab). RESULTS All 23Na-MRI examinations were successfully completed and were of diagnostic quality. Fusion of 23Na-MRI images with 1H-MRI, CT and FDG-PET-CT was feasible in all patients and showed differences in solid and necrotic tumor areas. The mean tumor SI and the tumor/CSF SI ratio were 13.3 ± 1.8 × 103 and 0.83 ± 0.14, respectively. In necrotic tumors, as suggested by central non-FDG-avid areas, the mean tumor SI and the tumor/CSF ratio were 19.4 × 103 and 1.10, respectively. CONCLUSION 23Na-MRI is feasible in patients with lung cancer and could provide valuable functional molecular information regarding tumor viability, and potentially treatment response.