Armin M. Nagel

Sodium MRI using a density‐adapted 3D radial acquisition technique

A density‐adapted three‐dimensional radial projection reconstruction pulse sequence is presented which provides a more efficient k‐space sampling than conventional three‐dimensional projection reconstruction sequences. The gradients of the density‐adapted three‐dimensional radial projection reconstruction pulse sequence are designed such that the averaged sampling density in each spherical shell of k‐space is constant. Due to hardware restrictions, an inner sphere of k‐space is sampled without density adaption. This approach benefits from both the straightforward handling of conventional three‐dimensional projection reconstruction sequence trajectories and an enhanced signal‐to‐noise ratio (SNR) efficiency akin to the commonly used three‐dimensional twisted projection imaging trajectories. Benefits for low SNR applications, when compared to conventional three‐dimensional projection reconstruction sequences, are demonstrated with the example of sodium imaging. In simulations of the point‐spread function, the SNR of small objects is increased by a factor 1.66 for the density‐adapted three‐dimensional radial projection reconstruction pulse sequence sequence. Using analytical and experimental phantoms, it is shown that the density‐adapted three‐dimensional radial projection reconstruction pulse sequence allows higher resolutions and is more robust in the presence of field inhomogeneities. High‐quality in vivo images of the healthy human leg muscle and the healthy human brain are acquired. For equivalent scan times, the SNR is up to a factor of 1.8 higher and anatomic details are better resolved using density‐adapted three‐dimensional radial projection reconstruction pulse sequence. Magn Reson Med, 2009.

MRI at 7 tesla and above: Demonstrated and potential capabilities

With more than 40 installed MR systems worldwide operating at 7 Tesla or higher, ultra‐high‐field (UHF) imaging has been established as a platform for clinically oriented research in recent years. Along with technical developments that, in part, have also been successfully transferred to lower field strengths, MR imaging and spectroscopy at UHF have demonstrated capabilities and potentials for clinical diagnostics in a variety of studies. In terms of applications, this overview article focuses on already achieved advantages for in vivo imaging, i.e., in imaging the brain and joints of the musculoskeletal system, but also considers developments in body imaging, which is particularly challenging. Furthermore, new applications for clinical diagnostics such as X‐nuclei imaging and spectroscopy, which only really become feasible at ultra‐high magnetic fields, will be presented. J. Magn. Reson. Imaging 2015;41:13–33.

Quantitative Susceptibility Mapping Differentiates between Blood Depositions and Calcifications in Patients with Glioblastoma

Objectives The application of susceptibility weighted imaging (SWI) in brain tumor imaging is mainly used to assess tumor-related “susceptibility based signals” (SBS). The origin of SBS in glioblastoma is still unknown, potentially representing calcifications or blood depositions. Reliable differentiation between both entities may be important to evaluate treatment response and to identify glioblastoma with oligodendroglial components that are supposed to present calcifications. Since calcifications and blood deposits are difficult to differentiate using conventional MRI, we investigated whether a new post-processing approach, quantitative susceptibility mapping (QSM), is able to distinguish between both entities reliably. Materials and Methods SWI, FLAIR, and T1-w images were acquired from 46 patients with glioblastoma (14 newly diagnosed, 24 treated with radiochemotherapy, 8 treated with radiochemotherapy and additional anti-angiogenic medication). Susceptibility maps were calculated from SWI data. All glioblastoma were evaluated for the appearance of hypointense or hyperintense correlates of SBS on the susceptibility maps. Results 43 of 46 glioblastoma presented only hyperintense intratumoral SBS on susceptibility maps, indicating blood deposits. Additional hypointense correlates of tumor-related SBS on susceptibility maps, indicating calcification, were identified in 2 patients being treated with radiochemotherapy and in one patient being treated with additional anti-angiogenic medication. Histopathologic reports revealed an oligodendroglial component in one patient that presented calcifications on susceptibility maps. Conclusions QSM provides a quantitative, local MRI contrast, which reliably differentiates between blood deposits and calcifications. Thus, quantitative susceptibility mapping appears promising to identify rare variants of glioblastoma with oligodendroglial components non-invasively and may allow monitoring the role of calcification in the context of different therapy regimes.

The potential of relaxation-weighted sodium magnetic resonance imaging as demonstrated on brain tumors

Objectives:Total tissue sodium (23Na) content is associated with the viability of cells and can be assessed by 23Na magnetic resonance imaging. However, the resulting total sodium signal (23NaT) represents a volume-weighted average of different sodium compartments assigned to the intra- and extracellular space. In addition to the spin-density weighted contrast of 23NaT imaging, relaxation-weighted (23NaR) sequences were applied. The aim of this study was to evaluate the potential of 23NaR imaging for tissue characterization and putative additional benefits to 23NaT imaging. Materials and Methods:For 23NaT and 23NaR imaging, novel magnetic resonance imaging sequences were established and applied in 16 patients suffering from brain tumors (14 WHO grade I–IV and 2 metastases). All 23Na sequences were based on density-adapted three-dimensional radial projection reconstruction to obtain short echo times and high signal-to-noise ratio efficiency. Results:23NaT imaging revealed increased signal intensities in 15 of 16 brain tumors before therapy. In addition, 23NaR imaging enabled further differentiation of these lesions; all glioblastomas demonstrated higher 23NaR signal intensities as compared with WHO grade I–III tumors. Thus, 23NaR imaging allowed for correct separation between WHO grade I–III and WHO grade IV gliomas. In contrast to the 23NaT signal, the 23NaR signal correlated with the MIB-1 proliferation rate of tumor cells. Conclusions:These results serve as a proof of concept that 23NaR imaging reveals important physiological tissue characteristics different from 23NaT imaging. Furthermore, they indicate that the combined use of 23NaT and 23NaR imaging might add valuable information for the functional in vivo characterization of brain tissue.

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.

3 Tesla Sodium Inversion Recovery Magnetic Resonance Imaging Allows for Improved Visualization of Intracellular Sodium Content Changes in Muscular Channelopathies

Objectives:To implement different sodium (23Na)-magnetic resonance imaging (MRI) contrasts at 3 Tesla and to evaluate if a weighting toward intracellular sodium can be achieved, using 2 rare muscular channelopathies as model diseases. Materials and Methods:Both lower legs of 6 patients with hypokalemic periodic paralysis (HypoPP), 5 patients with paramyotonia congenita (PC), and 5 healthy volunteers were examined on a 3 Tesla system with 3 different 23Na-MRI pulse sequences. HypoPP and PC are rare muscle diseases, which are well characterized by elevated myoplasmic sodium at rest and after cooling, respectively. Intra- and interindividual comparisons were performed before and after provocation of one lower leg muscle. Three different 23Na-MRI sequences were applied: (i) The total tissue sodium concentration was measured using a spin-density sequence (23Na-TSC). (ii) A T1-contrast was applied to assess whether the known changes of the intracellular sodium concentration can be visualized by T1-weighting (23Na-T1). (iii) An inversion recovery (23Na-IR) sequence was used to utmost suppress the sodium signal from extracellular or vasogenic edema. Furthermore, a potential influence of the temperature dependency of the sodium relaxation times was considered. Additionally, 1H-MRI was performed to examine potential lipomatous or edematous changes. Results:In HypoPP, all 23Na sequences showed significantly (P < 0.05) higher signal intensities compared with PC patients and healthy subjects. In muscles of PC patients, provocation induced a significant (P = 0.0007) increase (>20%) in the muscular 23Na-IR signal and a corresponding decrease of muscle strength. Additionally, a tendency to higher 23Na-T1 (P = 0.07) and 23Na-TSC (P = 0.07) signal intensities was observed. Provocation revealed no significant changes in 1H-MRI. In volunteers and in the contralateral, not cooled lower leg, there were no significant signal intensity changes after provocation. Furthermore, the 23Na-IR sequence allows for a suppression of signal emanating from intravascular sodium and vasogenic edema. Conclusions:Our results indicate that the 23Na-IR sequence allows for a weighting toward intracellular sodium. The combined application of the 23Na-TSC and the 23Na-IR sequence enables an improved analysis of pathophysiological changes that occur in muscles of patients with muscular channelopathies.

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.

Nuclear Overhauser Enhancement Mediated Chemical Exchange Saturation Transfer Imaging at 7 Tesla in Glioblastoma Patients

Background and Purpose Nuclear Overhauser Enhancement (NOE) mediated chemical exchange saturation transfer (CEST) is a novel magnetic resonance imaging (MRI) technique on the basis of saturation transfer between exchanging protons of tissue proteins and bulk water. The purpose of this study was to evaluate and compare the information provided by three dimensional NOE mediated CEST at 7 Tesla (7T) and standard MRI in glioblastoma patients. Patients and Methods Twelve patients with newly diagnosed histologically proven glioblastoma were enrolled in this prospective ethics committee–approved study. NOE mediated CEST contrast was acquired with a modified three-dimensional gradient-echo sequence and asymmetry analysis was conducted at 3.3ppm (B1 = 0.7 µT) to calculate the magnetization transfer ratio asymmetry (MTRasym). Contrast enhanced T1 (CE-T1) and T2-weighted images were acquired at 3T and used for data co-registration and comparison. Results Mean NOE mediated CEST signal based on MTRasym values over all patients was significantly increased (p<0.001) in CE-T1 tumor (−1.99±1.22%), tumor necrosis (−1.36±1.30%) and peritumoral CEST hyperintensities (PTCH) within T2 edema margins (−3.56±1.24%) compared to contralateral normal appearing white matter (−8.38±1.19%). In CE-T1 tumor (p = 0.015) and tumor necrosis (p<0.001) mean MTRasym values were significantly higher than in PTCH. Extent of the surrounding tumor hyperintensity was smaller in eight out of 12 patients on CEST than on T2-weighted images, while four displayed at equal size. In all patients, isolated high intensity regions (0.40±2.21%) displayed on CEST within the CE-T1 tumor that were not discernible on CE-T1 or T2-weighted images. Conclusion NOE mediated CEST Imaging at 7T provides additional information on the structure of peritumoral hyperintensities in glioblastoma and displays isolated high intensity regions within the CE-T1 tumor that cannot be acquired on CE-T1 or T2-weighted images. Further research is needed to determine the origin of NOE mediated CEST and possible clinical applications such as therapy assessment or biopsy planning.

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.

Sodium (23Na) MRI detects elevated muscular sodium concentration in Duchenne muscular dystrophy

Objective: In boys with Duchenne muscular dystrophy (DMD), 1H MRI suggested muscular edema before fatty degeneration. Using specific 23Na MRI sequences, we tested the hypothesis that the edema is caused by an osmotic effect due to increased myoplasmic Na+ content rather than inflammation that would lead to extracellular edema. Methods: Eleven patients with DMD (mean age, 10 ± 5 years) and 16 healthy volunteers of similar age were examined on a 3-T system with 1H MRI and 23Na density-adapted 3-dimensional radial MRI sequences. The muscle edema was quantified on short-tau inversion recovery images using background noise as reference. Fatty degeneration was quantified on T1-weighted images using subcutaneous fat as reference. Na+ was quantified by a muscular tissue sodium concentration (TSC) sequence. A novel inversion recovery (IR) sequence allowed us to determine mainly the myoplasmic Na+ by suppression of the extracellular 23Na signal from vasogenic edema. A reference tube containing 51.3 mmol/L Na+ with agarose gel was used for standardization. Results: The normalized muscular signal intensity of 23Na as assessed by the IR sequence was significantly higher for patients with DMD than for volunteers. TSC was markedly increased at 38.4 ± 6.8 mmol/L in patients with DMD compared with 25.4 ± 2.1 mmol/L in volunteers. The muscular edema-like changes were much more prominent in patients with DMD than in volunteers. In addition, the muscular fat content was significantly higher in patients with DMD than in volunteers. Conclusions: The elevated myoplasmic Na+ concentration in DMD is osmotically relevant and causes a mainly intracellular muscle edema that contributes to the pathogenesis of DMD.