An essentially radiation-transparent body coil integrated with a patient rotation system for MR-guided particle therapy.

BACKGROUND: The pursuit of adaptive radiotherapy using MR imaging for better precision in patient positioning puts stringent demands on the hardware components of the MR scanner. Particularly in particle therapy, the dose distribution and thus the efficacy of the treatment is susceptible to beam attenuation from interfering materials in the irradiation path. This severely limits the usefulness of conventional imaging coils, which contain highly attenuating parts such as capacitors and preamplifiers in an unknown position, and requires development of a dedicated radiofrequency (RF) coil with close consideration of the materials and components used. PURPOSE: In MR-guided radiation therapy in the human torso, imaging coils with a large FOV and homogeneous B1 field distribution are required for reliable tissue classification. In this work, an imaging coil for MR-guided particle therapy was developed with minimal ion attenuation while maintaining flexibility in treatment. METHODS: A birdcage coil consisting of nearly radiation-transparent materials was designed and constructed for a closed-bore 1.5 T MR system. Additionally, the coil was mounted on a rotatable patient capsule for flexible positioning of the patient relative to the beam. The ion attenuation of the RF coil was investigated in theory and via measurements of the Bragg peak position. To characterize the imaging quality of the RF coil, transmit and receive field distributions were simulated and measured inside a homogeneous tissue-simulating phantom for various rotation angles of the patient capsule ranging from 0° to 345° in steps of 15°. Furthermore, simulations with a heterogeneous human voxel model were performed to better estimate the effect of real patient loading, and the RF coil was compared to the internal body coil in terms of SNR for a full rotation of the patient capsule. RESULTS: The RF coil (total water equivalent thickness (WET) ≈ 420 µm, WET of conductor ≈ 210 µm) can be considered to be radiation-transparent, and a measured transmit power efficiency (B1 +/ P $\sqrt {\mathrm{P}} $ ) between 0.17 µT/ W $\sqrt {\mathrm{W}} $ and 0.26 µT/ W $\sqrt {\mathrm{W}} $ could be achieved in a volume (Δz = 216 mm, complete x and y range) for the 24 investigated rotation angles of the patient capsule. Furthermore, homogeneous transmit and receive field distributions were measured and simulated in the transverse, coronal and sagittal planes in a homogeneous phantom and a human voxel model. In addition, the SNR of the radiation-transparent RF coil varied between 103 and 150, in the volume (Δz = 216 mm) of a homogeneous phantom and surpasses the SNR of the internal body coil for all rotation angles of the patient capsule. CONCLUSIONS: A radiation-transparent RF coil was developed and built that enables flexible patient to beam positioning via full rotation capability of the RF coil and patient relative to the beam, with results providing promising potential for adaptive MR-guided particle therapy.

First implementation of dynamic oxygen-17 (17O) magnetic resonance imaging at 7 Tesla during neuronal stimulation in the human brain.

OBJECTIVE: First implementation of dynamic oxygen-17 (17O) MRI at 7 Tesla (T) during neuronal stimulation in the human brain. METHODS: Five healthy volunteers underwent a three-phase 17O gas (17O2) inhalation experiment. Combined right-side visual stimulus and right-hand finger tapping were used to achieve neuronal stimulation in the left cerebral hemisphere. Data analysis included the evaluation of the relative partial volume (PV)-corrected time evolution of absolute 17O water (H217O) concentration and of the relative signal evolution without PV correction. Statistical analysis was performed using a one-tailed paired t test. Blood oxygen level-dependent (BOLD) experiments were performed to validate the stimulation paradigm. RESULTS: The BOLD maps showed significant activity in the stimulated left visual and sensorimotor cortex compared to the non-stimulated right side. PV correction of 17O MR data resulted in high signal fluctuations with a noise level of 10% due to small regions of interest (ROI), impeding further quantitative analysis. Statistical evaluation of the relative H217O signal with PV correction (p = 0.168) and without (p = 0.382) did not show significant difference between the stimulated left and non-stimulated right sensorimotor ROI. DISCUSSION: The change of cerebral oxygen metabolism induced by sensorimotor and visual stimulation is not large enough to be reliably detected with the current setup and methodology of dynamic 17O MRI at 7 T.

Recent technical developments and clinical research applications of sodium (23Na) MRI.

Sodium is an essential ion that plays a central role in many physiological processes including the transmembrane electrochemical gradient and the maintenance of the body's homeostasis. Due to the crucial role of sodium in the human body, the sodium nucleus is a promising candidate for non-invasively assessing (patho-)physiological changes. Almost 10 years ago, Madelin et al. provided a comprehensive review of methods and applications of sodium (23Na) MRI (Madelin et al., 2014) [1]. More recent review articles have focused mainly on specific applications of 23Na MRI. For example, several articles covered 23Na MRI applications for diseases such as osteoarthritis (Zbyn et al., 2016, Zaric et al., 2020) [2,3], multiple sclerosis (Petracca et al., 2016, Huhn et al., 2019) [4,5] and brain tumors (Schepkin, 2016) [6], or for imaging certain organs such as the kidneys (Zollner et al., 2016) [7], the brain (Shah et al., 2016, Thulborn et al., 2018) [8,9], and the heart (Bottomley, 2016) [10]. Other articles have reviewed technical developments such as radiofrequency (RF) coils for 23Na MRI (Wiggins et al., 2016, Bangerter et al., 2016) [11,12], pulse sequences (Konstandin et al., 2014) [13], image reconstruction methods (Chen et al., 2021) [14], and interleaved/simultaneous imaging techniques (Lopez Kolkovsky et al., 2022) [15]. In addition, 23Na MRI topics have been covered in review articles with broader topics such as multinuclear MRI or ultra-high-field MRI (Niesporek et al., 2019, Hu et al., 2019, Ladd et al., 2018) [16-18]. During the past decade, various research groups have continued working on technical improvements to sodium MRI and have investigated its potential to serve as a diagnostic and prognostic tool. Clinical research applications of 23Na MRI have covered a broad spectrum of diseases, mainly focusing on the brain, cartilage, and skeletal muscle (see Fig. 1). In this article, we aim to provide a comprehensive summary of methodological and hardware developments, as well as a review of various clinical research applications of sodium (23Na) MRI in the last decade (i.e., published from the beginning of 2013 to the end of 2022).

First application of dynamic oxygen-17 magnetic resonance imaging at 7 Tesla in a patient with early subacute stroke.

Dynamic oxygen-17 (17O) magnetic resonance imaging (MRI) is an imaging method that enables a direct and non-invasive assessment of cerebral oxygen metabolism and thus potentially the distinction between viable and non-viable tissue employing a three-phase inhalation experiment. The purpose of this investigation was the first application of dynamic 17O MRI at 7 Tesla (T) in a patient with stroke. In this proof-of-concept experiment, dynamic 17O MRI was applied during 17O inhalation in a patient with early subacute stroke. The analysis of the relative 17O water (H217O) signal for the affected stroke region compared to the healthy contralateral side revealed no significant difference. However, the technical feasibility of 17O MRI has been demonstrated paving the way for future investigations in neurovascular diseases.

Assessment of Sodium MRI at 7 Tesla as Predictor of Therapy Response and Survival in Glioblastoma Patients.

The purpose of this work was to prospectively investigate sodium (23Na) MRI at 7 Tesla (T) as predictor of therapy response and survival in patients with glioblastoma (GBM). Thus, 20 GBM patients underwent 23Na MRI at 7T before, immediately after and 6 weeks after chemoradiotherapy (CRT). The median tissue sodium concentration (TSC) inside the whole tumor excluding necrosis was determined. Initial response to CRT was assessed employing the updated response assessment in neuro-oncology working group (RANO) criteria. Clinical parameters, baseline TSC and longitudinal TSC differences were compared between patients with initial progressive disease (PD) and patients with initial stable disease (SD) using Fisher's exact tests and Mann-Whitney-U-tests. Univariate proportional hazard models for progression free survival (PFS) and overall survival (OS) were calculated using clinical parameters and TSC metrics as predictor variables. The analyses demonstrated that TSC developed heterogeneously over all patients following CRT. None of the TSC metrics differed significantly between cases of initial SD and initial PD. Furthermore, TSC metrics did not yield a significant association with PFS or OS. Conversely, the initial response according to the RANO criteria could significantly predict PFS [univariate HR (95%CI) = 0.02 (0.0001-0.21), p < 0.001] and OS [univariate HR = 0.17 (0.04-0.65), p = 0.005]. In conclusion, TSC showed treatment-related changes in GBM following CRT, but did not significantly correlate with the initial response according to the RANO criteria, PFS or OS. In contrast, the initial response according to the RANO criteria was a significant predictor of PFS and OS. Future investigations need to elucidate the reasons for treatment-related changes in TSC and their clinical value for response prediction in glioblastoma patients receiving CRT.

7 Tesla and Beyond: Advanced Methods and Clinical Applications in Magnetic Resonance Imaging.

ABSTRACT: Ultrahigh magnetic fields offer significantly higher signal-to-noise ratio, and several magnetic resonance applications additionally benefit from a higher contrast-to-noise ratio, with static magnetic field strengths of B0 ≥ 7 T currently being referred to as ultrahigh fields (UHFs). The advantages of UHF can be used to resolve structures more precisely or to visualize physiological/pathophysiological effects that would be difficult or even impossible to detect at lower field strengths. However, with these advantages also come challenges, such as inhomogeneities applying standard radiofrequency excitation techniques, higher energy deposition in the human body, and enhanced B0 field inhomogeneities. The advantages but also the challenges of UHF as well as promising advanced methodological developments and clinical applications that particularly benefit from UHF are discussed in this review article.

3D sodium (23 Na) magnetic resonance fingerprinting for time-efficient relaxometric mapping.

PURPOSE: To develop a framework for 3D sodium (23 Na) MR fingerprinting (MRF), based on irreducible spherical tensor operators with tailored flip angle (FA) pattern and time-efficient data acquisition for simultaneous quantification of T1 , T2l∗ , T2s∗ , and T2∗ in addition to ΔB0 . METHODS: 23 Na-MRF was implemented in a 3D sequence and irreducible spherical tensor operators were exploited in the simulations. Furthermore, the Cramér Rao lower bound was used to optimize the flip angle pattern. A combination of single and double echo readouts was implemented to increase the readout efficiency. A study was conducted to compare results in a multicompartment phantom acquired with MRF and reference methods. Finally, the relaxation times in the human brain were measured in four healthy volunteers. RESULTS: Phantom experiments revealed a mean difference of 1.0% between relaxation times acquired with MRF and results determined with the reference methods. Simultaneous quantification of the longitudinal and transverse relaxation times in the human brain was possible within 32 min using 3D 23 Na-MRF with a nominal resolution of (5 mm)3 . In vivo measurements in four volunteers yielded average relaxation times of: T1,brain = (35.0 ± 3.2) ms, T2l,brain∗ = (29.3 ± 3.8) ms and T2s,brain∗ = (5.5 ± 1.3) ms in brain tissue, whereas T1,CSF = (61.9 ± 2.8) ms and T2,CSF∗ = (46.3 ± 4.5) ms was found in cerebrospinal fluid. CONCLUSION: The feasibility of in vivo 3D relaxometric sodium mapping within roughly ½ h is demonstrated using MRF in the human brain, moving sodium relaxometric mapping toward clinically relevant measurement times.

[Perspectives of X-nuclei magnetic resonance imaging in neuro-oncology]. / Perspektiven der X-Kern-Magnetresonanztomographie in der Neuroonkologie.

BACKGROUND: X­nuclei magnetic resonance imaging (MRI) yields a broad spectrum of metabolic and functional imaging techniques with increasing clinical feasibility. OBJECTIVE: Current X­nuclei techniques in (neuro)oncology with emphasis on potential clinical applications of sodium and oxygen MRI are described and discussed. MATERIALS AND METHODS: Review with discussion of state-of-the-art literature on X­nuclei imaging. RESULTS: X­nuclei MRI employs NMR-sensitive nonproton nuclei to enable both anatomical visualization as well as noninvasive imaging and quantification of physiological processes in the human body. At the moment, sodium MRI represents the most common application of X­nuclei MRI because of its comparatively high NMR signal. Moreover, its sensitivity to pathological cellular proliferation renders sodium MRI a good candidate for oncological imaging, yielding additional biochemical information to proton MRI. Oxygen MRI is currently primarily investigational, requiring high technical efforts and costs. However, preliminary results show a huge potential of this technique for metabolic characterization of tumors. CONCLUSIONS: X­nuclei MRI is a rapidly evolving field in metabolic and functional imaging. In coming years, sodium MRI is expected to be increasingly used as an additional clinical tool in oncology to enhance diagnostic accuracy.

Ultra-high-field sodium MRI as biomarker for tumor extent, grade and IDH mutation status in glioma patients.

PURPOSE: This prospective clinical trial investigated sodium (23Na) MRI at 7 Tesla (T) field strength as biomarker for tumor extent, isocitrate dehydrogenase (IDH) mutation and O6-methylguanine DNA methyltransferase (MGMT) promotor methylation in glioma patients. METHODS: 28 glioma patients underwent 23Na MRI on a 7T scanner (Siemens Healthcare, Erlangen, Germany) parallel to standard 3T MRI before chemoradiation. Areas of Gadolinium-contrast enhancement (gdce), non-enhancing T2-hyperintensity (regarded as edema), necrosis, and normal-appearing white matter (nawm) were segmented on 3T MRI imaging and were co-registered with the 23Na images. The median total 23Na concentrations of all areas were compared by pairwise t-tests. Furthermore, areas of gdce and edema were merged to yield the whole tumor area without necrosis. Subsequently, the difference in median of the 23Na concentration of this whole tumor area was compared between IDH-mutated and IDH wild-type gliomas as well as MGMT methylated and MGMT not-methylated glioblastomas using Whitney-Mann U-tests. All p-values were corrected after the Bonferroni-Holm procedure. RESULTS: The 23Na concentration increased successively from nawm to necrotic areas (mean ± sd: nawm = 37.84 ± 5.87 mM, edema = 54.69 ± 10.64 mM, gdce = 61.72 ± 12.95 mM, necrosis = 81.88 ± 17.53 mM) and the concentrations differed statistically significantly between all regarded areas (adjusted p-values for all pairwise comparisons < 0.05). Furthermore, IDH-mutated gliomas showed significantly higher 23Na concentrations than IDH wild-type gliomas (median [interquartile range]: IDH wild-type = 52.37 mM [45.98 - 58.56 mM], IDH mutated = 65.02 mM [58.87-67.05 mM], p = 0.039). Among the glioblastomas, there was a trend towards increased 23Na concentration in MGMT methylated tumors that did not reach statistical significance (median [interquartile range]: MGMT methylated = 57.59 mM [50.70 - 59.17 mM], MGMT not methylated = 48.78 mM [45.88 - 53.91 mM], p = 1.0). CONCLUSIONS: 23Na MRI correlates with the IDH mutation status and could therefore enhance image guidance towards biopsy sites as wells as image-guided surgery and radiotherapy. Furthermore, the successive decrease of 23Na concentration from central necrosis to normal-appearing white matter suggests a correlation with tumor infiltration.

Quantitative Dynamic Oxygen 17 MRI at 7.0 T for the Cerebral Oxygen Metabolism in Glioma.

Background Altered metabolism is a characteristic of cancer. Because of a shift in glucose metabolism from oxidative phosphorylation to lactate production for energy generation, malignant tumors are characterized by increased glycolysis followed by lactic acid fermentation, even in the presence of abundant oxygen (the Warburg effect). Purpose To quantitatively investigate dynamic oxygen 17 (17O) MRI in healthy participants and participants with untreated glioma to understand altered cerebral oxygen metabolism in glioma. Materials and Methods In this prospective study conducted from September 2016 to June 2018, individuals with newly diagnosed previously untreated glioma (World Health Organization grade II-IV) and healthy volunteers were included. Dynamic 17O MRI was performed with a 7.0-T whole-body system. 17O2 gas inhalation enabled dynamic measurement of the cerebral metabolic rate of oxygen (CMRO2) consumption. In healthy volunteers and participants with glioma, CMRO2 values in gray matter and white matter volumes were compared by using Wilcoxon signed rank tests. In participants with glioma, the tumor volume and tumor subcompartments were compared with normal-appearing gray matter and white matter by using Friedman test followed by Holm-Sidak post hoc tests. Results Ten participants (mean age, 42 years ± 18 [standard deviation]; nine men) with glioma and three healthy volunteers (mean age, 44 years ± 21; all men) were evaluated. CMRO2 was higher in normal-appearing gray matter compared with white matter in both participants with glioma (2.36 µmol/g/min ± 0.22 vs 0.75 µmol/g/min ± 0.10, respectively) and healthy volunteers (2.38 µmol/g/min ± 0.15 vs 0.63 µmol/g/min ± 0.05, respectively) (P < .001 and P = .03, respectively). In the tumor region, CMRO2 was reduced (high-grade tumor CMRO2, 0.23 µmol/g/min ± 0.07; low-grade tumor CMRO2, 0.39 µmol/g/min ± 0.16; overall CMRO2, 0.34 µmol/g/min ± 0.16) compared with normal-appearing gray matter (P < .001) and normal-appearing white matter (P < .001) in accordance with the Warburg theorem. Conclusion Dynamic oxygen 17 MRI method at 7.0 T as a direct metabolic imaging technique in glioma enabled quantitative visualization of the Warburg effect. A general reduction in oxidative glycolysis was observed in accordance with the Warburg theorem. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Rapalino in this issue.

Multinuclear MRI at Ultrahigh Fields.

In this article, an overview of the current developments and research applications for non-proton magnetic resonance imaging (MRI) at ultrahigh magnetic fields (UHFs) is given. Due to technical and methodical advances, efficient MRI of physiologically relevant nuclei, such as Na, Cl, Cl, K, O, or P has become feasible and is of interest to obtain spatially and temporally resolved information that can be used for biomedical and diagnostic applications. Sodium (Na) MRI is the most widespread multinuclear imaging method with applications ranging over all regions of the human body. Na MRI yields the second largest in vivo NMR signal after the clinically used proton signal (H). However, other nuclei such as O and P (energy metabolism) or Cl and K (cell viability) are used in an increasing number of MRI studies at UHF. One major advancement has been the increased availability of whole-body MR scanners with UHFs (B0 ≥7T) expanding the range of detectable nuclei. Nevertheless, efforts in terms of pulse sequence and post-processing developments as well as hardware designs must be made to obtain valuable information in clinically feasible measurement times. This review summarizes the available methods in the field of non-proton UHF MRI, especially for Na MRI, as well as introduces potential applications in clinical research.

Corrections of myocardial tissue sodium concentration measurements in human cardiac 23 Na MRI at 7 Tesla.

PURPOSE: To quantify the tissue sodium concentration (TSC) in cardiac 23 Na MRI. To evaluate the influence of different correction methods on the measured myocardial TSC. METHODS: 23 Na MRI of four healthy subjects was conducted at a whole-body 7T MRI system using an oval-shaped 23 Na birdcage coil. Data acquisition was performed with a density-adapted 3D radial pulse sequence using a golden angle projection scheme. 1 H MRI data were acquired at a 3T MRI system to generate a myocardial mask. Retrospective cardiac and respiratory gating were used to reconstruct 23 Na MRI data in the diastolic phase and exhaled state. B0 and B1 inhomogeneity and partial volume (PV) effects were corrected. Relaxation times and TSC of ex vivo blood samples and calf muscle were determined. These values were used in the PV correction to estimate myocardial TSC, which was compared with the measured TSC of calf muscle. RESULTS: Without any correction the measured myocardial TSC was (54 ± 5) mM. The applied correction methods reduced these values by (48 ± 5)% to (29 ± 3) mM, where PV correction had the largest effect (reduction of (34 ± 1)%). Respiratory and cardiac motion gating decreased the concentrations by (11 ± 1)%. With the applied setup, the corrections of B0 and B1 inhomogeneity (reduction of (3 ± 2)%) had negligible influences on TSC values. The resulting myocardial TSC was approximately 1.4-fold higher than the measured TSC of calf muscle tissue of the same healthy subjects ((20 ± 3) mM). CONCLUSION: For quantitative human cardiac 23 Na MRI several corrections are needed and ranked for our setup: PV correction, respiratory and cardiac gating, correction for B1 inhomogeneity effects.