Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer's disease (DEBBIE-AD): a prospective observational multicohort study protocol.

INTRODUCTION: Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer's disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). METHODS AND ANALYSIS: DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and AD-related pathologies. ETHICS AND DISSEMINATION: Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.

Blood-Brain Barrier Permeability to Water Measured Using Multiple Echo Time Arterial Spin Labeling MRI in the Aging Human Brain.

BACKGROUND: The blood-brain barrier (BBB) plays a vital role in maintaining brain homeostasis, but the integrity of this barrier deteriorates slowly with aging. Noninvasive water exchange magnetic resonance imaging (MRI) methods may identify changes in the BBB occurring with healthy aging. PURPOSE: To investigate age-related changes in the BBB permeability to water using multiple-echo-time (multi-TE) arterial spin labeling (ASL) MRI. STUDY TYPE: Prospective, cohort. POPULATION: Two groups of healthy humans-older group (≥50 years, mean age = 56 ± 4 years, N = 13, females = 5) and younger group (≤20 years, mean age = 18 ± 1, N = 13, females = 7). FIELD STRENGTH/SEQUENCE: A 3T, multi-TE Hadamard pCASL with 3D Gradient and Spin Echo (GRASE) readout. ASSESSMENT: Two different approaches of variable complexity were applied. A physiologically informed biophysical model with a higher complexity estimating time ( T ex ) taken by the labeled water to move across the BBB and a simpler model of triexponential decay measuring tissue transition rate ( k lin ) . STATISTICS: Two-tailed unpaired Student t-test, Pearson's correlation coefficient and effect size. P < 0.05 was considered significant. RESULTS: Older volunteers showed significant differences of 36% lower T ex , 29% lower cerebral perfusion, 17% pronged arterial transit time and 22% shorter intra-voxel transit time compared to the younger volunteers. Tissue fraction ( f EV ) at the earliest TI = 1600 msec was significantly higher in the older group, which contributed to a significantly lower k lin compared to the younger group. f EV at TI = 1600 msec showed significant negative correlation with T ex (r = -0.80), and k lin and T ex showed significant positive correlation (r = 0.73). DATA CONCLUSIONS: Both approaches of Multi-TE ASL imaging showed sensitivity to detect age-related changes in the BBB permeability. High tissue fractions at the earliest TI and short T ex in the older volunteers indicate that the BBB permeability increased with age. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Subject-specific timing adaption in time-encoded arterial spin labeling imaging.

OBJECTIVES: One challenge in arterial spin labeling (ASL) is the high variability of arterial transit times (ATT), which causes associated arterial transit delay (ATD) artifacts. In patients with pathological changes, these artifacts occur when post-labeling delay (PLD) and bolus durations are not optimally matched to the subject, resulting in difficult quantification of cerebral blood flow (CBF) and ATT. This is also true for the free lunch approach in Hadamard-encoded pseudocontinuous ASL (H-pCASL). MATERIAL AND METHODS: Five healthy volunteers were scanned with a 3 T MR-system. pCASL-subbolus timing was adjusted individually by the developed adaptive Walsh-ordered pCASL sequence and an automatic feedback algorithm. The quantification results for CBF and ATT and the respective standard deviations were compared with results obtained using recommended timings and intentionally suboptimal timings. RESULTS: The algorithm individually adjusted the pCASL-subbolus PLD for each subject within the range of recommended timing for healthy subjects, with a mean intra-subject adjustment deviation of 47.15 ms for single-shot and 44.5 ms for segmented acquisition in three repetitions. DISCUSSION: A first positive assessment of the results was performed on healthy volunteers. The extent to which the results can be transferred to patients and are of benefit must be investigated in follow-up studies.

Concordance of regional hypoperfusion by pCASL MRI and 15O-water PET in frontotemporal dementia: Is pCASL an efficacious alternative?

BACKGROUND: Clinical diagnosis of frontotemporal dementia (FTD) remains a challenge due to the overlap of symptoms among FTD subtypes and with other psychiatric disorders. Perfusion imaging by arterial spin labeling (ASL) is a promising non-invasive alternative to established PET techniques; however, its sensitivity to imaging parameters can hinder its ability to detect perfusion abnormalities. PURPOSE: This study evaluated the similarity of regional hypoperfusion patterns detected by ASL relative to the gold standard for imaging perfusion, PET with radiolabeled water (15O-water). METHODS AND MATERIALS: Perfusion by single-delay pseudo continuous ASL (SD-pCASL), free-lunch Hadamard encoded pCASL (FL_TE-pCASL), and 15O-water data were acquired on a hybrid PET/MR scanner in 13 controls and 9 FTD patients. Cerebral blood flow (CBF) by 15O-water was quantified by a non-invasive approach (PMRFlow). Regional hypoperfusion was determined by comparing individual patients to the control group. This was performed using absolute (aCBF) and CBF normalized to whole-brain perfusion (rCBF). Agreement was assessed based on the fraction of overlapping voxels. Sensitivity and specificity of pCASL was estimated using hypoperfused regions of interest identified by 15O-water. RESULTS: Region of interest (ROI) based perfusion measured by 15O-water strongly correlated with SD-pCASL (R = 0.85 ± 0.1) and FL_TE-pCASL (R = 0.81 ± 0.14). Good agreement in terms of regional hypoperfusion patterns was found between 15O-water and SD-pCASL (sensitivity = 70%, specificity = 78%) and between 15O-water and FL_TE-pCASL (sensitivity = 71%, specificity = 73%). However, SD-pCASL showed greater overlap (43.4 ± 21.3%) with 15O-water than FL_TE-pCASL (29.9 ± 21.3%). Although aCBF and rCBF showed no significant differences regarding spatial overlap and metrics of agreement with 15O-water, rCBF showed considerable variability across subtypes, indicating that care must be taken when selecting a reference region. CONCLUSIONS: This study demonstrates the potential of pCASL for assessing regional hypoperfusion related to FTD and supports its use as a cost-effective alternative to PET.

Sensitivity of Arterial Spin Labeling for Characterization of Longitudinal Perfusion Changes in Frontotemporal Dementia and Related Disorders.

BACKGROUND: Advances in the understanding of the pathophysiology of frontotemporal dementia (FTD) and related disorders, along with the development of novel candidate disease modifying treatments, have stimulated the need for tools to assess the efficacy of new therapies. While perfusion imaging by arterial spin labeling (ASL) is an attractive approach for longitudinal imaging biomarkers of neurodegeneration, sources of variability between sessions including arterial transit times (ATT) and fluctuations in resting perfusion can reduce its sensitivity. Establishing the magnitude of perfusion changes that can be reliably detected is necessary to delineate longitudinal perfusion changes related to disease processes from the effects of these sources of error. PURPOSE: To assess the feasibility of ASL for longitudinal monitoring of patients with FTD by quantifying between-session variability of perfusion on a voxel-by-voxel basis. METHODS AND MATERIALS: ASL data were collected in 13 healthy controls and 8 patients with FTD or progressive supra-nuclear palsy. Variability in cerebral blood flow (CBF) by single delay pseudo-continuous ASL (SD-pCASL) acquired one month apart were quantified by the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Additionally, CBF by SD-pCASL and ATT by low-resolution multiple inversion time ASL (LowRes-pCASL) were compared to Hadamard encoded sequences which are able to simultaneously measure CBF and ATT with improved time-efficiency. RESULTS: Agreement of grey-matter perfusion between sessions was found for both patients and controls (CV = 10.8% and 8.3% respectively) with good reliability for both groups (ICC > 0.6). Intensity normalization to remove day-to-day fluctuations in resting perfusion reduced the CV by 28%. Less than 5% of voxels had ATTs above the chosen post labelling delay (2 s), indicating that the ATT was not a significant source of error. Hadamard-encoded perfusion imaging yielded systematically higher CBF compared to SD-pCASL, but produced similar transit-time measurements. Power analysis revealed that SD-pCASL has the sensitivity to detect longitudinal changes as low as 10% with as few as 10 patient participants. CONCLUSION: With the appropriate labeling parameters, SD-pCASL is a promising approach for assessing longitudinal changes in CBF associated with FTD.

Improving magnetic resonance imaging with smart and thin metasurfaces.

Over almost five decades of development and improvement, Magnetic Resonance Imaging (MRI) has become a rich and powerful, non-invasive technique in medical imaging, yet not reaching its physical limits. Technical and physiological restrictions constrain physically feasible developments. A common solution to improve imaging speed and resolution is to use higher field strengths, which also has subtle and potentially harmful implications. However, patient safety is to be considered utterly important at all stages of research and clinical routine. Here we show that dynamic metamaterials are a promising solution to expand the potential of MRI and to overcome some limitations. A thin, smart, non-linear metamaterial is presented that enhances the imaging performance and increases the signal-to-noise ratio in 3T MRI significantly (up to eightfold), whilst the transmit field is not affected due to self-detuning and, thus, patient safety is also assured. This self-detuning works without introducing any additional overhead related to MRI-compatible electronic control components or active (de-)tuning mechanisms. The design paradigm, simulation results, on-bench characterization, and MRI experiments using homogeneous and structural phantoms are described. The suggested single-layer metasurface paves the way for conformal and patient-specific manufacturing, which was not possible before due to typically bulky and rigid metamaterial structures.

Portable and platform-independent MR pulse sequence programs.

PURPOSE: To introduce a new sequence description format for vendor-independent MR sequences that include all calculation logic portably. To introduce a new MRI sequence development approach which utilizes flexibly reusable modules. METHODS: The proposed sequence description contains a sequence module hierarchy for loop and group logic, which is enhanced by a novel strategy for performing efficient parameter and pulse shape calculation. These calculations are powered by a flow graph structure. By using the flow graph, all calculations are performed with no redundancy and without requiring preprocessing. The generation of this interpretable structure is a separate step that combines MRI techniques while actively considering their context. The driver interface is slim and highly flexible through scripting support. The sequences do not require any vendor-specific compiling or processing step. A vendor-independent frontend for sequence configuration can be used. Tests that ensure physical feasibility of the sequence are integrated into the calculation logic. RESULTS: The framework was used to define a set of standard sequences. Resulting images were compared to respective images acquired with sequences provided by the device manufacturer. Images were acquired using a standard commercial MRI system. CONCLUSIONS: The approach produces configurable, vendor-independent sequences, whose configurability enables rapid prototyping. The transparent data structure simplifies the process of sharing reproducible sequences, modules, and techniques.

Cerebral sodium (23Na) magnetic resonance imaging in patients with migraine - a case-control study.

OBJECTIVE: Evaluation of MRI-derived cerebral 23Na concentrations in patients with migraine in comparison with healthy controls. MATERIALS AND METHODS: In this case-control study, 24 female migraine patients (mean age, 34 ± 11 years) were enrolled after evaluation of standardized questionnaires. Half (n = 12) of the cohort suffered from migraine, the other half was impaired by both migraine and tension-type headaches (TTH). The combined patient cohort was matched to 12 healthy female controls (mean age, 34 ± 11 years). All participants underwent a cerebral 23Na-magnetic resonance imaging examination at 3.0 T, which included a T1w MP-RAGE sequence and a 3D density-adapted, radial gradient echo sequence for 23Na imaging. Circular regions of interests were placed in predetermined anatomic regions: cerebrospinal fluid (CSF), gray and white matter, brain stem, and cerebellum. External 23Na reference phantoms were used to calculate the total 23Na tissue concentrations. Pearson's correlation, Kendall Tau, and Wilcoxon rank sum test were used for statistical analysis. RESULTS: 23Na concentrations of all patients in the CSF were significantly higher than in healthy controls (p < 0.001). The CSF of both the migraine and mixed migraine/TTH group showed significantly increased sodium concentrations compared to the control group (p = 0.007 and p < 0.001). Within the patient cohort, a positive correlation between pain level and TSC in the CSF (r = 0.62) could be observed. CONCLUSION: MRI-derived cerebral 23Na concentrations in the CSF of migraine patients were found to be statistically significantly higher than in healthy controls. KEY POINTS: • Cerebral sodium MRI supports the theory of ionic imbalances and may aid in the challenging pathophysiologic understanding of migraine. • Case-control study shows significantly higher sodium concentrations in cerebrospinal fluid of migraineurs. • Cerebral sodium MRI may become a non-invasive imaging tool for drugs to modulate sodium, and hence migraine, on a molecular level, and influence patient management.

Repeatability and reproducibility of cerebral 23Na imaging in healthy subjects.

BACKGROUND: Initial reports of 23Na magnetic resonance imaging (MRI) date back to the 1970s. However, methodological challenges of the technique hampered its widespread adoption for many years. Recent technical developments have overcome some of these limitations and have led to more optimal conditions for 23Na-MR imaging. In order to serve as a reliable tool for the assessment of clinical stroke or brain tumor patients, we investigated the repeatability and reproducibility of cerebral sodium (23Na) imaging in healthy subjects. METHODS: In this prospective, IRB approved study 12 consecutive healthy volunteers (8 female, age 31 ± 8.3) underwent three cerebral 23Na-MRI examinations at 3.0 T (TimTrio, Siemens Healthineers) distributed between two separate visits with an 8 day interval. For each scan a T1w MP-RAGE sequence for anatomical referencing and a 3D-density-adapted, radial GRE-sequence for 23Na-imaging were acquired using a dual-tuned (23Na/1H) head-coil. On 1 day, these scans were repeated consecutively; on the other day, the scans were performed once. 23Na-sequences were reconstructed according to the MP-RAGE sequence, allowing direct cross-referencing of ROIs. Circular ROIs were placed in predetermined anatomic regions: gray and white matter (GM, WM), head of the caudate nucleus (HCN), pons, and cerebellum. External 23Na-reference phantoms were used to calculate the tissue sodium content. RESULTS: Excellent correlation was found between repeated measurements on the same day (r2 = 0.94), as well as on a different day (r2 = 0.86). No significant differences were found based on laterality other than in the HCN (63.1 vs. 58.7 mmol/kg WW on the right (p = 0.01)). Pronounced inter-individual differences were identified in all anatomic regions. Moderate to good correlation (0.310 to 0.701) was found between the readers. CONCLUSION: Our study has shown that intra-individual 23Na-concentrations in healthy subjects do not significantly differ after repeated scans on the same day and a pre-set time interval. This confirms the repeatability and reproducibility of cerebral 23Na-imaging. However, with manual ROI placement in predetermined anatomic landmarks, fluctuations in 23Na-concentrations can be observed.

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.

Sodium MRI of T1 High Signal Intensity in the Dentate Nucleus due to Gadolinium Deposition in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Recently, several studies reported increased signal intensity (SI) of the dentate nucleus (DN) on unenhanced T1-weighted magnetic resonance imaging (MRI) as a possible consequence of multiple applications of gadolinium-based contrast agents. The aim of this study was to investigate with sodium (23 Na) MRI possible tissue abnormalities of the DN in multiple sclerosis (MS) patients. METHODS: Sodium and conventional MRI were performed on a clinical 3T scanner. Total sodium concentrations (TSCs) of the DN, as well as DN-to-pons and DN-to-cerebellum SI ratios on unenhanced T1-weighted MRI were calculated. RESULTS: A total of 18 subjects (6/18 normal controls, 12/18 MS patients [6/12 with T1 hyperintense DN]) were investigated. There was no significant difference of TSC values of the DN in MS patients with a T1-hyperintense DN (33.70 ± 2.14 mM) compared to MS patients without those signal abnormalities (33.29 ± 1.67 mM; P = .67) or to healthy controls (33.14 ± 1.12; P = .32). CONCLUSIONS: Normal sodium signal in the T1-hyperintense DN in MS patients may point to relative tissue integrity despite gadolinium deposition in this area.

Renal Denervation in Patients with Resistant Hypertension-Assessment by 3T Renal 23Na-MRI: Preliminary Results.

BACKGROUND/AIM: Renal denervation (RDN) has been considered a promising therapy option for patients suffering from therapy-resistant hypertension. Besides, in blood-pressure regularization, the kidneys play a fundamental role in sodium ((23)Na) homeostasis. This study assesses the effect of RDN on renal (23)Na concentration using (23)Na magnetic resonance imaging (MRI). PATIENTS AND METHODS: Two patients with therapy-resistant hypertension underwent RDN. (23)Na-MRI, (1)H-MRI, including diffusion weighted imaging (DWI), as well as endothelial dysfunction assessment, were performed 1 day prior, as well as 1, 30 and 90 days after RDN. RESULTS: The renal corticomedullary (23)Na gradient did not change after RDN for all time points. Additionally, functional imaging and retinal vessel parameters were not influenced by RDN. Results regarding blood pressure changes and arterial stiffness, as well as patients' clinical outcome, were heterogeneous. CONCLUSION: RDN does not seem to alter renal (23)Na concentration gradients, as measured by MRI.

Heterogeneity of acute multiple sclerosis lesions on sodium (23Na) MRI.

BACKGROUND: Advanced magnetic resonance imaging (MRI) techniques provide a window into pathological processes in multiple sclerosis (MS). Nevertheless, to date only few studies have performed sodium MRI in MS. OBJECTIVES: We analysed total sodium concentration (TSC) in hyperacute, acute and chronic lesions in MS with (23)Na MRI. METHODS: (23)Na MRI and (1)H MRI were performed in 65 MS patients and 10 healthy controls (HC). Mean TSC was quantified in all MS lesions with a diameter of >5 mm and in the normal appearing white and grey matter (NAWM, NAGM). RESULTS: TSC in the NAWM and the NAGM of MS patients was significantly higher compared to HC (WM: 37.51 ± 2.65 mM versus 35.17 ± 3.40 mM; GM: 43.64 ± 2.75 mM versus 40.09 ± 4.64 mM). Acute and chronic MS lesions showed elevated TSC levels of different extent (contrast-enhancing lesions (49.07 ± 6.99 mM), T1 hypointense lesions (45.06 ± 6.26 mM) and remaining T1 isointense lesions (39.88 ± 5.54 mM)). However, non-enhancing hyperacute lesions with a reduced apparent diffusion coefficient showed a TSC comparable to the NAWM (37.22 ± 4.62 mM). CONCLUSIONS: TSC is not only a sensitive marker of the severity of chronic tissue abnormalities in MS but is also highly sensitive to opening of the blood-brain barrier and vasogenic tissue oedema in contrast-enhancing lesions.

Sodium-23 MRI of whole spine at 3 Tesla using a 5-channel receive-only phased-array and a whole-body transmit resonator.

Sodium magnetic resonance imaging ((23)Na MRI) is a unique and non-invasive imaging technique which provides important information on cellular level about the tissue of the human body. Several applications for (23)Na MRI were investigated with regard to the examination of the tissue viability and functionality for example in the brain, the heart or the breast. The (23)Na MRI technique can also be integrated as a potential monitoring instrument after radiotherapy or chemotherapy. The main contribution in this work was the adaptation of (23)Na MRI for spine imaging, which can provide essential information on the integrity of the intervertebral disks with respect to the early detection of disk degeneration. In this work, a transmit-only receive-only dual resonator system was designed and developed to cover the whole human spine using (23)Na MRI and increase the receive sensitivity. The resonator system consisted of an already presented (23)Na whole-body resonator and a newly developed 5-channel receive-only phased-array. The resonator system was first validated using bench top and phantom measurements. A threefold SNR improvement at the depth of the spine (∼7cm) over the whole-body resonator was achieved using the spine array. (23)Na MR measurements of the human spine using the transmit-only receive-only resonator system were performed on a healthy volunteer within an acquisition time of 10minutes. A density adapted 3D radial sequence was chosen with 6mm isotropic resolution, 49ms repetition time and a short echo time of 540µs. Furthermore, it was possible to quantify the tissue sodium concentration in the intervertebral discs in the lumbar region (120ms repetition time) using this setup.

Enhancing the quantification of tissue sodium content by MRI: time-efficient sodium B1 mapping at clinical field strengths.

Tissue sodium content (TSC) is a sensitive measure of pathological changes and can be detected non-invasively by MRI. For the absolute quantification of TSC, B1 inhomogeneities must be corrected, which is not well established beyond research applications. An in-depth analysis of B1 mapping methods which are suitable for application in TSC quantification is presented. On the basis of these results, a method for simultaneous B1 mapping and imaging is proposed in order to enhance accuracy and to reduce measurement time at clinical field strengths. The B1 mapping techniques used were phase-sensitive (PS), Bloch-Siegert shift (BSS), double-angle (DAM) and actual flip-angle imaging (AFI) methods. Experimental and theoretical comparisons demonstrated that the PS technique yields the most accurate field profiles and exhibits the highest signal-to-noise ratio (SNR). Simultaneous B1 mapping and imaging was performed for the PS method, employing both degrees of freedom of the MR signal: the B1 field is encoded into signal phase and the amplitude provides the concentration information. In comparison with the more established DAM, a 13% higher SNR was obtained and field effects could be corrected more accurately without the need for additional measurement time. The protocol developed was applied to measure TSC in the healthy human head at an isotropic resolution of 4 mm. TSC was determined to be 35 ± 1 mM in white matter and 134 ± 3 mM in vitreous humor. By employing the proposed simultaneous characterization of the B1 field and acquisition of the spin density-weighted sodium signal, the accuracy of the non-invasive measurement of TSC is enhanced and the measurement time is reduced. This should allow (23)Na MRI to be better incorporated into clinical studies and routine.

Quantitative sodium MRI of kidney.

One of the main tasks of the human kidneys is to maintain the homeostasis of the body's 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 ((23)Na MRI) allows for the absolute quantification of the tissue sodium concentration (TSC) and thereby provides a direct link between TSC and tissue viability. Renal (23)Na MRI can provide new insights into physiological tissue function and viability thought to differ from the information obtained by standard (1)H 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, (23)Na 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.

A double-tuned (1) H/(23) Na resonator allows (1) H-guided (23) Na-MRI in ischemic stroke patients in one session.

BACKGROUND: Established imaging methods are still not confident in the determination of stroke onset. Sodium imaging in animal models and lately in humans implicates that the sodium signal intensity within the ischemic lesion increases in a time-dependent fashion. Sodium imaging usually requires a time-consuming change of resonators or magnetic resonance imaging systems. To avoid this, we used a double-tuned (1) H/(23) Na birdcage head coil in combination with a protocol minimizing T1 - and T2 *-weighting effects for measurement of sodium intensity in acute stroke patients. METHODS: Multinuclear (1) H/(23) Na data sets were obtained from 16 stroke patients [75 ± 9·9 (standard deviation) years old] 4-130 h after symptom onset. The protocol was acquired on a clinical 3T magnetic resonance imaging site using a double-tuned (1) H/(23) Na birdcage head coil. Sodium signal intensity within the lesion and homologous contralateral side was measured and compared. RESULTS: With an acquisition time of the complete magnetic resonance imaging protocol of 22 min, a nonlinear sodium signal intensity increase within the lesion over time after stroke onset was acknowledged. Onset time within six-hours showed an increase of only 8% or less, whereas onset time beyond 8·5 h demonstrated increases of 36% or more reaching a maximum of 170% > 120 h. In addition, some patients showed a difference in sodium signal intensity compared with diffusion weighted imaging lesion. CONCLUSIONS: The use of a double-tuned (1) H/(23) Na birdcage head coil in a clinical setting 'allowed sodium intensity measurements' in a justifiable time also for acute stroke patients, and heterogenous sodium signal intensity in the diffusion weighted imaging lesion might represent differences in tissue damage or repair.

Dose-dependent changes in renal (1)H-/(23)Na MRI after adjuvant radiochemotherapy for gastric cancer.

PURPOSE: Combined radiochemotherapy (RCT) for gastric cancer with three-dimensional conformal radiotherapy (3D-CRT) results in ablative doses to the upper left kidney, while image-guided intensity-modulated radiotherapy (IG-IMRT) allows kidney sparing despite improved target coverage. Renal function in long-term gastric cancer survivors was evaluated with 3T functional magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) and (23)Na imaging. PATIENTS AND METHODS: Five healthy volunteers and 13 patients after radiotherapy were included: 11×IG-IMRT; 1×3D-CRT; 1× "positive control" with stereotactic body radiotherapy (SBRT) of a metastasis between the spleen/left kidney. Radiation doses were documented for the upper/middle/lower kidney subvolumes. Late toxicity was evaluated based on CTC criteria, questionnaire, and creatinine values. Morphological sequences, DWI images, and (23)Na images were acquired using a (1)H/(23)Na-tuned body-coil before/after intravenous water load (WL). Statistics for [(23)Na] (concentration) and apparent diffusion coefficient (ADC) values were calculated for upper/middle/lower renal subvolumes. Corticomedullary [(23)Na] gradients and [(23)Na] differences after WL were determined. RESULTS: No major morphological alteration was detected in any patient. Minor scars were observed in the cranial subvolume of the left kidney of the 3D-CRT and the whole kidney of the control SBRT patient. All participants presented a corticomedullary [(23)Na] gradient. After WL, a significant physiological [(23)Na] gradient decrease (p < 0.001) was observed in all HV and IG-IMRT patients. In the cranial left kidney of the 3D-CRT patient and the positive control SBRT patient, the decrease was nonsignificant (p = 0.01, p = 0.02). ADC values were altered nonsignificantly in all renal subvolumes (all participants). Renal subvolumes with doses ≥ 35 Gy showed a reduced change of the [(23)Na] gradient after WL (p = 0.043). No participants showed clinical renal impairment. CONCLUSIONS: Functional parameters of renal (23)Na MRI after gastric IG-IMRT are identical to those of healthy volunteers, in contrast to renal subvolumes after ablative doses in the control and 3D-CRT patient. While kidney doses to the cortex below 20-25 Gy in fractional doses of ~ 1 Gy in IG-IMRT (combined with intensified chemotherapy) do not seem to cause significant MRI morphological or functional alterations, doses of > 35 Gy in 1.5-2 Gy fractions clearly result in impairment.

Scan time reduction in ²³Na-Magnetic Resonance Imaging using the chemical shift imaging sequence: Evaluation of an iterative reconstruction method.

AIM: To evaluate potential scan time reduction in (23)Na-Magnetic Resonance Imaging with the chemical shift imaging sequence (CSI) using undersampled data of high-quality datasets, reconstructed with an iterative constrained reconstruction, compared to reduced resolution or reduced signal-to-noise ratio. MATERIALS AND METHODS: CSI (23)Na-images were retrospectively undersampled and reconstructed with a constrained reconstruction scheme. The results were compared to conventional methods of scan time reduction. The constrained reconstruction scheme used a phase constraint and a finite object support, which was extracted from a spatially registered (1)H-image acquired with a double-tuned coil. The methods were evaluated using numerical simulations, phantom images and in-vivo images of a healthy volunteer and a patient who suffered from cerebral ischemic stroke. RESULTS: The constrained reconstruction scheme showed improved image quality compared to a decreased number of averages, images with decreased resolution or circular undersampling with weighted averaging for any undersampling factor. Brain images of a stroke patient, which were reconstructed from three-fold undersampled k-space data, resulted in only minor differences from the original image (normalized root means square error < 12%) and an almost identical delineation of the stroke region (mismatch < 6%). CONCLUSION: The acquisition of undersampled (23)Na-CSI images enables up to three-fold scan time reduction with improved image quality compared to conventional methods of scan time saving.

²³Na-MRI of recurrent glioblastoma multiforme after intraoperative radiotherapy: technical note.

INTRODUCTION: We report the first case of an intraoperative radiotherapy (IORT) in a patient with recurrent glioblastoma multiforme (GBM) who was followed up with a novel magnetic resonance imaging (MRI) method-(23)Na-MRI-in comparison to a standard contrast-enhanced (1)H-MRI and (18)F-FET-PET. METHODS: A 56-year-old female patient with diagnosed GBM in July 2012 underwent tumor resection, radiochemotherapy, and three cycles of chemotherapy. After a relapse, 6 months after the initial diagnosis, an IORT was recommended which was performed in March 2013 using the INTRABEAM system (Carl Zeiss Meditec AG, Germany) with a 3-cm applicator and a surface dose of 20 Gy. Early post-operative contrast-enhanced and 1-month follow-up (1)H-MRI and a (18)F-FET-PET were performed. In addition, an IRB-approved (23)Na-MRI was performed on a 3.0-T MR scanner (MAGNETOM TimTrio, Siemens Healthcare, Germany). RESULTS: After re-surgery and IORT in March 2013, only a faint contrast enhancement but considerable surrounding edema was visible at the medio-posterior resection margins. In April 2013, new and progressive contrast enhancement, edema, (23)Na content, and increased uptake in the (18)F-FET-PET were visible, indicating tumor recurrence. Increased sodium content within the area of contrast enhancement was found in the (23)Na-MRI, but also exceeding this area, very similar to the increased uptake depicted in the (18)F-FET-PET. The clearly delineable zone of edema in both examinations exhibits a lower (23)Na content compared to areas with suspected proliferating tumor tissue. CONCLUSION: (23)Na-MRI provided similar information in the suspicious area compared to (18)F-FET-PET, exceeding conventional (1)H-MRI. Still, (23)Na-MRI remains an investigational technique, which is worth to be further evaluated.