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.

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.

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.

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.

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.

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.

Measurement techniques for magnetic resonance imaging of fast relaxing nuclei.

In this review article, techniques for sodium ((23)Na) magnetic resonance imaging (MRI) are presented. These techniques can also be used to image other nuclei with short relaxation times (e.g., (39)K, (35)Cl, (17)O). 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 T 2 (*) 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.

30 Years of sodium/X-nuclei magnetic resonance imaging.

In principle, all nuclei with nonzero spin can be employed for magnetic resonance imaging (MRI). Special scanner hardware and MR sequences are required to select the nucleus-specific frequency and to enable imaging with "sufficient" signal-to-noise ratio. This Special Issue starts with an overview of different nuclei that can be used for MRI today, followed by a review article about techniques required for imaging of quadrupolar nuclei with short relaxation times. Sequence developments to improve image quality and applications on different organs and diseases are presented for different nuclei ((23)Na, (35)Cl, (17)O, and (19)F), with a focus on imaging at natural abundance.

3T renal (23)Na-MRI: effects of desmopressin in patients with central diabetes insipidus.

PURPOSE: The purpose of this prospective study was to assess physiologic changes in the renal corticomedullary (23)Na-concentration ([(23)Na]) gradient with (23)Na-MRI at 3.0T in patients with central diabetes insipidus (CDI) before and after intranasal administration of 20 µg desmopressin (DDAVP). METHODS AND MATERIALS: Four patients with CDI (all male, mean age 60.2 years) were included in this IRB-approved study. For (23)Na-imaging, a 3D density adapted, radial GRE-sequence (TE = 0.55 ms; TR = 120 ms; projections = 8,000; spatial resolution = 5 × 5 × 5 mm(3)) was used in combination with a dedicated (23)Na-coil and reference phantoms. The corticomedullary [(23)Na] gradient (in mmol/L/mm) was calculated pixel-by-pixel along a linear region-of-interest (ROI) spanning from the renal cortex in the direction of the medulla. Mean ± SDs of [(23)Na] were calculated for each patient as well as for the entire group. RESULTS: Mean [(23)Na] increased along the corticomedullary gradient from the cortex (pre-DDAVP 38.0 ± 6.3 mmol/L vs. post-DDAVP 30.7 ± 3.5 mmol/L) to the medulla (pre-DDAVP 71.6 ± 14.8 mmol/L vs. post-DDAVP 59.7 ± 10.8 mmol/L). The overall mean decrease of [(23)Na] after DDAVP administration was 17.1 ± 1.1 %. CONCLUSION: (23)Na-MRI with state-of-the-art techniques at 3T depicts the physiologic renal response to the administration of desmopressin in patients with central diabetes insipidus.

Topography of brain sodium accumulation in progressive multiple sclerosis.

OBJECT: Sodium accumulation is involved in neuronal injury occurring in multiple sclerosis (MS). We aimed to assess sodium accumulation in progressive MS, known to suffer from severe neuronal injury. MATERIALS AND METHODS: 3D-(23)Na-MRI was obtained on a 3T-MR-scanner in 20 progressive MS patients [11 primary-progressive (PPMS) and nine secondary-progressive (SPMS)] and 15 controls. Total sodium concentrations (TSC) within grey matter (GM), normal-appearing white matter (WM) and lesions were extracted. Statistical mapping analyses of TSC abnormalities were also performed. RESULTS: Progressive MS patients presented higher GM-TSC values (48.8 ± 3.1 mmol/l wet tissue vol, p < 0.001) and T2lesions-TSC values (50.9 ± 2.2 mmol/l wet tissue vol, p = 0.01) compared to GM and WM of controls. Statistical mapping analysis showed TSC increases in PPMS patients confined to motor and somatosensory cortices, prefrontal cortices, pons and cerebellum. In SPMS, TSC increases were associated with areas involving: primary motor, premotor and somatosensory cortices; prefrontal, cingulate and visual cortices; the corpus callosum, thalami, brainstem and cerebellum. Anterior prefrontal and premotor cortices TSC were correlated with disability. CONCLUSION: Sodium accumulation is present in progressive MS patients, more restricted to the motor system in PPMS and more widespread in SPMS. Local brain sodium accumulation appears as a promising marker to monitor patients with progressive MS.

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.

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 T(RO). 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 T(RO)/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.

Two-dimensional radial sodium heart MRI using variable-rate selective excitation and retrospective electrocardiogram gating with golden angle increments.

PURPOSE: Two-dimensional projection reconstruction methods provide advantages over three-dimensional techniques because of higher flexibility regarding the resolution and shorter scan time needed. To optimize a two-dimensional radial sequence with respect to signal-to-noise ratio, variable-rate selective excitation and retrospective electrocardiogram gating is investigated. METHODS: The minimal radiofrequency pulse duration is simulated in dependence of the flip angle and coil parameters using sinc waveforms with two different variable-rate selective excitation approaches and a Fermi pulse. Retrospectively electrocardiogram-gated imaging with Golden Angle incremented projections was implemented to allow for continuous data acquisition enabling the possibility of dynamic electrocardiogram-gated heart imaging. RESULTS: Especially for abdominal coils with high transmitter voltages required, variable-rate selective excitation strongly reduces the radiofrequency pulse duration and echo time resulting in a signal-to-noise ratio gain up to 15.5% (if the fast relaxation component of sodium is in the order of the radiofrequency pulse duration) compared with standard sinc-shaped radiofrequency pulses. Retrospective electrocardiogram gating shows higher flexibility with regard to the trigger delay enabling the trade-off between heart motion artifacts and signal-to-noise ratio. CONCLUSION: A two-dimensional radial sequence is optimized for sodium heart imaging regarding signal-to-noise ratio. Different sodium contrasts of the human heart are shown, which can give additional information on heart diseases.

Quantitative in vivo 23Na MR imaging of the healthy human kidney: determination of physiological ranges at 3.0T with comparison to DWI and BOLD.

OBJECTIVES: The purpose of this prospective study was to assess the normal physiologic ranges of the renal corticomedullary 23Na-concentration ([23Na]) gradient at 3.0T in healthy volunteers. The corticomedullary [23Na] gradient was correlated with other functional MR imaging parameters--blood oxygenation level dependent (BOLD) and diffusion-weighted imaging (DWI)--and to individual and physiologic parameters--age, gender, estimated glomerular filtration rate (eGFR), body mass index (BMI), and blood serum sodium concentration ([23Na]serum). METHODS AND MATERIALS: 50 healthy volunteers (30 m, 20 w; mean age: 29.2 years) were included in this IRB-approved study, without a specific a priori preparation in regard to water or food intake. For 23Na-imaging a 3D density adapted, radial gradient echo (GRE)-sequence (spatial resolution=5×5×5 mm3) was used in combination with a dedicated 23Na-coil and 23Na-reference phantoms. [23Na] values of the corticomedullary [23Na] gradient were measured by placement of a linear region of interest (20×1 mm2) from the renal cortex in the direction of the renal medulla. By using external standard reference phantoms, [23Na] was calculated in mmol/L of wet tissue volume (mmol/l WTV). Axial diffusion-weighted images (spatial resolution=1.7×1.7×5.0 mm3) and 2D GRE BOLD images (spatial resolution=1.2×1.2×4.0 mm3) were acquired. Mean values±standard deviations for [23Na], apparent diffusion coefficient (ADC) values, and R2* values were computed for each volunteer. The corticomedullary 23Na-concentration gradient (in mmol/l/mm) was calculated along the area of linear concentration increase from the cortex in the direction of the medulla. Correlations between the [23Na] and DWI, BOLD, and the physiologic parameters were assessed with Pearson correlation coefficients. RESULTS: The mean corticomedullary [23Na] for all healthy volunteers increased from the renal cortex (58±17 mmol/l WTV) in the direction of the medulla (99±18 mmol/l WTV). The inter-individual differences ranged from respective cortical and medullary values of 27 and 63 mmol/L WTV to 126 and 187 mmol/L WTV. No statistically significant differences in renal [23Na] were found based on differences in individual or physiologic parameters (age, gender, [23Na]serum, BMI, GFR). No ADC or R2* gradients were identified, and [23Na] did not correlate with these parameters. CONCLUSION: Renal corticomedullary [23Na] values increase from the cortex in the direction of the medullary pyramid, demonstrating wide inter-individual ranges and no significant correlations with age, gender, [23Na]serum, BMI, GFR, ADC, or R2* values. For future clinical evaluations, an approach relying on renal stimulation (e.g. pharmacologically induced diuresis) may be applicable to account for wide inter-individual ranges of normal [23Na].

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.

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.