Safety and performance of a novel implantable sensor in the inferior vena cava under acute and chronic intravascular volume modulation.

AIMS: The management of congestion is one of the key treatment targets in heart failure. Assessing congestion is, however, difficult. The purpose of this study was to investigate the safety and dynamic response of a novel, passive, inferior vena cava (IVC) sensor in a chronic ovine model. METHODS AND RESULTS: A total of 20 sheep divided into three groups were studied in acute and chronic in vivo settings. Group I and Group II included 14 sheep in total with 12 sheep receiving the sensor and two sheep receiving a control device (IVC filter). Group III included an additional six animals for studying responses to volume challenges via infusion of blood and saline solutions. Deployment was 100% successful with all devices implanted; performing as expected with no device-related complications and signals were received at all observations. At similar volume states no significant differences in IVC area normalized to absolute area range were measured (55 ± 17% on day 0 and 62 ± 12% on day 120, p = 0.51). Chronically, the sensors were completely integrated with a thin, reendothelialized neointima with no loss of sensitivity to infused volume. Normalized IVC area changed significantly from 25 ± 17% to 43 ± 11% (p = 0.007) with 300 ml infused. In contrast, right atrial pressure required 1200 ml of infused volume prior to a statistically significant change from 3.1 ± 2.6 mmHg to 7.5 ± 2.0 mmHg (p = 0.02). CONCLUSION: In conclusion, IVC area can be measured remotely in real-time using a safe, accurate, wireless, and chronic implantable sensor promising to detect congestion with higher sensitivity than filling pressures.

Changes in inferior vena cava area represent a more sensitive metric than changes in filling pressures during experimental manipulation of intravascular volume and tone.

AIMS: Remote monitoring of pulmonary artery pressure has reduced heart failure (HF) hospitalizations in chronic HF as elevation of pulmonary artery pressure provides information that can guide treatment. The venous system is characterized by high capacitance, thus substantial increases in intravascular volume can occur before filling pressures increase. The inferior vena cava (IVC) is a highly compliant venous conduit and thus a candidate for early detection of change in intravascular volume. We aimed to compare IVC cross-sectional area using a novel sensor with cardiac filling pressures during experimental manipulation of volume status, vascular tone, and cardiac function. METHODS AND RESULTS: Experiments were conducted in sheep to manipulate volume status (colloid infusion), vascular tone (nitroglycerin infusion) and cardiac function (rapid cardiac pacing). A wireless implantable IVC sensor was validated ex-vivo and in-vivo, and then used to measure the cross-sectional area of the IVC. Right- and left-sided cardiac filling pressures were obtained via right heart catheterization. The IVC sensor provided highly accurate and precise measurements of cross-sectional area in ex-vivo and in-vivo validation. IVC area changes were more sensitive than the corresponding changes in cardiac filling pressures during colloid infusion (p < 0.001), vasodilatation (p < 0.001) and cardiac dysfunction induced by rapid pacing (p ≤ 0.02). CONCLUSIONS: Inferior vena cava area can be remotely and accurately measured in real time with a wireless implantable sensor. Changes in IVC area are more sensitive than corresponding changes in filling pressures following experimental volume loading and fluid redistribution. Additional research is warranted to understand if remote monitoring of the IVC may have advantages over pressure-based monitors in HF.

Investigating potentially salvageable penumbra tissue in an in vivo model of transient ischemic stroke using sodium, diffusion, and perfusion magnetic resonance imaging.

BACKGROUND: Diffusion magnetic resonance imaging (MRI) is the current-state-of-the-art technique to clinically investigate acute (0-24 h) ischemic stroke tissue. However, reduced apparent diffusion coefficient (ADC)-considered a marker of tissue damage-was observed to reverse spontaneously during the subacute stroke phase (24-72 h) which means that low ADC cannot be used to reflect the damaged tissue after 24 h in experimental and clinical studies. One reason for the change in ADC is that ADC values drop with cytotoxic edema (acute phase) and rise when vasogenic edema begins (subacute phase). Recently, combined 1H- and 23Na-MRI was proposed as a more accurate approach to improve delineation between reversible (penumbra) and irreversible ischemic injury (core). The aim of this study was to investigate the effects of reperfusion on the ADC and the sodium MRI signal after experimental ischemic stroke in rats in well-defined areas of different viability levels of the cerebral lesion, i.e. core and penumbra as defined via perfusion and histology. Transient middle cerebral artery occlusion was induced in male rats by using the intraluminal filament technique. MRI sodium, perfusion and diffusion measurement was recorded before reperfusion, shortly after reperfusion and 24 h after reperfusion. The animals were reperfused after 90 min of ischemia. RESULTS: Sodium signal in core did not change before reperfusion, increased after reperfusion while sodium signal in penumbra was significantly reduced before reperfusion, but showed no changes after reperfusion compared to control. The ADC was significantly decreased in core tissue at all three time points compared to contralateral side. This decrease recovered above commonly applied viability thresholds in the core after 24 h. CONCLUSIONS: Reduced sodium-MRI signal in conjunction with reduced ADC can serve as a viability marker for penumbra detection and complement hydrogen diffusion- and perfusion-MRI in order to facilitate time-independent assessment of tissue fate and cellular bioenergetics failure in stroke patients.

Local Multi-Channel RF Surface Coil versus Body RF Coil Transmission for Cardiac Magnetic Resonance at 3 Tesla: Which Configuration Is Winning the Game?

INTRODUCTION: The purpose of this study was to demonstrate the feasibility and efficiency of cardiac MR at 3 Tesla using local four-channel RF coil transmission and benchmark it against large volume body RF coil excitation. METHODS: Electromagnetic field simulations are conducted to detail RF power deposition, transmission field uniformity and efficiency for local and body RF coil transmission. For both excitation regimes transmission field maps are acquired in a human torso phantom. For each transmission regime flip angle distributions and blood-myocardium contrast are examined in a volunteer study of 12 subjects. The feasibility of the local transceiver RF coil array for cardiac chamber quantification at 3 Tesla is demonstrated. RESULTS: Our simulations and experiments demonstrate that cardiac MR at 3 Tesla using four-channel surface RF coil transmission is competitive versus current clinical CMR practice of large volume body RF coil transmission. The efficiency advantage of the 4TX/4RX setup facilitates shorter repetition times governed by local SAR limits versus body RF coil transmission at whole-body SAR limit. No statistically significant difference was found for cardiac chamber quantification derived with body RF coil versus four-channel surface RF coil transmission. Our simulation also show that the body RF coil exceeds local SAR limits by a factor of ~2 when driven at maximum applicable input power to reach the whole-body SAR limit. CONCLUSION: Pursuing local surface RF coil arrays for transmission in cardiac MR is a conceptually appealing alternative to body RF coil transmission, especially for patients with implants.

Single-Nucleotide Polymorphism of the FKBP5 Gene and Childhood Maltreatment as Predictors of Structural Changes in Brain Areas Involved in Emotional Processing in Depression.

The gene expressing the FK506 binding protein 51 (FKBP5) is involved in the regulation of glucocorticoid receptor sensitivity. The rs1360780 SNP in this gene (T allele vs C homozygous) has been found to be associated with major depressive disorder (MDD). The aim of our study was to investigate whether this polymorphism might be associated with altered brain structure and function in a cohort of 40 patients with MDD and 43 healthy controls. A functional magnetic resonance imaging (fMRI) emotional attention task was employed. Diffusion tensor imaging (DTI) was also conducted, extracting mean diffusivity (MD) and fractional anisotropy (FA) from brain areas that showed functional differences between patients expressing the two alleles of the rs1360780 SNP. Finally, the effect of the interaction of childhood adversity as measured by the Childhood trauma Questionnaire (CTQ) and rs1360780 allele status was analyzed in relation to DTI measures using a general linear model. All results presented are family-wise error (FWE) corrected. Functional interactions were found between genotype and diagnosis (p<0.01). Patients carrying the high-risk allele, compared with patients not carrying it, showed reduced activity in the rolandic operculum, Heschl gyrus, insula, parahippocampal gyrus, posterior cingulate cortex, inferior frontal gyrus (p<0.05 for all measures); and increased MD and reduced FA measures in many of these regions (p<0.05). An interaction between CTQ scores and allele status was associated with DTI changes in the insula, rolandic operculum, and inferior frontal gyrus. Here, the presence of both the high-risk allele and higher CTQ scores was associated with higher MD and lower FA values (p<0.05). In conclusion, MDD patients expressing the T allele of rs1360780, compared with C homozygous patients, exhibit functional and structural differences in areas involved in emotional perception and inhibition. The interaction between the T allele and childhood maltreatment explained our structural findings in these regions, suggesting that their altered maturation and function might be influenced by early chronic stress in the presence of this genetic trait.

Impaired reward processing in the human prefrontal cortex distinguishes between persistent and remittent attention deficit hyperactivity disorder.

Symptoms of attention deficit hyperactivity disorder (ADHD) in children often persist into adulthood and can lead to severe antisocial behavior. However, to-date it remains unclear whether neuro-functional abnormalities cause ADHD, which in turn can then provide a marker of persistent ADHD. Using event-related functional magnetic resonance imaging (fMRI), we measured blood oxygenation level dependent (BOLD) signal changes in subjects during a reversal learning task in which choice of the correct stimulus led to a probabilistically determined 'monetary' reward or punishment. Participants were diagnosed with ADHD during their childhood (N=32) and were paired with age, gender, and education matched healthy controls (N=32). Reassessment of the ADHD group as adults resulted in a split between either persistent (persisters, N=17) or remitted ADHDs (remitters, N=15). All three groups showed significantly decreased activation in the medial prefrontal cortex (PFC) and the left striatum during punished correct responses, however only remitters and controls presented significant psycho-physiological interaction between these fronto-striatal reward and outcome valence networks. Comparing persisters to remitters and controls showed significantly inverted responses to punishment (P<0.05, family-wise error corrected) in left PFC region. Interestingly, the decreased activation shown after punishment was located in different areas of the PFC for remitters compared with controls, suggesting that remitters might have learned compensation strategies to overcome their ADHD symptoms. Thus, fMRI helps understanding the neuro-functional basis of ADHD related behavior differences and differentiates between persistent and remittent ADHD.

Sodium MRI of the human heart at 7.0 T: preliminary results.

The objective of this work was to examine the feasibility of three-dimensional (3D) and whole heart coverage (23)Na cardiac MRI at 7.0 T including single-cardiac-phase and cinematic (cine) regimes. A four-channel transceiver RF coil array tailored for (23)Na MRI of the heart at 7.0 T (f = 78.5 MHz) is proposed. An integrated bow-tie antenna building block is used for (1)H MR to support shimming, localization and planning in a clinical workflow. Signal absorption rate simulations and assessment of RF power deposition were performed to meet the RF safety requirements. (23) Na cardiac MR was conducted in an in vivo feasibility study. 3D gradient echo (GRE) imaging in conjunction with Cartesian phase encoding (total acquisition time T(AQ) = 6 min 16 s) and whole heart coverage imaging employing a density-adapted 3D radial acquisition technique (T(AQ) = 18 min 20 s) were used. For 3D GRE-based (23)Na MRI, acquisition of standard views of the heart using a nominal in-plane resolution of (5.0 × 5.0) mm(2) and a slice thickness of 15 mm were feasible. For whole heart coverage 3D density-adapted radial (23)Na acquisitions a nominal isotropic spatial resolution of 6 mm was accomplished. This improvement versus 3D conventional GRE acquisitions reduced partial volume effects along the slice direction and enabled retrospective image reconstruction of standard or arbitrary views of the heart. Sodium cine imaging capabilities were achieved with the proposed RF coil configuration in conjunction with 3D radial acquisitions and cardiac gating. Cardiac-gated reconstruction provided an enhancement in blood-myocardium contrast of 20% versus the same data reconstructed without cardiac gating. The proposed transceiver array enables (23)Na MR of the human heart at 7.0 T within clinical acceptable scan times. This capability is in positive alignment with the needs of explorations that are designed to examine the potential of (23)Na MRI for the assessment of cardiovascular and metabolic diseases.

Biodistribution and pharmacokinetic studies of SPION using particle electron paramagnetic resonance, MRI and ICP-MS.

AIM: Superparamagnetic iron oxide nanoparticles (SPIONs) may play an important role in nanomedicine by serving as drug carriers and imaging agents. In this study, we present the biodistribution and pharmacokinetic properties of SPIONs using a new detection method, particle electron paramagnetic resonance (pEPR). MATERIALS & METHODS: The pEPR technique is based on a low-field and low-frequency electron paramagnetic resonance. pEPR was compared with inductively coupled plasma mass spectrometry and MRI, in in vitro and in vivo. RESULTS: The pEPR, inductively coupled plasma mass spectrometry and MRI results showed a good correlation between the techniques. CONCLUSION: The results indicate that pEPR can be used to detect SPIONs in both preclinical and clinical studies.

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.

Sodium-23 magnetic resonance imaging has potential for improving penumbra detection but not for estimating stroke onset time.

Tissue sodium concentration increases in irreversibly damaged (core) tissue following ischemic stroke and can potentially help to differentiate the core from the adjacent hypoperfused but viable penumbra. To test this, multinuclear hydrogen-1/sodium-23 magnetic resonance imaging (MRI) was used to measure the changing sodium signal and hydrogen-apparent diffusion coefficient (ADC) in the ischemic core and penumbra after rat middle cerebral artery occlusion (MCAO). Penumbra and core were defined from perfusion imaging and histologically defined irreversibly damaged tissue. The sodium signal in the core increased linearly with time, whereas the ADC rapidly decreased by >30% within 20 minutes of stroke onset, with very little change thereafter (0.5-6 hours after MCAO). Previous reports suggest that the time point at which tissue sodium signal starts to rise above normal (onset of elevated tissue sodium, OETS) represents stroke onset time (SOT). However, extrapolating core data back in time resulted in a delay of 72 ± 24 minutes in OETS compared with actual SOT. At the OETS in the core, penumbra sodium signal was significantly decreased (88 ± 6%, P=0.0008), whereas penumbra ADC was not significantly different (92 ± 18%, P=0.2) from contralateral tissue. In conclusion, reduced sodium-MRI signal may serve as a viability marker for penumbra detection and can complement hydrogen ADC and perfusion MRI in the time-independent assessment of tissue fate in acute stroke patients.

[Bilateral 23Na MR imaging of the breast and quantification of sodium concentration]. / Bilaterale 23Na-MR-Bildgebung der Mamma und Quantifizierung der Natriumkonzentration.

A novel setup for (23)Na MRI, which allows bilateral imaging of the breast, is presented. For this purpose a figure-eight receive-only (23)Na surface coil was developed. For our experiments on three samples with NaCl solutions of different sodium concentrations and two female subjects we used an asymmetric birdcage coil in transmit mode and the developed surface coil for receiving the signal at 3T. Imaging of the samples showed the applicability of the employed normalization method for measuring the distribution of sodium concentration. In a sample of concentration [Na(+)]=51mM we achieved SNR=70 at a nominal isotropic resolution of 2,5mm (TR=66ms, TE=0,6ms, TA=20min). Furthermore we showed that by means of this setup it is possible to quantify the sodium concentration in breast tissue (TSC) of a female subject with an accuracy of 23% (TR=150ms, TE=0,5ms, TA=45min).

Bilateral kidney sodium-MRI: Enabling accurate quantification of renal sodium concentration through a two-element phased array system.

PURPOSE: To develop a sodium-MRI ((23) Na-MRI) method for bilateral renal sodium concentration (RSC) measurements in rat kidneys at 9.4 Tesla (T). MATERIALS AND METHODS: To simultaneously achieve high B1 -field homogeneity and high receive sensitivity a dual resonator system composed of a double-tuned linearly polarized (1) H/(23) Na volume resonator and a newly developed two-element (23) Na receive array was used. In conjunction with three-dimensional (3D) ultra-short Time-to-Echo sequence a quantification accuracy of ± 10% was achieved for a nominal spatial resolution of (1 × 1 × 4) mm(3) in 10 min acquisition time. The technique was applied to study the RSC in six kidneys before and after furosemide-induced diuresis. RESULTS: The loop diuretic agent induced an increase of cortical RSC by 22% from 86 ± 16 mM to 105 ± 18 mM (P = 0.02), whereas the RSC in the inner medulla decreased by 38% from 213 ± 24 mM to 132 ± 25 mM (P = 0.8×10(-4) ). The RSC changes measured in this study agreed well with the qualitative sodium signal intensity variations reported elsewhere. CONCLUSION: Furosemide-induced diuresis has been investigated accurately with herein presented quantitative (23) Na-MRI technique. In the future, RSC quantification could allow for defining pathological and nonpathological RSC ranges to assess sodium concentration changes, e.g., induced by drugs.

Sodium-23 magnetic resonance imaging during and after transient cerebral ischemia: multinuclear stroke protocols for double-tuned (23)Na/(1)H resonator systems.

A double-tuned ²³Na/¹H resonator system was developed to record multinuclear MR image data during and after transient cerebral ischemia. ¹H-diffusion-, (¹H perfusion, ¹H T2-, ¹H arterial blood flow- and ²³Na spin density-weighted images were then acquired at three time points in a rodent stroke model: (I) during 90 min artery occlusion, (II) directly after arterial reperfusion and (III) one day after arterial reperfusion. Normal ²³Na was detected in hypoperfused stroke tissue which exhibited a low ¹H apparent diffusion coefficient (ADC) and no changes in ¹H T2 relaxation time during transient ischemia, while ²³Na increased and ADC values recovered to normal values directly after arterial reperfusion. For the first time, a similar imaging protocol was set-up on a clinical 3T MRI site in conjunction with a commercial double-tuned ¹H/²³Na birdcage resonator avoiding a time-consuming exchange of resonators or MRI systems. Multinuclear ²³Na/¹H MRI data sets were obtained from one stroke patient during both the acute and non-acute stroke phases with an aquisition time of 22 min. The lesion exhibiting low ADC was found to be larger compared to the lesion with high ²³Na at 9 h after symptom onset. It is hoped that the presented pilot data demonstrate that fast multinuclear ²³Na/¹H MRI preclinical and clinical protocols can enable a better understanding of how temporal and regional MRI parameter changes link to pathophysiological variations in ischemic stroke tissue.

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

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

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

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

The design of a double-tuned two-port surface resonator and its application to in vivo hydrogen- and sodium-MRI.

The design and construction of a two-port surface transceiver resonator for both (1)H-and (23)Na-MRI in the rodent brain at 7 T is described. Double-tuned resonators are required for accurately co-registering multi-nuclei data sets, especially when the time courses of (1)H and (23)Na signals are of interest as, for instance, when investigating the pathological progression of ischaemic stroke tissue in vivo. In the current study, a single-element two-port surface resonator was developed wherein both frequency components were measured with the same detector element but with each frequency signal routed along different output channels. This was achieved by using the null spot technique, allowing for optimal variable tuning and matching of each channel in situ within the MRI scanner. The (23)Na signal to noise ratio, measured in the ventricles of the rat brain, was increased by a factor of four compared to recent state-of-the-art rat brain studies reported in the literature. The resonator's performance was demonstrated in an in vivo rodent stroke model, where regional variations in (1)H apparent diffusion coefficient maps and the (23)Na signal were recorded in an interleaved fashion as a function of time in the acute phase of the stroke without having to exchange, re-adjust, or re-connect resonators between scans. Using the practical construction steps described in this paper, this coil design can be easily adapted for MRI of other X-nuclei, such as (17)O, (13)C, (39)K, and (43)Ca at various field strengths.

Regional and temporal variations in tissue sodium concentration during the acute stroke phase.

A technique for noninvasively quantifying the concentration of sodium ((23) Na) ions was applied to the study of ischemic stroke. (23) Na-magnetic resonance imaging techniques have shown considerable potential for measuring subtle changes in ischemic tissue, although studies to date have suffered primarily from poor signal/noise ratio. In this study, accurate quantification of tissue sodium concentration (TSC) was achieved in (23) Na images with voxel sizes of 1.2 µL acquired in 10 min. The evolution of TSC was investigated from 0.5 to 8 h in focal cortical and subcortical ischemic tissue following permanent middle cerebral artery occlusion in the rat (n = 5). Infarct volumes determined from TSC measurements correlated significantly with histology (P = 0.0006). A delayed linear model was fitted to the TSC time course data in each voxel, which revealed that the TSC increase was more immediate (0.2 ± 0.1 h delay time) in subcortical ischemic tissue, whereas it was delayed by 1.6 ± 0.5 h in ischemic cortex (P = 0.0002). No significant differences (P = 0.5) were measured between TSC slope rates in cortical (10.2 ± 1.1 mM/h) and subcortical (9.7 ± 1.1 mM/h) ischemic tissue. The data suggest that any TSC increase measured in ischemic tissue indicates infarction (core) and regions exhibiting a delay to TSC increase indicate potentially salvageable tissue (penumbra).

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

PURPOSE: To estimate changes in the (23)Na density and in the (23)Na relaxation time T(2) * in the anatomically small murine brain after stroke. MATERIALS AND METHODS: Three-dimensional acquisition weighted chemical shift imaging at a resolution of 0.6 × 0.6 × 1.2 mm(3) was used for sodium imaging and relaxation parameter mapping. In vivo measurements of the mouse brain (n = 4) were performed 24 hours after stroke, induced by microinjection of purified murine thrombin into the right middle cerebral artery. The measurement time was 14 minutes in one mouse and 65 minutes in the other three. An exponential fit estimation of the free induction decay was calculated for each voxel enabling the reconstruction of locally resolved relaxation parameter maps. RESULTS: The infarcted areas showed an increase in sodium density between 160% and 250%, while the T(2) * relaxation time increased by 5%-72% compared to unaffected contralateral brain tissue. CONCLUSION: (23)Na chemical shift imaging at a resolution of 0.6 × 0.6 × 1.2 mm(3) enabled sodium imaging of the anatomical small mouse brain and the acquired data allowed calculating relaxation parameter maps and hence a more exact evaluation of sodium signal changes after stroke.

A double-tuned (1)H/(23)Na dual resonator system for tissue sodium concentration measurements in the rat brain via Na-MRI.

A method for quantifying the tissue sodium concentration (TSC) in the rat brain from ²³Na-MR images was developed. TSC is known to change in a variety of common human diseases and holds considerable potential to contribute to their study; however, its accurate measurement in small laboratory animals has been hindered by the extremely low signal to noise ratio (SNR) in ²³Na images. To address this, the design, construction and characterization of a double-tuned ¹H/²³Na dual resonator system for ¹H-guided quantitative ²³Na-MRI are described. This system comprises an SNR-optimized surface detector coil for ²³Na image acquisition, and a volume resonator producing a highly homogeneous B1 field (<5% inhomogeneity) for the Na channel across the rat head. The resonators incorporated channel-independent balanced matching and tuning capabilities with active decoupling circuitry at the ²³Na resonance frequency. A quantification accuracy of TSC of <10 mM was achieved in Na-images with 1.2 µl voxel resolution acquired in 10 min. The potential of the quantification technique was demonstrated in an in vivo experiment of a rat model of cerebral stroke, where the evolution of the TSC was successfully monitored for 8 h after the stroke was induced.