Low rank off-resonance correction for double half-echo k-space acquisitions.

The present study describes a model-based approach for correcting off-resonance in the context of double half-echo k-space acquisitions. This technique employs center-out readouts in forward and reverse directions to reduce echo-times but is sensitive to off-resonance, which manifests as pixel shifts in both directions. Demodulating the k-space signal with a constant off-resonance term per slice removes pixel shifts and results in a marked reduction in blurring. Phantom and in vivo datasets are demonstrated from low bandwidth sodium imaging.

Distinctive ionic transport of freshly excised human epileptogenic brain tissue.

Epileptogenic lesions have higher concentrations of sodium than does normal brain tissue. Such lesions are palpably recognized by a surgeon and then excised in order to eliminate epileptic seizures with their associated abnormal electrical behavior. Here, we study the frequency-dependent electrical conductivities of lesion-laden tissues excised from the brains of epilepsy patients. The low-frequency (<1000 Hz) conductivity of biological tissue primarily probes extracellular solvated sodium-cations traveling parallel to membranes within regions bounded by blockages. This conductivity rises monotonically toward saturation as the frequency surpasses the rate with which diffusing solvated sodium cations encounter blockages. We find that saturation occurs at dramatically higher frequencies in excised brain tissue containing epileptogenic lesions than it does in normal brain tissue. By contrast, such an effect is not reported for tumors embedded in other excised biological tissue. All told, epileptogenic lesions generate frequency-dependent conductivities that differ qualitatively from those of both normal brain tissues and tumors.

Understanding the sodium cation conductivity of human epileptic brain tissue.

Transient and frequency-dependent conductivity measurements on excised brain-tissue lesions from epilepsy patients indicate that sodium cations are the predominant charge carriers. The transient conductivity ultimately vanishes as ions encounter blockages. The initial and final values of the transient conductivity correspond to the high-frequency and low-frequency limits of the frequency-dependent conductivity, respectively. Carrier dynamics determines the conductivity between these limits. Typically, the conductivity rises monotonically with increasing frequency. By contrast, when pathology examinations found exceptionally disorganized excised tissue, the conductivity falls with increasing frequency as it approaches its high-frequency limit. To analyze these measurements, excised tissues are modeled as mixtures of "normal" tissue within which sodium cations can diffuse and "abnormal" tissue within which sodium cations are trapped. The decrease in the conductivity with increasing frequency indicates the predominance of trapping. The high-frequency conductivity decreases as the rate with which carriers are liberated from traps decreases. A relatively low conductivity results when most sodium cations remain trapped in "abnormal" brain tissue, while few move within "normal" brain tissue. Thus, the high densities of sodium nuclei observed by 23Na-MRI in epilepsy patients' lesions are consistent with the low densities of diffusing sodium cations inferred from conductivity measurements of excised lesions.

Evaluation of Magnetonanoparticles Conjugated with New Angiogenesis Peptides in Intracranial Glioma Tumors by MRI.

Angiogenesis plays a critical role in progression of malignant gliomas. The development of glioma-specific labeling molecules that can aid detection and visualization of angiogenesis can help surgical planning and improve treatment outcome. The aim of this study was to evaluate if two peptides (GX1 and RGD-GX1) linked to angiogenesis can be used as an MR-imaging markers of angiogenesis. MR imaging was performed in U87 glioblastoma-bearing NOD-SCID mice at different time points between 15 and 120 min post-injection to visualize particle distribution. GX1 and RGD-GX1 exhibited the highest accumulation in U87 glioblastoma at 120 min post i.v. administration. GX1-conjugated agents lead to higher decrease in transverse relaxation time (T 2) (i.e., stronger contrast enhancement) than RGD-GX1-conjugated agents in U87 glioblastoma tumor model. In addition, we tested if U87-IDH1R132 mutated cell line had different pattern of GX1 or RGD-GX1 particle accumulation. Responses in U87-IDH1WT followed a similar pattern with GX1 contrast agents; however, lower contrast enhancement was observed with RGD-GX1 agents. The specific binding of these peptides to human glioblastoma xenograft in the brain was confirmed by magnetic resonance imaging. The contrast enhancement following injection of magnetonanoparticles conjugated to GX1 peptide matched well with CD31 staining and iron staining.

Ionic charge transport between blockages: Sodium cation conduction in freshly excised bulk brain tissue.

We analyze the transient-dc and frequency-dependent electrical conductivities between blocking electrodes. We extend this analysis to measurements of ions' transport in freshly excised bulk samples of human brain tissue whose complex cellular structure produces blockages. The associated ionic charge-carrier density and diffusivity are consistent with local values for sodium cations determined non-invasively in brain tissue by MRI (NMR) and diffusion-MRI (spin-echo NMR). The characteristic separation between blockages, about 450 microns, is very much shorter than that found for sodium-doped gel proxies for brain tissue, >1 cm.

High-speed real-time resting-state FMRI using multi-slab echo-volumar imaging.

We recently demonstrated that ultra-high-speed real-time fMRI using multi-slab echo-volumar imaging (MEVI) significantly increases sensitivity for mapping task-related activation and resting-state networks (RSNs) compared to echo-planar imaging (Posse et al., 2012). In the present study we characterize the sensitivity of MEVI for mapping RSN connectivity dynamics, comparing independent component analysis (ICA) and a novel seed-based connectivity analysis (SBCA) that combines sliding-window correlation analysis with meta-statistics. This SBCA approach is shown to minimize the effects of confounds, such as movement, and CSF and white matter signal changes, and enables real-time monitoring of RSN dynamics at time scales of tens of seconds. We demonstrate highly sensitive mapping of eloquent cortex in the vicinity of brain tumors and arterio-venous malformations, and detection of abnormal resting-state connectivity in epilepsy. In patients with motor impairment, resting-state fMRI provided focal localization of sensorimotor cortex compared with more diffuse activation in task-based fMRI. The fast acquisition speed of MEVI enabled segregation of cardiac-related signal pulsation using ICA, which revealed distinct regional differences in pulsation amplitude and waveform, elevated signal pulsation in patients with arterio-venous malformations and a trend toward reduced pulsatility in gray matter of patients compared with healthy controls. Mapping cardiac pulsation in cortical gray matter may carry important functional information that distinguishes healthy from diseased tissue vasculature. This novel fMRI methodology is particularly promising for mapping eloquent cortex in patients with neurological disease, having variable degree of cooperation in task-based fMRI. In conclusion, ultra-high-real-time speed fMRI enhances the sensitivity of mapping the dynamics of resting-state connectivity and cerebro-vascular pulsatility for clinical and neuroscience research applications.

Functionalized magnetonanoparticles in visualization of intracranial tumors on MRI.

PURPOSE: The development of nonradioactive and targeted magnetonanoparticles (MNP) capable of crossing the blood-brain barrier (BBB) and of concentrating in and enhancing the contrast of intracranial tumors on magnetic resonance imaging (MRI). PROCEDURE: Nonradioactive 2-deoxy-D-glucose (2DG) was covalently attached to magnetonanoparticles composed of iron oxide and dextran and prepared for intravenous (tail) injection in the naïve rats and mouse models of glioma. MR images were acquired at 3 and 7 T. RESULTS: 2DG-MNP increased tumor visibility and improved delineation of tumor margins. Histopathology confirmed that 2DG-MNP crossed the BBB and accumulated within brain parenchyma. CONCLUSION: Nonradioactive 2DG-MNP can cross an intact BBB on and improve visualization of tumor and tumor margins on MRI.

Imaging brain neuronal activity using functionalized magnetonanoparticles and MRI.

This study explored the use of non-radioactive 2-deoxy glucose (2DG)-labeled magnetonanoparticles (MNP) and magnetic resonance imaging (MRI) to detect functional activity during rest, peripheral stimulation, and epileptic seizures, in animal models. Non-radioactive 2DG was covalently attached to magnetonanoparticles composed of iron oxide and dextran and intravenous (tail) injections were performed. 2DG-MNP was injected in resting and stimulated naïve rodents and the subsequent MRI was compared to published (14)C-2DG autoradiography data. Reproducibility and statistical significance was established in one studied model. Negative contrast enhancement (NCE) in acute seizures and chronic models of epilepsy were investigated. MRI NCE due to 2DG-MNP particles was compared to that of plain (unconjugated) MNP in one animal. NCE due to 2DG-MNP particles at 3 T, which is approved for human use, was also investigated. Histology showed presence of MNP (following intravenous injection) in the brain tissues of resting naïve animal. 2DG-MNP intraparenchymal uptake was visible on MRI and histology. The locations of NCE agreed with published results of 2DG autoradiography in resting and stimulated animals and epileptic rats. Localization of epileptogenicity was confirmed by subsequent depth-electrode EEG (iEEG). Non-radioactive 2DG-MNP can cross the blood-brain barrier (BBB) and may accurately localize areas of increased activity. Although, this proof-of-principle study involves only a limited number of animals, and much more research and quantification are necessary to demonstrate that 2DG-MNP, or MNPs conjugated with other ligands, could eventually be used to image localized cerebral function with MRI in humans, this MNP-MRI approach is potentially applicable to the use of many bioactive molecules as ligands for imaging normal and abnormal localized cerebral functions.

Functionalized magnetonanoparticles for MRI diagnosis and localization in epilepsy.

PURPOSE: The development of nonradioactive and targeted magnetonanoparticles (MNP) capable of crossing the blood-brain barrier (BBB) and of concentrating in the epileptogenic tissues of acute and chronic animal models of temporal lobe epilepsy to render these tissues visible on magnetic resonance imaging (MRI). METHODS: Nonradioactive alpha methyl tryptophan (AMT) was covalently attached to MNP composed of iron oxide and dextran. A rodent model of temporal lobe epilepsy was prepared by injecting kainic acid into the right hippocampus. AMT-MNP or plain MNP was injected in the tail-vein of two animals during the acute stage 3 days after status epilepticus, and AMT-MNP in five animals during the chronic stage. MRIs were obtained before and after particle injection in all animals. Intracranial EEGs were obtained in all chronic animals after completion of MRI studies. RESULTS: AMT-MNP crossed the BBB and intraparenchymal uptake was visible on MRI. In the acute condition, AMT-MNP appeared to localize to both hippocampi, whereas plain MNP only identified unilateral, presumably inflammatory, changes. In the chronic condition, AMT-MNP uptake correlated with the occurrence of spontaneous seizures, and the location of uptake appeared to agree with bilateral or unilateral epileptogenicity confirmed by subsequent intracranial EEG. DISCUSSION: Nonradioactive AMT-MNP can cross the BBB and may accurately localize epileptogenic cerebral regions. The MNP-MRI approach is potentially applicable to the use of any bioactive molecules as ligands for imaging normal and abnormal localized cerebral functions, accurately, safely, and inexpensively.

Improving MRI differentiation of gray and white matter in epileptogenic lesions based on nonlinear feedback.

A new method for enhancing MRI contrast between gray matter (GM) and white matter (WM) in epilepsy surgery patients with symptomatic lesions is presented. This method uses the radiation damping feedback interaction in high-field MRI to amplify contrast due to small differences in resonance frequency in GM and WM corresponding to variations in tissue susceptibility. High-resolution radiation damping-enhanced (RD) images of in vitro brain tissue from five patients were acquired at 14 T and compared with corresponding conventional T(1)-, T(2) (*)-, and proton density (PD)-weighted images. The RD images yielded a six times better contrast-to-noise ratio (CNR = 44.8) on average than the best optimized T(1)-weighted (CNR = 7.92), T(2) (*)-weighted (CNR = 4.20), and PD-weighted images (CNR = 2.52). Regional analysis of the signal as a function of evolution time and initial pulse flip angle, and comparison with numerical simulations confirmed that radiation damping was responsible for the observed signal growth. The time evolution of the signal in different tissue regions was also used to identify subtle changes in tissue composition that were not revealed in conventional MR images. RD contrast is compared with conventional MR methods for separating different tissue types, and its value and limitations are discussed.

Magnetoencephalography-directed surgery in patients with neocortical epilepsy.

OBJECT: Magnetoencephalography (MEG) and magnetic source (MS) imaging are techniques that have been increasingly used for preoperative localization of epileptic foci and areas of eloquent cortex. The use of MEG examinations must be carefully balanced against the high cost and technological investments required to perform these studies, particularly when less expensive alternative localization methods are available. To help elucidate the value of MEG, the authors have critically reviewed their experience with whole-head MEG in the case management of patients undergoing epilepsy surgery. METHODS: The authors identified 23 patients with suspected focal epilepsy who underwent whole-head MEG and MS imaging at Huntington Memorial Hospital and, subsequently, underwent invasive intracranial electrode monitoring and electrocorticography (ECoG) to localize the zone of seizure origin for surgical resection. The results of the MS imaging were retrospectively stratified into three groups by the number of interictal spikes recorded during a 4-hour recording session: Class I (no spikes), Class II (< or = five spikes), and Class III (> or = six spikes). Class III was further subdivided according to the clustering density of the interictal spikes: Class IIIA represents a mean distance between interictal spikes of 4 mm or greater (that is, diffusely clustered) and Class IIIB represents a mean distance between interictal spikes of less than 4 mm (that is, densely clustered). The authors analyzed these groups to determine to what extent the results of MS imaging correlated with the ECoG-determined zone of seizure origin. In addition, they assessed whether the MS imaging study provided critical localization data and correlated with surgical outcome following resection. A statistical analysis of these correlations was also performed. Of the 40 patients studied, 23 underwent invasive monitoring, including 13 with neocortical epilepsy, four with mesial temporal lobe epilepsy, and six with suspected neocortical epilepsy that could not be clearly localized by ECoG. Depth electrodes were used in nine cases, subdural grids in nine cases, depth electrodes followed by subdural grids and strips in four cases, and intraoperative ECoG in one case. Electrocorticography was able to localize the zone of seizure origin in 16 (70%) of 23 cases. In 11 (69%) of the 16 cases in which ECoG was able to localize the zone of seizure origin, the interictal spikes on the MS images were classified as Class IIIB (densely clustered) and regionally correlated to the MS imaging-determined localization in all cases (that is, the same lobe). In contrast, no Class IIIB cases were identified when ECoG was unable to localize the zone of seizure origin. This difference showed a trend toward, but did not achieve, statistical significance (p < 0.23), presumably because of the relatively small number of cases available for analysis. In three cases (all Class IIIB), MS imaging was used to guide invasive electrodes to locations that otherwise would not have been targeted and provided unique localization data, not evident from other imaging modalities, that strongly influenced the surgical management of the patient. The classification of findings on MS images into subgroups and subsequent statistical analysis generated a model that predicted that Class IIIB MS imaging data are likely to provide reliable information to guide surgical placement of electrodes, but all other data groups do not provide localization information that is reliable enough to guide surgical decision making. CONCLUSIONS: Magnetic source imaging can provide unique localization information that is not available when other noninvasive methods are used. Magnetic source imaging appears most useful for cases of neocortical epilepsy. In particular, when an MS imaging study revealed six or more interictal spikes that were densely clustered in a single anatomical location, the MS image was highly correlated with the zone of seizure origin identified by ECoG. In these cases the MS imaging data may be useful to guide placement of intracranial electrodes.