Motion reduction for quantitative brain sodium MR imaging with a navigated flexible twisted projection imaging sequence at 9.4 T.

Quantitative measurement of the tissue sodium concentration (TSC) provides a metric for tissue cell volume fraction for monitoring tumor responses to therapy and neurodegeneration in the brain as well as applications outside the central nervous system such as the fixed charge density in cartilage. Despite the low detection sensitivity of the sodium MR signal compared to the proton signal and the requirement for a long repetition time to minimize longitudinal magnetization saturation, acquisition time has been reduced to less than 10 min for a nominal isotropic voxel size of 3.3 mm with the improved acquisition efficiency of twisted projection imaging (TPI) at 9.4 T. However, patient motion can degrade the accuracy of the quantification even within these acquisition times. Our goal has been to improve the robustness of quantitative sodium MR imaging by minimizing the impact of motion that may occur even in cooperative patients. We present a method to spatially encode a lower resolution navigator echo after encoding the free induction decay signal for the quantitative image at no time penalty. Both the imaging and navigator data are sampled with flexTPI readout trajectories. Navigator images are generated at a higher temporal resolution (∼1 min) albeit at lower spatial resolution (8 mm) than the quantitative high-resolution images. The multiple volumes of navigator echo images are then aligned to extract the translational and rotational motion parameters assuming rigid-body motion. These parameters are used to align the k-space data during the acquisition of each volume of the quantitative images. Our results show significantly reduced image blurring with this method when the subject's head moved randomly by up to 7° between the navigator acquisitions.

Residual Tumor Volume, Cell Volume Fraction, and Tumor Cell Kill During Fractionated Chemoradiation Therapy of Human Glioblastoma using Quantitative Sodium MR Imaging.

PURPOSE: Spatial and temporal patterns of response of human glioblastoma to fractionated chemoradiation are described by changes in the bioscales of residual tumor volume (RTV), tumor cell volume fraction (CVF), and tumor cell kill (TCK), as derived from tissue sodium concentration (TSC) measured by quantitative sodium MRI at 3 Tesla. These near real-time patterns during treatment are compared with overall survival. EXPERIMENTAL DESIGN: Bioscales were mapped during fractionated chemoradiation therapy in patients with glioblastomas (n = 20) using TSC obtained from serial quantitative sodium MRI at 3 Tesla and a two-compartment model of tissue sodium distribution. The responses of these parameters in newly diagnosed human glioblastomas undergoing treatment were compared with time-to-disease progression and survival. RESULTS: RTV following tumor resection showed decreased CVF due to disruption of normal cell packing by edema and infiltrating tumor cells. CVF showed either increases back toward normal as infiltrating tumor cells were killed, or decreases as cancer cells continued to infiltrate and extend tumor margins. These highly variable tumor responses showed no correlation with time-to-progression or overall survival. CONCLUSIONS: These bioscales indicate that fractionated chemoradiotherapy of glioblastomas produces variable responses with low cell killing efficiency. These parameters are sensitive to real-time changes within the treatment volume while remaining stable elsewhere, highlighting the potential to individualize therapy earlier in management, should alternative strategies be available.

SERIAL transmit - parallel receive (STxPRx) MR imaging produces acceptable proton image uniformity without compromising field of view or SAR guidelines for human neuroimaging at 9.4 Tesla.

PURPOSE: Non-uniform B1+ excitation and high specific absorption rates (SAR) compromise proton MR imaging of human brain at 9.4 T (400.5 MHz). By combining a transmit/receive surface coil array using serial transmission of individual coils with a total generalized variation reconstruction of images from all coils, acceptable quality human brain imaging is demonstrated. METHODS: B0 is shimmed using sodium MR imaging (105.4 MHz) with a birdcage coil. Proton MR imaging is performed with an excitation/receive array of surface coils. The modified FLASH pulse sequence transmits serially across each coil within the array thereby distributing SAR in time and space. All coils operate in receive mode. Although the excitation profile of each transmit coil is non-uniform, the sensitivity profile estimated from the non-transmit receive coils provides an acceptable sensitivity correction. Signals from all coils are combined in a total generalized variation (TGV) reconstruction to provide a full field of view image at maximum signal to noise (SNR) performance. RESULTS: High-resolution images across the human head are demonstrated with acceptable uniformity and SNR. CONCLUSION: Proton MR imaging of the human brain is possible with acceptable uniformity at low SAR at 9.4 Tesla using this serial excitation and parallel reception strategy with TGV reconstruction.

Quantitative sodium MRI of the human brain at 9.4 T provides assessment of tissue sodium concentration and cell volume fraction during normal aging.

Sodium ion homeostasis is a fundamental property of viable tissue, allowing the tissue sodium concentration to be modeled as the tissue cell volume fraction. The modern neuropathology literature using ex vivo tissue from selected brain regions indicates that human brain cell density remains constant during normal aging and attributes the volume loss that occurs with advancing age to changes in neuronal size and dendritic arborization. Quantitative sodium MRI performed with the enhanced sensitivity of ultrahigh-field 9.4 T has been used to investigate tissue cell volume fraction during normal aging. This cross-sectional study (n = 49; 21-80 years) finds that the in vivo tissue cell volume fraction remains constant in all regions of the brain with advancing age in individuals who remain cognitively normal, extending the ex vivo literature reporting constant neuronal cell density across the normal adult age range. Cell volume fraction, as measured by quantitative sodium MRI, is decreased in diseases of cell loss, such as stroke, on a time scale of minutes to hours, and in response to treatment of brain tumors on a time scale of days to weeks. Neurodegenerative diseases often have prodromal periods of decades in which regional neuronal cell loss occurs prior to clinical presentation. If tissue cell volume fraction can detect such early pathology, this quantitative parameter may permit the objective measurement of preclinical disease progression. This current study in cognitively normal aging individuals provides the basis for the pursuance of investigations directed towards such neurodegenerative diseases.

Feasibility of 39-potassium MR imaging of a human brain at 9.4 Tesla.

PURPOSE: To demonstrate the feasibility of performing 39-potassium MR imaging of a human brain. METHODS: 39-Potassium magnetic resonance imaging of a human brain was performed at 9.4 T using a flexible twisted projection imaging acquisition with a nominal isotropic spatial resolution of 10 mm in 40 min using a single-tuned birdcage radiofrequency coil. Co-registered sodium imaging with a nominal isotropic spatial resolution of 3.5 mm was performed on the same subject in 10 min. RESULTS: The 39-potassium flexible twisted projection imaging imaging had a signal-to-noise ratio of 5.2 in brain paranchyma. This qualitative imaging showed the expected features when compared to co-registered high- and low-resolution sodium imaging of the same subject. CONCLUSION: Potassium MR images may offer complementary information to that of sodium MR images by sampling the intracellular rather that interstitial environment. Quantification will require additional improvement in signal-to-noise ratio to produce clinically useful bioscales as are developing for sodium MR imaging.

PCr/ATP ratio mapping of the human head by simultaneously imaging of multiple spectral peaks with interleaved excitations and flexible twisted projection imaging readout trajectories at 9.4 T.

Quantitative (31)P magnetic resonance imaging of the whole human brain is often time-consuming even at low spatial resolution due to the low concentrations, long T(1) relaxation times, and low detection sensitivity of phosphorus metabolites. We report herein the results of combining the increased detection sensitivity of an ultra-high field 9.4 T scanner designed for human imaging with a new pulse sequence termed simultaneously imaging of multiple spectral peaks with interleaved excitations and flexible twisted projection imaging readout trajectories to rapidly sample multiple resonances in the (31)P spectrum. The phosphocreatine and γ-adenosine triphosphate images, obtained simultaneously from the entire human head, are demonstrated at 1.5 cm isotropic nominal resolution in a total acquisition time of 33 min. The phosphocreatine/γ-adenosine triphosphate ratio calculated for brain parenchyma (1-2) and the superficial temporalis muscle (3-5) are in agreement with literature values.

Preserving the accuracy and resolution of the sodium bioscale from quantitative sodium MRI during intrasubject alignment across longitudinal studies.

Emerging applications of sodium bioscales derived from quantitative sodium magnetic resonance imaging assess temporal changes in regional sodium concentration over intervals that vary from hours (monitoring tissue viability in stroke) to weeks (monitoring brain tumor treatment during radiation therapy) or even years (monitoring progression of neurodegenerative disease). Accurate interpretation of such quantitative data requires precise registration between magnetic resonance imaging sessions to avoid session-to-session changes in partial volume effects between normal tissue (∼38 mM sodium concentration), lesions (variable sodium concentration), and cerebrospinal fluid (∼144 mM sodium concentration). The existing Automated Image Registration algorithm is shown to be suitable for rapid, accurate, and precise determination of the transform that aligns sodium magnetic resonance images. Implementation of this transform during image reconstruction from the k-space data is shown to produce smaller errors than conventional image-domain interpolation. Experimental results at 9.4 T and 3.0 T demonstrating this registration approach to sodium data illustrate preservation of quantification accuracy during alignment of sodium magnetic resonance images acquired from the same subject during different imaging sessions.

Impact of gradient timing error on the tissue sodium concentration bioscale measured using flexible twisted projection imaging.

The rapid biexponential transverse relaxation of the sodium MR signal from brain tissue requires efficient k-space sampling for quantitative imaging in a time that is acceptable for human subjects. The flexible twisted projection imaging (flexTPI) sequence has been shown to be suitable for quantitative sodium imaging with an ultra-short echo time to minimize signal loss. The fidelity of the k-space center location is affected by the readout gradient timing errors on the three physical axes, which is known to cause image distortion for projection-based acquisitions. This study investigated the impact of these timing errors on the voxel-wise accuracy of the tissue sodium concentration (TSC) bioscale measured with the flexTPI sequence. Our simulations show greater than 20% spatially varying quantification errors when the gradient timing errors are larger than 10 µs on all three axes. The quantification is more tolerant of gradient timing errors on the Z-axis. An existing method was used to measure the gradient timing errors with <1 µs error. The gradient timing error measurement is shown to be RF coil dependent, and timing error differences of up to ∼16 µs have been observed between different RF coils used on the same scanner. The measured timing errors can be corrected prospectively or retrospectively to obtain accurate TSC values.

Clinically constrained optimization of flexTPI acquisition parameters for the tissue sodium concentration bioscale.

The rapid transverse relaxation of the sodium magnetic resonance signal during spatial encoding causes a loss of image resolution, an effect known as T(2)-blurring. Conventional wisdom suggests that spatial resolution is maximized by keeping the readout duration as short as possible to minimize T(2)-blurring. Flexible twisted projection imaging performed with an ultrashort echo time, relative to T(2), and a long repetition time, relative to T(1), has been shown to be effective for quantitative sodium magnetic resonance imaging. A minimized readout duration requires a very large number of projections and, consequentially, results in an impractically long total acquisition time to meet these conditions. When the total acquisition time is limited to a clinically practical duration (e.g., 10 min), the optimal parameters for maximal spatial resolution of a flexible twisted projection imaging acquisition do not correspond to the shortest possible readout. Simulation and experimental results for resolution optimized acquisition parameters of quantitative sodium flexible twisted projection imaging of parenchyma and cerebrospinal fluid are presented for the human brain at 9.4 and 3.0T. The effect of signal loss during data collection on sodium quantification bias and image signal-to-noise ratio are discussed.

Vital signs and cognitive function are not affected by 23-sodium and 17-oxygen magnetic resonance imaging of the human brain at 9.4 T.

PURPOSE: To evaluate the effect of 23-sodium ((23)Na) and 17-oxygen ((17)O) magnetic resonance imaging (MRI) at 9.4 (T) on vital signs and cognitive function of the human brain. MATERIALS AND METHODS: Vital sign and cognitive function measurements from healthy volunteers (N = 14) positioned outside and at isocenter of a 9.4 T scanner before and after (23)Na and (17)O MRI were compared for changes due to exposure to the static magnetic field and to the gradient switching and radiofrequency radiation during MRI. RESULTS: Exposure to the 9.4 T static magnetic field and (23)Na and (17)O MRI at 105.92 MHz and 54.25 MHz, respectively, did not have a statistically significant (P > 0.05) effect on the vital signs or cognitive function of healthy normal adults. CONCLUSION: (23)Na and (17)O MRI of the human brain at 9.4 T does not have any readily demonstrated health risks reflected in vital signs or change in cognitive performance.

Quantitative sodium imaging with a flexible twisted projection pulse sequence.

The quantification of sodium MR images from an arbitrary intensity scale into a bioscale fosters image interpretation in terms of the spatially resolved biochemical process of sodium ion homeostasis. A methodology for quantifying tissue sodium concentration using a flexible twisted projection imaging sequence is proposed that allows for optimization of tradeoffs between readout time, signal-to-noise ratio efficiency, and sensitivity to static field susceptibility artifacts. The gradient amplitude supported by the slew rate at each k-space radius regularizes the readout gradient waveform design to avoid slew rate violation. Static field inhomogeneity artifacts are corrected using a frequency-segmented conjugate phase reconstruction approach, with field maps obtained quickly from coregistered proton imaging. High-quality quantitative sodium images have been achieved in phantom and volunteer studies with real isotropic spatial resolution of 7.5 x 7.5 x 7.5 mm(3) for the slow T(2) component in approximately 8 min on a clinical 3-T scanner. After correcting for coil sensitivity inhomogeneity and water fraction, the tissue sodium concentration in gray matter and white matter was measured to be 36.6 +/- 0.6 micromol/g wet weight and 27.6 +/- 1.2 micromol/g wet weight, respectively.

Feasibility of mapping the tissue mass corrected bioscale of cerebral metabolic rate of oxygen consumption using 17-oxygen and 23-sodium MR imaging in a human brain at 9.4 T.

The reduction of molecular oxygen to water is the final step of oxidative phosphorylation that couples adenosine triphosphate production to the reoxidation of reducing equivalents formed during the oxidation of glucose to carbon dioxide. This coupling makes the cerebral metabolic rate of oxygen consumption (CMRO(2)) an excellent reflection of the metabolic health of the brain. A multi-nuclear magnetic resonance (MR) imaging based method for CMRO(2) mapping is proposed. Oxygen consumption is determined by applying a new three-phase metabolic model for water generation and clearance to the changing 17-oxygen ((17)O) labeled water MR signal measured using quantitative (17)O MR imaging during inhalation of (17)O-enriched oxygen gas. These CMRO(2) data are corrected for the regional brain tissue mass computed from quantitative 23-sodium MR imaging of endogenous tissue sodium ions to derive quantitative results of oxygen consumption in micromoles O(2)/g tissue/minute that agree with literature results reported from positron emission tomography. The proposed technique is demonstrated in the human brain using a 9.4 T MR scanner optimized for human brain imaging.

Quantitative sodium MR imaging and sodium bioscales for the management of brain tumors.

Treatment of high-grade primary brain tumors is based on experience from multicenter trials. However, the prognosis has changed little in 3 decades. This suggests that there is a fundamental oversight in treatment. This article provides an imaging perspective of how regional responses of primary brain tumors may be examined to guide a flexible treatment plan. Sodium imaging provides a measurement of cell density that can be used to measure regional cell kill. Such a bioscales of regionally and temporally sensitive biologic-based parameters may be helpful to guide tumor treatment. These suggestions are speculative and still being examined, but are presented to challenge the medical community to be receptive to changes in the standard of care when that standard continues to fail.

Investigating the consistency of brain activation using individual trial analysis of high-resolution fMRI in the human primary visual cortex.

Conventional functional magnetic resonance imaging using blood oxygenation level dependent contrast requires signal averaging and statistical methods to detect activation. Signal averaging implicitly assumes that brain activation in response to a stimulus is reproducible on the scale of the imaging voxel. This assumption is examined in the absence of averaging by analyzing individual trials of individual voxels that approach the size of the functional unit, the cortical column, in the human primary visual cortex. In the absence of spatial and temporal averaging, even highly active voxels demonstrate inconsistent activation to the same repeated stimulus despite consistent behavioral responses. This observation implies a variable selection of suitable cortical columns from a population of available functional units to produce consistent perception of the stimulus. The implication of this observation for neuroplasticity and behavioral consistency at the level of functional units is discussed.

Characterization and correction of system delays and eddy currents for MR imaging with ultrashort echo-time and time-varying gradients.

Reconstruction of high-quality MR images requires precise knowledge of the dynamic gradient magnetic fields used to perform spatial encoding. System delays and eddy currents can perturb the gradient fields in both time and space and significantly degrade the image quality for acquisitions with an ultrashort echo time or with rapidly varying readout gradient waveforms. A technique for simultaneously characterizing and correcting the system delay and linear- and zero-order eddy currents of an MR system is proposed. A single set of calibration scans were used to compute a set of system constants that describe the effects of system delays and eddy currents to enable accurate reconstruction of data collected before uncorrected eddy currents have decayed. The ability of the proposed technique to reproducibly characterize small fixed delays (<50 micros) and short-time constant (<1 ms) eddy currents is demonstrated.

Safety of human MRI at static fields above the FDA 8 T guideline: sodium imaging at 9.4 T does not affect vital signs or cognitive ability.

PURPOSE: To assess whether exposure to a 9.4 T static magnetic field during sodium imaging at 105.92 MHz affects human vital signs and cognitive function. MATERIALS AND METHODS: Measurements of human vital signs and cognitive ability made before and after exposure to a 9.4 T MR scanner and a mock scanner with no magnetic field are compared using a protocol approved by the U.S. Food and Drug Administration (FDA). RESULTS: Exposure to a 9.4 T static magnetic field during sodium imaging did not result in a statistically significant change in the vital signs or cognitive ability of healthy normal volunteers. CONCLUSION: Vital sign and cognitive ability measurements made before and after sodium imaging at 9.4 T suggest that performing human MRI at 105.92 MHz in a 9.4 T static magnetic field does not pose a health risk.