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Purpose To develop and evaluate a novel method for reconstruction of high-quality sodium MR images from noisy, limited k-space data. Theory and methods A novel reconstruction method was developed for reconstruction of high-quality sodium images from noisy, limited k-space data. This method is based on a novel image model that contains a motion-compensated generalized series model and a sparse model. The motion-compensated generalized series model enables effective use of anatomical information from a proton image for denoising and resolution enhancement of sodium data, whereas the sparse model enables high-resolution reconstruction of sodium-dependent novel features. The underlying model estimation problems were solved efficiently using convex optimization algorithms. Results The proposed method has been evaluated using both simulation and experimental data obtained from phantoms, healthy human volunteers, and tumor patients. Results showed a substantial improvement in spatial resolution and SNR over state-of-the-art reconstruction methods, including compressed sensing and anatomically constrained reconstruction methods. Quantitative tissue sodium concentration maps were obtained from both healthy volunteers and brain tumor patients. These tissue sodium concentration maps showed improved lesion fidelity and allowed accurate interrogation of small targets. Conclusion A new method has been developed to obtain high-resolution sodium images with good SNR at 3 T. The proposed method makes effective use of anatomical prior information for denoising, while using a sparse model synergistically to recover sodium-dependent novel features. Experimental results have been obtained to demonstrate the feasibility of achieving high-quality tissue sodium concentration maps and their potential for improved detection of spatially heterogeneous responses of tumor to treatment.

Background Atherosclerotic vertebrobasilar disease is a significant etiology of posterior circulation stroke. The prospective observational VER i TAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) study demonstrated that distal hemodynamic status is a robust predictor of subsequent vertebrobasilar stroke risk. We sought to compare predictive models using thresholds for posterior circulation vessel flows standardized to age and vascular anatomy to optimize risk prediction. Methods and Results VER i TAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis/occlusion in vertebral and/or basilar arteries. Quantitative magnetic resonance angiography measured large‐vessel vertebrobasilar territory flow, and patients were designated as low or normal flow based on a prespecified empiric algorithm considering distal territory regional flow and collateral capacity. For the present study, post hoc analysis was performed to generate additional predictive models using age‐specific normalized flow measurements. Sensitivity, specificity, and time‐to‐event analyses were compared between the algorithms. The original prespecified algorithm had 50% sensitivity and 79% specificity for future stroke risk prediction; using a predictive model based on age‐normalized flows in the basilar and posterior cerebral arteries, standardized to vascular anatomy, optimized flow status thresholds were identified. The optimized algorithm maintained sensitivity and increased specificity to 84%, while demonstrating a larger and more significant hazard ratio for stroke on time‐to‐event analysis. Conclusions These results indicate that flow remains a strong predictor of stroke across different predictive models, and suggest that prediction of future stroke risk can be optimized by use of vascular anatomy and age‐specific normalized flows.

Sodium magnetic resonance (MR) imaging in humans has promised metabolic information that can improve medical management in important diseases. This technology has yet to find a role in clinical practice, lagging proton MR imaging by decades. This review covers the literature that demonstrates that this delay is explained by initial challenges of low sensitivity at low magnetic fields and the limited performance of gradients and electronics available in the 1980s. These constraints were removed by the introduction of 3T and now ultrahigh (≥7T) magnetic field scanners with superior gradients and electronics for proton MR imaging. New projection pulse sequence designs have greatly improved sodium acquisition efficiency. The increased field strength has provided the expected increased sensitivity to achieve resolutions acceptable for metabolic interpretation even in small target tissues. Consistency of quantification of the sodium MR image to provide metabolic parametric maps has been demonstrated by several different pulse sequences and calibration procedures. The vital roles of sodium ion in membrane transport and the extracellular matrix will be reviewed to indicate the broad opportunities that now exist for clinical sodium MR imaging. The final challenge is for the technology to be supplied on clinical ≥3T scanners.

BACKGROUND AND PURPOSE: Loss of hemodynamic reserve in intracranial cerebrovascular disease reduces blood oxygenation level–dependent activation by fMRI and increases asymmetry in MTT measured by provocative DSC perfusion MR imaging before and after vasodilation with intravenous acetazolamide. The concordance for detecting hemodynamic reserve integrity has been compared. MATERIALS AND METHODS: Patients ( n = 40) with intracranial cerebrovascular disease and technically adequate DSA, fMRI and provocative DSC perfusion studies were retrospectively grouped into single vessels proximal to and distal from the circle of Willis, multiple vessels, and Moyamoya disease. The vascular territories were classified as having compromised hemodynamic reserve if the expected fMRI blood oxygenation level–dependent activation was absent or if MTT showed increased asymmetry following vasodilation. Concordance was examined in compromised and uncompromised vascular territories of each group with the Fischer exact test and proportions of agreement. RESULTS: Extensive leptomeningeal collateral circulation was present in all cases. Decreased concordance between the methods was found in vascular territories with stenosis distal to but not proximal to the circle of Willis. Multivessel and Moyamoya diseases also showed low concordance. A model of multiple temporally displaced arterial inputs from leptomeningeal collateral flow demonstrated that the resultant lengthening MTT mimicked compromised hemodynamic reserve despite being sufficient to support blood oxygenation level–dependent contrast. CONCLUSIONS: Decreased concordance between the 2 methods for assessment of hemodynamic reserve for vascular disease distal to the circle of Willis is posited to be due to well-developed leptomeningeal collateral circulation providing multiple temporally displaced arterial input functions that bias the perfusion analysis toward hemodynamic reserve compromise while blood oxygenation level–dependent activation remains detectable.

Introduction: Perfusion-weighted magnetic resonance imaging (MRP) has been used to assess changes in cerebral perfusion attributable to vascular stenosis or occlusion that may predict stroke risk. The ability of MRP to identify hemodynamic compromise in the posterior circulation, however, has not been well established. The observational Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study has previously demonstrated that flow status determined through large vessel flow measurements with quantitative magnetic resonance angiography (QMRA) predicts stroke risk in vertebrobasilar disease. We examined whether MRP parameters correlated with QMRA assessment of flow compromise in the VERiTAS cohort. Methods: VERiTAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries. Hemodynamic status using vertebrobasilar large vessel flow was measured using QMRA, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Dynamic susceptibility contrast MRP was performed concurrently with QMRA. Mean transit time (MTT) in the posterior cerebral artery (PCA) territory was used to evaluate posterior circulation perfusion. To normalize the values, an MTT ratio was calculated in reference to the anterior circulation (mean of the anterior cerebral artery (ACA) and middle cerebral artery (MCA) territories). The PCA to ACA/MCA MTT ratio from MRP was then assessed relative to flow status (normal vs. low) from QMRA. Results: Of the 72 enrolled subjects, 23 had MRP data available for review. On initial QMRA designation, 19 subjects were designated as normal flow vs. 4 as low flow. The mean MTT ratios for patients with normal vs. low flow were 1.02 (SD=0.05) vs.1.04 (SD=0.04), respectively (p=0.55, t test; p=0.50, Wilcoxon rank sum test). Among the subgroup of 23 patients, 1 patient with low flow, and MTT ratio of 1.00, experienced a recurrent stroke. Conclusions: These results suggest that MRP is a poor indicator of actual hemodynamic compromise in vertebrobasilar disease and is not a reliable substitute for large vessel flow measurements.

Purpose: To evaluate the safety of brain MR imaging examinations at 9.4 Tesla (T) as reflected in vital signs and cognitive performance in healthy and medically diagnosed adult volunteers as mandated by the regulatory agency of the Food and Drug Administration.Materials and Methods: Vital signs were measured on healthy (N=22) and for-cause (N=24) adult volunteers positioned outside (0.3T) and at isocenter (9.4T) of a 9.4 T MR scanner before and after sodium (23Na) MR imaging. Cognitive performance was evaluated at the Earth’s magnetic field before and after imaging. Measurements were compared for statistically significant changes due to exposure to the MR imaging at 9.4 Tesla static magnetic field.Results: No statistically significant changes in the vital signs or cognitive performance were detected for either the healthy or subjects with medical diagnoses as a result of MR imaging at 9.4 Tesla.Conclusion: Exposure to the static magnetic field and to MR neuroimaging at 9.4 Tesla do not have any readily demonstrated health risks reflected in alterations of vital signs or cognitive performance of healthy or for-cause adult volunteers.

An initiative to design and build magnetic resonance imaging (MRI) and spectroscopy (MRS) instruments at 14 T and beyond to 20 T has been underway since 2012. This initiative has been supported by 22 interested participants from the USA and Europe, of which 15 are authors of this review. Advances in high temperature superconductor materials, advances in cryocooling engineering, prospects for non-persistent mode stable magnets, and experiences gained from large-bore, high-field magnet engineering for the nuclear fusion endeavors support the feasibility of a human brain MRI and MRS system with 1 ppm homogeneity over at least a 16-cm diameter volume and a bore size of 68 cm. Twelve neuroscience opportunities are presented as well as an analysis of the biophysical and physiological effects to be investigated before exposing human subjects to the high fields of 14 T and beyond.

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.

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.

Two studies examined how the amount and type of computational demand are related to fMRI-measured activation in three bilateral cortical regions involved in the Shepard-Metzler (1971) mental-rotation paradigm. The amount of demand for the computation of visuospatial coordinates was manipulated by presenting mental rotation problems with increasing angular disparity (0, 40, 80, or 120°). Activation in both the left and right intraparietal sulcal regions increased linearly with angular disparity in two separate studies. Activation also occurred in the fusiform gyrus and inferior temporal regions, regions that are primarily associated with the processes of object and object-part identification. By contrast, the demand for object recognition and rotation processes was relatively low, and the demand for executing saccades was high in a control condition that required making a systematic visual scan of two grids. The grid-scanning condition resulted in relatively less activation in the parietal and inferior temporal regions but considerable activation in frontal areas that are associated with planning and executing saccades, including the precentral gyrus and sulcus into the posterior middle frontal region. These data suggest that the amount of activation in the various cortical regions that support visuospatial processing is related to the amount, as well as to the type, of computational demand.

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.

Measurement of volume flow rates in major cerebral vessels can be used to evaluate the hemodynamic effects of cerebrovascular disease. However, both age and vascular anatomy can affect flow rates independent of disease. We prospectively evaluated 325 healthy adult volunteers using phase contrast quantitative magnetic resonance angiography to characterize these effects on cerebral vessel flow rates and establish clinically useful normative reference values. Flows were measured in the major intracranial and extracranial vessels. The cohort ranged from 18 to 84 years old, with 157 (48%) females. All individual vessel flows and total cerebral blood flow (TCBF) declined with age, at 2.6 mL/minute per year for TCBF. Basilar artery (BA) flow was significantly decreased in individuals with one or both fetal posterior cerebral arteries (PCAs). Internal carotid artery flows were significantly higher with a fetal PCA and decreased with a hypoplastic anterior cerebral artery. Indexing vessel flows to TCBF neutralized the age effect, but anatomic variations continued to impact indexed flow in the BA and internal carotid artery. Variability in normative flow ranges were reduced in distal vessels and by examining regional flows. Cerebral vessel flows are affected by age and cerebrovascular anatomy, which has important implications for interpretation of flows in the disease state.

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.

SUMMARY: Functional neuroradiology represents a relatively new and ever-growing subspecialty in the field of neuroradiology. Neuroradiology has evolved beyond anatomy and basic tissue signal characteristics and strives to understand the underlying physiologic processes of central nervous system disease. The American Society of Functional Neuroradiology sponsors a yearly educational and scientific meeting, and the educational committee was asked to suggest a few cutting-edge functional neuroradiology techniques (hot topics). The following is a review of several of these topics and includes “Diffusion Tensor Imaging of the Pediatric Spinal Cord”; “Diffusional Kurtosis Imaging”; “From Standardization to Quantification: Beyond Biomarkers toward Bioscales as Neuro MR Imaging Surrogates of Clinical End Points”; Resting-State Functional MR Imaging”; and “Current Use of Cerebrovascular Reserve Imaging.”

BACKGROUND: The optimal revascularization strategy for symptomatic adult moyamoya remains controversial. Whereas direct bypass offers immediate revascularization, indirect bypass can effectively induce collaterals over time. OBJECTIVE: Using angiography and quantitative magnetic resonance angiography, we examined the relative contributions of direct and indirect bypass in moyamoya patients after combined direct superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass and indirect encephaloduroarteriosynangiosis (EDAS). METHODS: A retrospective review of moyamoya patients undergoing combined STA-MCA bypass and EDAS was conducted, excluding pediatric patients and hemorrhagic presentation. Patients with quantitative magnetic resonance angiography measurements of the direct bypass immediately and > 6 months postoperatively were included. Angiographic follow-up, when available, was used to assess EDAS collaterals at similar time intervals. RESULTS: Of 16 hemispheres in 13 patients, 11 (69%) demonstrated a significant (> 50%) decline in direct bypass flow at > 6 months compared with baseline, averaging a drop from 99 ± 35 to12 ± 7 mL/min. Conversely, angiography in these hemispheres demonstrated prominent indirect collaterals, in concert with shrinkage of the STA graft. Decline in flow was apparent at a median of 9 months but was evident as early as 2 to 3 months. CONCLUSION: In this small cohort, a reciprocal relationship between direct STA bypass flow and indirect EDAS collaterals frequently occurred. This substantiates the notion that combined direct/indirect bypass can provide temporally complementary revascularization.

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. Magn Reson Med 71:1819–1825, 2014. © 2013 Wiley Periodicals, Inc.

Quantitative sodium magnetic resonance imaging permits noninvasive measurement of the tissue sodium concentration (TSC) bioscale in the brain. Computing the TSC bioscale requires reconstructing and combining multiple datasets acquired with a non-Cartesian acquisition that highly oversamples the center of k-space. Even with an optimized implementation of the algorithm to compute TSC, the overall processing time exceeds the time required to collect data from the human subject. Such a mismatch presents a challenge for sustained sodium imaging to avoid a growing data backlog and provide timely results. The most computationally intensive portions of the TSC calculation have been identified and accelerated using a consumer graphics processing unit (GPU) in addition to a conventional central processing unit (CPU). A recently developed data organization technique called Compact Binning was used along with several existing algorithmic techniques to maximize the scalability and performance of these computationally intensive operations. The resulting GPU+CPU TSC bioscale calculation is more than 15 times faster than a CPU-only implementation when processing 256 × 256 × 256 data and 2.4 times faster when processing 128 × 128 × 128 data. This eliminates the possibility of a data backlog for quantitative sodium imaging. The accelerated quantification technique is suitable for general three-dimensional non-Cartesian acquisitions and may enable more sophisticated imaging techniques that acquire even more data to be used for quantitative sodium imaging. © 2013 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 23, 29–35, 2013.

Background: Fractional flow across an atherosclerotic lesion measured with TOF-MRA signal intensity ratio (SIR) may be used to gauge hemodynamic severity and to predict subsequent stroke. The degree of flow impairment may also be ascertained by quantitative MRA (QMRA). We analyzed performance of these noninvasive imaging parameters to estimate risk of subsequent posterior circulation events in VERiTAS. Methods: TOF-MRA data and QMRA were simultaneously acquired in VERiTAS. SIR were derived from TOF source images and normalized for analysis with volume flow ratios (VFR) on QMRA at standard anatomical landmarks and across the maximal stenosis. Statistics analyzed the correlation between SIR and VFR, and the ability of each to predict clinical events. Results: 72 subjects (mean age 65.6±10.3 years, 32 (44%) women) with posterior circulation atherosclerosis were enrolled in VERiTAS. Posterior communicating artery (PCOMM) flow to the posterior circulation was detected in 85% on the right, in 86% on the left, with bilateral PCOMM flow in 78%. Fractional flow measures or SIR across the maximal stenotic lesion evident on TOF MRA was reduced in 43%, increased in 16%, with no change in 40%. SIR from the proximal to distal basilar artery segments increased in 62%, was unchanged in 33% and decreased in 4% of cases. SI and VFR exhibited limited correlation at corresponding arterial segments. QMRA VFR indicative of low distal flow status predicted subsequent clinical events, unlike SIR. Conclusions: Evaluation of hemodynamics in posterior circulation atherosclerosis reveals superiority of QMRA to SIR in prospectively predicting recurrent ischemia. Collateral circulation, tandem disease and unique aspects of vertebrobasilar atherosclerosis likely influence the utility of SIR on TOF MRA.

This invited personal story, covering the period from 1979 to 2010, describes the discovery of the dependence of the transverse relaxation time of water in blood on the oxygenation state of hemoglobin in the erythrocytes. The underlying mechanism of the compartmentation of the different magnetic susceptibilities of hemoglobin in its different oxygenation states also explains the mechanism that underlies blood oxygenation level dependent contrast used in fMRI. The story begins with the initial observation of line broadening during ischemia in small rodents detected by in vivo 31P NMR spectroscopy at high field. This spectroscopic line broadening or T2* relaxation effect was demonstrated to be related to the oxygenation state of blood. The effect was quantified more accurately using T2 values measured by the Carr-Purcell-Meiboom-Gill method. The effect was dependent on the integrity of the erythrocytes to compartmentalize the different magnetic susceptibilities produced by the changing spin state of the ferrous iron of hemoglobin in its different oxygenation states between the erythrocytes and the suspending solution. The hematocrit and magnetic field dependence, the requirement for erythrocyte integrity and lack of T1 dependence confirmed that the magnetic susceptibility effect explained the oxygenation state dependence of T2* and T2. This T2/T2* effect was combined with T1 based measurements of blood flow to measure oxygen consumption in animals. This blood oxygenation assay and its underlying magnetic susceptibility gradient mechanism was published in the biochemistry literature in 1982 and largely forgotten. The observation was revived to explain evolving imaging features of cerebral hematoma as MR imaging of humans increased in field strength to 1.5 T by the mid 1980s. Although the imaging version of this assay was used to measure a global metabolic rate of cerebral oxygen consumption in humans at 1.5-T by 1991, the global measurement had little clinical value. By contrast, a decade after the spectroscopic observation, imaging experiments performed on rodents at 7 T by Ogawa and colleagues identified the extravascular T2* imaging characteristics of the blood oxygenation effect and, most importantly, associated that change with brain functional states. Ogawa appropriately branded this blood oxygenation level dependent mechanism as BOLD contrast. This mechanism was subsequently shown to be the basis of localized MR signal changes associated with local brain function. This connection led to the fMRI revolution in human brain mapping.

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.

The rapid transverse relaxation of the sodium magnetic resonance signal during spatial encoding causes a loss of image resolution, an effect known as T2-blurring. Conventional wisdom suggests that spatial resolution is maximized by keeping the readout duration as short as possible to minimize T2-blurring. Flexible twisted projection imaging performed with an ultrashort echo time, relative to T2, and a long repetition time, relative to T1, 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. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc.

Background and Purpose— In-stent restenosis (ISR) after angioplasty/stenting for intracranial stenosis has been reported in up to 25% to 30% of patients. Detection and monitoring of ISR relies primarily on serial catheter angiography, because noninvasive imaging methods are typically hampered by stent-related artifact. We examined the value of serial vessel flow measurements using quantitative magnetic resonance angiography (QMRA) in detection of ISR. Material and Methods— Records of patients undergoing stenting for intracranial symptomatic stenosis >50% between 2005 and 2009 were retrospectively reviewed. Angiographic images were graded by a blinded neurointerventionalist for stenosis pretreatment, immediately after treatment, and during follow-up. Flow in the affected vessel measured by QMRA was recorded; >25% reduction in flow was considered indicative of an adverse change. Clinical data regarding neurological outcome were also collected. Results— Twenty-eight patients underwent stenting during the time interval studied. Of these, 12 patients (mean age, 55.5 years; 8 female) had contemporaneous angiography and QMRA and were analyzed. Median follow-up was 9 months. Six patients (50%) demonstrated angiographic restenosis 2 to12 months after treatment; all had an analogous decrease in flow in the vessel of interest. Of 3 patients with more severe flow decrement (>50%), 2 experienced stroke. None of the patients without angiographic ISR demonstrated a flow decrease on QMRA. Conclusions— In this preliminary series, flow decrease on QMRA is highly predictive of angiographic ISR. Additionally, the degree of flow decrement correlates with symptomatic ISR. QMRA may provide a useful noninvasive tool for serial monitoring after intracranial stenting.

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.

The standard of care for the comprehensive treatment of high-grade primary brain tumors includes surgery, radiation treatment and chemotherapy. Magnetic resonance (MR) imaging is involved in the initial diagnosis for detection and characterization of the lesion, focusing on size, location and its effect on surrounding brain and then on the heterogeneity of the signal characteristics, the presence of hemorrhage, MR perfusion characteristics and integrity of the blood-brain-barrier. These imaging properties have been correlated with tumor grade that has prognostic significance. Functional MRI can be used for presurgical planning and for image guidance of the surgical procedures (biopsy, resection) to minimize disruption of eloquent cortex. The surgical debulking is not considered curative for high-grade tumors but a preliminary step towards improving response to the subsequent treatments. After a short recovery period to allow some degree of healing of the surgical site, radiation planning and treatment begins. The radiation planning uses the X-ray attenuation coefficients from computed tomography (CT) to design the distribution of the radiation used in the treatment plan. Advantage is taken of the better display of tumors on MRI by fusing the MR and CT images. The course of radiation involves fractionated targeted radiation projected along multiple beams at many angles to achieve high dose over the tumor volume and margins while minimizing the dose to surrounding normal brain. The radiation is fractionated, usually administered for 5 days per week over about 6 weeks to a total dose of about 55 Gy. Imaging is not routinely performed during radiation treatment. Symptoms of brain swelling are controlled by use of oral steroids. Chemotherapy at low dose may be delivered during radiation treatment. Full dose, single agent chemotherapy then follows after the completion of radiation and is administered over multiple cycles to maintain tumor control. Follow-up MR imaging studies begin after radiation treatment is completed and are then performed every few months or more frequently depending on the clinical status of the patient. Although this protocol has been developed based on experience from large numbers of patients in multi-center trials, the prognosis has not changed in three decades (20% survival at 2 yrs, [1]). This extremely poor success rate for a not insignificant neoplasm, despite such this comprehensive protocol after decades of experience, suggests that there is a fundamental oversight in the current treatment of this disease. This material provides an imaging perspective of how regional responses of primary brain tumors may be examined during treatment to guide a flexible treatment plan to the response of each patient’s tumor, rather than using a fixed rigid protocol based on population studies. Sodium imaging provides a direct measurement of cell density that can be used to measure regional cell kill during treatment. These bioscales of regionally and temporally sensitive biological-based parameters may be helpful to measure tumor responsiveness that the oncologists can use to guide treatment for each patient. The suggestions are speculative and still being examined experimentally but are presented to challenge the medical community to be receptive to changes in the standard of care when that standard continues to fail.

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.

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 (

Accurate detection of low contrast-to-noise ratio (CNR) blood oxygenation level dependent (BOLD) signals in functional magnetic resonance imaging (fMRI) data is important for presurgical planning and cognitive research. Robust detection is challenging in small regions of low CNR activation since the probability of detecting each individual voxel is low. We present a processing technique for improving the detection of localized low CNR BOLD signals in fMRI data. When applied to synthetic fMRI data, this blind estimation scheme significantly improves the probability of correctly detecting voxels in a small region of activation with a CNR between 0.5 and 1.0 compared to the standard general linear model approach. More activation is detected in expected (based on input stimulus) regions of experimental data after processing with the proposed technique.

Cerebrovascular disease is a heterogeneous disease that may require objective criteria for developing optimal recurrent stroke prevention strategies. Magnetic resonance (MR) imaging and angiography together with MR perfusion and functional MR imaging provide sufficient parameters to tailor medical and surgical interventions for each patient and to monitor disease compensation or progression. These MR imaging procedures are demonstrated by clinical cases of advanced cerebrovascular pathology in which treatment varied from medical management to surgical intervention.

Background and Purpose— Atherosclerotic vertebrobasilar disease is an important cause of posterior circulation stroke. To examine the role of hemodynamic compromise, a prospective multicenter study, Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS), was conducted. Here, we report clinical features and vessel flow measurements from the study cohort. Methods— Patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries (BA) were enrolled. Large-vessel flow in the vertebrobasilar territory was assessed using quantitative MRA. Results— The cohort (n=72; 44% women) had a mean age of 65.6 years; 72% presented with ischemic stroke. Hypertension (93%) and hyperlipidemia (81%) were the most prevalent vascular risk factors. BA flows correlated negatively with percentage stenosis in the affected vessel and positively to the minimal diameter at the stenosis site ( P P P =0.01). Distal flow status assessment, based on an algorithm incorporating collateral flow by examining distal vessels (BA and posterior cerebral arteries), correlated neither with multifocality of disease nor with severity of the maximal stenosis. Conclusions— Flow in stenotic posterior circulation vessels correlates with residual diameter and drops significantly with tandem disease. However, distal flow status, incorporating collateral capacity, is not well predicted by the severity or location of the disease.

Object Neural cell transplantation has been proposed as a treatment after stroke. The purpose of this study was to establish if human neural stem cells (HNSCs) could survive in the nonhuman primate brain after an ischemic event. Methods Three adult cynomolgus monkeys received a unilateral occlusion of the M1 segment of the right middle cerebral artery (MCA). One week later each animal received five magnetic resonance (MR) image–guided stereotactic intracerebral injections of HNSC neurospheres labeled with bromodeoxyuridine (BrdU) in the areas surrounding the ischemic lesion as defined in T1- and T2-weighted images. On the day of transplantation and throughout the study the monkeys received oral cyclosporine (10 mg/kg twice a day), and plasma levels were monitored routinely. The animals were killed at 45, 75, or 105 days after transplantation. Magnetic resonance images revealed a cortical and subcortical infarction in the MCA distribution area. Postmortem morphological brain analyses confirmed the distribution of the infarcted area seen in the MR images, with loss of tissue and necrosis in the ischemic region. Cells that were positive for BrdU were present in the three experimental monkeys, mainly along injection tracks. Double-label immuno-fluorescence for BrdU and βIII-tubulin (a marker of young neurons) revealed colocalization of few HNSCs, most of which were observed outside the immediate injection site. Colocalization with nestin was also observed, indicating an early neural/glial fate. Conclusions In a model of stroke in nonhuman primates, HNSCs can survive up to 105 days when transplanted 1 week after an ischemic event and can partly undergo neuronal differentiation.

This paper reviews a body of work conducted in our laboratory that applies functional magnetic resonance imaging (fMRI) to better understand the biological response and change that occurs during prototype-distortion learning. We review results from two experiments (Little, Klein, Shobat, McClure, & Thulborn, 2004; Little & Thulborn, 2005) that provide support for increasing neuronal efficiency by way of a two-stage model that includes an initial period of recruitment of tissue across a distributed network that is followed by a period of increasing specialization with decreasing volume across the same network. Across the two studies, participants learned to classify patterns of random-dot distortions (Posner & Keele, 1968) into categories. At four points across this learning process subjects underwent examination by fMRI using a category-matching task. A large-scale network, altered across the protocol, was identified to include the frontal eye fields, both inferior and superior parietal lobules, and visual cortex. As behavioral performance increased, the volume of activation within these regions first increased and later in the protocol decreased. Based on our review of this work we propose that: (i) category learning is reflected as specialization of the same network initially implicated to complete the novel task, and (ii) this network encompasses regions not previously reported to be affected by prototype-distortion learning.

Eighteen healthy young adults underwent event-related (ER) functional magnetic resonance imaging (fMRI) of the brain while performing a visual category learning task. The specific category learning task required subjects to extract the rules that guide classification of quasi-random patterns of dots into categories. Following each classification choice, visual feedback was presented. The average hemodynamic response was calculated across the eighteen subjects to identify the separate networks associated with both classification and feedback. Random-effects analyses identified the different networks implicated during the classification and feedback phases of each trial. The regions included prefrontal cortex, frontal eye fields, supplementary motor and eye fields, thalamus, caudate, superior and inferior parietal lobules, and areas within visual cortex. The differences between classification and feedback were identified as (i) overall higher volumes and signal intensities during classification as compared to feedback, (ii) involvement of the thalamus and superior parietal regions during the classification phase of each trial, and (iii) differential involvement of the caudate head during feedback. The effects of learning were then evaluated for both classification and feedback. Early in learning, subjects showed increased activation in the hippocampal regions during classification and activation in the heads of the caudate nuclei during the corresponding feedback phases. The findings suggest that early stages of prototype-distortion learning are characterized by networks previously associated with strategies of explicit memory and hypothesis testing. However as learning progresses the networks change. This finding suggests that the cognitive strategies also change during prototype-distortion learning.

Large individual differences are commonly observed during the early stages of category learning in both functional MRI (fMRI) activation maps and behavioral data. The current investigation characterizes this variability by correlating the volume of activation with behavioral performance. Healthy subjects were trained to classify patterns of random dots into categories. Training was carried out using a 4-choice categorization task with feedback. Functional MRI was performed prior to any training and then following each of 3 training sessions. The fMRI sessions involved the presentation of 3 separate paradigms which required the skill imparted by the training to determine whether two patterns of dots belonged to the same category. Contrasts between the 3 paradigms allowed the examination of the effects of training and of familiarity with the task. For fMRI performed with those materials used during training, increases in the volume of activation were observed initially. As behavioral performance continued to improve, reductions in activation were observed across regions involved in visuospatial processing and spatial attention. These reductions in activation were observed only for those materials used in training and only after high levels of performance were achieved. The magnitude of these reductions in activation correlated with each individual's own rate of learning. The present data support the observation that at least two stages of cortical activation underlie the use of newly learned categories. The first, recruitment of nearby tissue, is observed as initial increases in the volumes of activation. These initial stages of recruitment are followed by specialization across the same network which is observed as a reduction in activation with continued improvements in behavioral performance.

Pain-related cerebral activation in functional magnetic resonance imaging shows less consistent signals that decay earlier than in conventional task-related activation. This may result from pain's top-down inhibition mediated by cognitive or hemodynamic interaction that could affect activation by other modalities. Using event-related functional magnetic resonance imaging, we examined whether pain affects cerebral activation by a saccade task through such cross-modal interaction. Six right-handed volunteers underwent whole-brain echo-planar imaging on a 3.0 T magnetic resonance imaging scanner while they received thermal pain stimulus at 50 degrees C on the right forearm (P; n = 6), performed a visually guided saccade task (V; n = 6), and went through a simultaneous pain-plus-saccade paradigm (PV; n = 5). Averaged functional activation maps were synthesized and signal time courses were analyzed at activation clusters. P activated the bilateral secondary somatosensory cortex (S2). V activated the posterior, supplementary, frontal eye fields, and visual areas. PV enhanced the S2 activation and activated additional pain-related areas, including the bilateral premotor area, right insula, anterior, and posterior cingulate cortices. In contrast, V-related activation was attenuated in PV. We propose that pain caused cross-modal suppression on the oculomotor activity and that an oculomotor task enhanced pain-related activation by triggering attention toward pain.Pain-related cerebral activation is enhanced by attention toward pain. It may involve top-down suppression over the unrelated neural networks of saccade.

Sodium MR imaging at 3.0 T provides high-quality images in acceptable acquisition times that allow assessment of tissue viability as defined by maintenance of sodium ion homeostasis. This application is made feasible for clinical stroke evaluation by an efficient projection pulse sequence with extremely short echo time values. This twisted projection imaging provides high signal-to-noise images at adequate resolution (5 x 5 x 5 mm(3)) in less than 10 minutes at 3.0 T. The images are quantified as tissue sodium concentration (TSC) maps that can be interpreted directly in terms of tissue viability. With infarction, baseline TSC values of less than 45 mmol/L increase at variable rates to approximately 70 mmol/L, allowing monitoring of the progression of stroke pathophysiology.

The basal ganglia, motor cortex, and cerebellum have been implicated as a circuit that codes for movement velocity. Since movement velocity covaries with the magnitude of force exerted and previous studies have shown that similar regions scale in activation for velocity and force, the scaling of neuronal activity with movement velocity could be due to the force exerted. The present study implemented a parametric functional magnetic resonance imaging (fMRI) design to determine which brain regions directly scale with the rate of change of force production, independent of the magnitude of force exerted. Nine healthy adults produced force with their right middle finger and thumb at 25% of their maximal voluntary contraction across four conditions: (1) fast pulse, (2) fast hold, (3) medium hold, and (4) slow hold. There were three primary findings: (i) the activation volume in multiple regions increased with the duration of the force contraction, (ii) only the activation volume in the bilateral internal globus pallidus and left subthalamic nucleus parametrically scaled with the rate of change of force production, and (iii) there was an inverse relation between the activation volume in the subthalamic nucleus and internal globus pallidus with the rate of change of force production. The current findings are the first to have used neuroimaging techniques in humans to segregate the functional anatomy of the internal globus pallidus from external globus pallidus, distinguish functional activation in the globus pallidus from the putamen, and demonstrate task-dependent scaling in the subthalamic nucleus and internal globus pallidus. We conclude that fast, ballistic force production is preprogrammed, requiring a small metabolic demand from the basal ganglia. In contrast, movements that require the internal regulation of the rate of change of force are associated with increased metabolic demand from the subthalamic nucleus and internal segment of the globus pallidus.

In this paper, we propose an approach to modeling functional magnetic resonance imaging (fMRI) data that combines hierarchical polynomial models, Bayes estimation, and clustering. A cubic polynomial is used to fit the voxel time courses of event-related design experiments. The coefficients of the polynomials are estimated by Bayes estimation, in a two-level hierarchical model, which allows us to borrow strength from all voxels. The voxel-specific Bayes polynomial coefficients are then transformed to the times and magnitudes of the minimum and maximum points on the hemodynamic response curve, which are in turn used to classify the voxels as being activated or not. The procedure is demonstrated on real data from an event-related design experiment of visually guided saccades and shown to be an effective alternative to existing methods.

Objective: To test the hypothesis that deficits in spatial working memory in autism are due to abnormalities in prefrontal circuitry. Methods: Functional MRI (fMRI) at 3 T was performed in 11 rigorously diagnosed non–mentally retarded autistic and six healthy volunteers while they performed an oculomotor spatial working memory task and a visually guided saccade task. Results: Autistic subjects demonstrated significantly less task-related activation in dorsolateral prefrontal cortex (Brodmann area [BA] 9/46) and posterior cingulate cortex (BA 23) in comparison with healthy subjects during a spatial working memory task. In contrast, activation of autistic individuals was not reduced in other regions comprising the neural circuitry for spatial working memory including the cortical eye fields, anterior cingulate cortex, insula, basal ganglia, thalamus, and lateral cerebellum. Autistic subjects also did not demonstrate reduced activation in any brain regions while performing visually guided saccades. Conclusion: Impairments in executive cognitive processes in autism may be subserved by abnormalities in neocortical circuitry as evidenced by decreased activation in prefrontal and posterior cingulate circuitry during a spatial working memory task.

Recent positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies in humans have localized the frontal eye field (FEF) to the precentral sulcus (PCS). In macaque monkeys, low-threshold microstimulation and single unit recording studies have located a saccadic subregion of FEF in a restricted area along the anterior wall of the arcuate sulcus and a pursuit subregion located deeper in the sulcus close to the fundus. The functional organization and anatomical location of these two FEF subregions are still to be defined in humans. In the present study, we used fMRI with high spatial resolution image acquisition at 3.0 Tesla to map the saccade- and pursuit-related areas of FEF within the two walls of the PCS in 11 subjects. We localized the saccade-related area to the upper portion of the anterior wall of the precentral sulcus and the pursuit-related area to a deeper region along the anterior wall, extending in some subjects to the fundus or deep posterior wall. These findings localize distinct pursuit and saccadic subregions of FEF in humans and demonstrate a high degree of homology in the organization of these FEF subregions in the human and the macaque monkey.

Background Although pain-related activation was localized in multiple brain areas by functional imaging, the temporal profile of its signal has been poorly understood. The authors characterized the temporal evolution of such activation in comparison to that by conventional visual and motor tasks using functional magnetic resonance imaging. Methods Five right-handed volunteers underwent whole brain echo-planar imaging on a 3 T magnetic resonance imaging scanner while they received pain stimulus on the right and left forearm and performed visually guided saccade and finger tapping tasks. Pain stimulus on the right and left forearm consisted of four cycles of 15-s stimulus at 47.2-49.0 degrees C, interleaved with 30-s control at 32 degrees C, delivered by a Peltier-type thermode, and visually guided saccade and finger tapping of three cycles of 30-s active and 30-s rest conditions. Voxel-wise t statistical maps were standardized and averaged across subjects. Blood oxygenation level-dependent signal time courses were analyzed at local maxima of representative activation clusters (t > 3.5). Results Pain stimulus on the right forearm activated the secondary somatosensory (S2), superior temporal, anterior cingulate, insular, prefrontal cortices, premotor area, and lenticular nucleus. Pain stimulus on the left forearm activated similar but fewer areas at less signal intensity. The S2 activation was dominant on the contralateral hemisphere. Pain-related activation was statistically weaker and showed less consistent signal time courses than visually guided saccade- and finger tapping-related activation. Pain-related signals decayed earlier before the end of stimulus, in contrast to well-sustained signal plateaus induced by visually guided saccade and finger tapping. Conclusions The authors speculate that pain-related blood oxygenation level-dependent signals were attenuated by the pain-induced global cerebral blood flow decrease or activation of the descending pain inhibitory systems.

Introduction: Atherosclerotic vertebrobasilar disease (VBD) is a significant etiology of posterior circulation stroke. In addition to thromboembolism, regional hypoperfusion is considered an important potential contributor to stroke risk. To examine the role of hemodynamic compromise in VBD, a prospective observational multi-center study, Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS), has recently been conducted. Here we report baseline features and vessel flow measurements from the study cohort. Methods: Baseline demographic and clinical data was collected in patients with recent vertebrobasilar TIA or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative MRA (QMRA). Results: The cohort (n=75, 56% male) had a mean age of 65.5 (range 40 to 90) years; two thirds presented with ischemic stroke. Hypertension (93%) and hyperlipidemia (79%) were the most prevalent vascular risk factors. Vertebral and basilar artery flows correlated negatively with degree of stenosis in the affected vessel, and positively to the minimal diameter at the site of stenosis (p Conclusions: Flow in stenotic posterior circulation vessels correlate with residual diameter and stenosis and drop significantly in the setting of tandem disease. However, distal flow status, incorporating collateral capacity, is not well predicted by the severity or location of the disease. Final clinical outcome results from the ongoing VERiTAS study will further clarify the relevance of anatomic stenosis and hemodynamic assessment to predicting stroke risk in patients with vertebrobasilar disease.

Conventional clinical magnetic resonance (MR) imaging is the modality of choice when examining the human central nervous system. Exquisite anatomical images are readily derived from the MR signal of the hydrogen nuclei of water molecules. However, although biology is critically dependent on an aqueous milieu, the complex interactions of metabolism that constitute life processes involve many molecules containing other elements such as carbon, phosphorus, oxygen, nitrogen, sodium, and potassium, all of which have MR signals. The slow development of clinical applications exploiting these other nuclei reflects the lower MR sensitivity and greater MR complexity of these elements and the lower concentrations of the metabolites made up from these elements compared to water protons. The high clinical relevance of the information that can be derived from these nuclei continues to drive the development of ultrahigh magnetic field scanners for human studies and acquisition strategies that can provide the signal-to-noise ratio (SNR) for quantification of pertinent parametric maps that have been termed bioscales. This chapter will describe the methodology that can be used to meet the clinical potential of bioscales developed for sodium (23Na) and oxygen (17O). The SNR challenge for quantification of phosphorus (31P) and potassium (39K) imaging has yet to be met, even at 9.4 T, in acceptable acquisition times and at spatial resolutions pertinent to the human brain.