Neuropsychological Test Performance Differentiates Subgroups of Individuals With Adult Moyamoya Disease: A Cross-Sectional Clinical Study.

BACKGROUND AND OBJECTIVES: Moyamoya disease (MMD) is a rare noninflammatory disorder involving progressive intracranial vasculopathy and impaired cerebral blood flow in the anterior circulation, resulting in stroke and cognitive impairment. We aimed to characterize cognitive impairment and the possible predictive value of sociodemographic and clinical characteristics of adults with MMD. METHODS: This cross-sectional study examined neurocognitive performance in a group of 42 consecutive adult patients (mean age = 40.52 years; 69% female) referred for a presurgical neuropsychological evaluation. Neuropsychological functioning was assessed with a comprehensive battery, and cognitive dysfunction was defined as 1.5 SDs below the mean. Neurocognitive performance correlated with clinical/demographic characteristics and disease markers. RESULTS: Most patients (91%) had a history of stroke, and 45% had cognitive deficits, most notably on measures of attention/speed (48%), executive functioning (47%), visuoconstruction (41%), and memory (31%-54%). Only higher educational attainment and poor collateral blood flow in the right hemisphere differentiated cognitively impaired (n = 19) and intact groups (n = 23), and MMD-related characteristics (eg, disease duration, stroke history) did not differentiate the 2 groups. CONCLUSION: Consistent with previous work, frontal-subcortical cognitive deficits (eg, deficits in mental speed, attention, executive functioning) were found in nearly half of patients with MMD and better cognitive performance was associated with factors related to cognitive reserve. Angiographic metrics of disease burden (eg, Suzuki rating, collateral flow) and hemodynamic reserve were not consistently associated with poorer cognitive outcomes, suggesting that cognition is a crucial independent factor to assess in MMD and has relevance for treatment planning and functional status.

Gender differences in cell volume fraction (CVF): a structural parameter reflecting the energy efficiency of maintaining the resting membrane potential.

The cell volume fraction (CVF) of the human brain is high (~82%) and is preserved across healthy aging while the brain declines in volume. These two observations, supported by several independent techniques, suggest that CVF is an important structural parameter. A new biophysical model is presented that incorporates CVF into the Goldman equation of classical membrane electrophysiology. The Goldman equation contains few structural constraints beyond two compartments separated by a semipermeable membrane supporting ion gradients. As potassium is the most permeable ion in the resting state, the resting membrane potential is determined by the potassium ion gradient. This biophysical model indicates that the sodium-potassium ion pumps use less energy at high CVF to maintain the resting membrane potential, explaining the high value of CVF and its conservation with healthy aging. CVF is measured to be statistically significantly higher in the brains of males compared with females, suggesting a structural requirement for higher energy efficiency in the larger male brain to support the greater number of neurons and synapses. As CVF can be measured in humans using quantitative sodium MRI and has potential implications for brain health, CVF may be a quantitative parameter that is useful for assessment of brain health, especially in patients with diseases such as dementia and psychiatric disease that do not have anatomical correlates detectable by clinical proton MRI.

High-resolution sodium imaging using anatomical and sparsity constraints for denoising and recovery of novel features.

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.

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.

Stenosis Before Thrombosis: Intracranial Hypertension from Jugular Foramen Stenosis Secondary to Renal Osteodystrophy.

BACKGROUND: Venous outflow obstructions are rare anatomic findings that can appear with symptoms of elevated intracranial pressure, including headache and vision loss, and can be mistaken for more common diagnoses, such as idiopathic intracranial hypertension (IIH) or cerebral venous sinus thrombosis (CVST). Although venous outflow obstructions have been reported in rare bone dysplasias and congenital abnormalities, to date they have not been reported in renal osteodystrophy (ROD), a relatively common disorder seen in patients with chronic kidney disease. CASE DESCRIPTION: In this case, the authors describe a patient with marked intracranial hypertension from jugular foramen stenosis secondary to ROD. After diagnosis by CT and magnetic resonance venography, catheter venography confirmed an osseus band around the left jugular bulb, and a 40-mm Hg pressure gradient across the stenotic foramen. The patient subsequently underwent ventriculoperitoneal shunting and optic nerve sheath fenestration with symptom improvement. The postoperative course was significant for development of CVST, necessitating treatment. CONCLUSIONS: This report reviews the presentation, pathology, and neurosurgical treatment of patients with ROD and venous outflow obstructions, and explores the differential diagnoses of outflow obstructions, IIH, and CVST. To our knowledge, this is the first report of intracranial hypertension from jugular foramen stenosis secondary to renal osteodystrophy.

Quantitative sodium MR imaging: A review of its evolving role in medicine.

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.

Toward 20 T magnetic resonance for human brain studies: opportunities for discovery and neuroscience rationale.

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.

Effect of Hemodynamics on Stroke Risk in Symptomatic Atherosclerotic Vertebrobasilar Occlusive Disease.

IMPORTANCE: Atherosclerotic vertebrobasilar (VB) occlusive disease is a significant etiology of posterior circulation stroke, with regional hypoperfusion as an important potential contributor to stroke risk. OBJECTIVE: To test the hypothesis that, among patients with symptomatic VB stenosis or occlusion, those with distal blood flow compromise as measured by large-vessel quantitative magnetic resonance angiography (QMRA) are at higher risk of subsequent posterior circulation stroke. DESIGN, SETTING, AND PARTICIPANTS: A prospective, blinded, longitudinal cohort study was conducted at 5 academic hospital-based centers in the United States and Canada; 82 patients from inpatient and outpatient settings were enrolled. Participants with recent VB transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries underwent large-vessel flow measurement in the VB territory using QMRA. Physicians performing follow-up assessments were blinded to QMRA flow status. Follow-up included monthly telephone calls for 12 months and biannual clinical visits (for a minimum of 12 months, and up to 24 months or the final visit). Enrollment took place from July 1, 2008, to July 31, 2013, with study completion on June 30, 2014; data analysis was performed from October 1, 2014, to April 10, 2015. EXPOSURE: Standard medical management of stroke risk factors. MAIN OUTCOMES AND MEASURES: The primary outcome was VB-territory stroke. RESULTS: Of the 82 enrolled patients, 72 remained eligible after central review of their angiograms. Sixty-nine of 72 patients completed the minimum 12-month follow-up; median follow-up was 23 (interquartile range, 14-25) months. Distal flow status was low in 18 of the 72 participants (25%) included in the analysis and was significantly associated with risk for a subsequent VB stroke (P = .04), with 12- and 24-month event-free survival rates of 78% and 70%, respectively, in the low-flow group vs 96% and 87%, respectively, in the normal-flow group. The hazard ratio, adjusted for age and stroke risk factors, in the low distal flow status group was 11.55 (95% CI, 1.88-71.00; P = .008). Medical risk factor management at 6-month intervals was similar between patients with low and normal distal flow. Distal flow status remained significantly associated with risk even when controlling for the degree of stenosis and location. CONCLUSIONS AND RELEVANCE: Distal flow status determined using a noninvasive and practical imaging tool is robustly associated with risk for subsequent stroke in patients with symptomatic atherosclerotic VB occlusive disease. Identification of high-risk patients has important implications for future investigation of more aggressive interventional or medical therapies.

Hemodynamic Features of Symptomatic Vertebrobasilar Disease.

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<0.01). A relative threshold effect was evident, with flows dropping most significantly with ≥80% stenosis/occlusion (P<0.05). Tandem disease involving the BA and either/both vertebral arteries had the greatest negative impact on immediate downstream flow in the BA (43 mL/min versus 71 mL/min; 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.

Effect of age and vascular anatomy on blood flow in major cerebral vessels.

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.

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.

Combined direct and indirect bypass for moyamoya: quantitative assessment of direct bypass flow over time.

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 to 12 ± 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.

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.

Reproducibility of activation maps for longitudinal studies of visual function by functional magnetic resonance imaging.

PURPOSE: To test the intra- and intersubject reproducibility of brain activation patterns that underlie visually guided saccades and word recognition in normally sighted subjects and patients with macular degeneration using functional magnetic resonance imaging (fMRI). METHODS: Ten normally sighted subjects and five patients with macular degeneration were asked to perform two visually guided saccade tasks and two word-recognition tasks during fMRI with behavioral monitoring. The fMRI measurements were repeated three times at intervals of at least 4 weeks between sessions. The intrasubject reproducibility of the brain activation patterns was examined in a model-independent manner by comparing the distributions of activation across the frontal, parietal, temporal, and occipital brain lobes using Intraclass Correlation Coefficients (ICCs). Intersubject reproducibility was examined by repeated-measure ANOVA. Results. Control subjects showed overall higher intrasubject reproducibility of brain activation patterns (75% ICCs > 0.5) than that of patients with macular degeneration (56% ICCs > 0.5). The intrasubject reproducibility for the patients improved when the target location was fixed, as in the word-recognition tasks (75% ICCs > 0.5), compared with the visually saccade tasks (37% ICCs > 0.5). Intersubject variability of brain activation patterns was strikingly high for both the control and patient groups. CONCLUSIONS: The fMRI method can serve as a reliable within-subjects measure of brain activation that has potential for measuring longitudinal changes in brain networks associated with rehabilitation training. Striking intersubject variability reflected at the level of lobes of the brain among control subjects with similar behavioral performance, suggests individual analysis is necessary when implementing longitudinal brain activation studies.

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.

My starting point: the discovery of an NMR method for measuring blood oxygenation using the transverse relaxation time of blood water.

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.

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.