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Purpose Placental dysfunction plays a key role in diseases that affect the fetus in utero and after birth. Aiming to develop a platform for validating in vivo placental MRI and investigations into placental physiology, we designed and built a prototype MRI-compatible perfusion chamber with an integrated MRI receive coil for high SNR ex vivo placental imaging. Principal results After optimizing placenta vascular clearing and perfusion protocols, we performed contrast enhanced MR angiography and MR relaxometry on eight carefully selected placentas while they were perfused via the umbilical arteries (UAs). Additionally, two of these placentas underwent maternal perfusion via the intervillous space (IVS). Despite striving for homogenous perfusion across the whole placenta, imaging results were highly heterogeneous for both UA and IVS perfused placentas. By histology, we observed blood congestion in the villi in regions that showed low UA perfusion during MRI. In two placentas prominent chorionic arteries followed by adjacent veins underwent contrast enhancement in the absence of villous capillary blush. The single placenta from a pregnancy affected by IUGR had the most homogeneous villous capillary perfusion. Major conclusions A dual perfusion system for ex vivo placentas compatible with MRI permitted assessment of UA and IVS placental perfusion. We observed spatial UA perfusion heterogeneity and evidence for arteriovenous shunting in placentas from normal pregnancies and deliveries, but relative villous capillary perfusion homogeneity in a single IUGR placenta. Future work will focus on system optimization, followed by physiological manipulation and validation of in vivo placental MRI.

Metabolic imaging of the human brain by in-vivo magnetic resonance spectroscopic imaging (MRSI) can non-invasively probe neurochemistry in healthy and disease conditions. MRSI at ultra-high field (≥ 7 T) provides increased sensitivity for fast high-resolution metabolic imaging, but comes with technical challenges due to non-uniform B0 field. Here, we show that an integrated RF-receive/B0-shim (AC/DC) array coil can be used to mitigate 7 T B0 inhomogeneity, which improves spectral quality and metabolite quantification over a whole-brain slab. Our results from simulations, phantoms, healthy and brain tumor human subjects indicate improvements of global B0 homogeneity by 55%, narrower spectral linewidth by 29%, higher signal-to-noise ratio by 31%, more precise metabolite quantification by 22%, and an increase by 21% of the brain volume that can be reliably analyzed. AC/DC shimming provide the highest correlation (R2 = 0.98, P = 0.001) with ground-truth values for metabolite concentration. Clinical translation of AC/DC and MRSI is demonstrated in a patient with mutant-IDH1 glioma where it enables imaging of D-2-hydroxyglutarate oncometabolite with a 2.8-fold increase in contrast-to-noise ratio at higher resolution and more brain coverage compared to previous 7 T studies. Hence, AC/DC technology may help ultra-high field MRSI become more feasible to take advantage of higher signal/contrast-to-noise in clinical applications.

© 2020 Elsevier Ltd Introduction: Before using blood-oxygen-level-dependent magnetic resonance imaging (BOLD MRI) during maternal hyperoxia as a method to detect individual placental dysfunction, it is necessary to understand spatiotemporal variations that represent normal placental function. We investigated the effect of maternal position and Braxton-Hicks contractions on estimates obtained from BOLD MRI of the placenta during maternal hyperoxia. Methods: For 24 uncomplicated singleton pregnancies (gestational age 27–36 weeks), two separate BOLD MRI datasets were acquired, one in the supine and one in the left lateral maternal position. The maternal oxygenation was adjusted as 5 min of room air (21% O2), followed by 5 min of 100% FiO2. After datasets were corrected for signal non-uniformities and motion, global and regional BOLD signal changes in R2* and voxel-wise Time-To-Plateau (TTP) in the placenta were measured. The overall placental and uterine volume changes were determined across time to detect contractions. Results: In mothers without contractions, increases in global placental R2* in the supine position were larger compared to the left lateral position with maternal hyperoxia. Maternal position did not alter global TTP but did result in regional changes in TTP. 57% of the subjects had Braxton-Hicks contractions and 58% of these had global placental R2* decreases during the contraction. Conclusion: Both maternal position and Braxton-Hicks contractions significantly affect global and regional changes in placental R2* and regional TTP. This suggests that both factors must be taken into account in analyses when comparing placental BOLD signals over time within and between individuals.

MR spectroscopic imaging (MRSI) noninvasively maps the metabolism of human brains. In particular, the imaging of D-2-hydroxyglutarate (2HG) produced by glioma isocitrate dehydrogenase (IDH) mutations has become a key application in neuro-oncology. However, the performance of full field-of-view MRSI is limited by B0 spatial nonuniformity and lipid artifacts from tissues surrounding the brain. Array coils that multiplex RF-receive and B0 -shim electrical currents (AC/DC mixing) over the same conductive loops provide many degrees of freedom to improve B0 uniformity and reduce lipid artifacts. AC/DC coils are highly efficient due to compact design, requiring low shim currents (

In fetal-brain MRI, head-pose changes between prescription and acquisition present a challenge to obtaining the standard sagittal, coronal and axial views essential to clinical assessment. As motion limits acquisitions to thick slices that preclude retrospective resampling, technologists repeat ~55-second stack-of-slices scans (HASTE) with incrementally reoriented field of view numerous times, deducing the head pose from previous stacks. To address this inefficient workflow, we propose a robust head-pose detection algorithm using full-uterus scout scans (EPI) which take ~5 seconds to acquire. Our ~2-second procedure automatically locates the fetal brain and eyes, which we derive from maximally stable extremal regions (MSERs). The success rate of the method exceeds 94% in the third trimester, outperforming a trained technologist by up to 20%. The pipeline may be used to automatically orient the anatomical sequence, removing the need to estimate the head pose from 2D views and reducing delays during which motion can occur., Comment: 19 pages, 10 figures, 2 tables, fetal MRI, head-pose detection, MSER, scan automation, scan prescription, slice positioning, final published version

© 2017 International Society for Magnetic Resonance in Medicine Purpose: QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption (QUIXOTIC) is a recent technique that measures voxel-wise oxygen extraction fraction (OEF) but suffers from long scan times, limiting its application. We implemented multiecho QUIXOTIC dubbed turbo QUIXOTIC (tQUIXOTIC) that reduces scan time eightfold and then applied it in functional MRI. Methods: tQUIXOTIC utilizes a novel turbo gradient spin echo readout enabling measurement of venular blood transverse relaxation rate in a single tag-control acquisition. Using tQUIXOTIC, we estimated cortical gray matter (GM) OEF, created voxel-by-voxel GM OEF maps, and quantified changes in visual cortex OEF during a blocked design flashing checkerboard visual stimulus. Contamination from cerebrospinal fluid partial volume averaging was estimated and corrected. Results: The average cortical GM OEF was estimated as 0.38 ± 0.06 (n = 8) using a 3.4-min acquisition. The average OEF in the visual cortex was estimated as 0.43 ± 0.04 at baseline and 0.35 ± 0.05 during activation, with an average %ΔOEF of −20%. These values are consistent with those of past studies. Conclusion: tQUIXOTIC successfully estimated cortical GM OEF in clinical scan times and detected changes in OEF during blocked design visual stimulation. tQUIXOTIC will be useful to monitor regional OEF clinically and in blocked design or event-related functional MRI experiments. Magn Reson Med 79:2713–2723, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

BACKGROUND AND PURPOSE:Imaging CBF is important for managing pediatric moyamoya. Traditional arterial spin-labeling MR imaging detects delayed transit thorough diseased arteries but is inaccurate for measuring perfusion because of these delays. Velocity-selective arterial spin-labeling is insensitive to transit delay and well-suited for imaging Moyamoya perfusion. This study assesses the accuracy of a combined velocity-selective arterial spin-labeling and traditional pulsed arterial spin-labeling CBF approach in pediatric moyamoya, with comparison to blood flow patterns on conventional angiography. MATERIALS AND METHODS:Twenty-two neurologically stable pediatric patients with moyamoya and 5 asymptomatic siblings without frank moyamoya were imaged with velocity-selective arterial spin-labeling, pulsed arterial spin-labeling, and DSA (patients). Qualitative comparison was performed, followed by a systematic comparison using ASPECTS-based scoring. Quantitative pulsed arterial spin-labeling CBF and velocity-selective arterial spin-labeling CBF for the middle cerebral artery, anterior cerebral artery, and posterior cerebral artery territories were also compared. RESULTS:Qualitatively, velocity-selective arterial spin-labeling perfusion maps reflect the DSA parenchymal phase, regardless of postinjection timing. Conversely, pulsed arterial spin-labeling maps reflect the DSA appearance at postinjection times closer to the arterial spin-labeling postlabeling delay, regardless of vascular phase. ASPECTS comparison showed excellent agreement (88%, κ = 0.77, P < .001) between arterial spin-labeling and DSA, suggesting velocity-selective arterial spin-labeling and pulsed arterial spin-labeling capture key perfusion and transit delay information, respectively. CBF coefficient of variation, a marker of perfusion variability, was similar for velocity-selective arterial spin-labeling in patient regions of delayed-but-preserved perfusion compared to healthy asymptomatic sibling regions (coefficient of variation = 0.30 versus 0.26, respectively, Δcoefficient of variation = 0.04), but it was significantly different for pulsed arterial spin-labeling (coefficient of variation = 0.64 versus 0.34, Δcoefficient of variation = 0.30, P < .001). CONCLUSIONS:Velocity-selective arterial spin-labeling offers a powerful approach to image perfusion in pediatric moyamoya due to transit delay insensitivity. Coupled with pulsed arterial spin-labeling for transit delay information, a volumetric MR imaging approach capturing key DSA information is introduced.

Purpose: We generate 12 models from 4 pregnant individuals to evaluate individual differences in local specific absorption rate (SAR) for differing body habitus and fetal and maternal positions. Methods: Structural MR images from 4 pregnant subjects (including supine and left-lateral maternal positions) were manually segmented to create 12 body models by rotating the fetus, modifying the fat content, and altering the maternal arm position in 1 of the subjects. Electromagnetic simulations modeled at 3 Tesla determined the average and peak local SAR in the maternal trunk, fetus, fetal brain, and amniotic fluid. Results: We observed a significant range of fetal and maternal peak local SAR across the models (maternal trunk: 19.14-44.03 watts/kg, fetus: 9.93-18.79 watts/kg, fetal brain 3.36-10.3 watts/kg). We found that maternal body habitus changes introduced a significant variation in the maternal peak local SAR but not the fetal local SAR. However, the maternal position (either rotating the mother to left–lateral position or altering the arm position) introduced changes in fetal peak local SAR (range: 11.9-17.9 watts/kg). Rotating the fetus also introduced variation in the fetal and fetal brain peak local SAR. Conclusion: The observed variation in SAR emphasizes the need for more anatomical models to enable better safety management of individuals during fetal MRI, including a wider range of gestational ages., National Institutes of Health (Grants U01 HD087211, R01 EB017337)

The performance and diagnostic utility of magnetic resonance imaging (MRI) in pregnancy is fundamentally constrained by fetal motion. Motion of the fetus, which is unpredictable and rapid on the scale of conventional imaging times, limits the set of viable acquisition techniques to single-shot imaging with severe compromises in signal-to-noise ratio and diagnostic contrast, and frequently results in unacceptable image quality. Surprisingly little is known about the characteristics of fetal motion during MRI and here we propose and demonstrate methods that exploit a growing repository of MRI observations of the gravid abdomen that are acquired at low spatial resolution but relatively high temporal resolution and over long durations (10–30 minutes). We estimate fetal pose per frame in MRI volumes of the pregnant abdomen via deep learning algorithms that detect key fetal landmarks. Evaluation of the proposed method shows that our framework achieves quantitatively an average error of 4.47 mm and 96.4% accuracy (with error less than 10 mm). Fetal pose estimation in MRI time series yields novel means of quantifying fetal movements in health and disease, and enables the learning of kinematic models that may enhance prospective mitigation of fetal motion artifacts during MRI acquisition.

Purpose: Susceptibility-based blood oxygenation measurements in small vessels of the brain derive from gradient echo (GRE) phase and can provide localized assessment of brain function and pathology. However, when vessel diameter becomes smaller than the acquisition voxel size, partial volume effects compromise these measurements. The purpose of this study was to develop a technique to improve the reliability of vessel oxygenation estimates in the presence of partial volume effects. Methods: Intravoxel susceptibility variations are present when a vessel and parenchyma experience partial volume effects, modifying the voxel's GRE phase signal and attenuating the GRE magnitude signal. Using joint utilization of magnitude and phase (JUMP), both vessel susceptibility and voxel partial volume fraction can be estimated, providing measurements of venous oxygen saturation (Yv) in straight, nearly vertical vessels that have improved robustness to partial volume effects. Results: JUMP was demonstrated by estimating vessel Yv in numerical and in vivo experiments. Deviations from ground truth of Yv measurements in vessels tilted up to 30° from B0 were reduced by over 50% when using JUMP compared with phase-only techniques. Conclusion: JUMP exploits both magnitude and phase data in GRE imaging to mitigate partial volume effects in estimation of vessel oxygenation. ©2017, NIH NIBIB (grant no. R01EB017337), NIH NIBIB (grant no. P41-EB015896), NIH NIBIB (grant no. 1U01MH093765), NIH NIBIB (grant no. R00EB012107), NIH NIBIB (grant no. R24MH106096), NIH NIBIB (grant no. T32 EB001680)

© 2017 International Society for Magnetic Resonance in Medicine Purpose: This article introduces a constrained imaging method based on low-rank and subspace modeling to improve the accuracy and speed of MR fingerprinting (MRF). Theory and Methods: A new model-based imaging method is developed for MRF to reconstruct high-quality time-series images and accurate tissue parameter maps (e.g., T1, T2, and spin density maps). Specifically, the proposed method exploits low-rank approximations of MRF time-series images, and further enforces temporal subspace constraints to capture magnetization dynamics. This allows the time-series image reconstruction problem to be formulated as a simple linear least-squares problem, which enables efficient computation. After image reconstruction, tissue parameter maps are estimated via dictionary-based pattern matching, as in the conventional approach. Results: The effectiveness of the proposed method was evaluated with in vivo experiments. Compared with the conventional MRF reconstruction, the proposed method reconstructs time-series images with significantly reduced aliasing artifacts and noise contamination. Although the conventional approach exhibits some robustness to these corruptions, the improved time-series image reconstruction in turn provides more accurate tissue parameter maps. The improvement is pronounced especially when the acquisition time becomes short. Conclusions: The proposed method significantly improves the accuracy of MRF, and also reduces data acquisition time. Magn Reson Med 79:933–942, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

PURPOSE: MRI-based skull segmentation is a useful procedure for many imaging applications. This study describes a methodology for automatic segmentation of the complete skull from a single T1-weighted volume. METHODS: The skull is estimated using a multi-atlas segmentation approach. Using a whole head computed tomography (CT) scan database, the skull in a new MRI volume is detected by nonrigid image registration of the volume to every CT, and combination of the individual segmentations by label-fusion. We have compared Majority Voting, Simultaneous Truth and Performance Level Estimation (STAPLE), Shape Based Averaging (SBA), and the Selective and Iterative Method for Performance Level Estimation (SIMPLE) algorithms. RESULTS: The pipeline has been evaluated quantitatively using images from the Retrospective Image Registration Evaluation database (reaching an overlap of 72.46 ± 6.99%), a clinical CT-MR dataset (maximum overlap of 78.31 ± 6.97%), and a whole head CT-MRI pair (maximum overlap 78.68%). A qualitative evaluation has also been performed on MRI acquisition of volunteers. CONCLUSION: It is possible to automatically segment the complete skull from MRI data using a multi-atlas and label fusion approach. This will allow the creation of complete MRI-based tissue models that can be used in electromagnetic dosimetry applications and attenuation correction in PET/MR. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

The non-invasive assessment of (patho-)physiological parameters such as, perfusion and oxygenation, is of great importance for the characterization of pathologies e.g., tumors, which may be helpful to better predict treatment response and potential outcome. To better understand the influence of physiological parameters on the investigated oxygenation and perfusion sensitive MRI methods, MRI measurements were correlated with subsequent invasive micro probe measurements during free breathing conditions of air, air+10% CO2 and 100% O2 in healthy mice brain. MRI parameters were the irreversible (R2), reversible (R2') and effective (R2*) transverse relaxation rates, venous blood oxygenation level assessed by quantitative blood oxygenation level dependent (qBOLD) method and cerebral blood flow (CBF) assessed by arterial spin labeling (ASL) using a 7 T small animal MRI scanner. One to two days after MRI, tissue perfusion and pO2 were measured by Laser-Doppler flowmetry and fluorescence quenching micro probes, respectively. The tissue pO2 values were converted to blood oxygen saturation by using the Hill equation. The animals were anesthetized by intra peritoneal injection of ketamine-xylazine-acepromazine (10-2-0.3 mg/ml · kg). Results for normal/hypercapnia/hyperoxia conditions were: R2[s(∧)-1] = 20.7/20.4/20.1, R2*[s(∧)-1] = 31.6/29.6/25.9, R2'[s-(∧)1] = 10.9/9.2/5.7, qBOLD venous blood oxygenation level = 0.43/0.51/0.56, CBF[ml · min(∧)-1 · 100 g(∧)-1] = 70.6/105.5/81.8, Laser-Doppler flowmetry[a.u.] = 89.2/120.2/90.6 and pO2[mmHg] = 6.3/32.3/46.7. All parameters were statistically significantly different with P0.001 between all breathing conditions. All MRI and the corresponding micro probe measurements were also statistically significantly (P ≤ 0.03) correlated with each other. However, converting the tissue pO2 to blood oxygen saturation = 0.02/0.34/0.63, showed only very limited agreement with the qBOLD venous blood oxygenation level. We found good correlation between MRI and micro probe measurements. However, direct conversion of tissue pO2 to blood oxygen saturation by using the Hill equation is very limited. Furthermore, adverse effects of anesthesia and trauma due to micro probe insertion are strong confounding factors and need close attention for study planning and conduction of experiments. Investigation of the correlation of perfusion and oxygenation sensitive MRI methods with micro probe measurements in pathologic tissue such as tumors is now of compelling interest.

There is an unmet medical need for noninvasive imaging of regional brain oxygenation to manage stroke, tumor, and neurodegenerative diseases. Oxygenation imaging from magnetic susceptibility in MRI is a promising new technique to measure local venous oxygen extraction fraction (OEF) along the cerebral venous vasculature. However, this approach has not been tested in vivo at different levels of oxygenation. The primary goal of this study was to test whether susceptibility imaging of oxygenation can detect OEF changes induced by hypercapnia, via CO[subscript 2] inhalation, within selected a priori brain regions. Ten healthy subjects were scanned at 3 T with a 32-channel head coil. The end-tidal CO[subscript 2] (ETCO[subscript 2]) was monitored continuously and inspired gases were adjusted to achieve steady-state conditions of eucapnia (41 ± 3 mm Hg) and hypercapnia (50 ± 4 mm Hg). Gradient echo phase images and pseudo-continuous arterial spin labeling (pcASL) images were acquired to measure regional OEF and CBF respectively during eucapnia and hypercapnia. By assuming constant cerebral oxygen consumption throughout both gas states, regional CBF values were computed to predict the local change in OEF in each brain region. Hypercapnia induced a relative decrease in OEF of − 42.3% in the straight sinus, − 39.9% in the internal cerebral veins, and approximately − 50% in pial vessels draining each of the occipital, parietal, and frontal cortical areas. Across volunteers, regional changes in OEF correlated with changes in ETCO[subscript 2]. The reductions in regional OEF (via phase images) were significantly correlated (P < 0.05) with predicted reductions in OEF derived from CBF data (via pcASL images). These findings suggest that susceptibility imaging is a promising technique for OEF measurements, and may serve as a clinical biomarker for brain conditions with aberrant regional oxygenation.

Magnetic resonance fingerprinting (MRF) is a new quantitative imaging paradigm that enables simultaneous acquisition of multiple magnetic resonance tissue parameters (e.g., T 1 , T 2 , and spin density). Recently, MRF has been integrated with simultaneous multislice (SMS) acquisitions to enable volumetric imaging with faster scan time. In this paper, we present a new image reconstruction method based on low-rank and subspace modeling for improved SMS-MRF. Here the low-rank model exploits strong spatiotemporal correlation among contrast-weighted images, while the subspace model captures the temporal evolution of magnetization dynamics. With the proposed model, the image reconstruction problem is formulated as a convex optimization problem, for which we develop an algorithm based on variable splitting and the alternating direction method of multipliers. The performance of the proposed method has been evaluated by numerical experiments, and the results demonstrate that the proposed method leads to improved accuracy over the conventional approach. Practically, the proposed method has a potential to allow for a 3× speedup with minimal reconstruction error, resulting in less than 5 sec imaging time per slice., NIH (Grants R01-EB017219, F32-EB024381, R01-EB017337, R01-NS089212, P41-EB015896, U01-MH093765, and R24-MH106096)

Fetal health is critically dependent on placental function, especially placental transport of oxygen from mother to fetus. When fetal growth is compromised, placental insufficiency must be distinguished from modest genetic growth potential. If placental insufficiency is present, the physician must trade off the risk of prolonged fetal exposure to placental insufficiency against the risks of preterm delivery. Current ultrasound methods to evaluate the placenta are indirect and insensitive. We propose to use Blood-Oxygenation-Level-Dependent (BOLD) MRI with maternal hyperoxia to quantitatively assess mismatch in placental function in seven monozygotic twin pairs naturally matched for genetic growth potential. In-utero BOLD MRI time series were acquired at 29 to 34 weeks gestational age. Maps of oxygen Time-To-Plateau (TTP) were obtained in the placentas by voxel-wise fitting of the time series. Fetal brain and liver volumes were measured based on structural MR images. After delivery, birth weights were obtained and placental pathological evaluations were performed. Mean placental TTP negatively correlated with fetal liver and brain volumes at the time of MRI as well as with birth weights. Mean placental TTP positively correlated with placental pathology. This study demonstrates the potential of BOLD MRI with maternal hyperoxia to quantify regional placental function in vivo.

© 2017 International Society for Magnetic Resonance in Medicine Purpose: Subject motion may cause errors in estimates of blood T2 when using the T2-relaxation under spin tagging (TRUST) technique on noncompliant subjects like neonates. By incorporating 3D volume navigators (vNavs) into the TRUST pulse sequence, independent measurements of motion during scanning permit evaluation of these errors. Methods: The effects of integrated vNavs on TRUST-based T2 estimates were evaluated using simulations and in vivo subject data. Two subjects were scanned with the TRUST+vNav sequence during prescribed movements. Mean motion scores were derived from vNavs and TRUST images, along with a metric of exponential fit quality. Regression analysis was performed between T2 estimates and mean motion scores. Also, motion scores were determined from independent neonatal scans. Results: vNavs negligibly affected venous blood T2 estimates and better detected subject motion than fit quality metrics. Regression analysis showed that T2 is biased upward by 4.1 ms per 1 mm of mean motion score. During neonatal scans, mean motion scores of 0.6 to 2.0 mm were detected. Conclusion: Motion during TRUST causes an overestimate of T2, which suggests a cautious approach when comparing TRUST-based cerebral oxygenation measurements of noncompliant subjects. Magn Reson Med 78:2283–2289, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

© 2017 International Society for Magnetic Resonance in Medicine Purpose: To present a method for spatiotemporal alignment of in-utero magnetic resonance imaging (MRI) time series acquired during maternal hyperoxia for enabling improved quantitative tracking of blood oxygen level-dependent (BOLD) signal changes that characterize oxygen transport through the placenta to fetal organs. Materials and Methods: The proposed pipeline for spatiotemporal alignment of images acquired with a single-shot gradient echo echo-planar imaging includes 1) signal nonuniformity correction, 2) intravolume motion correction based on nonrigid registration, 3) correction of motion and nonrigid deformations across volumes, and 4) detection of the outlier volumes to be discarded from subsequent analysis. BOLD MRI time series collected from 10 pregnant women during 3T scans were analyzed using this pipeline. To assess pipeline performance, signal fluctuations between consecutive timepoints were examined. In addition, volume overlap and distance between manual region of interest (ROI) delineations in a subset of frames and the delineations obtained through propagation of the ROIs from the reference frame were used to quantify alignment accuracy. A previously demonstrated rigid registration approach was used for comparison. Results: The proposed pipeline improved anatomical alignment of placenta and fetal organs over the state-of-the-art rigid motion correction methods. In particular, unexpected temporal signal fluctuations during the first normoxia period were significantly decreased (P < 0.01) and volume overlap and distance between region boundaries measures were significantly improved (P < 0.01). Conclusion: The proposed approach to align MRI time series enables more accurate quantitative studies of placental function by improving spatiotemporal alignment across placenta and fetal organs. Level of Evidence: 1. Technical Efficacy: Stage 1. J. MAGN. RESON. IMAGING 2017;46:403–412.

Purpose We compare the performance of eight parallel transmit (pTx) body arrays with up to 32 channels and a standard birdcage design. Excitation uniformity, local specific absorption rate (SAR), global SAR, and power metrics are analyzed in the torso at 3 T for radiofrequency (RF)-shimming and 2-spoke excitations. Methods We used a fast cosimulation strategy for field calculation in the presence of coupling between transmit channels. We designed spoke pulses using magnitude least squares optimization with explicit constraint of SAR and power and compared the performance of the different pTx coils using the L-curve method. Results PTx arrays outperformed the conventional birdcage coil in all metrics except peak and average power efficiency. The presence of coupling exacerbated this power efficiency problem. At constant excitation fidelity, the pTx array with 24 channels arranged in three z-rows could decrease local SAR more than 4-fold (2-fold) for RF-shimming (2-spoke) compared to the birdcage coil for pulses of equal duration. Multi-row pTx coils had a marked performance advantage compared to single row designs, especially for coronal imaging. Conclusion PTx coils can simultaneously improve the excitation uniformity and reduce SAR compared to a birdcage coil when SAR metrics are explicitly constrained in the pulse design. Magn Reson Med 73:1137–1150, 2015. © 2014 Wiley Periodicals, Inc.

Athinoula A. Martinos Center for Biomedical Imaging (Advanced Multimodal Neuroimaging Training Program; Grant number: R90-DA023427)

Post-operative MRI of patients with deep brain simulation (DBS) implants is useful to assess complications and diagnose comorbidities, however more than one third of medical centers do not perform MRIs on this patient population due to stringent safety restrictions and liability risks. A new system of reconfigurable magnetic resonance imaging head coil composed of a rotatable linearly-polarized birdcage transmitter and a close-fitting 32-channel receive array is presented for low-SAR imaging of patients with DBS implants. The novel system works by generating a region with low electric field magnitude and steering it to coincide with the DBS lead trajectory. We demonstrate that the new coil system substantially reduces the SAR amplification around DBS electrodes compared to commercially available circularly polarized coils in a cohort of 9 patient-derived realistic DBS lead trajectories. We also show that the optimal coil configuration can be reliably identified from the image artifact on B 1+ field maps. Our preliminary results suggest that such a system may provide a viable solution for high-resolution imaging of DBS patients in the future. More data is needed to quantify safety limits and recommend imaging protocols before the novel coil system can be used on patients with DBS implants., NIH (Grants K99EB021320, R01EB006847, and P41EB015896)

Cerebral perfusion in neonates with congenital heart disease is a clinical concern. Combined measures of MRI and NIRS can provide complementary information to improve monitoring. We compare multimodal measures of cerebral hemodynamics in this group.

Quantifying tissue iron concentration in vivo is instrumental for understanding the role of iron in physiology and in neurological diseases associated with abnormal iron distribution. Herein, we use recently-developed Quantitative Susceptibility Mapping (QSM) methodology to estimate the tissue magnetic susceptibility based on MRI signal phase. To investigate the effect of different regularization choices, we implement and compare ℓ[subscript 1] and ℓ[subscript 2] norm regularized QSM algorithms. These regularized approaches solve for the underlying magnetic susceptibility distribution, a sensitive measure of the tissue iron concentration, that gives rise to the observed signal phase. Regularized QSM methodology also involves a pre-processing step that removes, by dipole fitting, unwanted background phase effects due to bulk susceptibility variations between air and tissue and requires data acquisition only at a single field strength. For validation, performances of the two QSM methods were measured against published estimates of regional brain iron from postmortem and in vivo data. The in vivo comparison was based on data previously acquired using Field-Dependent Relaxation Rate Increase (FDRI), an estimate of MRI relaxivity enhancement due to increased main magnetic field strength, requiring data acquired at two different field strengths. The QSM analysis was based on susceptibility-weighted images acquired at 1.5 T, whereas FDRI analysis used Multi-Shot Echo-Planar Spin Echo images collected at 1.5 T and 3.0 T. Both datasets were collected in the same healthy young and elderly adults. The in vivo estimates of regional iron concentration comported well with published postmortem measurements; both QSM approaches yielded the same rank ordering of iron concentration by brain structure, with the lowest in white matter and the highest in globus pallidus. Further validation was provided by comparison of the in vivo measurements, ℓ[subscript 1]-regularized QSM versus FDRI and ℓ[subscript 2]-regularized QSM versus FDRI, which again yielded perfect rank ordering of iron by brain structure. The final means of validation was to assess how well each in vivo method detected known age-related differences in regional iron concentrations measured in the same young and elderly healthy adults. Both QSM methods and FDRI were consistent in identifying higher iron concentrations in striatal and brain stem ROIs (i.e., caudate nucleus, putamen, globus pallidus, red nucleus, and substantia nigra) in the older than in the young group. The two QSM methods appeared more sensitive in detecting age differences in brain stem structures as they revealed differences of much higher statistical significance between the young and elderly groups than did FDRI. However, QSM values are influenced by factors such as the myelin content, whereas FDRI is a more specific indicator of iron content. Hence, FDRI demonstrated higher specificity to iron yet yielded noisier data despite longer scan times and lower spatial resolution than QSM. The robustness, practicality, and demonstrated ability of predicting the change in iron deposition in adult aging suggest that regularized QSM algorithms using single-field-strength data are possible alternatives to tissue iron estimation requiring two field strengths., National Institutes of Health (U.S.) (Grant NIH R01 EB007942), National Institutes of Health (U.S.) (Grant AG019717), National Institutes of Health (U.S.) (Grant AA005965), National Institutes of Health (U.S.) (Grant AA017168), National Institutes of Health (U.S.) (Grant EB008381), National Science Foundation (U.S.) (Grant 0643836), Siemens Corporation, Siemens-MIT Alliance, MIT-Center for Integration of Medicine and Innovative Technology (Medical Engineering Fellowship)

MRI-based bone segmentation is a challenging task because bone tissue and air both present low signal intensity on MR images, making it difficult to accurately delimit the bone boundaries. However, estimating bone from MRI images may allow decreasing patient ionization by removing the need of patient-specific CT acquisition in several applications. In this work, we propose a fast GPU-based pseudo-CT generation from a patient-specific MRI T1-weighted image using a group-wise patch-based approach and a limited MRI and CT atlas dictionary. For every voxel in the input MR image, we compute the similarity of the patch containing that voxel with the patches of all MR images in the database, which lie in a certain anatomical neighborhood. The pseudo-CT is obtained as a local weighted linear combination of the CT values of the corresponding patches. The algorithm was implemented in a GPU. The use of patch-based techniques allows a fast and accurate estimation of the pseudo-CT from MR T1-weighted images, with a similar accuracy as the patient-specific CT. The experimental normalized cross correlation reaches 0.9324±0.0048 for an atlas with 10 datasets. The high NCC values indicate how our method can accurately approximate the patient-specific CT. The GPU implementation led to a substantial decrease in computational time making the approach suitable for real applications.

Venous oxygen saturation (Yv) in cerebral veins and the cerebral metabolic rate of oxygen (CMRO2) are important indicators for brain function and disease. Although MRI has been used for global measurements of these parameters, currently there is no recognized technique to quantify regional Yv and CMRO2 using noninvasive imaging. This article proposes a technique to quantify CMRO2 from independent MRI estimates of Yv and cerebral blood flow. The approach uses standard gradient-echo and arterial spin labeling acquisitions to make these measurements. Using MR susceptometry on gradient-echo phase images, Yv was quantified for candidate vein segments in gray matter that approximate a long cylinder parallel to the main magnetic field. Local cerebral blood flow for the identified vessel was determined from a corresponding region in the arterial spin labeling perfusion map. Fick's principle of arteriovenous difference was then used to quantify CMRO2 locally around each vessel. Application of this method in young, healthy subjects provided gray matter averages of 59.6% ± 2.3% for Yv, 51.7 ± 6.4 mL/100 g/min for cerebral blood flow, and 158 ± 18 μmol/100 g/min for CMRO2 (mean ± SD, n = 12), which is consistent with values previously reported by positron emission tomography and MRI. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.

While oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) are fundamental parameters of brain health and function, a robust MRI-based mapping of OEF and CMRO2 amenable to functional MRI (fMRI) has not been established. To address this issue, a novel method called QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption, or QUIXOTIC, is introduced. The key innovation in QUIXOTIC is the use of velocity-selective spin labeling to isolate MR signal exclusively from postcapillary venular blood on a voxel-by-voxel basis. Measuring the T2 of this venular-targeted blood allows calibration to venular oxygen saturation (Yv) via theoretical and experimental T2 versus blood oxygen saturation relationships. Yv is converted to OEF, and baseline CMRO2 is subsequently estimated from OEF and additional cerebral blood flow and hematocrit measurements. Theory behind the QUIXOTIC technique is presented, and implications of cutoff velocity (VCUTOFF) and outflow time parameters are discussed. Cortical gray matter values obtained with QUIXOTIC in 10 healthy volunteers are Yv = 0.73 ± 0.02, OEF = 0.26 ± 0.02, and CMRO2 = 125 ± 15 μmol/100 g min. Results are compared to global measures obtained with the T2 relaxation under spin tagging (TRUST) technique. The preliminary data presented suggest that QUIXOTIC will be useful for mapping Yv, OEF, and CMRO2, in both clinical and functional MRI settings. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.

Diffusion tensor imaging (DTI) of the brain has become a mainstay in the study of normal aging of white matter, and only recently has attention turned to the use of DTI to examine aging effects in gray matter structures. Of the many changes in the brain that occur with advancing age is increased presence of iron, notable in selective deep gray matter structures. In vivo detection and measurement of iron deposition is possible with magnetic resonance imaging (MRI) because of iron's effect on signal intensity. In the process of a DTI study, a series of diffusion-weighted images (DWI) is collected, and while not normally considered as a major dependent variable in research studies, they are used clinically and they reveal striking conspicuity of the globus pallidus and putamen caused by signal loss in these structures, presumably due to iron accumulation with age. These iron deposits may in turn influence DTI metrics, especially of deep gray matter structures. The combined imaging modality approach has not been previously used in the study of normal aging. The present study used legacy DTI data collected in 10 younger (22–37 years) and 10 older (65–79 years) men and women at 3.0 T and fast spin-echo (FSE) data collected at 1.5 T and 3.0 T to derive an estimate of the field-dependent relaxation rate increase (the “FDRI estimate”) in the putamen, caudate nucleus, globus pallidus, thalamus, and a frontal white matter sample comparison region. The effect of age on the diffusion measures in the deep gray matter structures was distinctly different from that reported in white matter. In contrast to lower anisotropy and higher diffusivity typical in white matter of older relative to younger adults observed with DTI, both anisotropy and diffusivity were higher in the older than younger group in the caudate nucleus and putamen; the thalamus showed little effect of age on anisotropy or diffusivity. Signal intensity measured with DWI was lower in the putamen of elderly than young adults, whereas the opposite was observed for the white matter region and thalamus. As a retrospective study based on legacy data, the FDRI estimates were based on FSE sequences, which underestimated the classical FDRI index of brain iron. Nonetheless, the differential effects of age on DTI metrics in subcortical gray matter structures compared with white matter tracts appears to be related, at least in part, to local iron content, which in the elderly of the present study was prominent in the FDRI estimate of the putamen and visibly striking in the diffusion-weighted image of the basal ganglia structures., National Institutes of Health (U.S.) (Grant AG17919), National Institutes of Health (U.S.) (Grant AA05965), National Institutes of Health (U.S.) (Grant AA10723), National Institutes of Health (U.S.) (Grant AA12388)

This work examines feasibility, practical advantages, and disadvantages of a combined MRI/magnetic particle hyperthermia (MPH) system for cancerous tumor treatment in low perfusion tissue. Although combined MRI/hyperthermia systems have been proposed and constructed, the current proposal differs because the hyperthermia system would be specifically designed to interact with the magnetic nanoparticles injected at the tumor site. The proposal exploits the physical similarities between the magnetic nanoparticles currently employed for MPH and those used as superparamagnetic iron oxide (SPIO) contrast agents in MR imaging. The proposal involves the addition of a rotating magnetic field RF hyper- thermia source perpendicular to the MRI B0 field which operates in a similar manner to the MRI RF excitation fi eld,B1, but at significantly higher frequency and field strength such that the magnetic nanoparticles are forced to rotate in its presence. This rotation is the source of increases in temperature which are of therapeutic benefit in cancer therapy. For rotating magnetic fields with amplitudes much smaller than B0, the nanoparticles' suspension mag- netization rapidly saturates with increasing B0. Therefore, the proposal is best suited to low-field MRI systems when magnetic saturation is incomplete. In addition, careful design of the RF hyperthermia source is required to ensure no physical or RF interference with the B1 field used for MRI excitation. Notwithstanding these caveats, the authors have shown that localized steady-state temperature rises in small spherical tumors of up to 108 Ca re con- ceivable with careful selection of the nanoparticle radius and concentration, RF hyperther- mia field amplitude and frequency. 2010 Wiley Periodicals, Inc. Concepts Magn Reson Part A 36A: 36-47, 2010.

Traditional methods of measuring magnetization in magnetic fluid samples, such as vibrating sample magnetometry (VSM), are typically limited to maximum field strengths of about 1 T. This work demonstrates the ability of MRI to measure the magnetization associated with two commercial MRI contrast agents at 3 T by comparing analytical solutions to experimental imaging results for the field pattern associated with agents in cylindrical vials. The results of the VSM and fitted MRI data match closely. The method represents an improvement over VSM measurements since results are attainable at imaging field strengths. The agents investigated are Feridex, a superparamagnetic iron oxide suspension used primarily for liver imaging, and Magnevist, a paramagnetic, gadolinium-based compound used for tumors, inflammation and vascular lesions. MR imaging of the agents took place in sealed cylindrical vials in the presence of a surrounding volume of deionized water where the effects of the contrast agents had a measurable effect on the water's magnetization in the vicinity of the compartment of contrast agent. A pair of phase images were used to reconstruct a B0 fieldmap. The resultant B0 maps in the water region, corrected for shimming and container edge effects, were used to predict the agent's magnetization at 3 T. The results were compared with the results from VSM measurements up to 1.2 T and close correlation was observed. The technique should be of interest to those seeking quantification of the magnetization associated with magnetic suspensions beyond the traditional scope of VSM. The magnetization needs to be sufficiently strong (Ms ≳ 50 Am2/kg Fe for Feridex and Xm ≳ 5 × 10−5 m3/kg Gd for Magnevist) for a measurable dipole field in the surrounding water. For this reason, the technique is mostly suitable for undiluted agents. Copyright © 2009 John Wiley & Sons, Ltd.

A substantial proportion of individuals infected with human immunodeficiency virus (HIV) also abuse alcohol. Given that each condition can disrupt brain structural integrity, with a predilection for white matter, we used MR diffusion tensor imaging (DTI) and quantitative fibre tracking to examine the separate and combined effects on the microstructure of the corpus callosum. Subjects were men and women with alcoholism alone (n = 87), HIV infection alone (n = 42), alcoholism and HIV infection comorbidity (n = 52) and non-affected controls (n = 88). The two alcoholism groups had similar lifetime alcohol consumption histories; the two HIV-infected groups had similar CD4+ counts and viral loads; all groups were matched in body mass index, and no participant was demented. Compared with controls, all patient groups had lower fractional anisotropy (FA) and higher mean diffusivity (MD) in callosal regions and fibre bundles coursing through the genu and splenium, but these effects were only significant in the two groups with alcoholism, which exhibited 0.65-1.2 SD abnormalities in FA and MD. The callosal regions were differentially affected by alcoholism, with the genu more affected than the splenium, a pattern even more pronounced in the fibre tracks. When the HIV-infected groups were divided by disease severity defined as an acquired immunodeficiency syndrome (AIDS)-defining event or low CD4+ counts (200) and alcoholism comorbidity, the HIV-infected subgroup with AIDS and alcoholism exhibited approximately 2 SD FA and MD abnormalities in the callosal sectors and fibres, abnormalities that were more than twice the effect sizes observed in the other three HIV-infected subgroups. Degradation of the callosal microstructure was consistently associated with alcoholism, with evidence for compounded alcoholism-HIV effects. Functional relevance of the microstructural abnormalities was supported by associations between motor deficits and low FA or high MD within the diagnostic groups. The high prevalence of alcoholism in HIV-infected individuals and the interfering effect of alcohol on HIV pharmacological response and therapy compliance underscore the need to recognize the independent and synergistic contributions of each condition to brain structure and function.

Background: The alcohol-preferring (P) rat, a Wistar strain selectively bred to consume large amounts of alcohol voluntarily, has been used as an animal model of human alcoholism for 3 decades. Heretofore, knowledge about brain morphology has been confined to postmortem examination. Quantitative neuroimaging procedures make it feasible to examine the potential longitudinal effects of alcohol exposure in vivo, while controlling modifying factors, such as age, nutrition, and exercise. To date, few imaging studies have considered what morphological changes occur with age in the rodent brain, and none has systematically applied quantitative neuroimaging approaches to measure volume changes in regional brain structures over extended periods in the adult rat. Methods: We used structural magnetic resonance imaging (MRI) in a longitudinal design to examine 2 cohorts of adult P rats, never exposed to alcohol: Cohort A included 8 rats, 7 of which survived the entire study (578 days) and 4 MRI sessions; Cohort B included 9 rats, all of which survived the study (452 days) and 5 MRI sessions. Results: Growth in whole-brain volume reached maximal levels by about 450 days of age, whereas body weight continued its gain without asymptote. Growth was not uniform across the brain structures measured. Over the initial 12 months of the study, the corpus callosum area expanded 36%, cerebellum 17%, and hippocampus 10%, whereas ventricle size was unchanged. Factors affecting growth rate estimates included litter effects, MR image signal-to-noise ratio, and measurement error. Conclusion: Unlike longitudinal human reports of regional volume declines in aging brain tissue, several brain structures in adult rats continued growing, and some growth patterns were litter-dependent. Determining normal regional growth patterns of brain and of the substantial variance exerted by litter differences, even in selectively bred rats, is essential for establishing baselines against which normal and aberrant dynamic changes can be detected in animal models of aging and disease.

Chronic alcohol abuse is a ubiquitous health and societal problem, with a growing prevalence in the older population. Alcoholism is a source of substantial deterioration in brain tissue and has been consistently observed in vivo and postmortem in white matter. To quantify the potential compounded effect of age and alcoholism, we used conventional structural MRI and diffusion tensor imaging (DTI) to examine the macrostructural and microstructural integrity of the corpus callosum, one of the most prominent white matter structures of the brain, in 131 adults, age 27-75 years. Compared with the 74 controls, the 40 alcoholic men and 17 alcoholic women, who were abstinent from alcohol for an average of 3 months, showed similar patterns and extents of callosal shrinkage, which was greatest in the genu and body and less prominent in the splenium. Microstructural integrity was measured with DTI as fractional anisotropy, an index of intravoxel orientational coherence of white matter fibers, and bulk mean diffusivity, an index of the amount of intravoxel water motility. The macrostructural shrinkage was accompanied by abnormalities in anisotropy and diffusivity of the microstructural environment of these callosal regions, indicative of disruption of structural constituents of local brain white matter. Correlational analyses revealed an age-alcohol interaction, where older alcoholics had smaller genu and splenium and higher diffusivity in these regions than younger alcoholics. Significant correlations between regional MRI and DTI measures and performance on working memory, visuospatial ability, and gait and balance provided evidence for the functional ramifications of the callosal abnormalities in the alcoholics. Thus, despite abstinence from alcohol, the interaction of age and recent alcoholism history exerted a compounded untoward effect on callosal macrostructure and microstructure.

In vivo study of white matter microstructural integrity through magnetic resonance diffusion tensor imaging (DTI) permits examination of degradation of axonal circuitry that may underlie functional decline of frontally-based processes in normal adult aging. Determination of the pattern of age-related degradation of white matter microstructure requires quantitative comparison of the rostral–caudal and superior–inferior extents of the brain's white matter. To date, this has not been accomplished, probably because of significant artifacts from spatial distortion and poor signal resolution that precludes accurate analysis in prefrontal and inferior brain regions. Here, we report a profile analysis of the integrity of white matter microstructure across the supratentorium and in selected focal regions using DTI data collected at high-field strength (3 T), with isotropic voxel acquisition, and an analysis based on a concurrently-acquired field map to permit accurate quantification of artifact-prone, anterior and inferior brain regions. The groups comprised 10 younger and 10 older individuals; all were high functioning, highly educated, and in excellent health. The DTI profile analysis revealed a robust frontal distribution of low white matter anisotropy and high bulk mean diffusivity in healthy older compared with younger adults. In contrast to frontal fiber systems, posterior systems were largely preserved with age. A second analysis, based on focal samples of FA, confirmed that the age-related FA decline was restricted to frontal regions, leaving posterior and inferior brain regions relatively intact. The selective decline of anterior anisotropy with advancing age provides evidence for the potential of a microstructural white matter mechanism for the commonly observed decline in frontally-based functions.

This article represents a symposium of the 2004 ISBRA Congress held in Mannheim. The presentations were: Review of the neuropathological and neurochemical changes seen in alcohol-related ' brain shrinkage ' by Clive Harper; In Vivo Detection of Macrostructural and Microstructural Markers of Brain Integrity in Human Alcoholism and a Rodent Model of Alcoholism by Adolf Pfefferbaum, Elfar Adalsteinsson and Edith Sullivan; Gene and Protein Changes in the Brains of Alcoholics with ' Brain Shrinkage ' by Joanne Lewohl and Peter Dodd; Cross sectional and longitudinal MR spectroscopy studies of chronic adult alcoholics by Michael Taylor; Brain Atrophy Associated with Impairment on a Simulated Gambling Task in Long-Term Abstinent Alcoholics by George Fein and Bennett Landman.

Alcoholism comorbidity is highly prevalent in individuals infected with human immunodeficiency virus (HIV). Each condition is known to affect brain structure, function, and metabolism, but the combined effects on the brain have only recently been considered. Single-voxel, proton MR spectroscopy (MRS) has yielded sensitive measures of early brain deterioration in the progression of HIV, but has limited coverage of neocortex, whereas MRS imaging (MRSI) can simultaneously interrogate large regions of cortex. Included were 15 men with HIV+alcoholism, nine men with HIV alone, eight men with alcoholism alone (abstinent for 3-17 months), and 23 controls. The two HIV groups were matched in T-cell count and were not demented; the two alcoholism groups were relatively matched in lifetime alcohol consumption. We used MRSI with a variable-density spiral sequence to quantify major proton metabolites--N-acetylaspartate (NAA), creatine (Cr), and choline (Cho)-in the superior parietal-occipital cortex. Metabolites were expressed in absolute units and as the NAA/Cr ratio. Significant group effects were present for NAA and Cr. Only the HIV+alcoholism group was significantly affected, exhibiting a 0.8 SD deficit in NAA and a 1.0 SD deficit in Cr. The deficits were not related to highly active antiretroviral therapy (HAART) status. Neither HIV infection nor alcoholism independently resulted in parietal-occipital cortical metabolite abnormalities, yet each disease carried a liability that put affected individuals at a heightened risk of neuronal compromise when the diseases were compounded. Further, the use of absolute measures revealed deficits in NAA and Cr that would have gone undetected if these metabolites were expressed as a ratio.

Neuroimaging of animal models of alcoholism offers a unique path for translational research to the human condition. Animal models permit manipulation of variables that are uncontrollable in clinical, human investigation. This symposium, which took place at the annual meeting of the Research Society on Alcoholism in Vancouver, British Columbia, Canada, on June 29th, 2004, presented initial findings based on neuroimaging studies from the two centers of the Integrative Neuroscience Initiative on Alcoholism funded by the National Institute on Alcohol Abuse and Alcoholism. Effects of alcohol exposure were assessed with in vitro glucose metabolic imaging of rat brain, in vitro receptor imaging of monkey brain, in vivo magnetic resonance imaging of monkey brain, and in vivo magnetic resonance spectroscopic quantification of alcohol metabolism kinetics in rat brain.

Purpose To evaluate within-scanner and between-scanner reliability of fractional anisotropy (FA) and trace (sum of the diagonal elements of the diffusion tensor) as measured by diffusion tensor imaging (DTI). Materials and Methods Ten young healthy adults were scanned on three separate days, on two different systems made by the same manufacturer. One scan was acquired at one site, and two scans were acquired on two different occasions on another scanner at another site. Three levels of analysis were used to compare the DTI metrics: 1) a voxel-by-voxel analysis of all supratentorial brain (gray matter + white matter + cerebrospinal fluid) and of supratentorial white matter; 2) a slice-by-slice analysis of supratentorial white matter; and 3) a single-region analysis of the corpus callosum. Results The voxel-by-voxel analysis of all supratentorial brain found that FA and trace measures and correlations were equivalently and significantly higher within than across scanners. For supratentorial white matter, FA was similar within and across scanners, whereas trace demonstrated across-scanner bias. A similar pattern was observed for the slice-by-slice comparison. For the single-region analysis of the corpus callosum, within-scanner FA and trace measures were highly reproducible for FA (CV = 1.9%) and trace (CV = 2.6%), but both DTI measures showed a systematic mean bias across scanners (CV = 4.5% for FA and CV = 7.5% for trace). Conclusion These estimates of measurement variation and scanner bias can be used to predict effect sizes for longitudinal and multisite studies using diffusion tensor imaging. J. Magn. Reson. Imaging 2003;18:427–433. © 2003 Wiley-Liss, Inc.

This article contains the proceedings of a symposium at the 2002 RSA/ISBRA Meeting in San Francisco, organized and chaired by Clive Harper and co-chaired by Izuru Matsumoto. The presentations were (1) Introduction, by Clive Harper; (2) The quality of tissue-a critical issue, by Therese Garrick; (3) The first systematic brain tissue donor program in Japan, by Izuru Matsumoto; (4) Brain scans after death-really! by Adolf Pfefferbaum, Elfar Adalsteinsson, and Edith Sullivan; (5) Capture that (genial) expression, by Joanne Lewohl and Peter Dodd; and (6) Neurochemical/pharmacological studies: experimental design and limitations, by Roger Butterworth.

Studies based on animal models report that methamphetamine (MA) abuse diminishes dopamine (DA) and serotonin innervation in frontal brain regions. In this in vivo human study, we used proton magnetic resonance spectroscopy (MRS), which yields measures of N-acetyl-aspartate (NAA), a marker of living neurons, to examine frontal brain regions possibly affected by methamphetamine dependence (MD). We tested the hypothesis that MD subjects would exhibit abnormally low levels of NAA, referenced to creatine (Cr), in anterior cingulate gray matter. We further hypothesized that the primary visual cortex, which receives relatively less DA innervation than the frontal brain regions, would show normal NAA/Cr ratios in MD subjects. Subjects included nine MD men (mean+/-standard deviation (S.D.)=32.5+/-6.4 years) and nine age-matched control men (mean+/-S.D.=32.7+/-6.8 years). The MD subjects were MA-free for 4-13 weeks. Proton MRS metabolites were expressed as ratios of creatine; the absolute values of which did not distinguish controls and MD subjects. With regard to metabolite ratios, the MD men had significantly lower NAA/Cr in the cingulum (mean+/-standard error (S.E.): control=1.46+/-0.03; MD=1.30+/-0.03; Mann-Whitney P=0.01) but not in the visual cortex (mean+/-S.E.: control=1.64+/-0.06; MD=1.69+/-11; Mann-Whitney P=0.52) relative to controls. These results provide evidence for NAA/Cr deficit that is selective to the anterior cingulum, at least with respect to visual cortex, in MD subjects. The neuronal compromise that these changes reflect may contribute to the attentional deficits and dampened reward system in MD.

There is increasing evidence that iron deposition occurs in specific regions of the brain in normal aging and neurodegenerative disorders such as Parkinson's, Huntington's, and Alzheimer's disease. Iron deposition changes the magnetic susceptibility of tissue, which alters the MR signal phase, and allows estimation of susceptibility differences using quantitative susceptibility mapping (QSM). We present a method for quantifying susceptibility by inversion of a perturbation model, or “QSIP.” The perturbation model relates phase to susceptibility using a kernel calculated in the spatial domain, in contrast to previous Fourier-based techniques. A tissue/air susceptibility atlas is used to estimate B[subscript 0] inhomogeneity. QSIP estimates in young and elderly subjects are compared to postmortem iron estimates, maps of the Field-Dependent Relaxation Rate Increase, and the L1-QSM method. Results for both groups showed excellent agreement with published postmortem data and in vivo FDRI: statistically significant Spearman correlations ranging from Rho=0.905 to Rho=1.00 were obtained. QSIP also showed improvement over FDRI and L1-QSM: reduced variance in susceptibility estimates and statistically significant group differences were detected in striatal and brainstem nuclei, consistent with age-dependent iron accumulation in these regions., National Institutes of Health (U.S.) (Grant P41EB015902), National Institutes of Health (U.S.) (Grant P41RR013218), National Institutes of Health (U.S.) (Grant P41EB015898), National Institutes of Health (U.S.) (Grant P41RR019703), National Institutes of Health (U.S.) (Grant T32EB0011680-06), National Institutes of Health (U.S.) (Grant K05AA017168), National Institutes of Health (U.S.) (Grant R01AA012388)

Quantitative oxygen extraction fraction (OEF) in cortical veins was studied in patients with multiple sclerosis (MS) and healthy subjects via magnetic resonance imaging (MRI) phase images at 7 Tesla (7 T). Flow-compensated, three-dimensional gradient-echo scans were acquired for absolute OEF quantification in 23 patients with MS and 14 age-matched controls. In patients, we collected T2∗-weighted images for characterization of white matter, deep gray matter, and cortical lesions, and also assessed cognitive function. Variability of OEF across readers and scan sessions was evaluated in a subset of volunteers. OEF was averaged from 2 to 3 pial veins in the sensorimotor, parietal, and prefrontal cortical regions for each subject (total of ∼10 vessels). We observed good reproducibility of mean OEF, with intraobserver coefficient of variation (COV)=2.1%, interobserver COV=5.2%, and scan—rescan COV=5.9%. Patients exhibited a 3.4% reduction in cortical OEF relative to controls ( P=0.0025), which was not different across brain regions. Although oxygenation did not relate with measures of structural tissue damage, mean OEF correlated with a global measure of information processing speed. These findings suggest that cortical OEF from 7-T MRI phase is a reproducible metabolic biomarker that may be sensitive to different pathologic processes than structural MRI in patients with MS.

Diffusion tensor imaging was used to measure regional differences in brain white matter microstructure (intravoxel coherence) and macrostructure (intervoxel coherence) and age-related differences between men and women. Neuropsychiatrically healthy men and women, spanning the adult age range, showed the same pattern of variation in regional white matter coherence. The greatest coherence measured was in corpus callosum, where commissural fibers have one primary orientation, lower in the centrum semiovale, where fibers cross from multiple axes, and lowest in pericallosal areas, where fibers weave and interstitial fluid commonly pools. Age-related declines in intravoxel coherence was equally strong and strikingly similar in men and women, with evidence for greater age-dependent deterioration in frontal than parietal regions. Degree of regional white matter coherence correlated with gait, balance, and interhemispheric transfer test scores.

Background: Postmortem studies report degradation of brain white matter microstructure in chronic alcoholism, but until recently, in vivo neuroimaging could provide measurement only at a macrostructural level. The development of magnetic resonance diffusion tensor imaging (DTI) for clinical use offers a method for depicting and quantifying the diffusion properties of white matter expressed as intravoxel and intervoxel coherence of tracts and fibers. Methods: This study used DTI to examine the intravoxel coherence measured as fractional anisotropy (FA) and intervoxel coherence (C) of white matter tracts of the genu and splenium of the corpus callosum and of the centrum semiovale in 15 detoxified alcoholic men and 31 nonalcoholic control subjects. Exploratory correlational analyses examined the relationships between regional DTI measures and tests of attention and working memory in the alcoholic patients. Results: The alcoholic group had lower regional FA than the control group. C was lower in the alcoholics than controls in the splenium only. Working memory correlated positively with splenium FA, whereas attention correlated positively with genu C. Conclusions: These results provide in vivo evidence for disruption of white matter microstructure in alcoholism and suggest that interruption of white matter fiber coherence contributes to disturbance in attention and working memory in chronic alcoholism.

Background: N-acetyl aspartate (NAA) is an amino acid present in high concentrations in neurons and is thus a putative neuronal marker. In vivo proton magnetic resonance spectroscopy (1H MRS) studies have shown lower NAA concentrations in patients with various neurodegenerative disorders, suggesting decreased neuronal number, size, or function. Dorsolateral prefrontal (DLPF) NAA has not been extensively assessed in bipolar disorder patients, but it could be decreased in view of consistent reports of decreased DLPF cerebral blood flow and metabolism in mood disorders. We measured DLPF NAA in patients with bipolar disorder and healthy control subjects using in vivo 1H MRS. Methods: We obtained ratios of NAA, choline, and myoinositol (mI) to creatine-phosphocreatine (Cr-PCr) in bilateral DLPF 8-mL voxels of 20 bipolar patients (10 Bipolar I, 10 Bipolar II) and 20 age- and gender-matched healthy control subjects using 1H MRS. Results: DLPF NAA/Cr-PCr ratios were lower on the right hemisphere(p < .03) and the left hemisphere (p < .003) in bipolar disorder patients compared with healthy control subjects. Conclusions: These preliminary data suggest that bipolar disorder patients have decreased DLPF NAA/Cr-PCr. This finding could represent decreased neuronal density or neuronal dysfunction in the DLPF region.

Quantification of gray and white matter levels of spectroscopically visible metabolites can provide important insights into brain development and pathological conditions. Chemical shift imaging offers a gain in efficiency for estimation of global gray and white matter metabolite concentrations compared to single voxel methods. In the present study, the optimal voxel size is calculated from segmented human brain data and accompanying field maps. The optimal voxel size is found to be approximately 8 cc, but a wide range of values, 4-64 cc, can be chosen with little increase in estimated concentration error (

Echo planar (EP) diffusion tensor imaging (DTI) permits in vivo identification of the orientation and coherence of brain white matter tracts but suffers from field inhomogeneity-induced geometric distortion. To reduce spatial distortion, polynomial warping corrections were applied and the effects tested on measures of fractional anisotropy (FA) in the genu and splenium of corpus callosum. Implementation entailed spatially warping EP images obtained without diffusion weighting (b = 0) to long-echo T(2)-weighted fast spin echo images, collected for anatomical delineation, tissue segmentation, and coregistration with the diffusion images. Using the optimal warping procedure (third-order polynomial), the effects of age on FA and a quantitative measure of intervoxel coherence (C) in the genu, splenium, centrum semiovale, and frontal and parietal pericallosal white matter were examined in 31 healthy men (23-76 years). FA declined significantly with age in all regions except the splenium, whereas intervoxel coherence positively correlated with age in the genu. Magn Reson Med 44:259-268, 2000.

Volumetric proton magnetic resonance spectroscopic imaging (MRSI) was used to generate brain metabolite maps in 15 young and 19 elderly adult volunteers. All subjects also had structural MR scans, and a model, which took into account the underlying structural composition of the brain contributing to each metabolite voxel, was developed and used to estimate the concentration of the N-acetyl-moiety (NAc), creatine (Cr), and choline (Cho) in gray matter and white matter. NAc concentration (signal intensity per unit volume of brain) was higher in gray than white matter and did not differ between young and old subjects despite significant gray matter volume deficits in the older subjects. To the extent that NAc is an index of neuronal integrity, the available gray matter appears to be intact in these older healthy adults. Cr concentrations were much higher in gray than white matter and significantly higher in the old than young subjects. Cho concentration in gray matter was also significantly higher in old than young subjects. Independent determination of metabolite values rather than use of ratios is essential for characterizing age-related changes in brain MRS metabolites.