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Severe traumatic brain injury (TBI) results in cognitive dysfunction in part due to vascular perturbations. In contrast, the long-term vasculo-cognitive pathophysiology of mild TBI (mTBI) remains unknown. We evaluated mTBI effects on chronic cognitive and cerebrovascular function and assessed their interrelationships. Sprague-Dawley rats received midline fluid percussion injury (in =/i 20) or sham (in =/i 21). Cognitive function was assessed (3- and 6-month novel object recognition [NOR], novel object location [NOL], and temporal order object recognition [TOR]). Six-month cerebral blood flow (CBF) and cerebral blood volume (CBV) using contrast magnetic resonance imaging (MRI) andiex vivo/icircle of Willis artery endothelial and smooth muscle-dependent function were measured. mTBI rats showed significantly impaired NOR, with similar trends (non-significant) in NOL/TOR. Regional CBF and CBV were similar in sham and mTBI. NOR correlated with CBF in lateral hippocampus, medial hippocampus, and primary somatosensory barrel cortex, whereas it inversely correlated with arterial smooth muscle-dependent dilation. Six-month baseline endothelial and smooth muscle-dependent arterial function were similar among mTBI and sham, but post-angiotensin 2 stimulation, mTBI showed no change in smooth muscle-dependent dilation from baseline response, unlike the reduction in sham. mTBI led to chronic cognitive dysfunction and altered angiotensin 2-stimulated smooth muscle-dependent vasoreactivity. The findings of persistent pathophysiological consequences of mTBI in this animal model add to the broader understanding of chronic pathophysiological sequelae in human mild TBI.

PURPOSE: The purpose of this study was to develop a spiral-based combined spin- and gradient-echo (spiral-SAGE) method for simultaneous dynamic contrast-enhanced (DCE-MRI) and dynamic susceptibility contrast MRI (DSC-MRI). METHODS: Using this sequence, we obtained gradient-echo TEs of 1.69 and 26 ms, a SE TE of 87.72 ms, with a TR of 1663 ms. Using an iterative SENSE reconstruction followed by deblurring, spiral-induced image artifacts were minimized. Healthy volunteer images are shown to demonstrate image quality using the optimized reconstruction, as well as for comparison with EPI-based SAGE. A bioreactor phantom was used to compare dynamic-contrast time courses with both spiral-SAGE and EPI-SAGE. A proof-of-concept cohort of patients with brain tumors shows the range of hemodynamic maps available using spiral-SAGE. RESULTS: Comparison of spiral-SAGE images with conventional EPI-SAGE images illustrates substantial reductions of image distortion and artifactual image intensity variations. Bioreactor phantom data show similar dynamic contrast time courses between standard EPI-SAGE and spiral-SAGE for the second and third echoes, whereas first-echo data show improvements in quantifying T(1) changes with shorter echo times. In a cohort of patients with brain tumors, spiral-SAGE-based perfusion and permeability maps are shown with comparison with the standard single-echo EPI perfusion map. CONCLUSION: Spiral-SAGE provides a substantial improvement for the assessment of perfusion and permeability by mitigating artifacts typically encountered with EPI and by providing a shorter echo time for improved characterization of permeability. Spiral-SAGE enables quantification of perfusion, permeability, and vessel architectural parameters, as demonstrated in brain tumors.

(1) Background: This work characterizes the sensitivity of magnetic resonance-based Relaxivity Contrast Imaging (RCI) to Amyotrophic Lateral Sclerosis (ALS)-induced changes in myofiber microstructure. Transverse Relaxivity at Tracer Equilibrium (TRATE), an RCI-based parameter, was evaluated in the lower extremities of ALS patients and healthy subjects. (2) Methods: In this IRB-approved study, 23 subjects (12 ALS patients and 11 healthy controls) were scanned at 3T (Philips, The Netherlands). RCI data were obtained during injection of a gadolinium-based contrast agent. TRATE, fat fraction and T2 measures, were compared in five muscle groups of the calf muscle, between ALS and control populations. TRATE was also evaluated longitudinally (baseline and 6 months) and was compared to clinical measures, namely ALS Functional Rating Scale (ALSFRS-R) and Hand-Held Dynamometry (HHD), in a subset of the ALS population. (3) Results: TRATE was significantly lower (p &lt, 0.001) in ALS-affected muscle than in healthy muscle in all muscle groups. Fat fraction differences between ALS and healthy muscle were statistically significant for the tibialis anterior (p = 0.01), tibialis posterior (p = 0.004), and peroneus longus (p = 0.02) muscle groups but were not statistically significant for the medial (p = 0.07) and lateral gastrocnemius (p = 0.06) muscles. T2 differences between ALS and healthy muscle were statistically significant for the tibialis anterior (p = 0.004), peroneus longus (p = 0.004) and lateral gastrocnemius (p = 0.03) muscle groups but were not statistically significant for the tibialis posterior (p = 0.06) and medial gastrocnemius (p = 0.07) muscles. Longitudinally, TRATE, averaged over all patients, decreased by 28 ± 16% in the tibialis anterior, 47 ± 18% in the peroneus longus, 25 ± 19% in the tibialis posterior, 29 ± 14% in the medial gastrocnemius and 35 ± 18% in the lateral gastrocnemius muscles between two timepoints. ALSFRS-R scores were stable in two of four ALS patients. HHD scores decreased in three of four ALS patients. (4) Conclusion: RCI-based TRATE was shown to consistently differentiate ALS-affected muscle from healthy muscle and also provide a quantitative measure of longitudinal muscle degeneration.

Severe traumatic brain injury results in cognitive dysfunction in part due to vascular perturbations. In contrast, the long-term vasculo-cognitive pathophysiology of mild TBI (mTBI) remains unknown. We evaluated mTBI effects on chronic cognitive and cerebrovascular function and assessed their interrelationships. Sprague-Dawley rats received midline fluid percussion injury (N=20) or sham (N=21). Cognitive function was assessed (3- and 6-month novel object recognition (NOR), novel object location (NOL) and temporal order object recognition (TOR)). 6-month cerebral blood flow (CBF) and blood volume (CBV) using contrast MRI and ex vivo pial artery endothelial and smooth muscle-dependent function were measured. mTBI rats showed impaired NOR, with similar (non-significant) trends in NOL/TOR. Regional CBF and CBV were similar in sham and mTBI. NOR correlated with CBF in lateral hippocampus, medial hippocampus and primary somatosensory barrel cortex while inversely correlating with arterial smooth muscle-dependent dilation. 6-month baseline endothelial and smooth muscle-dependent arterial function were similar among mTBI and sham, but post-angiotensin II stimulation, mTBI showed no change in smooth muscle-dependent dilation from baseline response, unlike the reduction in sham. mTBI led to chronic cognitive dysfunction and altered angiotensin II-stimulated smooth muscle-dependent vasoreactivity, a paradigm that could advance understanding of the long-term sequelae of human mild TBI.

BACKGROUND Diffusion-weighted imaging (DWI) is commonly used to detect prostate cancer, and a major clinical challenge is differentiating aggressive from indolent disease. PURPOSE To compare 14 site-specific parametric fitting implementations applied to the same dataset of whole-mount pathologically validated DWI to test the hypothesis that cancer differentiation varies with different fitting algorithms. STUDY TYPE Prospective. POPULATION Thirty-three patients prospectively imaged prior to prostatectomy. FIELD STRENGTH/SEQUENCE 3 T, field-of-view optimized and constrained undistorted single-shot DWI sequence. ASSESSMENT Datasets, including a noise-free digital reference object (DRO), were distributed to the 14 teams, where locally implemented DWI parameter maps were calculated, including mono-exponential apparent diffusion coefficient (MEADC), kurtosis (K), diffusion kurtosis (DK), bi-exponential diffusion (BID), pseudo-diffusion (BID*), and perfusion fraction (F). The resulting parametric maps were centrally analyzed, where differentiation of benign from cancerous tissue was compared between DWI parameters and the fitting algorithms with a receiver operating characteristic area under the curve (ROC AUC). STATISTICAL TEST Levene's test, P

In the context of neurologic disorders, dynamic susceptibility contrast (DSC) and dynamic contrast enhanced (DCE) MRI provide valuable insights into cerebral vascular function, integrity, and architecture. Even after two decades of use, these modalities continue to evolve as their biophysical and kinetic basis is better understood, with improvements in pulse sequences and accelerated imaging techniques and through application of more robust and automated data analysis strategies. Here, we systematically review each of these elements, with a focus on how their integration improves kinetic parameter accuracy and the development of new hemodynamic biomarkers that provide sub-voxel sensitivity (e.g., capillary transit time and flow heterogeneity). Regarding contrast mechanisms, we discuss the dipole-dipole interactions and susceptibility effects that give rise to simultaneous T(1), T(2) and [Formula: see text] relaxation effects, including their quantification, influence on pulse sequence parameter optimization, and use in methods such as vessel size and vessel architectural imaging. The application of technologic advancements, such as parallel imaging, simultaneous multi-slice, undersampled k-space acquisitions, and sliding window strategies, enables improved spatial and/or temporal resolution of DSC and DCE acquisitions. Such acceleration techniques have also enabled the implementation of, clinically feasible, simultaneous multi-echo spin- and gradient echo acquisitions, providing more comprehensive and quantitative interrogation of T(1), T(2) and [Formula: see text] changes. Characterizing these relaxation rate changes through different post-processing options allows for the quantification of hemodynamics and vascular permeability. The application of different biophysical models provides insight into traditional hemodynamic parameters (e.g., cerebral blood volume) and more advanced parameters (e.g., capillary transit time heterogeneity). We provide insight into the appropriate selection of biophysical models and the necessary post-processing steps to ensure reliable measurements while minimizing potential sources of error. We show representative examples of advanced DSC- and DCE-MRI methods applied to pathologic conditions affecting the cerebral microcirculation, including brain tumors, stroke, aging, and multiple sclerosis. The maturation and standardization of conventional DSC- and DCE-MRI techniques has enabled their increased integration into clinical practice and use in clinical trials, which has, in turn, spurred renewed interest in their technological and biophysical development, paving the way towards a more comprehensive assessment of cerebral hemodynamics.

Arguably the most common methods for evaluating cerebral perfusion in the clinic are contrast agent-based perfusion MRI methods, consisting of dynamic susceptibility contrast (DSC) and dynamic contrast enhanced (DCE) methods. Decades of research and recent multi-institutional clinical trials have shown that these methods are able to facilitate and enhance clinical decision making by non-invasively providing hemodynamic and vascular parameters for various neurological diseases. This chapter focuses on the development of conventional DSC and DCE perfusion parameters by providing key mathematical models, commonly accepted analysis steps, and acquisition recommendations. Additionally, confusion regarding post-processing is often a hindrance to perfusion imaging, and this chapter aims to overcome this confusion by illustrating these theories and analysis steps with a worked example.

We have previously characterized the reproducibility of brain tumor relative cerebral blood volume (rCBV) using a dynamic susceptibility contrast magnetic resonance imaging digital reference object across 12 sites using a range of imaging protocols and software platforms. As expected, reproducibility was highest when imaging protocols and software were consistent, but decreased when they were variable. Our goal in this study was to determine the impact of rCBV reproducibility for tumor grade and treatment response classification. We found that varying imaging protocols and software platforms produced a range of optimal thresholds for both tumor grading and treatment response, but the performance of these thresholds was similar. These findings further underscore the importance of standardizing acquisition and analysis protocols across sites and software benchmarking.

The brain is arguably the most common application area of perfusion Magnetic Resonance Imaging (MRI), and all main techniques (arterial spin labeling [ASL], dynamic contrast-enhanced [DCE], dynamic susceptibility contrast [DSC]) have been proposed for clinical applications. This chapter discusses the three most common clinical application areas of perfusion MRI in the brain: (I) Cerebrovascular diseases are a heterogeneous group of disorders that affect the blood vessels of the brain. These are subdivided into ischemic and hemorrhagic. Since they affect the blood vessels of the brain, it stands to reason that perfusion mapping may be valuable in the diagnosis and treatment of cerebrovascular disease. This chapter will focus specifically on acute ischemic stroke and chronic cerebrovascular ischemia; (II) Gliomas, specifically glioblastomas (GBMs), are the most common type of brain cancer in adults, and result in a median survival rate of 15–16 months. In the last 50 years, the survival rate of GBMs has improved slowly compared to other types of cancer owing to the aggressive and difficult-to-treat nature of these tumors. Quantitative perfusion MRI parameters may serve as important imaging biomarkers for the evaluation of new drugs as well as improving the current standard of care. (III) Dementia covers a range of progressive, chronic neurodegenerative diseases, including Alzheimer's disease (AD), frontotemporal dementia (FTD), vascular dementia, and dementia with Lewy bodies. While the precise mechanisms of neurodegeneration caused by the accumulation of these neurotoxic proteins are not well understood, it is well known that these increases are accompanied by associated decreases in metabolism. These changes in metabolism are mirrored by local changes in cerebral perfusion, which can be measured by DSC or ASL, and which may act as a surrogate for metabolic change or potentially an early predictor.

BACKGROUND AND PURPOSE: Standard assessment criteria for brain tumors that only include anatomic imaging continue to be insufficient. While numerous studies have demonstrated the value of DSC-MR imaging perfusion metrics for this purpose, they have not been incorporated due to a lack of confidence in the consistency of DSC-MR imaging metrics across sites and platforms. This study addresses this limitation with a comparison of multisite/multiplatform analyses of shared DSC-MR imaging datasets of patients with brain tumors. MATERIALS AND METHODS: DSC-MR imaging data were collected after a preload and during a bolus injection of gadolinium contrast agent using a gradient recalled-echo–EPI sequence (TE/TR = 30/1200 ms; flip angle = 72°). Forty-nine low-grade ( n = 13) and high-grade ( n = 36) glioma datasets were uploaded to The Cancer Imaging Archive. Datasets included a predetermined arterial input function, enhancing tumor ROIs, and ROIs necessary to create normalized relative CBV and CBF maps. Seven sites computed 20 different perfusion metrics. Pair-wise agreement among sites was assessed with the Lin concordance correlation coefficient. Distinction of low- from high-grade tumors was evaluated with the Wilcoxon rank sum test followed by receiver operating characteristic analysis to identify the optimal thresholds based on sensitivity and specificity. RESULTS: For normalized relative CBV and normalized CBF, 93% and 94% of entries showed good or excellent cross-site agreement (0.8 ≤ Lin concordance correlation coefficient ≤ 1.0). All metrics could distinguish low- from high-grade tumors. Optimum thresholds were determined for pooled data (normalized relative CBV = 1.4, sensitivity/specificity = 90%:77%; normalized CBF = 1.58, sensitivity/specificity = 86%:77%). CONCLUSIONS: By means of DSC-MR imaging data obtained after a preload of contrast agent, substantial consistency resulted across sites for brain tumor perfusion metrics with a common threshold discoverable for distinguishing low- from high-grade tumors.

Background A previous study demonstrated the feasibility of using 3D radial ultrashort echo time (UTE) oxygen-enhanced MRI (UTE OE-MRI) for functional imaging of healthy human lungs. The repeatability of quantitative measures from UTE OE-MRI needs to be established prior to its application in clinical research. Purpose To evaluate repeatability of obstructive patterns in asthma and cystic fibrosis (CF) with UTE OE-MRI with isotropic spatial resolution and full chest coverage. Study Type Volunteer and patient repeatability. Population Eighteen human subjects (five asthma, six CF, and seven normal subjects). Field Strength/Sequence Respiratory-gated free-breathing 3D radial UTE (80 μs) sequence at 1.5T. Assessment Two 3D radial UTE volumes were acquired sequentially under normoxic and hyperoxic conditions. A subset of subjects underwent repeat acquisitions on either the same day or ≤15 days apart. Asthma and CF subjects also underwent spirometry. A workflow including deformable registration and retrospective lung density correction was used to compute 3D isotropic percent signal enhancement (PSE) maps. Median PSE (MPSE) and ventilation defect percent (VDP) of the lung were measured from the PSE map. Statistical Tests The relations between MPSE, VDP, and spirometric measures were assessed using Spearman correlations. The test–retest repeatability was evaluated using Bland–Altman analysis and intraclass correlation coefficients (ICC). Results Ventilation measures in normal subjects (MPSE = 8.0%, VDP = 3.3%) were significantly different from those in asthma (MPSE = 6.0%, P = 0.042; VDP = 21.7%, P = 0.018) and CF group (MPSE = 4.5%, P = 0.0006; VDP = 27.2%, P = 0.002). MPSE correlated significantly with forced expiratory lung volume in 1 second percent predicted (ρ = 0.72, P = 0.017). The ICC of the test–retest VDP and MPSE were both ≥0.90. In all subject groups, an anterior/posterior gradient was observed with higher MPSE and lower VDP in the posterior compared to anterior regions (P ≤ 0.0021 for all comparisons). Data Conclusion 3D radial UTE OE-MRI supports quantitative differentiation of diseased vs. healthy lungs using either whole lung VDP or MPSE with excellent test–retest repeatability. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017.

With DSC-MRI, contrast agent leakage effects in brain tumors can either be leveraged for percent signal recovery (PSR) measurements or be adequately resolved for accurate relative cerebral blood volume (rCBV) measurements. Leakage effects can be dimished by administration of a preload dose before imaging and/or specific postprocessing steps. This study compares the consistency of both PSR and rCBV measurements as a function of varying preload doses in a retrospective analysis of 14 subjects with high-grade gliomas. The scans consisted of 6 DSC-MRI scans during 6 sequential bolus injections (0.05 mmol/kg). Mean PSR was calculated for tumor and normal-appearing white matter regions of interest. DSC-MRI data were corrected for leakage effects before computing mean tumor rCBV. Statistical differences were seen across varying preloads for tumor PSR (P value = 4.57E-24). Tumor rCBV values did not exhibit statistically significant differences across preloads (P value = .14) and were found to be highly consistent for clinically relevant preloads (intraclass correlation coefficient = 0.93). For a 0.05 mmol/kg injection bolus and pulse sequence parameters used, the highest PSR contrast between normal-appearing white matter and tumor occurs when no preload is used. This suggests that studies using PSR as a biomarker should acquire DSC-MRI data without preload. The finding that leakage-corrected rCBV values do not depend on the presence or dose of preload contradicts that of previous studies with dissimilar acquisition protocols. This further confirms the sensitivity of rCBV to preload dosing schemes and pulse sequence parameters and highlights the importance of standardization efforts for achieving multisite rCBV consistency.

Background Dynamic susceptibility contrast (DSC)-MRI analysis pipelines differ across studies and sites, potentially confounding the clinical value and use of the derived biomarkers. Purpose/hypothesis To investigate how postprocessing steps for computation of cerebral blood volume (CBV) and residue function dependent parameters (cerebral blood flow [CBF], mean transit time [MTT], capillary transit heterogeneity [CTH]) impact glioma grading. Study type Retrospective study from The Cancer Imaging Archive (TCIA). Population Forty-nine subjects with low- and high-grade gliomas. Field strength/sequence 1.5 and 3.0T clinical systems using a single-echo echo planar imaging (EPI) acquisition. Assessment Manual regions of interest (ROIs) were provided by TCIA and automatically segmented ROIs were generated by k-means clustering. CBV was calculated based on conventional equations. Residue function dependent biomarkers (CBF, MTT, CTH) were found by two deconvolution methods: circular discretization followed by a signal-to-noise ratio (SNR)-adapted eigenvalue thresholding (Method 1) and Volterra discretization with L-curve-based Tikhonov regularization (Method 2). Statistical tests Analysis of variance, receiver operating characteristics (ROC), and logistic regression tests. Results MTT alone was unable to statistically differentiate glioma grade (P > 0.139). When normalized, tumor CBF, CTH, and CBV did not differ across field strengths (P > 0.141). Biomarkers normalized to automatically segmented regions performed equally (rCTH AUROC is 0.73 compared with 0.74) or better (rCBF AUROC increases from 0.74-0.84; rCBV AUROC increases 0.78-0.86) than manually drawn ROIs. By updating the current deconvolution steps (Method 2), rCTH can act as a classifier for glioma grade (P 0.577). Lastly, higher-order biomarkers (eg, rCBF and rCTH) along with rCBV increases AUROC to 0.92 for differentiating tumor grade as compared with 0.78 and 0.86 (manual and automatic reference regions, respectively) for rCBV alone. Data conclusion With optimized analysis pipelines, higher-order perfusion biomarkers (rCBF and rCTH) improve glioma grading as compared with CBV alone. Additionally, postprocessing steps impact thresholds needed for glioma grading. Level of evidence 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:547-553.

BACKGROUND AND PURPOSE: The percentage signal recovery in non-leakage-corrected (no preload, high flip angle, intermediate TE) DSC-MR imaging is known to differ significantly for glioblastoma, metastasis, and primary CNS lymphoma. Because the percentage signal recovery is influenced by preload and pulse sequence parameters, we investigated whether the percentage signal recovery can still differentiate these common contrast-enhancing neoplasms using a DSC-MR imaging protocol designed for relative CBV accuracy (preload, intermediate flip angle, low TE). MATERIALS AND METHODS: We retrospectively analyzed DSC-MR imaging of treatment-naive, pathology-proved glioblastomas (n = 14), primary central nervous system lymphomas (n = 7), metastases (n = 20), and meningiomas (n = 13) using a protocol designed for relative CBV accuracy (a one-quarter-dose preload and single-dose bolus of gadobutrol, TR/TE = 1290/40 ms, flip angle = 60° at 1.5T). Mean percentage signal recovery, relative CBV, and normalized baseline signal intensity were compared within contrast-enhancing lesion volumes. Classification accuracy was determined by receiver operating characteristic analysis. RESULTS: Relative CBV best differentiated meningioma from glioblastoma and from metastasis with areas under the curve of 0.84 and 0.82, respectively. The percentage signal recovery best differentiated primary central nervous system lymphoma from metastasis with an area under the curve of 0.81. Relative CBV and percentage signal recovery were similar in differentiating primary central nervous system lymphoma from glioblastoma and from meningioma. Although neither relative CBV nor percentage signal recovery differentiated glioblastoma from metastasis, mean normalized baseline signal intensity achieved 86% sensitivity and 50% specificity. CONCLUSIONS: Similar to results for non-preload-based DSC-MR imaging, percentage signal recovery for one-quarter-dose preload-based, intermediate flip angle DSC-MR imaging differentiates most pair-wise comparisons of glioblastoma, metastasis, primary central nervous system lymphoma, and meningioma, except for glioblastoma versus metastasis. Differences in normalized post-preload baseline signal for glioblastoma and metastasis, reflecting a snapshot of dynamic contrast enhancement, may motivate the use of single-dose multiecho protocols permitting simultaneous quantification of DSC-MR imaging and dynamic contrast-enhanced MR imaging parameters.

The use of rCBV as a response metric in clinical trials has been hampered, in part, due to variations in the biomarker consistency and associated interpretation across sites, stemming from differences in image acquisition and post-processing methods. This study leveraged a dynamic susceptibility contrast magnetic resonance imaging digital reference object to characterize rCBV consistency across 12 sites participating in the Quantitative Imaging Network (QIN), specifically focusing on differences in site-specific imaging protocols (IPs, n = 17), and PMs (n = 19) and differences due to site-specific IPs and PMs (n = 25). Thus, high agreement across sites occurs when 1 managing center processes rCBV despite slight variations in the IP. This result is most likely supported by current initiatives to standardize IPs. However, marked intersite disagreement was observed when site-specific software was applied for rCBV measurements. This study's results have important implications for comparing rCBV values across sites and trials, where variability in PMs could confound the comparison of therapeutic effectiveness and/or any attempts to establish thresholds for categorical response to therapy. To overcome these challenges and ensure the successful use of rCBV as a clinical trial biomarker, we recommend the establishment of qualifying and validating site- and trial-specific criteria for scanners and acquisition methods (eg, using a validated phantom) and the software tools used for dynamic susceptibility contrast magnetic resonance imaging analysis (eg, using a digital reference object where the ground truth is known).

PURPOSE Brain tumor dynamic susceptibility contrast (DSC) MRI is adversely impacted by T1 and T2∗ contrast agent leakage effects that result in inaccurate hemodynamic metrics. While multi-echo acquisitions remove T1 leakage effects, there is no consensus on the optimal set of acquisition parameters. Using a computational approach, we systematically evaluated a wide range of acquisition strategies to determine the optimal multi-echo DSC-MRI perfusion protocol. METHODS Using a population-based DSC-MRI digital reference object (DRO), we assessed the influence of preload dosing (no preload and full dose preload), field strength (1.5 and 3T), pulse sequence parameters (echo time, repetition time, and flip angle), and leakage correction on relative cerebral blood volume (rCBV) and flow (rCBF) accuracy. We also compared multi-echo DSC-MRI protocols with standard single-echo protocols. RESULTS Multi-echo DSC-MRI is highly consistent across all protocols, and multi-echo rCBV (with or without use of a preload dose) had higher accuracy than single-echo rCBV. Regression analysis showed that choice of repetition time and flip angle had minimal impact on multi-echo rCBV and rCBV, indicating the potential for significant flexibility in acquisition parameters. The echo time combination had minimal impact on rCBV, though longer echo times should be avoided, particularly at higher field strengths. Leakage correction improved rCBV accuracy in all cases. Multi-echo rCBF was less biased than single-echo rCBF, although rCBF accuracy was reduced overall relative to rCBV. CONCLUSIONS Multi-echo acquisitions were more robust than single-echo, essentially decoupling both repetition time and flip angle from rCBV accuracy. Multi-echo acquisitions obviate the need for preload dosing, although leakage correction to remove residual T2∗ leakage effects remains compulsory for high rCBV accuracy.

To demonstrate the feasibility of free-breathing three-dimensional (3D) radial ultrashort echo time (UTE) magnetic resonance (MR) imaging in the simultaneous detection of pulmonary embolism (PE) and high-quality evaluation of lung parenchyma.The institutional animal care committee approved this study. A total of 12 beagles underwent MR imaging and computed tomography (CT) before and after induction of PE with autologous clots. Breath-hold 3D MR angiography and free-breathing 3D radial UTE (1.0-mm isotropic spatial resolution; echo time, 0.08 msec) were performed at 3 T. Two blinded radiologists independently marked and graded all PEs on a four-point scale (1 = low confidence, 4 = absolutely certain) on MR angiographic and UTE images. Image quality of pulmonary arteries and lung parenchyma was scored on a four-point-scale (1 = poor, 4 = excellent). Locations and ratings of emboli were compared with reference standard CT images by using an alternative free-response receiver operating characteristic curve (AFROC) method. Areas under the curve and image quality ratings were compared by using the F test and the Wilcoxon signed-rank test.A total of 48 emboli were detected with CT. Both readers showed higher sensitivity for PE detection with UTE (83% and 79%) than with MR angiography (75% and 71%). The AFROC area under the curve was higher for UTE than for MR angiography (0.95 vs 0.89), with a significant difference in area under the curve of 0.06 (95% confidence interval: 0.01, 0.11; P = .018). UTE image quality exceeded that of MR angiography for subsegmental arteries (3.5 ± 0.7 vs 2.9 ± 0.5, P = .002) and lung parenchyma (3.8 ± 0.5 vs 2.2 ± 0.2, P.001). The apparent signal-to-noise ratio in pulmonary arteries and lung parenchyma was significantly higher for UTE than for MR angiography (41.0 ± 5.2 vs 24.5 ± 6.2 [P.001] and 10.2 ± 1.8 vs 3.5 ± 0.8 [P.001], respectively). The apparent contrast-to-noise ratio between arteries and PEs was higher for UTE than for MR angiography (20.3 ± 5.2 vs 15.4 ± 6.7, P = .055).In a canine model, free-breathing 3D radial UTE performs better than breath-hold 3D MR angiography in the detection of PE and yields better image quality for visualization of small vessels and lung parenchyma. Free-breathing 3D radial UTE for detection of PE is feasible and warrants evaluation in human subjects.

BACKGROUND AND PURPOSE: The accuracy of DSC-MR imaging CBV maps in glioblastoma depends on acquisition and analysis protocols. Multisite protocol heterogeneity has challenged standardization initiatives due to the difficulties of in vivo validation. This study sought to compare the accuracy of routinely used protocols using a digital reference object. MATERIALS AND METHODS: The digital reference object consisted of approximately 10,000 simulated voxels recapitulating typical signal heterogeneity encountered in vivo. The influence of acquisition and postprocessing methods on CBV reliability was evaluated across 6912 parameter combinations, including contrast agent dosing schemes, pulse sequence parameters, field strengths, and postprocessing methods. Accuracy and precision were assessed using the concordance correlation coefficient and coefficient of variation. RESULTS: Across all parameter space, the optimal protocol included full-dose contrast agent preload and bolus, intermediate (60°) flip angle, 30-ms TE, and postprocessing with a leakage-correction algorithm (concordance correlation coefficient = 0.97, coefficient of variation = 6.6%). Protocols with no preload or fractional dose preload and bolus using these acquisition parameters were generally less robust. However, a protocol with no preload, full-dose bolus, and low (30°) flip angle performed very well (concordance correlation coefficient = 0.93, coefficient of variation = 8.7% at 1.5T and concordance correlation coefficient = 0.92, coefficient of variation = 8.2% at 3T). CONCLUSIONS: Schemes with full-dose preload and bolus maximize CBV accuracy and reduce variability, which could enable smaller sample sizes and more reliable detection of CBV changes in clinical trials. When a lower total contrast agent dose is desired, use of a low flip angle, no preload, and full-dose bolus protocol may provide an attractive alternative.

Diffusion weighted MRI has become ubiquitous in many areas of medicine, including cancer diagnosis and treatment response monitoring. Reproducibility of diffusion metrics is essential for their acceptance as quantitative biomarkers in these areas. We examined the variability in the apparent diffusion coefficient (ADC) obtained from both postprocessing software implementations utilized by the NCI Quantitative Imaging Network and online scan time-generated ADC maps. Phantom and in vivo breast studies were evaluated for two ([Formula: see text]) and four ([Formula: see text]) [Formula: see text]-value diffusion metrics. Concordance of the majority of implementations was excellent for both phantom ADC measures and in vivo [Formula: see text], with relative biases [Formula: see text] ([Formula: see text]) and [Formula: see text] (phantom [Formula: see text]) but with higher deviations in ADC at the lowest phantom ADC values. In vivo [Formula: see text] concordance was good, with typical biases of [Formula: see text] to 3% but higher for online maps. Multiple b-value ADC implementations were separated into two groups determined by the fitting algorithm. Intergroup mean ADC differences ranged from negligible for phantom data to 2.8% for [Formula: see text] in vivo data. Some higher deviations were found for individual implementations and online parametric maps. Despite generally good concordance, implementation biases in ADC measures are sometimes significant and may be large enough to be of concern in multisite studies.

OBJECTIVES The objectives of this study were to compare pulmonary blood flow (PBF) measurements acquired with 3 previously published models (low-dose "single bolus," "dual bolus" and a "nonlinear correction" algorithm) for addressing the nonlinear relationship between contrast agent concentration and magnetic resonance signal in the arterial input function (AIF) and to compare both lung signal and PBF measurements obtained using gadopentetate dimeglumine (Gd-DTPA, Magnevist) with those obtained using the high-relaxivity agent gadobenate dimeglumine (Gd-BOPTA, Multihance). MATERIALS AND METHODS Ten of 12 healthy humans were successfully scanned on 2 consecutive days at 1.5 T. Contrast-enhanced pulmonary perfusion scans were acquired with a 3-dimensional spoiled gradient echo pulse sequence and interleaved variable density k-space sampling with a 1-second frame rate and 4 × 4 × 4-mm resolution. Each day, 2 perfusion scans were acquired with either Gd-DTPA or Gd-BOPTA; the order of the administered contrast agent was randomized. Region of interest analysis was used to determine PBF on the basis of the indicator dilution theory. Linear mixed-effects modeling was used to compare the AIF models and contrast agents. RESULTS With Gd-DTPA, no significant differences were observed between the mean PBF calculated for the single bolus (323 ± 110 mL/100mL/min), dual bolus (315 ± 177 mL/100mL/min), and nonlinear correction (298 ± 100 mL/100mL/min) approach. With Gd-BOPTA, the mean PBF using the dual bolus approach (245 ± 103 mL/100mL/min) was lower than with the single bolus (345 ± 130 mL/100mL/min P < 0.01) and nonlinear correction (321 ± 115 mL/100mL/min; P = 0.02). Peak lung enhancement was significantly higher in all regions with Gd-BOPTA than with Gd-DTPA (P << 0.01). CONCLUSIONS The dual bolus approach with Gd-BOPTA resulted in a significantly lower PBF than did the other combinations of contrast agent and AIF model. No other statistically significant differences were found. Given the much higher signal in the lung parenchyma using Gd-BOPTA, the use of Gd-BOPTA with either single bolus or the nonlinear correction method appears most promising for voxelwise perfusion quantification using 3-dimensional dynamic contrast-enhanced pulmonary perfusion magnetic resonance imaging.

The standardization and broad-scale integration of dynamic susceptibility contrast (DSC)-magnetic resonance imaging (MRI) have been confounded by a lack of consensus on DSC-MRI methodology for preventing potential relative cerebral blood volume inaccuracies, including the choice of acquisition protocols and postprocessing algorithms. Therefore, we developed a digital reference object (DRO), using physiological and kinetic parameters derived from in vivo data, unique voxel-wise 3-dimensional tissue structures, and a validated MRI signal computational approach, aimed at validating image acquisition and analysis methods for accurately measuring relative cerebral blood volume in glioblastomas. To achieve DSC-MRI signals representative of the temporal characteristics, magnitude, and distribution of contrast agent-induced T1 and T2* changes observed across multiple glioblastomas, the DRO's input parameters were trained using DSC-MRI data from 23 glioblastomas (&gt, 40 000 voxels). The DRO's ability to produce reliable signals for combinations of pulse sequence parameters and contrast agent dosing schemes unlike those in the training data set was validated by comparison with in vivo dual-echo DSC-MRI data acquired in a separate cohort of patients with glioblastomas. Representative applications of the DRO are presented, including the selection of DSC-MRI acquisition and postprocessing methods that optimize CBV accuracy, determination of the impact of DSC-MRI methodology choices on sample size requirements, and the assessment of treatment response in clinical glioblastoma trials.

BACKGROUND AND PURPOSE: The optimal TE must be calculated to minimize the variance in CBV measurements made with DSC MR imaging. Simulations can be used to determine the influence of the TE on CBV, but they may not adequately recapitulate the in vivo heterogeneity of precontrast T2*, contrast agent kinetics, and the biophysical basis of contrast agent–induced T2* changes. The purpose of this study was to combine quantitative multiecho DSC MRI T2* time curves with error analysis in order to compute the optimal TE for a traditional single-echo acquisition. MATERIALS AND METHODS: Eleven subjects with high-grade gliomas were scanned at 3T with a dual-echo DSC MR imaging sequence to quantify contrast agent–induced T2* changes in this retrospective study. Optimized TEs were calculated with propagation of error analysis for high-grade glial tumors, normal-appearing white matter, and arterial input function estimation. RESULTS: The optimal TE is a weighted average of the T2* values that occur as a contrast agent bolus transverses a voxel. The mean optimal TEs were 30.0 ± 7.4 ms for high-grade glial tumors, 36.3 ± 4.6 ms for normal-appearing white matter, and 11.8 ± 1.4 ms for arterial input function estimation (repeated-measures ANOVA, P CONCLUSIONS: Greater heterogeneity was observed in the optimal TE values for high-grade gliomas, and mean values of all 3 ROIs were statistically significant. The optimal TE for the arterial input function estimation is much shorter; this finding implies that quantitative DSC MR imaging acquisitions would benefit from multiecho acquisitions. In the case of a single-echo acquisition, the optimal TE prescribed should be 30–35 ms (without a preload) and 20–30 ms (with a standard full-dose preload).

Purpose To assess the feasibility of spatial–temporal constrained reconstruction for accelerated regional lung perfusion using highly undersampled dynamic contrast-enhanced (DCE) three-dimensional (3D) radial MRI with ultrashort echo time (UTE). Methods A combined strategy was used to accelerate DCE MRI for 3D pulmonary perfusion with whole lung coverage. A highly undersampled 3D radial UTE MRI acquisition was combined with an iterative constrained reconstruction exploiting principal component analysis and wavelet soft-thresholding for dimensionality reduction in space and time. The performance of the method was evaluated using a 3D fractal-based DCE digital lung phantom. Simulated perfusion maps and contrast enhancement curves were compared with ground truth using the structural similarity index (SSIM) to determine robust threshold and regularization levels. Feasibility studies were then performed in a canine and a human subject with 3D radial UTE (TE = 0.08 ms) acquisition to assess feasibility of mapping regional 3D perfusion. Results The method was able to accurately recover perfusion maps in the phantom with a nominal isotropic spatial resolution of 1.5 mm (SSIM of 0.949). The canine and human subject studies demonstrated feasibility for providing artifact-free perfusion maps in a simple 3D breath-held acquisition. Conclusion The proposed method is promising for fast and flexible 3D pulmonary perfusion imaging. Magn Reson Med 73:555–564, 2015. © 2014 Wiley Periodicals, Inc.

Dynamic susceptibility contrast (DSC) MRI measures of brain tumor cerebral blood volume (CBV) are able to predict grade, overall survival and response to treatment. Wide-spread acceptance of DSC-MRI has been challenged by the need to balance contrast agent dose and CBV accuracy. The goal of this study was to identify and validate single-dose, BTIP compliant, DSC-MRI protocols. Using a validated, patient-based DRO, we evaluated CBV accuracy across a range of acquisition parameters (field strength, TR, TE, flip angle, multi-echo acquisitions, dosing protocols) and post-processing steps. To validate the optimal protocols, we next collected DSC-MRI data following ASFNR’s recommended “double – dose” approach, where a single-dose preload (to minimize T1 effects) is given prior to a second bolus injection (for DSC-MRI data acquisition). The single-dose DSC-MRI data was collected during the preload bolus injection. Consistency of the derived CBV data, visual agreement and data characteristics (e.g. CNR) was statistically evaluated. When using a single-dose and routine single-echo pulse sequence, the DRO analysis found that a low flip angle (LFA = 30o) and 30ms TE provided the highest CBV accuracy (concordance correlation coefficient (CCC) = 0.92) and precision (coefficient of variation (CV) = 8.2%)). For comparison, the maximum accuracy found with the DRO utilizes a double-dose injection protocol and yielded a CCC of 0.98 and CV of 6.8%. Single-dose, multi-echo acquisitions provided higher accuracy than the LFA data and matched that found with the double-dose approach. In patients (data collection ongoing), the agreement between single-dose LFA (n > 40) or multi-echo (n > 40) based CBV values and the reference double-dose approach was very high (CCC > 0.94) and were statistically equivalent. Optimized single-dose DSC-MRI protocols provide highly accurate CBV data, use lower doses of contrast agent, and simplify scan procedures, indicating their potential for robust use in clinical practice and trials.

Purpose To develop and demonstrate a breathheld 3D radial ultrashort echo time (UTE) acquisition to visualize co-registered lung perfusion and vascular structure. Materials and Methods Nine healthy dogs were scanned twice at 3 Tesla (T). Contrast-enhanced pulmonary perfusion scans were acquired with a temporally interleaved three-dimensional (3D) radial UTE (TE = 0.08 ms) sequence in a breathhold (1 s time frames over a 33 s breathhold). The 3D breathheld volume was reconstructed into time-resolved perfusion datasets, and a composite vascular structure dataset. For structural comparison, a 5 min respiratory-gated 3D radial UTE scan was acquired. Data were analyzed by quantitative metrics and radiologist scoring. Results Appropriate time-course of contrast was seen in all subjects. Right ventricle to aorta transit times were 7.4 ± 2.0 s. Relative lung enhancement was a factor of 8.4 ± 1.5. Radiologist scoring showed similarly excellent visualization of the pulmonary arteries to the subsegmental level in breathheld (94% of cases) and respiratory-gated (100% of cases) acquisitions (P = 0.33) despite the aggressive under sampling in the breathheld scan. Similarly, differentiation of lung tissue and airways was achieved by both acquisition methods. Conclusion A time-resolved 3D radial UTE sequence for simultaneous imaging of pulmonary perfusion and co-registered vascular structure is feasible. J. Magn. Reson. Imaging 2015;41:52–59. © 2013 Wiley Periodicals, Inc.

Purpose To demonstrate the feasibility of direct virtual coil (DVC) in the setting of 4D dynamic imaging used in multiple clinical applications. Theory and Methods Three dynamic imaging applications were chosen: pulmonary perfusion, liver perfusion, and peripheral MR angiography (MRA), with 18, 11, and 10 subjects, respectively. After view-sharing, the k-space data were reconstructed twice: once with channel-by-channel (CBC) followed by sum-of-squares coil combination and once with DVC. Images reconstructed using CBC and DVC were compared and scored based on overall image quality by two experienced radiologists using a five-point scale. Results The CBC and DVC showed similar image quality in image domain. Time course measurements also showed good agreement in the temporal domain. CBC and DVC images were scored as equivalent for all pulmonary perfusion cases, all liver perfusion cases, and four of the 10 peripheral MRA cases. For the remaining six peripheral MRA cases, DVC were scored as slightly better (not clinically significant) than the CBC images by Radiologist A and as equivalent by Radiologist B. Conclusion For dynamic contrast-enhanced MR applications, it is clinically feasible to reduce image reconstruction time while maintaining image quality and time course measurement using the DVC technique. Magn Reson Med 71:783–789, 2014. © 2013 Wiley Periodicals, Inc.

Purpose: To demonstrate the feasibility of performing single breathhold, noncardiac gated, ultrafast, high spatial-temporal resolution whole chest MR pulmonary perfusion imaging in humans. Materials and Methods: Eight subjects (five male, three female) were scanned with the proposed method on a 3 Tesla clinical scanner using a 32-channel phased-array coil. Seven (88%) were healthy volunteers, and one was a patient volunteer with sarcoidosis. The peak lung enhancement phase for each subject was scored for gravitational effect, peak parenchymal enhancement and severity of artifacts by three cardiothoracic radiologists independently. Results: All studies were successfully performed by MR technologists without any additional training. Mean parenchymal signal was very good, measuring 0.78 ± 0.13 (continuous scale, 0 = “none” 1 = “excellent”). Mean level of motion artifacts was low, measuring 0.13 ± 0.08 (continuous scale, 0 = “none” 1 = “severe”). Conclusion: It is feasible to perform single breathhold, noncardiac gated, ultrafast, high spatial-temporal resolution whole chest MR pulmonary perfusion imaging in humans. J. Magn. Reson. Imaging 2013;38:751–756. © 2013 Wiley Periodicals, Inc.

This paper reports on results of a multisite collaborative project launched by the MRI subgroup of Quantitative Imaging Network to assess current capability and provide future guidelines for generating a standard parametric diffusion map Digital Imaging and Communication in Medicine (DICOM) in clinical trials that utilize quantitative diffusion-weighted imaging (DWI). Participating sites used a multivendor DWI DICOM dataset of a single phantom to generate parametric maps (PMs) of the apparent diffusion coefficient (ADC) based on two models. The results were evaluated for numerical consistency among models and true phantom ADC values, as well as for consistency of metadata with attributes required by the DICOM standards. This analysis identified missing metadata descriptive of the sources for detected numerical discrepancies among ADC models. Instead of the DICOM PM object, all sites stored ADC maps as DICOM MR objects, generally lacking designated attributes and coded terms for quantitative DWI modeling. Source-image reference, model parameters, ADC units and scale, deemed important for numerical consistency, were either missing or stored using nonstandard conventions. Guided by the identified limitations, the DICOM PM standard has been amended to include coded terms for the relevant diffusion models. Open-source software has been developed to support conversion of site-specific formats into the standard representation.

To assess the feasibility of spatial-temporal constrained reconstruction for accelerated regional lung perfusion using highly undersampled dynamic contrast-enhanced (DCE) three-dimensional (3D) radial MRI with ultrashort echo time (UTE).A combined strategy was used to accelerate DCE MRI for 3D pulmonary perfusion with whole lung coverage. A highly undersampled 3D radial UTE MRI acquisition was combined with an iterative constrained reconstruction exploiting principal component analysis and wavelet soft-thresholding for dimensionality reduction in space and time. The performance of the method was evaluated using a 3D fractal-based DCE digital lung phantom. Simulated perfusion maps and contrast enhancement curves were compared with ground truth using the structural similarity index (SSIM) to determine robust threshold and regularization levels. Feasibility studies were then performed in a canine and a human subject with 3D radial UTE (TE=0.08 ms) acquisition to assess feasibility of mapping regional 3D perfusion.The method was able to accurately recover perfusion maps in the phantom with a nominal isotropic spatial resolution of 1.5 mm (SSIM of 0.949). The canine and human subject studies demonstrated feasibility for providing artifact-free perfusion maps in a simple 3D breath-held acquisition.The proposed method is promising for fast and flexible 3D pulmonary perfusion imaging. Magn Reson

To develop and demonstrate a breathheld 3D radial ultrashort echo time (UTE) acquisition to visualize co-registered lung perfusion and vascular structure.Nine healthy dogs were scanned twice at 3 Tesla (T). Contrast-enhanced pulmonary perfusion scans were acquired with a temporally interleaved three-dimensional (3D) radial UTE (TE = 0.08 ms) sequence in a breathhold (1 s time frames over a 33 s breathhold). The 3D breathheld volume was reconstructed into time-resolved perfusion datasets, and a composite vascular structure dataset. For structural comparison, a 5 min respiratory-gated 3D radial UTE scan was acquired. Data were analyzed by quantitative metrics and radiologist scoring.Appropriate time-course of contrast was seen in all subjects. Right ventricle to aorta transit times were 7.4 ± 2.0 s. Relative lung enhancement was a factor of 8.4 ± 1.5. Radiologist scoring showed similarly excellent visualization of the pulmonary arteries to the subsegmental level in breathheld (94% of cases) and respiratory-gated (100% of cases) acquisitions (P = 0.33) despite the aggressive under sampling in the breathheld scan. Similarly, differentiation of lung tissue and airways was achieved by both acquisition methods.A time-resolved 3D radial UTE sequence for simultaneous imaging of pulmonary perfusion and co-registered vascular structure is feasible.

To demonstrate the feasibility of direct virtual coil (DVC) in the setting of 4D dynamic imaging used in multiple clinical applications.Three dynamic imaging applications were chosen: pulmonary perfusion, liver perfusion, and peripheral MR angiography (MRA), with 18, 11, and 10 subjects, respectively. After view-sharing, the k-space data were reconstructed twice: once with channel-by-channel (CBC) followed by sum-of-squares coil combination and once with DVC. Images reconstructed using CBC and DVC were compared and scored based on overall image quality by two experienced radiologists using a five-point scale.The CBC and DVC showed similar image quality in image domain. Time course measurements also showed good agreement in the temporal domain. CBC and DVC images were scored as equivalent for all pulmonary perfusion cases, all liver perfusion cases, and four of the 10 peripheral MRA cases. For the remaining six peripheral MRA cases, DVC were scored as slightly better (not clinically significant) than the CBC images by Radiologist A and as equivalent by Radiologist B.For dynamic contrast-enhanced MR applications, it is clinically feasible to reduce image reconstruction time while maintaining image quality and time course measurement using the DVC technique.

Although the concept of general reading skill has been assumed to be the primary contribution to comprehension, a demonstration that reading skill contributes to comprehension independent of domain knowledge has been lacking. This research investigates the relative contribution and trade‐off effects of children's knowledge and reading skill in text comprehension in a single study. Children in Grades 4 through 7, grouped as high or low reading skill and high or low knowledge on the basis of a domain‐specific topic, participated in this study. Comprehension was measured in two parallel texts: one domain specific and one domain general. The results suggested that domain knowledge and reading skill can be traded in order to achieve similar levels of comprehension. Reading skill compensates for deficient knowledge and specific knowledge compensates for deficient reading ability.

Three groups of college readers were compared on several information-processing and language comprehension tasks that tap the cognitive components of reading. The groups were skilled readers with high verbal and nonverbal abilities, low-skilled readers with a disparity between verbal and nonverbal abilities, and low-skilled readers who were low in both verbal and nonverbal ability. Results confirm the importance of word processing and general language comprehension in distinguishing skilled from less skilled readers. Results also support the view that reading ability is best described as a continuous function and provide evidence of the reemergence of lower level processing skills in adults as a function of text difficulty

This study investigated phonetic activation in reading a nonalphabetic script – Chinese. Since the Chinese ideographic script can be read with more than one dialectal pronunciation, a reader who has learned to read in two dialects will have two pronunciations for the same word stored in his memory. Thus, interference effects will occur. Sixteen subjects who read in Cantonese and Mandarin and 16 subjects who read in Mandarin but not in Cantonese were tested in a similarity judgment task based on pairs of Chinese words that were pronounced the same or differently in one or both of the dialects. That automatic phonetic activation would occur even for an ideographic script such as Chinese was supported by the results.

When a briefly exposed target word is followed by a pseudoword mask, the disruptive masking effect is reduced when the mask shares graphemes with the target word and is further reduced when the mask shares phonemes with the target word (Perfetti, Bell, & Delaney, 1988,Journal of Memory and Language27, 59–70). These results implicate early (prelexical) phonemic activation during word identification. In Experiment 1, this phonemic masking effect was found to hold through target exposure durations ranging from 35 to 55 ms and to be independent of word frequency and spelling pattern consistency. In Experiment 3, completely convergent results were found in a masked priming paradigm that varied the exposure of a masked pseudoword prime from 25 to 65 ms. Phonemic priming effects were found by 45 ms correcting earlier conclusions favoring direct visual access based on this paradigm. Together, the masking and priming results strongly support a process of early phonemic activation prior to word identification. The results are most naturally handled by a single-mechanism activation model, but are also consistent with restricted versions of dual route theories.

We use ultrafast terahertz spectroscopy to observe terahertz-frequency electron oscillations in a modulation-doped InGaAs∕AlGaAs parabolic quantum well with subband spacing 0.01eV. Our study examined how the extrinsic electron density in the well influences terahertz emission efficiency and we found no strong dependence. This indicates that terahertz emission in this structure arises from quantum beating of the photogenerated electrons. Terahertz emission from the cold extrinsic electrons due to ultrafast field screening plays at most a secondary role.

IN TWO STUDIES, the authors examine the tongue-twister effect (McCutchen & Perfetti, 1982) in order to help determine the role of phonological information during silent reading. In the first experiment, U.S. college students took longer to judge the semantic acceptability of sentences containing several words with the same initial consonants (tongue-twisters) than of matched control sentences. In addition, when their working memory was pre-loaded with digits whose names repeated the same consonants as occurred in the sentences, a specific phonetic interference was observed. The authors conclude that the tongue-twister effect results from phonetic rather than visual confusion, and that the locus of the effect is within working memory. In a second experiment employing a similar methodology but using a lexical decision task, no tongue-twister effect was found. Thus, the tongue-twister effect appears to occur during the memory and comprehension processes involved in sentence processing, not during processes involved in isolated word reading.

Visual access to a printed word may be accompanied by a very rapid activation of phonetic properties of the word as well as its constituent letters. We suggest that such automatic activation during word identification, rather than only postlexical recoding, routinely occurs in reading. To demonstrate such activation, we varied the graphemic and phonetic properties shared by a word target and a following pseudoword mask. Graphemic ( mard ) and homophonic ( mayd ) masks, equated for number of letters shared with a word target ( made ), both showed a masking reduction effect relative to a control mask. There was an additional effect of the homophonic mask over the graphemic mask, attributable to phonetic activation. A second experiment verified this pattern of mask reduction effects using conditions that ruled out any explanation of the effect that does not take account of the target-mask relationship. We take the results to suggest that a phonetic activation nonoptionally occurs (prelexically) during lexical access.