Clinical Feasibility of Ultrafast Contrast-Enhanced T1-Weighted 3D-EPI for Evaluating Intracranial Enhancing Lesions in Oncology Patients: Comparison with Standard 3D MPRAGE Sequence.

BACKGROUND AND PURPOSE: Contrast-enhanced 3D T1WI is a preferred sequence for brain tumor imaging despite the long scan time. This study investigated the clinical feasibility of ultrafast contrast-enhanced T1WI by 3D echo-planar imaging compared with a standard contrast-enhanced 3D MPRAGE sequence for evaluating intracranial enhancing lesions in oncology patients. MATERIALS AND METHODS: Sixty-one patients in oncology underwent brain MR imaging including both contrast-enhanced T1WI, 3D-EPI and 3D MPRAGE, in a single examination session for evaluating intracranial tumors. Two neuroradiologists evaluated image quality, lesion conspicuity, diagnostic confidence, number and size of the lesions, and contrast-to-noise ratio measurements from the 2 different sequences. RESULTS: Ultrafast 3D-EPI T1WI did not reveal significant differences in diagnostic confidence, contrast-to-noise ratiolesion/parenchyma, and the number of enhancing lesions compared with MPRAGE (P > .05). However, ultrafast 3D-EPI T1WI revealed inferior image quality, inferior anatomic delineation and greater susceptibility artifacts with fewer motion artifacts than images obtained with MPRAGE. The mean contrast-to-noise ratioWM/GM and visual conspicuity of the lesion on ultrafast 3D-EPI T1WI were lower than those of MPRAGE (P < .001). CONCLUSIONS: Ultrafast 3D-EPI T1WI showed comparable diagnostic performance with sufficient image quality and a 7-fold reduction in scan time for evaluating intracranial enhancing lesions compared with standard MPRAGE, even though it was limited by an inferior image quality and frequent susceptibility artifacts. Therefore, we believe that ultrafast 3D-EPI T1WI may be a viable option in oncology patients prone to movement during imaging studies.

Clinical Experience of 1-Minute Brain MRI Using a Multicontrast EPI Sequence in a Different Scan Environment.

BACKGROUND AND PURPOSE: The long scan time of MR imaging is a major drawback limiting its clinical use in neuroimaging; therefore, we aimed to investigate the clinical feasibility of a 1-minute full-brain MR imaging using a multicontrast EPI sequence on a different MR imaging scanner than the ones previously reported. MATERIALS AND METHODS: We retrospectively reviewed the records of 146 patients who underwent a multicontrast EPI sequence, including T1-FLAIR, T2-FLAIR, T2WI, DWI, and T2*WI sequences. Two attending neuroradiologists assessed the image quality of each sequence to compare the multicontrast EPI sequence with routine MR imaging protocols. We used the Wilcoxon signed rank test and McNemar test to compare the 2 MR imaging protocols. RESULTS: The multicontrast EPI sequence generally showed sufficient image quality of >2 points using a 4-point assessment scale. Regarding image quality and susceptibility artifacts, there was no significant difference between the multicontrast EPI sequence DWI and routine DWI (P > .05), attesting to noninferiority of the multicontrast EPI, whereas there were significant differences in the other 4 sequences between the 2 MR imaging protocols. CONCLUSIONS: The multicontrast EPI sequence showed sufficient image quality for clinical use with a shorter scan time; however, it was limited by inferior image quality and frequent susceptibility artifacts compared with routine brain MR imaging. Therefore, the multicontrast EPI sequence cannot completely replace the routine MR imaging protocol at present; however, it may be a feasible option in specific clinical situations such as screening, time-critical diseases or for use with patients prone to motion.

Fast susceptibility-weighted imaging with three-dimensional short-axis propeller (SAP)-echo-planar imaging.

BACKGROUND: Susceptibility-weighted imaging (SWI) in neuroimaging can be challenging due to long scan times of three-dimensional (3D) gradient recalled echo (GRE), while faster techniques such as 3D interleaved echo-planar imaging (iEPI) are prone to motion artifacts. Here we outline and implement a 3D short-axis propeller echo-planar imaging (SAP-EPI) trajectory as a faster, motion-correctable approach for SWI. METHODS: Experiments were conducted on a 3T MRI system. The 3D SAP-EPI, 3D iEPI, and 3D GRE SWI scans were acquired on two volunteers. Controlled motion experiments were conducted to test the motion-correction capability of 3D SAP-EPI. The 3D SAP-EPI SWI data were acquired on two pediatric patients as a potential alternative to 2D GRE used clinically. RESULTS: The 3D GRE images had a better target resolution (0.47 × 0.94 × 2 mm, scan time = 5 min), iEPI and SAP-EPI images (resolution = 0.94 × 0.94 × 2 mm) were acquired in a faster scan time (1:52 min) with twice the brain coverage. SAP-EPI showed motion-correction capability and some immunity to undersampling from rejected data. CONCLUSION: While 3D SAP-EPI suffers from some geometric distortion, its short scan time and motion-correction capability suggest that SAP-EPI may be a useful alternative to GRE and iEPI for use in SWI, particularly in uncooperative patients.

Diffusion-weighted imaging with dual-echo echo-planar imaging for better sensitivity to acute stroke.

BACKGROUND AND PURPOSE: Parallel imaging facilitates the acquisition of echo-planar images with a reduced TE, enabling the incorporation of an additional image at a later TE. Here we investigated the use of a parallel imaging-enhanced dual-echo EPI sequence to improve lesion conspicuity in diffusion-weighted imaging. MATERIALS AND METHODS: Parallel imaging-enhanced dual-echo DWI data were acquired in 50 consecutive patients suspected of stroke at 1.5T. The dual-echo acquisition included 2 EPI for 1 diffusion-preparation period (echo 1 [TE = 48 ms] and echo 2 [TE = 105 ms]). Three neuroradiologists independently reviewed the 2 echoes by using the routine DWI of our institution as a reference. Images were graded on lesion conspicuity, diagnostic confidence, and image quality. The apparent diffusion coefficient map from echo 1 was used to validate the presence of acute infarction. Relaxivity maps calculated from the 2 echoes were evaluated for potential complementary information. RESULTS: Echo 1 and 2 DWIs were rated as better than the reference DWI. While echo 1 had better image quality overall, echo 2 was unanimously favored over both echo 1 and the reference DWI for its high sensitivity in detecting acute infarcts. CONCLUSIONS: Parallel imaging-enhanced dual-echo diffusion-weighted EPI is a useful method for evaluating lesions with reduced diffusivity. The long TE of echo 2 produced DWIs that exhibited superior lesion conspicuity compared with images acquired at a shorter TE. Echo 1 provided higher SNR ADC maps for specificity to acute infarction. The relaxivity maps may serve to complement information regarding blood products and mineralization.

Clinical assessment of standard and generalized autocalibrating partially parallel acquisition diffusion imaging: effects of reduction factor and spatial resolution.

BACKGROUND AND PURPOSE: PI improves routine EPI-based DWI by enabling higher spatial resolution and reducing geometric distortion, though it remains unclear which of these is most important. We evaluated the relative contribution of these factors and assessed their ability to increase lesion conspicuity and diagnostic confidence by using a GRAPPA technique. MATERIALS AND METHODS: Four separate DWI scans were obtained at 1.5T in 48 patients with independent variation of in-plane spatial resolution (1.88 mm(2) versus 1.25 mm(2)) and/or reduction factor (R = 1 versus R = 3). A neuroradiologist with access to clinical history and additional imaging sequences provided a reference standard diagnosis for each case. Three blinded neuroradiologists assessed scans for abnormalities and also evaluated multiple imaging-quality metrics by using a 5-point ordinal scale. Logistic regression was used to determine the impact of each factor on subjective image quality and confidence. RESULTS: Reference standard diagnoses in the patient cohort were acute ischemic stroke (n = 30), ischemic stroke with hemorrhagic conversion (n = 4), intraparenchymal hemorrhage (n = 9), or no acute lesion (n = 5). While readers preferred both a higher reduction factor and a higher spatial resolution, the largest effect was due to an increased reduction factor (odds ratio, 47 ± 16). Small lesions were more confidently discriminated from artifacts on R = 3 images. The diagnosis changed in 5 of 48 scans, always toward the reference standard reading and exclusively for posterior fossa lesions. CONCLUSIONS: PI improves DWI primarily by reducing geometric distortion rather than by increasing spatial resolution. This outcome leads to a more accurate and confident diagnosis of small lesions.

Clinical application of readout-segmented- echo-planar imaging for diffusion-weighted imaging in pediatric brain.

BACKGROUND AND PURPOSE: RS-EPI has been suggested as an alternative approach to EPI for high-resolution DWI with reduced distortions. To determine whether RS-EPI is a useful approach for routine clinical use, we implemented GRAPPA-accelerated RS-EPI DWI at our pediatric hospital and graded the images alongside standard accelerated (ASSET) EPI DWI used routinely for clinical studies. MATERIALS AND METHODS: GRAPPA-accelerated RS-EPI DWIs and ASSET EPI DWIs were acquired on 35 pediatric patients using a 3T system in 35 pediatric patients. The images were graded alongside each other by using a 7-point Likert scale as follows: 1, nondiagnostic; 2, poor; 3, acceptable; 4, standard; 5, above average; 6, good; and 7, outstanding. RESULTS: The following were the average scores for EPI and RS-EPI, respectively: resolution, 3.5/5.2; distortion level, 2.9/6.0; SNR, 3.4/4.1; lesion conspicuity, 3.3/5.9; and diagnostic confidence, 3.2/6.0. Overall, the RS-EPI had significantly improved diagnostic confidence and more reliably defined the extent and structure of several lesions. Although ASSET EPI scans had better SNR per scanning time, the higher spatial resolution as well as reduced blurring and distortions on RS-EPI scans helped to better reveal important anatomic details at the cortical-subcortical levels, brain stem, temporal and inferior frontal lobes, skull base, sinonasal cavity, cranial nerves, and orbits. CONCLUSIONS: This work shows the importance of both resolution and decreased distortions in the clinics, which can be accomplished by a combination of parallel imaging and alternative k-space trajectories such as RS-EPI.

Correction of MR image distortions induced by metallic objects using a 3D cubic B-spline basis set: application to stereotactic surgical planning.

Metallic implants in MRI cause spin-echo (SE) images to be distorted in the slice and frequency-encoding directions. Chang and Fitzpatrick (IEEE Trans Med Imaging 1992;11:319-329) proposed a distortion correction method (termed the CF method) based on the magnitude images from two SE acquisitions that differ only in the polarity of the frequency-encoding and slice-selection gradients. In the present study we solved some problems with the CF method, primarily by modeling the field inhomogeneities as a single 3D displacement field built by 3D cubic B-splines. The 3D displacement field was applied in the actual distortion direction in the slice/frequency-encoding plane. To account for patient head motion, a 3D rigid body motion correction was also incorporated in the model. Experiments on a phantom containing an aneurysm clip showed that the knot spacing between the B-splines is a very important factor in both the final image quality and the processing speed. Depending on the knot spacing and the image volume size, the number of unknowns range from a few thousands to over 100,000, leading to processing times ranging from minutes to days. Optimal knot spacing, a means of increasing the processing speed, and other parameters are investigated and discussed.

On the effects of gating in diffusion imaging of the brain using single shot EPI.

To reduce image artifacts in diffusion tensor imaging using single shot EPI, cardiac gating may be performed to prevent brain motion induced signal void in the DWI data. In this work the necessity of performing cardiac gating with single shot echo planar imaging has been explored using F statistics of the variance in DWI data. Peripheral measurement of the cardiac cycle has been employed because of its greater convenience, and hence use, compared to ECG gating. Four volunteers have been studied. Six different trigger delays have been evaluated in the range 18-500 ms relative the peripheral pulse wave. Brain motion was found significant in and inferior to the corpus callosum area. A trigger delay of 500 ms was found to be optimal. However, a long delay allows only for one slice per R-R interval. Therefore, a minimum trigger delay may be the best choice in terms of SNR per unit of experiment time.

Abnormal brain white matter in schizophrenia: a diffusion tensor imaging study.

Fractional anisotropy and the mean diffusion coefficient were measured in the cerebral volume in 20 schizophrenic and 24 healthy subjects, men and women, using diffusion tensor imaging. In addition, 3D SPGR was used for segmentation of brain tissue into grey and white matter and cerebrospinal fluid. In schizophrenic patients, fractional anisotropy was reduced in the splenium of the corpus callosum and in adjacent occipital white matter. The segmentation revealed no tissue deficits in the volume of reduced fractional anisotropy. The mean diffusion was increased in the total white and grey matter volume of the schizophrenic patients compared with the healthy subjects. The findings support the view that global and regional white matter abnormalities occur in chronic schizophrenia.

Condition number as a measure of noise performance of diffusion tensor data acquisition schemes with MRI.

Diffusion tensor mapping with MRI can noninvasively track neural connectivity and has great potential for neural scientific research and clinical applications. For each diffusion tensor imaging (DTI) data acquisition scheme, the diffusion tensor is related to the measured apparent diffusion coefficients (ADC) by a transformation matrix. With theoretical analysis we demonstrate that the noise performance of a DTI scheme is dependent on the condition number of the transformation matrix. To test the theoretical framework, we compared the noise performances of different DTI schemes using Monte-Carlo computer simulations and experimental DTI measurements. Both the simulation and the experimental results confirmed that the noise performances of different DTI schemes are significantly correlated with the condition number of the associated transformation matrices. We therefore applied numerical algorithms to optimize a DTI scheme by minimizing the condition number, hence improving the robustness to experimental noise. In the determination of anisotropic diffusion tensors with different orientations, MRI data acquisitions using a single optimum b value based on the mean diffusivity can produce ADC maps with regional differences in noise level. This will give rise to rotational variances of eigenvalues and anisotropy when diffusion tensor mapping is performed using a DTI scheme with a limited number of diffusion-weighting gradient directions. To reduce this type of artifact, a DTI scheme with not only a small condition number but also a large number of evenly distributed diffusion-weighting gradients in 3D is preferable.

Noise considerations in the determination of diffusion tensor anisotropy.

In this study the noise sensitivity of various anisotropy indices has been investigated by Monte-Carlo computer simulations and magnetic resonance imaging (MRI) measurements in a phantom and 5 healthy volunteers. Particularly, we compared the noise performance of indices defined solely in terms of eigenvalues and those based on both the eigenvalues and eigenvectors. It is found that anisotropy indices based on both eigenvalues and eigenvectors are less sensitive to noise, and spatial averaging with neighboring pixels can further reduce the standard deviation. To reduce the partial volume effect caused by the spatial averaging with neighboring voxels, an averaging method in the time domain based on the orientation coherence of eigenvectors in repeated experiments has been proposed.

Tickling expectations: neural processing in anticipation of a sensory stimulus.

Predictions of the near future can optimize the accuracy and speed of sensory processing as well as of behavioral responses. Previous experience and contextual cues are essential elements in the generation of a subjective prediction. Using a blocked fMRI paradigm, we investigated the pattern of neural activation in anticipation of a sensory stimulus and during the processing of the somatosensory stimulus itself. Tickling was chosen as the somatosensory stimulus rather than simple touch in order to increase the probability to get a high degree of anticipation. The location and nature of the stimulus were well defined to the subject. The state of anticipation was initiated by attributing an uncertainty regarding the time of stimulus onset. The network of activation and deactivation during anticipation of the expected stimulus was similar to that engaged during the actual sensory stimulation. The areas that were activated during both states included the contralateral primary sensory cortex, bilateral areas in the inferior parietal lobules, the putative area SII, the right anterior cingulate cortex and areas in the right prefrontal cortex. Similarly, common decreases were observed in areas of sensorimotor cortex located outside the area representing the target of stimulus, i.e., areas that process information which is irrelevant to the attended process. The overlapping pattern of change, during the somatosensory stimulation and the anticipation, furthers the idea that predictions are subserved by a neuronal network similar to that which subserves the processing of actual sensory input. Moreover, this study indicates that activation of primary somatosensory cortex can be obtained without intra-modal sensory input. These findings suggest that anticipation may invoke a tonic top-down regulation of neural activity.

Convergent and criterion-related validity of the Behavior Assessment System for Children-Parent Rating Scale.

Examined aspects of the validity of the Behavior Assessment System for Children (BASC; Reynolds & Kamphaus, 1992) Parent Rating Scale (BASC-PRS) in 156 children with cross-setting disruptive behavior. The BASC-PRS is a recently published multidimensional measure composed of conceptually derived scales created for use in conjunction with psychiatric and educational classification systems. Convergent validity was assessed through correlations of BASC-PRS scale scores with scale scores on the Child Behavior Checklist/4-18 (CBCL/4-18; Achenbach, 1991b). Criterion-related validity was evaluated as the ability of BASC-PRS and CBCL/4-18 scales to predict membership in diagnostic groupings (no diagnosis, attention deficit hyperactivity disorder [ADHD] only, and ADHD with a comorbid externalizing disorder) derived via structured interviews based on the third, revised edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1987). Results showed the validity of the BASC-PRS to be comparable to that of the CBCL/4-18. Given its conceptually derived scales, the BASC-PRS may prove to be a useful-tool for assessing childhood disruptive behavior.

School-based secondary prevention for children with disruptive behavior: initial outcomes.

First through fourth graders from 22 suburban elementary schools were screened for cross-setting disruptive behavior as eligibility criteria for participation in a longitudinal secondary prevention study aimed at reducing the risk for serious externalizing behavioral disorders. Three hundred nine subjects participated in either a multicomponent competence enhancement intervention (MCEI) or an information/attention control (IAC) condition over a 2-year period. Following baseline requirements, initial intervention effects were assessed at the end of intervention Year 1, at the beginning of intervention Year 2 (fall of the next school year), and at the end of intervention Year 2. Multisource assessments were not supportive of the efficacy of the MCEI over the IAC condition. Children in both groups rated themselves as improved over time in terms of increased adaptive skills and decreased school problems and internalizing symptoms. Teacher and parent ratings of externalizing behavior did not yield evidence of positive change, but teachers noted improved problem solving and observers noted a decrease in behavioral interference in both groups over time, possibly as a result of maturation.

A review of GHRH stimulation test in psychiatry.

We critically reviewed controlled investigations of the growth hormone releasing hormone (GHRH) stimulation test in depression, anorexia nervosa, bulimia, panic disorder, schizophrenia, and Alzheimer's disease. Comparisons of GH responsiveness between patients and controls within each diagnostic category were equivocal and in some cases contradictory. Factors that may contribute substantially to the inconsistent findings within diagnostic categories include (1) the variability of GHRH-simulated GH among control groups; (2) the lack of uniformity in test procedures and outcome measures; and (3) the age and gender of subjects. In addition, the individual reproducibility of the GHRH stimulation test has not been adequately investigated and until the test's stability within subjects can be determined, the validity of interpretations resulting from the GHRH simulation test are in question.

Intrasubject reproducibility of growth hormone-releasing hormone-stimulated growth hormone in older women, older men, and younger men.

Intrasubject reproducibility of growth hormone (GH) response to growth hormone-releasing hormone (GHRH) was studied in healthy older women (n = 9), older men (n = 8), and younger men (n = 10). Subjects received IV injections of 0.1 ml/kg saline, 1 micrograms/kg GHRH, and 2 micrograms/kg GHRH, three times each, and blood was sampled at 0, 15, 30, 45, 60, and 120 min for GH concentration. There was no significant difference in peak GH response between the 1- and 2-micrograms/kg GHRH dosages. GH responsiveness, group variance of peak GH, and intrasubject variability were greatest for younger men, less for older men, and least for older women at both dosages of GHRH. Because of the large intrasubject variability observed in this study, it appears necessary to test subjects more than once to obtain a valid characterization of GH responsiveness.

Distribution of peripheral lymphocytes in Alzheimer patients and controls.

Deficient immunoregulation has been postulated to play a role in the pathogenesis of Alzheimer's dementia. Recently, lymphopenia was reported to be more prevalent in Alzheimer patients than in control subjects. In addition, a decreasing number of total lymphocytes was found to be significantly correlated with increasing severity of dementia. In an attempt to replicate these findings, we studied 55 Alzheimer patients and 41 healthy controls of comparable age and gender, but found no significant difference in the distribution of total lymphocytes between these groups. Furthermore, total lymphocytes were not significantly correlated with dementia severity. Our findings, therefore, do not lend further support to an immune hypothesis for Alzheimer's dementia.

Haloperidol and reduced haloperidol in saliva and blood.

A total of 18 outpatients (17 male, 1 female) ranging in age from 36-66 years old were on a constant dosage of haloperidol in equally divided doses at 9:00 a.m. and 9:00 p.m. for at least 1 month. DSM-III-R diagnoses included schizophrenia (N = 9), schizoaffective disorder (N = 3), bipolar disorder (N = 4), organic mental disorder (N = 1), and delusional disorder (N = 1). Blood samples for steady-state concentrations of plasma and red blood cell haloperidol (H) and reduced haloperidol (RH) were drawn at 9:00 a.m. (12 hr trough). The haloperidol dosage was held at 9:00 a.m. until samples of whole saliva and parotid saliva could be collected for flow rates and concentrations of H and RH. Haloperidol dosages ranged from 1 mg/day to 60 mg/day (mean 11 +/- 15). Correlation coefficients were calculated for saliva concentrations versus blood levels and for saliva secretion rates versus blood levels. The correlations between whole saliva measures and blood concentrations were all higher than the correlations between parotid saliva measures and blood concentrations. In one case the higher correlation reached statistical significance. There was only one case in which substitution of saliva secretion rate improved the correlation between measures with saliva concentration. Our findings suggest that saliva measures of H and RH are useful alternatives to plasma concentrations in monitoring maintenance haloperidol treatment.

Milacemide: a placebo-controlled study in senile dementia of the Alzheimer type.

OBJECTIVE: Milacemide, a MAO-B inhibitor that is also a prodrug for glycine, was tested as a treatment for senile dementia of the Alzheimer type (SDAT) because of its potential for enhancing cognition in animal models of impaired learning and memory. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: Sixteen study sites, both university-affiliated and private. PATIENTS: A total of 228 outpatients (116 men and 112 women) with SDAT, ranging in age from 49-93 years. INTERVENTION: 1200 mg/day milacemide treatment for 1 month (113 patients received milacemide, and 115 patients received placebo). MAIN OUTCOME MEASURES: Alzheimer's Disease Assessment Scale and the Mini-Mental State Examination. RESULTS: Milacemide-treated SDAT patients did not show significant improvement in any of the outcome measures used. Significant elevations in liver enzymes in four subjects were of sufficient magnitude to necessitate withdrawal from the study. CONCLUSIONS: Milacemide does not appear to be an effective treatment in enhancing cognition in SDAT patients.

Haloperidol decanoate pharmacokinetics in red blood cells and plasma.

Red blood cell (RBC) and plasma concentrations of haloperidol (H) and reduced haloperidol (RH) were determined in nine patients (five men, four women) who had been receiving monthly injections of haloperidol decanoate (HD) for at least 3 months. A very sensitive high performance liquid chromatography method was used to measure H and RH, which could be detected at levels as low as 0.1 ng/ml. Blood samples for H and RH were drawn at the end of weeks 1, 2, 3, and 4 of a 4-week cycle. Monthly HD dosages ranged from 50 mg to 200 mg. At each time point RBC H did not differ significantly from plasma H. RBC RH and plasma RH did not change significantly over time and were consistently lower than RBC H and plasma H. However, RBC RH levels were higher than plasma RH levels. Also, the ratios of RBC RH/H were higher than were the ratios of plasma RH/H, which reflect an accumulation of RH intracellularly. HD dosage was highly correlated with both RBC H and plasma H, but RBC RH and plasma RH were not significantly related to dosage at any time point. Significant correlations were observed between HD dosage and prolactin concentration at week 1 and between prolactin concentration and RBC H and plasma H at weeks 1 and 4. Blood concentrations of H and RH and the corresponding standardized areas under the curve were not significantly related to smoking.