Echo-planar Imaging Technique Research Articles

Correction of concomitant magnetic field-induced image artifacts in nonaxial echo-planar imaging.

Echo-planar images acquired in nonaxial planes are often distorted. Such image distortion has limited the applications of the echo-planar imaging (EPI) technique. In this article, it is demonstrated that a considerable amount of the distortion is caused by the higher-order magnetic field concomitant with the linear magnetic field gradient, or the concomitant magnetic field. The image distortion caused by the concomitant magnetic field is more prominent when a higher gradient amplitude is used for readout. It is also shown that the concomitant magnetic field can cause ghosting and blurring. A theoretical analysis is performed for the concomitant field effect in nonaxial EPI images. A point-by-point (or line-by-line) phase correction algorithm is developed to correct the image distortion, ghosting, and blurring. A postreconstruction processing algorithm is also developed to correct image distortion with much higher computational efficiency. Experimental results show that both correction methods effectively reduce the image distortion in coronal or sagittal images.

Image Distortion Correction in fMRI: A Quantitative Evaluation

A well-recognized problem with the echo-planar imaging (EPI) technique most commonly used for functional magnetic resonance imaging (fMRI) studies is geometric distortion caused by magnetic field inhomogeneity. This makes it difficult to achieve an accurate registration between a functional activation map calculated from an EPI time series and an undistorted, high resolution anatomical image. A correction method based on mapping the spatial distribution of field inhomogeneities can be used to reduce these distortions. This approach is attractive in its simplicity but requires postprocessing to improve the robustness of the acquired field map and reduce any secondary artifacts. Furthermore, the distribution of the internal magnetic field throughout the head is position dependent resulting in an interaction between distortion and head motion. Therefore, a single field map may not be sufficient to correct for the distortions throughout a whole fMRI time series. In this paper we present a quantitative evaluation of image distortion correction for fMRI at 2T. We assess (i) methods for the acquisition and calculation of field maps, (ii) the effect of image distortion correction on the coregistration between anatomical and functional images, and (iii) the interaction between distortion and head motion, assessing the feasibility of using field maps to reduce this effect. We propose that field maps with acceptable noise levels can be generated easily using a dual echo-time EPI sequence and demonstrate the importance of distortion correction for anatomical coregistration, even for small distortions. Using a dual echo-time series to generate a unique field map at each time point, we characterize the interaction between head motion and geometric distortion. However, we suggest that the variance between successively measured field maps introduces additional unwanted variance in the voxel time-series and is therefore not adequate to correct for time-varying distortions.

Does dichotic listening probe temporal lobe functions?

To explore cortical hemodynamic responses using fMRI in the context of three dichotic listening tasks. Dichotic listening is a widely used behavioral technique indicating brain laterality during which subjects are presented with two different auditory signals at the same time, one arriving at each ear. fMRI offers the potential to explore the hemodynamic response during dichotic listening and to relate the behavioral indices with these cortical measures. fMRI was performed for 10 right-handed normal subjects listening to consonant-vowel syllable pairs with the task of detecting a "target" syllable by pressing a button. The target stimulus appeared equally often in the left and right ear. The subjects were instructed to either concentrate on the stimuli presented in both ears (DIV) or only in the left ear (FL) or right ear (FR). In addition, a control condition was used during which the syllables were presented binaurally. Hemodynamic responses were measured by applying whole-head echo planar imaging techniques and statistically analyzed by using statistical parametric mapping (SPM99) software. During dichotic listening, there were generally extended activations in frontotemporal networks. For the DIV condition, the authors found strong bilateral activations in the inferior frontal gyrus, Broca's area, the left middle frontal gyrus, and in the left superior temporal gyrus. During the FL condition, there was an additional cluster in the right inferior frontal gyrus. For the FR condition, there were stronger activations in Broca's area and the left superior temporal gyrus. These findings were taken as evidence that dichotic listening is more demanding, requiring more processing capacity distributed in frontotemporal networks. The behavioral measures of dichotic listening were not simply a function of temporal lobe activation. Rather, the cortical activations support the notion that different processing strategies controlled by different neural structures are applied during dichotic listening.

Diffusion Weighted MR Image of Intracranial Hemorrhage

Purpose: To determine changes in the signal intensity of intracerebral hemorrhagic lesions according to the time interval, between the onset of symptoms and MR imaging in the T1-weighted (T1W1), T2-weighted (T2W1) and diffusion-weighted modes. Materials and Methods: Thirty-four patients with hemorrhagic stroke who underwent DWI and conventional MRI were involved in this study. Hemorrhagic phase was determined according to the time interval between the onset of symptoms and MR scanning, and was as follows: acute (3 days or less): eight patients); early subacute (7 days or less): ten patients; late subacute (4 weeks or less): seven patients; early chronic (3 months or less) : four patients); and late chronic (more than 3 months): five patients. Using a 1.5T MR imager and the single-shot echo-planar imaging technique, T1-weighted, fast spin-echo T2-weighted, and diffusion-weighted were obtained. In all cases qualitative signal intensity (SI) at the center of a lesion was recorded, and the ratio between this and normal brain parenchyma was calculated. Results: SI at the center of a lesion was found to be iso or high/high/high (T1WI/T2WI/DWI) in five of eight acute-phase cases (interval of 24 hours or less) and low/low/low in the remaining three (interval of 72 hours or less). Other signal intensities were as follows: early subacute phase: high/low/low (all ten cases); late subacute phase: high/high/high (all seven cases); early chronic phase: high/high/high (all four cases); late chronic phase: low/high/low (all five cases). Mean SIRs were as follows: in the five acute-phase cases in which SI was iso or high: 1.420.78 / 2.580.84 / 1.350.08 (T1WI / T2WI / DWI); in the remaining three acute-phase cases: 0.94 0.18 / 0.630.16 / 0.270.10; in the early subacute phase, 1.350.01 / 0.970.21 / 0.860.22 in early subacute phase, 1.580.04 / 1.540.09 / 1.440.14; in the early chronic phase: 1.260.11 / 1.060.14 / 0.970.12; and in the late chronic phase: 0.652.23 / 1.510.12 / 0.230.18. Conclusion: The DWI findings of intracerebral hemorrhage reflect the findings of T2WI. When interpreting the DWI findings in patients with intracerebral hemorrhage, an understanding of the temporal evolution of this is very helpful . The no-show rate, patient distribution, chief complaint, type and number of additional radiologic examinations, patient compliance rate, biopsy result, rate of cancer detection, and staging of cancers were determined. The merits and demerits of the clinic were also assessed. Results: A total of 671 patients attended, with a no-show rate of 13.2%. Referrals from the Health Promation Centre accounted for 90.4% of patient visits. The most frequent complaint was a suspicious nodule at mammography. One additional radiologic examination was performed in 429 patients, two examinations in 70, and three or more examations in five. The most frequent type of examination was ultrasonography, followed by magnification compression view, mammography, and ultrasound-guided aspiration biopsy. An additional radiologic examination was recommended in 81.2% of patients and compliance rate was 96.7%. Primary breast cancer was diagnosed in 16 patients (2.1%), and was found to be stage 0 and 1 in 64.3% of these. No significant demerits were apparent. Conclusion: Radiologic examinations play a very important role in the detection of early-stage breast cancer, and the establishment of an early detection clinic lead by a radiologist is a very effective and recommendable approach to screening.',PY = '2002-00-00',RF = '5',BN = '

Human Ocular Dominance Columns as Revealed by High-Field Functional Magnetic Resonance Imaging

We mapped ocular dominance columns (ODCs) in normal human subjects using high-field (4 T) functional magnetic resonance imaging (fMRI) with a segmented echo planar imaging technique and an in-plane resolution of 0.47 × 0.47 mm 2. The differential responses to left or right eye stimulation could be reliably resolved in anatomically well-defined sections of V1. The orientation and width (∼1 mm) of mapped ODC stripes conformed to those previously revealed in postmortem brains stained with cytochrome oxidase. In addition, we showed that mapped ODC patterns could be largely reproduced in different experiments conducted within the same experimental session or over different sessions. Our results demonstrate that high-field fMRI can be used for studying the functions of human brains at columnar spatial resolution.

Diffusion tensor trace mapping in normal adult brain using single-shot EPI technique. . A methodological study of the aging brain

To quantify age-related changes of the average diffusion coefficient value in normal adult brain using orientation-independent diffusion tensor trace mapping and to address the methodological influences on diffusion quantification. Fifty-four normal subjects (aged 20-79 years) were studied on a 1.5-T whole-body MR medical unit using a diffusion-weighted single-shot echo-planar imaging technique. Orientation-independent diffusion tensor trace maps were constructed for each subject using diffusion-weighted MR measurements in four different directions using a tetrahedral gradient combination pattern. The global average (including cerebral spinal fluid) and the tissue average of diffusion coefficients in adult brains were determined by analyzing the diffusion coefficient distribution histogram for the entire brain. Methodological influences on the measured diffusion coefficient were also investigated by comparing the results obtained using different experimental settings. Both global and tissue averages of the diffusion coefficient are significantly correlated with age (p<0.03). The global average of the diffusion coefficient increases 3% per decade after the age of 40, whereas the increase in the tissue average of diffusion coefficient is about 1% per decade. Experimental settings for self-diffusion measurements, such as data acquisition methods and number of b-values, can slightly influence the statistical distribution histogram of the diffusion tensor trace and its average value. Increased average diffusion coefficient in adult brains with aging are consistent with findings regarding structural changes in the brain that have been associated with aging. The study also demonstrates that it is desirable to use the same experimental parameters for diffusion coefficient quantification when comparing between different subjects and groups of interest.

Diffusion tensor trace mapping in normal adult brain using single-shot EPI technique. A methodological study of the aging brain.

To quantify age-related changes of the average diffusion coefficient value in normal adult brain using orientation-independent diffusion tensor trace mapping and to address the methodological influences on diffusion quantification. Fifty-four normal subjects (aged 20-79 years) were studied on a 1.5-T whole-body MR medical unit using a diffusion-weighted single-shot echo-planar imaging technique. Orientation-independent diffusion tensor trace maps were constructed for each subject using diffusion-weighted MR measurements in four different directions using a tetrahedral gradient combination pattern. The global average (including cerebral spinal fluid) and the tissue average of diffusion coefficients in adult brains were determined by analyzing the diffusion coefficient distribution histogram for the entire brain. Methodological influences on the measured diffusion coefficient were also investigated by comparing the results obtained using different experimental settings. Both global and tissue averages of the diffusion coefficient are significantly correlated with age (p<0.03). The global average of the diffusion coefficient increases 3% per decade after the age of 40, whereas the increase in the tissue average of diffusion coefficient is about 1% per decade. Experimental settings for self-diffusion measurements, such as data acquisition methods and number of b-values, can slightly influence the statistical distribution histogram of the diffusion tensor trace and its average value. Increased average diffusion coefficient in adult brains with aging are consistent with findings regarding structural changes in the brain that have been associated with aging. The study also demonstrates that it is desirable to use the same experimental parameters for diffusion coefficient quantification when comparing between different subjects and groups of interest.

An inverse problem approach to the correction of distortion in EPI images.

Magnetic resonance imaging using the echo planar imaging (EPI) technique is particularly sensitive to main (B0) field inhomogeneities. The primary effect is geometrical distortion in the phase encoding direction. In this paper, we present a method based on the conjugate gradient algorithm to correct for this geometrical distortion, by solving the EPI imaging equation. Two versions are presented: one that attempts to solve the full four-dimensional (4-D) imaging equation, and one that independently solves for each profile along the blip encoding direction. Results are presented for both phantom and in vivo brain EPI images and compared with other proposed correction methods.

High-resolution diffusion imaging using phase-corrected segmented echo-planar imaging

Diffusion magnetic resonance imaging (MRI) was performed with a high-resolution segmented echo-planar imaging technique, which provided images with substantially less susceptibility artifacts than images obtained with single-shot echo-planar imaging (EPI). Diffusion imaging performed with any multishot pulse sequence is inherently sensitive to motion artifacts and in order to reduce motion artifacts, the presented method utilizes navigator echo phase corrections, performed after a one-dimensional Fourier transform along the frequency-encoding direction. Navigator echo phases were fitted to a straight line prior to phase correction to avoid errors from internal motion. In vivo imaging was performed using electro cardiographic (ECG) triggering. Apparent diffusion coefficient (ADC) maps were calculated on a pixel-by-pixel basis using up to seven diffusion sensitivities, ranging from b = 0 to 1129 × 10 6 s/m 2.

On the use of water phantom images to calibrate and correct eddy current induced artefacts in MR diffusion tensor imaging

The accurate determination of absolute measures of diffusion anisotropy in vivo using single-shot, echo-planar imaging techniques requires the acquisition of a set of high signal-to-noise ratio, diffusion-weighted images that are free from eddy current induced image distortions. Such geometric distortions can be characterized and corrected in brain imaging data using magnification ( M), translation ( T), and shear ( S) distortion parameters derived from separate water phantom calibration experiments. Here we examine the practicalities of using separate phantom calibration data to correct high b-value diffusion tensor imaging data by investigating the stability of these distortion parameters, and hence the eddy currents, with time. It is found that M, T, and S vary only slowly with time (i.e., on the order of weeks), so that calibration scans need not be performed after every patient examination. This not only minimises the scan time required to collect the calibration data, but also the computational time needed to characterize these eddy current induced distortions. Examples of how measurements of diffusion anisotropy are improved using this post-processing scheme are also presented.

Detection of a relation between respiration and CSF pulsation with an echoplanar technique.

The flow of cerebrospinal fluid (CSF) through the aqueduct was studied with an echoplanar imaging technique. Images (1024) of a slice perpendicular to the aqueduct were acquired with a repetition time of 107 msec and a flip angle of 90 degrees. This imaging technique is very sensitive for flow into the selected slice, although a quantitative assessment of flow velocities is not possible. Simultaneously with the image data acquisition, data from a pulse oximeter and a respiration belt were recorded. For each data point, a delay time to the preceding cardiac pulse was determined from the recorded pulse wave. The signal intensities could then be assigned to the cardiac cycle. Each cardiac interval was assigned to one of eight respiratory phases, and an average signal curve during the cardiac interval was calculated for each respiration phase. The evaluation showed to signal maxima within the cardiac interval, which could be identified as a downward flow at 10% and an upward flow at 80% of the cardiac pulse interval by measurements with additional saturation pulses. In examinations of 22 healthy volunteers, an influence of respiration on the flow through the aqueduct was found. In spite of interindividual variability, comparable effects could be observed in all volunteers. In the late expiration phase the caudally directed flow was at its maximum, whereas the cranially directed flow was maximal in the post-inspiration phase.

Gastric Response to Increased Meal Viscosity Assessed by Echo-Planar Magnetic Resonance Imaging in Humans

Normal meals are highly viscous, and viscosity is a key factor in influencing gastric emptying of food. However, the process of meal dilution and mixing is difficult to assess with the use of conventional methods. The aim of this study was to validate an in vivo, novel, noninvasive, echo-planar magnetic resonance imaging (EPI) technique, capable of monitoring the viscosity of a model meal, and to use this to investigate the effects of viscosity on gastric emptying, meal dilution and satiety. Healthy volunteers (n = 8) ingested 500 mL of locust bean gum (0.25, 0.5, 1.0 or 1.5 g/100 g), nonnutrient, liquid meals of varying viscosities, and labeled with a nonabsorbable marker, phenol red. Meal viscosity was calibrated against the water proton transverse relaxation rate (T(2)(-1)) in vitro before ingestion, thus viscosity was measured in vivo via EPI measurements of T(2)(-1). Viscosity and dilution were also measured directly using nasogastric aspirates. Gastric volumes as measured by EPI, fullness, appetite and hunger were also assessed serially. Before ingestion, the log of initial meal viscosity was linearly related to T(2)(-1) (n = 8, r(2) = 0.95). Similarly, T(2)(-1) measured in vivo was also linearly related to the viscosity of the aspirates (r(2) = 0.88). All meals underwent rapid dilution, leading to a reduction in viscosity, which was greatest for the most viscous meal (P < 0.01). Surprisingly, despite the fact that the initial meal viscosity varied 1000-fold, there was only a small delay in gastric emptying (P for trend < 0.05). The area under the curve for satiety increased with initial meal viscosity, whereas that for hunger decreased (P < 0.05). In conclusion, the viscosity of a meal in vivo can be measured noninvasively using EPI. The stomach responds to meal ingestion by rapid intragastric dilution, causing a reduction of meal viscosity, and gastric emptying is minimally delayed. However, increased viscosity is associated with more prolonged satiety.

Magnetic resonance diffusion tensor imaging for characterizing diffuse and focal white matter abnormalities in multiple sclerosis.

High-resolution diffusion tensor imaging (DTI) was performed in 14 patients with clinically definite multiple sclerosis (MS) and the trace of the diffusion tensor (<D>) and the fractional anisotropy (FA) were determined in normal appearing white matter (NAWM) and in different types of focal MS lesions. A small but significant increase of the <D> in NAWM compared to control white matter ((840 +/- 85) x 10(-6) mm(2)/sec vs. (812 +/- 59) x 10(-6) mm(2)/sec; P < 0.01) was found. In addition, there was a significant decrease in the FA of normal-appearing regions containing well-defined white matter tracts, such as the genu of the internal capsule. In non-acute lesions, the <D> of T(1)-hypointense areas was significantly higher than that of T(1)-isointense lesions ((1198 +/- 248) x 10(-6) mm(2)/sec vs. (1006 +/- 142) x 10(-6) mm(2)/sec; P < 0. 001), and there was a corresponding inverse relation of FA. Diffusion characteristics of active lesions with different enhancement patterns were also significantly different. DTI with a phase navigated interleaved echo planar imaging technique may be used to detect abnormalities of isotropic and anisotropic diffusion in the NAWM and selected fiber tracts of patients with MS throughout the entire brain, and it demonstrates substantial differences between various types of focal lesions.

Diffusion-weighted spin-echo fMRI at 9.4 T: microvascular/tissue contribution to BOLD signal changes.

The nature of vascular contribution to blood oxygenation level dependent (BOLD) contrast used in functional MRI (fMRI) is poorly understood. To investigate vascular contributions at an ultrahigh magnetic field of 9.4 T, diffusion-weighted fMRI techniques were used in a rat forepaw stimulation model. Tissue and blood T(2) values were measured to optimize the echo time for fMRI. The T(2) of arterial blood was 40.8 +/- 3.4 msec (mean +/- SD; n = 5), similar to the tissue T(2) of 38.6 +/- 2.1 msec (n = 16). In comparison, the T(2) of venous blood at an oxygenation level of 79.6 +/- 6.1% was 9. 2 +/- 2.3 msec (n = 11). The optimal spin-echo time of 40 msec was confirmed from echo-time dependency fMRI studies. The intravascular contribution was examined using a graded diffusion-weighted spin-echo echo-planar imaging technique with diffusion weighting factor (b) values of up to 1200 sec/mm(2). Relative BOLD signal changes induced by forepaw stimulation showed no dependence on the strength or direction of the diffusion-sensitizing gradients, suggesting that the large vessel contribution to the BOLD signal is negligible at 9.4 T. However, gradient-echo fMRI performed with bipolar diffusion sensitizing gradients, which suppress intravascular components from large vessels, showed higher percent signal changes in the surface of the brain. This effect was attributed to the extravascular contribution from large vessels. These findings demonstrate that caution should be exercised when interpreting that higher percent changes obtained with gradient-echo BOLD fMRI are related to stronger neural activation. Magn Reson Med 42:919-928, 1999.

A keyhole echo planar hybrid imaging technique

A keyhole echo planar hybrid imaging technique

A keyhole echo planar hybrid imaging technique.

A hybrid keyhole imaging method is presented which demonstrates the combination of two distinctly different MR imaging techniques. In this work single shot EPI was used as a dynamic update scan for a conventional high resolution gradient echo acquisition. Problems associated with the integration of MR data from distinctly different imaging techniques are addressed. Illustration is provided by way of diffusion weighted imaging. This novel development requires further investigation which need not be limited to the hybridization of strictly Cartesian based scanning methods.

Tactile stimulation of the hand causes bilateral cortical activation: a functional magnetic resonance study in humans

The purpose of the present study was to assess the somatotopy of the cortical sensory representation of the fingers using a natural tactile stimulation of the glabrous skin. Multislice echoplanar imaging techniques were utilized to investigate blood oxygen level dependent (BOLD) signal changes as a measure of cortical activation. Repetitive sensory stimulation of the glabrous skin of digit II–III and digit IV–V resulted in a multifocal signal increase in a restricted area near the central sulcus in the contralateral hemisphere with a considerable overlap between the activated areas of digit II–III and digit IV–V. In addition, in all subjects tactile stimulation resulted in ipsilateral signal increase near the central sulcus, which was 15–22% of the contralateral effect. Stimulation of digit II–III caused significantly ( P<0.05) more activated voxels than digit IV–V in the contralateral hemisphere for both hands and for the left hand in the ipsilateral hemisphere. These findings suggest an ipsilateral activation of the primary somatosensory cortex during a natural tactile stimulation of the digits in humans.

Value of dynamic susceptibility contrast magnetic resonance imaging in the evaluation of intracranial tumors.

The degree of tumor malignancy generally correlates to tumor grade, and the direct measurement of tumor vasculature is desired. Dynamic susceptibility contrast magnetic resonance imaging can provide relative cerebral blood volume and, therefore, is one of the most reliable methods to evaluate tumor vasculature in vivo. Tumor vessel size is extremely variable due to complex tumor angiogenesis, and the gradient-echo echo-planar imaging (GE-EPI) technique, which is sensitive to the total vascular bed, is well suited for this purpose. As many studies have shown, dynamic susceptibility contrast magnetic resonance imaging is more useful for grading glioma than conventional magnetic resonance imaging. We found that this technique can also provide supplementary information to differentiate between malignant lymphoma and glioma because the absence of tumor neovascularization of malignant lymphoma leads to low rCBV, which is in contrast to those of malignant gliomas. Indeed, this technique can be used for the differentiation of extra-axial tumors such as between meningioma and neurinoma. Recently, this technique has been focused toward determining the stereotactic biopsy site, monitoring the embolization of effect in meningioma, or evaluation of treatment effects after radiation therapy. However, the value of tumor rCBV is affected by many conditions such as the T1 relaxivity effects of gadolinium in the extravascular space. To establish the usefulness of this technique, further examination will be needed.

Optimization of fast acquisition methods for whole-brain relative cerebral blood volume (rCBV) mapping with susceptibility contrast agents.

Fast gradient-echo magnetic resonance scan techniques with spiral and rectilinear (echoplanar) k-space trajectories were optimized to perform bolus-tracking studies of human brain. Cerebral hemodynamics were studied with full brain coverage, a spatial resolution of 4 mm, and a temporal resolution of 2 seconds. The sensitivity of the techniques to detect image signal-intensity changes during the first pass of the contrast agent was studied at a range of TEs using dedicated experiments. For single-shot versions of spiral scanning and echoplanar imaging techniques with a 0.1-mmol/kg injection of gadolinium diethylenetriamine pentaacetic acid using a mechanical injector at 10 mL/sec under 1.5 T, the maximum sensitivity was obtained at TEs between 35 and 45 msec. At TEs less than 35 msec, signal-intensity artifacts were observed in the images. Analysis of the point-spread function revealed that susceptibility changes induced by the contrast agent can result in signal shifts to neighboring voxels. These artifacts are attributed to susceptibility-related signal changes during the acquisition window.

Two-dimensional proton echo-planar spectroscopic imaging of brain metabolic changes during lactate-induced panic.

A fast, proton echo-planar spectroscopic imaging (PEPSI) technique, capable of simultaneously measuring metabolites from multiple brain regions, was used to investigate the anatomical distribution and magnitude of brain lactate responses to intravenous lactate infusion among subjects with panic disorder and control subjects. Fifteen subjects with panic disorder and 10 control subjects were studied. All subjects were medication free and met DSM-IV criteria for panic disorder, or, for controls, no Axis I psychiatric disorder. Two-dimensional axial metabolite images having 1-cm3 spatial resolution were acquired at 61/2-minute intervals during 3 conditions: a 20-minute baseline, 20-minute 0.5-mol/L sodium lactate infusion, and 15-minute postinfusion period. Intravenous lactate infusion increased brain lactate levels throughout the axial brain section studied in all subjects. Panic-disordered subjects had significantly greater global brain lactate increases in response to lactate infusion. Lateralization of brain lactate response did not occur, nor were discrete regional loci of elevated lactate observed. Cerebrospinal fluid lactate changes corresponded to lactate changes in brain tissue. Severity of symptoms provoked by lactate infusion did not directly correlate with brain lactate response. Greater overall rises in brain lactate among subjects with panic disorder compared with controls occurred in response to lactate infusion. We were unable to detect a distinct regional pattern for magnitude differences in brain lactate rise by which to identify a specific neuroanatomical substrate underlying a lactate-induced panic response. The wide anatomical distribution of these brain lactate increases suggest metabolic and/or neurovascular mechanisms for the abnormal rise in subjects with panic disorder.