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1.
Magnetic resonance imaging (MRI) is well suited for small animal model investigations to study various human pathologies. However, the assessment of microscopic information requires a high-spatial resolution (HSR) leading to a critical problem of signal-to-noise ratio limitations in standard whole-body imager. As contrast mechanisms are field dependent, working at high field do not allow to derive MRI criteria that may apply to clinical settings done in standard whole-body systems. In this work, a contrast-enhanced dynamic MRI protocol with improved spatial and time resolution was used to perform in vivo tumor model imaging on the mouse at 1.5 T. The needed sensitivity is provided by the use of a 12-mm superconducting surface coil operating at 77 K. High quality in vivo images were obtained and revealed well-defined internal structures of the tumor. A 3-D HSR sequence with voxels of 59x59x300 microm3 encoded within 6.9 min and a 2-D sequence with subsecond acquisition time and isotropic in-plane resolution of 234 microm were used to analyze the contrast enhancement kinetics in tumoral structures at long and short time scales. This work is a first step to better characterize and differentiate the dynamic behavior of tumoral heterogeneities.  相似文献   

2.
Sensitivity-encoded phase undersampling has been combined with simultaneous slice excitation to produce a parallel MRI method with a high volumetric acquisition acceleration factor without the need for auxiliary stepped field coils. Dual-slice excitation was produced by modulating both spin and gradient echo sequences at +/-6 kHz. Frequency aliasing of simultaneously excited slices was prevented by using an additional gradient applied along the slice axis during data acquisition. Data were acquired using a four-channel receiver array and x4 sensitivity encoding on a 1.5 T MR system. The simultaneous parallel inclined readout image technique has been successfully demonstrated in both phantoms and volunteers. A multiplicative image acquisition acceleration factor of up to x8 was achieved. Image SNR and resolution was dependent on the ratio of the readout gradient to the additional slice gradient. A ratio of approximately 2:1 produced acceptable image quality. Use of RF pulses with additional excitation bands should enable the technique to be extended to volumetric acquisition acceleration factors in the range of x16-24 without the SNR limitations of pure partially parallel phase reduction methods.  相似文献   

3.
Sodium MRI has been shown to be highly specific for glycosaminoglycan (GAG) content in articular cartilage, the loss of which is an early sign of osteoarthritis (OA). Quantitative sodium MRI techniques are therefore under development in order to detect and assess early biochemical degradation of cartilage, but due to low sodium NMR sensitivity and its low concentration, sodium images need long acquisition times (15-25 min) even at high magnetic fields and are typically of low resolution. In this preliminary study, we show that compressed sensing can be applied to reduce the acquisition time by a factor of 2 at 7 T without losing sodium quantification accuracy. Alternatively, the nonlinear reconstruction technique can be used to denoise fully-sampled images. We expect to even further reduce this acquisition time by using parallel imaging techniques combined with SNR-improved 3D sequences at 3T and 7 T.  相似文献   

4.
A measure of the sharpness of vessel wall interfaces in carotid artery MRI may be useful for assessing the conspicuity of the wall's features. An edge detection technique was used to measure the signal intensity gradients in 2D time-of-flight (2D-TOF) and double-inversion recovery black-blood (DIR-BB) carotid artery images of normal subjects that were acquired at 1.5 T with 0.55 x 0.55 x 2.0-mm (0.6 mm3) acquisition voxels and zero filled to reduce the in-plane reconstructed voxel size by one half in each dimension as well as with 0.27 x 0.27 x 2.0-mm (0.15 mm3) acquisition voxels and at 3.0 T with 0.27 x 0.27 x 2.0-mm (0.15 mm3) acquisition voxels using surface coils. The gradient intensities of the lumen-to-background interface varied closely with the contrast-to-noise ratio of the 2D-TOF imaging. For the DIR-BB imaging, in which higher spatial frequency artery structures are visible, the gradient intensities at the interfaces were higher than theoretically predicted at both field strengths with smaller acquisition voxels. The use of acquisition voxels smaller than those previously used at 1.5 T can improve the visualization of carotid artery structures at 1.5 and 3.0 T with surface coil reception.  相似文献   

5.
We introduce an accelerated gradient echo (GRE) sequence combining simultaneous multislice excitation (SMS) with echo-shifting technique for high spatial resolution blood oxygen level dependent (BOLD) functional MRI (fMRI). The simulation was conducted to optimize scan parameters. To validate the feasibility of the proposed technique, the visual and motor task experiments were performed at 7.0 Tesla (T). The single-shot EPI sequence was also applied in comparison with the proposed technique. The simulation results showed that an optimized flip angle of 9° provided maximal BOLD contrast for our scanning scheme, allowing low power deposition and SMS acceleration factor of 5. Additionally, parallel acquisition imaging with acceleration factor of 2 was utilized, which allowed a total acceleration factor of 10 in volunteer study. The experiment results showed that geometric distortion-free BOLD images with voxel size of 1.0 × 1.0 × 2.5 mm3 were obtained. Significant brain activation was identified in both visual and motor task experiments, which were in accordance with previous investigations. The proposed technique has potential for high spatial resolution fMRI at ultra-high field because of its sufficient BOLD sensitivity as well as improved acquisition speed over conventional GRE-based techniques.  相似文献   

6.
We investigated the effects of transcranial magnetic stimulation (TMS) coils and electroencephalographic (EEG) electrodes on T(2)*-weighted echo-planar images (EPI) at 2.0 T (gradient-echo EPI, mean TE = 53 ms, 2x2x4 mm(3)). In comparison with anatomic gradient-echo images (3D FLASH, TE = 4 ms, 1x1x1 mm(3)), T(2)*-weighted EPI acquisitions of a water-filled spherical phantom revealed severe signal losses and geometric distortions in the vicinity of TMS coils. Even remote effects were observed for image orientations perpendicular to the coil plane. EEG electrodes and the fixation gel caused milder localized distortions. In humans, complications were avoided by the large distance between the TMS coil and the cortical surface and when using an EPI orientation parallel to the plane of the coil. It is concluded that T(2)*-weighted EPI studies of human brain function may be performed without distortions caused by TMS coils and EEG electrodes.  相似文献   

7.
A magnetic resonance imaging (MRI) method is described that allows interleaved measurements of transverse (R(2)(*) and R(2)) and longitudinal (R(1)) relaxation rates of tissue water in conjunction with spin labeling. The image-contrasts are intrinsically blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) weighted, but each contrast is made quantitative by two echo time (TE) and inversion recovery time (TIR) acquisitions with gradient echo (GE) and spin echo (SE) weighted echo-planar imaging (EPI). The EPI data were acquired at 7 Tesla with nominal spatial resolution of 430 x 430 x 1000 microm(3) in rat brain in vivo. The method is termed as blood oxygenation level dependent exponential decays adjusted for flow attenuated inversion recovery (BOLDED AFFAIR) and allows acquisition of R(2)(*), R(2), and CBF maps in an interleaved manner within approximately 12 minute. The basic theory of the method, associated experimental/systematic errors, and temporal restrictions are discussed. The method is validated by comparison of multi-modal maps obtained by BOLDED AFFAIR (i.e., two TE and TIR values with GE and SE sequences) and conventional approach (i.e., multiple TE and TIR values with GE and SE sequences) during varied levels of whole brain activity. Preliminary functional data from a rat forepaw stimulation model demonstrate the feasibility of this method for functional MRI (fMRI) studies. It is expected that with appropriate precautions this method in conjunction with contrast agent-based MRI has great potential for quantitative fMRI studies of mammalian cortex.  相似文献   

8.
Diffusion tensor magnetic resonance imaging (DT-MRI) is generally performed using an echo planar imaging (EPI) acquisition to map directional water diffusion. However, the oscillating magnetic field gradients of the EPI acquisition can result in considerable mechanical vibrations, which lead, in turn, to magnetic field fluctuations causing Nyquist ghosting in the EPI data. The objective of this study was to investigate effects of EPI readout gradient modulation frequency, which is directly associated with the EPI readout bandwidth (BW), on the accuracy of DT-MRI measurements in a high magnetic field system. A spherical water phantom was used to study the relationship between the EPI BW and the Nyquist ghost for a spin-echo EPI acquisition with a matrix size of 128x128, complemented by diffusion sensitization gradients of up to b=800 s/mm(2) along six directions for DT-MRI. Nine volunteers (four males and five females) were studied using EPI at different BW acquisitions. Analysis of variance was used to investigate the EPI BW effects. The phantom studies demonstrated a systematic relationship between BWs and the intensities of Nyquist ghosts. In the human brain studies, EPI BW variations substantially corrupted diffusion anisotropy indexes (i.e., fractional anisotropy and relative anisotropy) (F=10.5, P=.0001) but were unrelated to diffusion-encoding directions (F=0.14, P=.98). It was possible to minimize BW dependence (F=1.48, P=.25) by tuning the modulation frequency of the EPI readout gradient. In conclusion, diffusion anisotropic indexes are sensitive to the readout BW of EPI due to associated Nyquist ghosting. However, the effect can be minimized by tuning the modulation frequency of the EPI readout gradient, that is, the EPI BW, to a range outside the harmonics of mechanical gradient vibrations.  相似文献   

9.
Super-paramagnetic iron oxide (SPIO) nanoparticles are actively investigated to enhance disease detection through molecular imaging using magnetic resonance imaging (MRI). Detection of the cells labeled by SPIO depends on the MRI protocols and pulse sequence parameters that can be optimized. To evaluate the sensitivity and specificity of the image acquisition methods and to obtain optimal imaging parameters for single-cell detection, we further developed an MRI simulator. The simulator models an object (tissue) at a microscopic level to evaluate effects of spatial distribution and concentration of nanoparticles on the resulting image. In this study, the simulator was used to evaluate and compare imaging of the labeled cells by the gradient-echo (GE), true-FISP [fast imaging employing steady-state acquisition (FIESTA)] and echo-planar imaging (EPI) pulse sequences. Effects of the imaging and object parameters, such as field strength, imaging protocol and pulse sequence parameters, imaging resolution, cell iron load, position of SPIO within the voxel and cell division within the voxel, were investigated in the work. The results suggest that true-FISP has the highest sensitivity for single-cell detection by MRI.  相似文献   

10.
Research on the functions of the human brain requires that functional magnetic resonance imaging (MRI) moves towards producing images with less distortion and higher temporal and spatial resolution. This study compares passband balanced steady-state free precession (bSSFP) acquisitions with and without parallel imaging (PI) to investigate whether combining PI with this pulse sequence is a viable option for functional MRI. Such a novel combination has the potential to offer the distortion-free advantages of bSSFP with the reduced acquisition time of PI. Scans were done on a Philips 3T Intera, using the installed bSSFP pulse sequence, both with and without the sensitivity encoding (SENSE) PI option. The task was a visual flashing checkerboard, and the viewing window covered the visual cortex. Sensitivity comparisons with and without PI were done using the same manually drawn region of interest for each time course of the subject, and comparing the z-score summary statistics: number of voxels with z>2.3, the mean of those voxels, their 90th percentile and their maximum value. We show that PI greatly improves the temporal resolution in bSSFP, reducing the volume acquisition time by more than half in this study to 0.67 s with 3-mm isotropic voxels. At the same time, a statistically significant increase was found for the maximum z-score using bSSFP with PI as compared to without it (P=.02). This improvement can be understood in terms of physiological noise, as demonstrated by noise measurements. This produces observed increases in the overall temporal signal to noise of the functional time series, giving greater sensitivity to functional activations with PI. This study demonstrates for the first time the possibility of combining PI with bSSFP to achieve distortion-free functional images without loss of sensitivity and with high temporal resolution.  相似文献   

11.
As the amygdala is involved in various aspects of emotional processing, its characterization using neuroimaging modalities, such as functional magnetic resonance imaging (fMRI), is of great interest. However, in fMRI, the amygdala region suffers from susceptibility artifacts that are composed of signal dropouts and image distortions. Various technically demanding approaches to reduce these artifacts have been proposed, and most require alterations beyond a mere change of the acquisition parameters and cannot be easily implemented by the user without changing the MR sequence code. In the present study, we therefore evaluated the impact of simple alterations of the acquisition parameters of a standard gradient-echo echo-planar imaging technique at 3 T composed of echo times (TEs) of 27 and 36 ms as well as section thicknesses of 2 and 4 mm while retaining a section orientation parallel to the intercommissural plane and an in-plane resolution of 2x2 mm(2). In contrast to previous studies, we based our evaluation on the resulting activation maps using an emotional stimulation paradigm rather than on MR raw image quality only. Furthermore, we tested the effects of spatial smoothing of the functional raw data in the course of postprocessing using spatial filters of 4 and 8 mm. Regarding MR raw image quality, a TE of 27 ms and 2-mm sections resulted in the least susceptibility artifacts in the anteromedial aspect of the temporal lobe. The emotional stimulation paradigm resulted in robust bilateral amygdala activation for the approaches with 2-mm sections only -- but with larger activation volumes for a TE of 36 ms as compared with that of 27 ms. Moderate smoothing with a 4-mm spatial filter represented a good compromise between increased sensitivity and preserved specificity. In summary, we showed that rather than applying advanced modifications of the MR sequence, a simple increase in spatial resolution (i.e., the reduction of section thickness) is sufficient to improve the detectability of amygdala activation.  相似文献   

12.
Synchronized EPI phase contrast velocimetry in a mixing reactor   总被引:3,自引:0,他引:3  
Notwithstanding its widespread use in cardiovascular and functional MRI studies, Echo Planar Imaging (EPI) has only recently been subjected to systematic validation studies. Most velocity measurement studies employing such ultrafast MRI methods involve the use of phantoms characterized by rigid or deformable solid motion. The current implementation involves a rotating phantom (angular velocity up to 10.5 rpm) with a superimposed swirling liquid flow (with axial velocities ranging between 0.145 and 0.27 cm/s) of water doped with copper sulfate. The standard implementation of single-shot EPI with phase contrast velocity encoding allows the complete mapping of the Eulerian velocity field in slices perpendicular to the rotation axis following a subtractive procedure requiring the synchronized acquisition of each velocity component on each selected transverse slice during two revolutions of the rotor. The image acquisition time is 100 ms (per velocity component) at each 64 x 64 slice. In addition to acquiring full-field velocity data for future direct comparisons with other techniques, EPI is employed here for the first time to reconstruct the three-dimensional flow field between the blades of a partitioned pipe mixer.  相似文献   

13.
Development and initial evaluation of 7-T q-ball imaging of the human brain   总被引:1,自引:0,他引:1  
Diffusion tensor imaging (DTI) noninvasively depicts white matter connectivity in regions where the Gaussian model of diffusion is valid but yields inaccurate results in those where diffusion has a more complex distribution, such as fiber crossings. q-ball imaging (QBI) overcomes this limitation of DTI by more fully characterizing the angular dependence of intravoxel diffusion with larger numbers of diffusion-encoding directional measurements at higher diffusion-weighting factors (b values). However, the former technique results in longer acquisition times and the latter technique results in a lower signal-to-noise ratio (SNR). In this project, we developed specialized 7-T acquisition methods utilizing novel radiofrequency pulses, eight-channel parallel imaging EPI and high-order shimming with a phase-sensitive multichannel B0 field map reconstruction. These methods were applied in initial healthy adult volunteer studies, which demonstrated the feasibility of performing 7-T QBI. Preliminary comparisons of 3 T with 7 T within supratentorial crossing white matter tracts documented a 79.5% SNR increase for b=3000 s/mm2 (P=.0001) and a 38.6% SNR increase for b=6000 s/mm2 (P=.015). With spherical harmonic reconstruction of the q-ball orientation distribution function at b=3000 s/mm2, 7-T QBI allowed for accurate visualization of crossing fiber tracts with fewer diffusion-encoding acquisitions as compared with 3-T QBI. The improvement of 7-T QBI at b factors as high as 6000 s/mm2 resulted in better angular resolution as compared with 3-T QBI for depicting fibers crossing at shallow angles. Although the increased susceptibility effects at 7 T caused problematic distortions near brain-air interfaces at the skull base and posterior fossa, these initial 7-T QBI studies demonstrated excellent quality in much of the supratentorial brain, with significant improvements as compared with 3-T acquisitions in the same individuals.  相似文献   

14.
Single-shot echo planar imaging (EPI) is one of the most suitable techniques for very fast image acquisition, especially in functional MRI. In standard EPI schemes the k-space center is sampled in the middle of the acquisition train. This leads to longer echo times for higher spatial resolutions, as well as reduced signal intensity and signal-to-noise ratio. Therefore, echo shifting to lower echo times is often used. After a brief overview on the theoretical background of various point-spread-functions (PSF) computational simulations are presented, which quantify the modulation amplitude of a binary test object sampled with either standard, zero-filled or shifted k-space acquisition. The results suggest that echo-shifting with zero-filling is not advantageous, not even with small matrix sizes, and that echo-shifting with additional acquisition of outer k-space lines decreases the modulation amplitude only slightly. Simulations were also performed on noise-corrupted test objects, indicating that the use of the echo-shifted scheme causes resolution loss of up to 30% compared to the standard scheme for a 128 by 128 pixel matrix at a noise level of 20%. Finally, in vivo experiments using different echo shifts are presented and the characteristics of signal and noise with varying TE are quantified.  相似文献   

15.
BACKGROUND: Ultrahigh-field MRI at 8 T offers unprecedented resolution for imaging brain structures and microvasculature. OBJECTIVE: The aim of this study is to apply high-resolution MRI for stroke imaging and to characterize findings at 1.5 and 8 T. METHODS: Seventeen subjects with minor ischemic infarcts were studied using T2-weighted gradient echo (GE) and rapid acquisition with relaxation enhancement (RARE) images at 8 T with resolution up to 200 microm. In 10 subjects, T1- and T2-weighted fast spin echo (FSE) and fluid-attenuated inversion recovery (FLAIR) images were also acquired at 1.5-T MRI. RESULTS: The 8-T images showed infarcts as sharply demarcated areas of high-signal intensity (n=21) and revealed more infarctions than 1.5-T images (n=14) (P<.003). The low-signal intensity areas that surrounded infarctions were suggestive of hemosiderin deposits. The 8-T characteristics of microvessels terminating within the infractions were distinct from normal vasculature. The 8-T images revealed an angioma at the site of a second stroke, not apparent on 1.5-T images. CONCLUSIONS: Ultrahigh-field MRI at 8 T is feasible for stroke imaging. The 8-T MRI visualized infarcts and microvasculature with high resolution, revealing infarcts and vascular pathologies that were not apparent at 1.5 T.  相似文献   

16.
Localized high-resolution diffusion tensor images (DTI) from the midbrain were obtained using reduced field-of-view (rFOV) methods combined with SENSE parallel imaging and single-shot echo planar (EPI) acquisitions at 7 T. This combination aimed to diminish sensitivities of DTI to motion, susceptibility variations, and EPI artifacts at ultra-high field. Outer-volume suppression (OVS) was applied in DTI acquisitions at 2- and 1-mm2 resolutions, b = 1000 s/mm2, and six diffusion directions, resulting in scans of 7- and 14-min durations. Mean apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in various fiber tract locations at the two resolutions and compared. Geometric distortion and signal-to-noise ratio (SNR) were additionally measured and compared for reduced-FOV and full-FOV DTI scans. Up to an eight-fold data reduction was achieved using DTI-OVS with SENSE at 1 mm2, and geometric distortion was halved. The localization of fiber tracts was improved, enabling targeted FA and ADC measurements. Significant differences in diffusion properties were observed between resolutions for a number of regions suggesting that FA values are impacted by partial volume effects even at a 2-mm2 resolution. The combined SENSE DTI-OVS approach allows large reductions in DTI data acquisition and provides improved quality for high-resolution diffusion studies of the human brain.  相似文献   

17.
Parallel MRI at microtesla fields   总被引:2,自引:2,他引:0  
Parallel imaging techniques have been widely used in high-field magnetic resonance imaging (MRI). Multiple receiver coils have been shown to improve image quality and allow accelerated image acquisition. Magnetic resonance imaging at ultra-low fields (ULF MRI) is a new imaging approach that uses SQUID (superconducting quantum interference device) sensors to measure the spatially encoded precession of pre-polarized nuclear spin populations at microtesla-range measurement fields. In this work, parallel imaging at microtesla fields is systematically studied for the first time. A seven-channel SQUID system, designed for both ULF MRI and magnetoencephalography (MEG), is used to acquire 3D images of a human hand, as well as 2D images of a large water phantom. The imaging is performed at 46 mu T measurement field with pre-polarization at 40 mT. It is shown how the use of seven channels increases imaging field of view and improves signal-to-noise ratio for the hand images. A simple procedure for approximate correction of concomitant gradient artifacts is described. Noise propagation is analyzed experimentally, and the main source of correlated noise is identified. Accelerated imaging based on one-dimensional undersampling and 1D SENSE (sensitivity encoding) image reconstruction is studied in the case of the 2D phantom. Actual threefold imaging acceleration in comparison to single-average fully encoded Fourier imaging is demonstrated. These results show that parallel imaging methods are efficient in ULF MRI, and that imaging performance of SQUID-based instruments improves substantially as the number of channels is increased.  相似文献   

18.
Echo-planar imaging is widely used in functional neuroimaging but suffers from its pronounced sensitivity to field inhomogeneities that cause geometric distortions and image blurring which both limit the effective in-plane resolution achievable. In this work, it is shown how inner-field-of-view techniques based on 2D-selective RF excitations (2DRF) can be applied to reduce the field-of-view in the phase-encoding direction without aliasing and increase the in-plane resolution accordingly. Free-induction-decay (FID) EPI and echo-train-shifted (T2*-weighted) and standard (T2-weighted) spin-echo (SE) EPI with in-plane resolutions of up to 0.5×1.0 mm2 (slice thickness 5 mm) were acquired at 3 T. Unwanted signal contributions of 2DRF side excitations were shifted out of the object (FID-EPI) or of the refocusing plane by tilting the excitation plane (SE-EPI). Brain activation in healthy volunteers was investigated with checkerboard and finger-tapping block-design paradigms. Brain activation could be detected with all sequences and contrasts, most reliably with FID-EPI due to its higher signal amplitude and the longer 2DRF excitation that are more sensitive to magnetic field inhomogeneities. In conclusion, inner-FOV EPI based on 2DRF excitations could help to improve the spatial resolution of fMRI of focal target regions, e.g. for applications in the spinal cord.  相似文献   

19.
Magnetic resonance imaging (MRI) is very useful spectroscopy to visualize a three-dimensional (3D) real structure inside the sample without physical destruction. The spatial resolution of the readily available MRI spectrometer is, however, limited by a few ten to hundreds of microns due to a technological boundary of generating larger magnetic field gradient and to the insensitivity inherent to the inductive signal detection. Magnetic resonance force microscopy (MRFM) is new alternative MRI spectroscopy which is anticipated to significantly surpass the conventional MRI in both resolution and sensitivity. We report two imaging experiments on our MRFM spectrometer operated at room temperature and in vacuum approximately 10(-3)Pa. One is for approximately 20 microm liposome membrane labeled entirely by a nitroxide imaging agent and the other for approximately 15 microm DPPH particles, both are nearly the same size as that of human cell. The reconstructed images at spatial resolution approximately 1 microm were in satisfactory agreement with the scanning electron microscope images. The potential capability of visualizing intrinsic radicals in the cell is suggested to investigate redox process from a microscopic point of view.  相似文献   

20.
Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies using parallel imaging to reduce the readout window have reported a loss in temporal signal-to-noise ratio (SNR) that is less than would be expected given a purely thermal noise model. In this study, the impact of parallel imaging on the noise components and functional sensitivity of both BOLD and perfusion-based fMRI data was investigated. Dual-echo arterial spin labeling data were acquired on five subjects using sensitivity encoding (SENSE), at reduction factors (R) of 1, 2 and 3. Direct recording of cardiac and respiratory activity during data acquisition enabled the retrospective removal of physiological noise. The temporal SNR of the perfusion time series closely followed the thermal noise prediction of a √R loss in SNR as the readout window was shortened, with temporal SNR values (relative to the R=1 data) of 0.72 and 0.56 for the R=2 and R=3 data, respectively, after accounting for physiological noise. However, the BOLD temporal SNR decreased more slowly than predicted even after accounting for physiological noise, with relative temporal SNR values of 0.80 and 0.63 for the R=2 and R=3 data, respectively. Spectral analysis revealed that the BOLD trends were dominated by low-frequency fluctuations, which were not dominant in the perfusion data due to signal processing differences. The functional sensitivity, assessed using mean F values over activated regions of interest (ROIs), followed the temporal SNR trends for the BOLD data. However, results for the perfusion data were more dependent on the threshold used for ROI selection, most likely due to the inherently low SNR of functional perfusion data.  相似文献   

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