A multi‐compartmental SE‐BOLD interpretation for stimulus‐related signal changes in diffusion‐weighted functional MRI

A new interpretation is proposed for stimulus‐induced signal changes in diffusion‐weighted functional MRI. T₂‐weighted spin‐echo echo‐planar images were acquired at different diffusion‐weightings while visual stimulation was presented to human volunteers. The amplitudes of the positive stimulus‐correlated response and post‐stimulus undershoot (PSU) in the functional time‐courses were found to follow different trends as a function of b‐value. Data were analysed using a three‐compartment signal model, with one compartment being purely vascular and the other two dominated by fast‐ and slow‐diffusing molecules in the brain tissue. The diffusion coefficients of the tissue were assumed to be constant throughout the experiments. It is shown that the stimulus‐induced signal changes can be decomposed into independent contributions originating from each of the three compartments. After decomposition, the fast‐diffusion phase displays a substantial PSU, while the slow‐diffusion phase demonstrates a highly reproducible and stimulus‐correlated time‐course with minimal undershoot. The decomposed responses are interpreted in terms of the spin‐echo blood oxygenation level dependent (SE‐BOLD) effect, and it is proposed that the signal produced by fast‐ and slow‐diffusing molecules reflect a sensitivity to susceptibility changes in arteriole/venule‐ and capillary‐sized vessels, respectively. This interpretation suggests that diffusion‐weighted SE‐BOLD imaging may provide subtle information about the haemodynamic and neuronal responses. Copyright © 2009 John Wiley & Sons, Ltd.     

Implementation of spin‐echo blood oxygen level‐dependent (BOLD) functional MRI in birds

The advent of high‐field MRI systems has allowed the implementation of blood oxygen level‐dependent functional MRI (BOLD fMRI) on small animals. An increased magnetic field improves the signal‐to‐noise ratio and thus allows an improvement in the spatial resolution. However, it also increases susceptibility artefacts in the commonly acquired gradient‐echo images. This problem is particularly prominent in songbird MRI because of the presence of numerous air cavities in the skull of birds. These T₂*‐related image artefacts can be circumvented using spin‐echo BOLD fMRI. In this article, we describe the implementation of spin‐echo BOLD fMRI in zebra finches, a small songbird of 15–25 g, extensively studied in the behavioural neurosciences of birdsong. Because the main topics in this research domain are song perception and song learning, the protocol implemented used auditory stimuli. Despite the auditory nature of the stimuli and the weak contrast‐to‐noise ratio of spin‐echo BOLD fMRI compared with gradient‐echo BOLD fMRI, we succeeded in detecting statistically significant differences in BOLD responses triggered by different stimuli. This study shows that spin‐echo BOLD fMRI is a viable approach for the investigation of auditory processing in the whole brain of small songbirds. It can also be applied to study auditory processing in other small animals, as well as other sensory modalities. Copyright © 2010 John Wiley & Sons, Ltd.     

Simultaneous multi‐slice spin‐ and gradient‐echo dynamic susceptibility‐contrast perfusion‐weighted MRI of gliomas

Although combined spin‐ and gradient‐echo (SAGE) dynamic susceptibility‐contrast (DSC) MRI can provide perfusion quantification that is sensitive to both macrovessels and microvessels while correcting for T₁‐shortening effects, spatial coverage is often limited in order to maintain a high temporal resolution for DSC quantification. In this work, we combined a SAGE echo‐planar imaging (EPI) sequence with simultaneous multi‐slice (SMS) excitation and blipped controlled aliasing in parallel imaging (blipped CAIPI) at 3 T to achieve both high temporal resolution and whole brain coverage. Two protocols using this sequence with multi‐band (MB) acceleration factors of 2 and 3 were evaluated in 20 patients with treated gliomas to determine the optimal scan parameters for clinical use. ΔR₂*(t) and ΔR₂(t) curves were derived to calculate dynamic signal‐to‐noise ratio (dSNR), ΔR₂*‐ and ΔR₂‐based relative cerebral blood volume (rCBV), and mean vessel diameter (mVD) for each voxel. The resulting SAGE DSC images acquired using MB acceleration of 3 versus 2 appeared visually similar in terms of image distortion and contrast. The difference in the mean dSNR from normal‐appearing white matter (NAWM) and that in the mean dSNR between NAWM and normal‐appearing gray matter were not statistically significant between the two protocols. ΔR₂*‐ and ΔR₂‐rCBV maps and mVD maps provided unique contrast and spatial heterogeneity within tumors.     

Determination of the appropriate b value and number of gradient directions for high‐angular‐resolution diffusion‐weighted imaging

High‐angular‐resolution diffusion‐weighted imaging (HARDI) is one of the most common MRI acquisition schemes for use with higher order models of diffusion. However, the optimal b value and number of diffusion‐weighted (DW) directions for HARDI are still undetermined, primarily as a result of the large number of available reconstruction methods and corresponding parameters, making it impossible to identify a single criterion by which to assess performance. In this study, we estimate the minimum number of DW directions and optimal b values required for HARDI by focusing on the angular frequency content of the DW signal itself. The spherical harmonic (SH) series provides the spherical analogue of the Fourier series, and can hence be used to examine the angular frequency content of the DW signal. Using high‐quality data acquired along 500 directions over a range of b values, we estimate that SH terms above l = 8 are negligible in practice for b values up to 5000 s/mm², implying that a minimum of 45 DW directions is sufficient to fully characterise the DW signal. l > 0 SH terms were found to increase as a function of b value, levelling off at b = 3000 s/mm², suggesting that this value already provides the highest achievable angular resolution. In practice, it is recommended to acquire more than the minimum of 45 DW directions to avoid issues with imperfections in the uniformity of the DW gradient directions and to meet signal‐to‐noise requirements of the intended reconstruction method. Copyright © 2013 John Wiley & Sons, Ltd.     

Interrelations of muscle functional MRI,diffusion‐weighted MRI and 31P‐MRS in exercised lower back muscles

Exercise‐induced changes of transverse proton relaxation time (T₂), tissue perfusion and metabolic turnover were investigated in the lower back muscles of volunteers by applying muscle functional MRI (mfMRI) and diffusion‐weighted imaging (DWI) before and after as well as dynamic ³¹P‐MRS during the exercise. Inner (M. multifidus, MF) and outer lower back muscles (M. erector spinae, ES) were examined in 14 healthy young men performing a sustained isometric trunk‐extension. Significant phosphocreatine (PCr) depletions ranging from 30% (ES) to 34% (MF) and Pi accumulations between 95% (left ES) and 120%–140% (MF muscles and right ES) were observed during the exercise, which were accompanied by significantly decreased pH values in all muscles (?pH ≈ –0.05). Baseline T₂ values were similar across all investigated muscles (approximately 27 ms at 3 T), but revealed right–left asymmetric increases (T₂,_inc) after the exercise (right ES/MF: T₂,_inc = 11.8/9.7%; left ES/MF: T₂,_inc = 4.6/8.9%). Analyzed muscles also showed load‐induced increases in molecular diffusion D (p = .007) and perfusion fraction f (p = .002). The latter parameter was significantly higher in the MF than in the ES muscles both at rest and post exercise. Changes in PCr (p = .03), diffusion (p < .01) and perfusion (p = .03) were strongly associated with T_2,inc, and linear mixed model analysis revealed that changes in PCr and perfusion both affect T_2,inc (p < .001). These findings support previous assumptions that T₂ changes are not only an intra‐cellular phenomenon resulting from metabolic stress but are also affected by increased perfusion in loaded muscles. Copyright © 2014 John Wiley & Sons, Ltd.     

Comparison of different MRI sequences in lesion detection and early response evaluation of diffuse large B‐cell lymphoma – a whole‐body MRI and diffusion‐weighted imaging study

To compare different MRI sequences for the detection of lesions and the evaluation of response to chemotherapy in patients with diffuse large B‐cell lymphoma (DLBCL), 18 patients with histology‐confirmed DLBCL underwent 3‐T MRI scanning prior to and 1 week after chemotherapy. The MRI sequences included T₁‐weighted pre‐ and post‐contrast, T₂‐weighted with and without fat suppression, and a single‐shot echo‐planar diffusion‐weighted imaging (DWI) with two b values (0 and 800 s/mm²). Conventional MRI sequence comparisons were performed using the contrast ratio between tumor and normal vertebral body instead of signal intensity. The apparent diffusion coefficient (ADC) of the tumor was measured directly on the parametric ADC map. The tumor volume was used as a reference for the evaluation of chemotherapy response. The mean tumor volume was 374 mL at baseline, and decreased by 65% 1 week after chemotherapy (p < 0.01). The T₂‐weighted image with fat suppression showed a significantly higher contrast ratio compared with images from all other conventional MRI sequences, both before and after treatment (p < 0.01, respectively). The contrast ratio of the T₂‐weighted image with fat suppression decreased significantly (p < 0.01), and that of the T₁‐weighted pre‐contrast image increased significantly (p < 0.01), after treatment. However, there was no correlation between the change in contrast ratio and tumor volume. The mean ADC value was 0.68 × 10^–3 mm²/s at baseline; it increased by 89% after chemotherapy (p < 0.001), and the change in ADC value correlated with the change in tumor volume (r = 0.66, p < 0.01). The baseline ADC value also correlated inversely with the percentage change in ADC after treatment (r = ?0.62, p < 0.01). In conclusion, this study indicates that T₂‐weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI. Copyright © 2013 John Wiley & Sons, Ltd.     

Diffusion‐weighted MRI with intravoxel incoherent motion modeling for assessment of muscle perfusion in the thigh during post‐exercise hyperemia in younger and older adults

Aging is associated with impaired endothelium‐dependent vasodilation that leads to muscle perfusion impairment and contributes to organ dysfunction. Impaired muscle perfusion may result in inadequate delivery of oxygen and nutrients during and after muscle contraction, leading to muscle damage. The ability to study the relationship between perfusion and muscle damage has been limited using traditional muscle perfusion measures, which are invasive and risky. To overcome this limitation, we optimized a diffusion‐weighted MRI sequence and validated an intravoxel incoherent motion (IVIM) analysis based on Monte Carlo simulation to study muscle perfusion impairment with aging during post‐exercise hyperemia. Simulation results demonstrated that the bias of IVIM‐derived perfusion fraction (f_p ) and diffusion of water molecules in extra‐vascular tissue (D ) ranged from ?3.3% to 14% and from ?16.5% to 0.002%, respectively, in the optimized experimental condition. The dispersion in f_p and D ranged from 3.2% to 9.5% and from 0.9% to 1.1%, respectively. The mid‐thigh of the left leg of four younger (21–30 year old) and four older (60–90 year old) healthy females was studied using the optimized protocol at baseline and at seven time increments occurring every 3.25 min following in‐magnet dynamic knee extension exercise performed using a MR‐compatible ergometer with a workload of 0.4 bar for 2.5 min. After exercise, both f_p and D significantly increased in the rectus femoris (active muscle during exercise) but not in adductor magnus (inactive muscle), reflecting the fact that the local increase in perfusion with both groups showed a maximum value in the second post‐exercise time‐point. A significantly greater increase in perfusion from the baseline (p < 0.05) was observed in the younger group (37 ± 12.05%) compared with the older group (17.57 ± 15.92%) at the first post‐exercise measurement. This work establishes a reliable non‐invasive method that can be used to study the effects of aging on dynamic changes in muscle perfusion as they relate to important measures of physical function.     

Imaging quality of PROPELLER diffusion‐weighted MR imaging and its diagnostic performance in distinguishing pleomorphic adenomas from Warthin tumors of the parotid gland

The aim of this study was to evaluate the imaging quality and diagnostic performance of fast spin echo diffusion‐weighted imaging with periodically rotated overlapping parallel lines with enhanced reconstruction (FSE‐PROP‐DWI) in distinguishing parotid pleomorphic adenoma (PMA) from Warthin tumor (WT). This retrospective study enrolled 44 parotid gland tumors from 34 patients, including 15 PMAs and 29 WTs with waived written informed consent. All participants underwent 1.5 T diffusion‐weighted imaging including FSE‐PROP‐DWI and single‐shot echo‐planar diffusion‐weighted imaging (SS‐EP‐DWI). After imaging resizing and registration among T2WI, FSE‐PROP‐DWI and SS‐EP‐DWI, imaging distortion was quantitatively analyzed by using the Dice coefficient. Signal‐to‐noise ratio and contrast‐to‐noise ratio were qualitatively evaluated. The mean apparent diffusion coefficient (ADC) of parotid gland tumors was calculated. Wilcoxon signed‐rank test was used for paired comparison between FSE‐PROP‐DWI versus SS‐EP‐DWI. Mann–Whitney U test was used for independent group comparison between PMAs versus WTs. Diagnostic performance was evaluated by receiver operating characteristics curve analysis. P < 0.05 was considered statistically significant. The Dice coefficient was statistically significantly higher on FSE‐PROP‐DWI than SS‐EP‐DWI for both tumors (P < 0.005). Mean ADC was statistically significantly higher in PMAs than WTs on both FSE‐PROP‐DWI and SS‐EP‐DWI (P < 0.005). FSE‐PROP‐DWI and SS‐EP‐DWI successfully distinguished PMAs from WTs with an AUC of 0.880 and 0.945, respectively (P < 0.05). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy in diagnosing PMAs were 100%, 69.0%, 62.5%, 100% and 79.5% for FSE‐PROP‐DWI, and 100%, 82.8%, 75%, 100% and 88.6% for SS‐EP‐DWI, respectively. FSE‐PROP‐DWI is useful to distinguish parotid PMAs from WTs with less distortion of tumors but lower AUC than SS‐EP‐DWI.     

Rapid simultaneous acquisition of T1 and T2 mapping images using multishot double spin‐echo EPI and automated variations of TR and TE (ms‐DSEPI‐T12)

A rapid method of simultaneous T₁ and T₂ measurement is presented which uses a segmented echo‐planar readout with varying repetition times (TR) and echo times (TE). This method is useful in T₁ mapping for analysis of dynamic contrast enhanced MRI (DCE‐MRI), where T₁ can be used to estimate contrast agent concentration. In the application of this method to dynamic imaging, the equilibrium magnetization is measured on pre‐contrast images and incorporated into post‐contrast T₁ calculations for improved accuracy. Simultaneous T₂ measurement allows correction of T₂ effects in the T₁ map which may occur at high contrast agent concentrations, and is performed without significant imaging time penalty. Phantom and in vivo results show the usefulness of this technique for analysis of contrast enhancement kinetics. Accurate rapid contrast agent concentration measurement may be useful for analyzing the distribution and kinetics of contrast agents or labeled pharmaceuticals. Copyright © 2009 John Wiley & Sons, Ltd.