Real-time phase-contrast MRI of cardiovascular blood flow using undersampled radial fast low-angle shot and nonlinear inverse reconstruction

Velocity‐encoded phase‐contrast MRI of cardiovascular blood flow commonly relies on electrocardiogram‐synchronized cine acquisitions of multiple heartbeats to quantitatively determine the flow of an averaged cardiac cycle. Here, we present a new method for real‐time phase‐contrast MRI that combines flow‐encoding gradients with highly undersampled radial fast low‐angle shot acquisitions and phase‐sensitive image reconstructions by regularized nonlinear inversion. Apart from calibration studies using steady and pulsatile flow, preliminary in vivo applications focused on through‐plane flow in the ascending aorta of healthy subjects. With bipolar velocity‐encoding gradients of alternating polarity that overlap the slice‐refocusing gradient, the method yields flow‐encoded images with an in‐plane resolution of 1.8 mm, section thickness of 6 mm and measuring time at 3 T of 24 ms (TR/TE = 3.44/2.76 ms; flip angle, 10º; seven radial spokes per image). Accordingly, phase‐contrast maps and corresponding velocity profiles achieve a temporal resolution of 48 ms. The evaluated peak velocities, stroke volumes, flow rates and respective variances over at least 20 consecutive heartbeats are in general agreement with literature data. Copyright © 2011 John Wiley & Sons, Ltd.     

Non‐water‐suppressed short‐echo‐time magnetic resonance spectroscopic imaging using a concentric ring k‐space trajectory

Water‐suppressed MRS acquisition techniques have been the standard MRS approach used in research and for clinical scanning to date. The acquisition of a non‐water‐suppressed MRS spectrum is used for artefact correction, reconstruction of phased‐array coil data and metabolite quantification. Here, a two‐scan metabolite‐cycling magnetic resonance spectroscopic imaging (MRSI) scheme that does not use water suppression is demonstrated and evaluated. Specifically, the feasibility of acquiring and quantifying short‐echo (T_E = 14 ms), two‐dimensional stimulated echo acquisition mode (STEAM) MRSI spectra in the motor cortex is demonstrated on a 3 T MRI system. The increase in measurement time from the metabolite‐cycling is counterbalanced by a time‐efficient concentric ring k‐space trajectory. To validate the technique, water‐suppressed MRSI acquisitions were also performed for comparison. The proposed non‐water‐suppressed metabolite‐cycling MRSI technique was tested for detection and correction of resonance frequency drifts due to subject motion and/or hardware instability, and the feasibility of high‐resolution metabolic mapping over a whole brain slice was assessed. Our results show that the metabolite spectra and estimated concentrations are in agreement between non‐water‐suppressed and water‐suppressed techniques. The achieved spectral quality, signal‐to‐noise ratio (SNR) > 20 and linewidth <7 Hz allowed reliable metabolic mapping of five major brain metabolites in the motor cortex with an in‐plane resolution of 10 × 10 mm² in 8 min and with a Cramér‐Rao lower bound of less than 20% using LCModel analysis. In addition, the high SNR of the water peak of the non‐water‐suppressed technique enabled voxel‐wise single‐scan frequency, phase and eddy current correction. These findings demonstrate that our non‐water‐suppressed metabolite‐cycling MRSI technique can perform robustly on 3 T MRI systems and within a clinically feasible acquisition time.     

Comparing diagnostic accuracy of luminal water imaging with diffusion‐weighted and dynamic contrast‐enhanced MRI in prostate cancer: A quantitative MRI study

Luminal water imaging (LWI) is a new MRI T₂ mapping technique that has been developed with the aim of diagnosis of prostate carcinoma (PCa). This technique measures the fractional amount of luminal water in prostate tissue, and has shown promising preliminary results in detection of PCa. To include LWI in clinical settings, further investigation on the accuracy of this technique is required. In this study, we compare the diagnostic accuracy of LWI with those of diffusion‐weighted imaging (DWI) and dynamic contrast‐enhanced (DCE) MRI in detection and grading of PCa. Fifteen patients with biopsy‐proven PCa consented to participate in this ethics‐board‐approved prospective study. Patients were examined with LWI, DWI, and DCE sequences at 3 T prior to radical prostatectomy. Maps of MRI parameters were generated and registered to whole‐mount histology. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic accuracy of individual and combined MR parameters. Correlation with Gleason score (GS) was evaluated using Spearman's rank correlation test. The results show that area under the ROC curve (AUC) obtained from LWI was equal to or higher than the AUC obtained from DWI, DCE, or their combination, in peripheral zone (0.98 versus 0.90, 0.89, and 0.91 respectively), transition zone (0.99 versus 0.98, n/a, and 0.98), and the entire prostate (0.85 versus 0.81, 0.75, and 0.84). The strongest correlation with GS was achieved from LWI (ρ = ?0.81 ± 0.09, P < 0.001). Results of this pilot study show that LWI performs equally well as, or better than, DWI and DCE in detection of PCa. LWI provides significantly higher correlation with GS than DWI and DCE. This technique can potentially be included in clinical MRI protocols to improve characterization of tumors. However, considering the small size of the patient population in this study, a further study with a larger cohort of patients and broader range of GS is required to confirm the findings and draw a firm conclusion on the applicability of LWI in clinical settings.     

Classification of prostatic diseases by means of multivariate analysis on in vivo proton MRSI and DCE‐MRI data

Multivariate analysis has been applied on proton magnetic resonance spectroscopic imaging (¹H‐MRSI) and dynamic contrast enhanced MRI (DCE‐MRI) data of patients with different prostatic diseases such as chronic inflammation, fibrosis and adenocarcinoma. Multivariate analysis offers a global view of the entire range of information coming from both the imaging and spectroscopic side of NMR technology, leading to an integrated picture of the system relying upon the entire metabolic and dynamic profile of the studied samples. In this study, we show how this approach, applied to ¹H‐MRSI/DCE‐MRI results, allows us to differentiate among the various prostatic diseases in a non‐invasive way with a 100% accuracy. These findings suggest that multivariate analysis of ¹H‐MRSI/DCE‐MRI can significantly improve the diagnostic accuracy for these pathological entities. From a more theoretical point of view, the complementation of a single biomarker approach with an integrated picture of the entire metabolic and dynamic profile allows for a more realistic appreciation of pathological entities. Copyright © 2009 John Wiley & Sons, Ltd.     

Characterization and stratification of prostate lesions based on comprehensive multiparametric MRI using detailed whole‐mount histopathology as a reference standard

The purpose of this study was to characterize prostate cancer (PCa) based on multiparametric MR (mpMR) measures derived from MRI, diffusion, spectroscopy, and dynamic contrast‐enhanced (DCE) MRI, and to validate mpMRI in detecting PCa and predicting PCa aggressiveness by correlating mpMRI findings with whole‐mount histopathology. Seventy‐eight men with untreated PCa received 3 T mpMR scans prior to radical prostatectomy. Cancerous regions were outlined, graded, and cancer amount estimated on whole‐mount histology. Regions of interest were manually drawn on T₂‐weighted images based on histopathology. Logistic regression was used to identify optimal combinations of parameters for the peripheral zone and transition zone to separate: (i) benign from malignant tissues; (ii) Gleason score (GS) ≤3 + 3 disease from ≥GS3 + 4; and (iii) ≤ GS3 + 4 from ≥GS4 + 3 cancers. The performance of the models was assessed using repeated fourfold cross‐validation. Additionally, the performance of the logistic regression models created under the assumption that one or more modality has not been acquired was evaluated. Logistic regression models yielded areas under the curve (AUCs) of 1.0 and 0.99 when separating benign from malignant tissues in the peripheral zone and the transition zone, respectively. Within the peripheral zone, combining choline, maximal enhancement slope, apparent diffusion coefficient (ADC), and citrate measures for separating ≤GS3 + 3 from ≥GS3 + 4 PCa yielded AUC = 0.84. Combining creatine, choline, and washout slope yielded AUC = 0.81 for discriminating ≤GS3 + 4 from ≥GS4 + 3 disease. Within the transition zone, combining washout slope, ADC, and creatine yielded AUC = 0.93 for discriminating ≤GS3 + 3 and ≥GS3 + 4 cancers. When separating ≤GS3 + 4 from ≥GS4 + 3 PCa, combining choline and washout slope yielded AUC = 0.92. MpMRI provides excellent separation between benign tissues and PCa, and across PCa tissues of different aggressiveness. The final models prominently feature spectroscopy and DCE‐derived metrics, underlining their value within a comprehensive mpMRI examination.     

Undersampled linogram trajectory for fast imaging (ULTI): experiments at 3 T and 7 T

In this study, the performance of linogram acquisition was investigated for the reconstruction of images from undersampled data using parallel imaging methods. The point spread function (PSF) of linogram sampling was analyzed for image sharpness and artifacts. Generalized auto‐calibrating partially parallel acquisition was implemented for this new sampling scheme, and images were reconstructed with high acceleration rates. The results were compared with conventional radial sampling methods using simulations and phantom experiments at 3 T. Additionally, a human volunteer was scanned at 7 T. The results demonstrated that the PSF was sharper and the mean artifact power was lower for linogram sampling compared with radial sampling. Results of simulations and phantom experiments were in accord with the findings of the PSF analysis. In simulations, errors in the reconstructed images were lower for linogram sampling. In phantom experiments, fine details and sharp edges were preserved for linogram sampling, while details were blurred for radial sampling. The in vivo human study demonstrated that linogram sampling could provide high quality images of anatomy, even at high acceleration rates. Linogram sampling not only possesses the advantages of radial sampling, such as reduced sensitivity to motion and higher acceleration rates, but it also provides sharper images with fewer artifacts. Moreover, it is less prone to off‐resonance artifacts compared with radial sampling. Copyright © 2016 John Wiley & Sons, Ltd.     

Arterial spin labeling‐fast imaging with steady‐state free precession (ASL‐FISP): a rapid and quantitative perfusion technique for high‐field MRI

Arterial spin labeling (ASL) is a valuable non‐contrast perfusion MRI technique with numerous clinical applications. Many previous ASL MRI studies have utilized either echo‐planar imaging (EPI) or true fast imaging with steady‐state free precession (true FISP) readouts, which are prone to off‐resonance artifacts on high‐field MRI scanners. We have developed a rapid ASL‐FISP MRI acquisition for high‐field preclinical MRI scanners providing perfusion‐weighted images with little or no artifacts in less than 2 s. In this initial implementation, a flow‐sensitive alternating inversion recovery (FAIR) ASL preparation was combined with a rapid, centrically encoded FISP readout. Validation studies on healthy C57/BL6 mice provided consistent estimation of in vivo mouse brain perfusion at 7 and 9.4 T (249 ± 38 and 241 ± 17 mL/min/100 g, respectively). The utility of this method was further demonstrated in the detection of significant perfusion deficits in a C57/BL6 mouse model of ischemic stroke. Reasonable kidney perfusion estimates were also obtained for a healthy C57/BL6 mouse exhibiting differential perfusion in the renal cortex and medulla. Overall, the ASL‐FISP technique provides a rapid and quantitative in vivo assessment of tissue perfusion for high‐field MRI scanners with minimal image artifacts. Copyright © 2014 John Wiley & Sons, Ltd.     

Combining parallel detection of proton echo planar spectroscopic imaging (PEPSI) measurements with a data‐consistency constraint improves SNR

One major challenge of MRSI is the poor signal‐to‐noise ratio (SNR), which can be improved by using a surface coil array. Here we propose to exploit the spatial sensitivity of different channels of a coil array to enforce the k‐space data consistency (DC) in order to suppress noise and consequently to improve MRSI SNR. MRSI data were collected using a proton echo planar spectroscopic imaging (PEPSI) sequence at 3 T using a 32‐channel coil array and were averaged with one, two and eight measurements (avg‐1, avg‐2 and avg‐8). The DC constraint was applied using a regularization parameter λ of 1, 2, 3, 5 or 10. Metabolite concentrations were quantified using LCModel. Our results show that the suppression of noise by applying the DC constraint to PEPSI reconstruction yields up to 32% and 27% SNR gain for avg‐1 and avg‐2 data with λ = 5, respectively. According to the reported Cramer–Rao lower bounds, the improvement in metabolic fitting was significant (p < 0.01) when the DC constraint was applied with λ ≥ 2. Using the DC constraint with λ = 3 or 5 can minimize both root‐mean‐square errors and spatial variation for all subjects using the avg‐8 data set as reference values. Our results suggest that MRSI reconstructed with a DC constraint can save around 70% of scanning time to obtain images and spectra with similar SNRs using λ = 5. Copyright © 2015 John Wiley & Sons, Ltd.     

Simultaneous measurement of T1/B1 and pharmacokinetic model parameters using active contrast encoding (ACE)‐MRI

The aim of this study was to assess the feasibility of combining dynamic contrast enhanced‐magnetic resonance imaging (DCE‐MRI) with the measurement of the radiofrequency (RF) transmit field B ₁ and pre‐contrast longitudinal relaxation time T ₁₀. A novel approach has been proposed to simultaneously estimate B ₁ and T ₁₀ from a modified DCE‐MRI scan that actively encodes the washout phase of the curve with different amounts of T ₁ and B ₁ weighting using multiple flip angles and repetition times, hence referred to as active contrast encoding (ACE)‐MRI. ACE‐MRI aims to simultaneously measure B ₁ and T ₁₀, together with contrast kinetic parameters, such as the transfer constant K ^trans, interstitial space volume fraction v _e and vascular space volume fraction v _p. The proposed method was tested using numerical simulations and in vivo studies with mouse models of breast cancer implanted in the flank and mammary fat pad, and glioma in the brain. In the numerical simulation study with a signal‐to‐noise ratio of 10, both B ₁ and T ₁₀ were estimated accurately with errors of 5.1 ± 3.5% and 12.3 ± 8.8% and coefficients of variation (CV) of 14.9 ± 8.6% and 15.0 ± 5.0%, respectively. Using the same ACE‐MRI data, the kinetic parameters K ^trans, v _e and v _p were also estimated with errors of 14.2 ± 8.3% (CV = 13.5 ± 4.6%), 14.7 ± 9.9% (CV = 13.3 ± 4.5%) and 14.0 ± 9.3% (CV = 14.0 ± 4.5%), respectively. For the in vivo tumor data from 11 mice, voxel‐wise comparisons between ACE‐MRI and DCE‐MRI methods showed that the mean differences for the five parameters were as follows: ΔK ^trans = 0.006 (/min), Δv _e = 0.016, Δv _p = 0.000, ΔB ₁ = ?0.014 and ΔT ₁ = ?0.085 (s), which suggests a good agreement between the two methods. When compared with separately measured B ₁ and T ₁₀, and DCE‐MRI estimated kinetic parameters as a reference, the mean relative errors of ACE‐MRI estimation were B ₁ = ?0.3%, T ₁₀ = ?8.5%, K ^trans = 11.4%, v _e = 14.5% and v _p = 4.5%. This proof‐of‐concept study demonstrates that the proposed ACE‐MRI method can be used to estimate B ₁ and T ₁₀, together with contrast kinetic model parameters.     

Differentiating the histologic grades of gliomas preoperatively using amide proton transfer‐weighted (APTW) and intravoxel incoherent motion MRI

The purpose of this work was to investigate the diagnostic performance of amide proton transfer‐weighted (APTW) and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the preoperative grading of gliomas. Fifty‐one patients with suspected gliomas were recruited and underwent a preoperative MRI examination that included APTW and IVIM sequences. All cases were confirmed by postsurgical histopathology. APTW signal intensity, true diffusion coefficient (D), perfusion fraction (f) and pseudo‐diffusion coefficient (D*) were applied to assess the solid tumor component and contralateral normal‐appearing white matter. The relative APTW signal intensity (rAPTW) was also used. Independent‐sample and paired‐sample t‐tests were used to compare differences in MRI parameters between low‐grade glioma (LGG) and high‐grade glioma (HGG) groups. The diagnostic performance was assessed with the receiver operating characteristic curve. Twenty‐six patients were pathologically diagnosed with LGG and 25 were diagnosed with HGG. APTW, rAPTW and f values were significantly higher (all p < 0.001), whereas D values were significantly lower (p < 0.001) in the HGG group than in the LGG group. There was no significant difference between D* values for the two groups. rAPTW had an area under the curve (AUC) of 0.957, with a sensitivity of 100% and a specificity of 84.6%, followed by APTW, f, D and D*. The combined use of APTW and IVIM showed the best diagnostic performance, with an AUC of 0.986. In conclusion, APTW and IVIM, as two promising supplementary sequences for routine MRI, could be valuable in differentiating LGGs from HGGs.     

Tract‐specific and age‐related variations of the spinal cord microstructure: a multi‐parametric MRI study using diffusion tensor imaging (DTI) and inhomogeneous magnetization transfer (ihMT)

Being able to finely characterize the spinal cord (SC) microstructure and its alterations is a key point when investigating neural damage mechanisms encountered in different central nervous system (CNS) pathologies, such as multiple sclerosis, amyotrophic lateral sclerosis or myelopathy. Based on novel methods, including inhomogeneous magnetization transfer (ihMT) and dedicated SC probabilistic atlas post‐processing, the present study focuses on the in vivo characterization of the healthy SC tissue in terms of regional microstructure differences between (i) upper and lower cervical vertebral levels and (ii) sensory and motor tracts, as well as differences attributed to normal aging. Forty‐eight healthy volunteers aged from 20 to 70 years old were included in the study and scanned at 3 T using axial high‐resolution T₂*‐w imaging, diffusion tensor imaging (DTI) and ihMT, at two vertebral levels (C2 and C5). A processing pipeline with minimal user intervention, SC segmentation and spatial normalization into a reference space was implemented in order to assess quantitative morphological and structural parameters (cross‐sectional areas, scalar DTI and MT/ihMT metrics) in specific white and gray matter regions of interest. The multi‐parametric MRI metrics collected allowed upper and lower cervical levels to be distinguished, with higher ihMT ratio (ihMTR), higher axial diffusivity (λ_∥) and lower radial diffusivity (λ_⊥) at C2 compared with C5. Significant differences were also observed between white matter fascicles, with higher ihMTR and lower λ_∥ in motor tracts compared with posterior sensory tracts. Finally, aging was found to be associated with significant metric alterations (decreased ihMTR and λ_∥). The methodology proposed here, which can be easily transferred to the clinic, provides new insights for SC characterization. It bears great potential to study focal and diffuse SC damage in neurodegenerative and demyelinating diseases. Copyright © 2016 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.     

Functional characterization of ryanodine receptor (RYR1) sequence variants using a metabolic assay in immortalized B‐lymphocytes

Mutations in the RYR1 gene are linked to malignant hyperthermia (MH), central core disease and multi‐minicore disease. We screened by DHPLC the RYR1 gene in 24 subjects for mutations, and characterized functional alterations caused by some RYR1 variants. Three novel sequence variants and twenty novel polymorphisms were identified. Immortalized lymphoblastoid cell lines from patients with RYR1 variants and from controls were stimulated with 4‐chloro‐m‐cresol (4‐CmC) and the rate of extracellular acidification was recorded. We demonstrate that the increased acidification rate of lymphoblastoid cells in response to 4‐CmC is mainly due to RYR1 activation. Cells expressing RYR1 variants in the N‐terminal and in the central region of the protein (p.Arg530His, p.Arg2163Pro, p.Asn2342Ser, p.Glu2371Gly and p.Arg2454His) displayed higher activity compared with controls; this could account for the MH‐susceptible phenotype. Cell lines harboring RYR1^Cys4664Arg were significantly less activated by 4‐CmC. This result indicates that the p.Cys4664Arg variant causes a leaky channel and depletion of intracellular stores. The functional changes detected corroborate the variants analyzed as disease‐causing alterations and the acidification rate measurements as a means to monitor Ca²⁺‐induced metabolic changes in cells harboring mutant RYR1 channels. © 2009 Wiley‐Liss, Inc.     

Diffusion‐prepared stimulated‐echo turbo spin echo (DPsti‐TSE): An eddy current‐insensitive sequence for three‐dimensional high‐resolution and undistorted diffusion‐weighted imaging

In this study, we present a new three‐dimensional (3D), diffusion‐prepared turbo spin echo sequence based on a stimulated‐echo read‐out (DPsti‐TSE) enabling high‐resolution and undistorted diffusion‐weighted imaging (DWI). A dephasing gradient in the diffusion preparation module and rephasing gradients in the turbo spin echo module create stimulated echoes, which prevent signal loss caused by eddy currents. Near to perfect agreement of apparent diffusion coefficient (ADC) values between DPsti‐TSE and diffusion‐weighted echo planar imaging (DW‐EPI) was demonstrated in both phantom transient signal experiments and phantom imaging experiments. High‐resolution and undistorted DPsti‐TSE was demonstrated in vivo in prostate and carotid vessel wall. 3D whole‐prostate DWI was achieved with four b values in only 6 min. Undistorted ADC maps of the prostate peripheral zone were obtained at low and high imaging resolutions with no change in mean ADC values [(1.60 ± 0.10) × 10^?3 versus (1.60 ± 0.02) × 10^?3 mm²/s]. High‐resolution 3D DWI of the carotid vessel wall was achieved in 12 min, with consistent ADC values [(1.40 ± 0.23) × 10^?3 mm²/s] across different subjects, as well as slice locations through the imaging volume. This study shows that DPsti‐TSE can serve as a robust 3D diffusion‐weighted sequence and is an attractive alternative to the traditional two‐dimensional DW‐EPI approaches.     

Linking non‐invasive parametric MRI with invasive physiological measurements (MR‐PHYSIOL): towards a hybrid and integrated approach for investigation of acute kidney injury in rats

Acute kidney injury of various origins shares a common link in the pathophysiological chain of events: imbalance between renal medullary oxygen delivery and oxygen demand. For in vivo assessment of kidney haemodynamics and oxygenation in animals, quantitative but invasive physiological methods are established. A very limited number of studies attempted to link these invasive methods with parametric Magnetic Resonance Imaging (MRI) of the kidney. Moreover, the validity of parametric MRI (pMRI) as a surrogate marker for renal tissue perfusion and renal oxygenation has not been systematically examined yet. For this reason, we set out to combine invasive techniques and non‐invasive MRI in an integrated hybrid setup (MR‐PHYSIOL) with the ultimate goal to calibrate, monitor and interpret parametric MR and physiological parameters by means of standardized interventions. Here we present a first report on the current status of this multi‐modality approach. For this purpose, we first highlight key characteristics of renal perfusion and oxygenation. Second, concepts for in vivo characterization of renal perfusion and oxygenation are surveyed together with the capabilities of MRI for probing blood oxygenation‐dependent tissue stages. Practical concerns evoked by the use of strong magnetic fields in MRI and interferences between MRI and invasive physiological probes are discussed. Technical solutions that balance the needs of in vivo physiological measurements together with the constraints dictated by small bore MR scanners are presented. An early implementation of the integrated MR‐PHYSIOL approach is demonstrated including brief interventions of hypoxia and hyperoxia.     

High‐field (11.75T) multimodal MR imaging of exercising hindlimb mouse muscles using a non‐invasive combined stimulation and force measurement device

We have designed and constructed an experimental set‐up allowing electrical stimulation of hindlimb mouse muscles and the corresponding force measurements at high‐field (11.75T). We performed high‐resolution multimodal MRI (including T₂‐weighted imaging, angiography and diffusion) and analysed the corresponding MRI changes in response to a stimulation protocol. Mice were tested twice over a 1‐week period to investigate the reliability of mechanical measurements and T₂ changes associated with the stimulation protocol. Additionally, angiographic images were obtained before and immediately after the stimulation protocol. Finally, multislice diffusion imaging was performed before, during and immediately after the stimulation session. Apparent diffusion coefficient (ADC) maps were calculated on the basis of diffusion weighted images (DWI). Both force production and T₂ values were highly reproducible as illustrated by the low coefficient of variation (<8%) and high intraclass correlation coefficient (≥0.75) values. Maximum intensity projection angiographic images clearly showed a strong vascular effect resulting from the stimulation protocol. Although a motion sensitive imaging sequence was used (echo planar imaging) and in spite of the strong muscle contractions, motion artifacts were minimal for DWI recorded under exercising conditions, thereby underlining the robustness of the measurements. Mean ADC values increased under exercising conditions and were higher during the recovery period as compared with the corresponding control values. The proposed experimental approach demonstrates accurate high‐field multimodal MRI muscle investigations at a preclinical level which is of interest for monitoring the severity and/or the progression of neuromuscular diseases but also for assessing the efficacy of potential therapeutic interventions. Copyright © 2014 John Wiley & Sons, Ltd.     

Region‐specific impairment of the cervical spinal cord (SC) in amyotrophic lateral sclerosis: A preliminary study using SC templates and quantitative MRI (diffusion tensor imaging/inhomogeneous magnetization transfer)

In this preliminary study, our objective was to investigate the potential of high‐resolution anatomical imaging, diffusion tensor imaging (DTI) and conventional/inhomogeneous magnetization transfer imaging [magnetization transfer (MT)/inhomogeneous magnetization transfer (ihMT)] at 3 T, analyzed with template‐extracted regions of interest, to measure the atrophy and structural changes of white (WM) and gray (GM) matter spinal cord (SC) occurring in patients with amyotrophic lateral sclerosis (ALS). Ten patients with ALS and 20 age‐matched healthy controls were recruited. SC GM and WM areas were automatically segmented using dedicated templates. Atrophy indices were evaluated from T ₂*‐weighted images at each vertebral level from cervical C1 to C6. DTI and ihMT metrics were quantified within the corticospinal tract (CST), posterior sensory tract (PST) and anterior GM (aGM) horns at the C2 and C5 levels. Clinical disabilities of patients with ALS were evaluated using the Revised ALS Functional Rating Scale, upper motor neuron (UMN) and Medical Research Council scorings, and correlated with MR metrics. Compared with healthy controls, GM and WM atrophy was observed in patients with ALS, especially at lower cervical levels, where a strong correlation was also observed between GM atrophy and the UMN score (R  = ?0.75, p  = 0.05 at C6). Interestingly, a significant decrease in ihMT ratio was found in all regions of interest (p  < 0.0008), fractional anisotropy (FA) and MT ratios decreased significantly in CST, especially at C5 (p  < 0.005), and λ_// (axial diffusivity) decreased significantly in CST (p  = 0.0004) and PST (p  = 0.003) at C2. Strong correlations between MRI metrics and clinical scores were also found (0.47 < |R | < 0.87, p  < 0.05). Altogether, these preliminary results suggest that high‐resolution anatomical imaging and ihMT imaging, in addition to DTI, are valuable for the characterization of SC tissue impairment in ALS. In this study, in addition to an important SC WM demyelination, we also observed, for the first time in ALS, impairments of cervical aGM.     

Feasibility and repeatability of localized 31P‐MRS four‐angle saturation transfer (FAST) of the human gastrocnemius muscle using a surface coil at 7 T

Phosphorus (³¹P) MRS, combined with saturation transfer (ST), provides non‐invasive insight into muscle energy metabolism. However, even at 7 T, the standard ST method with T₁^app measured by inversion recovery takes about 10 min, making it impractical for dynamic examinations. An alternative method, i.e. four‐angle saturation transfer (FAST), can shorten the examination time. The aim of this study was to test the feasibility, repeatability, and possible time resolution of the localized FAST technique measurement on an ultra‐high‐field MR system, to accelerate the measurement of both P_i‐to‐ATP and PCr‐to‐ATP reaction rates in the human gastrocnemius muscle and to test the feasibility of using the FAST method for dynamic measurements. We measured the exchange rates and metabolic fluxes in the gastrocnemius muscle of eight healthy subjects at 7 T with the depth‐resolved surface coil MRS (DRESS)‐localized FAST method. For comparison, a standard ST localized method was also used. The measurement time for the localized FAST experiment was 3.5 min compared with the 10 min for the standard localized ST experiment. In addition, in five healthy volunteers, P_i‐to‐ATP and PCr‐to‐ATP metabolic fluxes were measured in the gastrocnemius muscle at rest and during plantar flexion by the DRESS‐localized FAST method. The repeatability of PCr‐to‐ATP and P_i‐to‐ATP exchange rate constants, determined by the slab‐selective localized FAST method at 7 T, is high, as the coefficients of variation remained below 20%, and the results of the exchange rates measured with the FAST method are comparable to those measured with standard ST. During physical activity, the PCr‐to‐ATP metabolic flux decreased (from F_CK = 8.21 ± 1.15 mM s^?1 to F_CK = 3.86 ± 1.38 mM s^?1) and the P_i‐to‐ATP flux increased (from F_ATP = 0.43 ± 0.14 mM s^?1 to F_ATP = 0.74 ± 0.13 mM s^?1). In conclusion, we could demonstrate that measurements in the gastrocnemius muscle are feasible at rest and are short enough to be used during exercise with the DRESS‐localized FAST method at 7 T. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.