NMR in Biomedicine

Arterial spin labeling (ASL) MRI is increasingly used in research and clinical settings. The purpose of this work is to develop a cloud‐based tool for ASL data processing, referred to as ASL‐MRICloud, which may be useful to the MRI community. In contrast to existing ASL toolboxes, which are based on software installation on the user's local computer, ASL‐MRICloud uses a web browser for data upload and results download, and the computation is performed on the remote server. As such, this tool is independent of the user's operating system, software version, and CPU speed. The ASL‐MRICloud tool was implemented to be compatible with data acquired by scanners from all major MRI manufacturers, is capable of processing several common forms of ASL, including pseudo‐continuous ASL and pulsed ASL, and can process single‐delay and multi‐delay ASL data. The outputs of ASL‐MRICloud include absolute and relative values of cerebral blood flow, arterial transit time, voxel‐wise masks indicating regions with potential hyper‐perfusion and hypo‐perfusion, and an image quality index. The ASL tool is also integrated with a T₁‐based brain segmentation and normalization tool in MRICloud to allow generation of parametric maps in standard brain space as well as region‐of‐interest values. The tool was tested on a large data set containing 309 ASL scans as well as on publicly available ASL data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study.

Recent technical developments have significantly increased the signal‐to‐noise ratio (SNR) of arterial spin labeled (ASL) perfusion MRI. Despite this, typical ASL acquisitions still employ large voxel sizes. The purpose of this work was to implement and evaluate two ASL sequences optimized for whole‐brain high‐resolution perfusion imaging, combining pseudo‐continuous ASL (pCASL), background suppression (BS) and 3D segmented readouts, with different in‐plane k‐space trajectories.

Identical labeling and BS pulses were implemented for both sequences. Two segmented 3D readout schemes with different in‐plane trajectories were compared: Cartesian (3D GRASE) and spiral (3D RARE Stack‐Of‐Spirals). High‐resolution perfusion images (2 × 2 × 4 mm³) were acquired in 15 young healthy volunteers with the two ASL sequences at 3 T. The quality of the perfusion maps was evaluated in terms of SNR and gray‐to‐white matter contrast. Point‐spread‐function simulations were carried out to assess the impact of readout differences on the effective resolution.

The combination of pCASL, in‐plane segmented 3D readouts and BS provided high‐SNR high‐resolution ASL perfusion images of the whole brain. Although both sequences produced excellent image quality, the 3D RARE Stack‐Of‐Spirals readout yielded higher temporal and spatial SNR than 3D GRASE (spatial SNR = 8.5 ± 2.8 and 3.7 ± 1.4; temporal SNR = 27.4 ± 12.5 and 15.6 ± 7.6, respectively) and decreased through‐plane blurring due to its inherent oversampling of the central k‐space region, its reduced effective T_E and shorter total readout time, at the expense of a slight increase in the effective in‐plane voxel size. Copyright © 2014 John Wiley & Sons, Ltd.

Single‐shot diffusion‐weighted MRI sensitive to different types of incoherent motion inside tissue shows sporadic signal voids with a considerable size (>1 cm) in calf musculature at rest. Spatial and temporal patterns of these signal voids and their dependence on measurement conditions were tested systematically in order to obtain more insight into the underlying mechanism. Lower leg muscles of 10 healthy subjects were examined by recording series of 1000 echo‐planar single‐shot scans with repetition time 500 ms and b‐value 100 s/mm². Effects of strength and orientation of motion sensitization gradients and of repetition times were analysed. Potential influences of arterial blood pulsations and positioning of the subject were studied. Comparison of calf muscle groups showed more frequent signal voids in gastrocnemius and soleus muscle compared with tibialis muscles. Large inter‐individual variance in the total number of signal voids visible in a transverse slice of the lower leg was observed (minimum 40/1000 scans; maximum >550/1000 scans). Typical sizes of the affected muscular areas ranged from 1.5 to 2.5 cm in the transverse and from 1.5 to 7 cm in the head–feet direction. Signal voids occurred nearly independent of the cardiac phase and with similar frequencies for supine and prone positions. Resting calf muscles show spontaneous signal voids in single‐shot DWI at low b‐values with an irregular temporal and spatial pattern. Values of mean diffusivity, diffusion tensor parameters, and IVIM‐derived perfusion are expected to be clearly distorted by such signal voids if no rejection of affected data is applied. Several potential causes for the signal voids are discussed. The most probable explanation for the phenomenon is seen in the occurrence of spontaneous incoherent mechanical activity in musculature based on weak muscle fibre contractions. If this is the case it opens up a new field for studies on the physiological role and regulation of these unintended muscle activities. Copyright © 2015 John Wiley & Sons, Ltd.

Recent studies have described some of the new opportunities that have arisen within the context of ultrafast two‐dimensional imaging with the advent of spatiotemporal encoding methods. This article explores the potential of integrating these non‐Fourier, single‐scan, two‐dimensional MRI principles, with multi‐slice and phase‐encoding schemes acting along a third dimension. In unison, these combinations enable the acquisition of complete three‐dimensional images from volumes of interest within a 1‐s timescale. A number of alternatives are explored for carrying out these very rapid three‐dimensional acquisitions, including the use of two‐dimensional, slice‐selective, spatiotemporal encoding radiofrequency pulses, driven‐equilibrium slice‐selective schemes, and phase‐encoded volumetric approaches. When tested under in vivo conditions, the ‘hybrid’ schemes combining spatiotemporal encoding with k‐encoding imaging principles, proved to be superior to traditional schemes based on echo planar imaging. The resulting images were found to be less affected by field inhomogeneities and by other potential offset‐derived distortions owing to a combination of factors whose origin is discussed. Further features, extensions and applications of these principles are also addressed. Copyright © 2011 John Wiley & Sons, Ltd.

This study investigates T₂* quantification in carotid plaques before and after the administration of ultrasmall superparamagnetic iron oxide particles (USPIOs) in a cohort of patients receiving statin therapy. Phantom studies were performed using gels with varying concentrations of USPIOs. In the phantom study, 12 gels were prepared with a range of freely distributed concentrations of USPIO nanoparticles (0–0.05 mg/mL). Relative signal intensity measurements were obtained from a T₂*‐weighted sequence as well as quantitative T₂* (qT₂*) measurements. In the patient study, 40 patients with >40% carotid stenosis were randomised to low‐ and high‐dose statin therapy (10 and 80 mg of atorvastatin). Pre‐ and post‐ (36 h) USPIO‐enhanced MRI were performed at baseline, and at 6 and 12 weeks. A linear mixed‐effects model was applied to account for the inherent correlation of multiple‐plaque measurements from the same patient and to assess dose–response differences to statin therapy. In the phantom study, the T₂*‐weighted sequence demonstrated an initial increase (T₁ effect), followed by a decrease (T₂* effect), in relative signal intensity with increasing concentrations of USPIO. The qT₂* values decreased exponentially with increasing concentrations of USPIO. In the patient study, there was a highly significant difference in post‐USPIO T₂* measurements in plaques between the low‐ and high‐dose statin groups. This was observed for both the difference in qT₂* measurements (post‐USPIO minus pre‐USPIO) (p < 0.001) and for qT₂* post‐USPIO only (p < 0.001). The post‐USPIO qT₂* values were as follows: baseline: low dose, 13.6 ± 5.5 ms; high dose, 12.9 ± 6.2 ms; 6 weeks: low dose, 13.3 ± 6.7 ms; high dose, 14.3 ± 7.7 ms; 12 weeks: low dose, 14.0 ± 7.6 ms; high dose, 18.3 ± 11.2 ms. It can be concluded that qT₂* measurements provide an alternative method of quantifying USPIO uptake. These results also demonstrate that changes in USPIO uptake can be measured using post‐USPIO imaging only. Copyright © 2010 John Wiley & Sons, Ltd.

The purpose of the study was to evaluate the accuracy of transrectal ultrasound biopsy (TRUS‐biopsy) performed on regions with abnormal MRI and/or MRSI for both the transition (TZ) and the peripheral (PZ) zones in patients with suspected prostate cancer with prior negative biopsy, and to analyze the relationship between MRSI and histopathological findings. MRI and MRSI were performed in 54 patients (mean age: 63.9 years, mean PSA value: 11.4 ng/mL) and the ability of MRI/MRSI‐directed TRUS biopsy was evaluated. A three‐point score system was used for both techniques to distinguish healthy from malignant regions. Descriptive statistics and ROC analyses were performed to evaluate the accuracy and the best cut‐off in the three‐point score system. Twenty‐two out of 54 patients presented cancer at MRI/MRSI‐directed TRUS biopsy, nine presented cancer only in PZ, eight both in PZ and TZ, and five exclusively in TZ. On a patient basis the highest accuracy was obtained by assigning malignancy on a positive finding with MRSI and MRI even though it was not significantly greater than that obtained using MRI alone (area under the ROC curve, AUC: 0.723 vs 0.676). On a regional (n = 648) basis the best accuracy was also obtained by considering positive both MRSI and MRI for PZ (0.768) and TZ (0.822). MRSI was false positive in 11.9% of the regions. Twenty‐eight percent of cores with prostatitis were false positive findings on MRSI, whereas only 2.7% of benign prostatic hyperplasia was false positive. In conclusion, the accuracy of MRI/MRSI‐directed biopsies in localization of prostate cancer is good in patient (0.723) and region analyses (0.768). The combination of both MRI and MRSI results makes TRUS‐biopsy more accurate, particularly in the TZ (0.822) for patients with prior negative biopsies. Histopathological analysis showed that the main limitation of MRSI is the percentage of false positive findings due to prostatitis. Copyright © 2010 John Wiley & Sons, Ltd.

Results of the evaluation of transrectal ultrasound (TRUS) guided needle biopsy of voxels identified as suspicious of malignancy on magnetic resonance spectroscopic imaging (MRSI) in a large cohort of men (n = 83) with abnormal digital rectal examination (DRE) [prostate specific antigen (PSA) 0–4 ng/ml] or PSA less than 10 ng/ml, are reported. Three‐dimensional ¹H MRSI was carried out at 1.5 T using a pelvic‐phased array coil in combination with an endorectal surface coil. Voxels were classified as suspicious of malignancy based on Cit/(Cho + Cr) metabolite ratio. TRUS‐guided biopsy of suspicious voxels was performed using the z‐ and x‐coordinates obtained from MR images and two to three cores were taken from the suspected site. A systematic sextant biopsy was also carried out. MRSI showed voxels suspicious of malignancy in 44 patients while biopsy revealed cancer in 11 patients (25%). Patients who were negative for malignancy on MRSI were also negative on biopsy. An overall sensitivity of 100%, specificity of 54%, negative predictive value of 100% and accuracy of 60% were obtained. The site of biopsy was confirmed (n = 20) as a hypo‐intense area on repeat MRI while repeat MRSI revealed high choline and low citrate. The overall success rate of MRI‐directed TRUS‐guided biopsy of 25% was higher compared with a 9% success rate achieved without MR guidance in another group of 120 patients. Our results indicate that TRUS‐guided biopsy of suspicious area identified as malignant from MRSI can be performed using the coordinates of the voxel derived from MR images. This increases the detection rate of prostate cancer in men with PSA level <10 ng/ml or abnormal DRE and also demonstrates the potential of MR in routine clinical practice. Copyright © 2006 John Wiley & Sons, Ltd.

Diffusion NMR is the only method available today that noninvasively provides information on molecular displacements over distances comparable to cell dimensions. This information can be used to infer tissue microstructure and microdynamics. However, data may be fairly difficult to interpret in biological tissues which differ markedly from the theoretical “infinite isotrope medium”, as many factors may affect the NMR signal. The object of this paper is to analyze the expected effects of temperature, restriction, hindrance, membrane permeability, anisotropy and tissue inhomogeneity on the diffusion measurements. Powerful methods, such as q‐space imaging, diffusion tensor imaging and diffusion spectroscopy of metabolites further enhance the specificity of the information obtained from diffusion NMR experiments.