Mapping the human brainstem: Brain nuclei and fiber tracts at 3 T and 7 T

Structural high‐resolution imaging of the brainstem can be of high importance in clinical practice. However, ultra‐high field magnetic resonance imaging (MRI) is still restricted in use due to limited availability. Therefore, quantitative MRI techniques (quantitative susceptibility mapping [QSM], relaxation measurements [ , R₁ ], diffusion tensor imaging [DTI]) and T₂ ‐ and proton density (PD)‐weighted imaging in the human brainstem at 3 T and 7 T are compared. Five healthy volunteers (mean age: 21.5 ± 1.9 years) were measured at 3 T and 7 T using multi‐echo gradient echo sequences for susceptibility mapping and relaxometry, magnetization‐prepared 2 rapid acquisition gradient echo sequences for R₁ relaxometry, turbo‐spin echo sequences for PD‐ and T₂ ‐weighted imaging and readout‐segmented echo planar sequences for DTI. Susceptibility maps were computed using Laplacian‐based phase unwrapping, V‐SHARP for background field removal and the streaking artifact reduction for QSM algorithm for dipole inversion. Contrast‐to‐noise ratios (CNRs) were determined at 3 T and 7 T in ten volumes of interest (VOIs). Data acquired at 7 T showed higher CNR. However, in four VOIs, lower CNR was observed for at 7 T. QSM was shown to be the contrast with which the highest number of structures could be identified. The depiction of very fine tracts such as the medial longitudinal fasciculus throughout the brainstem was only possible in susceptibility maps acquired at 7 T. DTI effectively showed the main tracts (crus cerebri, transverse pontine fibers, corticospinal tract, middle and superior cerebellar peduncle, pontocerebellar tract, and pyramid) at both field strengths. Assessing the brainstem with quantitative MRI methods such as QSM, , as well as PD‐ and T₂ ‐weighted imaging with great detail, is also possible at 3 T, especially when using susceptibility mapping calculated from a gradient echo sequence with a wide range of echo times from 10.5 to 52.5 ms. However, tracing smallest structures strongly benefits from imaging at ultra‐high field.     

Correlation of hyperpolarized 13C‐MRI data with tissue extract measurements

Hyperpolarized (HP) MRI provides the means to monitor lactate metabolism noninvasively in tumours. Since ‐lactate signal levels obtained from HP imaging depend on multiple factors, such as the rate of substrate delivery via the vasculature, the expression level of monocarboxylate transporters (MCTs) and lactate dehydrogenase (LDH), and the local lactate pool size, the interpretation of HP metabolic images remains challenging. In this study, ex vivo tissue extract measurements (i.e., NMR isotopomer analysis, western blot analysis) derived from an MDA‐MB‐231 xenograft model in nude rats were used to test for correlations between the in vivo data and the ex vivo measures. The lactate‐to‐pyruvate ratio from HP MRI was strongly correlated with [1‐ ]lactate concentration measured from the extracts using NMR (R = 0.69, p 0.05), as well as negatively correlated with tumour wet weight (R =  0.60, p 0.05). In this tumour model, both MCT1 and MCT4 expressions were positively correlated with wet weight ( = 0.78 and 0.93, respectively, p 0.01). Lactate pool size and the lactate‐to‐pyruvate ratio were not significantly correlated.     

Comparison of spoiled gradient echo and steady‐state free‐precession imaging for native myocardial T1 mapping using the slice‐interleaved T1 mapping (STONE) sequence

Cardiac T₁ mapping allows non‐invasive imaging of interstitial diffuse fibrosis. Myocardial T₁ is commonly calculated by voxel‐wise fitting of the images acquired using balanced steady‐state free precession (SSFP) after an inversion pulse. However, SSFP imaging is sensitive to B₁ and B₀ imperfection, which may result in additional artifacts. A gradient echo (GRE) imaging sequence has been used for myocardial T₁ mapping; however, its use has been limited to higher magnetic field to compensate for the lower signal‐to‐noise ratio (SNR) of GRE versus SSFP imaging. A slice‐interleaved T₁ mapping (STONE) sequence with SSFP readout (STONE–SSFP) has been recently proposed for native myocardial T₁ mapping, which allows longer recovery of magnetization (>8 R–R) after each inversion pulse. In this study, we hypothesize that a longer recovery allows higher SNR and enables native myocardial T₁ mapping using STONE with GRE imaging readout (STONE–GRE) at 1.5T. Numerical simulations and phantom and in vivo imaging were performed to compare the performance of STONE–GRE and STONE–SSFP for native myocardial T₁ mapping at 1.5T. In numerical simulations, STONE–SSFP shows sensitivity to both T₂ and off resonance. Despite the insensitivity of GRE imaging to T₂, STONE–GRE remains sensitive to T₂ due to the dependence of the inversion pulse performance on T₂. In the phantom study, STONE–GRE had inferior accuracy and precision and similar repeatability as compared with STONE–SSFP. In in vivo studies, STONE–GRE and STONE–SSFP had similar myocardial native T₁ times, precisions, repeatabilities and subjective T₁ map qualities. Despite the lower SNR of the GRE imaging readout compared with SSFP, STONE–GRE provides similar native myocardial T₁ measurements, precision, repeatability, and subjective image quality when compared with STONE–SSFP at 1.5T.     

Quantitative T2* imaging of metastatic human breast cancer to brain in the nude rat at 3 T

This study uses quantitative T₂* imaging to track ferumoxides–protamine sulfate (FEPro)‐labeled MDA‐MB‐231BR‐Luc (231BRL) human breast cancer cells that metastasize to the nude rat brain. Four cohorts of nude rats were injected intracardially with FEPro‐labeled, unlabeled or tumor necrosis factor‐related apoptosis‐inducing ligand(TRAIL)‐treated (to induce apoptosis) 231BRL cells, or saline, in order to develop metastatic breast cancer in the brain. The heads of the rats were imaged serially over 3–4 weeks using gradient multi‐echo and turbo spin‐echo pulse sequences at 3 T with a solenoid receive‐only 4‐cm‐diameter coil. Quantitative T₂* maps of the whole brain were obtained by the application of single‐exponential fitting to the signal intensity of T₂* images, and the distribution of T₂* values in brain voxels was calculated. MRI findings were correlated with Prussian blue staining and immunohistochemical staining for iron in breast cancer and macrophages. Quantitative analysis of T₂* from brain voxels demonstrated a significant shift to lower values following the intracardiac injection of FEPro‐labeled 231BRL cells, relative to animals receiving unlabeled cells, apoptotic cells or saline. Quartile analysis based on the T₂* distribution obtained from brain voxels demonstrated significant differences (p < 0.0083) in the number of voxels with T₂* values in the ranges 10–35 ms (Q1), 36–60 ms (Q2) and 61–86 ms (Q3) from 1 day to 3 weeks post‐infusion of labeled 231BRL cells, compared with baseline scans. There were no significant differences in the distribution of T₂* obtained from serial MRI in rats receiving unlabeled or TRAIL‐treated cells or saline. Histologic analysis demonstrated isolated Prussian blue‐positive breast cancer cells scattered in the brains of rats receiving labeled cells, relative to animals receiving unlabeled or apoptotic cells. Quantitative T₂* analysis of FEPro‐labeled metastasized cancer cells was possible even after the hypointense voxels were no longer visible on T₂*‐weighted images. Published in 2010 by John Wiley & Sons, Ltd.     

Value of whole breast magnetic resonance elastography added to MRI for lesion characterization

The purpose of this work was to assess the diagnostic value of magnetic resonance elastography (MRE) in addition to MRI to differentiate malignant from benign breast tumors, and the feasibility of performing MRE on the whole breast. MRE quantified biomechanical properties within the entire breast (50 slices) using an 11 min acquisition protocol at an isotropic image acquisition resolution of 2 × 2 × 2 mm³. Fifty patients were included. Finally, 43 patients (median age 52) with a suspect breast lesion detected by mammography and/or ultrasound were examined by MRI and MRE at 1.5 T. The viscoelastic parameters, i.e. elasticity (G_d), viscosity (G_l), the magnitude of the complex shear modulus , and the phase angle , were measured via MRE and correlated with MRI Breast Imaging—Reporting and Data System (BI‐RADS) score, histological type, and histological grade. Stroma component and angiogenesis were also correlated with viscoelastic properties. In the 43 lesions, G_d decreased and y increased with the MRI BI‐RADS score (p_Gd = 0.02, p_y = 0.002), whereas (G_l) and y were increased in malignant lesions (p_Gl = 0.045, p_y = 0.0004). The area under the curve increased from 0.84 for MRI BI‐RADS alone to 0.92 with the MRI BI‐RADS and y (AUC increase +0.08; 95% CI (?0.003; 0.16)). Lesion characterization using the y parameter increased the diagnostic accuracy. The phase angle y was found to have a significant role (p = 0.01) in predicting malignancy independently of the MRI BI‐RADS. Interestingly, histological analysis showed no correlation between viscoelastic parameters and percentage and type of stroma, CD34 quantification of vessels, or histological grade. The combination of MRE and MRI improves the diagnostic accuracy for breast lesions in the studied cohort. In particular, the phase angle y was found to have a significant role in predicting malignancy in addition to BI‐RADS.     

MRI accurately identifies early murine mammary cancers and reliably differentiates between in situ and invasive cancer: correlation of MRI with histology

MRI methods that accurately identify various stages of mouse mammary cancer could provide new knowledge that may have a direct impact on the management of breast cancer in patients. This research investigates whether we can accurately follow the progression from in situ to invasive cancer by the evaluation of in vivo and ex vivo MRI, and in comparison with histology as the gold standard for the diagnosis and staging of cancer. Six C3(1)SV40Tag virgin female mice, aged 12–16 weeks, were studied. At this age, these mice develop in situ cancer that resembles human ductal carcinoma in situ (DCIS). Fast spin‐echo images of inguinal mammary glands were acquired at 9.4 T. After in vivo MRI, mice were sacrificed; inguinal mammary glands were excised and fixed in formalin for ex vivo MRI. Three‐dimensional, volume‐rendered, in vivo and ex vivo MR images were then correlated with histology. High‐resolution ex vivo scans facilitated the comparison of in vivo scans with histology. The sizes of mammary cancers classified as in situ on the basis of histology ranged from 150 to 400 µm in largest diameter, and the average signal intensity relative to muscle was 1.40 ± 0.18 on T₂‐weighted images. Cancers classified as invasive on the basis of histology were >400 µm in largest diameter, and the average intensity relative to muscle on T₂‐weighted images was 2.34 ± 0.26. Using a cut‐off of 400 µm in largest diameter to distinguish between in situ and invasive cancers, a T₂‐weighted signal intensity of at least 1.4 times that of muscle for in situ cancer, and at least 2.3 times that of muscle for invasive cancer, 96% of in situ and 100% of invasive cancers were correctly identified on in vivo MRI, using histology as the gold standard. Precise MRI–histology correlation demonstrates that MRI reliably detects early in situ cancer and differentiates in situ from invasive cancers in the SV40Tag mouse model of human breast cancer. Copyright © 2015 John Wiley & Sons, Ltd.     

Impact of uncertainty in longitudinal T1 measurements on quantification of dynamic contrast‐enhanced MRI

The objective of this study was to assess the uncertainty in T₁ measurement, by estimating the repeatability coefficient (RC) from two repeated scans, in normal appearing brain tissues employing two different T₁ mapping methods. All brain MRI scans were performed on a 3 T MR scanner in 10 patients who had low grade/benign tumors and partial brain radiation therapy (RT) without chemotherapy, at pre‐RT, 3 weeks into RT, end RT (6 weeks) and 11, 33, and 85 weeks after RT. T₁‐weighted images were acquired using (1) a spoiled gradient echo sequence with two flip angles (2FA: 5° and 15°) and (2) a progressive saturation recovery sequence (pSR) with five different TR values (100–2000 ms). Manually drawn volumes of interest (VOIs) included left and right normal putamen and thalamus in gray matter, and frontal and parietal white matter, which were distant from tumors and received a total of accumulated radiation doses less than 5 Gy at 3 weeks. No significant changes or even trends in mean T₁ from pre‐RT to 3 weeks into RT in these VOIs (p ≥ 0.11, Wilcoxon sign test) allowed us to calculate the repeatability statistics of between‐subject means of squares, within‐subject means of squares, F‐score, and RC. The 2FA method produced RCs in the range of (9.7–11.7)% in gray matter and (12.2–14.5)% in white matter; while the pSR method led to RCs ranging from 10.9 to 17.9% in gray matter and 7.5 to 10.3% in white matter. The overall mean (±SD) RCs produced by the two methods, 12.0 (±1.6)% for 2FA and 12.0 (±3.8)% for pSR, were not significantly different (p = 0.97). A similar repeatability in T₁ measurement produced by the time efficient 2FA method compared with the time consuming pSR method demonstrates that the 2FA method is desirable to integrate into dynamic contrast‐enhanced MRI for rapid acquisition. Copyright © 2016 John Wiley & Sons, Ltd.     

Spatial location and strength of BOLD activation in high-spatial-resolution fMRI of the motor cortex: a comparison of spin echo and gradient echo fMRI at 7 T

The increased blood oxygenation level‐dependent contrast‐to‐noise ratio at ultrahigh field (7 T) has been exploited in a comparison of the spatial location and strength of activation in high‐resolution (1.5 mm isotropic) gradient echo (GE) and spin echo (SE), echo planar imaging data acquired during the execution of a simple motor task in five subjects. SE data were acquired at six echo times from 30 to 55 ms. Excellent fat suppression was achieved in the SE echo planar images using slice‐selective gradient reversal. Threshold‐free cluster enhancement was used to define regions of interest (ROIs) containing voxels showing significant stimulus‐locked signal changes from the GE and average SE data. These were used to compare the signal changes and spatial locations of activated regions in SE and GE data. T₂ and T₂* values were measured, with means of 48.3 ± 1.1 ms and 36.5 ± 3.4 ms in the SE ROI. In addition, we identified a dark band in SE images of the motor cortex corresponding to a region in which T₂ and T₂* were significantly lower than in the surrounding grey matter. The fractional SE signal change in the ROI was found to vary linearly as a function of TE, with a slope that was dependent on the particular ROI assessed: the mean ΔR₂ value was found to be 0.85 ± 0.11 s^–1 for the SE ROI and ?0.37 ± 0.05 s^–1 for the GE ROI. The fractional signal change relative to the shortest TE revealed that the largest signal change occurred at a TE of 45 ms outside of the dark band. At this TE, the ratio of the fractional signal change in GE and SE data was found to be 0.48 ± 0.05. Phase maps produced from high‐resolution GE images spanning the right motor cortex were used to identify veins. The GE ROI was found to contain 18% more voxels overlying the venous mask than the SE ROI. Copyright © 2011 John Wiley & Sons, Ltd.     

Effects of diffusion on high‐resolution quantitative T2 MRI

Carr–Purcell–Meiboom–Gill‐based sequences are often assumed to be insensitive to diffusion. However, imaging gradients always contribute some degree of diffusion weighting which increases with resolution. This may cause an apparent decrease in T₂ when using a multi‐echo sequence, such as quantitative T₂ (qT2) at high resolution. This study investigated the impact of diffusion on the qT2 sequence. An equation was developed relating the diffusion factor associated with each echo (b_qT2) to the underestimation of T₂, which was strongly dependent on both the actual T₂ and the apparent diffusion coefficient of the tissue. The diffusion dependence of the measured T₂ was demonstrated in rat spinal cord. The measured T₂ was independent of the imaging plane in gray matter, where diffusion was isotropic, and orientation dependent in white matter, where diffusion was strongly anisotropic. The dependence of the measured T₂ on the actual T₂ value was also demonstrated in MnCl₂ phantoms. The relationship between the resolution and underestimation of T₂ was investigated both theoretically and experimentally for the original readout and a fully refocused readout. The fully refocused readout increased the resolution at which diffusion effects could be neglected whilst measuring T₂. To avoid the misidentification of cerebrospinal fluid when applying qT2 in the brain or spinal cord, a minimum in‐plane voxel dimension of 0.2 mm was suggested for the standard qT2 sequence and 0.1 mm for the refocused readout. Simulations of myelin water fraction measurement indicated that signal‐to‐noise ratio requirements were increased in the presence of diffusion. Finally, the use of decreasing spoiler gradients to attenuate stimulated echoes should be avoided, as it was found to distort the T₂ distribution when the slice thickness was less than 1 mm. Copyright © 2014 John Wiley & Sons, Ltd.     

Analysis and improvement of motion encoding in magnetic resonance elastography

Magnetic resonance elastography (MRE) utilizes phase contrast magnetic resonance imaging (MRI), which is phase locked to externally generated mechanical vibrations, to measure the three‐dimensional wave displacement field. At least four measurements with linear‐independent encoding directions are necessary to correct for spurious phase contributions if effects from imaging gradients are non‐negligible. In MRE, three encoding schemes have been used: unbalanced four‐ and six‐point and balanced four‐point (‘tetrahedral’) encoding. The first two sensitize to motion with orthogonal gradients, with the four‐point method acquiring a single reference scan without motion sensitization, whereas three additional scans with inverted gradients are used with six‐point encoding, leading to two‐fold higher displacement‐to‐noise ratio (DNR) and 50% longer scan duration. Balanced four‐point (tetrahedral) encoding encodes along the four diagonals of a cube, with one direction serving as a reference for the other three encoding directions, similar to four‐point encoding. The objective of this work is to introduce a theoretical framework to compare different motion sensitization strategies with respect to their motion encoding efficiency in two fundamental encoding limits, the gradient strength limit and the dynamic range limit, which are both placed in relation to conventional gradient recalled echo (GRE)‐ and spin echo (SE)‐based MRE sequences. We apply the framework to the three aforementioned schemes and show that the motion encoding efficiency of unbalanced four‐ and six‐point encoding schemes in the gradient‐limited regime can be increased by a factor of 1.5 when using all physical gradient channels concurrently. Furthermore, it is demonstrated that reversing the direction of the reference in balanced four‐point (tetrahedral) encoding results in the Hadamard encoding scheme, which leads to increased DNR by compared with balanced four‐point encoding and 2.8 compared with unbalanced four‐point encoding. As an example, we show that optimal encoding can be utilized to reduce the acquisition time of standard liver MRE in vivo from four to two breath holds.     

Quantification of MRI signal of transgenic grafts overexpressing ferritin in murine myocardial infarcts

The noninvasive detection of transplanted cells in damaged organs and the longitudinal follow‐up of cell fate and graft size are important for the evaluation of cell therapy. We have shown previously that the overexpression of the natural iron storage protein, ferritin, permits the detection of engrafted cells in mouse heart by MRI, but further imaging optimization is required. Here, we report a systematic evaluation of ferritin‐based stem cell imaging in infarcted mouse hearts in vivo using three cardiac‐gated pulse sequences in a 3‐T scanner: black‐blood proton‐density‐weighted turbo spin echo (PD TSE BB), bright‐blood T₂*‐weighted gradient echo (GRE) and black‐blood T₂*‐weighted GRE with improved motion‐sensitized‐driven equilibrium (iMSDE) preparation. Transgenic C2C12 myoblast grafts overexpressing ferritin did not change MRI contrast in the PD TSE BB images, but showed a 20% reduction in signal intensity ratio in black‐blood T₂*‐weighted iMSDE (p < 0.05) and a 30% reduction in bright‐blood T₂*‐weighted GRE (p < 0.0001). Graft size measurements by T₂* iMSDE and T₂* GRE were highly correlated with histological assessments (r = 0.79 and r = 0.89, respectively). Unlabeled wild‐type C2C12 cells transplanted to mouse heart did not change the MRI signal intensity, although endogenous hemosiderin was seen in some infarcts. These data support the use of ferritin to track the survival, growth and migration of stem cells transplanted into the injured heart. Copyright © 2012 John Wiley & Sons, Ltd.     

Oxygenation in cervical cancer and normal uterine cervix assessed using blood oxygenation level‐dependent (BOLD) MRI at 3T

Hypoxia is reported to be a biomarker for poor prognosis in cervical cancer. However, a practical noninvasive method is needed for the routine clinical evaluation of tumor hypoxia. This study examined the potential use of blood oxygenation level‐dependent (BOLD) contrast MRI as a noninvasive technique to assess tumor vascular oxygenation at 3T. Following Institutional Review Board‐approved informed consent and in compliance with the Health Insurance Portability and Accountability Act, successful results were achieved in nine patients with locally advanced cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) stage IIA to IVA] and three normal volunteers. In the first four patients, dynamic T₂*‐weighted MRI was performed in the transaxial plane using a multi‐shot echo planar imaging sequence whilst patients breathed room air followed by oxygen (15 dm³/min). Later, a multi‐echo gradient echo examination was added to provide quantitative R₂* measurements. The baseline T₂*‐weighted signal intensity was quite stable, but increased to various extents in tumors on initiation of oxygen breathing. The signal in normal uterus increased significantly, whereas that in the iliacus muscle did not change. R₂* responded significantly in healthy uterus, cervix and eight cervical tumors. This preliminary study demonstrates that BOLD MRI of cervical cancer at 3T is feasible. However, more patients must be evaluated and followed clinically before any prognostic value can be determined. Copyright © 2012 John Wiley & Sons, Ltd.     

Diffusion tensor imaging and T2 relaxometry of bilateral lumbar nerve roots: feasibility of in‐plane imaging

Lower back pain is a common problem frequently encountered without specific biomarkers that correlate well with an individual patient's pain generators. MRI quantification of diffusion and T₂ relaxation properties may provide novel insight into the mechanical and inflammatory changes that occur in the lumbosacral nerve roots in patients with lower back pain. Accurate imaging of the spinal nerve roots is difficult because of their small caliber and oblique course in all three planes. Two‐dimensional in‐plane imaging of the lumbosacral nerve roots requires oblique coronal imaging with large field of view (FOV) in both dimensions, resulting in severe geometric distortions using single‐shot echo planar imaging (EPI) techniques. The present work describes initial success using a reduced‐FOV single‐shot spin‐echo EPI acquisition to obtain in‐plane diffusion tensor imaging (DTI) and T₂ mapping of the bilateral lumbar nerve roots at the L4 level of healthy subjects, minimizing partial volume effects, breathing artifacts and geometric distortions. A significant variation in DTI and T₂ mapping metrics is also reported along the course of the normal nerve root. The fractional anisotropy is statistically significantly lower in the dorsal root ganglia (0.287 ± 0.068) than in more distal regions in the spinal nerve (0.402 ± 0.040) (p < 10^–5). The T₂ relaxation value is statistically significantly higher in the dorsal root ganglia (78.0 ± 11.9 ms) than in more distal regions in the spinal nerve (59.5 ± 7.4 ms) (p < 10^–5). The quantification of nerve root DTI and T₂ properties using the proposed methodology may identify the specific site of any degenerative and inflammatory changes along the nerve roots of patients with lower back pain. Copyright © 2012 John Wiley & Sons, Ltd.     

Exercising calf muscle changes correlate with pH,PCr recovery and maximum oxidative phosphorylation

Skeletal muscle metabolism is impaired in disorders like diabetes mellitus or peripheral vascular disease. The skeletal muscle echo planar imaging (EPI) signal (S_EPI) and its relation to energy metabolism are still debated. Localised 31P MRS and S_EPI data from gastrocnemius medialis of 19 healthy subjects were combined in one scanning session to study direct relationships between phosphocreatine (PCr), pH kinetics and parameters of time courses. Dynamic spectroscopy (semi‐LASER) and EPI were performed immediately before, during and after 5 min of plantar flexions. Data were acquired in a 7 T MR scanner equipped with a custom‐built ergometer and a dedicated ³¹P/¹H radio frequency (RF) coil array. Using a form‐fitted multi‐channel ³¹P/¹H coil array resulted in high signal‐to‐noise ratio (SNR). PCr and pH in the gastrocnemius medialis muscle were quantified from each ³¹P spectrum, acquired every 6 s. During exercise, S_EPI(t) was found to be a linear function of tissue pH(t) (cross‐correlation r = –0.85 ± 0.07). Strong Pearson's correlations were observed between post exercise time‐to‐peak (TTP) of S_EPI and (a) the time constant of PCr recovery τ_{PCr recovery} (r = 0.89, p < 10^{? 6}), (b) maximum oxidative phosphorylation using the linear model, Q_{max, lin} (r = 0.65, p = 0.002), the adenosine‐diphosphate‐driven model, Q_max,ADP (r = 0.73, p = 0.0002) and (c) end exercise pH (r = 0.60, p = 0.005). Based on combined accurately localised 31P MRS and weighted MRI, both with high temporal resolution, strong correlations of the skeletal muscle S_EPI during exercise and tissue pH time courses and of post exercise S_EPI and parameters of energy metabolism were observed. In conclusion, a tight coupling between skeletal muscle metabolic activity and tissue signal weighting, probably induced by osmotically driven water shift, exists and can be measured non‐invasively, using NMR at 7 T. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

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.     

MRI of neonatal necrotizing enterocolitis in a rodent model

Neonatal necrotizing enterocolitis (NEC) is a poorly understood life‐threatening illness afflicting premature infants. Research is hampered by the absence of a suitable method to monitor disease progression noninvasively. The primary goal of this research was to test in vivo MRI methods for the noninvasive early detection and staging of inflammation in the ileum of an infant rat model of NEC. Neonatal rats were delivered by cesarean section at embryonic stage of day 20 after the beginning of pregnancy and stressed with formula feeding, hypoxia and bacterial colonization to induce NEC. Naturally born and dam‐fed neonatal rats were used as healthy controls. In vivo MRI studies were performed using a Bruker 9.4‐T scanner to obtain high‐resolution anatomical MR images using both gradient echo and spin echo sequences, pixel‐by‐pixel T₂ maps using a multi‐slice–multi‐echo sequence, and maps of the apparent diffusion coefficient (ADC) of water using a spin echo sequence, to assess the degree of ileal damage. Pups were sacrificed at the end of the MRI experiment on day 2 or 4 for histology. T₂ measured by MRI was increased significantly in the ileal regions of pups with NEC by histology (106.3 ± 6.1 ms) compared with experimentally stressed pups without NEC (85.2 ± 6.8 ms) and nonstressed, control rat pups (64.9 ± 2.3 ms). ADC values measured by diffusion‐weighted MRI were also increased in the ileal regions of pups with NEC by histology [(1.98 ± 0.15) × 10^–3 mm²/s] compared with experimentally stressed pups without NEC [(1.43 ± 0.16) × 10^–3 mm²/s] and nonstressed control pups [(1.10 ± 0.06) × 10^–3 mm²/s]. Both T₂ and ADC values between these groups were found to be significantly different (p < 0.03). The correlation of MRI results with histologic images of the excised ileal tissue samples strongly suggests that MRI can noninvasively identify NEC and assess intestinal injury prior to clinical symptoms in a physiologic rat pup model of NEC. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

Validation of surface‐to‐volume ratio measurements derived from oscillating gradient spin echo on a clinical scanner using anisotropic fiber phantoms

A diffusion measurement in the short‐time surface‐to‐volume ratio (S/V) limit (Mitra et al., Phys Rev Lett. 1992;68:3555) can disentangle the free diffusion coefficient from geometric restrictions to diffusion. Biophysical parameters, such as the S/V of tissue membranes, can be used to estimate microscopic length scales non‐invasively. However, due to gradient strength limitations on clinical MRI scanners, pulsed gradient spin echo (PGSE) measurements are impractical for probing the S/V limit. To achieve this limit on clinical systems, an oscillating gradient spin echo (OGSE) sequence was developed. Two phantoms containing 10 fiber bundles, each consisting of impermeable aligned fibers with different packing densities, were constructed to achieve a range of S/V values. The frequency‐dependent diffusion coefficient, D(ω), was measured in each fiber bundle using OGSE with different gradient waveforms (cosine, stretched cosine, and trapezoidal), while D(t) was measured from PGSE and stimulated‐echo measurements. The S/V values derived from the universal high‐frequency behavior of D(ω) were compared against those derived from quantitative proton density measurements using single spin echo (SE) with varying echo times, and from magnetic resonance fingerprinting (MRF). S/V estimates derived from different OGSE waveforms were similar and demonstrated excellent correlation with both SE‐ and MRF‐derived S/V measures (ρ ≥ 0.99). Furthermore, there was a smoother transition between OGSE frequency f and PGSE diffusion time when using , rather than the commonly used t_eff = 1/(4f), validating the specific frequency/diffusion time conversion for this regime. Our well‐characterized fiber phantom can be used for the calibration of OGSE and diffusion modeling techniques, as the S/V ratio can be measured independently using other MR modalities. Moreover, our calibration experiment offers an exciting perspective of mapping tissue S/V on clinical systems.     

A phantom system for assessing the effects of membrane lipids on water proton relaxation

Quantitative MRI (qMRI) is a method for the non‐invasive study of brain‐structure‐associated changes expressed with measurable units. The qMRI‐derived parameters have been shown to reflect brain tissue composition such as myelin content. Nevertheless, it remains a major challenge to identify and quantify the contributions of specific molecular components to the MRI signal. Here, we describe a phantom system that can be used to evaluate the contribution of membrane lipids to qMRI‐derived parameters. We used a hydration‐dehydration dry film technique to formulate liposomes that can be used as a model of the bilayer lipid membrane. The liposomes were comprised of the most abundant types of lipid found in the human brain. We then applied clinically available qMRI techniques with adjusted bias corrections in order to test the ability of the phantom system to estimate multiple qMRI parameters such as proton density (PD), T₁, T₂, T₂* and magnetization transfer. In addition, we accurately measured the phantom sample water fraction (normalized PD). A similar protocol was also applied to the human brain in vivo. The phantom system allows for a reliable estimation of qMRI parameters for phantoms composed of various lipid types using a clinical MRI scanner. We also found a comparable reproducibility between the phantom and in vivo human brain qMRI estimations. To conclude, we have successfully created a biologically relevant liposome phantom system whose lipid composition can be fully controlled. Our lipid system and analysis can be used to measure the contributions to qMRI parameters of membrane lipids found in the human brain under scanning conditions that are relevant to in vivo human brain scans. Such a model system can be used to test the contributions of lipidomic changes in normal and pathological brain states.     

Quantitative analysis of lumbar intervertebral disc abnormalities at 3.0 Tesla: value of T(2) texture features and geometric parameters

T₂ relaxation time mapping provides information about the biochemical status of intervertebral discs. The present study aimed to determine whether texture features extracted from T₂ maps or geometric parameters are sensitive to the presence of abnormalities at the posterior aspect of lumbar intervertebral discs, i.e. bulging and herniation. Thirty‐one patients (21 women and 10 men; age range 18–51 years) with low back pain were enrolled. MRI of the lumbar spine at 3.0 Tesla included morphological T₁‐ and T₂‐weighted fast spin‐echo sequences, and multi‐echo spin‐echo sequences that were used to construct T₂ maps. On morphological MRI, discs were visually graded into ‘normal’, ‘bulging’ or ‘herniation’. On T₂ maps, texture analysis (based on the co‐occurrence matrix and wavelet transform) and geometry analysis of the discs were performed. The three T₂ texture features and geometric parameters best‐suited for distinguishing between normal discs and discs with bulging or herniation were determined using Fisher coefficients. Statistical analysis comprised ANCOVA and post hoc t‐tests. Eighty‐two discs were classified as ‘normal’, 49 as ‘bulging’ and 20 showed ‘herniation.’ The T₂ texture features Entropy and Difference Variance, and all three pre‐selected geometric parameters differed significantly between normal and bulging, normal and herniated, and bulging and herniated discs (p < 0.05). These findings suggest that T₂ texture features and geometric parameters are sensitive to the presence of abnormalities at the posterior aspect of lumbar intervertebral discs, and may thus be useful as quantitative biomarkers that predict disease. Copyright © 2011 John Wiley & Sons, Ltd. Copyright © 2011 John Wiley & Sons, Ltd.     

Proton change of parotid glands after gustatory stimulation examined by magnetic resonance imaging

The aim of this study was to investigate proton changes of the parotid gland after gustatory stimulation by semi‐quantitative parameters and an empirical mathematical model (EMM) using high‐temporal‐resolution, double‐echo, echo‐planar imaging (EPI). Approved by a local institutional review board, this study examined 20 parotid glands from 10 healthy volunteers (male:female = 6: 4; age ± standard deviation =35.1 ± 14.1 years) with written informed consent obtained. All participants underwent 1.5‐T, double‐echo EPI with gustatory stimulation. Semi‐quantitative parameters, including maximal drop ratio (MDR), time to peak (TTP), drop slope (DS), recovery slope (RS) and recovery ratio (RR), were calculated. The effect of temporal resolution on parotid functional parameters was evaluated. An EMM comprising an output function ( ) and an input function ( ) was also applied to fit all dynamic curves. Kruskal–Wallis test, Wilcoxon test, linear regression analysis and goodness of fit were used for statistical analysis. p < 0.05 was considered to be statistically significant. The signal intensity dropped significantly after gustatory stimulation on the proton density (PD) image (p < 0.01). MDR was 8.26% in the PD image. MDR and RR were negatively associated with time interval, whereas DS and TTP were significantly positively associated with time interval (all p < 0.05). EMM parametric values derived from PD–time curves of parotid glands were 12.04 ± 6.81%, 6.43 ± 4.23 min^–1, 88.73 ± 6.18%, 8.41 ± 4.86 min^–1 and 1.09 ± 1.35 for A_o, k_o, B, A_in and k_in, respectively. Semi‐quantitative functional parameters and EMM parameters using high‐temporal‐resolution, double‐echo EPI allow the quantification of parotid proton changes after gustatory stimulation.