Influence of Magnetic Field Strength on Intravoxel Incoherent Motion Parameters in Diffusion MRI of the Calf.

Background: The purpose of this study was to investigate the dependence of Intravoxel Incoherent Motion (IVIM) parameters measured in the human calf on B0. Methods: Diffusion-weighted image data of eight healthy volunteers were acquired using five b-values (0-600 s/mm2) at rest and after muscle activation at 0.55 and 7 T. The musculus gastrocnemius mediale (GM, activated) was assessed. The perfusion fraction f and diffusion coefficient D were determined using segmented fits. The dependence on field strength was assessed using Student's t-test for paired samples and the Wilcoxon signed-rank test. A biophysical model built on the three non-exchanging compartments of muscle, venous blood, and arterial blood was used to interpret the data using literature relaxation times. Results: The measured perfusion fraction of the GM was significantly lower at 7 T, both for the baseline measurement and after muscle activation. For 0.55 and 7 T, the mean f values were 7.59% and 3.63% at rest, and 14.03% and 6.92% after activation, respectively. The biophysical model estimations for the mean proton-density-weighted perfusion fraction were 3.37% and 6.50% for the non-activated and activated states, respectively. Conclusions: B0 may have a significant effect on the measured IVIM parameters. The blood relaxation times suggest that 7 T IVIM may be arterial-weighted whereas 0.55 T IVIM may exhibit an approximately equal weighting of arterial and venous blood.

Fast online spectral-spatial pulse design for subject-specific fat saturation in cervical spine and foot imaging at 1.5 T.

OBJECTIVE: To compensate subject-specific field inhomogeneities and enhance fat pre-saturation with a fast online individual spectral-spatial (SPSP) single-channel pulse design. METHODS: The RF shape is calculated online using subject-specific field maps and a predefined excitation k-space trajectory. Calculation acceleration options are explored to increase clinical viability. Four optimization configurations are compared to a standard Gaussian spectral selective pre-saturation pulse and to a Dixon acquisition using phantom and volunteer (N = 5) data at 1.5 T with a turbo spin echo (TSE) sequence. Measurements and simulations are conducted across various body parts and image orientations. RESULTS: Phantom measurements demonstrate up to a 3.5-fold reduction in residual fat signal compared to Gaussian fat saturation. In vivo evaluations show improvements up to sixfold for dorsal subcutaneous fat in sagittal cervical spine acquisitions. The versatility of the tailored trajectory is confirmed through sagittal foot/ankle, coronal, and transversal cervical spine experiments. Additional measurements indicate that excitation field (B1) information can be disregarded at 1.5 T. Acceleration methods reduce computation time to a few seconds. DISCUSSION: An individual pulse design that primarily compensates for main field (B0) inhomogeneities in fat pre-saturation is successfully implemented within an online "push-button" workflow. Both fat saturation homogeneity and the level of suppression are improved.

UTE-T2* versus conventional T2* mapping to assess posterior cruciate ligament ultrastructure and integrity-an in-situ study.

Background: Clinical-standard morphologic magnetic resonance imaging (MRI) is limited in the refined diagnosis of posterior cruciate ligament (PCL) injuries. Quantitative MRI sequences such as ultrashort echo-time (UTE)-T2* mapping or conventional T2* mapping have been theorized to quantify ligament (ultra-) structure and integrity beyond morphology. This study evaluates their diagnostic potential in identifying and differentiating partial and complete PCL injuries in a standardized graded injury model. Methods: Ten human cadaveric knee joint specimens were imaged on a clinical 3.0 T MRI scanner using morphologic, conventional T2* mapping, and UTE-T2* mapping sequences before and after standardized arthroscopic partial and complete PCL transection. Following manual segmentation, quantitative T2* and underlying texture features (i.e., energy, homogeneity, and variance) were analyzed for each specimen and PCL condition, both for the entire PCL and its subregions. For statistical analysis, Friedman's test followed by Dunn's multiple comparison test was used against the level of significance of P≤0.01. Results: For the entire PCL, T2* was significantly increased as a function of injury when acquired with the UTE-T2* sequence [entire PCL: 11.1±3.1 ms (intact); 10.9±4.6 ms (partial); 14.3±4.9 ms (complete); P<0.001], but not when acquired with the conventional T2* sequence [entire PCL: 10.0±3.2 ms (intact); 11.4±6.2 ms (partial); 15.5±7.8 ms (complete); P=0.046]. The PCL subregions and texture variables showed variable changes indicative of injury-associated disorganization. Conclusions: In contrast to the conventional T2* mapping, UTE-T2* mapping is more receptive in the detection of structural damage of the PCL and allows quantitative assessment of ligament (ultra-)structure and integrity that may help to improve diagnostic differentiation of distinct injury states. Once further substantiated beyond the in-situ setting, UTE-T2* mapping may refine diagnostic evaluation of PCL injuries and -possibly- monitor ligament healing, ageing, degeneration, and inflammation.

Segmentation of the fascia lata and reproducible quantification of intermuscular adipose tissue (IMAT) of the thigh.

OBJECTIVE: To develop a precise semi-automated segmentation of the fascia lata (FL) of the thigh to quantify IMAT volume in T1w MR images and fat fraction (FF) in Dixon MR images. MATERIALS AND METHODS: A multi-step segmentation approach was developed to identify fibrous structures of the FL and combining them into a closed 3D surface. 23 healthy young men with low and 50 elderly sarcopenic men with moderate levels of IMAT were measured by T1w and 6pt Dixon MRI at 3T. 20 datasets were used to determine reanalysis precision errors. IMAT volume was compared using the new FL segmentation versus an easier to segment but less accurate, tightly fitting envelope of the thigh muscle ensemble. RESULTS: The segmentation was successfully applied to all 73 datasets and took about 7 min per 28 slices. In particular, in elderly subjects, it includes a large amount of adipose tissue below the FL typically not accounted for in other segmentation approaches. Inter- and intra-operator RMS-CVs were 0.33% and 0.14%, respectively, for IMAT volume and 0.04% and 0.02%, respectively, for FFMT. DISCUSSION: The FL segmentation is an important step to quantify IMAT with high precision and may be useful to investigate effects of aging and treatment on changes of IMAT and FF. ClinicalTrials.gov identifier NCT2857660, August 5, 2016. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT2857660, August 5, 2016.

In vivo potassium MRI of the human heart.

PURPOSE: Potassium ions (K+ ) play a critical role in cardiac electrophysiology, and changes in their concentration reflect pathophysiological processes related to cardiovascular diseases. Here, we investigated the feasibility of in vivo 39 K MRI of the human heart. To achieve this, we developed, evaluated, and applied a 39 K/1 H RF coil, which is tailored for 39 K MRI of human heart at 7.0T. METHODS: The performance of the 39 K/1 H RF coil was evaluated by electromagnetic field and specific absorption ratio simulations using 2 (male/female) human voxel models. The RF coil was evaluated at the bench and applied in an in vivo proof-of-principle study involving 7 healthy volunteers. The experiments were performed using a 7.0T whole-body MR system in conjunction with a 3D density-adapted projection reconstruction imaging technique. RESULTS: For in vivo 39 K MRI of the human heart, a nominal spatial resolution of 14.5 × 14.5 × 14.5 mm3 within a total scan time of 30 min was achieved. The average SNR within the heart was 9.6 ± 2.4. CONCLUSION: This work validates the design of a 39 K/1 H RF coil for cardiac MR at 7.0T and demonstrates for the first time in vivo the feasibility of 39 K MRI of the human heart.

On the Field Strength Dependence of Bi- and Triexponential Intravoxel Incoherent Motion (IVIM) Parameters in the Liver.

BACKGROUND: Studies on intravoxel incoherent motion (IVIM) imaging are carried out with different acquisition protocols. PURPOSE: To investigate the dependence of IVIM parameters on the B0 field strength when using a bi- or triexponential model. STUDY TYPE: Prospective. STUDY POPULATION: 20 healthy volunteers (age: 19-28 years). FIELD STRENGTH/SEQUENCE: Volunteers were examined at two field strengths (1.5 and 3T). Diffusion-weighted images of the abdomen were acquired at 24 b-values ranging from 0.2 to 500 s/mm2 . ASSESSMENT: ROIs were manually drawn in the liver. Data were fitted with a bi- and a triexponential IVIM model. The resulting parameters were compared between both field strengths. STATISTICAL TESTS: One-way analysis of variance (ANOVA) and Kruskal-Wallis test were used to test the obtained IVIM parameters for a significant field strength dependency. RESULTS: At b-values below 6 s/mm2 , the triexponential model provided better agreement with the data than the biexponential model. The average tissue diffusivity was D = 1.22/1.00 µm2 /msec at 1.5/3T. The average pseudodiffusion coefficients for the biexponential model were D* = 308/260 µm2 /msec at 1.5/3T; and for the triexponential model D1* = 81.3/65.9 µm2 /msec, D2* = 2453/2333 µm2 /msec at 1.5/3T. The average perfusion fractions for the biexponential model were f = 0.286/0.303 at 1.5/3T; and for the triexponential model f1 = 0.161/0.174 and f2 = 0.152/0.159 at 1.5/3T. A significant B0 dependence was only found for the biexponential pseudodiffusion coefficient (ANOVA/KW P = 0.037/0.0453) and tissue diffusivity (ANOVA/KW: P < 0.001). DATA CONCLUSION: Our experimental results suggest that triexponential pseudodiffusion coefficients and perfusion fractions obtained at different field strengths could be compared across different studies using different B0 . However, it is recommended to take the field strength into account when comparing tissue diffusivities or using the biexponential IVIM model. Considering published values for oxygenation-dependent transversal relaxation times of blood, it is unlikely that the two blood compartments of the triexponential model represent venous and arterial blood. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1883-1892.

In vivo imaging of the time-dependent apparent diffusional kurtosis in the human calf muscle.

PURPOSE: To evaluate the time dependency of apparent diffusion coefficient Dapp and apparent diffusional kurtosis Kapp in vivo in the human calf. MATERIALS AND METHODS: Diffusion-weighted images of five healthy male volunteers were acquired using a 1.5T MR scanner. A stimulated echo sequence with echo planar imaging readout was used with diffusion gradients oriented along the three main axes. Mixing times (TM) of 100, 300, 500, and 700 ms and b-values ranging from 0 to 5600 s/mm(2) were used. Dapp and Kapp were determined. RESULTS: Dapp and Kapp decreased with increasing TM. As an example for absolute values, Dapp of the tibialis anterior drops from 1.18 ± 0.04 µm(2) /ms (TM = 100 ms) to 0.86 ± 0.02 µm(2) /ms (TM = 700 ms) (P = 0.001) and Kapp from 0.38 ± 0.06 to 0.32 ± 0.03 (P = 0.046) for a diffusion weighting along the left-right direction. Kapp was smaller than 0.43 in all muscles and at all TMs. CONCLUSION: The clearly observed time-dependence of Dapp and Kapp is an indicator of restricted diffusion in muscle tissue and may thus be a promising marker to investigate alterations of the microstructure. Compared to typical kurtosis values in white matter tissue of the brain, the kurtosis in muscle tissue is much smaller, which we attribute to the absence of the almost impermeable myelin sheath.

Quantification of tumor vessels in glioblastoma patients using time-of-flight angiography at 7 Tesla: a feasibility study.

PURPOSE: To analyze if tumor vessels can be visualized, segmented and quantified in glioblastoma patients with time of flight (ToF) angiography at 7 Tesla and multiscale vessel enhancement filtering. MATERIALS AND METHODS: Twelve patients with newly diagnosed glioblastoma were examined with ToF angiography (TR = 15 ms, TE = 4.8 ms, flip angle = 15°, FOV = 160 × 210 mm(2), voxel size: 0.31 × 0.31 × 0.40 mm(3)) on a whole-body 7 T MR system. A volume of interest (VOI) was placed within the border of the contrast enhancing part on T1-weighted images of the glioblastoma and a reference VOI was placed in the non-affected contralateral white matter. Automated segmentation and quantification of vessels within the two VOIs was achieved using multiscale vessel enhancement filtering in ImageJ. RESULTS: Tumor vessels were clearly visible in all patients. When comparing tumor and the reference VOI, total vessel surface (45.3 ± 13.9 mm(2) vs. 29.0 ± 21.0 mm(2) (p<0.035)) and number of branches (3.5 ± 1.8 vs. 1.0 ± 0.6 (p<0.001) per cubic centimeter were significantly higher, while mean vessel branch length was significantly lower (3.8 ± 1.5 mm vs 7.2 ± 2.8 mm (p<0.001)) in the tumor. DISCUSSION: ToF angiography at 7-Tesla MRI enables characterization and quantification of the internal vascular morphology of glioblastoma and may be used for the evaluation of therapy response within future studies.

Nuclear overhauser enhancement mediated chemical exchange saturation transfer imaging at 7 Tesla in glioblastoma patients.

BACKGROUND AND PURPOSE: Nuclear Overhauser Enhancement (NOE) mediated chemical exchange saturation transfer (CEST) is a novel magnetic resonance imaging (MRI) technique on the basis of saturation transfer between exchanging protons of tissue proteins and bulk water. The purpose of this study was to evaluate and compare the information provided by three dimensional NOE mediated CEST at 7 Tesla (7T) and standard MRI in glioblastoma patients. PATIENTS AND METHODS: Twelve patients with newly diagnosed histologically proven glioblastoma were enrolled in this prospective ethics committee-approved study. NOE mediated CEST contrast was acquired with a modified three-dimensional gradient-echo sequence and asymmetry analysis was conducted at 3.3 ppm (B1 = 0.7 µT) to calculate the magnetization transfer ratio asymmetry (MTR(asym)). Contrast enhanced T1 (CE-T1) and T2-weighted images were acquired at 3T and used for data co-registration and comparison. RESULTS: Mean NOE mediated CEST signal based on MTR(asym) values over all patients was significantly increased (p<0.001) in CE-T1 tumor (-1.99 ± 1.22%), tumor necrosis (-1.36 ± 1.30%) and peritumoral CEST hyperintensities (PTCH) within T2 edema margins (-3.56 ± 1.24%) compared to contralateral normal appearing white matter (-8.38 ± 1.19%). In CE-T1 tumor (p = 0.015) and tumor necrosis (p<0.001) mean MTR(asym) values were significantly higher than in PTCH. Extent of the surrounding tumor hyperintensity was smaller in eight out of 12 patients on CEST than on T2-weighted images, while four displayed at equal size. In all patients, isolated high intensity regions (0.40 ± 2.21%) displayed on CEST within the CE-T1 tumor that were not discernible on CE-T1 or T2-weighted images. CONCLUSION: NOE mediated CEST Imaging at 7 T provides additional information on the structure of peritumoral hyperintensities in glioblastoma and displays isolated high intensity regions within the CE-T1 tumor that cannot be acquired on CE-T1 or T2-weighted images. Further research is needed to determine the origin of NOE mediated CEST and possible clinical applications such as therapy assessment or biopsy planning.

Quantitative susceptibility mapping differentiates between blood depositions and calcifications in patients with glioblastoma.

OBJECTIVES: The application of susceptibility weighted imaging (SWI) in brain tumor imaging is mainly used to assess tumor-related "susceptibility based signals" (SBS). The origin of SBS in glioblastoma is still unknown, potentially representing calcifications or blood depositions. Reliable differentiation between both entities may be important to evaluate treatment response and to identify glioblastoma with oligodendroglial components that are supposed to present calcifications. Since calcifications and blood deposits are difficult to differentiate using conventional MRI, we investigated whether a new post-processing approach, quantitative susceptibility mapping (QSM), is able to distinguish between both entities reliably. MATERIALS AND METHODS: SWI, FLAIR, and T1-w images were acquired from 46 patients with glioblastoma (14 newly diagnosed, 24 treated with radiochemotherapy, 8 treated with radiochemotherapy and additional anti-angiogenic medication). Susceptibility maps were calculated from SWI data. All glioblastoma were evaluated for the appearance of hypointense or hyperintense correlates of SBS on the susceptibility maps. RESULTS: 43 of 46 glioblastoma presented only hyperintense intratumoral SBS on susceptibility maps, indicating blood deposits. Additional hypointense correlates of tumor-related SBS on susceptibility maps, indicating calcification, were identified in 2 patients being treated with radiochemotherapy and in one patient being treated with additional anti-angiogenic medication. Histopathologic reports revealed an oligodendroglial component in one patient that presented calcifications on susceptibility maps. CONCLUSIONS: QSM provides a quantitative, local MRI contrast, which reliably differentiates between blood deposits and calcifications. Thus, quantitative susceptibility mapping appears promising to identify rare variants of glioblastoma with oligodendroglial components non-invasively and may allow monitoring the role of calcification in the context of different therapy regimes.

3 Tesla sodium inversion recovery magnetic resonance imaging allows for improved visualization of intracellular sodium content changes in muscular channelopathies.

OBJECTIVES: To implement different sodium (²³Na)-magnetic resonance imaging (MRI) contrasts at 3 Tesla and to evaluate if a weighting toward intracellular sodium can be achieved, using 2 rare muscular channelopathies as model diseases. MATERIALS AND METHODS: Both lower legs of 6 patients with hypokalemic periodic paralysis (HypoPP), 5 patients with paramyotonia congenita (PC), and 5 healthy volunteers were examined on a 3 Tesla system with 3 different ²³Na-MRI pulse sequences. HypoPP and PC are rare muscle diseases, which are well characterized by elevated myoplasmic sodium at rest and after cooling, respectively. Intra- and interindividual comparisons were performed before and after provocation of one lower leg muscle. Three different ²³Na-MRI sequences were applied: (i) The total tissue sodium concentration was measured using a spin-density sequence (²³Na-TSC). (ii) A T1-contrast was applied to assess whether the known changes of the intracellular sodium concentration can be visualized by T1-weighting (²³Na-T1). (iii) An inversion recovery (²³Na-IR) sequence was used to utmost suppress the sodium signal from extracellular or vasogenic edema. Furthermore, a potential influence of the temperature dependency of the sodium relaxation times was considered. Additionally, H-MRI was performed to examine potential lipomatous or edematous changes. RESULTS: In HypoPP, all Na sequences showed significantly (P<0.05) higher signal intensities compared with PC patients and healthy subjects. In muscles of PC patients, provocation induced a significant (P=0.0007) increase (>20%) in the muscular ²³Na-IR signal and a corresponding decrease of muscle strength. Additionally, a tendency to higher ²³Na-T1 (P=0.07) and ²³Na-TSC (P=0.07) signal intensities was observed. Provocation revealed no significant changes in ¹H-MRI. In volunteers and in the contralateral, not cooled lower leg, there were no significant signal intensity changes after provocation. Furthermore, the ²³Na-IR sequence allows for a suppression of signal emanating from intravascular sodium and vasogenic edema. CONCLUSIONS: Our results indicate that the ²³Na-IR sequence allows for a weighting toward intracellular sodium. The combined application of the ²³Na-TSC and the ²³Na-IR sequence enables an improved analysis of pathophysiological changes that occur in muscles of patients with muscular channelopathies.

The potential of relaxation-weighted sodium magnetic resonance imaging as demonstrated on brain tumors.

OBJECTIVES: : Total tissue sodium (Na) content is associated with the viability of cells and can be assessed by Na magnetic resonance imaging. However, the resulting total sodium signal (NaT) represents a volume-weighted average of different sodium compartments assigned to the intra- and extracellular space. In addition to the spin-density weighted contrast of NaT imaging, relaxation-weighted (NaR) sequences were applied. The aim of this study was to evaluate the potential of NaR imaging for tissue characterization and putative additional benefits to NaT imaging. MATERIALS AND METHODS: : For NaT and NaR imaging, novel magnetic resonance imaging sequences were established and applied in 16 patients suffering from brain tumors (14 WHO grade I-IV and 2 metastases). All Na sequences were based on density-adapted three-dimensional radial projection reconstruction to obtain short echo times and high signal-to-noise ratio efficiency. RESULTS: : NaT imaging revealed increased signal intensities in 15 of 16 brain tumors before therapy. In addition, NaR imaging enabled further differentiation of these lesions; all glioblastomas demonstrated higher NaR signal intensities as compared with WHO grade I-III tumors. Thus, NaR imaging allowed for correct separation between WHO grade I-III and WHO grade IV gliomas. In contrast to the NaT signal, the NaR signal correlated with the MIB-1 proliferation rate of tumor cells. CONCLUSIONS: : These results serve as a proof of concept that NaR imaging reveals important physiological tissue characteristics different from NaT imaging. Furthermore, they indicate that the combined use of NaT and NaR imaging might add valuable information for the functional in vivo characterization of brain tissue.

Functional imaging in muscular diseases.

OBJECTIVE: The development of morphological and functional imaging techniques has improved the diagnosis of muscular disorders. METHODS: With the use of whole-body magnetic resonance imaging (MRI) the possibility of imaging the entire body has been introduced. In patients with suspected myositis, oedematous and inflammatory changed muscles can be sufficiently depicted and therefore biopsies become more precise. RESULTS: Functional MR methods visualise different aspects of muscular (patho)physiology: muscular sodium (Na(+)) homeostasis can be monitored with (23)Na MRI; the muscular energy and lipid metabolism can be monitored using (31)P and (1)H MR spectroscopy. (23)Na MRI has reached an acceptable value in the diagnosis and follow-up of patients with muscular Na(+) channelopathies that are characterised by myocellular Na(+) overload and consecutive muscle weakness. Besides MRI, low mechanical index contrast-enhanced ultrasound (CEUS) methods have also been introduced. For evaluation of myositis, CEUS is more efficient in the diagnostic work-up than usual b-mode ultrasound, because CEUS can detect the inflammatory-induced muscular hyperperfusion in acute myositis. Moreover, the arterial perfusion reserve in peripheral arterial disease can be adequately examined using CEUS. CONCLUSION: Modern muscular imaging techniques offer deeper insights in muscular (patho)physiology than just illustrating unspecific myopathic manifestations like oedematous or lipomatous changes, hypertrophy or atrophy.