Quantification and localization of contrast agents using delta relaxation enhanced magnetic resonance at 1.5?T

Object

Delta relaxation enhanced magnetic resonance (dreMR) is a new imaging technique based on the idea of cycling the magnetic field B ₀ during an imaging sequence. The method determines the field dependency of the relaxation rate (relaxation dispersion dR ₁/dB). This quantity is of particular interest in contrast agent imaging because the parameter can be used to determine contrast agent concentrations and increases the ability to localize the contrast agent.

Materials and methods

In this paper dreMR imaging was implemented on a clinical 1.5?T MR scanner combining conventional MR imaging with fast field-cycling. Two improvements to dreMR theory are presented describing the quantification of contrast agent concentrations from dreMR data and a correction for field-cycling with finite ramp times.

Results

Experiments demonstrate the use of the extended theory and show the measurement of contrast agent concentrations with the dreMR method. A second experiment performs localization of a contrast agent with a significant improvement in comparison to conventional imaging.

Conclusion

dreMR imaging has been extended by a method to quantify contrast agent concentrations and improved for field-cycling with finite ramp times. Robust localization of contrast agents using dreMR imaging has been performed in a sample where conventional imaging delivers inconclusive results.     

ViP MRI: virtual phantom magnetic resonance imaging

Object

The ability to generate reference signals is of great benefit for quantitation of the magnetic resonance (MR) signal. The aim of the present study was to implement a dedicated experimental set-up to generate MR images of virtual phantoms.

Materials and methods

Virtual phantoms of a given shape and signal intensity were designed and the k-space representation was generated. A waveform generator converted the k-space lines into a radiofrequency (RF) signal that was transmitted to the MR scanner bore by a dedicated RF coil. The k-space lines of the virtual phantom were played line-by-line in synchronization with the magnetic resonance imaging data acquisition.

Results

Virtual phantoms of complex patterns were reproduced well in MR images without the presence of artifacts. Time-series measurements showed a coefficient of variation below 1 % for the signal intensity of the virtual phantoms. An excellent linearity (coefficient of determination r ² = 0.997 as assessed by linear regression) was observed in the signal intensity of virtual phantoms.

Conclusion

Virtual phantoms represent an attractive alternative to physical phantoms for providing a reference signal. MR images of virtual phantoms were here generated using a stand-alone, independent unit that can be employed with MR scanners from different vendors.     

Quantitative biodistribution and pharmacokinetics of multimodal gadolinium-based nanoparticles for lungs using ultrashort TE MRI

Objective

To study the biodistribution and lung pharmacokinetics of tracheally administered gadolinium-based contrast agents [gadoteric acid and multimodal ultra-small rigid platforms (USRPs)], to validate their pharmacokinetics against optical imaging of fluorescent USRPs, and to test their short-term toxicity.

Materials and methods

Ultrashort echo-time (UTE) lung proton magnetic resonance imaging (MRI) was performed at 4.7-Tesla (T) after the intratracheal instillation of different concentrations of contrast agent solutions in mice. Pharmacokinetic models were implemented on the absolute concentration calculated from the MRI signal enhancement measurements. Fluorescent USRPs were used to obtain optical images with the same protocol. Bronchoalveolar lavage inflammatory cell count and serum creatinine measurement were performed on four groups of instilled mice (sham, saline, USRPs, lipopolysaccharide).

Results

MR and optical imaging showed similar kinetics of the USRPs, passing from the airways to the lung tissue and to the kidneys, with negligible hepatic clearance. No significant increase of lung and renal inflammation markers were observed in USRP-instilled animals.

Conclusion

A T ₁-weighted radial UTE sequence was found to be valuable in quantitatively monitoring the biodistribution and pharmacokinetics of nanoparticles in the lungs of mice. The observed favorable pharmacokinetics, which was validated by fluorescence imaging, ensures the negligible toxicity of the nanoprobes, making the USRPs and the developed protocol good candidates for applications on selected lung diseases.     

Anti-EpCAM scFv gadolinium chelate: a novel targeted MRI contrast agent for imaging of colorectal cancer

Objectives

The development of targeted contrast agents for magnetic resonance imaging (MRI) facilitates enhanced cancer imaging and more accurate diagnosis. In the present study, a novel contrast agent was developed by conjugating anti-EpCAM humanized scFv with gadolinium chelate to achieve target specificity.

Materials and methods

The material design strategy involved site-specific conjugation of the chelating agent to scFv. The scFv monomer was linked to maleimide-DTPA via unpaired cysteine at the scFv C-terminus, followed by chelation with gadolinium (Gd). Successful scFv-DTPA conjugation was achieved at 1:10 molar ratio of scFv to maleimide-DTPA at pH 6.5. The developed anti-EpCAM-Gd-DTPA MRI contrast agent was evaluated for cell targeting ability, in vitro serum stability, cell cytotoxicity, relaxivity, and MR contrast enhancement.

Results

A high level of targeting efficacy of anti-EpCAM-Gd-DTPA to an EpCAM-overexpressing HT29 colorectal cell was demonstrated by confocal microscopy. Good stability of the contrast agent was obtained and no cytotoxicity was observed in HT29 cells after 48 h incubation with 25–100 µM of Gd. Favorable imaging was obtained using anti-EpCAM-Gd-DTPA, including 1.8-fold enhanced relaxivity compared with Gd-DTPA, and MR contrast enhancement observed after binding to HT29.

Conclusion

The potential benefit of this contrast agent for in vivo MR imaging of colorectal cancer, as well as other EpCAM positive cancers, is suggested and warrants further investigation.

     

Automatic gallbladder segmentation using combined 2D and 3D shape features to perform volumetric analysis in native and secretin-enhanced MRCP sequences

Objectives

We aimed to develop the first fully automated 3D gallbladder segmentation approach to perform volumetric analysis in volume data of magnetic resonance (MR) cholangiopancreatography (MRCP) sequences. Volumetric gallbladder analysis is performed for non-contrast-enhanced and secretin-enhanced MRCP sequences.

Materials and methods

Native and secretin-enhanced MRCP volume data were produced with a 1.5-T MR system. Images of coronal maximum intensity projections (MIP) are used to automatically compute 2D characteristic shape features of the gallbladder in the MIP images. A gallbladder shape space is generated to derive 3D gallbladder shape features, which are then combined with 2D gallbladder shape features in a support vector machine approach to detect gallbladder regions in MRCP volume data. A region-based level set approach is used for fine segmentation. Volumetric analysis is performed for both sequences to calculate gallbladder volume differences between both sequences.

Results

The approach presented achieves segmentation results with mean Dice coefficients of 0.917 in non-contrast-enhanced sequences and 0.904 in secretin-enhanced sequences.

Conclusion

This is the first approach developed to detect and segment gallbladders in MR-based volume data automatically in both sequences. It can be used to perform gallbladder volume determination in epidemiological studies and to detect abnormal gallbladder volumes or shapes. The positive volume differences between both sequences may indicate the quantity of the pancreatobiliary reflux.

     

FID modulus: a simple and efficient technique to phase and align MR spectra

Object

The post-processing of MR spectroscopic data requires several steps more or less easy to automate, including the phase correction and the chemical shift assignment. First, since the absolute phase is unknown, one of the difficulties the MR spectroscopist has to face is the determination of the correct phase correction. When only a few spectra have to be processed, this is usually performed manually. However, this correction needs to be automated as soon as a large number of spectra is involved, like in the case of phase coherent averaging or when the signals collected with phased array coils have to be combined. A second post-processing requirement is the frequency axis assignment. In standard mono-voxel MR spectroscopy, this can also be easily performed manually, by simply assigning a frequency value to a well-known resonance (e.g. the water or NAA resonance in the case of brain spectroscopy). However, when the correction of a frequency shift is required before averaging a large amount of spectra (due to B ₀ spatial inhomogeneities in chemical shift imaging, or resulting from motion for example), this post-processing definitely needs to be performed automatically.

Materials and methods

Zero-order phase and frequency shift of a MR spectrum are linked respectively to zero-order and first-order phase variations in the corresponding free induction decay (FID) signal. One of the simplest ways to remove the phase component of a signal is to calculate the modulus of this signal: this approach is the basis of the correction technique presented here.

Results

We show that selecting the modulus of the FID allows, under certain conditions that are detailed, to automatically phase correct and frequency align the spectra. This correction technique can be for example applied to the summation of signals acquired from combined phased array coils, to phase coherent averaging and to B ₀ shift correction.

Conclusion

We demonstrate that working on the modulus of the FID signal is a simple and efficient way to both phase correct and frequency align MR spectra automatically. This approach is particularly well suited to brain proton MR spectroscopy.     

Automated segmentation and volumetric analysis of renal cortex,medulla, and pelvis based on non-contrast-enhanced T1- and T2-weighted MR images

Object

The aim of our study was to enable automatic volumetry of the entire kidneys as well as their internal structures (cortex, medulla, and pelvis) from native magnetic resonance imaging (MRI) data sets.

Materials and methods

Segmentation of the entire kidneys and differentiation of their internal structures were performed in 12 healthy volunteers based on non-contrast-enhanced T1- and T2-weighted MR images. Two data sets (each acquired in one breath-hold) were co-registered using a rigid registration algorithm compensating for possible breathing-related displacements. An automatic algorithm based on thresholding and shape detection segmented the kidneys into their compartments and was compared to a manual labeling procedure.

Results

The resulting kidney volumes of the automated segmentation correlated well with those created manually (R ² = 0.96). Average volume errors were determined to be 4.97 ± 4.08 % (entire kidney parenchyma), 7.03 ± 5.56 % (cortex), 12.33 ± 7.35 % (medulla), and 17.57 ± 14.47 % (pelvis). The variation of the kidney volume resulting from the automatic algorithm was found to be 4.76 % based on the measuring of one volunteer with three independent examinations.

Conclusion

The results demonstrate the feasibility of an accurate and repeatable automatic segmentation of the kidneys and their internal structures from non-contrast-enhanced magnetic resonance images.     

In vivo visualization of cells labeled with superparamagnetic iron oxides by a sub-millisecond gradient echo sequence

Object

In vivo magnetic resonance imaging (MRI) of iron-labeled pancreatic islets (PIs) transplanted into the liver is still challenging in humans. The aim of this study was to develop and evaluate a double contrast method for the detection of PIs labeled with superparamagnetic iron oxide (SPIO) nanoparticles.

Materials and methods

A double-echo three-dimensional (3D) spoiled gradient echo sequence was adapted to yield a sub-millisecond first echo time using variable echo times and highly asymmetric Cartesian readout. Positive contrast was achieved by conventional and relative image subtraction. Experiments for cell detection efficiency were performed in vitro on gelatin phantoms, in vivo on a Lewis rat and on a patient 6 months after PI transplantation.

Results

It was demonstrated that the proposed method can be used for the detection of transplanted PIs with positive contrast in vitro and in vivo. For all experiments, relative subtraction yielded comparable and in some cases better contrast than conventional subtraction. For the first time, positive contrast imaging of transplanted human PIs was performed in vivo in patients.

Conclusion

The proposed method allows 3D data acquisition within a single breath-hold and yields enhanced contrast-to-noise ratios of transplanted SPIO labeled pancreatic islets relative to negative contrast images, therefore providing improved identification.     

PET/MR for therapy response evaluation in malignant lymphoma: initial experience

Object

To evaluate the feasibility of positron emission tomography/magnetic resonance imaging (PET/MR) with ¹⁸fluoro-2-deoxyglucose (FDG) for therapy response evaluation of malignant lymphoma.

Materials and methods

Nine patients with malignant lymphoma who underwent FDG-PET/MR before and after chemotherapy were included in this retrospective study. Average time between the two scans was 70 days. The scans were evaluated independently by two nuclear medicine physicians. The Ann Arbor classification was used to describe lymphoma stage. Furthermore, the readers also rated PET image quality using a five point scale. Weighted kappa (κ) was used to calculate interrater agreement.

Results

The initial scan showed foci of increased FDG uptake in all patients, with Ann Arbor stage varying between I and IV. In the follow-up examination, all but one patient showed complete response to chemotherapy. PET image quality was rated as very good or excellent for all scans. Interrater agreement was excellent regarding Ann Arbor stage (κ = 0.97) and good regarding image quality (κ = 0.41).

Conclusion

PET/MR shows promising initial results for therapy response evaluation in lymphoma patients.     

Investigating the state-of-the-art in whole-body MR-based attenuation correction: an intra-individual,inter-system,inventory study on three clinical PET/MR systems

Objective

We assess inter- and intra-subject variability of magnetic resonance (MR)-based attenuation maps (MRμMaps) of human subjects for state-of-the-art positron emission tomography (PET)/MR imaging systems.

Materials and methods

Four healthy male subjects underwent repeated MR imaging with a Siemens Biograph mMR, Philips Ingenuity TF and GE SIGNA PET/MR system using product-specific MR sequences and image processing algorithms for generating MRμMaps. Total lung volumes and mean attenuation values in nine thoracic reference regions were calculated. Linear regression was used for comparing lung volumes on MRμMaps. Intra- and inter-system variability was investigated using a mixed effects model.

Results

Intra-system variability was seen for the lung volume of some subjects, (p = 0.29). Mean attenuation values across subjects were significantly different (p < 0.001) due to different segmentations of the trachea. Differences in the attenuation values caused noticeable intra-individual and inter-system differences that translated into a subsequent bias of the corrected PET activity values, as verified by independent simulations.

Conclusion

Significant differences of MRμMaps generated for the same subjects but different PET/MR systems resulted in differences in attenuation correction factors, particularly in the thorax. These differences currently limit the quantitative use of PET/MR in multi-center imaging studies.

     

Spatial phase encoding exploiting the Bloch–Siegert shift effect

Objective

The present work introduces an alternative to the conventional \(B_{0}\) -gradient spatial phase encoding technique. By applying far off-resonant radiofrequency (RF) pulses, a spatially dependent phase shift is introduced to the on-resonant transverse magnetization. This so-called Bloch–Siegert (BS) phase shift has been recently used for \(B_{1}^{ + }\) -mapping. The current work presents the theoretical background for the BS spatial encoding technique (BS-SET) using RF-gradients.

Materials and methods

Since the BS-gradient leads to nonlinear encoding, an adapted reconstruction method was developed to obtain undistorted images. To replace conventional phase encoding gradients, BS-SET was implemented in a two-dimensional (2D) spin echo sequence on a 0.5 T portable MR scanner.

Results

A 2D spin echo (SE) measurement imaged along a single dimension using the BS-SET was compared to a conventional SE 2D measurement. The proposed reconstruction method yielded undistorted images.

Conclusions

BS-gradients were demonstrated as a feasible option for spatial phase encoding. Furthermore, undistorted BS-SET images could be obtained using the proposed reconstruction method.     

Magnetic resonance imaging in patients with granulomatosis with polyangiitis (Wegener’s) and subglottic stenosis

Objective

To evaluate the ability of MRI to detect subglottic stenosis and to differentiate between active and inactive subglottic inflammation in patients with granulomatosis with polyangiitis (GPA).

Materials and methods

MRI studies of the larynx of 18 GPA patients with suspected SGS were included. The MRI protocol included T1- and T2-weighted and STIR-sequences, dynamic contrast enhancement (DCE) and diffusion weighted imaging (DWI). Two independent observers reviewed the MR images. SGS were identified and quantified, inflammatory activity was assessed using edema imaging, DCE and DWI. Final MRI diagnoses were compared to the clinical, laryngoscopic and histopathologic results.

Results

MRI confirmed SGS in all GPA patients with significant narrowing of the airway lumen and thickening of subglottic wall. Assessing the subglottic inflammatory activity, MRI showed a sensitivity of 87.5 % and a specificity of 60.0 %. Interrater agreement was κ = 0.769. Of the different MR technical approaches tested, edema imaging was most sensitive and specific. DWI led to significant differences in the apparent diffusion coefficient between active and inactive subglottic inflammation. No significant differences were found with DCE imaging.

Conclusion

MR imaging has shown the ability to detect and grade SGS in patients with GPA. It non-invasively assesses the status of inflammatory activity utilizing edema sensitive sequences and DWI.     

An embedded optical tracking system for motion-corrected magnetic resonance imaging at 7T

Object

Prospective motion correction using data from optical tracking systems has been previously shown to reduce motion artifacts in MR imaging of the head. We evaluate a novel optical embedded tracking system.

Materials and methods

The home-built optical embedded tracking system performs image processing within a 7T scanner bore, enabling high speed tracking. Corrected and uncorrected in vivo MR volumes are acquired interleaved using a modified 3D FLASH sequence, and their image quality is assessed and compared.

Results

The latency between motion and correction of the slice position was measured to be (19?±?5)?ms, and the tracking noise has a standard deviation no greater than 10???m/0.005° during conventional MR scanning. Prospective motion correction improved the edge strength by 16?% on average, even though the volunteers were asked to remain motionless during the acquisitions.

Conclusion

Using a novel method for validating the effectiveness of in vivo prospective motion correction, we have demonstrated that prospective motion correction using motion data from the embedded tracking system considerably improved image quality.     

Eddy current compensation for delta relaxation enhanced MR by dynamic reference phase modulation

Object

Eddy current compensation by dynamic reference phase modulation (eDREAM) is a compensation method for eddy current fields induced by B ₀ field-cycling which occur in delta relaxation enhanced MR (dreMR) imaging. The presented method is based on a dynamic frequency adjustment and prevents eddy current related artifacts. It is easy to implement and can be completely realized in software for any imaging sequence.

Materials and methods

In this paper, the theory of eDREAM is derived and two applications are demonstrated. The theory describes how to model the behavior of the eddy currents and how to implement the compensation. Phantom and in vivo measurements are carried out and demonstrate the benefits of eDREAM.

Results

A comparison of images acquired with and without eDREAM shows a significant improvement in dreMR image quality. Images without eDREAM suffer from severe artifacts and do not allow proper interpretation while images with eDREAM are artifact free. In vivo experiments demonstrate that dreMR imaging without eDREAM is not feasible as artifacts completely change the image contrast.

Conclusion

eDREAM is a flexible eddy current compensation for dreMR. It is capable of completely removing the influence of eddy currents such that the dreMR images do not suffer from artifacts.     

A highly parallelized framework for computationally intensive MR data analysis

Object

The goal of this study was to develop a comprehensive magnetic resonance (MR) data analysis framework for handling very large datasets with user-friendly tools for parallelization and to provide an example implementation.

Materials and methods

Commonly used software packages (AFNI, FSL, SPM) were connected via a framework based on the free software environment R, with the possibility of using Nvidia CUDA GPU processing integrated for high-speed linear algebra operations in R. Three hundred single-subject datasets from the 1,000 Functional Connectomes project were used to demonstrate the capabilities of the framework.

Results

A framework for easy implementation of processing pipelines was developed and an R package for the example implementation of Fully Exploratory Network ICA was compiled. Test runs on data from 300 subjects demonstrated the computational advantages of a processing pipeline developed using the framework compared to non-parallelized processing, reducing computation time by a factor of 15.

Conclusion

The feasibility of computationally intensive exploratory analyses allows broader access to the tools for discovery science.     

Image artifacts from MR-based attenuation correction in clinical, whole-body PET/MRI

Purpose

Integrated whole-body PET/MRI tomographs have become available. PET/MR imaging has the potential to supplement, or even replace combined PET/CT imaging in selected clinical indications. However, this is true only if methodological pitfalls and image artifacts arising from novel MR-based attenuation correction (MR-AC) are fully understood.

Results

Here we present PET/MR image artifacts following routine MR-AC, as most frequently observed in clinical operations of an integrated whole-body PET/MRI system.

Conclusion

A clinical adoption of integrated PET/MRI should entail the joint image display and interpretation of MR data, MR-based attenuation maps and uncorrected plus attenuation-corrected PET images in order to recognize potential pitfalls from MR-AC and to ensure clinically accurate image interpretation.     

Visualization of immune cell infiltration in experimental viral myocarditis by 19F MRI in vivo

Objective

This paper introduces a new approach permitting for the first time a specific, non-invasive diagnosis of myocarditis by visualizing the infiltration of immune cells into the myocardium.

Materials and methods

The feasibility of this approach is shown in a murine model of viral myocarditis. Our study uses biochemically inert perfluorocarbons (PFCs) known to be taken up by circulating monocytes/macrophages after intravenous injection.

Results

In vivo ¹⁹F MRI at 9.4 T demonstrated that PFC-loaded immune cells infiltrate into inflamed myocardial areas. Because of the lack of any fluorine background in the body, detected ¹⁹F signals of PFCs are highly specific as confirmed ex vivo by flow cytometry and histology.

Conclusion

Since PFCs are a family of compounds previously used clinically as blood substitutes, the technique described in our paper holds the potential as a new imaging modality for the diagnosis of myocarditis in man.     

Cardiac magnetic resonance T1 and extracellular volume mapping with motion correction and co-registration based on fast elastic image registration

Objective

Our aim was to investigate the technical feasibility of a novel motion compensation method for cardiac magntic resonance (MR) T1 and extracellular volume fraction (ECV) mapping.

Materials and methods

Native and post-contrast T1 maps were obtained using modified look-locker inversion recovery (MOLLI) pulse sequences with acquisition scheme defined in seconds. A nonrigid, nonparametric, fast elastic registration method was applied to generate motion-corrected T1 maps and subsequently ECV maps. Qualitative rating was performed based on T1 fitting-error maps and overlay images. Local deformation vector fields were produced for quantitative assessment. Intra- and inter-observer reproducibility were compared with and without motion compensation.

Results

Eighty-two T1 and 39 ECV maps were obtained in 21 patients with diverse myocardial diseases. Approximately 60% demonstrated clear quality improvement after motion correction for T1 mapping, particularly for the poor-rating cases (23% before vs 2% after). Approximately 67% showed further improvement with co-registration in ECV mapping. Although T1 and ECV values were not clinically significantly different before and after motion compensation, there was improved intra- and inter-observer reproducibility after motion compensation.

Conclusions

Automated motion correction and co-registration improved the qualitative assessment and reproducibility of cardiac MR T1 and ECV measurements, allowing for more reliable ECV mapping.

     

Blood longitudinal (T 1) and transverse (T 2) relaxation time constants at 11.7 Tesla

Object

The goal of the study was to determine blood T ₁ and T ₂ values as functions of oxygen saturation (Y), temperature (Temp) and hematocrit (Hct) at an ultrahigh MR field (11.7?T) and explore their impacts on physiological measurements, including cerebral blood flow (CBF), blood volume (CBV) and oxygenation determination.

Materials and methods

T ₁ and T ₂ were simultaneously measured. Temperature was adjusted from 25 to 40°C to determine Temp dependence; Hct of 0.17?C0.51 to evaluate Hct dependence at 25 and 37°C; and Y of 40?C100% to evaluate Y dependence at 25 and 37°C. Comparisons were made with published data obtained at different magnetic field strengths (B ₀).

Results

T ₁ was positively correlated with Temp, independent of Y, and negatively correlated with Hct. T ₂ was negatively correlated with Temp and Hct, but positively correlated with Y, in a non-linear fashion. T ₁ increased linearly with B ₀, whereas T ₂ decreased exponentially with B₀.

Conclusion

This study reported blood T ₁ and T ₂ measurements at 11.7?T for the first time. These blood relaxation data could have implications in numerous functional and physiological MRI studies at 11.7?T.