Improved estimation of MR relaxation parameters using complex-valued data.

PURPOSE: In MR image analysis, T1 , T2 , and T2* maps are generally calculated using magnitude MR data. Without knowledge of the underlying noise variance, parameter estimates at low signal to noise ratio (SNR) are usually biased. This leads to confounds in studies that compare parameters across SNRs and or across scanners. This article compares several estimation techniques which use real or complex-valued MR data to achieve unbiased estimation of MR relaxation parameters without the need for additional preprocessing. THEORY AND METHODS: Several existing and new techniques to estimate relaxation parameters using complex-valued data were compared with widely used magnitude-based techniques. Their bias, variance and processing times were studied using simulations covering various aspects of parameter variations. Validation on noise-degraded experimental measurements was also performed. RESULTS: Simulations and experiments demonstrated the superior performance of techniques based on complex-valued data, even in comparison with magnitude-based techniques that account for Rician noise characteristics. This was achieved with minor modifications to data modeling and at computational costs either comparable to or higher ( ≈two fold) than magnitude-based estimators. Theoretical analysis shows that estimators based on complex-valued data are statistically efficient. CONCLUSION: The estimation techniques that use complex-valued data provide minimum variance unbiased estimates of parametric maps and markedly outperform commonly used magnitude-based estimators under most conditions. They additionally provide phase maps and field maps, which are unavailable with magnitude-based methods. Magn Reson Med 77:385-397, 2017. © 2016 Wiley Periodicals, Inc.

Simultaneous R2*, R2, and R2' quantification by combining S0 estimation of the free induction decay with a single spin echo: A single acquisition method for R2 insensitive quantification of holmium-166-loaded microspheres.

PURPOSE: To present a new method, S0 estimation of the free induction decay combined with a single spin echo measurement (SOFIDSE), that enables simultaneous measurements of R2*, R2, and R2' in order to quantify the local concentration of holmium microspheres (Ho-MS) for radioembolization. THEORY AND METHODS: SOFIDSE estimates R2* and the signal magnitude at time point 0, S0, from a multigradient echo readout of the free induction decay and subsequently estimates R2 using S0 and a single spin echo, from which R2' is deducted. The method was evaluated by comparing SOFIDSE R2 values with values obtained from shifted spin echo (SSE) measurements on a phantom setup containing Ho-MS and from dual spin echo measurements on a healthy volunteer. RESULTS: On average, SOFIDSE showed a small overestimation of R2 values compared with SSE independent of the microsphere concentration. R2' values determined by subtraction of either SOFIDSE R2 or SSE R2 from R2* showed excellent agreement (correlation coefficient = 1; P = 9 · 10(-11)). The Ho-MS-induced R2' values obtained by SOFIDSE were insensitive to the R2 value of the tissue in which they resided. CONCLUSION: SOFIDSE enables quantification of Ho-MS, in media with spatially or temporally varying R2 values, in a single acquisition.

Center-out radial sampling with off-resonant reconstruction for efficient and accurate localization of punctate and elongated paramagnetic structures.

Accurate localization of interventional devices, for example, needles and brachytherapy seeds, is desired for interventional procedures. MRI is usually considered unsuitable for this purpose, as the induced signal voids and signal pile-ups do not necessarily represent the exact location of the devices. Center-out radial sampling with off-resonance reception (co-RASOR) has been shown to solve this problem by repositioning the signal pile-up into the geometrical center of the interventional devices. However, the multiple acquisitions required for co-RASOR resulted in a low efficiency and unsuitability for near real-time interventional purposes. Herein, we aim to increase the efficiency of co-RASOR by relying on multiple off-resonance reconstructions of a single acquisition rather than on multiple acquisitions. The soundness of this approach is shown by demonstrating the equivalence of acquisition co-RASOR and reconstruction co-RASOR, both theoretically and experimentally. An algorithm is proposed and evaluated to obtain the geometric centers of the devices, while suppressing the background. This procedure is shown to be effective, in vitro as well as ex vivo, and to yield signal intensity increases in the order of 150-400% of the average signal, in the geometric center of a brachytherapy seed and a needle, respectively. The geometric accuracy of the resultant images is confirmed by computed tomography.

Towards inherently distortion-free MR images for image-guided radiotherapy on an MRI accelerator.

In MR-guided interventions, it is mandatory to establish a solid relationship between the imaging coordinate system and world coordinates. This is particularly important in image-guided radiotherapy (IGRT) on an MRI accelerator, as the interaction of matter with γ-radiation cannot be visualized. In conventional acquisitions, off-resonance effects cause discrepancies between coordinate systems. We propose to mitigate this by using only phase encoding and to reduce the longer acquisitions by under-sampling and regularized reconstruction. To illustrate the performance of this acquisition in the presence of off-resonance phenomena, phantom and in vivo images are acquired using spin-echo (SE) and purely phase-encoded sequences. Data are retrospectively under-sampled and reconstructed iteratively. We observe accurate geometries in purely phase-encoded images for all cases, whereas SE images of the same phantoms display image distortions. Regularized reconstruction yields accurate phantom images under high acceleration factors. In vivo images were reconstructed faithfully while using acceleration factors up to 4. With the proposed technique, inherently undistorted images with one-to-one correspondence to world coordinates can be obtained. It is a valuable tool in geometry quality assurance, treatment planning and online image guidance. Under-sampled acquisition combined with regularized reconstruction can be used to accelerate the acquisition while retaining geometrical accuracy.

Correction of gradient echo images for first and second order macroscopic signal dephasing using phase derivative mapping.

Gradient echo techniques are often hampered by signal dephasing due to macroscopic phase perturbations because of system imperfections (shimming) or object induced perturbations of the magnetic field (hemorrhagic lesions, calcified tissue, air-tissue interfaces). Many techniques have been proposed to reduce the effects of macroscopic phase variations. Among these techniques are tuned pulse sequences, fitting techniques and reconstruction algorithms. These methods, however, suffer from one or more of the following drawbacks: they require longer acquisition times, require additional acquisitions, compensate only locally, can only be applied to multi-gradient echo data or may result in inaccurate results. In this work a generally applicable post-processing technique is presented to evaluate and compensate signal alterations invoked by first and second order macroscopic phase incoherences. In this technique, the derivatives of the signal phase are determined by applying the Fourier derivative theorem on the complex data. As a result, the phase derivatives are obtained without phase unwrapping and without compromising the resolution. The method is validated for single and multi-echo acquisitions by experiments on a co-axial cylinder phantom with known macroscopic field disturbances. The potential of the method is demonstrated on a multi-gradient echo acquisition on the head of a human volunteer. In general a first order correction is shown to be sufficient, however higher order correction is found to be beneficial near sharp transitions of the magnetic field.

Holmium-166 poly(L-lactic acid) microsphere radioembolisation of the liver: technical aspects studied in a large animal model.

OBJECTIVE: To assess the accuracy of a scout dose of holmium-166 poly(L-lactic acid) microspheres ((166)Ho-PLLA-MS) in predicting the distribution of a treatment dose of (166)Ho-PLLA-MS, using single photon emission tomography (SPECT). METHODS: A scout dose (60 mg) was injected into the hepatic artery of five pigs and SPECT acquired. Subsequently, a 'treatment dose' was administered (540 mg) and SPECT, computed tomography (CT) and magnetic resonance imaging (MRI) of the total dose performed. The two SPECT images of each animal were compared. To validate quantitative SPECT an ex vivo liver was instilled with (166)Ho-PLLA-MS and SPECT acquired. The liver was cut into slices and planar images were acquired, which were registered to the SPECT image. RESULTS: Qualitatively, the scout dose and total dose images were similar, except in one animal because of catheter displacement. Quantitative analysis, feasible in two animals, tended to confirm this similarity (r(2) = 0.34); in the other animal the relation was significantly better (r(2) = 0.66). The relation between the SPECT and planar images acquired from the ex vivo liver was strong (r(2) = 0.90). CONCLUSION: In the porcine model a scout dose of (166)Ho-PLLA-MS can accurately predict the biodistribution of a treatment dose. Quantitative (166)Ho SPECT was validated for clinical application.

Microspheres with ultrahigh holmium content for radioablation of malignancies.

PURPOSE: The aim of this study was to develop microspheres with an ultra high holmium content which can be neutron activated for radioablation of malignancies. These microspheres are proposed to be delivered selectively through either intratumoral injections into solid tumors or administered via an intravascularly placed catheter. METHODS: Microspheres were prepared by solvent evaporation, using holmium acetylacetonate (HoAcAc) crystals as the sole ingredient. Microspheres were characterized using light and scanning electron microscopy, coulter counter, titrimetry, infrared and Raman spectroscopy, differential scanning calorimetry, X-ray powder diffraction, magnetic resonance imaging (MRI), and X-ray computed tomography (CT). RESULTS: Microspheres, thus prepared displayed a smooth surface. The holmium content of the HoAcAc microspheres (44% (w/w)) was higher than the holmium content of the starting material, HoAcAc crystals (33% (w/w)). This was attributed to the loss of acetylacetonate from the HoAcAc complex, during rearrangement of acetylacetonate around the holmium ion. The increase of the holmium content allows for the detection of (sub)microgram amounts of microspheres using MRI and CT. CONCLUSIONS: HoAcAc microspheres with an ultra-high holmium content were prepared. These microspheres are suitable for radioablation of tumors by intratumoral injections or treatment of liver tumors through transcatheter administration.

Characterization of holmium loaded alginate microspheres for multimodality imaging and therapeutic applications.

In this paper the preparation and characterization of holmium-loaded alginate microspheres is described. The rapid development of medical imaging techniques offers new opportunities for the visualisation of (drug-loaded) microparticles. Therefore, suitable imaging agents have to be incorporated into these particles. For this reason, the element holmium was used in this study in order to utilize its unique imaging characteristics. The paramagnetic behaviour of this element allows visualisation with MRI and holmium can also be neutron-activated resulting in the emission of gamma-radiation, allowing visualisation with gamma cameras, and beta-radiation, suitable for therapeutic applications. Almost monodisperse alginate microspheres were obtained by JetCutter technology where alginate droplets of a uniform size were hardened in an aqueous holmium chloride solution. Ho(3+) binds via electrostatic interactions to the carboxylate groups of the alginate polymer and as a result alginate microspheres loaded with holmium were obtained. The microspheres had a mean size of 159 microm and a holmium loading of 1.3 +/- 0.1% (w/w) (corresponding with a holmium content based on dry alginate of 18.3 +/- 0.3% (w/w)). The binding capacity of the alginate polymer for Ho(3+) (expressed in molar amounts) is equal to that for Ca(2+), which is commonly used for the hardening of alginate. This indicates that Ho(3+) has the same binding affinity as Ca(2+). In line herewith, dynamic mechanical analyses demonstrated that alginate gels hardened with Ca(2+) or Ho(3+) had similar viscoelastic properties. The MRI relaxation properties of the microspheres were determined by a MRI phantom experiment, demonstrating a strong R(2)* effect of the particles. Alginate microspheres could also be labelled with radioactive holmium by adding holmium-166 to alginate microspheres, previously hardened with calcium (labelling efficiency 96%). The labelled microspheres had a high radiochemical stability (94% after 48 h incubation in human serum), allowing therapeutic applications for treatment of cancer. The potential in vivo application of the microspheres for a MR-guided renal embolization procedure was illustrated by selective administration of microspheres to the left kidney of a pig. Anatomic MR-imaging showed the presence of holmium-loaded microspheres in the kidney. In conclusion, this study demonstrates that the incorporation of holmium into alginate microspheres allows their visualisation with a gamma camera and MRI. Holmium-loaded alginate microspheres can be used therapeutically for embolization and, when radioactive, for local radiotherapy of tumours.

Development and testing of passive tracking markers for different field strengths and tracking speeds.

Susceptibility markers for passive tracking need to be small in order to maintain the shape and mechanical properties of the endovascular device. Nevertheless, they also must have a high magnetic moment to induce an adequate artefact at a variety of scan techniques, tracking speeds and, preferably, field strengths. Paramagnetic markers do not satisfy all of these requirements. Ferro- and ferrimagnetic materials were therefore investigated with a vibrating sample magnetometer and compared with the strongly paramagnetic dysprosium oxide. Results indicated that the magnetic behaviour of stainless steel type AISI 410 corresponds the best with ideal marker properties. Markers with different magnetic moments were constructed and tested in in vitro and in vivo experiments. The appearance of the corresponding artefacts was field strength independent above magnetic saturation of 1.5 T. Generally, the contrast-to-noise ratio decreased at increasing tracking speed and decreasing magnetic moment. Device depiction was most consistent at a frame rate of 20 frames per second.

Dynamic CE-MRA for endoleak classification after endovascular aneurysm repair.

AIM: To evaluate the value of dynamic contrast enhanced magnetic resonance angiography (CE-MRA) for classification of endoleaks after endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: Twenty-eight patients, between 2 days and 54 months after EVAR, were evaluated with CTA, MRI and dynamic CE-MRA. The additional diagnostic value of the dynamic 3D CE-MRA was evaluated by determining the ability of the dynamic series in pinpointing the site of inflow of an endoleak. RESULTS: An endoleak was detected in 23 patients. Seventeen of the 23 dynamic series were technically successful (no disturbing artifacts limiting the diagnostic value). Using MRI our findings were: 2 type I, 6 type II, 1 type III, no type IV endoleaks and in 14 cases classification could not be made. The classification results for MRI plus the dynamic CE-MRA were: 2 type I, 12 type II, 1 type III, no type IV endoleaks and in eight cases classification could not be made. In six cases the dynamic MRA allowed classification of the endoleak, which was not possible with the non-dynamic images alone (p=0.091, Fisher exact). CONCLUSION: This pilot study shows that dynamic CE-MRA can have additional value in the classification of endoleaks. Dynamic CE-MRA might obviate the need for diagnostic digital subtraction angiography and aid planning for intervention.

Lanthanide bearing microparticulate systems for multi-modality imaging and targeted therapy of cancer.

The rapid developments of high-resolution imaging techniques are offering unique possibilities for the guidance and follow up of recently developed sophisticated anticancer therapies. Advanced biodegradable drug delivery systems, e.g. based on liposomes and polymeric nanoparticles or microparticles, are very effective tools to carry these anticancer agents to their site of action. Elements from the group of lanthanides have very interesting physical characteristics for imaging applications and are the ideal candidates to be co-loaded either in their non-radioactive or radioactive form into these advanced drug delivery systems because of the following reasons: Firstly, they can be used both as magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents and for single photon emission computed tomography (SPECT). Secondly, they can be used for radionuclide therapies which, importantly, can be monitored with SPECT, CT, and MRI. Thirdly, they have a relatively low toxicity, especially when they are complexed to ligands. This review gives a survey of the currently developed lanthanide-loaded microparticulate systems that are under investigation for cancer imaging and/or cancer therapy.

[Nobel Prize for physiology or medicine in 2003 awarded to the fathers of magnetic resonance imaging]. / Nobelprijs Fysiologie of Geneeskunde 2003 voor de grondleggers van MRI.

The 2003 Nobel Prize for Physiology or Medicine has been awarded to the American physical chemist Paul Lauterbur (1929) and the British physicist Peter Mansfield (1933) for their discoveries in the field of magnetic resonance imaging (MRI). Lauterbur devised a method to encode the nuclear magnetic resonance relaxation information in an object spatially and to reproduce it as an image. Mansfield succeeded in exciting a slice perpendicular to the gradient direction, which enabled him to define a third dimension directly. In addition, he developed methods to enhance the speed of imaging. A third scientist, the physician Raymond Damadian, although equally a pioneer in the field of MRI, was--disputably--not a laureate.

Endovascular interventional magnetic resonance imaging.

Minimally invasive interventional radiological procedures, such as balloon angioplasty, stent placement or coiling of aneurysms, play an increasingly important role in the treatment of patients suffering from vascular disease. The non-destructive nature of magnetic resonance imaging (MRI), its ability to combine the acquisition of high quality anatomical images and functional information, such as blood flow velocities, perfusion and diffusion, together with its inherent three dimensionality and tomographic imaging capacities, have been advocated as advantages of using the MRI technique for guidance of endovascular radiological interventions. Within this light, endovascular interventional MRI has emerged as an interesting and promising new branch of interventional radiology. In this review article, the authors will give an overview of the most important issues related to this field. In this context, we will focus on the prerequisites for endovascular interventional MRI to come to maturity. In particular, the various approaches for device tracking that were proposed will be discussed and categorized. Furthermore, dedicated MRI systems, safety and compatibility issues and promising applications that could become clinical practice in the future will be discussed.

Magnetic resonance techniques in hemodialysis access management.

In this review we describe current applications and future perspectives of MR angiography, MR flow quantification, and interventional MRI in hemodialysis access management. Each section starts with a brief overview of the main techniques that are currently available or under development. This is followed by a survey of the pertinent literature. Each section concludes with a discussion of the reported findings and an indication of research opportunities.

Quantitative cerebral perfusion MRI and CO2 reactivity measurements in patients with symptomatic internal carotid artery occlusion.

Quantitative perfusion MRI is a promising new technique capable of offering information on cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). However, it is still unclear how these perfusion parameters relate to the underlying physiological indicators and how they compare to conventional techniques. The purpose of this study was to investigate how quantitative perfusion MRI is related to the cerebrovascular reactivity as measured by transcranial Doppler ultrasonography (TCD) in combination with a CO2 stimulus in patients with a symptomatic occlusion of the internal carotid artery (ICA). Thirty-nine patients with transient or minor disabling retinal or hemispheric ischemic symptoms and an occlusion of the ICA underwent quantitative perfusion MRI and CO2 reactivity measurements by TCD. Perfusion parameters were correlated with cerebrovascular reactivity measurements and compared with measurements of control subjects. The results of this study show a negative correlation between the cerebrovascular reactivity and the time to bolus peak (TBP) both for gray (r = -0.26, P = 0.035) and white matter (r = -0.28, P = 0.026). No correlation between resting CBV, CBF, or MTT and cerebrovascular reactivity was found. Our results indicate that an increase in TBP reflects a poor development of collateral flow, which is supported by a relatively low CO2 reactivity in these patients.

Localization of intravascular devices with paramagnetic markers in MR images.

Magnetic resonance imaging (MRI) offers potential advantages over conventional X-ray techniques for guiding and evaluating intravascular interventions. The development of methods to safely and robustly localize and track devices under MRI guidance is mandatory to enable automatic scan plane adaptation so as to exploit the three-dimensional imaging capabilities of the MRI scanner. With regard to the issue of radiofrequency-induced heating, passive approaches to catheter tracking are inherently safe. These techniques visualize intravascular devices by exploiting the susceptibility artifacts associated with the devices. To promote conspicuity, the devices are equipped with paramagnetic markers. This paper introduces a method to enable automatic localization of devices by its ability to recognize markers in two-dimensional MR images. The method requires a coarse segmentation of the vasculature of interest, and consists of two steps. First, it performs a series of postprocessing operations including calculation of the winding number image and of the Laplacian image to detect marker candidates in the image. Second, the device is localized by matching the detected pattern of candidates to the known distance template of the device markers. Results of an animal experiment and of a clinical application are demonstrated. Validation in phantom experiments shows that the method is able to localize the device in 95% of the cases.

Background suppression using magnetization preparation for contrast-enhanced MR projection angiography.

In contrast-enhanced MR projection angiography, vessel conspicuity is determined by the T(1)-weighted signal difference between blood and surrounding tissues. For slice-selective excitation pulses, the excitation angle varies across the slice, leading to poor saturation of the background signal at the slice edge and reducing the blood-background signal difference. This work reports on the use of magnetization preparation to enhance the T(1)-weighted contrast between blood and background tissue. Applying the prepulse nonselectively reduces the influence of the slice profile imperfections of the excitation pulse by keeping the background tissue at the slice edge saturated. Analytical calculations and in vitro experiments show that a prepulse angle of 110 degrees -130 degrees and a delay time of 20-25 ms enhance the contrast between contrast-enhanced blood (T(1) < 50 ms) and background tissues (T(1) > 200 ms), and improve the slice weighting profile. Magnetization preparation is shown to effectively suppress signal from background tissue, resulting in a threefold increase of the vessel-to-background signal ratio. Magnetization preparation eliminates the need for subtraction at the cost of a slight increase in scan time. Possible applications, such as projection MRA, detection of contrast arrival, and test-bolus tracking are demonstrated in a pig model. Magn Reson Med 46:78-87, 2001.

MRA of hemodialysis access grafts and fistulae using selective contrast injection and flow interruption.

MR is a potentially attractive modality for evaluating hemodialysis access anatomy and function. However, the wide range of flow rates in the hemodialysis access complicates interpretation of phase contrast, time-of-flight, and even contrast-enhanced MR angiograms. At high flow rates, signal voids may easily arise at mild narrowings or sharp-angled anastomoses. A method is proposed which visualizes hemodialysis accesses without flow artifacts. Diluted Gd-DTPA is hand-injected directly into the access, while a cuff is used to reduce and subsequently interrupt access flow. Filling of the access is monitored using a fast projection technique with complex subtraction. When filling is satisfactory, a 3D acquisition is started. The feasibility of this selective contrast-enhanced MR angiography technique is demonstrated in four Cimino-fistulae and four PTFE grafts. Magn Reson Med 45:557-561, 2001.

MR imaging of vascular stents: effects of susceptibility, flow, and radiofrequency eddy currents.

PURPOSE: The purpose of this in vitro study was to examine the various sources of artifacts in magnetic resonance (MR) imaging and angiography of vascular stents. MATERIALS AND METHODS: Five low-artifact stents-Wallstent (cobalt alloy), Memotherm (nitinol), Perflex (stainless steel), Passager (tantalum), and Smart (nitinol)-were imaged in a vascular flow phantom, consisting of a thin-walled cellulose vessel model connected to a pump system. The echo time and the angulation of the stents with respect to the direction of the main magnetic field were varied. Spin echo and gradient echo images as well as three-dimensional MR angiograms were obtained to study the effects of flow, magnetic susceptibility, and radiofrequency-induced eddy currents. RESULTS: Susceptibility artifacts were restricted to the stents' direct environment and were mildest at short echo times and with the stents aligned with the main magnetic field. Nitinol stents showed less artifacts than steel stents did. Radiofrequency artifacts obscuring the stent lumen and flow-related lumen displacement were seen in all stents. The extent to which these occurred depended on strut geometry and orientation. CONCLUSIONS: For low-artifact stents, the material the stent is made of is not the only important factor in the process of artifact formation. Susceptibility artifacts, radiofrequency eddy currents and flow-related artifacts all contribute to the image distortion, and are dependent on the geometry and orientation of the struts and on the orientation of the stent in the main magnetic field.

Correcting partial volume artifacts of the arterial input function in quantitative cerebral perfusion MRI.

To quantify cerebral perfusion with dynamic susceptibility contrast MRI (DSC-MRI), one needs to measure the arterial input function (AIF). Conventionally, one derives the contrast concentration from the DSC sequence by monitoring changes in either the amplitude or the phase signal on the assumption that the signal arises completely from blood. In practice, partial volume artifacts are inevitable because a compromise has to be reached between the temporal and spatial resolution of the DSC acquisition. As the concentration of the contrast agent increases, the vector of the complex blood signal follows a spiral-like trajectory. In the case of a partial-volume voxel, the spiral is located around the static contribution of the surrounding tissue. If the static contribution of the background tissue is disregarded, estimations of the contrast concentration will be incorrect. By optimizing the correspondence between phase information and amplitude information one can estimate the origin of the spiral, and thereupon correct for partial volume artifacts. This correction is shown to be accurate at low spatial resolutions for phantom data and to improve the AIF determination in a clinical example. Magn Reson Med 45:477-485, 2001.