isoPhasor: a generic and precise marker visualization, localization, and quantification method based on phase saddles in 3D MR imaging.

PURPOSE: To derive a generic approach for accurate localization and characterization of susceptibility markers in MRI, compatible with many common types of pulse sequences, sampling trajectories, and acceleration methods. THEORY AND METHODS: A susceptibility marker's dipolar phase evolution creates 3 saddles in the phase gradient of the spatial encoding, for each sampled data point in k-space. The signal originating from these saddles can be focused at the location of the marker to create positive contrast. The required phase shift can be calculated from the scan parameters and the marker properties, providing a marker detection algorithm generic for different scan types. The method was validated numerically and experimentally for a broad range of spherical susceptibility markers (0.3 < radius < 1.6 mm, 10 < |∆χ| < 3300 ppm), under various conditions. RESULTS: For all numerical and experimental phantoms, the average localization error was below one third of the voxel size, whereas the average error in magnetic strength quantification was 7%. The experiments included different pulse sequences (gradient echo, spin echo [SE], and free induction decay scans), sampling strategies (Cartesian, radial), and acceleration methods (echo planar imaging EPI, turbo SE). CONCLUSION: Spherical markers can be identified from their phase saddles, enabling clear visualization, precise localization, and accurate quantification of their magnetic strength, in a wide range of clinically relevant pulse sequences and sampling strategies.

Short and long time MR signal behavior of randomly distributed water and fat-numerical simulations.

The MR time-signal behavior of water has been reported to be different on short and long time scales for systems of randomly distributed perturbers in water in the static dephasing regime. Up to now, the signal of the perturbers in such systems has not been taken into consideration. Water-fat emulsions are macroscopically homogeneous systems and can be considered as microscopically randomly distributed perturbing fat spheres embedded in water. In such water-fat systems, the signal of the perturber, fat, cannot be ignored. Since water and fat are within the same system, the fat signal behavior may show similarities with water, with differences in short and long time scales. This could complicate fat-referenced MR thermometry (MRT) methods such as multi-gradient echo-based (MGE) MRT. Simulations were performed using a numerical phantom comprising spherical fat objects embedded in a spherical water medium. To characterize the fat signal, the theoretical signal description of water was fitted to the simulated fat signal. The simulated signals were sampled as an MGE signal and MGE MRT was used to calculate temperatures. The sampling was done with and without delay, to investigate the effect on the temperature error of the time ranges in which the signal was sampled. It was confirmed that the fat signal behavior was similar to that of water and consisted of two regimes. The separation between the short and long time scales was approximately at 55 ms for fat, as compared with 8.9 ms for water. Without delayed signal sampling, the MGE MRT temperature error was about 2.5°C. With delayed sampling such that both the water and the fat signals were either in the short or in the long time scale the error was reduced to 0.2°C.

Influence of water and fat heterogeneity on fat-referenced MR thermometry.

PURPOSE: To investigate the effect of the aqueous and fatty tissue magnetic susceptibility distribution on absolute and relative temperature measurements as obtained directly from the water/fat (w/f) frequency difference. METHODS: Absolute thermometry was investigated using spherical phantoms filled with pork and margarine, which were scanned in three orthogonal orientations. To evaluate relative fat referencing, multigradient echo scans were acquired before and after heating pork tissue via high-intensity focused ultrasound (HIFU). Simulations were performed to estimate the errors that can be expected in human breast tissue. RESULTS: The sphere experiment showed susceptibility-related errors of 8.4 °C and 0.2 °C for pork and margarine, respectively. For relative fat referencing measurements, fat showed pronounced phase changes of opposite polarity to aqueous tissue. The apparent mean temperature for a numerical breast model assumed to be 37 °C was 47.2 ± 21.6 °C. Simulations of relative fat referencing for a HIFU sonication (ΔT = 29.7 °C) yielded a maximum temperature error of 6.6 °C compared with 2.5 °C without fat referencing. CONCLUSION: Variations in the observed frequency difference between water and fat are largely due to variations in the w/f spatial distribution. This effect may lead to considerable errors in absolute MR thermometry. Additionally, fat referencing may exacerbate rather than correct for proton resonance frequency shift-temperature measurement errors.

Geometrically undistorted MRI in the presence of field inhomogeneities using compressed sensing accelerated broadband 3D phase encoded turbo spin-echo imaging.

In this study, we explore the potential of compressed sensing (CS) accelerated broadband 3D phase-encoded turbo spin-echo (3D-PE-TSE) for the purpose of geometrically undistorted imaging in the presence of field inhomogeneities. To achieve this goal 3D-PE-SE and 3D-PE-TSE sequences with broadband rf pulses and dedicated undersampling patterns were implemented on a clinical scanner. Additionally, a 3D multi-spectral spin-echo (ms3D-SE) sequence was implemented for reference purposes. First, we demonstrated the influence of susceptibility induced off-resonance effects on the spatial encoding of broadband 3D-SE, ms3D-SE, 3D-PE-SE and 3D-PE-TSE using a grid phantom containing a titanium implant (Δχ = 182 ppm) with x-ray CT as a gold standard. These experiments showed that the spatial encoding of 3D-PE-(T)SE was unaffected by susceptibility induced off-resonance effects, which caused geometrical distortions and/or signal hyper-intensities in broadband 3D-SE and, to a lesser extent, in ms3D-SE frequency encoded methods. Additionally, an SNR analysis was performed and the temporally resolved signal of 3D-PE-(T)SE sequences was exploited to retrospectively decrease the acquisition bandwidth and obtain field offset maps. The feasibility of CS acceleration was studied retrospectively and prospectively for the 3D-PE-SE sequence using an existing CS algorithm adapted for the reconstruction of 3D data with undersampling in all three phase encoded dimensions. CS was combined with turbo-acceleration by variable density undersampling and spherical stepwise T2 weighting by randomly sorting consecutive echoes in predefined spherical k-space layers. The CS-TSE combination resulted in an overall acceleration factor of 60, decreasing the original 3D-PE-SE scan time from 7 h to 7 min. Finally, CS accelerated 3D-PE-TSE in vivo images of a titanium screw were obtained within 10 min using a micro-coil demonstrating the feasibility of geometrically undistorted MRI near severe field inhomogeneities.

Holmium-lipiodol-alginate microspheres for fluoroscopy-guided embolotherapy and multimodality imaging.

Embolotherapy is a minimally invasive transcatheter technique aiming at reduction or complete obstruction of the blood flow by infusion of micro-sized particles in order to induce tumor regression. A major drawback of the current commercially available and clinically used microspheres is that they cannot be detected in vivo with medical imaging techniques, impeding intra- and post-procedural feedback. It can be expected that real-time monitoring of microsphere infusion and post-procedural imaging will result in better predictability and higher efficacy of the treatment. In this study, a novel microsphere formulation has been developed that can be visualized with fluoroscopy, X-ray computed tomography (CT) and magnetic resonance imaging (MRI). The microspheres were prepared with the JetCutter technique and consist of alginate (matrix-forming polymer), holmium (cross-linking and MRI contrast agent), lipiodol (radiopaque contrast agent) and Pluronic F-68 (surfactant). The mean size (±SEM) of the hydrated holmium-lipiodol-alginate microspheres (Ho-lip-ams) was 570±12 µm with a holmium content of 0.38±0.01% (w/w). Stability studies showed that the microspheres remained intact during incubation for two weeks in fetal calf serum (FCS) at 37 °C. The inclusion of lipiodol in the microspheres rendered excellent visualization capabilities for fluoroscopy and CT, whereas the holmium ions, which keep the alginate network together, also allow MR imaging. In this study it was shown that single sphere detection was possible by fluoroscopy, CT and MRI. The Ho-lip-ams were visualized in real-time, during infusion in a porcine kidney using fluoroscopy, and post-procedural, the deposition of the microspheres was examined with fluoroscopy, (cone beam rotational) CT and MRI. The different imaging modalities showed similar deposition patterns of the microspheres within the organ. The combination of intra-procedural visualization, multimodality imaging for patient follow-up and the possibility of quantification offers a new and promising method for more safe, efficient and successful embolization treatment.

A setup for administering TMS to medial and lateral cortical areas during whole-brain FMRI recording.

SUMMARY: Stimulating brain areas with transcranial magnetic stimulation (TMS) while concurrently and noninvasively recording brain activity changes through functional MRI enables a new range of investigations about causal interregional interactions in the human brain. However, standard head-coil arrangements for current methods for concurrent TMS-functional MRI somewhat restrict the cortical brain regions that can be targeted with TMS because space in typical MR head coils is limited. Another limitation for concurrent TMS-functional MRI approaches concerns the estimation of the precise stimulation site, which can limit the interpretation of the activity changes induced by TMS and increase the variability of the stimulation effects. Here, we present a novel approach using flexible MR receiver coils, allowing for stimulation of a large part of the cortex including more lateral areas. Furthermore, we present a fast and economical method to determine the precise location of the stimulation coil during scanning. This point-based registration method can accurately compute, during scanning, where TMS pulses are delivered. We validated this approach by stimulating medial (M1) and more lateral (dorsal part of the supramarginal gyrus) brain areas concurrently with functional MRI. Activation close to but not directly at the stimulated location and in distal areas connected to the targeted site was observed. This study provides a proof of concept that TMS of medial and lateral brain areas is feasible without significantly compromising brain coverage and that one can precisely determine the exact coil location inside the bore to verify targeting of brain areas.

Absolute MR thermometry using nanocarriers.

Accurate time-resolved temperature mapping is crucial for the safe use of hyperthermia-mediated drug delivery. We here propose a magnetic resonance imaging temperature mapping method in which drug delivery systems serve not only to improve tumor targeting, but also as an accurate and absolute nano-thermometer. This method is based on the temperature-dependent chemical shift difference between water protons and the protons in different groups of drug delivery systems. We show that the chemical shift of the protons in the ethylene oxide group in polyethylene glycol (PEG) is temperature-independent, whereas the proton resonance of water decreases with increasing temperature. The frequency difference between both resonances is linear and does not depend on pH and physiological salt conditions. In addition, we show that the proton resonance of the methyl group in N-(2-hydroxypropyl)-methacrylamide (HPMA) is temperature-independent. Therefore, PEGylated liposomes, polymeric mPEG-b-pHPMAm-Lac2 micelles and HPMA copolymers can provide a temperature-independent reference frequency for absolute magnetic resonance (MR) thermometry. Subsequently, we show that multigradient echo MR imaging with PEGylated liposomes in situ allows accurate, time-resolved temperature mapping. In conclusion, nanocarrier materials may serve as highly versatile tools for tumor-targeted drug delivery, acting not only as hyperthermia-responsive drug delivery systems, but also as accurate and precise nano-thermometers.

Detecting breast microcalcifications with high-field MRI.

The aim of this study was to detect microcalcifications in human whole breast specimens using high-field MRI. Four mastectomy specimens, obtained with approval of the institutional review board, were subjected to gradient-echo MRI acquisitions on a high-field MR scanner. The phase derivative was used to detect microcalcifications. The echo time and imaging resolution were varied to study the sensitivity of the proposed method. Computed tomography images of the mastectomy specimens and prior acquired mammography images were used to validate the results. A template matching algorithm was designed to detect microcalcifications automatically. The three spatial derivatives of the signal phase surrounding a field-perturbing object allowed three-dimensional localization, as well as the discrimination of diamagnetic field-perturbing objects, such as calcifications, and paramagnetic field-perturbing structures, e.g. blood. A longer echo time enabled smaller disturbances to be detected, but also resulted in shading as a result of other field-disturbing materials. A higher imaging resolution increased the detection sensitivity. Microcalcifications in a linear branching configuration that spanned over 8 mm in length were detected. After manual correction, the automatic detection tool identified up to 18 microcalcifications within the samples, which was in close agreement with the number of microcalcifications found on previously acquired in vivo mammography images. Microcalcifications can be detected by MRI in human whole breast specimens by the application of phase derivative imaging.

Correction of proton resonance frequency shift MR-thermometry errors caused by heat-induced magnetic susceptibility changes during high intensity focused ultrasound ablations in tissues containing fat.

PURPOSE: In this study, we aim to demonstrate the sensitivity of proton resonance frequency shift (PRFS) -based thermometry to heat-induced magnetic susceptibility changes and to present and evaluate a model-based correction procedure. THEORY AND METHODS: To demonstrate the expected temperature effect, field disturbances during high intensity focused ultrasound sonications were monitored in breast fat samples with a three-dimensional (3D) gradient echo sequence. To evaluate the correction procedure, the interface of tissue-mimicking ethylene glycol gel and fat was sonicated. During sonication, the temperature was monitored with a 2D dual flip angle multi-echo gradient echo sequence, allowing for PRFS-based relative and referenced temperature measurements in the gel and T1 -based temperature measurements in fat. The PRFS-based measurement in the gel was corrected by minimizing the discrepancy between the observed 2D temperature profile and the profile predicted by a 3D thermal model. RESULTS: The HIFU sonications of breast fat resulted in a magnetic field disturbance which completely disappeared after cooling. For the correction method, the 5th to 95th percentile interval of the PRFS-thermometry error in the gel decreased from 3.8°C before correction to 2.0-2.3°C after correction. CONCLUSION: This study has shown the effects of magnetic susceptibility changes induced by heating of breast fatty tissue samples. The resultant errors can be reduced by the use of a model-based correction procedure.

A dual-plane co-RASOR technique for accurate and rapid tracking and position verification of an Ir-192 source for single fraction HDR brachytherapy.

Effective high-dose-rate (HDR) treatment requires accurate and independent treatment verification to ensure that the treatment proceeds as prescribed, in particular if a high dose is given, as in single fraction therapy. Contrary to CT imaging and fluoroscopy, MR imaging provides high soft tissue contrast. Conventional MR techniques, however, do not offer the temporal resolution in combination with the 3D spatial resolution required for accurate brachytherapy source localization. We have developed an MR imaging method (center-out RAdial Sampling with Off-Resonance (co-RASOR)) that generates high positive contrast in the geometrical center of field perturbing objects, such as HDR brachytherapy sources. co-RASOR generates high positive contrast in the geometric center of an Ir-192 source by applying a frequency offset to center-out encoded data. To obtain high spatial accuracy in 3D with adequate temporal resolution, two orthogonal center-out encoded 2D images are applied instead of a full 3D acquisition. Its accuracy in 3D is demonstrated by 3D MRI and CT. The 2D images show high positive contrast in the geometric center of non-radioactive Ir-192 sources, with signal intensities up to 160% of the average signal intensity in the surrounding medium. The accuracy with which the center of the Ir-192 source is located by the dual-plane MRI acquisition corresponds closely to the accuracy obtained by 3D MRI and CT imaging. The positive contrast is shown to be obtained in homogeneous and in heterogeneous tissue. The dual-plane MRI technique allows the brachytherapy source to be tracked in 3D with millimeter accuracy with a temporal resolution of approximately 4 s.

Multiple single-point imaging (mSPI) as a tool for capturing and characterizing MR signals and repetitive signal disturbances with high temporal resolution: the MRI scanner as a high-speed camera.

In this paper we aim to lay down and demonstrate the use of multiple single-point imaging (mSPI) as a tool for capturing and characterizing steady-state MR signals and repetitive disturbances thereof with high temporal resolution. To achieve this goal, various 2D mSPI sequences were derived from the nearest standard 3D imaging sequences by (i) replacing the excitation of a 3D slab by the excitation of a 2D slice orthogonal to the read axis, (ii) setting the readout gradient to zero, and (iii) leaving out the inverse Fourier transform in the read direction. The thus created mSPI sequences, albeit slow with regard to the spatial encoding part, were shown to result into a series of densely spaced 2D single-point images in the time domain enabling monitoring of the evolution of the magnetization with a high temporal resolution and without interference from any encoding gradients. The high-speed capabilities of mSPI were demonstrated by capturing and characterizing the free induction decays and spin echoes of substances with long T2s (>30 ms) and long and short T2*s (4 - >30 ms) and by monitoring the perturbation of the transverse magnetization by, respectively, a titanium cylinder, representing a static disturbance; a pulsed magnetic field gradient, representing a stimulus inherent to a conventional MRI experiment; and a pulsed electric current, representing an external stimulus. The results of the study indicate the potential of mSPI for assessing the evolution of the magnetization and, when properly synchronized with the acquisition, repeatable disturbances thereof with a temporal resolution that is ultimately limited by the bandwidth of the receiver, but in practice governed by the SNR of the experiment and the magnitude of the disturbance. Potential applications of mSPI can be envisaged in research areas that are concerned with MR signal behavior, MR system performance and MR evaluation of magnetically evoked responses.

Direct in vitro comparison of six three-dimensional positive contrast methods for susceptibility marker imaging.

PURPOSE: To compare different techniques for positive contrast imaging of susceptibility markers with MRI for three-dimensional visualization. As several different techniques have been reported, the choice of the suitable method depends on its properties with regard to the amount of positive contrast and the desired background suppression, as well as other imaging constraints needed for a specific application. MATERIALS AND METHODS: Six different positive contrast techniques are investigated for their ability to image at 3 Tesla a single susceptibility marker in vitro. The white marker method (WM), susceptibility gradient mapping (SGM), inversion recovery with on-resonant water suppression (IRON), frequency selective excitation (FSX), fast low flip-angle positive contrast SSFP (FLAPS), and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) were implemented and investigated. RESULTS: The different methods were compared with respect to the volume of positive contrast, the product of volume and signal intensity, imaging time, and the level of background suppression. Quantitative results are provided, and strengths and weaknesses of the different approaches are discussed. CONCLUSION: The appropriate choice of positive contrast imaging technique depends on the desired level of background suppression, acquisition speed, and robustness against artifacts, for which in vitro comparative data are now available.

Microbrachytherapy using holmium-166 acetylacetonate microspheres: a pilot study in a spontaneous cancer animal model.

PURPOSE: Holmium-166 acetylacetonate microspheres ((166)Ho-AcAc-MS) are proposed as an intratumoral radioablation device. This article presents a pilot study in housecats with unresectable liver cancer. Feasibility and tolerability of intratumoral administrations of (166)Ho-AcAc-MS was investigated. METHODS AND MATERIALS: Three cats with unresectable liver tumors of different histotype were included. One cat had hepatocellular carcinoma (HCC), one had cholangiocarcinoma (CC), and one had a malignant epithelial liver tumor (MELT) of unspecified histotype. (166)Ho-AcAc-MS were injected percutaneously under ultrasound guidance into the tumors. Followup consisted of physical examinations and hematologic and biochemical analyses. RESULTS: (166)Ho-AcAc-MS were administered to three liver tumor-bearing cats. The treatment was well tolerated and the clinical condition, that is body weight, alertness, mobility, and coat condition of the animals improved markedly. Most biochemical and hematologic parameters normalized shortly after treatment. Life of all cats was extended and associated with a good quality of life. The HCC cat that received 33-Gy tumor-absorbed dose was euthanized 6 months after the first administration owing to disease progression. The MELT cat received 99-Gy tumor dose and was euthanized 3 months posttreatment owing to bacterial meningitis. The CC cat received 333Gy and succumbed 4 months after the first treatment owing to the formation of a pulmonary embolism. CONCLUSIONS: Percutaneous intratumoral injection of radioactive (166)Ho-AcAc-MS is feasible in liver tumor-bearing cats. The findings of this pilot study indicate that (166)Ho-AcAc-MS may constitute safe brachytherapeutic microspheres and warrant studies to confirm the clinical utility of this novel brachytherapy device.

Alginate-lanthanide microspheres for MRI-guided embolotherapy.

In cancer therapy, a promising treatment option to accomplish a high tumor-to-normal-tissue ratio is endovascular intervention with microsized particles, such as embolotherapy. In this study, alginate microspheres (ams) were prepared with the JetCutter technique, which is based on cutting a sodium alginate solution jet stream into small droplets of uniform size which are then cross-linked with different lanthanides or iron-III, resulting in microspheres of a predefined size which can be visualized by magnetic resonance imaging (MRI). The microspheres were investigated for their size and morphology (light microscopy and scanning electron microscopy analysis), cation content and MRI properties. The lanthanide-ams formulations, with a uniform size of 250 µm and a cation content between 0.72-0.94%, showed promising results for MR imaging. This was further demonstrated for Ho(3+)-cross-linked alginate microspheres (Ho(3+)-ams), the most potent microsphere formulation with respect to MR visualization, allowing single sphere detection and detailed microsphere distribution examination. Intravascular infusion of Ho(3+)-ams by catherization of ex vivo rabbit and porcine liver tissue and assessment of the procedure with MRI clearly showed accumulation and subsequently embolization of the targeted vessels, allowing accurate monitoring of the microsphere biodistribution throughout the tissue. Therefore, the different alginate-lanthanide microsphere formulations developed in this study show great potential for utilization as image-guided embolotherapy agents.

On the utility of spectroscopic imaging as a tool for generating geometrically accurate MR images and parameter maps in the presence of field inhomogeneities and chemical shift effects.

Lack of spatial accuracy is a recognized problem in magnetic resonance imaging (MRI) which severely detracts from its value as a stand-alone modality for applications that put high demands on geometric fidelity, such as radiotherapy treatment planning and stereotactic neurosurgery. In this paper, we illustrate the potential and discuss the limitations of spectroscopic imaging as a tool for generating purely phase-encoded MR images and parameter maps that preserve the geometry of an object and allow localization of object features in world coordinates. Experiments were done on a clinical system with standard facilities for imaging and spectroscopy. Images were acquired with a regular spin echo sequence and a corresponding spectroscopic imaging sequence. In the latter, successive samples of the acquired echo were used for the reconstruction of a series of evenly spaced images in the time and frequency domain. Experiments were done with a spatial linearity phantom and a series of test objects representing a wide range of susceptibility- and chemical-shift-induced off-resonance conditions. In contrast to regular spin echo imaging, spectroscopic imaging was shown to be immune to off-resonance effects, such as those caused by field inhomogeneity, susceptibility, chemical shift, f(0) offset and field drift, and to yield geometrically accurate images and parameter maps that allowed object structures to be localized in world coordinates. From these illustrative examples and a discussion of the limitations of purely phase-encoded imaging techniques, it is concluded that spectroscopic imaging offers a fundamental solution to the geometric deficiencies of MRI which may evolve toward a practical solution when full advantage will be taken of current developments with regard to scan time reduction. This perspective is backed up by a demonstration of the significant scan time reduction that may be achieved by the use of compressed sensing for a simple phantom.

MRI-based biodistribution assessment of holmium-166 poly(L-lactic acid) microspheres after radioembolisation.

OBJECTIVES: To demonstrate the feasibility of MRI-based assessment of the intrahepatic Ho-PLLA-MS biodistribution after radioembolisation in order to estimate the absorbed radiation dose. METHODS: Fifteen patients were treated with holmium-166 ((166)Ho) poly(L-lactic acid)-loaded microspheres (Ho-PLLA-MS, mean 484 mg; range 408-593 mg) in a phase I study. Multi-echo gradient-echo MR images were acquired from which R (2) maps were constructed. The amount of Ho-PLLA-MS in the liver was determined by using the relaxivity r (2) of the Ho-PLLA-MS and compared with the administered amount. Quantitative single photon emission computed tomography (SPECT) was used for comparison with MRI regarding the whole liver absorbed radiation dose. RESULTS: R (2) maps visualised the deposition of Ho-PLLA-MS with great detail. The mean total amount of Ho-PLLA-MS detected in the liver based on MRI was 431 mg (range 236-666 mg) or 89 ± 19 % of the delivered amount (correlation coefficient r = 0.7; P < 0.01). A good correlation was found between the whole liver mean absorbed radiation dose as assessed by MRI and SPECT (correlation coefficient r = 0.927; P < 0.001). CONCLUSION: MRI-based dosimetry for holmium-166 radioembolisation is feasible. Biodistribution is visualised with great detail and quantitative measurements are possible.

Alias subtraction more efficient than conventional zero-padding in the Fourier-based calculation of the susceptibility induced perturbation of the magnetic field in MR.

Forward calculation of the susceptibility induced field shift by Fourier-based procedures requires spatial zero-padding to prevent aliasing artifacts (periodic wrap-around). Padding with a factor of two gives accurate results, however, halves the maximal attainable resolution, and slows down the calculation, which may hamper the feasibility of real-time calculations. Herein is proposed to first perform the calculation at the original resolution--allowing aliasing-and to remove aliasing with an additional convolution in a lower resolution, to alleviate these restrictions regarding memory size and calculation speed, a procedure we termed "virtual" zero-padding. Virtual zero-padding was numerically and experimentally tested and validated with conventional zero-padding and the analytical solution (in the case of spheres) on several phantoms. A demonstration of the increased efficiency is given by implementing virtual zero-padding in a dynamic calculation procedure. The improved efficiency is expected to be relevant regarding the ongoing increase in spatial and temporal resolution in ultra-high-field MRI. Procedures are presented for circular convolution using the discrete Green's function and k-space filtering using the continuous Green's function.

Magnetic resonance imaging-based radiation-absorbed dose estimation of 166Ho microspheres in liver radioembolization.

PURPOSE: To investigate the potential of magnetic resonance imaging (MRI) for accurate assessment of the three-dimensional (166)Ho activity distribution to estimate radiation-absorbed dose distributions in (166)Ho-loaded poly (L-lactic acid) microsphere ((166)Ho-PLLA-MS) liver radioembolization. METHODS AND MATERIALS: MRI, computed tomography (CT), and single photon emission CT (SPECT) experiments were conducted on an anthropomorphic gel phantom with tumor-simulating gel samples and on an excised human tumor-bearing liver, both containing known amounts of (166)Ho-PLLA-MS. Three-dimensional radiation-absorbed dose distributions were estimated at the voxel level by convolving the (166)Ho activity distribution, derived from quantitative MRI data, with a (166)Ho dose point-kernel generated by MCNP (Monte Carlo N-Particle transport code) and from Medical Internal Radiation Dose Pamphlet 17. MRI-based radiation-absorbed dose distributions were qualitatively compared with CT and autoradiography images and quantitatively compared with SPECT-based dose distributions. Both MRI- and SPECT-based activity estimations were validated against dose calibrator measurements. RESULTS: Evaluation on an anthropomorphic phantom showed that MRI enables accurate assessment of local (166)Ho-PLLA-MS mass and activity distributions, as supported by a regression coefficient of 1.05 and a correlation coefficient of 0.99, relating local MRI-based mass and activity calculations to reference values obtained with a dose calibrator. Estimated MRI-based radiation-absorbed dose distributions of (166)Ho-PLLA-MS in an ex vivo human liver visually showed high correspondence to SPECT-based radiation-absorbed dose distributions. Quantitative analysis revealed that the differences in local and total amounts of (166)Ho-PLLA-MS estimated by MRI, SPECT, and the dose calibrator were within 10%. Excellent agreement was observed between MRI- and SPECT-based dose-volume histograms. CONCLUSIONS: Quantitative MRI was demonstrated to provide accurate three-dimensional (166)Ho-PLLA-MS activity distributions, enabling localized intrahepatic radiation-absorbed dose estimation by convolution with a (166)Ho dose point-kernel for liver radioembolization treatment optimization and evaluation.

Selective depiction of susceptibility transitions using Laplace-filtered phase maps.

In this work, we aim to demonstrate the ability of Laplace-filtered three-dimensional (3D) phase maps to selectively depict the susceptibility transitions in an object. To realize this goal, it is first shown that both the Laplace derivative of the z component of the static magnetic field in an object and the Laplacian of the corresponding phase distribution may be expected to be zero in regions of constant or linearly varying susceptibility and to be nonzero when there is an abrupt change in susceptibility, for instance, at a single point, a ridge, an interface, an edge or a boundary. Next, a method is presented by which the Laplace derivative of a 3D phase map can be directly extracted from the complex data, without the need for phase unwrapping or subtraction of a reference image. The validity of this approach and of the theory behind it is subsequently demonstrated by simulations and phantom experiments with exactly known susceptibility distributions. Finally, the potential of the Laplace derivative analysis is illustrated by simulations with a Shepp-Logan digital brain phantom and experiments with a gel phantom containing positive and negative focal susceptibility deviations.

Quantification of holmium-166 loaded microspheres: estimating high local concentrations using a conventional multiple gradient echo sequence with S0-fitting.

PURPOSE: To provide a best estimate of the R 2* value and hence of the local concentration of highly paramagnetic holmium-166 loaded microspheres (HoMS) in voxels for which R 2* cannot be characterized by conventional fitting of multigradient echo (MGE) data because of fast signal decay due to high local concentrations. MATERIALS AND METHODS: A postprocessing method, S(0)-fitting, was implemented in a conventional R 2* fitting method that is used for quantification of HoMS. S(0)-fitting incorporates the estimated initial amplitude of the free induction decay (FID) curve, S(0), of neighboring voxels into the fitting procedure for voxels for which the conventional algorithm failed. The method was applied to HoMS in vitro and ex vivo in a rabbit liver. The performance of the S(0)-fitting method was evaluated by comparing results qualitatively and quantitatively with results obtained with quantitative ultrashort TE imaging (qUTE). RESULTS: Applying S(0)-fitting provided a best estimate for R 2* up to a value of about 2300 s(-1) compared with a maximum value of about 1000 s(-1) that could be characterized using conventional fitting. A good agreement was observed both qualitatively and quantitatively for in vitro experiments as well as for ex vivo rabbit liver experiments between results obtained with S(0)-fitting and results obtained with qUTE imaging. CONCLUSION: S(0)-fitting is a postprocessing method that can provide a best estimate of high R 2* values that cannot be characterized by conventional relaxometry. The method can be applied to conventional MGE datasets and was shown to be beneficial for quantification of high local concentrations of holmium-loaded microspheres.