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.

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.

Radioactive holmium acetylacetonate microspheres for interstitial microbrachytherapy: an in vitro and in vivo stability study.

PURPOSE: The clinical application of holmium acetylacetonate microspheres (HoAcAcMS) for the intratumoral radionuclide treatment of solid malignancies requires a thorough understanding of their stability. Therefore, an in vitro and an in vivo stability study with HoAcAcMS was conducted. METHODS: HoAcAcMS, before and after neutron irradiation, were incubated in a phosphate buffer at 37°C for 6 months. The in vitro release of holmium in this buffer after 6 months was 0.5%. Elemental analysis, scanning electron microscopy, infrared spectroscopy and time of flight secondary ion mass spectrometry were performed on the HoAcAcMS. RESULTS: After 4 days in buffer the acetylacetonate ligands were replaced by phosphate, without altering the particle size and surface morphology. HoAcAcMS before and after neutron irradiation were administered intratumorally in VX2 tumor-bearing rabbits. No holmium was detected in the faeces, urine, femur and blood. Histological examination of the tumor revealed clusters of intact microspheres amidst necrotic tissue after 30 days. CONCLUSION: HoAcAcMS are stable both in vitro and in vivo and are suitable for intratumoral radionuclide treatment.

Highly localized positive contrast of small paramagnetic objects using 3D center-out radial sampling with off-resonance reception.

In this article, we present a 3D imaging technique, applying center-out RAdial Sampling with Off-Resonance reception, to accurately depict and localize small paramagnetic objects with high positive contrast while suppressing long T(2) (*) components. The center-out RAdial Sampling with Off-Resonance reception imaging technique is a fully frequency-encoded 3D ultrashort echo time acquisition method, which uses a large excitation bandwidth and off-resonance reception. By manually introducing an offset, Δf(0), to the central reception frequency (f(0)), the typical radial signal pileup observed in 3D center-out sampling caused by a dipolar magnetic field disturbance can be shifted toward the source of the field disturbance, resulting in a hyperintense signal at the magnetic center of the small paramagnetic object. This was demonstrated both theoretically and using 1D time domain simulations. Experimental verification was done in a gel phantom and in inhomogeneous porcine tissue containing various objects with very different geometry and susceptibility, namely, subvoxel stainless steel spheres, a puncture needle, and paramagnetic brachytherapy seeds. In all cases, center-out RAdial Sampling with Off-Resonance reception was shown to generate high positive contrast exactly at the location of the paramagnetic object, as was confirmed by X-ray computed tomography.

Single shot MR tagging to quantify local tissue deformation during MRI-guided needle interventions: a feasibility study.

PURPOSE: In MRI-guided needle interventions, such as biopsies and brachytherapy, tissue deformation caused by needle movement may result in localization errors and thus hamper the outcome of the procedure. Monitoring the local tissue deformation provides the ability to compensate for it, e.g., by increasing the needle insertion depth. Fast MR scans are useful to track the needle, but cannot be used to quantify local tissue deformation, in case anatomical landmarks are missing. Artificial landmarks can be created by MR tagging. This method provides a spatial saturation pattern (tag) in the tissue. Deformation of this pattern reflects the tissue motion between tag creation and tag imaging. As the needle movement is nonperiodic, k-space cannot be acquired with a multishot approach, like is usually done for cardiac imaging. Hence, a single shot MR tagging sequence is needed, which entails tag creation, needle movement and tag acquisition. In this study, the feasibility of single shot MR tagging for MRI-guided needle interventions in phantom and volunteer experiments is shown. METHODS: Four different experiments were performed on a 1.5 T MR scanner: the first to quantify translations, the second to quantify rotations, the third to mimic a needle intervention, and the fourth to investigate the tag persistence in a volunteer. The tag pattern is created by a 1331 composite pulse. A balanced steady state free precession sequence is used for imaging. To minimize undesired changes in contrast or sharpness of the tag pattern, we chose a relatively small flip angle and a short imaging time in all experiments. In the volunteer experiments, we modified the sequence to also be able to inspect the influence of the used k-space sampling profile and the flip angle on the temporal persistence of image contrast and tag pattern. In all scans, head or surface coils were used for signal reception. RESULTS: In all experiments, the tag pattern was clearly visible and could be used to quantify the local tissue deformation caused by (needle) movement. Strong correlations between the actual and measured (angular) phantom motions were obtained. In the needle intervention experiment, the tag lines were perfectly horizontal when there was no needle movement. With needle movement, local tissue displacements up to 5 mm were observed. Volunteer's anatomy could be discriminated, despite the tag pattern. The tag pattern in the prostate, for example, could still be read in all tagging images acquired 2 s after creating the tag pattern. With optimized scan parameters the tag persistence was even longer. The best image tag contrast was obtained using a large flip angle and the profile order low-high, although the image was slightly blurred. CONCLUSIONS: This study demonstrates that single shot MR tagging can be used to quantify tissue deformation caused by needle movement. The in-vivo tag persistence is sufficient to enable the application of the tagging sequence during MRI-guided needle interventions in patients.

Holmium nanoparticles: preparation and in vitro characterization of a new device for radioablation of solid malignancies.

PURPOSE: The present study introduces the preparation and in vitro characterization of a nanoparticle device comprising holmium acetylacetonate for radioablation of unresectable solid malignancies. METHODS: HoAcAc nanoparticles were prepared by dissolving holmium acetylacetonate in chloroform, followed by emulsification in an aqueous solution of a surfactant and evaporation of the solvent. The diameter, surface morphology, holmium content, and zeta potential were measured, and thermal behavior of the resulting particles was investigated. The stability of the particles was tested in HEPES buffer. The r(2)* relaxivity of protons and mass attenuation coefficient of the nanoparticles were determined. The particle diameter and surface morphology were studied after neutron activation. RESULTS: Spherical particles with a smooth surface and diameter of 78 ± 10 nm were obtained, and the particles were stable in buffer. Neutron irradiation did not damage the particles, and adequate amounts of activity were produced for nuclear imaging and radioablation of malignancies through intratumoral injections. CONCLUSIONS: The present study demonstrates that HoAcAc nanoparticles were prepared using a solvent evaporation process. The particle diameter can easily be adapted and can be optimized for specific therapeutic applications and tumor types.

Phase gradient mapping as an aid in the analysis of object-induced and system-related phase perturbations in MRI.

In this note we wish to demonstrate the utility of phase gradient mapping (PGM) as an aid in the analysis and characterization of object-induced and system-related macroscopic phase perturbations in MRI. To achieve this goal, phase gradient maps and, if applicable, field gradient maps were derived from standard phase images via a forward difference operator taking into account phase wraps. By way of phantom experiments, PGM was shown to provide reliable phase and field gradient information, even in regions with multiple phase wraps. Phase gradient mapping was further shown to allow positive identification of local phase and field perturbations and global discrimination between positive and negative local susceptibility deviations. The suitability of PGM for in vivo studies was demonstrated by a 3D brain examination of a healthy volunteer.

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.

Regional brain perfusion in 12 cats measured with technetium-99m-ethyl cysteinate dimer pinhole single photon emission computed tomography (SPECT).

With the use of perfusion tracers, in vivo examination of the regional cerebral blood flow in cats can be performed with single photon emission computed tomography (SPECT). Reliable perfusion data of normal, healthy cats are necessary for future clinical studies or other research use. Therefore, this dataset of the regional perfusion pattern of the normal feline brain was created. Twelve cats were used in this study. Technetium-99m-ethyl cysteinate dimer ((99m)Tc-ECD) was injected intravenously and the acquisition, using a triple head gamma camera equipped with three multi-pinhole collimators (pinhole SPECT), was started 40 mins after tracer administration under general anaesthesia. Nineteen regions of interest were defined using 7T magnetic resonance images of the feline brain and a topographical atlas. Regional counts were normalised to the counts of two reference regions: the total brain and the cerebellum. The highest tracer uptake was noticed in the subcortical structures, and the lowest in the frontal cortex and the cerebellum. Also left-right asymmetry in the temporal cortex and a rostrocaudal gradient of 5% were observed.

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.

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.

MRI-guided robotic system for transperineal prostate interventions: proof of principle.

In this study, we demonstrate the proof of principle of the University Medical Center Utrecht (UMCU) robot dedicated to magnetic resonance imaging (MRI)-guided interventions in patients. The UMCU robot consists of polymers and non-ferromagnetic materials. For transperineal prostate interventions, it can be placed between the patient's legs inside a closed bore 1.5T MR scanner. The robot can manually be translated and rotated resulting in five degrees of freedom. It contains a pneumatically driven tapping device to automatically insert a needle stepwise into the prostate using a controller unit outside the scanning room. To define the target positions and to verify the needle insertion point and the needle trajectory, a high-resolution 3D balanced steady state free precession (bSSFP) scan that provides a T2/T1-weighted contrast is acquired. During the needle insertion fast 2D bSSFP images are generated to track the needle on-line. When the target position is reached, the radiation oncologist manually places a fiducial gold marker (small seed) at this location. In total two needle trajectories are used to place all markers. Afterwards, a high-resolution 3D bSSFP scan is acquired to visualize the fiducial gold markers. Four fiducial gold markers were placed transperineally into the prostate of a patient with a clinical stage T3 prostate cancer. In the generated scans, it was possible to discriminate the patient's anatomy, the needle and the markers. All markers were delivered inside the prostate. The procedure time was 1.5 h. This study proves that MRI-guided needle placement and seed delivery in the prostate with the UMCU robot are feasible.