Optimum selection for multi-interaction events in Compton-PET hybrid reconstruction: a Monte Carlo study.

In Compton PET, that has a scatterer inserted inside a PET ring, there are multi-interaction events that can be treated as both PET and Compton events. A PET event from multi-interaction events that include a Compton event and a photoelectric absorption event or two Compton events can be extracted by applying a PET recovery method. In this study, we aimed to establish a method to maximize image quality by utilizing such redundant events. We conducted brain-scale Monte Carlo simulations of a C-shaped Compton-PET geometry and a whole gamma imaging (WGI) geometry. Images were reconstructed by a hybrid image reconstruction method combining both PET and Compton events. The result showed that the spatial resolution was improved when treated as PET events while keeping the noise level. The effect of improvement was more significant in WGI than in C-shaped Compton PET because the number of events recovered as PET events having more accurate spatial information was much larger in WGI. When the PET-recovered multi-interaction events were also included as Compton events in the hybrid reconstruction, we did not observe any improvement in image quality, while the number of used events was largest. The results suggested that treating events as PET events exclusively was better for image quality.

Shear wave speed measurement bias in a viscoelastic phantom across six ultrasound elastography systems: a comparative study with transient elastography and magnetic resonance elastography.

PURPOSE: To quantify the bias of shear wave speed (SWS) measurements in a viscoelastic phantom across six different ultrasound (US) systems and to compare the SWS with those from transient elastography (TE) and magnetic resonance elastography (MRE). METHODS: A viscoelastic phantom of stiffness representing fibrotic liver or healthy thyroid was measured with nine (linear probe) and 10 (convex probe) modes of six different US-based shear wave elastography (SWE) systems using linear and convex probes. SWS measurements of three regions of interest were repeated thrice at two focal depths, coupling the probe to the phantom using a jig. An MRE system using three motion-encoding gradient frequencies of 60, 90, and 120 Hz and TE were also used to measure the stiffness of the phantom. RESULTS: The SWS from different SWE systems had mean coefficients of variation of 9.0-9.2% and 5.4-5.6% with linear and convex probes, respectively, in viscoelastic phantom measurement. The focal depth was a less significant source of SWS variability than the system. The total average SWS obtained with US-SWE systems was 19.9% higher than that obtained with MRE at 60 Hz, which is commonly used in clinical practice, and 31.5% higher than that obtained with TE using the M probe. CONCLUSIONS: Despite the measurement biases associated with the SWE systems, biases were not necessarily consistent, and they changed with the probes used and depth measured. The SWS of the viscoelastic phantom obtained using different modalities increased according to the shear wave frequency used.

Development of three-dimensional integral-type reconstruction formula for magnetic resonance elastography.

PURPOSE: The viscoelasticity (storage modulus and loss modulus) of living tissues is known to be related to diseases. Magnetic resonance elastography (MRE) is a quantitative method for non-invasive measuring viscoelasticity. The viscoelasticity is calculated from the elastic wave images using an inversion algorithm. The estimation accuracy of the inversion algorithm is degraded by background noise. This study aims to propose novel inversion algorithms that are applicable for noisy elastic wave images. METHODS: The proposed algorithms are based on the Voigt-type viscoelastic equation. The algorithms are designed to improve the noise robustness by avoiding direct differentiation of measurement data by virtue of Green's formula. Similarly, stabilization is introduced to the curl-operator which works to eliminate the compression waves in measurement data. To clarify the characteristics of the algorithms, the proposed algorithms were compared with the conventional algorithms using isotropic and anisotropic voxel numerical simulations and phantom experimental data. RESULTS: From the results of the numerical simulations, normalized errors of stiffness of proposed algorithms were 3% or less. The proposed algorithms mostly showed better results than the conventional algorithms despite noisy elastic wave images. From the gel phantom experiment, we confirmed the same tendency as the characteristics of the algorithms observed in the numerical simulation results. CONCLUSION: We have developed a novel inversion algorithm and evaluated it quantitatively. The results confirm that the proposed algorithms are highly quantitative and noise-robust methods for estimating storage and loss modulus regardless of noise, voxel anisotropy, and propagation direction. Therefore, the proposed algorithms will appropriate to various three-dimensional MRE systems.

Longitudinal stability of a multimodal visco-elastic polyacrylamide gel phantom for magnetic resonance and ultrasound shear-wave elastography.

We evaluated the long-term stability of a newly developed viscoelastic phantom made of polyacrylamide (PAAm) gel for magnetic resonance elastography (MRE) and ultrasound-based shear-wave elastography (US SWE). The stiffness of the cylindrical phantom was measured at 0, 13 and 18 months. Storage and loss moduli were measured with MRE, and shear-wave speed (SWS) was measured with US SWE. Long-term stability was evaluated in accordance with the Quantitative Imaging Biomarker Alliance (QIBA) profiles for each modality. The initial storage and loss moduli of the phantom were 5.01±0.22 and 1.11±0.15 respectively, and SWS was 2.57±0.04 m/s. The weight of the phantom decreased by 0.6% over the 18 months. When measured with MRE, the stiffness of the phantom decreased and changes to the storage and loss moduli were -3.0% and -4.6% between 0 and 13 months, and -4.3% and 0.0% between 0 and 18 months. The US measurements found that SWS decreased by 2.4% over the first 13 months and 3.6% at 18 months. These changes were smaller than the tolerances specified in the QIBA profiles, so the viscoelastic PAAm gel phantom fulfilled the condition for long-term stability. This new phantom has the potential to be used as a quality assurance and quality control phantom for MRE and US SWE.

Stiffness change of the supraspinatus muscle can be detected by magnetic resonance elastography.

Magnetic resonance elastography (MRE) and ultrasound shear wave elastography (SWE) are imaging techniques to measure stiffness of the soft tissue using magnetic resonance imaging (MRI) and ultrasound images, respectively. The purpose of this study was to explore the feasibility of the MRE measurement to evaluate the change in supraspinatus (SSP) muscle stiffness before and after rotator cuff tear, and to compare the result with those of SWE. Six swine shoulders were used. The skin and subcutaneous fat were removed, and the stiffness value of the SSP muscle was measured by MRE and SWE. The MRE measurement was performed with 0.3 T open MRI and the vibration from a pneumatic driver system with active driver to a passive driver to create the shear wave in the tissue. The passive driver was placed on the center of the SSP muscle. The stiffness was estimated from the wave images using local frequency estimation methods. In the SWE measurement, the probe of the ultrasound was placed on the center of the SSP muscle. The shear wave propagation speed was measured at a depth of 1 cm from the surface, and the stiffness was calculated. After those measurements, the rotator cuff tendon was detached from the greater tuberosity, and MRE and SWE measurements were then performed in the same manner again. The differences in the stiffness values were compared between before and after the rotator cuff tendon tear on both the MRE and SWE measurements. The results indicated that stiffness values on MRE and SWE were 9.3 ± 1.8 and 10.0 ± 1.2 kPa respectively before the rotator cuff tear, and 7.3 ± 1.3 and 8.0 ± 0.8 kPa respectively after the tendon detachment. Stiffness values were significantly lower after the tendon detachment on both the MRE and SWE measurements (p < 0.05). Our results demonstrated that stiffness values of the SSP muscle on MRE and SWE were lower after rotator cuff detachment. From this result, MRE may be a feasible method for quantification of the change in rotator cuff muscle stiffness.

Intra- and inter-operator reproducibility of US point shear-wave elastography in various organs: evaluation in phantoms and healthy volunteers.

PURPOSE: This study was conducted in order to assess the intra- and interoperator reproducibility of shear-wave speed (SWS) measurement on elasticity phantoms and healthy volunteers using ultrasound-based point shear-wave elastography. MATERIALS AND METHODS: This study was approved by the institutional review board. Two operators measured the SWS of five elasticity phantoms and seven organs (thyroid, lymph node, muscle, spleen, kidney, pancreas, and liver) of 30 healthy volunteers with 1.0-4.5 MHz convex (4C1) and 4.0-9.0 MHz linear (9L4) transducers. The phantom measurements were repeated ten times, while the volunteer measurements were performed five times each. Intra- and interoperator reproducibility was assessed. Interoperator reproducibility was also evaluated with the 95% Bland-Altman limits of agreement (LOA). RESULTS: In phantoms, all intraclass correlation coefficients (ICCs) were above 0.90 and the 95% LOA between the two operators were less than ± 18%. In volunteers, intraoperator ICCs were > 0.75 for all regions except the pancreas. Interoperator ICC was above 0.75 for the right lobe of the liver (depth 4 cm) and the kidney, but the 95% LOA was less than ± 25% only for the liver. CONCLUSION: Although excellent in phantoms, interoperator reproducibility was insufficient for all regions in the volunteers other than the right hepatic lobe at a depth of 4 cm. Clinicians should be aware of the 95% LOA when using SWS in patients. KEY POINTS: • Our phantom study indicated a high reproducibility for shear-wave speed (SWS) measurements with point shear-wave elastography (pSWE). • In volunteers, intraoperator reproducibility was generally high, but the interoperator reproducibility was not high enough except for the right hepatic lobe at 4 cm depth. • To evaluate interoperator reproducibility, the 95% limits of agreement (LOA) between operators should be considered in addition to the intraclass correlation coefficient (ICC).

Numerical simulations of magnetic resonance elastography using finite element analysis with a linear heterogeneous viscoelastic model.

ABSTRACT: Magnetic resonance elastography (MRE) is a technique to identify the viscoelastic moduli of biological tissues by solving the inverse problem from the displacement field of viscoelastic wave propagation in a tissue measured by MRI. Because finite element analysis (FEA) of MRE evaluates not only the viscoelastic model for a tissue but also the efficiency of the inversion algorithm, we developed FEA for MRE using commercial software called ANSYS, the Zener model for displacement field of a wave inside tissue, and an inversion algorithm called the modified integral method. The profile of the simulated displacement field by FEA agrees well with the experimental data measured by MRE for gel phantoms. Similarly, the value of storage modulus (i.e., stiffness) recovered using the modified integral method with the simulation data is consistent with the value given in FEA. Furthermore, applying the suggested FEA to a human liver demonstrates the effectiveness of the present simulation scheme.

MRI compatibility study of an integrated PET/RF-coil prototype system at 3T.

We have been working on the development of a PET insert for existing magnetic resonance imaging (MRI) systems for simultaneous PET/MR imaging, which integrates radiofrequency (RF)-shielded PET detector modules with an RF head coil. In order to avoid interferences between the PET detector circuits and the different MRI-generated electromagnetic fields, PET detector circuits were installed inside eight Cu-shielded fiber-reinforced plastic boxes, and these eight shielded PET modules were integrated in between the eight elements of a 270-mm-diameter and 280-mm-axial-length cylindrical birdcage RF coil, which was designed to be used with a 3-T clinical MRI system. The diameter of the PET scintillators with a 12-mm axial field-of-view became 255mm, which was very close to the imaging region. In this study, we have investigated the effects of this PET/RF-coil integrated system on the performance of MRI, which include the evaluation of static field (Bo) inhomogeneity, RF field (B1) distribution, local specific absorption rate (SAR) distribution, average SAR, and signal-to-noise ratio (SNR). For the central 170-mm-diameter and 80-mm-axial-length of a homogenous cylindrical phantom (with the total diameter of 200mm and axial-length of 100mm), an increase of about a maximum of 3µT in the Bo inhomogeneity was found, both in the central and 40-mm off-centered transverse planes, and a 5 percentage point increase of B1 field inhomogeneity was observed in the central transverse plane (from 84% without PET to 79% with PET), while B1 homogeneity along the coronal plane was almost unchanged (77%) following the integration of PET with the RF head coil. The average SAR and maximum local SAR were increased by 1.21 and 1.62 times, respectively. However, the SNR study for both spin-echo and gradient-echo sequences showed a reduction of about 70% and 60%, respectively, because of the shielded PET modules. The overall results prove the feasibility of this integrated PET/RF-coil system for using with the existing MRI system.

Measuring shear-wave speed with point shear-wave elastography and MR elastography: a phantom study.

OBJECTIVES: To compare shear-wave speed (SWS) measured by ultrasound-based point shear-wave elastography (pSWE) and MR elastography (MRE) on phantoms with a known shear modulus, and to assess method validity and variability. METHODS: 5 homogeneous phantoms of different stiffnesses were made. Shear modulus was measured by a rheometer, and this value was used as the standard. 10 SWS measurements were obtained at 4 different depths with 1.0-4.5 MHz convex (4C1) and 4.0-9.0 MHz linear (9L4) transducers using pSWE. MRE was carried out once per phantom, and SWSs at 5 different depths were obtained. These SWSs were then compared with those from a rheometer using linear regression analyses. RESULTS: SWSs obtained with both pSWE as well as MRE had a strong correlation with those obtained by a rheometer (R2>0.97). The relative difference in SWS between the procedures was from -25.2% to 25.6% for all phantoms, and from -8.1% to 6.9% when the softest and hardest phantoms were excluded. Depth dependency was noted in the 9L4 transducer of pSWE and MRE. CONCLUSIONS: SWSs from pSWE and MRE showed a good correlation with a rheometer-determined SWS. Although based on phantom studies, SWSs obtained with these methods are not always equivalent, the measurement can be thought of as reliable and these SWSs were reasonably close to each other for the middle range of stiffness within the measurable range.

Development of a small single-ring OpenPET prototype with a novel transformable architecture.

The single-ring OpenPET (SROP), for which the detector arrangement has a cylinder shape cut by two parallel planes at a slant angle to form an open space, is our original proposal for in-beam PET. In this study, we developed a small prototype of an axial-shift type SROP (AS-SROP) with a novel transformable architecture for a proof-of-concept. In the AS-SROP, detectors originally forming a cylindrical PET are axially shifted little by little. We designed the small AS-SROP prototype for 4-layer depth-of-interaction detectors arranged in a ring diameter of 250 mm. The prototype had two modes: open and closed. The open mode formed the SROP with the open space of 139 mm and the closed mode formed a conventional cylindrical PET. The detectors were simultaneously moved by a rotation handle allowing them to be transformed between the two modes. We evaluated the basic performance of the developed prototype and carried out in-beam imaging tests in the HIMAC using (11)C radioactive beam irradiation. As a result, we found the open mode enabled in-beam PET imaging at a slight cost of imaging performance; the spatial resolution and sensitivity were 2.6 mm and 5.1% for the open mode and 2.1 mm and 7.3% for the closed mode. We concluded that the AS-SROP can minimize the decrease of resolution and sensitivity, for example, by transforming into the closed mode immediately after the irradiation while maintaining the open space only for the in-beam PET measurement.

Development of 1.45-mm resolution four-layer DOI-PET detector for simultaneous measurement in 3T MRI.

Recently, various types of PET-MRI systems have been developed by a number of research groups. However, almost all of the PET detectors used in these PET-MRI systems have no depth-of-interaction (DOI) capability. The DOI detector can reduce the parallax error and lead to improvement of the performance. We are developing a new PET-MRI system which consists of four-layer DOI detectors positioned close to the measured object to achieve high spatial resolution and high scanner sensitivity. As a first step, we are investigating influences the PET detector and the MRI system have on each other using a prototype four-layer DOI-PET detector. This prototype detector consists of a lutetium yttrium orthosilicate crystal block and a 4 × 4 multi-pixel photon counter array. The size of each crystal element is 1.45 mm × 1.45 mm × 4.5 mm, and the crystals are arranged in 6 × 6 elements × 4 layers with reflectors. The detector and some electric components are packaged in an aluminum shielding box. Experiments were carried out with 3.0 T MRI (GE, Signa HDx) and a birdcage-type RF coil. We demonstrated that the DOI-PET detector was normally operated in simultaneous measurements with no influence of the MRI measurement. A slight influence of the PET detector on the static magnetic field of the MRI was observed near the PET detector. The signal-to-noise ratio was decreased by presence of the PET detector due to environmental noise entering the MRI room through the cables, even though the PET detector was not powered up. On the other hand, no influence of electric noise from the PET detector in the simultaneous measurement on the MRI images was observed, even though the PET detector was positioned near the RF coil.

Restoration of lost frequency in OpenPET imaging: comparison between the method of convex projections and the maximum likelihood expectation maximization method.

We are developing a new PET scanner based on the "OpenPET" geometry, which consists of two detector rings separated by a gap. One item to which attention must be paid is that OpenPET image reconstruction is classified into an incomplete inverse problem, where low-frequency components are truncated. In our previous simulations and experiments, however, the OpenPET imaging was made feasible by application of iterative image reconstruction methods. Therefore, we expect that iterative methods have a restorative effect to compensate for the lost frequency. There are two types of reconstruction methods for improving image quality when data truncation exists: one is the iterative methods such as the maximum-likelihood expectation maximization (ML-EM) and the other is an analytical image reconstruction method followed by the method of convex projections, which has not been employed for the OpenPET. In this study, therefore, we propose a method for applying the latter approach to the OpenPET image reconstruction and compare it with the ML-EM. We found that the proposed analytical method could reduce the occurrence of image artifacts caused by the lost frequency. A similar tendency for this restoration effect was observed in ML-EM image reconstruction where no additional restoration method was applied. Therefore, we concluded that the method of convex projections and the ML-EM had a similar restoration effect to compensate for the lost frequency.

Simulation study optimizing the number of photodetection faces for the X'tal cube PET detector with separated crystal segments.

We are developing a novel PET detector with 3D isotropic resolution called a crystal (X'tal) cube. The X'tal cube detector consists of a crystal block all 6 surfaces of which are covered with silicon photomultipliers (SiPMs). We have developed a prototype detector with 3D isotropic 1 mm resolution. On the other hand, when the X'tal cubes are arranged to form a PET scanner, insensitive inter-detector gaps made by the SiPM arrays should not be too wide, or, better yet, they should be removed. Reduction of the number of SiPMs will also be reflected in the production costs. Therefore, reducing the number of faces to be connected to the SiPMs has become our top priority. In this study, we evaluated the effect of reducing the number of SiPMs on the positioning accuracy through numerical simulations. Simulations were performed with the X'tal cube, which was composed of a 6 × 6 × 6 array of Lu2x Gd2(1-x)SiO5:Ce crystal elements with dimensions of (3.0 mm)(3). Each surface of the crystal block was covered with a 4 × 4 array of SiPMs, each of which had a (3.0 mm)(2) active area. For material between crystal elements, we compared two: optical glue and an air gap. The air gap showed a better crystal identification performance than did the optical glue, although a good crystal identification performance was obtained even with optical glue for the 6-face photodetection. In conclusion, the number of photodetection faces could be reduced to two when the gap material was air.

A SiPM-based isotropic-3D PET detector X'tal cube with a three-dimensional array of 1 mm(3) crystals.

We are developing a novel, general purpose isotropic-3D PET detector X'tal cube which has high spatial resolution in all three dimensions. The research challenge for this detector is implementing effective detection of scintillation photons by covering six faces of a segmented crystal block with silicon photomultipliers (SiPMs). In this paper, we developed the second prototype of the X'tal cube for a proof-of-concept. We aimed at realizing an ultimate detector with 1.0 mm(3) cubic crystals, in contrast to our previous development using 3.0 mm(3) cubic crystals. The crystal block was composed of a 16 × 16 × 16 array of lutetium gadolinium oxyorthosilicate (LGSO) crystals 0.993 × 0.993 × 0.993 mm(3) in size. The crystals were optically glued together without inserting any reflector inside and 96 multi-pixel photon counters (MPPCs, S10931-50P, i.e. six faces each with a 4 × 4 array of MPPCs), each having a sensitive area of 3.0 × 3.0 mm(2), were optically coupled to the surfaces of the crystal block. Almost all 4096 crystals were identified through Anger-type calculation due to the finely adjusted reflector sheets inserted between the crystal block and light guides. The reflector sheets, which formed a belt of 0.5 mm width, were placed to cover half of the crystals of the second rows from the edges in order to improve identification performance of the crystals near the edges. Energy resolution of 12.7% was obtained at 511 keV with almost uniform light output for all crystal segments thanks to the effective detection of the scintillation photons.

Development of a small prototype for a proof-of-concept of OpenPET imaging.

The OpenPET geometry is our new idea to visualize a physically opened space between two detector rings. In this paper, we developed the first small prototype to show a proof-of-concept of OpenPET imaging. Two detector rings of 110 mm diameter and 42 mm axial length were placed with a gap of 42 mm. The basic imaging performance was confirmed through phantom studies; the open imaging was realized at the cost of slight loss of axial resolution and 24% loss of sensitivity. For a proof-of-concept of PET image-guided radiation therapy, we carried out the in-beam tests with (11)C radioactive beam irradiation in the heavy ion medical accelerator in Chiba to visualize in situ distribution of primary particles stopped in a phantom. We showed that PET images corresponding to dose distribution were obtained. For an initial proof-of-concept of real-time multimodal imaging, we measured a tumor-inoculated mouse with (18)F-FDG, and an optical image of the mouse body surface was taken during the PET measurement by inserting a digital camera in the ring gap. We confirmed that the tumor in the gap was clearly visualized. The result also showed the extension effect of an axial field-of-view (FOV); a large axial FOV of 126 mm was obtained with the detectors that originally covered only an 84 mm axial FOV. In conclusion, our initial imaging studies showed promising performance of the OpenPET.

Magnetic resonance elastography to observe deep areas: comparison of external vibration systems.

MRE methods deform the sample using an external vibration system. We have been using a transverse driver, which generates shear waves at the object surface. One of the problems is that shear waves rapidly attenuate at the surface of tissue and do not propagate into the body. In this study, we compared the shear waves generated by transverse and longitudinal drivers. The longitudinal driver was found to induce shear waves deep inside a porcine liver phantom. These results suggest that the longitudinal driver will allow measurement of the shear modulus deep inside the body.

Evaluation of static physics performance of the jPET-D4 by Monte Carlo simulations.

The jPET-D4 is the first PET scanner to introduce a unique four-layer depth-of-interaction (DOI) detector scheme in order to achieve high sensitivity and uniform high spatial resolution. This paper compares measurement and Monte Carlo simulation results of the static physics performance of this prototype research PET scanner. Measurement results include single and coincidence energy spectra, point and line source sensitivities, axial sensitivity profile (slice profile) and scatter fraction. We use GATE (Geant4 application for tomographic emission) as a Monte Carlo radiation transport model. Experimental results are reproduced well by the simulation model with reasonable assumptions on characteristic responses of the DOI detectors. In a previous study, the jPET-D4 was shown to provide a uniform spatial resolution as good as 3 mm (FHWM). In the present study, we demonstrate that a high sensitivity, 11.3 +/- 0.5%, is provided at the FOV centre. However, about three-fourths of this sensitivity is related to multiple-crystal events, for which some misidentification of the crystal cannot be avoided. Therefore, it is crucial to develop a more efficient way to identify the crystal of interaction and to reduce misidentification in order to make use of these high performance values simultaneously. We expect that effective sensitivity can be improved by replacing the GSO crystals with more absorptive crystals such as BGO and LSO. The results we describe here are essential to take full advantage of the next generation PET systems that have DOI recognition capability.

Development of a magnetic resonance elastic microscope system.

Magnetic resonance elastography (MRE) is a method that can visualize the propagating acoustic strain waves in elastic materials under mechanical excitation. The local quantitative values of shear modulus are derived from the acquired data. The MRE could improve early detection of pathology because it is known that malignant tumors tend to be much harder than normal tissues and most benign tumors. In order to observe tissues such as the early stage of tumors in mouse embryo, spatial resolution of the MRE image is not enough because of hardware limitation of the conventional MRI system. We developed the elasticity measurement system using the MR microscope which spatial resolution is about 200 mm. The external vibration system and MR pulse sequences are developed for an MR elastic microscope. Experiments were performed with homogeneous and heterogeneous agarose gel phantoms. These results suggest the developed MR elastic microscope system makes it possible to generate image that depict distribution of stiffness.