Development of a suitable vibration pad for renal MR elastography.

The aim of this study was to develop a vibration pad suitable for renal MR elastography (MRE). Chronic kidney disease (CKD) is a progressive condition affecting >800 million people worldwide. Renal fibrosis is a common pathological feature of CKD that causes fibrotic regions to be much stiffer than those in normal renal tissues. Therefore, MRE can be used to diagnose CKD because it can image organ stiffness. In MRE, the shear modulus is obtained from the wavelength of the shear waves. Therefore, it is highly important to propagate shear waves with sufficient vibration strength in the tissue. By using a three-dimensional (3D) printer, we created a "Flexible Pad" suitable for renal MRE. The Flexible Pad was placed under the back of the participant in the supine position and deformed in response to the participant's weight, adhering closely to the body surface. Six healthy volunteers participated in this study. Our Flexible Pad allowed for coherent shear waves (clear waves with little scattering and interference) to be efficiently transmitted to the kidney deep-lying tissues in the abdomen. The shear moduli of the kidney (n = 6) were 8.95 ± 0.84 kPa in the right kidney and 9.70 ± 0.99 kPa in the left kidney. Our results indicate that using our Flexible Pad for renal MRE can provide a more reliable measurement of renal shear modulus.

Fast abdominal magnetic resonance elastography with simultaneous encoding of three-dimensional displacements.

Three-dimensional (3D) magnetic resonance elastography (MRE) is more accurate than two-dimensional (2D) MRE; however, it requires long-term acquisition. This study aimed to reduce the acquisition time of abdominal 3D MRE using a new sample interval modulation (short-SLIM) approach that can acquire all three motions faster while reducing the prolongation of echo time and flow compensation. To this end, two types of phantom studies and an in vivo test of the liver in three healthy volunteers were performed to compare the performances of conventional spin-echo echo-planar (SE-EPI) MRE, conventional SLIM and short-SLIM. One phantom study measured the mean amplitude and shear modulus within the overall region of a homogeneous phantom by changing the mechanical vibration power to assess the robustness to the lowered phase-to-noise ratio in short-SLIM. The other measured the mean shear modulus in the stiff and background materials of a phantom with an embedded stiffer rod to assess the performance of short-SLIM for complex wave patterns with wave interference. The Spearman's rank correlation coefficient was used to assess similarity of elastograms in the rod-embedded phantom and liver between methods. The results of the phantom study changing the vibration power indicated that there was little difference between conventional MRE and short-SLIM. Moreover, the elastogram pattern and the mean shear modulus in the rod-embedded phantom in conventional SLIM and short-SLIM did not change for conventional MRE; the liver test also showed a small difference between the acquisition techniques. This study demonstrates that short-SLIM can provide MRE results comparable to those of conventional MRE. Short-SLIM can reduce the total acquisition time by a factor of 2.25 compared to conventional 3D MRE time, leading to an improvement in the accuracy of shear modulus estimation by suppressing the patient movements.

A Versatile MR Elastography Research Tool with a Modified Motion Signal-to-noise Ratio Approach.

PURPOSE: This study aimed to facilitate research progress in MR elastography (MRE) by providing a versatile and convenient application for MRE reconstruction, namely the MRE research tool (MRE-rTool). It can be used for a series of MRE image analyses, including phase unwrapping, arbitrary bandpass and directional filtering, noise assessment of the wave propagation image (motion SNR), and reconstruction of the elastogram in both 2D and 3D MRE acquisitions. To reinforce the versatility of MRE-rTool, the conventional method of motion SNR was modified into a new method that reflects the effects of image filtering. METHODS: MRE tests of the phantom and liver were performed using different estimation algorithms for stiffness value (algebraic inversion of the differential equation [AIDE], local frequency estimation [LFE] in MRE-rTool, and multimodel direct inversion [MMDI] in clinical reconstruction) and acquiring dimensions (2D and 3D acquisitions). This study also tested the accuracy of masking low SNR regions using modified and conventional motion SNR under various mechanical vibration powers. RESULTS: The stiffness values estimated using AIDE/LFE in MRE-rTool were comparable to that of MMDI (phantom, 3.71 ± 0.74, 3.60 ± 0.32, and 3.60 ± 0.54 kPa in AIDE, LFE, and MMDI; liver, 2.26 ± 0.31, 2.74 ± 0.16, and 2.21 ± 0.26 kPa in AIDE, LFE, and MMDI). The stiffness value in 3D acquisition was independent of the direction of the motion-encoding gradient and was more accurate than that of 2D acquisition. The masking of low SNR regions using the modified motion SNR worked better than that in the conventional motion SNR for each vibration power, especially when using a directional filter. CONCLUSION: The performance of MRE-rTool on test data reached the level required in clinical MRE studies. MRE-rTool has the potential to facilitate MRE research, contribute to the future development of MRE, and has been freely released online.

Time-course of physical properties of the psoas major muscle after exercise as assessed by MR elastography.

This study aimed to analyze the time-course of the physical properties of the psoas major muscle (PM) before and after exercise using magnetic resonance elastography (MRE). Muscle stiffness is one of the important properties associated with muscle function. However, there was no research on the stiffness of the PM after exercise. In this study, we investigated time-course changes of the shear modulus of the PM after exercise. Furthermore, T2 values and apparent diffusion coefficient (ADC), as the additional information associated with muscular physical properties, were also measured simultaneously. Healthy young male volunteers were recruited in this study (n = 9) and they were required to perform a hand-to-knee isometric and unilateral exercise (left side). At each time-point before and after exercise, a set of 3 types of MR scans to measure multiple physical properties of the PM [shear modulus (MRE), T2 values, and ADC] were repeatedly taken. On day 1, a single set MR scan was taken before exercise (pre-exercise MR scan), and 6 sets MR scans were taken (5.5 to 38.0 min after exercise). After about 10-min rest (46.0 to 56.0 min after exercise), 4 sets MR scans were taken (57.5 to 77.0 min after exercise). About 10-min rest was taken again (85.0-95.0 min after exercise), 4 sets MR scans were taken (96.5 to 116.0 min after exercise). On days 2 and 7, a single set MR scan (MRE, T2 value, and ADC) was taken on each experimental day. The data were analyzed as relative changes (%) of the given parameters to the pre-exercise values. The results indicated significant decreases in PM shear modulus up to about 30 min after exercise. Then, it gradually increased and showed significant increases at about 100 min after exercise compared to that before exercise. T2 values and ADC showed significant increases up to about 65 min after exercise compared to those before exercise, and then returned to the pre-exercise values. On days 2 and 7, all values showed no significant changes compared to the pre-exercise values. This study is the first to report the time-course of the physical properties of the PM after exercise.

A novel technique for automating stiffness measurement and emphasizing the main wave: Coherent-wave auto-selection (CHASE).

This study aims to develop and assess a new automated processing technique in MR elastography (MRE), namely coherent-wave auto-selection (CHASE). CHASE enables automatic selection of the region of interest (ROI) for stiffness measurement by extraction of the coherent wave region (CHASE ROI), and it improves the reconstruction of stiffness by a directional filter oriented along the main wave in each pixel (CHASE filtering). In this study, MRE of a phantom and of the liver of four healthy volunteers was performed. To investigate the potential of CHASE, this study assessed the CHASE according to three indices through the phantom study: 1) agreement on the ROI settings between CHASE and expert observers, 2) noise dependency, and 3) effect of the CHASE on stiffness variability within the CHASE ROI. The agreements on the ROI settings were analyzed by Cohen's kappa coefficient (κ). The noise dependency was analyzed by the mean absolute percentage errors (MAPEs) within the ROI between low (20%-80% amplitudes) and high vibration amplitudes (100% amplitude). The stiffness variability was assessed by standard deviation (SD) within the ROI. In the volunteer study, agreements on the ROI settings (or stiffness value) and stiffness variability within the CHASE ROI were assessed using κ-value (or intraclass correlation coefficient: ICC) and coefficient of variation, respectively. The results showed close agreement on the ROI settings and stiffness (κ-value: greater than 0.61 in both the phantom and volunteer studies, ICC: 0.97 in the volunteer study). The MAPEs within the CHASE ROI were much smaller than those in the whole region of the phantom (CHASE ROI vs. the whole region at 20% amplitude: 10.3% vs. 50.8%). Moreover, in both the phantom and volunteer studies, the stiffness variation within the CHASE ROI was smaller in the elastogram processed with CHASE filtering than in the unprocessed one. Our results demonstrated that the CHASE has high robustness against noise and the potential to provide ROI settings for stiffness measurement comparable to expert observers, as well as improve the reconstruction of stiffness.

Examinations for creating an image of unacquired dose from the images of two types of dose in digital radiography.

BACKGROUND: Digital radiography (DR) is grayscale adjustable and it can be unclear whether an acquired DR image is captured with the minimum radiation dose required. It is necessary to make an image of the amount of noise when taken at a lower dose than the acquired image, without increased exposure. OBJECTIVE: To examine whether an image of unacquired dose can be created from two types of dose DR images acquired using a phantom. METHODS: To create an additive image from two images of different doses, the pixel value of one image is multiplied by a coefficient and added to the other. The normalized noise power spectra (NNPS) of the normal image and the additive image with the same signal-to-noise ratio (SNR) are compared. The image noise of the unacquired doses is estimated from the graph changes of the pixel values and standard deviations of two images. The error between the SNR of the image obtained by changing the dose and the estimated SNR is measured. We propose a multiplication coefficient calculation formula that theoretically adjusts the additive image to the target SNR. The SNR error of the image created based on this formula is measured. RESULTS: The NNPS curves of the additive and normal images show a difference on the high frequency side. According to the statistics considering the preset of mAs value, there is no significant difference at 85%. The SNR estimation error is approximately 1%. The SNR error of the additive image created based on the formula is approximately 5%. CONCLUSION: The noise of the image of unacquired dose can be estimated, and the additive image adjusted to this value can be considered equivalent to the image taken at the actual dose.

[Improvement of SNR When Adding X-ray Images with Different SNRs].

Some radiologic patient positioning techniques that can be used for X-ray examinations can be difficult to apply. One method involves using ultra-low-dose X-ray images to confirm positioning. These positioning images are typically discarded and not used for diagnosis. The purpose of this study was to improve the signal-to-noise ratio (SNR) in diagnostic imaging by including these ultra-low-dose positioning images rather than discarding them. To add two images together, we devised a method in which one image is multiplied by the coefficient calculated from its SNR before the addition. The images were dichotomized into a high SNR group and a low SNR group. The images in the high SNR group and the low SNR group were summed. When doing so, the images of the low SNR group were multiplied. There was one maximum SNR point while the SNR was being changed. The maximum SNR of the synthesized images was equal to the value of the square root of the sum of the squares of the two images. The multiplication coefficient, in the case of the maximum SNR, was near 1 when an image agreed with the Poisson distribution; when it did not, it was far from 1. The difference between the calculated values of the hypothetical measurement of the multiplication coefficient was small. In this study, we showed that improving SNR of a diagnostic image could be achieved by adding a positioning image. The multiplication coefficient in the case of the SNR maximum of a synthesized image is calculable. The measurement of a Wiener spectrum is needed for noise evaluation. There can be problems where there is motion after a positioning image is exposed.

Magnetic resonance elastography of the supraspinatus muscle: A preliminary study on test-retest repeatability and wave quality with different frequencies and image filtering.

The purpose of this study was to determine an optimal condition (vibration frequency and image filtering) for stiffness estimation with high accuracy and stiffness measurement with high repeatability in magnetic resonance elastography (MRE) of the supraspinatus muscle. Nine healthy volunteers underwent two MRE exams separated by at least a 30 min break, on the same day. MRE acquisitions were performed with a gradient-echo type multi-echo MR sequence at 75, 100, and 125 Hz pneumatic vibration. Wave images were processed by a bandpass filter or filter combining bandpass and directional filters (bandpass-directional filter). An observer specified the region of interest (ROI) on clear wave propagation in the supraspinatus muscle, within which the observer measured the stiffness. This study assessed wave image quality according to two indices, as a substitute for the assessment of the accuracy of the stiffness estimation. One is the size of the clear wave propagation area (ROI size used to measure the stiffness) and the other is the qualitative stiffness resolution score in that area. These measurements made by the observer were repeated twice at least one month apart after each MRE exam. This study assessed the intra-examiner and observer repeatability of the stiffness value, ROI size and resolution score in each combination of vibration frequency and image filter. Repeatability of the data was analyzed using the intraclass correlation coefficient (ICC) and 95% limits-of-agreement (LOA) in Bland-Altman analysis. The analyses on intra-examiner and observer repeatability of stiffness indicated that the ICC and 95% LOA were not varied greatly depending on vibration frequency and image filter (intra-examiner repeatability, ICC range, 0.79 to 0.88; 95% LOA range, ±23.95 to ±32.42%, intra-observer repeatability, ICC range, 0.98 to 1.00; 95% LOA range, ±5.10 to ±10.99%). In the analyses on intra-examiner repeatability of ROI size, ICCs were rather low (ranging from: 0.03 to 0.69) while 95% LOA was large in all the combinations of vibration frequency and image filter (ranging from: ±62.66 to ±83.33%). In the analyses on intra-observer repeatability of ROI size, ICCs were sufficiently high in the total combination of vibration frequency and image filter (ranging from 0.80 to 0.87) while the 95% LOAs were better (lower) in the bandpass-directional filter than the bandpass filter (bandpass directional filter vs. bandpass filter, ±28.81 vs. ±54.83% at 75 Hz; ±25.63 vs. ±37.83% at 100 Hz; ±34.51 vs. ±43.36% at 125 Hz). In the analyses on intra-examiner and observer repeatability of resolution score, the mean difference (bias) between the two exams (or observations) was significantly low and there was almost no difference across all the combinations of vibration frequency and image filter (range of bias: -0.11-0.11 and -0.17-0.00, respectively). Additionally, effects of vibration frequency and image filter on wave image quality (ROI size and resolution score) were assessed separately in each exam. Both mean ROI size and resolution score in the bandpass-directional filter were larger than those in the bandpass filter. Among the data in the bandpass-directional filter, mean ROI size was larger at 75 and 100 Hz, and mean resolution score was larger at 100 and 125 Hz. Taking into consideration with the results of repeatability and wave image quality, the present results suggest that optimal vibration frequency and image filter for MRE of the supraspinatus muscles is 100 Hz and bandpass-directional filter, respectively.

A new technique for motion encoding gradient-less MR elastography of the psoas major muscle: A gradient-echo type multi-echo sequence.

The present study aimed to develop vibration techniques for magnetic resonance (MR) elastography (MRE) of the psoas major muscle (PM). Seven healthy volunteers were included. MRE was performed with motion-encoding gradient (MEG)-less multi-echo MRE sequence, which allows clinicians to perform MRE using conventional MR imaging. In order to transmit mechanical vibration of the pneumatic type to the PM, a long narrow vibration pad was designed using a 3D printer, and the optimum vibration techniques were verified. The vibration pad was placed under the lower back, with the volunteers in the supine position. The results indicated that the PM vibrated well through the transmitted vibration from the lumbar spine, which suggests that the placement of a narrow vibration pad under the supine body, along the lumbar spine, allows the vibration of the PM. The shear modulus of the PM (n = 7) was 1.23 ±â€¯0.09 kPa (mean ±â€¯SEM) on the right side and 1.22 ±â€¯0.15 kPa on the left side, with no significant difference (t-test, P > 0.05). Increased stiffness of the muscle due to continuous local contraction may be an important cause of non-specific low back pain (LBP). The present vibration techniques for MRE of the PM provide a quantitative diagnostic tool for changes in muscle stiffness associated with non-specific LBP.

[Influence of Vibration Waveform on MR Elastography].

The purpose of this study was to investigate an influence of vibration waveform on magnetic resonance elastography (MRE). MRE is an innovative imaging technique for the non-invasive quantification of the elasticity of soft tissues through the direct visualization of propagating shear waves in vivo using a special phase-contrast magnetic resonance imaging sequence. Since the elasticity of soft tissue calculates from the wavelength of propagating shear waves, it is necessary to propagate sine-wave-shape shear wave at the target soft tissue. However, due to the various factors; i.e. overload of vibration generator, poor contact between imaging object and vibration pad, etc.; it may be difficult to generate a simple sine wave. This work was focused on change vibration waveforms; i.e. square wave, triangle wave, saw-tooth wave; which is induced by the various factors. Phantom experimental results demonstrated that when square and saw-tooth waveforms of 25 Hz vibration frequency, into the phantom, the waveform of propagating wave was not similar to sine waveform. It may influence on the MRE that in case of the waveforms has low frequency and square or saw-tooth like waveforms.

Simultaneous acquisition of magnetic resonance elastography of the supraspinatus and the trapezius muscles.

We developed a Magnetic Resonance elastography (MRE) technique using a conventional magnetic resonance imaging (MRI), which allows a simultaneous elastography of the supraspinatus and trapezius muscles, by designing a new wave transducer (vibration pad) and optimizing the mechanical vibration frequency. Five healthy volunteers underwent an MRE. In order to transmit the mechanical vibration (pneumatic vibration) to the supraspinatus and trapezius muscles, a new vibration pad was designed using a three-dimensional (3D) printer. The vibration pad was placed on the skin 2 cm medial and 2 cm cephalad the deltoid tubercle. MRE acquisition was performed with a multi-slice gradient-echo type multi-echo MR sequence, which allows MREs even in a conventional MRI; two oblique axial images of the supraspinatus and trapezius muscles were obtained simultaneously. Vibration frequencies were set at 50-150 Hz, with a 25 Hz step. Wave image quality in each frequency was analyzed using a phase-to-noise ratio (PNR) and clarity of propagating wave that was assessed by two readers qualitatively. In the supraspinatus muscle, the wave images were of good quality especially at frequencies >75 Hz. In the trapezius muscle, the wave images were of better quality at low frequencies (50 and 75 Hz) compared with high frequencies (100-150 Hz). The PNR of both muscles were higher at low frequencies. The mean stiffness in the trapezius muscle (7.26 ±â€¯2.13 kPa at 75 Hz) was larger than those in the supraspinatus muscle (4.16 ±â€¯0.50 kPa at 75 Hz). The results demonstrated that our MRE technique allows simultaneous assessment of the stiffness in the supraspinatus and trapezius muscles using a conventional MRI, and that optimal vibration frequency for simultaneous MRE of these muscles is 75 Hz. This technique provides a new means for early detection of abnormality in the shoulder.

Development of a robust diffusion-MR elastography (dMRE) technique to mitigate intravoxel phase dispersion.

Diffusion-magnetic resonance elastography (dMRE) is an emerging practical technique that can acquire diffusion magnetic resonance imaging and MRE simultaneously. However, a signal loss attributable to intravoxel phase dispersion (IVPD) interferes with the calculation of the apparent diffusion coefficient (ADC). This study presents an approach to dMRE that reduces the influence of IVPD by introducing a new pulse sequence. The existing and proposed techniques were performed using a phantom comprising five rods with different elasticities at 60 Hz vibration to investigate the accuracy of previous and proposed dMRE techniques. The measures of ADC and stiffness, obtained by using both dMRE techniques, were compared with conventional spin-echo (SE) diffusion and SE-MRE. Then, we evaluated those differences by using the mean of absolute differences (MAD) in each rod within the phantom. The results of the MAD of the stiffness from both dMRE techniques showed almost no difference. In contrast, the value of the ADC MAD (MAD ≒ 0.16 × 10-3 mm2/s), obtained in the soft region within the phantom with the previous dMRE technique, was large. This value was about 2.7 times that of the value produced by the proposed dMRE technique. This difference must reflect the degree of influence of IVPD in both techniques. These results demonstrate that our dMRE technique is a robust method for addressing the signal loss attributable to IVPD.

Facile one-pot fabrication of calcium phosphate-based composite nanoparticles as delivery and MRI contrast agents for macrophages.

We developed a facile one-pot fabrication process for magnetic iron oxide-calcium phosphate (IO-CaP) composite nanoparticles via coprecipitation in labile supersaturated CaP solutions containing IO nanocrystals. All the source solutions used were clinically approved for injection, including water and magnetic IO nanocrystals (ferucarbotran, used as a negative magnetic resonance imaging (MRI) contrast agent). This ensured that the resulting nanoparticles were pathogen- and endotoxin-free. The dispersants used were clinically approved heparin sodium (heparin) or adenosine triphosphate disodium hydrate (ATP), which were added to the IO-containing labile supersaturated CaP solutions. Both heparin and ATP coprecipitated with CaP and ferucarbotran to form heparin- and ATP-modified IO-CaP nanoparticles, respectively, with a hydrodynamic diameter of a few hundred nanometers. Both the resulting nanoparticles exhibited relatively large negative zeta potentials, caused by the negatively charged functional groups in heparin and ATP, which improved the particle dispersibility when compared to non-modified IO-CaP nanoparticles. The heparin-modified IO-CaP nanoparticles were effectively ingested by murine macrophages (RAW264.7) without showing significant cytotoxicity but barely ingested by non-phagocytotic human umbilical vein endothelial cells, indicating the potential of these nanoparticles for targeted delivery to macrophages. The heparin-modified IO-CaP nanoparticles exhibited a negative contrast enhancing ability for MRI. Our results show that IO-CaP nanoparticles have potential as delivery and MRI contrast agents for macrophages.

The Development of Vibration System for Applying Magnetic Resonance Elastography (MRE) to the Supraspinatus Muscle.

Palpation is a standard clinical tool to diagnose abnormal stiffness changes in soft tissues. However, it is difficult to palpate the supraspinatus muscle because it locates under the trapezius muscle. The magnetic resonance elastography (MRE) uses harmonic mechanical excitation to quantitatively measure the stiffness (shear modulus) of both the superficial and deep tissues. The purpose of this study was to build a vibration system for applying the MRE to the supraspinatus muscle. In this study, a power amplifier and a pneumatic pressure generator were used to supply vibrations to a vibration pad. Six healthy volunteers underwent MRE. We investigated the effects of position (the head of the humerus and the trapezius muscle) of the vibration pad on the patterns of wave propagation (wave image). When the vibration pad was placed in the trapezius muscle, the wave images represented clear wave propagation. On the other hand, when the vibration pad was placed in the head of the humerus, the wave images represented unclear wave propagation. This result might be caused by wave interferences resulting from the vibrations from bones and an intramuscular tendon of the supraspinatus muscle. The mean shear modulus also was 8.12 ± 1.83 (mean ± SD) kPa, when the vibration pad was placed in the trapezius muscle. Our results demonstrated that the vibration pad should be placed in the trapezius muscle in the MRE of the supraspinatus muscle.

A new technique for MR elastography of the supraspinatus muscle: A gradient-echo type multi-echo sequence.

Magnetic resonance elastography (MRE) can measure tissue stiffness quantitatively and noninvasively. Supraspinatus muscle injury is a significant problem among throwing athletes. The purpose of this study was to develop an MRE technique for application to the supraspinatus muscle by using a conventional magnetic resonance imaging (MRI). MRE acquisitions were performed with a gradient-echo type multi-echo MR sequence at 100Hz pneumatic vibration. A custom-designed vibration pad was used as a pneumatic transducer in order to adapt to individual shoulder shapes. In a gradient-echo type multi-echo MR sequence, without motion encoding gradient (MEG) that synchronizes with vibrations, bipolar readout gradient lobes achieved a similar function to MEG (MEG-like effect). In other words, a dedicated MRE sequence (built-in MEG) is not always necessary for MRE. In this study, 7 healthy volunteers underwent MRE. We investigated the effects of direction of the MEG-like effect and selected imaging planes on the patterns of wave propagation (wave image). The results indicated that wave images showed clear wave propagation on a condition that the direction of the MEG-like effect was nearly perpendicular to the long axis of the supraspinatus muscle, and that the imaging plane was superior to the proximal supraspinatus muscle. This limited condition might be ascribed to specific features of fibers in the supraspinatus muscle and wave reflection from the boundaries of the supraspinous fossa. The mean stiffness of the supraspinatus muscle was 10.6±3.17kPa. Our results demonstrated that using MRE, our method can be applied to the supraspinatus muscle by using conventional MRI.

T2 and Apparent Diffusion Coefficient of MRI Reflect Maturation of Tissue-Engineered Auricular Cartilage Subcutaneously Transplanted in Rats.

In cartilage regenerative medicine, autologous chondrocyte implantation (ACI) has been applied clinically for partial defects of joint cartilage or nasal augmentation. To make treatment with ACI more effective and prevalent, modalities to evaluate the quality of transplanted constructs noninvasively are necessary. In this study, we compared the efficacy of several noninvasive modalities for evaluating the maturation of tissue-engineered auricular cartilage containing a biodegradable polymer scaffold. We first transplanted tissue-engineered cartilage consisting of human auricular chondrocytes, atelocollagen gel, and a poly-l-lactic acid (PLLA) porous scaffold subcutaneously into the back of athymic nude rats. Eight weeks after transplantation, the rats were examined by magnetic resonance imaging (MRI), X-ray, and ultrasound as noninvasive modalities. Then, the excised constructs were examined by histological and biochemical analysis including toluidine blue (TB) staining, glycosaminoglycans content, and enzyme-linked immunosorbent assay of type II collagen. Among the modalities examined, transverse relaxation time (T2) and apparent diffusion coefficient of MRI showed quite a high correlation with histological and biochemical results, suggesting that these can effectively detect the maturation of tissue-engineered auricular cartilage. Since these noninvasive modalities would realize time-course analysis of the maturation of tissue-engineered auricular cartilage, this study provides a substantial insight for improving the quality of tissue-engineered cartilage, leading to improvement of the quality and technique in cartilage regenerative medicine.

Characteristic X-ray absorptiometry applied to the assessment of tissue-engineered cartilage development.

BACKGROUND: Transmission and tomographic X-ray measurements are useful in assessing bone structures, but only a few studies have examined cartilage growth because of the poor contrast in conventional X-ray imaging. OBJECTIVE: In this study, we attempted to use the linear attenuation coefficient (LAC) as a metric of tissue-engineered cartilage development, which would be useful in high-throughput screening of cartilage products. METHODS: Assuming that the LAC is related to the amount of extracellular matrix (ECM) in terms of the density and its atomic components, we measured X-ray absorption through tissue-engineered cartilage constructs. Characteristic X-ray beams from a molybdenum microfocus X-ray tube were employed to avoid beam hardening. The correlation of the LAC with mechanical properties was analyzed for verification. RESULTS: The LAC was higher for chondrocyte constructs and lower for fibroblast-dominant constructs and was consistent with the quantification of toluidine blue staining, which is a proof of ECM production. The LAC was positively correlated with the bending modulus but negatively correlated with the dynamic elastic modulus and stiffness, possibly because of the remaining scaffold. CONCLUSIONS: The LAC has the potential to be used as a metric of development of tissue-engineered cartilage. However, the calcified regions should be excluded from analysis to avoid decreasing the correlation between the LAC and the amount of ECM.

A simple method for MR elastography: a gradient-echo type multi-echo sequence.

To demonstrate the feasibility of a novel MR elastography (MRE) technique based on a conventional gradient-echo type multi-echo MR sequence which does not need additional bipolar magnetic field gradients (motion encoding gradient: MEG), yet is sensitive to vibration. In a gradient-echo type multi-echo MR sequence, several images are produced from each echo of the train with different echo times (TEs). If these echoes are synchronized with the vibration, each readout's gradient lobes achieve a MEG-like effect, and the later generated echo causes a greater MEG-like effect. The sequence was tested for the tissue-mimicking agarose gel phantoms and the psoas major muscles of healthy volunteers. It was confirmed that the readout gradient lobes caused an MEG-like effect and the later TE images had higher sensitivity to vibrations. The magnitude image of later generated echo suffered the T2 decay and the susceptibility artifacts, but the wave image and elastogram of later generated echo were unaffected by these effects. In in vivo experiments, this method was able to measure the mean shear modulus of the psoas major muscle. From the results of phantom experiments and volunteer studies, it was shown that this method has clinical application potential.

Magnetic resonance elastography using an air ball-actuator.

The purpose of this study was to develop a new technique for a powerful compact MR elastography (MRE) actuator based on a pneumatic ball-vibrator. This is a compact actuator that generates powerful centrifugal force vibrations via high speed revolutions of an internal ball using compressed air. This equipment is easy to handle due to its simple principles and structure. Vibration frequency and centrifugal force are freely adjustable via air pressure changes (air flow volume), and replacement of the internal ball. In order to achieve MRI compatibility, all parts were constructed from non-ferromagnetic materials. Vibration amplitudes (displacements) were measured optically by a laser displacement sensor. From a bench test of displacement, even though the vibration frequency increased, the amount of displacement did not decrease. An essential step in MRE is the generation of mechanical waves within tissue via an actuator, and MRE sequences are synchronized to several phase offsets of vibration. In this system, the phase offset was detected by a four-channel optical-fiber sensor, and it was used as an MRI trigger signal. In an agarose gel phantom experiment, this actuator was used to make an MR elastogram. This study shows that the use of a ball actuator for MRE is feasible.

Characteristics of diffusion-weighted stimulated echo pulse sequence in human skeletal muscle.

The aim of our study was to simulate an effective diffusion-weighted imaging (DWI) pulse sequence and to evaluate the best b value in skeletal muscle. The evaluated pulse sequences were spin echo (SE), stimulated echo (STE), and gradient-recalled echo (GRE). The signal intensity changed in some DWI pulse sequences when the b value was changed. Moreover, the static magnetic field of 1.5 T was compared with that of 3.0 T. Next, diffusion tensor imaging of the human skeletal muscle was measured. The experimental subjects were healthy male volunteers (n = 7; age 21.8 ± 1.1 years). We changed the b value in steps of 100 s/mm(2) from 0 to 2000 s/mm(2), and the diffusion values [fractional anisotropy (FA), λ(1), λ(2), and λ(3)] were calculated based on the data. The STE method could maintain signals up to b values of 1300 s/mm(2), but the SE and GRE methods suffered from high noise. In the human study, the mean FA (±SD) was 0.41 ± 0.02 in the tibialis anterior muscle (TA) and 0.31 ± 0.02 in the soleus muscle (SOL) at a b value of 1000 s/mm(2). The correlation of the FA with the b value coefficient and the P value by Student's t test were r = 0.981 and P < 0.001 for the TA and r = 0.982, P < 0.001 for the SOL. However, the FA became high with a low b value. In conclusion, STE was very useful for DWI in a short T (2)-value tissue. Moreover, a minimum b value of 800 s/mm(2) was necessary for evaluation of human skeletal muscle.