Ability of ultrasound backscattering to predict mechanical properties of bovine trabecular bone

Ultrasound (US) backscatter measurements have been proposed for the quantitative evaluation of bone quality. In this study, we explored the ability of broadband US backscatter (BUB) and integrated reflection coefficient (IRC) to predict density and mechanical properties of trabecular bone, as compared to normalized broadband US attenuation (nBUA) and speed of sound (SOS). These acoustic parameters were measured in 41 in vitro samples of bovine trabecular bone and correlated with a number of mechanical parameters and with volumetric bone mineral density (BMDvol). BUB correlated statistically significantly with the volumetric bone mineral density (r = 0.61, p < 0.01), Young's modulus (r = 0.40, p < 0.01) and ultimate strength (r = 0.40, p < 0.01). IRC was even more strongly correlated with BMD(vol) (r = 0.92, p < 0.01) and most of the mechanical parameters (0.81 < r < 0.85). Strong correlations were also found between mechanical parameters and SOS (0.87 < r < 0.90). No significant correlation was found between attenuation (nBUA) and either BMD(vol) or mechanical parameters. Reproducibilities (standardized CV%) of BUB (3.5%) and IRC (1.5%) were comparable to those of nBUA (2.3%) and SOS (0.5%). To conclude, BUB and IRC are promising parameters for the evaluation of density and mechanical properties of trabecular bone. Advantageously, BUB and IRC can be determined with a single transducer, hypothetically enabling measurements at many clinically relevant fracture sites.     

Ultrasonic Through-Transmission Measurements of Human Musculoskeletal and Fat Properties

The study described here was aimed at investigating the feasibility of using the ultrasonic through-transmission technique to estimate human musculoskeletal and fat properties. Five hundred eighty-two volunteers were assessed by dual-energy X-ray absorptiometry (DXA) and ultrasonic transmission techniques. Bone mineral density (BMD), muscle and fat mass were measured for both legs and the whole body. Hip BMD and spine BMD were also measured. Ultrasonic transmission measurements were performed on the heel, and the measured parameters were broadband ultrasound attenuation (BUA), speed of sound (SOS), ultrasonic stiffness index (SI), T-score and Z-score, which were significantly correlated with all measured BMDs. The optimal correlation was observed between SI and left-leg BMD (p < 0.001) before and after adjustment for age, sex and body mass index (BMI). The linear and partial correlation analyses revealed that BUA and SOS were closely associated with muscle and fat mass, respectively. Multiple regressions revealed that muscle and fat mass significantly contributed to the prediction of transmission parameters, explaining up to 17.83% (p < 0.001) variance independently of BMD. The results suggest that the ultrasonic through-transmission technique could help in the clinical diagnosis of skeletal and muscular system diseases.     

Measurements of ultrasonic backscattered spectral centroid shift from spine in vivo: methodology and preliminary results

Ultrasonic backscatter measurements from vertebral bodies (L3 and L4) in nine women were performed using a clinical ultrasonic imaging system. Measurements were made through the abdomen. The location of a vertebra was identified from the bright specular reflection from the vertebral anterior surface. Backscattered signals were gated to isolate signal emanating from the cancellous interiors of vertebrae. The spectral centroid shift of the backscattered signal, which has previously been shown to correlate highly with bone mineral density (BMD) in human calcaneus in vitro, was measured. BMD was also measured in the nine subjects' vertebrae using a clinical bone densitometer. The correlation coefficient between centroid shift and BMD was r = -0.61. The slope of the linear fit was -160 kHz / (g/cm(2)). The negative slope was expected because the attenuation coefficient (and therefore magnitude of the centroid downshift) is known from previous studies to increase with BMD. The centroid shift may be a useful parameter for characterizing bone in vivo.     

Interlaboratory comparison of ultrasonic backscatter coefficient measurements from 2 to 9 MHz.

OBJECTIVE: As are the attenuation coefficient and sound speed, the backscatter coefficient is a fundamental ultrasonic property that has been used to characterize many tissues. Unfortunately, there is currently far less standardization for the ultrasonic backscatter measurement than for the other two, as evidenced by a previous American Institute of Ultrasound in Medicine (AIUM)-sponsored interlaboratory comparison of ultrasonic backscatter, attenuation, and speed measurements (J Ultrasound Med 1999; 18:615-631). To explore reasons for these disparities, the AIUM Endowment for Education and Research recently supported this second interlaboratory comparison, which extends the upper limit of the frequency range from 7 to 9 MHz. METHODS: Eleven laboratories were provided with standard test objects designed and manufactured at the University of Wisconsin (Madison, WI). Each laboratory was asked to perform ultrasonic measurements of sound speed, attenuation coefficients, and backscatter coefficients. Each laboratory was blinded to the values of the ultrasonic properties of the test objects at the time the measurements were performed. RESULTS: Eight of the 11 laboratories submitted results. The range of variation of absolute magnitude of backscatter coefficient measurements was about 2 orders of magnitude. If the results of 1 outlier laboratory are excluded, then the range is reduced to about 1 order of magnitude. Agreement regarding frequency dependence of backscatter was better than reported in the previous interlaboratory comparison. For example, when scatterers were small compared with the ultrasonic wavelength, experimental frequency-dependent backscatter coefficient data obtained by the participating laboratories were usually consistent with the expected Rayleigh scattering behavior (proportional to frequency to the fourth power). CONCLUSIONS: Greater standardization of backscatter measurement methods is needed. Measurements of frequency dependence of backscatter are more consistent than measurements of absolute magnitude.     

Evaluation of lens hardness in cataract surgery using high-frequency ultrasonic parameters in vitro

Ultrasonic parameters of sound velocity and frequency-dependent attenuation ranging from 25 to 45 MHz were measured for the purpose of evaluating the hardness of lenses in cataract surgery (phacoemulsification). Measurements were performed with a 35-MHz ultrasonic transducer on porcine lenses in which artificially cataracts were induced. The hardness of the cataractous lens was also evaluated by mechanical measurement of its elastic properties. The results indicated that the ultrasonic attenuation coefficients in normal porcine lenses were approximately 4.49 +/- 0.05 (mean +/- SD) and 6.32 +/- 0.04 dB/mm at 30 and 40 MHz, respectively. The development progression of the cataracts resulted in the attenuation coefficient increasing linearly to 7.36 +/- 0.25 and 11.1 +/- 0.92 dB/mm, respectively, corresponding to an increase of Young's modulus from 2.6 to 101.2 kPa. The sound velocity concomitantly increased from 1639.8 +/- 4.2 to 1735.6 +/- 10.4 m/s. Evaluation of the relationship between the phacoemulsification energy level and ultrasonic parameters in vitro by surgeons revealed that both the attenuation coefficient and sound velocity were linearly correlated with the phacoemulsification energy (r = 0.941 and 0.915, respectively). These results showed that measuring high-frequency ultrasonic parameters provides surgeons with good capability and reproducibility for selecting the optimal energy level for phacoemulsification.     

Bone marrow influences quantitative ultrasound measurements in human cancellous bone

Quantitative ultrasound (QUS) transmission and backscatter measurements were made in 46 human cancellous bone specimens from the calcaneus. All QUS measurements were made at 35 degrees C, initially with marrow filling the pores and then repeated after substituting water for marrow. Bone mineral density (BMD) was determined using x-ray absorptiometry. Marrow significantly decreased ultrasound (US) velocity, but increased attenuation, attenuation slope and backscatter (p < 0.001 for all) compared to the water-saturated state. The impact of marrow on QUS measurements was greater at lower BMD values (p < 0.05), and was greater in women than in men (p < 0.05). QUS measurements in marrow-saturated specimens correlated less strongly with BMD than did corresponding measurements in water-saturated specimens (p < 0.05), consistent with interspecimen marrow heterogeneity. These data indicate that the potential impact of marrow should be considered when interpreting clinical QUS measurements. Understanding and exploiting these effects could lead to novel approaches for ultrasonic characterisation of both bone and marrow.     

Estimation of wrist fracture load using phalangeal speed of sound: an in vitro study

This study aimed to evaluate the ability of speed of sound (SOS) measured at the phalanges to estimate simulated wrist fracture load and stress. SOS was measured along the proximal phalanges of the second, third and fourth fingers using an ultrasound (US) system operating in axial transmission mode. The bone mineral density (BMD) of the radius and the phalanges was also measured with quantitative computed tomography (QCT) and dual x-ray absorptiometry (DXA), and the combined cortical thickness (CCT) of the phalanges was measured from hand radiographs. After the measurements were completed, the radius was excised from the cadaver, embedded in polymethylmethacrylate and tested to failure on a servohydraulic testing machine. The configuration of the radius was chosen to simulate a fall onto the hand. Linear regression analysis showed a highly significant correlation between SOS (r = 0.76–0.94, p < 0.001), CCT (r = 0.86–0.90, p < 0.001) and BMD (r = 0.92–0.96, p < 0.0001) in the three proximal phalanges measured. SOS, BMD and CCT were significant predictors of fracture load (r = 0.60–0.69, p < 0.03) and stress (r = 0.65–0.77, p < 0.02). Cortical area and bone mineral content (BMC) of the radius were consistently higher predictors of fracture load (r = 0.76–0.82, p < 0.01 for area and R = 0.78–0.88, p < 0.01 for BMC) than BMD. The correlation of BMC and area was poorer with fracture stress. In a step-wise regression analysis using both phalangeal BMD and SOS, only SOS remained a significant predictor of fracture stress. In forward stepwise regression analysis, both cortical area and SOS were entered into the regression model to estimate fracture load. Only SOS remained significant in the model for estimating fracture stress. Phalangeal BMD was only entered in the combined model with the cortical area at the 4% site (r = 0.84, p = 0.002). Phalangeal SOS is a useful parameter in the assessment of bone status of the radius.     

Estimation of wrist fracture load using phalangeal speed of sound: an in vitro study

This study aimed to evaluate the ability of speed of sound (SOS) measured at the phalanges to estimate simulated wrist fracture load and stress. SOS was measured along the proximal phalanges of the second, third and fourth fingers using an ultrasound (US) system operating in axial transmission mode. The bone mineral density (BMD) of the radius and the phalanges was also measured with quantitative computed tomography (QCT) and dual x-ray absorptiometry (DXA), and the combined cortical thickness (CCT) of the phalanges was measured from hand radiographs. After the measurements were completed, the radius was excised from the cadaver, embedded in polymethylmethacrylate and tested to failure on a servohydraulic testing machine. The configuration of the radius was chosen to simulate a fall onto the hand. Linear regression analysis showed a highly significant correlation between SOS (r = 0.76–0.94, p < 0.001), CCT (r = 0.86–0.90, p < 0.001) and BMD (r = 0.92–0.96, p < 0.0001) in the three proximal phalanges measured. SOS, BMD and CCT were significant predictors of fracture load (r = 0.60–0.69, p < 0.03) and stress (r = 0.65–0.77, p < 0.02). Cortical area and bone mineral content (BMC) of the radius were consistently higher predictors of fracture load (r = 0.76–0.82, p < 0.01 for area and R = 0.78–0.88, p < 0.01 for BMC) than BMD. The correlation of BMC and area was poorer with fracture stress. In a step-wise regression analysis using both phalangeal BMD and SOS, only SOS remained a significant predictor of fracture stress. In forward stepwise regression analysis, both cortical area and SOS were entered into the regression model to estimate fracture load. Only SOS remained significant in the model for estimating fracture stress. Phalangeal BMD was only entered in the combined model with the cortical area at the 4% site (r = 0.84, p = 0.002). Phalangeal SOS is a useful parameter in the assessment of bone status of the radius.     

The experimental investigation of ultrasonic properties for a sonicated contrast agent and its application in biomedicine

The ultrasonic properties of a promising ultrasound (US) contrast agent, named SDA (sonicated dextrose albumin) are reported in this paper. SDA is a suspension of stable microencapsulated gas bubbles with average diameter 2.0 microm prepared from sonicated dextrose albumin. The ultrasonic linear and nonlinear parameters, such as acoustic velocity, sound attenuation and acoustic nonlinearity parameter B/A of SDA, as a function of its bubble concentration from 1.0 x 10(7) to 2.05 x 10(8) microbubbles/mL in the frequency range of 2-6 MHz are measured in vitro. The sound attenuation coefficients over 2-6 MHz are linearly proportional to the bubble concentration and frequency. It is important to point out that the acoustic nonlinearity parameter B/A for SDA has a very large value that nonlinearly increases with the increase of bubble concentration.     

慢性阻塞性肺疾病患者的骨超声和骨矿含量的改变

目的　通过观察慢性阻塞性肺疾病 (COPD)患者的跟骨超声振幅衰减 (BUA)、超声声速 (SOS)、髋部骨矿含量(BMC)及骨密度 (BMD)变化 ,进一步了解COPD与骨质疏松的关系。方法　测定COPD老年男性患者及对照组各 3 0例的跟骨BUA、SOS和股骨颈、Ward’s三角、股骨粗隆的BMD、BMC以及动脉血气。结果　老年COPD组的股骨颈、Ward’s三角、股骨粗隆的BMD、BMC以及跟骨的BUA、SOS均较对照组的测定值低 ,差异有显著性。COPD组动脉血气分析氧分压较对照组低 (P <0 .0 1)。结论　COPD患者因缺氧引起各脏器受损 ,加速骨量丢失而易患骨质疏松症     

Feasibility study of ultrasonic fatty liver biopsy: texture vs. attenuation and backscatter

The objective of this study was to compare textural to attenuation/backscatter indices of fatty liver correlated to histology to suggest the better approach for an objective noninvasive ultrasonic "biopsy". Forty-four patients with severe steatosis by histopathology were selected for this study. Ten patients had "pure" fatty liver and 34 had in addition fibrosis and/or inflammation. Ultrasonic images were acquired before needle insertion. The ROI used for biopsy was marked on the ultrasonic image and characterized by three attenuation/backscatter and 18 textural related indices. Statistical analysis was performed using logistic regression. Twenty-one healthy subjects served as control. The attenuation/backscatter indices were superior to textural indices in differentiating between the categories studied. Pure fatty livers could be reliably identified (AUC = 1, SE = 0). Among the 18 textural indices, "co-occurrences sum entropy" and "co-occurrences entropy" presented the best results. Attenuation/backscatter based indices appear to have better potential than the textural based indices.     

Tissue-mimicking phantoms for photoacoustic and ultrasonic imaging

In both photoacoustic (PA) and ultrasonic (US) imaging, overall image quality is influenced by the optical and acoustical properties of the medium. Consequently, with the increased use of combined PA and US (PAUS) imaging in preclinical and clinical applications, the ability to provide phantoms that are capable of mimicking desired properties of soft tissues is critical. To this end, gelatin-based phantoms were constructed with various additives to provide realistic acoustic and optical properties. Forty-micron, spherical silica particles were used to induce acoustic scattering, Intralipid(?) 20% IV fat emulsion was employed to enhance optical scattering and ultrasonic attenuation, while India Ink, Direct Red 81, and Evans blue dyes were utilized to achieve optical absorption typical of soft tissues. The following parameters were then measured in each phantom formulation: speed of sound, acoustic attenuation (from 6 to 22 MHz), acoustic backscatter coefficient (from 6 to 22 MHz), optical absorption (from 400 nm to 1300 nm), and optical scattering (from 400 nm to 1300 nm). Results from these measurements were then compared to similar measurements, which are offered by the literature, for various soft tissue types. Based on these comparisons, it was shown that a reasonably accurate tissue-mimicking phantom could be constructed using a gelatin base with the aforementioned additives. Thus, it is possible to construct a phantom that mimics specific tissue acoustical and/or optical properties for the purpose of PAUS imaging studies.     

Further studies on ultrasonic properties of blood clots

Two-dimensional echocardiography has been found to be an effective clinical tool in diagnosing intracardiac thrombi. Misdiagnosis may, however, still frequently occur because of the difficulty in differentiating the thrombi from other intracavitary masses based only on the echographic appearance of these structures. Ultrasonic tissue characterization techniques have been used in attempts to minimize this diagnostic uncertainty. Previously, we have shown that all ultrasonic parameters of blood, including ultrasonic backscatter, a quantitative measure of echogenicity, at 7.5 MHz increase rapidly following clotting. In this article, we report recent results on the measurements of attenuation and backscatter of thrombi as a function of time following clotting over the frequency range of 3 MHz to 8 MHz. These results indicate that ultrasonic backscatter from thrombi 12 h old is at least 18 dB higher than that of unclotted blood over the frequency range of 3 MHz to 8 MHz, and the slope of the attenuation coefficient is increased to 0.43 dB/cm-MHz. Comparison with the backscatter of bovine myocardium shows that the myocardium is more echogenic than fresh thrombi and is less echogenic than thrombi 12 to 24 h old. Similar results were also obtained for integrated backscatter measurements over the same frequency range.     

Detection of blood coagulation and clot formation using quantitative ultrasonic parameters

The ultrasonic parameters of sound velocity, attenuation and integrated backscatter were applied to detect the process of coagulation and clot formation in porcine blood. Fresh porcine blood containing 15% anticoagulant solution was collected. Blood samples with a hematocrit of 45% were obtained by reconstituting the packed erythrocytes with the separated plasma for ultrasound measurements performed with a 10-MHz focused transducer. A 24-mL aliquot of blood was placed in a container and 12 mL of 0.2 mol/L CaCl2 solution was added to induce clot formation. In each measurement, radio-frequency signals of the blood digitized at 100 MHz were collected for 50 min at a temporal resolution of 1 A-line per s. Results showed that all of the parameters increased within the initial 3 min and, then, immediately decreased dramatically as the CaCl2 solution was added. Subsequently, the sound velocity gradually increased with time and the integrated backscatter and attenuation increased in accordance with blood coagulation until approximately 500 and 2600 s, respectively. The integrated backscatter, attenuation and sound velocity can be divided into different stages, including red cell aggregation, reduction in hematocrit, blood coagulation and clot formation, corresponding to variations in the physical and chemical properties of the blood. The integrated backscatter, attenuation and sound velocity increased because of the changes in blood properties during the process of coagulation and clot formation: by 8.2 dB, 0.65 dB/cm, and 0.6%, respectively. These results provide a feasibility for further applying ultrasonic parameters to in vivo monitor the progress of clotting and thrombosis research.     

Quantitative ultrasound predicts bone mineral density and failure load in human lumbar vertebrae

BACKGROUND: Quantitative ultrasound is in widespread clinical use for assessment of bone quality at peripheral skeletal sites, but has not yet been applied to those sites in the axial skeleton, such as the spine and hip, where osteoporotic fractures are common. METHODS: Ultrasound measurements were made in 11 cadaveric vertebrae and relationships with bone mineral density and failure load were investigated. An ultrasonic imaging system was used to measure speed of sound, broadband ultrasonic attenuation, and attenuation at a single frequency, through the vertebral body in the sagittal plane. Ultrasonic measurements were averaged over a region of interest centrally within the vertebral body, and were calculated with and without normalization for bone size. Vertebral bone mineral density was measured in antero-posterior and lateral projections using dual energy X-ray absorptiometry. Compressive mechanical testing was performed to determine vertebral failure load. FINDINGS: Bone mineral density correlated with failure load (r=0.74-0.78, all P<0.01), and with quantitative ultrasound (r=0.63-0.82, P=0.038-0.004), in line with previous studies. Of the ultrasonic measurements, those parameters not normalized for bone size gave the highest correlations with failure load, ranging from r=0.71 (P=0.021) for speed of sound to r=0.93 (P<0.001) for attenuation. When ultrasonic measurements were normalized for bone size, the correlations with both failure load and bone mineral density were lower. INTERPRETATION: These results confirm the feasibility of vertebral quantitative ultrasound in vitro, and indicate that ultrasound does provide information on both bone mineral density and failure load. The predictive performance of ultrasonic measurements for failure load was comparable to or greater than that of bone mineral density, suggesting that ultrasound has the potential to be at least as useful as mineral density in the assessment of vertebral bone. Normalizing ultrasonic measurements for bone size reduced the strength of correlations because both bone mineral density and bone strength reflect bone size to a certain extent.     

Oil-in-gelatin dispersions for use as ultrasonically tissue-mimicking materials

A form of tissue-mimicking material is reported in which oil droplets are dispersed in a water-based gelatin. Broad ranges of ultrasonic parameters, including speed of sound, attenuation coefficient, density and backscatter level, exist for this material. Very important, the attenuation coefficients are nearly proportional to the frequency as in the case of mammalian tissue and the available attenuation coefficient slopes span the range of mammalian tissues. The available range of slopes is 0.1 dB/cm/MHz through at least 2.0 dB/cm/MHz. The available speeds of sound range from a minimum below that of mammalian fat (～1460 m/s) to a maximum above the accepted average for human tissue (1540 m/s). Densities available range from below that of fat (～0.92 gm/cm³) through about 1.00 gm/cm³. Backscatter levels are easily made negligible compared to clinical levels and compared to those exhibited in previously reported tissue-mimicking materials in which the suspended particles are solid (Madsen, 1978; Burlew, 1980). Addition of solid or hollow glass scatterers allows backscatter levels to be made comparable to those clinically observed.     

A particulate contrast agent with potential for ultrasound imaging of liver

Ultrasonic backscatter and attenuation coefficients of a medium can be increased by the addition of solid, micron sized inhomogeneities. A potentially useful agent for ultrasonic contrast of liver images has been identified. Iodipamide ethyl ester (IDE) particles can be produced in the form of dense, relatively incompressible solids with high impedance mismatch to water. The chemical, biomechanical, and pharmacological properties of the small, uniform diameter IDE particles permit safe intravenous injection followed by rapid accumulation by reticuloendothelial (RE) cells of the liver and spleen, and later elimination from these organs. Since the particles are phagocytized by RE cells, present in normal liver but not in tumors and many lesions, the selective enhancement of ultrasonic backscatter should improve detectability of lesions which are hypo- or iso-echoic compared to surrounding tissue. The mechanisms of particle-ultrasound interaction may be described by relative motion attenuation, and scattering from a cloud of dense, incompressible spheres for the case of IDE particles in agar. Thus, values of attenuation and backscatter can be controlled by choice of ultrasound frequency and particle concentration and size. When the particles are accumulated in rat livers, additional mechanisms induce attenuation and backscatter in excess of that predicted by IDE in agar. This preliminary work demonstrates that solid, biocompatible particles may be useful as an ultrasonic contrast agent.     

Interlaboratory comparison of ultrasonic backscatter, attenuation, and speed measurements.

In a study involving 10 different sites, independent results of measurements of ultrasonic properties on equivalent tissue-mimicking samples are reported and compared. The properties measured were propagation speed, attenuation coefficients, and backscatter coefficients. Reasonably good agreement exists for attenuation coefficients, but less satisfactory results were found for propagation speeds. As anticipated, agreement was not impressive in the case of backscatter coefficients. Results for four sites agreed rather well in both absolute values and frequency dependence, and results from other sites were lower by as much as an order of magnitude. The study is valuable for laboratories doing quantitative studies.     

In vivo measurements of ultrasound transmission through the human proximal femur

Quantitative ultrasound (QUS) measurements can be used to estimate osteoporotic fracture risk. The commonly used variables are the speed of sound (SOS) and the frequency dependent sound attenuation (broadband ultrasound attenuation, [BUA]) of a wave propagating through the bone, preferably the calcaneus. The technology, so far, is less suitable for direct measurement in vivo at the spine or the femur for prediction of bone mineral density (BMD) or fracture risk at the main osteoporotic fracture sites. To improve the clinical performance of QUS, we built a device for direct QUS measurements at the human femur in vivo. In vivo images of ultrasound transmission at one of the main fracture sites, the proximal femur, could be acquired. The estimated precision of SOS measurements of 0.5% achieved at the femur is comparable with the precision of peripheral QUS devices.     

Wavelet-based signal processing of in vitro ultrasonic measurements at the proximal femur

To estimate osteoporotic fracture risk, several techniques for quantitative ultrasound (QUS) measurements at peripheral sites have been developed. As these techniques are limited in the prediction of fracture risk of the central skeleton, such as the hip, we are developing a QUS device for direct measurements at the femur. In doing so, we noticed the necessity to improve the conventional signal processing because it failed in a considerable number of measurements due to multipath transmission. Two sets of excised human femurs (n = 6 + 34) were scanned in transmission mode. Instead of using the conventional methods, the radio-frequency signals were processed with the continuous wavelet transform to detect their time-of-flights for the calculation of speed-of-sound (SOS) in bone. The SOS-values were averaged over a region similar to the total hip region of dual X-ray absorptiometry (DXA) measurements and compared with bone mineral density (BMD) measured with DXA. Testing six standard wavelets, this algorithm failed for only 0% to 6% of scan in test set 1 compared with 29% when using conventional algorithms. For test set 2, it failed for 2% to 12% compared with approximately 40%. SOS and BMD correlated significantly in both test sets (test set 1: r2 = 0.87 to 0.92, p < 0.007; test set 2: r2 = 0.68 to 0.79, p < 0.0001). The correlations are comparable with correlations recently reported. However, the number of evaluable signals could be substantially increased, which improves the perspectives of the in vivo measurements.