The Effect of Steatosis on Shear-Wave Velocity and Viscoelastic Properties Related to Liver Fibrosis Progression in Rat Models.

OBJECTIVE: Hepatic fibrosis has recently been evaluated using ultrasonography or magnetic resonance elastography. Although the shear wave velocity (SWV) obtained using point shear wave elastography (pSWE) provides a valuable measure of fibrosis, underlying steatosis may affect its measurement. METHODS: Using hepatic fibrosis samples, this study evaluated the effect of steatosis on the shear wave velocity of pSWE (Vs) and viscoelastic properties (assessed by dynamic mechanical analysis) of rat liver. Fifty rats with various grades of steatosis and fibrosis underwent open abdominal in vivo Vs measurements using a commercial ultrasound scanner. The mechanical properties of hepatic tissue were also characterized under ex vivo conditions using dynamic mechanical analysis and the Zener model of viscoelasticity. RESULTS: Fibrosis and steatosis progression influenced Vs and elasticity. The SWV computed using the Zener model and Vs showed a substantial correlation (r > 0.8). Fibrosis progression increased SWV. Steatosis was also related to SWV. Steatosis progression obscured the SWV change associated with fibrosis progression. CONCLUSION: We conclude that steatosis progression affects the evaluation of fibrosis progression. This finding could aid discrimination of non-alcoholic steatohepatitis from non-alcoholic fatty liver disease using SWV.

Ultrasound Assessment of Gaze-induced Posterior Eyewall Deformation in Highly Myopic Eyes.

Purpose: To establish a quantitative metric of posterior eyewall deformability in different directions of gaze in highly myopic eyes with and without posterior staphyloma. Methods: A prospective study was performed on 53 highly myopic patients (106 eyes). Ultrasound scans were acquired in primary, up, downward, nasal, and temporal gazes. A validated intensity-based segmentation algorithm was used to quantify the posterior eyewall geometry on digitalized B-scan images. Posterior eyewall local curvature (K) and distance (L) to the transducer were calculated. The associations between directions of gaze, axial length (AL), and presence of staphyloma with the K and L parameters were assessed. Results: A total of 53 participants (106 eyes) were studied. Multivariate regression analysis demonstrated that, after accounting for longer AL, and presence of staphyloma, eccentric gaze was often independently associated with various K and L parameters. Specifically, downward gaze was associated with increased posterior eyewall concavity as reflected in the maximum of K (KMax) (ß = 0.050, P < 0.001) and absolute value of KMax (ß = 0.041, P = 0.011). Both downward gaze and upgaze were independently associated with increase in the derivative of absolute KMax (which is consistent with more apparent, steeper staphyloma ridges), local KMax (which detects KMax at smaller intervals), and Kstd (which represents likelihood of staphyloma presence) and decrease in maximum of L (which represents movement of the staphyloma apex) with all P < 0.05. The ß coefficients for downward gaze were consistently greater in magnitude compared with those in upgaze. After accounting for AL and presence of staphyloma, horizontal gazes were independently associated only with decrease in the standard deviation of L (which also represents likelihood of staphyloma presence) and maximum of L. Conclusions: Downward gaze results in a significant increase in posterior eyewall concavity in highly myopic eyes after accounting for AL and staphyloma presence. In comparison with downward gaze, upgaze resulted in a lower magnitude, but significant changes in staphyloma ridge steepness and the likelihood of staphyloma presence. Horizontal gazes seemed to be associated with less posterior eyewall geometric parameters. Studies are required to further assess the association between downward gaze during near work on posterior eyewall concavity and possible effects on myopia development and progression.

Automated Classification and Detection of Staphyloma with Ultrasound Images in Pathologic Myopia Eyes.

The aim of this study was to develop an eyewall curvature- and axial length (AxL)-based algorithm to automate detection (clinician-free) of staphyloma ridge and apex locations using ultrasound (US). Forty-six individuals (with emmetropia, high myopia or pathologic myopia) were enrolled in this study (AxL range: 22.3-39.3 mm), yielding 130 images in total. An intensity-based segmentation algorithm automatically tracked the posterior eyewall, calculating the posterior eyewall local curvature (K) and distance (L) to the transducer and the location of the staphyloma apex. By use of the area under the receiver operator characteristic (AUROC) curve to evaluate the diagnostic ability of eight local statistics derived from K, L and AxL, the algorithm successfully quantified non-uniformity of eye shape with an AUROC > 0.70 for most K-based parameters. The performance of binary classification (staphyloma absence vs. presence) was assessed with the best classifier (the combination of AxL, standard deviation of K and standard deviation of L) yielding a diagnostic validation performance of 0.897, which was comparable to the diagnostic performance of junior clinicians. The staphyloma apex was localized with an average error of 1.35 ± 1.34 mm. Combined with the real-time data acquisition capabilities of US, this method can be employed as a screening tool for clinician-free in vivo staphyloma detection.

Assessment of the frequency dependence of acoustic properties on material, composition, and scatterer size of the medium.

PURPOSE: The aim of this study was to elucidate the frequency dependence of the speed of sound (SoS) and attenuation coefficients in phantoms with controlled attenuation properties (scatterer density, scatterer size, absorption control material) and rat livers. METHODS: The frequency dependence of SoS and attenuation coefficients were evaluated with ultrasound (1-15 MHz) by observing multiple phantoms with different scatterer sizes, densities, and presence or absence of evaporated milk as absorbing media. Normal and fatty model rat livers were examined with the same protocol. RESULTS: The phantom results revealed that the scatterer density and SoS of the base media were the dominant factors causing the changes in SoS. Frequency dependence was not observed in SoS. Assessment of the attenuation coefficient showed that the frequency dependence was mainly affected by absorption attenuation when the scatterer was as small as a hepatocyte (i.e. ≤ 10 µm). Scattering attenuation was also observed to affect frequency dependence when the scatterer was as large as lipid droplets (i.e. ≤ 40 µm). CONCLUSION: Assuming a consistent size of the main scatterers in the evaluation medium, the frequency dependence of the SoS and attenuation coefficients may provide insight into the scatterer density and the contribution of absorption and scattering attenuation. Further studies in the higher frequency band (up to about 50 MHz) are expected to advance the clinical application of high-frequency ultrasound.

Quantitative Assessment of Asymmetric Choroidal Outflow in Pachychoroid Eyes on Ultra-Widefield Indocyanine Green Angiography.

Purpose: To quantitatively demonstrate asymmetric choroidal outflow in pachychoroid (central serous chorioretinopathy [CSC]/pachychoroid pigment epitheliopathy [PPE]) eyes using mid-phase, ultra-widefield indocyanine green angiography (UWF ICGA) images. Methods: Eyes with a clinical diagnosis of CSC/PPE were imaged with multimodal imaging including UWF ICGA (Optos California). Quadrant brightness was measured by manually segmenting based on vortex vein location, calculating the brightness "max-min" value to assess nonuniformity between quadrants, and comparing between CSC/PPE and control eyes. A multivariate linear regression was performed to determine, across individual eyes, which specific quadrants have the greatest brightness in pachychoroid eyes, after taking into account patient-eye-specific variability. Results: Thirty-three eyes (18 patients) with CSC/PPE along with 16 eyes of 9 controls had a mean age of 51.94 ± 9.72 vs. 53.78 ± 17.92 years (P = 0.731), respectively. Max-min analysis showed significantly increased likelihood of nonuniform drainage between vortex veins in both CSC/PPE and control eyes. Multivariate linear regression in control eyes showed that on average, the inferotemporal quadrant was significantly brighter than the superonasal quadrant (9.72 units, P < 0.001). Among CSC/PPE eyes, adjusting for the preferential, nonuniform drainage in control eyes, the inferonasal and inferotemporal quadrants in CSC/PPE eyes remained significantly brighter than the reference quadrant by 5.36 units (P = 0.034) and 7.51 units (P = 0.008), respectively. Conclusions: Asymmetric choroidal venous outflow occurs in both control and CSC/PPE eyes based on UWF ICGA quantitative brightness levels in each quadrant. Increased brightness levels along inferior quadrants in mid-phase ICGA images suggest venous outflow congestion among eyes with CSC or PPE.

Free fatty acid-based low-impedance liver image: a characteristic appearance in nonalcoholic steatohepatitis (NASH).

BACKGROUND: To examine in vitro acoustic property of nonalcoholic fatty disease in mouse and human liver to identify nonalcoholic steatohepatitis (NASH). METHODS: The acoustic impedance (× 106 kg/m2/s) was measured in 35 free fatty acids (FFAs, 500 mmol/L) and histologically-diagnosed liver samples of twelve mice (four control, four simple steatosis [SS], and four NASH) and eight humans (two control, three SS, and three NASH), using 80-MHz acoustic microscopy. The sum of percentage (SP) composition of FFAs (SP-FFAs) was also assessed. RESULTS: Median impedance of all FFAs was 0.7 (5 FFAs with impedance 0.7); 17 FFAs with impedance < 0.7 were classified as low-impedance group; and, 13 FFAs with impedance > 0.7 were classified as high-impedance group. The median impedance of the mouse liver decreased from control (1.715), to SS (1.68), to NASH (1.635) (control versus NASH, p = 0.039 without significant differences for the other comparisons, p ≥ 0.1). Similarly, the median impedance of human liver showed decreased from control (1.825), to SS (1.788), to NASH (1.76) (control versus SS, p = 0.023; control versus NASH, p = 0.003; SS versus NASH, p = 0.050). The ratio of SP-FFAs between the low-impedance and high-impedance groups showed an increase in both mice and humans, with significant differences in mice (control versus SS, p < 0.001; control versus NASH, p < 0.001; SS versus NASH, p = 0.003), without significant differences in humans (p ≥ 0.671). CONCLUSION: Lower acoustic impedance based on the intrahepatic composition of FFAs may be characteristic of NASH.

Material Properties of Human Ocular Tissue at 7-µm Resolution.

Quantitative assessment of the material properties of ocular tissues can provide valuable information for investigating several ophthalmic diseases. Quantitative acoustic microscopy (QAM) offers a means of obtaining such information, but few QAM investigations have been conducted on human ocular tissue. We imaged the optic nerve (ON) and iridocorneal angle in 12-µm deparaffinized sections of the human eye using a custom-built acoustic microscope with a 250-MHz transducer (7-µm lateral resolution). The two-dimensional QAM maps of ultrasound attenuation (α), speed of sound ( c), acoustic impedance ( Z), bulk modulus ( K), and mass density (ρ) were generated. Scanned samples were then stained and imaged by light microscopy for comparison with QAM maps. The spatial resolution and contrast of scanning acoustic microscopy (SAM) maps were sufficient to resolve anatomic layers of the retina (Re); anatomic features in SAM maps corresponded to those seen by light microscopy. Significant variations of the acoustic parameters were found. For example, the sclera was 220 MPa stiffer than Re, choroid, and ON tissue. To the authors' knowledge, this is the first systematic study to assess c, Z, K, ρ, and α of human ocular tissue at the high ultrasound frequencies used in this study.

Acoustic Impedance Analysis with High-Frequency Ultrasound for Identification of Fatty Acid Species in the Liver.

Acoustic properties of free fatty acids present in the liver were studied as a possible basis for non-invasive ultrasonic diagnosis of non-alcoholic steatohepatitis. Acoustic impedance was measured for the following types of tissue samples: Four pathologic types of mouse liver, five kinds of FFAs in solvent and five kinds of FFAs in cultured Huh-7 cells. A transducer with an 80-MHz center frequency was incorporated into a scanning acoustic microscopy system. Acoustic impedance was calculated from the amplitude of the signal reflected from the specimen surface. The Kruskal-Wallis test revealed statistically significant differences (p < 0.01) in acoustic impedance not only among pathologic types, but also among the FFAs in solvent and in cultured Huh-7 cells. These results suggest that each of the FFAs, especially palmitate, oleate and palmitoleate acid, can be distinguished from each other, regardless of whether they were in solution or absorbed by cells.

Prepubertal testicular tumors: a single-center experience of 44years.

PURPOSE: To present the clinical and histological features of prepubertal testicular tumors (PTTs), the long-term experience of a single institution was reviewed. MATERIALS AND METHODS: A total of 62 prepubertal children who were treated for testicular tumors at Kanagawa Children's Medical Center from 1971 to 2014 were retrospectively reviewed. Histopathological findings, age at operation, clinical stage, and outcomes were analyzed. Clinical findings between the two eras, 1971-1990 and 1991-2014, were also compared. RESULT: The median age at operation was 17months. Pathology revealed 29 teratomas (47%), 26 yolk sac tumors (42%), 5 epidermoid cysts (8%), 1 Sertoli cell tumor (1.5%), and 1 benign cyst (1.5%). Teratoma was the most common tumor in this series, and children with immature teratomas were operated at a significantly younger age than those with mature teratomas. Yolk sac tumor was the second most common. The clinical stages of yolk sac tumors were stage I in 23 (89%) and stage II in 3 (11%). Clinical findings were not significantly different between the early and late eras. CONCLUSIONS: To the best of our knowledge, this is the largest single-center study of PTTs in Japan. The most common PTT in this study was teratoma, followed by yolk sac tumor. There was no significant difference in the histological distribution of PTTs between the two eras. Compared with the current data of single-center series in North America, the incidence of yolk sac tumor was markedly higher in the present study. This discrepancy is possibly explained by racial differences.

Cystic local recurrence of renal cell carcinoma after laparoscopic radical nephrectomy in a hemodialysis patient.

Although local recurrence of renal cell carcinoma after laparoscopic radical nephrectomy is sometimes reported, cystic local recurrence of renal cell carcinoma has rarely been reported. We report the case of a 59-year-old man with hemodialysis who developed cystic local recurrence of renal cell carcinoma accompanied by acquired cystic disease of the kidney in the retroperitoneal space after laparoscopic radical nephrectomy. A cystic tumor of 5.1 cm in diameter occurred in the left retroperitoneal space 15 months after left laparoscopic radical nephrectomy, and enlarged to 7.2 cm in diameter with enhanced mass along the wall of the cyst 36 months after surgery. The cystic tumor was removed and showed local recurrence of renal cell carcinoma on pathological examination.