Diagnostic Performance of Quantitative Ultrasound Parameters in Non-alcoholic Fatty Liver Disease.

RATIONALE AND OBJECTIVES: Marked liver steatosis, steatohepatitis, and significant fibrosis are risk factors for unfavorable outcomes in non-alcoholic fatty liver disease (NAFLD). In this study, the diagnostic performance of attenuation coefficient (AC), liver stiffness (LS), and dispersion slope (DS) was evaluated separately and combined in the diagnosis of liver steatosis and fibrosis in NAFLD suspects using biopsy or magnetic resonance imaging (MRI) as a reference standard. MATERIALS AND METHODS: Seventy-four NAFLD suspects were prospectively imaged with an Aplio i800 ultrasound scanner (Canon Medical Systems, Tustin, CA). AC, LS, and DS measurements were obtained from the right liver lobe. RESULTS: Thirty-four patients underwent liver biopsy, and 40 had MRI. There were 32 patients (43%) with liver steatosis and fibrosis (S + F), 22 (30%) with steatosis (S), 5 (7%) with fibrosis (F), and 15 (20%) with normal liver (N). Mean ACs were significantly higher in steatotic livers (n = 54) than in non-steatotic livers (n = 20) (P < 0.0001). LS and DS were significantly higher in patients with liver fibrosis (n = 37) compared to non-fibrotic livers (n = 37) (P = 0.0004 and P = 0.0002, respectively). In detecting (S + F), the area under the receiver operating characteristic curve (AUROCC) was 0.87 for combined ultrasound parameters of LS and AC (negative predictive value [NPV]: 75%, positive predictive value [PPV]: 77%, P < 0.0001). In detecting patients with liver steatosis and fibrosis stage ≥2, LS had an AUROCC of 0.93 (NPV: 87%, PPV: 82%, P < 0.0001). In the biopsy group, 32% (11/34) were diagnosed with non-alcoholic steatohepatitis (NASH). DS values showed a significant difference among patients with (n = 23) or without (n = 11) hepatocellular ballooning (P = 0.02). AUROCC was 0.87 for combined ultrasound parameters of AC, LS, and DS with body mass index (BMI) in detecting NASH (NPV: 80%, PPV: 87%, P = 0.0006). CONCLUSION: AC and LS showed high diagnostic value in detecting liver steatosis and fibrosis, respectively. The combined AC and LS values further improved the diagnostic accuracy in detecting NAFLD and high-risk NAFLD patients.

Anxiety and Uterine Artery Doppler Flow in A Population of Pregnant Women of High Risk Down Syndrome Fetus: A Prospective Cohort Study.

BACKGROUND: Fetal exposure to maternal anxiety is associated with low birth weight and maternal stress may be led to constriction of uterine arteries. This study compared the relation of anxiety and uterine artery doppler flow indices in pregnant women with the high and low-risk of Down syndrome. MATERIALS AND METHODS: This prospective cohort study was conducted among pregnant women in the second trimester that were classified as having a high or low risk according to their prenatal aneuploidy screening outcome. The high risk group underwent amniocentesis. Anxiety was initially assessed using the Spielberger State-Anxiety Inventory (STAI) and uterine artery blood flow indices were evaluated 2 times for the both groups. For the high-risk group first: immediately before amniocentesis and second: after two weeks follow up, when receiving the karyotype results and for the low-risk group in the first admission and two weeks later. RESULTS: Totally, 375 pregnant women participated in our study that sorted into 2 risk populations based on the aneuploidy screening test, low-risk=176 and high-risk women=199. The high-risk group for Down syndrome amniocentesis showed abnormal results in the 23 cases (23/199). The mean state (P=0.003) and trait (P=0.033) of the Anxiety Inventory scores were significantly different between the groups. Baseline uterine artery indices were no significant difference between the groups. Baseline Uterine artery indices in the high-risk group was significantly different with follow-up (in both positive-amniocentesis and negative amniocentesis sub-groups) indices. Also, there was a weak and significant correlation in the uterine resistance index and STAI scores (P=0.008, r=0.137) during the follow-up period. CONCLUSION: All pregnant women experienced high level anxiety, especially in the high-risk group that may reduce after confirmation of prenatal aneuploidy screening test and also affects the Doppler indices. For all pregnant women; Stress management and emotional support training is recommended before and during pregnancy.

Improving diagnostic accuracy of ultrasound texture features in detecting and quantifying hepatic steatosis using various beamforming sound speeds.

Objective.While ultrasound image texture has been utilized to detect and quantify hepatic steatosis, the texture features extracted using a single (conventionally 1540 m s-1) beamforming speed of sound (SoS) failed to achieve reliable diagnostic performance. This study aimed to investigate if the texture features extracted using various beamforming SoSs can improve the accuracy of hepatic steatosis detection and quantification.Approach.Patients with suspected non-alcoholic fatty liver disease underwent liver biopsy or MRI proton density fat fraction (PDFF) as part of standard of care, were prospectively enrolled. The radio-frequency data from subjects' right and left liver lobes were collected using 6 beamforming SoSs: 1300, 1350, 1400, 1450, 1500 and 1540 m s-1and analyzed offline. The texture features, i.e. Contrast, Correlation, Energy and Homogeneity from gray-level co-occurrence matrix of normalized envelope were obtained from a region of interest in the liver parenchyma.Main results.Forty-three subjects (67.2%) were diagnosed with steatosis while 21 had no steatosis. Homogeneity showed the area under the curve (AUC) of 0.75-0.82 and 0.58-0.81 for left and right lobes, respectively with varying beamforming SoSs. The combined Homogeneity value over 1300-1540 m s-1from left and right lobes showed the AUC of 0.90 and 0.81, respectively. Furthermore, the combined Homogeneity values from left and right lobes over 1300-1540 m s-1improved the AUC to 0.94. The correlation between texture features and steatosis severity was improved by using the images from various beamforming SoSs. The combined Contrast values over 1300-1540 m s-1from left and right lobes demonstrated the highest correlation (r= 0.90) with the MRI PDFF while the combined Homogeneity values over 1300-1540 m s-1from left and right lobes showed the highest correlation with the biopsy grades (r= -0.81).Significance.The diagnostic accuracy of ultrasound texture features in detecting and quantifying hepatic steatosis was improved by combining its values extracted using various beamforming SoSs.

Diagnostic Performance Comparison Between Ultrasound Attenuation Measurements From Right and Left Hepatic Lobes for Steatosis Detection in Non-alcoholic Fatty Liver Disease.

RATIONALE AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is currently diagnosed by liver biopsy or MRI proton density fat fraction (MRI-PDFF) from left hepatic lobe (LTHL) and/or right hepatic lobe (RTHL). The objective of this study was to compare the diagnostic value of ultrasound attenuation coefficients (ACs) from RTHL and LTHL in detecting hepatic steatosis using biopsy or MRI-PDFF as a reference standard. MATERIALS AND METHODS: Sixty-six patients with suspected NAFLD were imaged with an Aplio i800 ultrasound scanner (Canon Medical Systems, Tustin, CA). Five AC measurements from RTHL and LTHL were averaged separately and together to be compared with the reference standard. RESULTS: Forty-seven patients (71%) were diagnosed with NAFLD. Mean ACs were significantly higher in fatty livers than non-fatty livers (RTHL: 0.73 ± 0.10 vs. 0.63 ± 0.07 dB/cm/MHZ; p < 0.0001, LTHL: 0.78 ± 0.11 vs. 0.63 ± 0.06 dB/cm/MHz; p < 0.0001, RTHL & LTHL: 0.76 ± 0.09 vs. 0.63 ± 0.05 dB/cm/MHz; p < 0.0001). Biopsy steatosis grades (n =31) were better correlated with the mean ACs of RTHL & LTHL (r = 0.72) compared to LTHL (r = 0.67) or RTHL (r = 0.61). Correlation between MRI-PDFF (n = 35) and mean ACs was better for LTHL (r = 0.69) compared to the RTHL & LTHL (r = 0.66) or RTHL (r = 0.45). Higher diagnostic accuracy was shown for the mean ACs of RTHL & LTHL (AUC 0.89, specificity 94%, sensitivity 78%) compared to LTHL (AUC 0.89, specificity 88%, sensitivity 82%) or RTHL (AUC 0.81, specificity 89%, sensitivity 68%). CONCLUSION: Ultrasound ACs from RTHL and LTHL showed comparable diagnostic values in detection of hepatic steatosis with the highest diagnostic accuracy when they were averaged together.

A Systematic Review of Reproductive Counseling in Cases of Parental Constitutional Reciprocal Translocation (9;22) Mimicking BCR-ABL1.

We aim to determine the spectrum of cytogenetic abnormalities and outcomes in unbalanced offspring of asymptomatic constitutional balanced t(9;22) carriers through a systematic literature review. We also include a case of a constitutional balanced t(9;22) carrier from our institution. Among the 16 balanced t(9;22) carriers in our review, 13 were maternal and 3 were paternal. Of the 15 unbalanced translocation cases identified, 13 were live births, one was a missed abortion, and one resulted in pregnancy termination. The spectrum of established syndromes reported among the live births was the following: trisomy 9p syndrome (6/13), dual trisomy 9p and DiGeorge syndrome (3/13), dual 9q subtelomere deletion syndrome and DiGeorge syndrome (1/13), 9q subtelomere deletion syndrome (1/13), and DiGeorge syndrome (1/13). One unbalanced case did not have a reported syndrome. The phenotype of the unbalanced cases included cardiac abnormalities (5/13), neurological findings (7/13), intellectual disability (6/10), urogenital anomalies (3/13), respiratory or immune dysfunction (3/13), and facial or skeletal dysmorphias (13/13). Any constitutional balanced reciprocal t(9;22) carrier should be counseled regarding the increased risk of having a child with an unbalanced translocation, the spectrum of possible cytogenetic abnormalities, and predicted clinical phenotype for the unbalanced derivative.

Atypical presentation of ileocecal volvulus in a postpartum woman: a case report.

Volvulus appears with unusual symptoms in pregnancy and postpartum, and if the clinicians do not consider it, the patient becomes complicated quickly. It seems that volvulus may cause obstetrics complications such as preterm delivery.

Selecting the optimal parameters for sonoporation of pancreatic cancer in a pre-clinical model.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the modern world, in part due to poor delivery of chemotherapeutics. Sonoporation can be used to enhance the efficacy of standard of care therapies for PDAC. Using xenograft models of PDAC we investigate sonoporation using four ifferent ultrasound contrast agents (UCAs) and two ultrasound regimens to identify the ideal parameters to increase therapeutic efficacy. MIA-PaCa2 xenografts in over 175 immunodeficient mice were treated with gemcitabine and paclitaxel and subjected to low or high power ultrasound (60 and 200 mW/cm2 respectively) in conjunction with one of four different UCAs. The UCAs investigated were Definity®, SonoVue®, Optison™ or Sonazoid™. Tumor volumes, vascularity, hemoglobin, and oxygenation were measured and compared to controls. High power treatment in conjunction with Sonazoid sonoporation led to significantly smaller tumors when started early (tumors ~50mm3; p = .0105), while no UCAs significantly increased efficacy in the low power cohort. This trend was also found in larger tumors (~250mm3) where all four UCA agents significantly increased therapeutic efficacy in the high power group (p < .01), while only Definity and SonoVue increased efficacy in the low power cohort (p < .03). Overall, the higher power ultrasound treatment modality was more consistently effective at decreasing tumor volume and increasing vascularity characteristics. In conclusion, Sonazoid was the most consistently effective UCA at decreasing tumor volume and increasing vascularity. Thus, we are pursuing a larger phase II clinical trial to validate the increased efficacy of sonoporation in conjunction with chemotherapy in PDAC patients.

Contrast-Enhanced Ultrasound for Monitoring Non-surgical Treatments of Uterine Fibroids: A Systematic Review.

Non-surgical treatment options for uterine fibroids are uterine artery embolization (UAE), high-intensity focused ultrasound ablation (HIFUA), and percutaneous microwave ablation (PMWA). Magnetic resonance imaging (MRI) is the reference standard imaging method before and after these procedures. Contrast-enhanced ultrasound (CEUS) has been studied as an alternative to MRI for evaluating the fibroids' characteristics and responses to non-surgical treatments. PubMed, Ovid MEDLINE and Scopus databases were searched for literature published from January 2000 through June 7, 2020, that investigated the application of CEUS as an adjunct to monitor UAE, HIFUA or PMWA in human uterine fibroid treatments. Two independent reviewers analyzed 128 publications, out of which 17 were included. Based on this systematic review, CEUS provides detailed data about fibroid volume and vascularization prior, during and post UAE, and it helps determine the endpoint of the procedure. HIFUA with intra-procedural CEUS has faster volume shrinkage over a shorter time period with less needed energy and provides early detection of residual tissue after HIFUA. CEUS and contrast-enhanced MRI have sufficient agreement to be used interchangeably in the clinic to evaluate the therapeutic effect of PMWA and HIFUA on fibroids.

Superb Microvascular Imaging Improves Detection of Vascularity in Indeterminate Renal Masses.

OBJECTIVES: Vascular assessment of indeterminate renal masses (iRMs) remains a crucial element of diagnostic imaging, as the presence of blood flow within renal lesions suggests malignancy. We compared the utility of Superb Microvascular Imaging (SMI; Canon Medical Systems, Tustin, CA), a novel Doppler technique, to standard color Doppler imaging (CDI) and power Doppler imaging (PDI) for the detection of vascularity within iRMs. METHODS: Patients undergoing contrast-enhanced ultrasound (CEUS) evaluations for iRMs first underwent a renal ultrasound examination with the following modes: CDI, PDI, color Superb Microvascular Imaging (cSMI), and monochrome Superb Microvascular Imaging (mSMI), using an Aplio i800 scanner with an i8CX1 transducer (Canon Medical Systems). After image randomization, each mode was assessed for iRM vascularity by 4 blinded readers on a diagnostic confidence scale of 1 to 5 (5 = most confident). The results were compared to CEUS as the reference standard. RESULTS: Forty-one patients with 50 lesions met inclusion criteria. Relative to the other 3 modalities, mSMI had the highest sensitivity (63.3%), whereas cSMI had the highest specificity (62.1%). Both cSMI and mSMI also had the highest diagnostic accuracy (0.678 and 0.680, respectively; both P < 0.001) compared to CDI (0.568) and PDI (0.555). Although the reader-reported confidence interval of mSMI (mean ± SD, 3.6 ± 1.1) was significantly lower than CDI (4.1 ± 1.0) and PDI (4.0 ± 1.0; P < 0.001), the confidence level of cSMI (4.1 ± 0.9) was not (P > 0.173). CONCLUSIONS: Preliminary data suggest that SMI is a potentially useful modality in detecting microvasculature in iRMs compared to standard Doppler techniques. Future studies should aim to compare the efficacy of both SMI and CEUS and to assess the ability of SMI to characterize malignancy in iRMs.

Characterization of Adnexal Masses Using Contrast-Enhanced Subharmonic Imaging: A Pilot Study.

OBJECTIVES: This pilot study evaluated whether contrast-enhanced subharmonic imaging (SHI) could be used to characterize adnexal masses before surgical intervention. METHODS: Ten women (with 12 lesions) scheduled for surgery of an ovarian mass underwent an SHI examination of their adnexal region using a modified LOGIQ E9 scanner (GE Healthcare, Waukesha, WI) with an endocavitary transducer, in which digital clips were acquired by pulse destruction-replenishment SHI across the lesions. Time-intensity curves were created offline to quantitatively evaluate SHI parameters (fractional tumor perfusion, peak contrast intensity, time to peak contrast enhancement, and area under the time-intensity curve), which were compared to pathologic characterizations of the lesions. RESULTS: Of the 12 masses, 8 were benign, and 4 were malignant. A qualitative analysis of the SHI images by an experienced radiologist resulted in diagnostic accuracy of 70%, compared to 56% without contrast, whereas an inexperienced radiologist improved from 50% to 58% accuracy, demonstrating the benefit of SHI. A quantitative analysis of SHI parameters produced diagnostic accuracy as high as 81%. Peak contrast intensity was significantly greater in malignant than benign masses (mean ± SD, 0.109 ± 0.088 versus 0.046 ± 0.030 arbitrary units; P = .046). Malignant masses also showed significantly greater perfusion than benign masses (24.79% ± 25.34% versus 7.62% ± 6.50%; P = .045). When the radiologist reads were combined with the most predictive quantitative SHI parameter (percent perfusion), diagnostic accuracy improved to 84% for the experienced radiologist and 96% for the novice radiologist. CONCLUSIONS: Results indicate that SHI for presurgical characterization of adnexal masses may improve the determination of malignancy and diagnostic accuracy, albeit based on a small sample size.

Maternal ornithine transcarbamylase deficiency, a genetic condition associated with high maternal and neonatal mortality every clinician should know: A systematic review.

Ornithine transcarbamylase deficiency (OTCD) is a rare X-linked urea cycle disorder. Maternal OTCD can lead to life-threatening hyperammonemia if untreated. We aimed to compare the outcomes of maternal OTCD when diagnosis is known prior to pregnancy to when diagnosis is made during pregnancy. We performed a systematic literature review on maternal OTCD using the databases Ovid MEDLINE and PubMed from 1982 through 2018. Studies were included if addressed maternal OTCD signs, symptoms, and detailed pregnancy outcomes. We calculated the median or the mean for continuous variables and percentages for categorical variables. Of 36 cases of maternal OTCD, 20 (55%) were diagnosed prior to pregnancy while 16 (45%) were not. In the 20 patients diagnosed prior to pregnancy, 7 (35%) had either a neurologic or psychiatric presentation during pregnancy or postpartum. Two hyperammonemic patients (11%) experienced ICU admission, dialysis, and coma with no maternal deaths. All had a favorable outcome. In the 16 patients not known to have maternal OTCD prior to pregnancy, 13 (81%) had neurologic or psychiatric presentation during pregnancy or postpartum. Four presented with hyperemesis gravidarum. Eleven (69%) hyperammonemic patients had ICU admission and coma and 7 (47%) of them had dialysis. There were 5 (31%) maternal deaths. Three patients (19%) had prolonged hospitalization course. Overall, three male neonatal deaths were reported. Three other male children had liver transplant. Maternal OTCD is associated with high maternal and neonatal morbidity and mortality when diagnosis is made during pregnancy compared to when diagnosis is known prior to pregnancy.