Randomised clinical trial: a leucine-metformin-sildenafil combination (NS-0200) vs placebo in patients with non-alcoholic fatty liver disease.

BACKGROUND: Sirtuin 1 (Sirt1) is suppressed in non-alcoholic fatty liver disease (NAFLD), while its' stimulation or overexpression results in reduced disease severity in pre-clinical NAFLD models. Leucine allosterically activates Sirt1 and synergise with other Sirt/AMPK/NO pathway activators. We developed a triple combination of leucine, metformin and sildenafil (NS-0200), which was effective in a mouse model of non-alcoholic steatohepatitis (NASH). AIM: To report the results from a Phase 2, randomised clinical trial of of NS-0200 in 91 subjects with NAFLD (liver fat ≥15% by magnetic resonance imaging-proton-density fat fraction (MRI-PDFF)). METHODS: Subjects were randomised to placebo, low-dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil) or high-dose NS-0200 (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) b.d. for 16 weeks; change in hepatic fat was assessed via MRI-PDFF, and lipid metabolism was assessed via changes in the lipidomic signature. Seventy subjects completed the trial and met a priori compliance criteria. Analyses were conducted on the full cohort and on those with alanine aminotransferase (ALT) values above median (50 U/L; n = 35). RESULTS: In the full cohort, active treatments did not separate from placebo. High dose NS-0200 reduced hepatic fat by 15.7% (relative change from baseline) in the high ALT group (P < 0.005) while low dose NS-0200 and placebo did not significantly change hepatic fat. Lipidomic analysis showed dose-responsive treatment effects in both overall and high ALT cohorts, with significant decreases in metabolically active lipids and up-regulation of fatty acid oxidation. CONCLUSION: These data support further evaluation of high-dose NS-0200 for treating NASH, especially in those with elevated ALT (NCT 02546609).

Diagnostic per-lesion performance of a simulated gadoxetate disodium-enhanced abbreviated MRI protocol for hepatocellular carcinoma screening.

AIM: To evaluate the diagnostic per-lesion performance of a simulated gadoxetate disodium-enhanced abbreviated MRI (AMRI) in cirrhotic and chronic hepatitis B (CHB) patients for hepatocellular carcinoma (HCC) screening. MATERIALS AND METHODS: Seventy-nine consecutive patients at risk for HCC due to cirrhosis and/or CHB were included in this retrospective study. For each patient, the first gadoxetate disodium-enhanced MRI between 2008 through 2014 was analysed. Two independent readers read an anonymised abbreviated image set comprising axial T1-weighted (W) images with fat saturation in the hepatobiliary phase, 20 minutes or more after gadoxetate injection, and axial T2W single-shot fast spin echo images. Each observation >10 mm was scored as negative or suspicious for HCC. Inter-reader agreement was assessed. A composite reference standard was used to determine the per-lesion diagnostic performance for each reader. RESULTS: Inter-reader agreement was substantial (κ = 0.75). The final reference standard showed 27 HCCs in 13 patients (median 21 mm, range 11-100 mm). The two readers each correctly scored 23 as suspicious for HCC (sensitivity = 85.2%), scored a total of 27 and 32 observations as suspicious for HCC (positive predictive value [PPV] = 85.2% and 71.9%), and scored 83 and 78 observations or complete examinations as negative for HCC (negative predictive value [NPV] = 95.2% and 94.9%). CONCLUSIONS: The AMRI protocol provides higher per-lesion sensitivity and NPV than reported values for ultrasound, the current recommended technique for screening, and similar per-lesion sensitivity and PPV to reported values for complete dynamic contrast-enhanced MRI.

Bone marrow fat content is correlated with hepatic fat content in paediatric non-alcoholic fatty liver disease.

AIM: To investigate the relationship between bone marrow fat content and hepatic fat content in children with known or suspected non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This was an institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant, cross-sectional, prospective analysis of data collected between October 2010 to March 2013 in 125 children with known or suspected NAFLD. Written informed consent was obtained for same-day research magnetic resonance imaging (MRI) of the lumbar spine, liver, and abdominal adiposity. Lumbar spine bone marrow proton density fat fraction (PDFF) and hepatic PDFF were estimated using complex-based MRI (C-MRI) techniques and magnitude-based MRI (M-MRI), respectively. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT) were quantified using high-resolution MRI. All images were acquired by two MRI technologists. Hepatic M-MRI images were analysed by an image analyst; all other images were analysed by a single investigator. The relationship between lumbar spine bone marrow PDFF and hepatic PDFF was assessed with and without adjusting for the presence of covariates using correlation and regression analysis. RESULTS: Lumbar spine bone marrow PDFF was positively associated with hepatic PDFF in children with known or suspected NAFLD prior to adjusting for covariates (r=0.33, p=0.0002). Lumbar spine bone marrow PDFF was positively associated with hepatic PDFF in children with known or suspected NAFLD (r=0.24, p=0.0079) after adjusting for age, sex, body mass index z-score, VAT, and SCAT in a multivariable regression analysis. CONCLUSION: Bone marrow fat content is positively associated with hepatic fat content in children with known or suspected NAFLD. Further research is needed to confirm these results and understand their clinical and biological implications.

Assessment of treatment response in non-alcoholic steatohepatitis using advanced magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging-derived measures of liver fat and volume are emerging as accurate, non-invasive imaging biomarkers in non-alcoholic steatohepatitis (NASH). Little is known about these measures in relation to histology longitudinally. AIM: To examine any relationship between MRI-derived proton-density fat-fraction (PDFF), total liver volume (TLV), total liver fat index (TLFI), vs. histology in a NASH trial. METHODS: This is a secondary analysis of a 24-week randomised, double-blind, placebo-controlled trial of 50 patients with biopsy-proven NASH randomised to oral ezetimibe 10 mg daily (n = 25) vs. placebo (n = 25). Baseline and post-treatment anthropometrics, biochemical profiling, MRI and biopsies were obtained. RESULTS: Baseline mean PDFF correlated strongly with TLFI (Spearman's ρ = 0.94, n = 45, P < 0.0001) and had good correlation with TLV (ρ = 0.57, n = 45, P < 0.0001). Mean TLV correlated strongly with TLFI (ρ = 0.78, n = 45, P < 0.0001). After 24 weeks, PDFF remained strongly correlated with TLFI (ρ = 0.94, n = 45, P < 0.0001), maintaining good correlation with TLV (ρ = 0.51, n = 45, P = 0.0004). TLV remained strongly correlated with TLFI (ρ = 0.74, n = 45, P < 0.0001). Patients with Grade 1 vs. 3 steatosis had lower PDFF, TLV, and TLFI (P < 0.0001, P = 0.0003, P < 0.0001 respectively). Regression analysis of changes in MRI-PDFF vs. TLV indicates that 10% reduction in MRI-PDFF predicts 257 mL reduction in TLV. CONCLUSIONS: The MRI-PDFF and TLV strongly correlated with TLFI. Decreases in steatosis were associated with an improvement in hepatomegaly. Lower values of these measures reflect lower histologic steatosis grades. MRI-derived measures of liver fat and volume may be used as dynamic and more responsive imaging biomarkers in a NASH trial, than histology.

Magnetic resonance elastography identifies fibrosis in adults with alpha-1 antitrypsin deficiency liver disease: a prospective study.

BACKGROUND: Limited data exist on the clinical presentation and non-invasive detection of liver fibrosis in adults with homozygous Z genotype alpha-1 antitrypsin (AAT) deficiency. AIMS: To compare demographic, biochemical, histological and imaging data of AAT deficient patients to normal-control and biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients, and to assess the diagnostic accuracy of magnetic resonance elastography (MRE) in detecting fibrosis in AAT deficiency. METHODS: Study includes 33 participants, 11 per group, who underwent clinical research evaluation, liver biopsy (AAT and NAFLD groups), and MRE. Histological fibrosis was quantified using a modified Ishak 6-point scale and liver stiffness by MRE. Diagnostic performance of MRE in detecting fibrosis was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Mean (±s.d.) of age and BMI of normal-control, AAT and NAFLD groups was 57 (±19), 57 (±18), and 57 (±13) years, and 22.7 (±2.5), 24.8 (±4.0) and 31.0 (±5.1) kg/m(2) respectively. Serum ALT [mean ± s.d.] was similar within normal-control [16.4 ± 4.0] and AAT groups [23.5 ± 10.8], but was significantly lower in AAT than NAFLD even after adjustment for stage of fibrosis (P < 0.05, P = 0.0172). For fibrosis detection, MRE-estimated stiffness had an area under the ROC curve of 0.90 (P < 0.0001); an MRE threshold of ≥3.0 kPa provided 88.9% accuracy, with 80% sensitivity and 100% specificity to detect presence of any fibrosis (stage ≥1). CONCLUSIONS: This pilot prospective study suggests magnetic resonance elastography may be accurate for identifying fibrosis in patients with alpha-1 antitrypsin deficiency. Larger validation studies are warranted.

Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE.

BACKGROUND: Current guidelines do not recommend screening for non-alcoholic fatty liver disease (NAFLD) or advanced fibrosis. Patients with type 2 diabetes mellitus (T2DM) are known to be at increased risk for NAFLD and advanced fibrosis. AIM: To assess the feasibility in diabetics in a primary care setting of screening for NAFLD and advanced fibrosis, by using non-invasive magnetic resonance imaging (MRI) to estimate the hepatic proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE) to estimate hepatic stiffness. METHODS: We performed a cross-sectional analysis of a prospective study that included 100 (53% men) consecutively enrolled diabetics who did not have any other aetiology of liver disease. All patients underwent a standardised research visit, laboratory tests, MRI-PDFF, and MRE. RESULTS: Mean (±s.d.) age and body mass index (BMI) was 59.7 (±11.2) years and 30.8 (±6.5) kg/m(2) , respectively. The prevalence of NAFLD (defined as MRI-PDFF ≥5%) and advanced fibrosis (defined as MRE ≥3.6 kPa) was 65% and 7.1%, respectively. One patient with advanced fibrosis had definite hepatocellular carcinoma. When compared to those without NAFLD, patients with NAFLD were younger (P = 0.028) and had higher mean BMI (P = 0.0008), waist circumference (P < 0.0001) and prevalence of metabolic syndrome (84.6% vs. 40.0%, P < 0.0001). Only 26% of those with NAFLD had elevated alanine aminotransferase. CONCLUSIONS: This proof-of-concept study demonstrates that T2DM has significant rates of both NAFLD and advanced fibrosis. Concomitant screening for NAFLD and advanced fibrosis by using MRI-proton density fat fraction and magnetic resonance elastography in T2DM is feasible and may be considered after validation in a larger cohort.

Comparative diagnostic accuracy of magnetic resonance elastography vs. eight clinical prediction rules for non-invasive diagnosis of advanced fibrosis in biopsy-proven non-alcoholic fatty liver disease: a prospective study.

BACKGROUND: Two-dimensional magnetic resonance elastography (2D-MRE) is an advanced magnetic resonance method with high diagnostic accuracy for predicting advanced fibrosis in non-alcoholic fatty liver disease (NAFLD) patients. However, no prospective, head-to-head comparisons between 2D-MRE and clinical prediction rules (CPRs) have been performed in patients with biopsy-proven NAFLD. AIM: To compare the diagnostic utility of 2D-MRE against that of eight CPRs (AST:ALT ratio, APRI, BARD, FIB-4, NAFLD Fibrosis Score, Bonacini cirrhosis discriminant score, Lok Index and NASH CRN model) for predicting advanced fibrosis in a prospective cohort with paired liver biopsy as the gold standard. METHODS: This is a cross-sectional analysis of a prospective study of 102 patients (58.8% women) with biopsy-proven NAFLD, 2D-MRE and clinical research assessment within 90 days of biopsy. Receiver operating characteristic (ROC) analysis was performed to assess the performance of 2D-MRE and CPRs for predicting advanced fibrosis. RESULTS: The mean (±s.d.) age and BMI were 51.3 (±14.0) years and 31.7 (±5.5) kg/m(2) respectively. 48, 26, 9, 13 and 6 patients had stage 0, 1, 2, 3 and 4 fibrosis respectively. The area under ROC curve (AUROC) was 0.957 for 2D-MRE and between 0.796 and 0.861 for the CPRs. FIB-4 was the best-performing CPR at predicting advanced fibrosis with AUROC of 0.861. In head-to-head comparisons using the DeLong test, 2D-MRE had significantly better AUROC (P < 0.05) than each CPR for predicting advanced fibrosis. CONCLUSION: Compared to clinical prediction rules, 2D-MRE provides significantly higher accuracy for the diagnosis of advanced fibrosis in NAFLD patients.

Review article: epidemiology, pathogenesis and potential treatments of paediatric non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of paediatric liver disease. Similar to NAFLD in adults, NAFLD in children is associated with obesity and insulin resistance and requires liver histology for diagnosis and staging. However, significant histological differences exist between adult and paediatric NAFLD to warrant caution in extrapolation of adult data. AIM: To review the available data on the epidemiology, pathogenesis, diagnosis and treatment of paediatric NAFLD. METHODS: Relevant articles were identified by Medline searches using the keywords: nonalcoholic fatty liver disease, steatohepatitis, obesity and children. RESULTS: The rise in childhood obesity has been accompanied by an increase in paediatric NAFLD. Age, gender and race/ethnicity are significant determinants of risk, and sex hormones, insulin sensitivity and adipocytokines are implicated in the pathogenesis of paediatric NAFLD. There is no consensus for treatment of NAFLD; however, data suggest that diet, exercise and some pharmacological therapies may be of benefit. CONCLUSIONS: To evaluate and effectively treat paediatric NAFLD, the pathophysiology and natural history of the disease should be clarified and non-invasive methods for screening, diagnosis, and longitudinal assessment developed. Randomized, controlled, double-blind trials of pharmacological therapies in children with biopsy-proven disease are necessary.

B-mode enhancement of the liver with microbubble contrast agent: a blinded study in rabbits with VX2 tumors.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the accuracy of contrast material-enhanced sonography in the detection of liver lesions by using an animal model. MATERIALS AND METHODS: A total of 36 rabbits, 12 normal and 24 with one, two, or more VX2 tumors implanted percutaneously, were imaged on an Acuson 128XP/10 with a 7-MHz sector transducer by a sonographer blinded to the study assignments. The sonographer assigned rabbits to four groups (no, one, two, more than two tumors) based on the number of lesions detected before and then after the intravenous bolus injection of 0.5 mL of AF0150. S-VHS video segments or pre- and postcontrast images were separated, randomized, and evaluated by a blinded reader. Necropsy served as the gold standard. RESULTS: Classification of rabbits as normal or tumor bearing on the precontrast images produced three false-positive results and three false-negative results for the blinded sonographer and six false-positive results and two false-negative results for the blinded reader. On postcontrast images, all rabbits were correctly classified by both observers. The correlation of the classification of whether rabbits had no, one, two, or more tumors relative to the pathologic classification on precontrast images was poor to fair (K = 0.349 +/- 0.099 for the sonographer and 0.274 +/- 0.111 for the reader), whereas the postcontrast correlation was good to excellent (K = 0.924 +/- 0.099 for the sonographer and 0.809 +/- 0.076 for the reader). CONCLUSION: AF0150 markedly increased the ability of the sonographer and the blinded reader to distinguish normal from tumor-bearing animals and improved the classification of rabbits with more than one liver tumor.

Importance of evaluating organ parenchyma during screening abdominal ultrasonography after blunt trauma.

OBJECTIVE: To determine the benefit of screening ultrasonography for parenchymal abnormalities as well as free fluid during screening abdominal ultrasonography in patients with blunt trauma. METHODS: A total of 2693 patients with blunt trauma who were triaged to a level 1 trauma center underwent screening abdominal ultrasonography in the resuscitation suite. Examinations were performed by experienced sonographers and included a screen for free intraperitoneal fluid and evaluation of the abdominal organ parenchyma and heart for traumatic injury. Screening ultrasonographic findings were reviewed and compared with findings from autopsy, laparotomy, diagnostic peritoneal lavage, computed tomography, repeated ultrasonography, cystography, and clinical outcome. Imaging studies of all patients with confirmed or suspected injuries were reviewed to identify those in whom parenchymal findings aided diagnosis. RESULTS: One hundred seventy-two patients were found to have evidence of abdominal injury due to blunt trauma on the basis of clinical data, imaging, laparotomy, or autopsy. Forty-four of these patients had no sonographic evidence of hemoperitoneum at the time of initial ultrasonography. Screening ultrasonographic findings were positive for injury in 19 of 44 patients on the basis of parenchymal findings or small retroperitoneal collections of fluid thought to be indicative of trauma. In the remaining 25 patients, screening ultrasonography showed no abnormalities, and injuries were detected by repeated ultrasonography, subsequent computed tomography, or diagnostic peritoneal lavage performed for suspected occult injury on the basis of clinical parameters. In addition, 47 of 126 injured patients with sonographically detected free fluid had parenchymal findings that helped localize injury. Sixteen of those patients were taken to the operating room on the basis of clinical and sonographic findings without undergoing computed tomography. CONCLUSIONS: The inability to show injuries with no hemoperitoneum or with delayed hemoperitoneum has been shown to be a limitation of ultrasonography in patients with blunt trauma. In our series, 26% of all patients with documented injuries had no free fluid visible on screening ultrasonography Attention to findings other than free fluid allowed detection in 43% of injured patients without sonographic evidence of hemoperitoneum.

Patterns of fluid accumulation on screening ultrasonography for blunt abdominal trauma: comparison with site of injury.

The objectives of this study were to define where fluid accumulation is shown on screening ultrasonography after blunt abdominal trauma and to determine how fluid accumulation patterns are associated with the site of injury. From 1994 to 1998, 2,693 screening examinations for blunt abdominal trauma were performed, in which 7 regions were examined for fluid. On the basis of a preliminary analysis of patients with solitary injuries, all 194 patients with sonographically detected fluid were grouped by fluid accumulation pattern. Fluid patterns were compared with sites of injury. The patterns differed between hepatic and splenic injuries. Fluid in the left upper quadrant, in both upper quadrants, or diffusely distributed suggested splenic injury, whereas fluid in the right upper quadrant or the right upper quadrant and lower recesses suggested hepatic injury (P < .0001). Fluid accumulation was random after enteric injury. Patients with extraperitoneal injury had no fluid or had fluid focally at the injury site. The ability to predict the injury site on the basis of fluid patterns should expedite treatment of hemodynamically unstable patients with blunt abdominal trauma.

Quantification of fluid on screening ultrasonography for blunt abdominal trauma: a simple scoring system to predict severity of injury.

A simple ultrasonographic method of fluid quantification, which counted the number of fluid recesses, was developed to predict the severity of injury after blunt abdominal trauma. From 1994 to 1998, 2,693 screening ultrasonographic examinations were performed for blunt abdominal trauma. Of this group, 2,499 patients had a fluid score of 0 (no fluid), and 1.4% had injuries (0.4% requiring surgery); 110 had a score of 1 (fluid in a single examined region), and 59% had injuries (13% requiring surgery); 33 had a score of 2, and 85% had injuries (36% requiring surgery); 30 had a score of 3, and 83% had injuries (63% requiring surgery); and 21 had a score of 4, and 95% had injuries (81 % requiring surgery). Patients with scores of 3 or greater had significantly higher rates of injury (P < .002) and injury requiring surgery (P < .0001) than patients with lower scores. The ability to predict injury severity on the basis of a simple ultrasonographic scoring system should expedite treatment of patients with severe trauma.

Contrast-enhanced B-mode US angiography in the assessment of experimental in vivo and in vitro atherosclerotic disease.

RATIONALE AND OBJECTIVES: This study was performed to (a) test the hypothesis that filling the arterial lumen with echoes at B-mode ultrasound (US) enables the assessment of wall and luminal abnormalities and (b) compare contrast material-enhanced B-mode US with color and power Doppler US angiography. MATERIALS AND METHODS: Atherosclerotic lesions were created in 14 rabbit aortas and imaged with color Doppler and B-mode US before and after the intravenous administration of 0.3 mL of AF0150, a US contrast agent. In addition, four replicas of diseased human carotid arteries were immersed in a tissue-mimicking phantom and imaged with B-mode and color and power Doppler US before and after the administration of 1 mL of AF0150 per liter of porcine blood. Radiopaque plastic casts of the rabbit aortas and contact radiographs of the plastic replicas served as standards. RESULTS: Although color and power Doppler US allowed immediate localization of the lumen, precise estimation of stenoses and reliable visualization of surface irregularities were not possible. After AF0150 administration, angiogram-like images of the lumen were created with B-mode US, allowing rapid assessment of the entire vessel lumen and wall. Consequently, luminal stenoses were more accurately measured than with unenhanced B-mode US (r2 = 0.94, P < .0001 vs r2 = 0.21, P = .25) or Doppler (r2 = 0.42, P < .03). In addition, plaques and ulcerations were visible only with contrast-enhanced B-mode US. CONCLUSION: Microbubbles fill the arterial lumen with echoes at B-mode US, creating an angiogram-like image. The ability to visualize the inner and outer surfaces of the vascular wall improved the evaluation of luminal and wall abnormalities.

Shell osteochondral allografts of the knee: comparison of mr imaging findings and immunologic responses.

PURPOSE: To define the magnetic resonance (MR) imaging appearance of shell osteochondral allografts of the knee and compare the MR findings with antibody responses. MATERIALS AND METHODS: Thirty-six grafts were evaluated with a 1.5-T unit with T1-, intermediate-, and T2-weighted, and three-dimensional spoiled gradient-recalled MR imaging at 3, 6, 12, 24, and/or 36 months after surgery. Nineteen patients underwent imaging serially. Two osteoradiologists scored by consensus host marrow edema, thickness of graft-host interface, signal intensity of graft marrow, cyst formation, joint effusion, articular cartilage defects, and surface collapse. Patients were divided into antibody-positive (AP) (n = 11) and antibody-negative (AN) (n = 25) groups evenly distributed across the different time points on the basis of results of anti-human leukocyte antigen antibody screening. MR findings for the two groups were compared. RESULTS: AP patients demonstrated greater mean edema (P<.002), thicker interface (P<.03), and more abnormal graft marrow (P<.04) than AN patients, and they had a higher proportion of surface collapse (P<.03). CONCLUSION: Humoral immune responses were associated with more inflammation and less complete incorporation after allograft placement. MR imaging shows promise as a surrogate biomarker for success of shell osteochondral allograft implantation.

Us of blunt abdominal trauma: importance of free pelvic fluid in women of reproductive age.

PURPOSE: To assess the importance of free fluid and to determine the accuracy of screening ultrasonography (US) in female patients of reproductive age with trauma. MATERIALS AND METHODS: US was performed in 1,047 patients, aged 10-60 years, to evaluate blunt trauma. Patients were retrospectively assigned to groups on the basis of presence and location of intraperitoneal free fluid. Injury and surgical injury rates were assessed by comparing US results with computed tomographic, repeat US, cystographic, peritoneal lavage, surgical, and/or autopsy findings in 144 patients and with final clinical outcome in 903. US scans were positive if fluid was outside the cul-de-sac or if suspicious parenchymal abnormalities were present. RESULTS: In 939 patients, no fluid was seen: Eight had injuries; three were surgical. In 56, anechoic fluid was isolated to the cul-de-sac: Two had injuries; one was surgical. In 26, fluid was isolated to the upper abdomen: Fifteen had injuries; five were surgical. In 22, fluid involved the pelvis and abdomen: Nineteen had injuries; 14 were surgical. In four, questionable fluid was isolated to the supravesical space. Patients with fluid in the cul-de-sac had similar injury and surgical injury rates as those with no fluid but had lower rates than those of patients with fluid elsewhere (P<.02 to P<.001). US screening had 89% sensitivity, 98% specificity, 97% accuracy, a 61% positive predictive value, and a 99% negative predictive value. CONCLUSION: In female patients of reproductive age with trauma, free fluid isolated to the cul-de-sac is likely physiologic; clinical follow-up should suffice. Patients with fluid elsewhere usually have clinically important injury and require further evaluation.

Blunt abdominal trauma: screening us in 2,693 patients.

PURPOSE: To evaluate the accuracy of screening abdominal ultrasonography (US) in patients with blunt abdominal trauma. MATERIALS AND METHODS: Patients with blunt abdominal trauma underwent US. The abdomen and pelvis were scanned for free fluid, the visceral organs were assessed for heterogeneity, and duplex US was performed if necessary. Empty bladders were filled with 200-300 mL of sterile saline through a Foley catheter. US findings were considered positive if free fluid was present or if parenchymal abnormalities that could be consistent with trauma were detected. Screening US results were compared with findings of diagnostic peritoneal lavage, repeat US, computed tomography (CT), cystography, surgery, and/or autopsy and/or the clinical course. RESULTS: Findings from 2,693 US examinations were evaluated and were positive in 145 of 172 patients with injuries (sensitivity, 84%) and 64 (89%) of 72 patients who ultimately underwent laparotomy with surgical repair of injuries. False-negative findings were retroperitoneal injury, bowel injury, and intraperitoneal solid organ injury without hemoperitoneum. No patient with false-negative findings died. Specificity of US was 96% (2,429 of 2,521 patients), and overall accuracy was 96% (2,574 of 2,693 patients). Positive predictive value was 61% (145 of 237 patients), and negative predictive value was 99% (2,429 of 2,456 patients). CONCLUSION: Abdominal US is useful in screening for injury in patients with blunt abdominal trauma, and its use represents a notable change in institutional practice. Diagnostic peritoneal lavage is rarely performed, and CT is used when screening US findings are positive, when injury is clinically suspected despite negative US findings, or when US is not available.

Polydioxanone biodegradable pins in the knee: MR imaging.

OBJECTIVE: Biodegradable solid implants have been developed as an alternative to metallic orthopedic fixation. In animal models, implants degrade within and are replaced by bone. This study documents the resorption of these devices in human patients with MR imaging. SUBJECTS AND METHODS: One hundred seventy-five 1.3-mm biodegradable pins made of polydioxanone were used to secure a total of 59 osteochondral allografts of the knee. Patients with the pins underwent scanning on a 1.5-T unit with 3.3- to 4-mm contiguous T1-weighted spin-echo (TR/TE, 600/15), fat-saturated proton density-weighted (3000/40), T2-weighted fast spin-echo (3000/63), and three-dimensional spoiled gradient-recalled (47/7; flip angle, 60 degrees ) sequences at 3, 6, 12, 24, or 36 months after surgery. Eighty-nine pins were imaged on multiple occasions. Two osteoradiologists interpreted the MR examinations. RESULTS: More than 80% of the pin channels were visible at 3 and at 6 months after surgery. By 24 months, only 20% of the pin channels were visible, with the remainder having been replaced by bone. At 3 months, nearly 40% of the pins were associated with adjacent marrow edema. Edema generally diminished, involving less than 20% of pins at later time points. Focal cartilage defects were evident at 32% of the pin insertion sites during the first 6 months, but these defects were present in only 4% of the insertion sites thereafter. CONCLUSION: Biodegradable polydioxanone pins usually resorb completely by 24 months. Marrow edema, presumably representing inflammation related to pin resorption, is infrequent and tends to resolve. Cartilage defects related to pin placement heal spontaneously.

Effect of acquisition rate on liver and portal vein enhancement with microbubble contrast.

We showed that tissue enhancement with microbubbles is dependent upon transmit power. Because intermittent imaging decreases bubble exposure to ultrasound, and also decreases the ability of the sonographer to maintain anatomic orientation, we aimed to determine the optimum frame rate that maximizes enhancement and allows for continued anatomic orientation. Seven rabbits with an avascular liver lesion created by percutaneous injection of 1 mL ethyl alcohol 7 days earlier were imaged with an Acuson 128XP/10 using a 7-MHz sector transducer at fixed transmit power. Each rabbit was imaged 5 times in random order, at 1 frame/30 s, 1frame/5 s, 1frame/s, 4 frames/s, and 28 frames/s. The same plane was imaged at all frame rates from before to 15 min after the bolus injection of 0.3-mL (0.1-0.12 mL/kg) of AF0150 (Imagent, Alliance Pharmaceutical Corp., San Diego, CA). Liver and portal vein videointensity relative to the lesion were evaluated over time. In this study, liver enhancement progressively increased as the frame rate was reduced (p<0.001). Peak, duration, and area under the time-intensity curve were all greater at the lower frame rates (1 fr/30 s, 1 fr/5 s, and 1 fr/s) than at 28 fr/s (p<0.05). Anatomic orientation was maintained at 1 frame/s rate at which peak enhancement was 44% greater and duration was 100% longer than at 28 frames/s (p<.05). Portal vein enhancement was not affected by frame rate. In conclusion, with intermittent imaging, enhancement was dependent upon frame rate and the ability of the region being imaged to replenish its bubbles between consecutive acquisitions. The 1 frame/s allowed for anatomic orientation and adequate tissue contrast.

Chronic thromboembolism: diagnosis with helical CT and MR imaging with angiographic and surgical correlation.

PURPOSE: To evaluate the accuracy of identification of central and segmental chronic thromboembolic disease on helical computed tomographic (CT) scans and on magnetic resonance (MR) images. MATERIALS AND METHODS: Radiologic findings in 55 patients suspected of having chronic thromboembolic pulmonary hypertension were analyzed; these included findings from angiography (n = 55), helical CT (n = 47), and MR imaging (n = 26). Forty patients underwent thromboendarterectomy. CT and MR images were independently interpreted by two readers for the presence of thromboembolic material in central and segmental vessels. Surgical findings and angiographic findings were the reference standards for disease in central and segmental vessels, respectively. RESULTS: Central vessel disease was determined more accurately with helical CT scans (accuracy of 0.79 for each of the two readers) than with angiograms (accuracy of 0.74) or with MR images (accuracy of 0.39 and 0.46 for two readers). Segmental vessel disease was also more accurately determined with CT scans (accuracy of 0.75 and 0.76 for two readers) than with MR images (accuracy of 0.61 and 0.57 for two readers). CONCLUSION: Helical CT is a useful alternative to conventional angiography for diagnosis of chronic thromboembolism but may not be sufficient for selecting candidates for surgery in all cases.