Standardization in Quantitative Imaging: A Multicenter Comparison of Radiomic Features from Different Software Packages on Digital Reference Objects and Patient Data Sets.

Radiomic features are being increasingly studied for clinical applications. We aimed to assess the agreement among radiomic features when computed by several groups by using different software packages under very tightly controlled conditions, which included standardized feature definitions and common image data sets. Ten sites (9 from the NCI's Quantitative Imaging Network] positron emission tomography-computed tomography working group plus one site from outside that group) participated in this project. Nine common quantitative imaging features were selected for comparison including features that describe morphology, intensity, shape, and texture. The common image data sets were: three 3D digital reference objects (DROs) and 10 patient image scans from the Lung Image Database Consortium data set using a specific lesion in each scan. Each object (DRO or lesion) was accompanied by an already-defined volume of interest, from which the features were calculated. Feature values for each object (DRO or lesion) were reported. The coefficient of variation (CV), expressed as a percentage, was calculated across software packages for each feature on each object. Thirteen sets of results were obtained for the DROs and patient data sets. Five of the 9 features showed excellent agreement with CV < 1%; 1 feature had moderate agreement (CV < 10%), and 3 features had larger variations (CV ≥ 10%) even after attempts at harmonization of feature calculations. This work highlights the value of feature definition standardization as well as the need to further clarify definitions for some features.

Lacunar stroke: transoesophageal echocardiographic factors influencing long-term prognosis.

OBJECTIVE: Since little is known concerning factors which may influence long-term prognosis of patients presenting with lacunar stroke, we conducted a longitudinal study of this stroke subtype. Variables likely to affect outcome were assessed at baseline, including those from transoesophageal echocardiographic studies. METHODS: Consecutive patients presenting with first-ever lacunar stroke underwent diagnostic workup that included brain CT or MRI, carotid duplex, and transthoracic and transoesophageal echocardiography. An assessment of patients was planned at entry (baseline), and thereafter every 12 months (clinic visit or telephone call), drop-out, or endpoint. The primary endpoint was nonfatal or fatal stroke. Secondary endpoint was death due to any cause. RESULTS: Among 60 consecutive lacunar patients with the mean follow-up period of 3.9 years, 12 patients (20%) had stroke recurrence. The mean annual rate for stroke was 5.2%, and for death 2.8%. For multivariate Cox proportional hazards analysis, the following three variables with the values of p < 0.1 after univariate testing were chosen: age (p = 0.095); aortic atheroma (p = 0.066); and any source of embolism from heart (p = 0.007). Any source of embolism from heart was the only factor which significantly enhanced the risk of stroke recurrence (p = 0.015). Using Kaplan-Meier life table analysis, the curves of percent free of recurrent stroke were significantly different (log rank test p = 0.002). CONCLUSIONS: Until the mechanism of lacunar stroke is better understood, it is reasonable to suggest that its investigation and prevention should be directed at all potential causes of future strokes including cardioembolism.

Action perception and outcome valence: effects on children's inferences of intentionality and moral and liking judgments.

The influences of different action-outcome scenarios on children's evaluative judgments and inferences of outcome intentionality were assessed. One hundred forty-five kindergartners, 2nd graders, and 4th graders heard 4 stories about child actors who engaged in 1 action or 3 equifinal actions and caused a positive or negative outcome. The stories made no mention of the actors' anticipated outcome so that we could assess the children's inferences of whether the actors wanted and had tried to cause the outcome. Children also rated their liking for the actors and the actors' morality. Children's moral and liking judgments were not significantly differentiated by action condition. However, actors who caused positive outcomes received favorable liking and moral judgments, and actors who caused negative outcomes received neutral liking and moral judgments. Children's intentionality inferences varied by the actors' actions and were moderated by outcome valence. The authors discuss children's apparent use of the valence rule when inferring intentionality and their reluctance to judge harshly actors who cause negative outcomes when not privy to the actors' intentions.

Risk factors for lacunar stroke: a case-control transesophageal echocardiographic study.

To reassess the independent risk factors for lacunar stroke and to clarify the role of potential embolic sources, we conducted a case-control study using transesophageal echocardiography and duplex ultrasonography. Among 62 consecutive patients with their first lacunar stroke and 202 normal controls, we found that hypertension (p < 0.001), smoking (p = 0.001), and aortic arch atheroma (p = 0.006) were independently associated with an increased risk of lacunar stroke. Whether proximal aortic arch atheroma is mechanistically associated with lacunar stroke or merely coexistent is uncertain.

The influences of behavior valence and actor race on black and white children's moral and liking judgments.

Preschoolers, 1st graders, and 4th graders were shown line drawings that depicted 2 prosocial and 2 aggressive behaviors. Black actors or White actors were depicted in the scenarios, and a brief description of each behavior was read to the child. For each scenario, children rated their liking for the actor and the morality of the actor's behavior. Findings indicated that children at each age level significantly differentiated the actors by behavior valence for moral and liking judgements. However, the moral judgements of White preschoolers were more differentiated by behavior valence than the judgments of Black preschoolers. Also, there was more differentiation of actors by behavior valence for liking judgments as the age levels of the children increased. Black actors received more negative moral judgments than did White actors only at the preschool level.

Assessment of Herpesvirus saimiri as a potential human gene therapy vector.

Herpesvirus saimiri has characteristics that make it amenable to development as a gene therapy vector. The viral genome is thought to be capable of accommodating large quantities of heterologous DNA while the virus itself can infect many different cell types. Virus infection has been shown in many cases to be persistent by virtue of episomal maintenance in the target cell. In this article we examine the ability of nonselectable recombinant viruses expressing the beta-galactosidase gene product to infect a variety of human cells and demonstrate that this virus could be developed as an alternative hematopoietic stem cell gene therapy vector. In contrast to earlier observations, we demonstrate by a number of methods that the virus has the ability to replicate in many human cell types, suggesting the need for the development of a disabled virus for use as a gene therapy vector.

Cardiovascular hypertrophy does not predispose to genetic hypertension.

It has been proposed that cardiovascular hypertrophy precedes and contributes to the development of genetic hypertension. In a genetically segregating population we determined whether susceptibility to high blood pressure was associated with cardiovascular structural abnormalities in youth. In 9-week old male F2 rats derived from a cross of spontaneously hypertensive rats (SHR) and inbred normotensive Donryu (DRY) rats we determined left ventricular mass (LVM) by echocardiography and the media-lumen ratio (MLR) of mesenteric resistance vessels by biopsy. Direct mean arterial pressure was measured in the same rats at 20 weeks of age. The ranges of LVM and MLR in young F2 rats encompassed values seen SHR and DRY at this age. However, no correlation was observed between LVM or MLR and subsequent blood pressures at 20 weeks of age. The blood pressure of F2 rats with cardiovascular structural phenotypes within the SHR range was no higher than the remainder of the F2 population. These studies do not support the hypothesis that hypertrophy of the heart or mesenteric resistance vessels confer susceptibility to the development of genetic hypertension.

A placebo-controlled trial verifying the efficacy of milrinone in weaning high-risk patients from cardiopulmonary bypass.

OBJECTIVE: To establish the efficacy of the phosphodiesterase inhibitor milrinone in facilitating weaning from cardiopulmonary bypass of high-risk patients with left ventricular dysfunction and/or pulmonary hypertension. DESIGN: A double-blinded, placebo-controlled longitudinal study. SETTING: A university teaching hospital. PARTICIPANTS: Thirty-two patients with preoperative left ventricular ejection fraction < or = 35% and/or mean pulmonary artery pressure > or = 20 mmHg were studied after their written informed consent. INTERVENTION: Patients were randomized to commence either intravenous milrinone, 50 micrograms/kg loading dose over 20 minutes followed by 0.5 microgram/kg/min infusion, or matching placebo 15 minutes before withdrawal of cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Two patients were withdrawn from the study and their results not analyzed: one because of early failure of hemodynamic monitoring and the other because of gross surgical bleeding. In the remaining 30 patients, who were well matched for clinical and baseline hemodynamic variables, bypass support was successfully withdrawn in all 15 patients randomized to receive milrinone but in only 5 of the 15 patients randomized to receive placebo. In the 10 patients who initially failed to wean from bypass while on placebo, bypass was reinstituted and open-label milrinone was administered in the dose outlined. After treatment with open-label milrinone, these patients could also be withdrawn from bypass support. During the period of hemodynamic monitoring, cardiac index increased in both milrinone- and placebo-treated patients, although this change was greater in those treated with milrinone. Perhaps related to routine clinical treatment, there were no significant differences between the two groups with mean pulmonary artery or pulmonary capillary wedge pressures, the other major hemodynamic endpoints. There were no significant adverse effects related to milrinone. CONCLUSIONS: This placebo-controlled, double-blind study has conclusively demonstrated the benefits of milrinone in facilitating weaning of high-risk patients from cardiopulmonary bypass.

Orthotopic liver transplantation in two patients with hypertrophic obstructive cardiomyopathy.

Orthotopic liver transplantation (OLT) in patients with end-stage liver disease is a procedure associated with high cardiac output, low systemic vascular resistance (SVR), coagulopathy and the potential for significant blood loss. A feature of hypertrophic obstructive cardiomyopathy (HOCM) is left ventricular outflow tract obstruction which may be exacerbated by reduced SVR, reduced filling pressures, tachycardia and positive inotropy. We report two cases of OLT in patients with HOCM. Our anaesthetic technique involved the use of halothane and vecuronium and avoidance of drugs causing tachycardia and positive inotropy. Management was aided by intraoperative transoesophageal echocardiography which showed that filling pressures poorly reflected end-diastolic volumes. Volume administration, vasoconstrictors and avoidance of inotropes and chronotropes reduced the outflow tract obstruction which was particularly severe in the reperfusion period.

The influences of goal-related actions and reward information on children's and adults' perceptions of effort expenditure and goal desire.

An action perception approach (i.e., Heider, 1958) was used to investigate the influences of qualitatively different goal-related actions on 2nd- and 5th-grade children's and college students' perceptions of actors' effort expenditure (i.e., trying) and goal desire (i.e., wanting). Actors performed three repetitive actions or three equifinal actions within 2 reward conditions (offer of reward or no reward, for attempting to attain a prosocial goal). At each age level, perceptions of effort and want varied significantly by goal-related actions, whereas reward information did not emerge as an influential factor in differentiating perceptions of effort and want. Age-related findings suggested that, compared with the college students, the children overattributed trying and wanting to the actors. In the repetitive-actions condition, both 2nd and 5th graders gave significantly higher effort and want ratings than college students did. In the equifinal-actions condition, 2nd and 5th graders gave significantly higher effort ratings than college students did.

Atrial fibrillation with left atrial spontaneous contrast detected by transesophageal echocardiography is a potent risk factor for stroke.

Nonrheumatic atrial fibrillation (AF) frequently coexists with other risk factors for cerebral ischemia. This study was originally designed to determine which combinations of clinical and echocardiographic abnormalities were most closely associated with the risk of cerebral ischemic events. Patients with cerebral ischemic events (n = 214) and community-based control subjects (n = 201) underwent transesophageal echocardiography and carotid artery imaging. Adjusted odds ratios (ORs) were determined using multiple logistic regression analysis. Independent risk factors for cerebral ischemia included diabetes, carotid stenosis, aortic sclerosis, left ventricular dysfunction, left ventricular hypertrophy, left atrial (LA) spontaneous contrast, and proximal aortic atheroma. Nonrheumatic AF in combination with LA spontaneous contrast and LA enlargement showed a strong association with cerebral ischemic events (OR 33.7 [95% confidence interval 4.53 to 251]). In subjects with sinus rhythm or nonrheumatic AF, LA enlargement was not associated with an increased risk of cerebral ischemic events in the absence of LA spontaneous contrast. However, only 2 patients and 1 control subject had nonrheumatic AF without LA spontaneous contrast or LA enlargement. Therefore, study of a larger number of subjects is required to address the issue of whether nonrheumatic AF itself carries increased risk. The combination of nonrheumatic AF with LA spontaneous contrast is a potent risk factor for cerebral ischemia. Ascertaining the risk factor in nonrheumatic AF requires adequate examination for underlying cardiac, aortic, and carotid vascular disease. Transesophageal echocardiography may contribute to this assessment.

Low energy endocardial cardioversion of atrial arrhythmias in humans.

We assessed the feasibility of low energy endocardial defibrillation in patients with atrial fibrillation or atrial flutter who had failed a trial of pharmacological reversion with amiodarone. Low energy endocardial defibrillation under general anesthesia was attempted in 9 patients, 5 with atrial flutter and 4 with atrial fibrillation (median duration of arrhythmia 3.75 months). Two large surface area endocardial leads were introduced percutaneously and sited in the right atrial appendage and at the right ventricular apex. A cutaneous patch electrode was placed on the left thorax. Biphasic shocks synchronized to the ventricular electrogram were used to terminate atrial arrhythmias. Three electrode configurations were evaluated in the following sequence at each energy level: atrial cathode to ventricular anode; ventricular cathode to atrial anode; atrial cathode to a combined ventricular and cutaneous anode. If endocardial defibrillation failed (0.5-10 J), transthoracic defibrillation using 200 joules followed by 360 joules, if required, was performed. Endocardial defibrillation was successful in all five patients with atrial flutter (0.5 J, 1.0 J, 1.0 J, 4.0 J, and 10.0 J) but in only one patient with atrial fibrillation (10 J). On no occasion did successful defibrillation occur with one configuration when it had failed with an alternate configuration at that particular energy level. Ventricular fibrillation did not occur, and there were no other significant complications. Low energy endocardial defibrillation is feasible in patients with atrial flutter using large surface area electrodes. Although the success rate of atrial defibrillation was low, further work is required, particularly in patients with more recent onset of the arrhythmia and using a right to left electrode configuration.

The proximal aorta: a source of stroke.

The availability of the sophisticated imaging techniques of transoesophageal echocardiography and epiaortic ultrasound scanning have drawn attention to the ascending aorta and aortic arch as a potential source of embolic stroke. Several studies have shown an association between atheroma in this region and cerebral ischaemic events. Although aortic atheroma is associated with vascular disease in other arterial territories, two large controlled studies have shown it to be a risk factor for stroke, independently of other major risk factors such as carotid vascular disease, cardiac disease and hypertension. In observational and case-control studies, the risk of stroke is higher in the presence of certain echocardiographic appearances of atheromatous plaque--these include plaque thickness of > 4-5 mm, surface irregularity suggesting plaque ulceration and mobile elements suggesting superimposed thrombus. However, longitudinal studies are required to evaluate the prognostic significance of such findings. Several therapeutic options have been described or suggested in patients with and without stroke in whom aortic atheroma is demonstrated, but the optimal management of such patients is yet to be determined in prospective controlled trials.

The influences of goal-related action and goal information on children's perceptions of trying and wanting: an action-perception approach.

The influences of goal-related actions and goal information on children's try-and-want perceptions were investigated with an action-perception approach (i.e., Heider, 1958). Kindergartners, second graders, and fifth graders heard stories that depicted actors engaged in one action, that same action three times, or three equifinal actions to attain a positive or negative goal. The children rated how much actors tried and wanted to attain the goal. The findings indicate that the actors who engaged in only one action were perceived to have tried and wanted the least, and the actors who engaged in equifinal actions were perceived to have tried and wanted the most. The actors who engaged in one action were not significantly differentiated from those who engaged in repetitive actions. However, the actors who engaged in repetitive actions were significantly differentiated from those who engaged in equifinal actions. For try ratings only, the children made all expected differentiations of actors by goal-related action in negative goal conditions, whereas fewer differentiations were made of actors in positive goal conditions. Age-related findings indicate that only younger children perceived that the actors who pursued positive goals tried and wanted more than those who pursued negative goals.

Proximal aortic atheroma. An independent risk factor for cerebral ischemia.

BACKGROUND AND PURPOSE: Transesophageal echocardiography frequently demonstrates aortic atheroma in patients with cerebral and peripheral emboli. The aim of this study was to determine whether atheroma in the ascending aorta and arch is an independent risk factor for cerebral ischemia. METHODS: We studied 215 consecutive patients with a first stroke or transient ischemic attack and 202 community-based control subjects using transesophageal echocardiography to detect aortic atheroma and potential cardiac sources for embolism. Information about other stroke risk factors was obtained from a structured interview, and the presence of carotid vascular disease was assessed by means of duplex ultrasonography or digital subtraction angiography. Multiple logistic regression analysis was used to determine adjusted odds ratios for each risk factor. RESULTS: Atheroma in the ascending aorta and aortic arch was a significant risk factor for cerebral ischemia, independent of other well-established risk factors including high-grade carotid stenosis. The odds ratio for simple atheroma was 2.3 (95% confidence interval, 1.2 to 4.2) and for complex atheroma 7.1 (2.7 to 18.4). CONCLUSIONS: Ascending aortic and arch atheroma detected by transesophageal echocardiography is an important new independent risk factor for cerebral ischemia. Further characterization of the embolic potential of atheroma with different echocardiographic appearances and development of optimal management strategies are now needed.

Evidence that patent foramen ovale is not a risk factor for cerebral ischemia in the elderly.

Patent foramen ovale (PFO) may be a risk factor for ischemic stroke in young patients. The aim of this study was to assess the importance of PFO in subjects with a wider age range using patient-control methodology. Transesophageal contrast echocardiography and carotid imaging were performed in 220 consecutive patients with cerebral ischemia (mean age 66 +/- 13 years) and in 202 community-based control subjects (mean age 64 +/- 11 years). Of patients with stroke, 35 (16%) had PFO compared with 31 control subjects (15%) (p = 0.98). Analysis of PFO prevalence by age did not show a significant difference between patients and controls subjects in the age groups < 50 years (27% vs 11%; p = 0.33), 50 to 69 years (17% vs 15%; p = 0.78), and > or = 70 years (12% vs 17%; p = 0.43). However, the group aged < 50 years was relatively small (26 cases, 19 controls). No significant difference in PFO prevalence was detected between patients with cryptogenic stroke (20%), noncryptogenic stroke (14%), and control subjects (15%). These results suggest that PFO is not a risk factor for cerebral ischemia in subjects aged > 50 years, which would have major implications for the investigation and management of stroke patients in this age group. Longitudinal studies are now required to assess the incidence of stroke in symptom-free patients with PFO.

Evaluation of mitral valve repair by intraoperative transoesophageal echocardiography.

BACKGROUND: Mitral valve repair is the procedure of choice in the surgical management of mitral regurgitation. Intraoperative confirmation of successful repair is essential to the effectiveness of this procedure. AIMS: The aims of this study were: (a) to compare intraoperative transoesophageal echocardiography (TOE) with the surgeon's assessment of valve competence; (b) to assess the impact of routine intraoperative imaging on the hospital echocardiography laboratory. METHODS: Eighty-six consecutive patients undergoing mitral valve repair formed the study population. Valve competence following repair was assessed intraoperatively by: TOE; saline insufflation of the flaccid left ventricle; and evaluation of the pulmonary capillary wedge pressure for the presence of a significant V wave. RESULTS: TOE demonstrated successful valve repair (< or = 1 + residual regurgitation) in 75 patients (87%) and detected significant residual regurgitation (> or = 3+) in seven (8.2%). The mechanism of regurgitation was also clearly shown. Of these seven patients, four underwent immediate valve replacement, two had successful revision of the initial repair and one required valve replacement one week later. In all seven patients the valve repair had been assessed as successful by saline testing and only one had a post-repair V wave 10 mmHg above the mean pulmonary capillary wedge pressure. In 30 non-selected patients the imaging equipment was required in theatre for 43 +/- 18 minutes. CONCLUSIONS: TOE is currently the most sensitive method for detection and quantitation of residual mitral regurgitation following valve repair. Evaluation can be performed within a similar time to that required for one complete transthoracic study and can usually be performed with minimal disruption to the hospital echocardiography laboratory.

Transoesophageal echocardiography in the investigation of stroke: experience in 135 patients with cerebral ischaemic events.

BACKGROUND: The importance of cardiogenic embolism as a cause of cerebral ischaemic events may be underestimated if potential cardiac sources of embolism remain undetected. Transoesophageal echocardiography (TOE) is more sensitive in detecting such abnormalities than earlier methods and may result in more frequent recognition of cardiogenic embolism. AIMS: To establish in an unselected stroke population the prevalence of potential cardiac sources of embolism detectable on TOE and their relationship to atrial fibrillation and carotid stenosis. METHODS: One hundred and thirty-five consecutive patients with cerebral ischaemic events were studied using transthoracic and monoplane transoesophageal contrast echocardiography and carotid Duplex imaging or cerebral angiography. RESULTS: Thirty patients (22%) had atrial fibrillation. In 43 patients (32%), no cardiac source of embolism was identified; in eight echocardiography was normal. At least one potential cardiac source of embolism was identified in 92 patients (68%) with multiple findings in 41; these patients were older (70 +/- 9 years vs 61 +/- 14 years; p = 0.0001), more frequently in atrial fibrillation (28/92 vs 2/43; p = 0.0017) and more frequently had cortical or large subcortical stroke (71/92 vs 23/43; p = 0.005). Carotid stenoses were detected in 55% of patients, not significantly different in those with and without cardiac abnormalities. CONCLUSION: When bias in selection of patients is avoided, TOE detects a potential cardiac source of embolism in most patients with cerebral ischaemia, particularly those older and in atrial fibrillation. Multiple cardiac abnormalities and coexistent carotid disease are common. The implication of these findings for prevention of stroke awaits age-matched controlled studies.

A 2-year clinical evaluation of two pit and fissure sealants placed with and without the use of a bonding agent.

The purpose of the study was to evaluate whether the clinical effectiveness of pit and fissure sealant was increased (as demonstrated by an increased retention rate) when a bonding agent was used prior to the placement of the sealant. Two pit and fissure sealants, Concise Light Cured White Sealant and Prisma Shield Light Cured Sealant, were placed in vivo with and without the use of the bonding agents, Scotchbond 2 and Prisma Universal Bond. After 2 years, 55% of the sample was available for recall. The retention rates for the sealants were 77% for Concise with Scotchbond 2, 84% for Concise with no bonding agent, 77% for Prisma Shield with Universal Bond, and 77% for Prisma Shield with no bonding agent. Results of this study indicated that the use of a bonding agent prior to the application of a pit and fissure sealant does not increase the retention rate.

Development and validation of echocardiographic methods for estimating left ventricular mass in rats.

1. The aim of this study was to develop non-invasive echocardiographic methods of measuring left ventricular mass (LVM) in rats, and to determine their usefulness in detecting left ventricular hypertrophy. 2. After initial studies to identify the optimum transducer and to ascertain the resolution limits of echocardiography, the repeatability of LVM estimates was studied. The average difference between two independent estimates in 86 male rats (average LVM = 674.7 mg) was 5.4 mg, and the standard deviation of the difference was 107.6 mg. 3. To determine agreement between direct and indirect methods, LVM was measured in 38 male rats by echocardiography and compared with direct measurement of the left ventricular weight at sacrifice. The mean difference between the two methods was 9.14 +/- 56.6 mg. The limits of agreement were from -122.4 to +104.1 mg. 4. Echocardiography was then used to measure LVM in eight male spontaneously hypertensive rats and eight male normotensive Donryu rats at 9 weeks of age. The mean LVM of SHR was 768.2 mg +/- 152.6, which was significantly (2P less than 0.001) greater than the LVM of DRY (435.4 mg +/- 32.2). 5. We conclude that echocardiography provides a non-invasive, repeatable and relatively accurate estimate of LVM in rats. The method is a potentially useful tool for studying the development or regression of cardiac hypertrophy in longitudinal experiments.