Intravenous stem cell dose and changes in quantitative lung fibrosis and DLCO in the AETHER trial: a pilot study.

OBJECTIVE: Our purpose was to compare quantitative CT-derived changes in lung fibrosis with pulmonary function, including DLCO, in human subjects with idiopathic pulmonary fibrosis who received an injection of one of two different intravenous doses of human bone-marrow-derived mesenchymal stem cells. PATIENTS AND METHODS: Two three-subject cohorts from the AETHER trial (Allogeneic Human Cells in subjects with Idiopathic Pulmonary Fibrosis via Intravenous Delivery) underwent high-resolution CT and clinical testing at baseline, 24 weeks, and 48 weeks after injection. Cohort 1 received 2x107 stem cells, and cohort 2 received 1x108 stem cells. CT scans were quantitatively analyzed for lung fibrosis using 510K cleared validated software. The percent predicted DLCO and other pulmonary function studies were obtained. RESULTS: The cohorts were well matched in lung fibrosis at baseline as assessed by CT scan and lung function. The mean QLF in cohort 1 increased from 13.1% at baseline to 17.1% at 48 weeks, while mean QLF in cohort 2 increased from 15.4% at baseline to 16.5% at 48 weeks. The subjects in cohort 2 progressed more slowly in whole lung fibrosis by a mean of 2.87% compared with cohort 1 (p=0.001 with adjustment of baseline covariates) during the baseline to the 48-week interval. The baseline DLCO was lower in cohort 2 than in cohort 1 (p<0.0001). Over 48 weeks of the study, cohort 2 subjects demonstrated a mean DLCO decline of only 2% compared with a decline of 17% in cohort 1 subjects (p=0.02). CONCLUSIONS: In this pilot study, the subjects receiving 1x108 stem cells demonstrated slower progression in quantitative lung fibrosis and a smaller decrease in DLCO than subjects receiving 2x107 stem cells.

A prospective cohort study of thoracic ultrasound in acute respiratory failure: the C3PO protocol.

OBJECTIVES: This study was performed to assess the clinical utility of a standardised thoracic ultrasound examination when added to standard care in patients with acute respiratory failure admitted to an intermediate care unit. This study aimed to assess the impact on clinical diagnosis, clinician confidence and management. Ultrasound has been shown to have utility in patients admitted to intensive care and emergency; however, utility in a ward setting is unknown. DESIGN: Prospective cohort study. SETTING: Tertiary hospital in Melbourne, Australia. PARTICIPANTS: 50 patients with acute respiratory failure requiring admission to an intermediate care unit. MAIN OUTCOME MEASURES: (1) Change in clinical diagnosis or additional clinical diagnosis following thoracic ultrasound. (2) Change in diagnostic confidence following thoracic ultrasound. (3) Change to management following thoracic ultrasound. RESULTS: In 34% of patients, ultrasound detected unexpected findings that changed or added to the clinical diagnosis. Diagnostic confidence was increased in 44%, and the treating clinician altered the management plan in 30% as a result of the ultrasound. Ultrasound was particularly useful in clarifying the diagnosis in patients with multiple initial diagnoses, reducing to a single diagnosis in 69%. CONCLUSIONS: Thoracic ultrasound has clinical utility in non-intubated adults with acute respiratory failure managed outside intensive care settings. It changed aetiological diagnosis, increases diagnostic confidence and altered clinical management in one out of three patients scanned. Our results suggest extended utility of thoracic ultrasound in acute respiratory failure to a broader context outside the intensive care unit population.

Between-Scanner and Between-Visit Variation in Normal White Matter Apparent Diffusion Coefficient Values in the Setting of a Multi-Center Clinical Trial.

PURPOSE: To study the between-scanner variation and the between-visit reproducibility of brain apparent diffusion coefficient (ADC) measurements in the setting of a multi-center chemotherapy clinical trial for glioblastoma multiforme. METHODS AND MATERIALS: ADC maps of 52 patients at six sites were calculated in-house from diffusion-weighted images obtained by seven individual scanner models of two vendors. The median and coefficient of variation (CV) of normal brain white matter ADC values from a defined region of interest were used to evaluate the differences among scanner models, vendors, magnetic fields, as well as successive visits. All patients participating in this study signed institutional review board approved informed consent. Data acquisition was performed in compliance with all applicable Health Insurance Portability and Accountability Act regulations. The study spanned from August 1, 2006, to January 29, 2008. RESULTS: For baseline median ADC, no difference was observed between the different scanner models, different vendors, and different magnetic field strength. For baseline ADC CV, a significant difference was found between different scanner models (p = 0.0002). No between-scanner difference was observed in ADC changes between two visits. For between-visit reproducibility, significant difference was seen between the ADC values measured at two successive visits for the whole patient group. CONCLUSION: The CVs varied significantly between scanners, presumably due to image noise. Consistent scanner parameter setup can improve reproducibility of the ADC measurements between visits.

Assessment of previous tuberculosis status using questionnaires, chest X-rays and computed tomography scans.

SETTING: Accurate diagnosis of previous pulmonary tuberculosis disease (PPTB) status is important clinically and in research. Reliable records of bacteriologically confirmed tuberculosis (TB) are frequently unavailable. OBJECTIVES: To evaluate the use of questionnaires and chest imaging to determine PPTB status in a high TB prevalence population. DESIGN: PPTB status was assessed using two questionnaires, chest X-ray (CXR) and high-resolution chest computed tomography (CT) scans reported by experienced readers. The study population comprised adults aged >40 years diagnosed with obstructive lung disease in a community-based prevalence survey. RESULTS: The Burden of Obstructive Lung Disease (BOLD) questionnaire and a second comprehensive questionnaire (PTbQ) provided a history of PPTB in respectively 38% (n = 41) and 36.4% (n = 39) of 107 participants. On CXR, 43.3% (45/104) had evidence of PPTB, with good inter-reader agreement (κ = 0.73). Changes compatible with PPTB were identified on chest CT in 68.3% (71/104) of the subjects. Questionnaire and CXR had negative predictive values for PPTB of 48% and 47%, respectively, compared to a composite definition. CONCLUSION: Both questionnaire and CXR markedly underestimate the prevalence of previous TB in patients with chronic obstructive pulmonary disease. The combination of a structured questionnaire and CT scan is more useful when a diagnosis of PPTB needs to be ruled out.

Cyst-based measurements for assessing lymphangioleiomyomatosis in computed tomography.

PURPOSE: To investigate the efficacy of a new family of measurements made on individual pulmonary cysts extracted from computed tomography (CT) for assessing the severity of lymphangioleiomyomatosis (LAM). METHODS: CT images were analyzed using thresholding to identify a cystic region of interest from chest CT of LAM patients. Individual cysts were then extracted from the cystic region by the watershed algorithm, which separates individual cysts based on subtle edges within the cystic regions. A family of measurements were then computed, which quantify the amount, distribution, and boundary appearance of the cysts. Sequential floating feature selection was used to select a small subset of features for quantification of the severity of LAM. Adjusted R(2) from multiple linear regression and R(2) from linear regression against measurements from spirometry were used to compare the performance of our proposed measurements with currently used density based CT measurements in the literature, namely, the relative area measure and the D measure. RESULTS: Volumetric CT data, performed at total lung capacity and residual volume, from a total of 49 subjects enrolled in the MILES trial were used in our study. Our proposed measures had adjusted R(2) ranging from 0.42 to 0.59 when regressing against the spirometry measures, with p < 0.05. For previously used density based CT measurements in the literature, the best R(2) was 0.46 (for only one instance), with the majority being lower than 0.3 or p > 0.05. CONCLUSIONS: The proposed family of CT-based cyst measurements have better correlation with spirometric measures than previously used density based CT measurements. They show potential as a sensitive tool for quantitatively assessing the severity of LAM.

Cardiac dual-source CT for the preoperative assessment of patients undergoing bariatric surgery.

AIM: To assess the diagnostic value of coronary dual-source computed tomography (DSCT) as a comprehensive, non-invasive tool in the preoperative cardiac evaluation of patients undergoing bariatric surgery. MATERIALS AND METHODS: Thirty consecutive obese [average body mass index (BMI): 45 ± 7.6, range: 35-59] patients (24 women; six men; median age: 52 ± 15 years) were enrolled in this institutional review board (IRB)-approved, Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant prospective study. Calcium scoring (CaS) and electrocardiography (ECG)-gated images of the coronary arteries were obtained with a large body habitus protocol (120 kV; 430 mAs; 100 ml iodinated contrast medium at 7 ml/s injection rate) on a DSCT machine. Qualitative (four-point: 1 = excellent to 4 = not delineable) coronary segmental analysis, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) measurements were performed. The presence and degree of vascular disease (four-grade scale: mild to severe) was correlated with CaS and cardiovascular (CV) risk stratification blood tests. In patients with severe stenosis (>70%), findings were compared with cardiac nuclear medicine imaging (single photon-emission computed tomography; SPECT) imaging. RESULTS: The average HR, enhancement, and quality score were 64 ± 7 beats/min, 288 ± 66 HU and 1.8 ± .5, respectively. Ninety-three percent (417/450) of the coronary segments were rated diagnostic. The SNRs and CNRs were 17 ± 9 and 12 ± 7 for the right coronary artery; 17 ± 8 and 12 ± 7 for the left main coronary artery; 16 ± 9 and 11 ± 7 for the left anterior descending coronary artery; and 15 ± 7 and 10 ± 6 for the left circumflex coronary artery. Ten of the 30 patients (33%) demonstrated coronary artery disease (CAD) of which two (6%) showed three-vessel disease. Four (13%) patients showed severe disease: in three of which the presence of significant stenosis was confirmed by SPECT and by catheter angiography in the fourth patient. Neither the CaS, nor the CV risk stratification tests showed significant correlation with presence or degree of CAD (p > 0.05). CONCLUSIONS: Coronary DSCT is a robust alternative imaging tool in the preoperative assessment of patients undergoing bariatric surgery.

Sleep disturbance in menopause.

Sleep disturbance during menopause is a common and important complaint faced by many women. There are many factors that may play a role in this problem, including vasomotor symptoms and changing hormone levels, circadian rhythm abnormalities, exacerbation of primary insomnia, mood disorders, coexistent medical conditions as well as lifestyle factors. Sleep can be measured both objectively and subjectively; however, correlation between the two measures is not high. Most of the menopause-related sleep disturbances have been reported as qualitative in nature; however, there have also been studies showing changes in objective measures. This discrepancy has implications with regard to evaluation of research in sleep and menopause, as well as application in the clinical setting. Investigations of inadequate sleep and sleep problems during the menopausal period and obtaining a thorough understanding of the factors contributing to these problems are essential in formulating treatment strategies. Such strategies can vary from hormonal treatment and medications to lifestyle and behavioural modification.

Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial.

BACKGROUND: Airway bypass is a bronchoscopic lung-volume reduction procedure for emphysema whereby transbronchial passages into the lung are created to release trapped air, supported with paclitaxel-coated stents to ease the mechanics of breathing. The aim of the EASE (Exhale airway stents for emphysema) trial was to evaluate safety and efficacy of airway bypass in people with severe homogeneous emphysema. METHODS: We undertook a randomised, double-blind, sham-controlled study in 38 specialist respiratory centres worldwide. We recruited 315 patients who had severe hyperinflation (ratio of residual volume [RV] to total lung capacity of ≥0·65). By computer using a random number generator, we randomly allocated participants (in a 2:1 ratio) to either airway bypass (n=208) or sham control (107). We divided investigators into team A (masked), who completed pre-procedure and post-procedure assessments, and team B (unmasked), who only did bronchoscopies without further interaction with patients. Participants were followed up for 12 months. The 6-month co-primary efficacy endpoint required 12% or greater improvement in forced vital capacity (FVC) and 1 point or greater decrease in the modified Medical Research Council dyspnoea score from baseline. The composite primary safety endpoint incorporated five severe adverse events. We did Bayesian analysis to show the posterior probability that airway bypass was superior to sham control (success threshold, 0·965). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00391612. FINDINGS: All recruited patients were included in the analysis. At 6 months, no difference between treatment arms was noted with respect to the co-primary efficacy endpoint (30 of 208 for airway bypass vs 12 of 107 for sham control; posterior probability 0·749, below the Bayesian success threshold of 0·965). The 6-month composite primary safety endpoint was 14·4% (30 of 208) for airway bypass versus 11·2% (12 of 107) for sham control (judged non-inferior, with a posterior probability of 1·00 [Bayesian success threshold >0·95]). INTERPRETATION: Although our findings showed safety and transient improvements, no sustainable benefit was recorded with airway bypass in patients with severe homogeneous emphysema. FUNDING: Broncus Technologies.

Apparent diffusion coefficient histogram analysis stratifies progression-free survival in newly diagnosed bevacizumab-treated glioblastoma.

BACKGROUND AND PURPOSE: Currently it is difficult to predict tumor response to anti-angiogenic therapy in individual patients. Our aim was to determine if ADC histogram analysis can stratify progression-free and overall survival in patients with newly diagnosed GBM treated "up-front" (ie, before tumor recurrence) with bevacizumab. MATERIALS AND METHODS: Up-front bevacizumab-treated and control patients (n = 59 and 62, respectively) with newly diagnosed GBM were analyzed by using an ADC histogram approach based on enhancing tumor. Progression-free and overall survival was determined by using Cox proportional HRs and the Kaplan-Meier method with logrank and Wilcoxon tests. RESULTS: For up-front bevacizumab-treated patients, lower ADC(L) was associated with significantly longer progression-free survival (median, 459 days for ADC(L) < 1200 versus 315 days for ADC(L) ≥ 1200 10(-6)mm(2)/s; P = .008, logrank test) and trended with longer overall survival (581 versus 429 days, P = .055). ADC values did not stratify progression-free or overall survival for patients in the control group (P = .92 and P = .22, respectively). Tumors with MGMT promoter methylation had lower ADC(L) values than unmethylated tumors (mean, 1071 versus 1183 10(-6)mm(2)/s; P = .01, 2-group t test). CONCLUSIONS: Pretreatment ADC histogram analysis can stratify progression-free survival in bevacizumab-treated patients with newly diagnosed GBM. Lower ADC is associated with tumor MGMT promoter methylation, which may, in part, account for the favorable outcome associated with low ADC(L) tumors.

Patterns of progression in patients with recurrent glioblastoma treated with bevacizumab.

OBJECTIVE: We evaluated patterns of tumor progression in patients with recurrent glioblastoma who were treated with bevacizumab (BEV) alone or in combination with irinotecan (CPT-11) while participating in the BRAIN study. METHODS: An independent neuroradiologist reviewed MRI scans at baseline and progression in patients who received BEV (n = 85) or BEV+CPT-11 (n = 82) while on BRAIN. Tumor patterns were scored as local, distant, diffuse, or multifocal. Median progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. Hazard ratios for PFS and OS were estimated using a Cox regression model. RESULTS: Twenty-eight percent of patients who participated in BRAIN had nonlocal disease at baseline (72% local disease). Sixty-seven (79%) patients treated with single-agent BEV and 57 (70%) patients treated with BEV+CPT-11 experienced disease progression while on BRAIN. Most patients in each treatment group did not have a change in the radiographic pattern of their tumor (i.e., "no shift") at the time of progression. The proportion of BEV patients with no shift (82%) was greater than that of BEV+CPT-11 patients (53%, χ(2) p = 0.0004), and a greater proportion of BEV+CPT-11 patients (39%) compared with BEV patients (16%) experienced local-to-diffuse tumor pattern at progression (χ(2) p = 0.002). Patients treated with BEV or BEV+CPT-11 who had local-to-local or local-to-diffuse progression patterns had similar efficacy outcomes, including objective response, PFS, and OS. CONCLUSIONS: Most patients treated with BEV or BEV+CPT-11 on BRAIN did not experience a change from baseline in radiographic characteristics of disease at the time of progression.

A computer-aided diagnosis system for quantitative scoring of extent of lung fibrosis in scleroderma patients.

OBJECTIVES: To evaluate an improved quantitative lung fibrosis score based on a computer-aided diagnosis (CAD) system that classifies CT pixels with the visual semi-quantitative pulmonary fibrosis score in patients with scleroderma-related interstitial lung disease (SSc-ILD). METHODS: High-resolution, thin-section CT images were obtained and analysed on 129 subjects with SSc-ILD (36 men, 93 women; mean age 48.8±12.1 years) who underwent baseline CT in the prone position at full inspiration. The CAD system segmented each lung of each patient into 3 zones. A quantitative lung fibrosis (QLF) score was established via 5 steps: 1) images were denoised; 2) images were grid sampled; 3) the characteristics of grid intensities were converted into texture features; 4) texture features classified pixels as fibrotic or non-fibrotic, with fibrosis defined by a reticular pattern with architectural distortion; and 5) fibrotic pixels were reported as percentages. Quantitative scores were obtained from 709 zones with complete data and then compared with ordinal scores from two independent expert radiologists. ROC curve analyses were used to measure performance. RESULTS: When the two radiologists agreed that fibrosis affected more than 1% or 25% of a zone or zones, the areas under the ROC curves for QLF score were 0.86 and 0.96, respectively. CONCLUSIONS: Our technique exhibited good accuracy for detecting fibrosis at a threshold of both 1% (i.e. presence or absence of pulmonary fibrosis) and a clinically meaningful threshold of 25% extent of fibrosis in patients with SSc-ILD.

Detection of myocardial perfusion abnormalities: standard dual-source coronary computed tomography angiography versus rest/stress technetium-99m single-photo emission CT.

We compared coronary dual-source computed tomography angiography (corDSCTA) with technetium-99m single-photon emission computed tomography (SPECT) for the detection of myocardial perfusion abnormalities. Fifty-five consecutive patients underwent both gated myocardial perfusion SPECT and corDSCTA, the latter during a single arterial-phase injection of contrast agent. The perfusion defects visualised by corDSCTA correlated with the findings of rest/stress SPECT. Abnormal findings on stress SPECT, which were due to either ischaemia or infarct, were found in 24 patients. In comparison to SPECT at rest, corDSCTA detected perfusion defects with a sensitivity and specificity of 100% and 78%, respectively. Compared to SPECT at stress, the sensitivity and specificity values of corDSCTA were 83.3% and 90.3%, respectively. On corDSCTA , the average attenuation values of perfusion defects that corresponded to chronic infarcts (-8.5+/-22.2 HU) were significantly lower (p = 0.002) than those of non-infarct-related perfusion defects (43.1+/-17.5 HU). Using rest/stress SPECT is the gold standard for the diagnosis of myocardial ischaemia, corDSCTA was able to diagnose ischaemic disease (defined as the presence of high-grade stenotic CAD (>or=50% luminal narrowing)) with a sensitivity and specificity of 59% and 89%, respectively, in patients with no known history of myocardial infarction (n = 4). Thus, corDSCTA may serve as a diagnostic tool for the detection of perfusion abnormalities (first) visualised by SPECT. There appears to be a limited correlation between coronary stenotic disease and SPECT findings.

Left ventricular ejection fraction using 64-slice CT coronary angiography and new evaluation software: initial experience.

The purpose of this study was to evaluate the feasibility and reliability of software-based quantification of left ventricular function using 64-slice CT coronary angiography. Data were collected from 26 subjects who underwent a 64-slice coronary CT angiography study. Two volumetric data sets at end diastole and end systole were reconstructed from each scan by means of retrospective electrocardiogram gating. Data sets were evaluated with a prototype of now commercially available software (Syngo Circulation I; Siemens Medical Solutions, Erlangen, Germany), which automatically segments the blood volume in the left ventricle after the user defines the mitral valve plane and any point within the ventricle. After segmentation of the blood pool in end systole and end diastole, the software automatically measures end systolic and end diastolic volume and calculates stroke volume and ejection fraction (EF). Two readers processed all CT data sets twice to assess for intra- and inter-observer variation. In addition, CT EF measurements were compared with those obtained by clinical echocardiography. Intra-observer variation for the calculated EF with CT were 13.6% and 15.6% for Readers 1 and 2, respectively. No significant difference in left ventricular functional parameters on CT existed between the readers (p > 0.05). A Bland-Altman plot revealed a slight mean difference between EF measurements on CT and echocardiography, with all differences falling within two standard deviations of the mean in the setting of wide limits of agreement. In conclusion, assessment of left ventricular EF from CT coronary data using the new analysis software is rapid and easy. The software is user-friendly and provides good reproducibility for EF measurements with CT.

Montelukast improves regional air-trapping due to small airways obstruction in asthma.

Quantitative image analysis of high-resolution computed tomography (HRCT) performed at residual volume, before and after methacholine, is a sensitive method of detecting small airways involvement in asthma and response to therapy targeted to the small airways. Since an oral anti-leukotriene reaches the small airways via the circulation, the present authors hypothesised that treatment with montelukast would lead to improved small airway patency. A double-blind crossover study compared the effect of montelukast versus placebo for 4 weeks in 16 mild-to-moderate steroid-naïve asthmatics. Small airways function was evaluated by HRCT at residual volume before and after methacholine to assess regional air-trapping and airways hyperresponsiveness, as well as by physiological studies of small airways. Montelukast treatment resulted in significantly less regional air-trapping on HRCT on the pre-methacholine images when compared with placebo, as well as improvement in total quality of life scores and symptom sub-scores. However, montelukast treatment had no effect on increases in regional air-trapping on HRCT in response to methacholine. No differences were noted in global measures of small airways physiology between placebo and montelukast. In conclusion, distal airways disease improves in asthmatic subjects treated with montelukast. This improvement can be detected with high-resolution computed tomography, but not with conventional physiological studies.

Spiral versus electron-beam CT for coronary artery calcium scoring.

PURPOSE: To determine differences in coronary artery calcium detection, quantification, and reproducibility, as measured at electron-beam computed tomography (CT) and subsecond spiral CT with retrospective electrocardiogram gating in an asymptomatic adult population. MATERIALS AND METHODS: Seventy subjects asymptomatic for coronary heart disease underwent both electron-beam CT and subsecond spiral CT. In all subjects, two images each were obtained with both scanners. Two experienced readers using three different algorithms scored each of the four scans: one score for the electron-beam CT images and two scores for the spiral CT images. RESULTS: With a 130-HU threshold for the quantification of calcium, there were no significant differences in interscan and interobserver variation in calcium scores between the electron-beam CT and spiral CT images. There was greater interobserver (P <.001) and interscan (P <.03) variation in scores when a 90-HU threshold was used for spiral CT images. With a 130-HU threshold, when calcium scores were used for clinical risk stratification, there was a significant difference between the results obtained with electron-beam CT and those obtained with spiral CT (P <.05). CONCLUSION: Spiral CT has not yet proved to be a feasible alternative to electron-beam CT for coronary artery calcium quantification. There are systematic differences between calcium scores obtained with single-detector array subsecond spiral CT and those obtained with electron-beam CT.

The effect of imaging modality on patient management in the evaluation of pulmonary thromboembolism.

A retrospective medical record review was performed to study the differences in clinical risk profiles and the relationships between test results versus management for suspected pulmonary thromboembolism (TE) in patients undergoing either radionuclide ventilation perfusion (V/Q) scans or pulmonary computed tomographic angiography (CTA), as the initial test. Data of 138 consecutive V/Q patients were compared with that of 149 consecutive CTA patients during equivalent 6-month intervals before and after the introduction of CTA. Information on risk factors, signs and symptoms, all diagnostic test results, and the relationships between the test results and ultimate physician management were collected and analyzed. V/Q results predicted physician management in all patients with high probability scans and 91% with normal to low probability scans. There were 35 patients with indeterminate V/Q scans--43% of these patients were managed without any other diagnostic test. CTA results predicted management in all patients with positive studies and 99% of patients with negative studies. In contrast to the V/Q cohort, only seven CTA studies were inconclusive--additional diagnostic tests determined management in all but one case. Compared with V/Q, CTA has fewer indeterminate results, is more directly reflective of management, and reduces the number of patients managed with inconclusive data.

Genetic loci determining bone density in mice with diet-induced atherosclerosis.

This study investigates the phenotypic and genetic relationships among bone-density-related traits and those of adipose tissue and plasma lipids in mice with diet-induced atherosclerosis. Sixteen-month-old female F2 progeny of a C57BL/6J and DBA/2J intercross, which had received an atherogenic diet for 4 mo, were examined for multiple measures of femoral bone mass, density, and biomechanical properties using both computerized tomographic and radiographic methods. In addition, body weight and length, adipose tissue mass, plasma lipids and insulin, and aortic fatty lesions were assessed. Bone mass was inversely correlated with extent of atherosclerosis and with a prooxidant lipid profile and directly correlated with body weight, length, and, most strongly, adipose tissue mass. Quantitative trait locus (QTL) analysis, using composite interval mapping (CIM) and multi-trait analysis, identified six loci with multi-trait CIM LOD scores > 5. Three of these coincided with loci linked with adipose tissue and plasma high-density lipoprotein. Application of statistical tests for distinguishing close linkage vs. pleiotropy supported the presence of a potential pleiotropic effect of two of the loci on these traits. This study shows that bone mass in older female mice with atherosclerosis has multiple genetic determinants and provides phenotypic and genetic evidence linking the regulation of bone density with adipose tissue and plasma lipids.

Problem-oriented prefetching for an integrated clinical imaging workstation.

Prefetching methods have traditionally been used to restore archived images from picture archiving and communication systems to diagnostic imaging workstations prior to anticipated need, facilitating timely comparison of historical studies and patient management. The authors describe a problem-oriented prefetching scheme, detailing 1) a mechanism supporting selection of patients for prefetching via characterizations of clinical problems, using multiple data sources (picture archiving and communication systems, hospital information systems, and radiology information systems), classifying patients into cohorts on the basis of their medical conditions (e.g., lung cancer); and 2) prefetching of multimedia data (imaging, laboratory, and medical reports) from clinical databases to enable the viewing of an integrated patient record. Preliminary evaluation of the prefetching algorithm using classic information retrieval measures showed that the system had high recall (100 percent), correctly identifying and retrieving data for all patients belonging to a target cohort, but low precision (50 percent). A key finding during testing was that the recall of the system was increased through the use of multiple data sources (compared with one data source), because of better patient descriptors. Medical problems and patient cohorts were more specifically defined by combining information from heterogeneous databases.

Patient-specific models for lung nodule detection and surveillance in CT images.

The purpose of this work is to develop patient-specific models for automatically detecting lung nodules in computed tomography (CT) images. It is motivated by significant developments in CT scanner technology and the burden that lung cancer screening and surveillance imposes on radiologists. We propose a new method that uses a patient's baseline image data to assist in the segmentation of subsequent images so that changes in size and/or shape of nodules can be measured automatically. The system uses a generic, a priori model to detect candidate nodules on the baseline scan of a previously unseen patient. A user then confirms or rejects nodule candidates to establish baseline results. For analysis of follow-up scans of that particular patient, a patient-specific model is derived from these baseline results. This model describes expected features (location, volume and shape) of previously segmented nodules so that the system can relocalize them automatically on follow-up. On the baseline scans of 17 subjects, a radiologist identified a total of 36 nodules, of which 31 (86%) were detected automatically by the system with an average of 11 false positives (FPs) per case. In follow-up scans 27 of the 31 nodules were still present and, using patient-specific models, 22 (81%) were correctly relocalized by the system. The system automatically detected 16 out of a possible 20 (80%) of new nodules on follow-up scans with ten FPs per case.