Robert J. Wentz

Development of a Cathartic-Free Colorectal Cancer Screening Test Using Virtual Colonoscopy: A Feasibility Study

OBJECTIVE The purpose of our study was to develop a method to subtract barium-labeled stool from the colon using a phantom and to evaluate the performance of the technique in a pilot human population. MATERIALS AND METHODS A phantom containing 6-mm flat polyps and three types of simulated stool (homogeneous, moderately heterogeneous, and severely heterogeneous) mixed with barium was created, scanned, and tested using three stool subtraction algorithms but no cathartic. Thirty patients with suspected colorectal polyps were studied using stool tagging to determine which was the most effective stool subtraction algorithm. Colonoscopy was the reference standard. Examinations were evaluated blindly using the unsubtracted and 6 weeks later both the unsubtracted and subtracted data sets. RESULTS A threshold of 200 H and expansion and convolution techniques were the most effective tools for subtracting stool and minimizing artifacts. When applied to the human population, sensitivities using the unsubtracted data sets were 90% (18/20) and 68% (26/38) for polyps > or = 1 cm and > or = 5 mm, respectively. Specificities were 100% (4/4) and 75% (3/4) for polyps > or = 1 cm and > or = 5 mm. For the stool-subtracted data sets, sensitivities were 90% (18/20) and 71% (27/38) for polyps > or = 1 cm and > or = 5 mm. Per patient sensitivities were 88% (15/17) and 77% (20/26) for > or = 1 cm and > or = 5 mm polyps. Specificities were 100% (4/4) for large polyps and 25% (1/4) for smaller polyps. CONCLUSION Image processing tools combining thresholding, expansion, and convolution were the most useful for stool subtraction. Laxative-free colon examinations using barium for stool labeling can be performed at CT colonography with or without stool subtraction with high accuracy. Further study is warranted.

CT colonography of the unprepared colon: An evaluation of electronic stool subtraction

CT colonography (CTC) is being extensively studied for its potential value in colon examinations, since it offers many advantages such as lower risk and less patient discomfort. However, CTC, like all other types of full structural colorectal examinations to date, requires complete bowel preparation. The inconvenience and discomfort associated with this preparation is an important obstacle to compliance with currently recommended colorectal screening guidelines. To maximize compliance, CTC would ideally be performed on an unprepared colon. However, in an unprepared colon residual stool and fluid can mimic soft tissue density and thus confound the identification of polyps. An alternative is to tag the stool with an opacifying agent so that it is brighter than soft tissue and thus easily recognized automatically and then reset to air values. However, such electronic stool subtraction in a totally unprepared colon is difficult to perform accurately for several reasons, including poorly labeled areas of stool, the need to accurately quantify partial volume effects, and noise. In this study the performance of a novel stool subtraction algorithm was assessed in unprepared CT colonography exams of 25 consecutive volunteers who had undergone colonoscopy with positive findings. Results showed 81% sensitivity to clinically relevant lesions > 1 cm with 0.52 false positives per patient compared to colonoscopy findings. Although further study and refinement of the stool subtraction process is required, CT colonography of the unprepared colon with electronic stool subtraction is feasible at detection levels comparable to the prepared colon.

Reproducibility of aortic pulsatility measurements from ECG-gated abdominal CTA in patients with abdominal aortic aneurysms

Purpose: ECG-gated abdominal CT angiography with reconstruction of multiple, temporally overlapping CT angiography datasets has been proposed for measuring aortic pulsatility. The purpose of this work is to develop algorithms to segment the aorta from surrounding structures from CTA datasets across cardiac phases, calculate registered centerlines and measurements of regional aortic pulsatility in patients with AAA, and to assess the reproducibility of these measurements. Methods: ECG-gated CTA was performed with a temporal resolution of 165 ms, reconstructed to 1 mm slices ranging at 14 cardiac phase points. Data sets were obtained from 17 patients on which two such scans were performed 6 to 12 months apart. Automated segmentation, centerline generation, and registration of centerlines between phases was performed, followed by calculation of cross-sectional areas and regional and local pulsatility. Results: Pulsatility calculations for the supraceliac region were very reproducible between earlier and later scans of the same patient, with average differences less than 1% for pulsatility values ranging from 2% to 13%. Local radial pulsatilities were also reproducible to within ~1%. Aneurysm volume changes between scans can also be quantified. Conclusion: Automated segmentation, centerline generation, and registration of temporally resolved CTA datasets permit measurements of regional changes in cross-sectional area over the course of the cardiac cycle (i.e., regional aortic pulsatility). These measurements are reproducible between scans 6-12 months apart, with differences in aortic areas reflecting both aneurysm remodeling and changes in blood pressure. Regional pulsatilities ranged from 2 to 13% but were reproducible at the 1% level.

Automatic segmentation and co-registration of gated CT angiography datasets: measuring abdominal aortic pulsatility

Purpose: To develop robust, novel segmentation and co-registration software to analyze temporally overlapping CT angiography datasets, with an aim to permit automated measurement of regional aortic pulsatility in patients with abdominal aortic aneurysms. Methods: We perform retrospective gated CT angiography in patients with abdominal aortic aneurysms. Multiple, temporally overlapping, time-resolved CT angiography datasets are reconstructed over the cardiac cycle, with aortic segmentation performed using a priori anatomic assumptions for the aorta and heart. Visual quality assessment is performed following automatic segmentation with manual editing. Following subsequent centerline generation, centerlines are cross-registered across phases, with internal validation of co-registration performed by examining registration at the regions of greatest diameter change (i.e. when the second derivative is maximal). Results: We have performed gated CT angiography in 60 patients. Automatic seed placement is successful in 79% of datasets, requiring either no editing (70%) or minimal editing (less than 1 minute; 12%). Causes of error include segmentation into adjacent, high-attenuating, nonvascular tissues; small segmentation errors associated with calcified plaque; and segmentation of non-renal, small paralumbar arteries. Internal validation of cross-registration demonstrates appropriate registration in our patient population. In general, we observed that aortic pulsatility can vary along the course of the abdominal aorta. Pulsation can also vary within an aneurysm as well as between aneurysms, but the clinical significance of these findings remain unknown. Conclusions: Visualization of large vessel pulsatility is possible using ECG-gated CT angiography, partial scan reconstruction, automatic segmentation, centerline generation, and coregistration of temporally resolved datasets.

Association of Cognitive Performance with Time at Altitude, Sleep Quality, and Acute Mountain Sickness Symptoms

OBJECTIVE It is well documented that cognitive performance may be altered with ascent to altitude, but the association of various cognitive performance tests with symptoms of acute mountain sickness (AMS) is not well understood. Our objective was to assess and compare cognitive performance during a high-altitude expedition using several tests and to report the association of each test with AMS, headache, and quality of sleep. METHODS During an expedition to Mount Everest, 3 cognitive tests (Stroop, Trail Making, and the real-time cognitive assessment tool, an in-house developed motor accuracy test) were used along with a questionnaire to assess health and AMS. Eight team members were assessed pre-expedition, postexpedition, and at several time points during the expedition. RESULTS There were no significant differences (P >.05) found among scores taken at 3 time points at base camp and the postexpedition scores for all 3 tests. Changes in the Stroop test scores were significantly associated with the odds of AMS (P <.05). The logistic regression results show that the percent change from baseline for Stroop score (β = -5.637; P = .032) and Stroop attempts (β = -5.269; P = .049) are significantly associated with the odds of meeting the criteria for AMS. CONCLUSIONS No significant changes were found in overall cognitive performance at altitude, but a significant relationship was found between symptoms of AMS and performance in certain cognitive tests. This research shows the need for more investigation of objective physiologic assessments to associate with self-perceived metrics of AMS to gauge effect on cognitive performance.

Impact of chronic systolic heart failure on lung structure–function relationships in large airways

Heart failure (HF) is often associated with pulmonary congestion, reduced lung function, abnormal gas exchange, and dyspnea. We tested whether pulmonary congestion is associated with expanded vascular beds or an actual increase in extravascular lung water (EVLW) and how airway caliber is affected in stable HF. Subsequently we assessed the influence of an inhaled short acting beta agonist (SABA). Thirty‐one HF (7F; age, 62 ± 11 years; ht. 175 ± 9 cm; wt. 91 ± 17 kg; LVEF, 28 ± 15%) and 29 controls (11F; age; 56 ± 11 years; ht. 174 ± 8 cm; wt. 77 ± 14 kg) completed the study. Subjects performed PFTs and a chest computed tomography (CT) scan before and after SABA. CT measures of attenuation, skew, and kurtosis were obtained from areas of lung tissue to assess EVLW. Airway luminal areas and wall thicknesses were also measured. CT tissue density suggested increased EVLW in HF without differences in the ratio of airway wall thickness to luminal area or luminal area to TLC (skew: 2.85 ± 1.08 vs. 2.11 ± 0.79, P < 0.01; Kurtosis: 15.5 ± 9.5 vs. 9.3 ± 5.5 P < 0.01; control vs. HF). PFTs were decreased in HF at baseline (% predicted FVC:101 ± 15% vs. 83 ± 18%, P < 0.01;FEV1:103 ± 15% vs. 82 ± 19%, P < 0.01;FEF25–75: 118 ± 36% vs. 86 ± 36%, P < 0.01; control vs. HF). Airway luminal areas, but not CT measures, were correlated with PFTs at baseline. The SABA cleared EVLW and decreased airway wall thickness but did not change luminal area. Patients with HF had evidence of increased EVLW, but not an expanded bronchial circulation. Airway caliber was maintained relative to controls, despite reductions in lung volume and flow rates. SABA improved lung function, primarily by reducing EVLW.

Influence of Inhaled Amiloride on Lung Fluid Clearance in Response to Normobaric Hypoxia in Healthy Individuals

Wheatley, Courtney M., Sarah E. Baker, Bryan J. Taylor, Manda L. Keller-Ross, Steven C. Chase, Alex R. Carlson, Robert J. Wentz, Eric M. Snyder, and Bruce D. Johnson. Influence of inhaled amiloride on lung fluid clearance in response to normobaric hypoxia in healthy individuals. High Alt Med Biol 18:343-354, 2017. AIM To investigate the role of epithelial sodium channels (ENaC) on lung fluid clearance in response to normobaric hypoxia, 20 healthy subjects were exposed to 15 hours of hypoxia (fraction of inspired oxygen [FiO2] = 12.5%) on two randomized occasions: (1) inhaled amiloride (A) (1.5 mg/5 mL saline); and (2) inhaled saline placebo (P). Changes in lung fluid were assessed through chest computed tomography (CT) for lung tissue volume (TV), and the diffusion capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO) for pulmonary capillary blood volume (VC). Extravascular lung water (EVLW) was derived as TV-VC and changes in the CT attenuation distribution histograms were reviewed. RESULTS Normobaric hypoxia caused (1) a reduction in EVLW (change from baseline for A vs. P, -8.5% ± 3.8% vs. -7.9% ± 5.2%, p < 0.05), (2) an increase in VC (53.6% ± 28.9% vs. 53.9% ± 52.3%, p < 0.05), (3) a small increase in DLCO (9.6% ± 29.3% vs. 9.9% ± 23.9%, p > 0.05), and (4) CT attenuation distribution became more negative, leftward skewed, and kurtotic (p < 0.05). CONCLUSION Acute normobaric hypoxia caused a reduction in lung fluid that was unaffected by ENaC inhibition through inhaled amiloride. Although possible amiloride-sensitive ENaC may not be necessary to maintain lung fluid balance in response to hypoxia, it is more probable that normobaric hypoxia promotes lung fluid clearance rather than accumulation for the majority of healthy individuals. The observed reduction in interstitial lung fluid means alveolar fluid clearance may not have been challenged.

Vascularity of myocardium and gastrocnemius muscle in rats selectively bred for endurance running capacity

We tested the hypothesis that changes in the arteriolar branching architecture contributed to increased running capacity of rats subjected to two-way artificial selection for intrinsic aerobic endurance treadmill running capacity resulting in strains of low-capacity and high-capacity endurance rats. Hearts and gastrocnemius muscles were harvested from each strain, and the microvasculatures branching geometry measured from micro-CT images. The vascular branching geometry of the hearts and skeletal muscle from the high capacity was indistinguishable from low-capacity rats. Our hypothesis was not supported. Neither remodeling nor an increase in arteriolar microvasculature branching appears to play a role in the enhanced performance of the high capacity rats. We are led to speculate that endothelial tolerance for shear stress and/or increased coupling of myocardial muscle fiber metabolic-to-contractile function is increased in the high-capacity runner strain to the effect of allowing either higher flow rate per unit volume of muscle or more efficient use of oxygen and nutrients in the high-capacity endurance rats.