Automated chest X-ray reading for tuberculosis in the Philippines to improve case detection: a cohort study.

BACKGROUND: DetecTB (Diagnostic Enhanced Tools for Extra Cases of TB), an intensified tuberculosis (TB) case-finding programme targeting prisons and high-risk communities was implemented on Palawan Island, the Philippines.OBJECTIVE: To evaluate the performance of TB detection based on computerised chest radiography (CXR) readings.DESIGN: Data from 14 094 subjects were analysed from September 2012 to June 2014. All CXRs were read by a physician and by software. Individuals with TB symptoms or CXR abnormalities according to the physician underwent Xpert® MTB/RIF testing, the remaining persons were considered TB-negative (screening reference). A subset of 200 CXRs was read by an independent human reader (radiological reference). This reader also re-read a subset of the most abnormal cases as identified using the software but read as normal by the physician (discordant cases).RESULTS: A total of 10 755 individuals were included in the analysis, 2534 of whom had a positively assessed CXR; 298 cases were Xpert-positive. Using the screening reference, the area under the receiver operating characteristic curve for software readings was 0.93 (95%CI 0.92-0.94), with a sensitivity of 0.98 (95%CI 0.97-0.99) and a specificity of 0.69 (95%CI 0.40-0.98). Based on the radiological reference, the physician performed slightly worse than the software (sensitivity, 0.82, 95%CI 0.74-0.89 and specificity, 0.87, 95%CI 0.81-0.96 vs. sensitivity, 0.83, 95%CI 0.71-0.93 and specificity, 0.87, 95%CI 0.75-0.95), although this was not statistically significant. Of the 291 discordant cases, 70% were assessed as positive, resulting in a 22% increase in TB detection when extrapolated to the full cohort.CONCLUSION: The performance of automated CXR reading is comparable to that of the attending physicians in DetecTB, and its use as a second reader could increase TB detection.

Computer-assisted chest radiography reading for tuberculosis screening in people living with diabetes mellitus.

BACKGROUND: Diabetes mellitus is a significant risk factor for tuberculosis (TB). We evaluated the performance of computer-aided detection for tuberculosis (CAD4TB) in people living with diabetes mellitus (PLWD) in Indonesia. METHODS: PLWD underwent symptom screening and chest X-ray (CXR); sputum was examined in those with positive symptoms and/or CXR. Digital CXRs were scored using CAD4TB and analysed retrospectively using clinical and microbiological diagnosis as a reference. The area under the receiver operator curve (AUC) of CAD4TB scores was determined, and an optimal threshold score established. Agreement between CAD4TB and the radiologist's reading was determined. RESULTS: Among 346 included PLWD, seven (2.0%) had microbiologically confirmed and two (0.6%) had clinically diagnosed TB. The highest agreement of CAD4TB with radiologist reading was achieved using a threshold score of 70 (κ = 0.41, P < 0.001). The AUC for CAD4TB was 0.89 (95%CI 0.73-1.00). A threshold score of 65 for CAD4TB resulted in a sensitivity, specificity, positive predictive value and negative predictive value of respectively 88.9% (95%CI 51.8-99.7), 88.5% (95%CI 84.6-91.7), 17.0% (95%CI 7.6-30.8) and 99.6% (95%CI 98.2-100). With this threshold, 48 (13.9%) individuals needed microbiological examination and no microbiologically confirmed cases were missed. CONCLUSIONS: CAD4TB has potential as a triage tool for TB screening in PLWD, thereby significantly reducing the need for microbiological examination.

Accuracy of an automated system for tuberculosis detection on chest radiographs in high-risk screening.

SETTING: Tuberculosis (TB) screening programmes can be optimised by reducing the number of chest radiographs (CXRs) requiring interpretation by human experts. OBJECTIVE: To evaluate the performance of computerised detection software in triaging CXRs in a high-throughput digital mobile TB screening programme. DESIGN: A retrospective evaluation of the software was performed on a database of 38 961 postero-anterior CXRs from unique individuals seen between 2005 and 2010, 87 of whom were diagnosed with TB. The software generated a TB likelihood score for each CXR. This score was compared with a reference standard for notified active pulmonary TB using receiver operating characteristic (ROC) curve and localisation ROC (LROC) curve analyses. RESULTS: On ROC curve analysis, software specificity was 55.71% (95%CI 55.21-56.20) and negative predictive value was 99.98% (95%CI 99.95-99.99), at a sensitivity of 95%. The area under the ROC curve was 0.90 (95%CI 0.86-0.93). Results of the LROC curve analysis were similar. CONCLUSION: The software could identify more than half of the normal images in a TB screening setting while maintaining high sensitivity, and may therefore be used for triage.

Automatic versus human reading of chest X-rays in the Zambia National Tuberculosis Prevalence Survey.

SETTING: Tuberculosis (TB) prevalence survey in Zambia between 2013 and 2014. OBJECTIVE: To compare the performance of automatic software (CAD4TB 5) in chest X-ray (CXR) reading with that of field (general practitioners) and central (radiologists) readers. DESIGN: A retrospective study comparing the performance of human and automatic reading was conducted. Two scenarios for central reading were evaluated: abnormalities not consistent with TB were considered to be 'normal' or 'abnormal'. Sputum culture was defined as the reference standard. Measures derived from receiver operating characteristic analysis were used to assess readers' performances. RESULTS: Of 46 099 participants, 23 838 cases included all survey information; of these, 106 cases were culture-confirmed TB-positive. The performance of CAD4TB 5 was similar to that of field and central readers. Although there were significant differences in specificity when compared with field readings (P = 0.002) and central readings considering the first scenario (P < 0.001), these differences were not substantial (93.2% vs. 92.6% and 98.4% vs. 99.6%, respectively).CONCLUSIONp: The performance of automatic CXR readings is comparable with that of human experts in a TB prevalence survey setting using culture as reference.

Automated chest-radiography as a triage for Xpert testing in resource-constrained settings: a prospective study of diagnostic accuracy and costs.

Molecular tests hold great potential for tuberculosis (TB) diagnosis, but are costly, time consuming, and HIV-infected patients are often sputum scarce. Therefore, alternative approaches are needed. We evaluated automated digital chest radiography (ACR) as a rapid and cheap pre-screen test prior to Xpert MTB/RIF (Xpert). 388 suspected TB subjects underwent chest radiography, Xpert and sputum culture testing. Radiographs were analysed by computer software (CAD4TB) and specialist readers, and abnormality scores were allocated. A triage algorithm was simulated in which subjects with a score above a threshold underwent Xpert. We computed sensitivity, specificity, cost per screened subject (CSS), cost per notified TB case (CNTBC) and throughput for different diagnostic thresholds. 18.3% of subjects had culture positive TB. For Xpert alone, sensitivity was 78.9%, specificity 98.1%, CSS $13.09 and CNTBC $90.70. In a pre-screening setting where 40% of subjects would undergo Xpert, CSS decreased to $6.72 and CNTBC to $54.34, with eight TB cases missed and throughput increased from 45 to 113 patients/day. Specialists, on average, read 57% of radiographs as abnormal, reducing CSS ($8.95) and CNTBC ($64.84). ACR pre-screening could substantially reduce costs, and increase daily throughput with few TB cases missed. These data inform public health policy in resource-constrained settings.

Localized Energy-Based Normalization of Medical Images: Application to Chest Radiography.

Automated quantitative analysis systems for medical images often lack the capability to successfully process images from multiple sources. Normalization of such images prior to further analysis is a possible solution to this limitation. This work presents a general method to normalize medical images and thoroughly investigates its effectiveness for chest radiography (CXR). The method starts with an energy decomposition of the image in different bands. Next, each band's localized energy is scaled to a reference value and the image is reconstructed. We investigate iterative and local application of this technique. The normalization is applied iteratively to the lung fields on six datasets from different sources, each comprising 50 normal CXRs and 50 abnormal CXRs. The method is evaluated in three supervised computer-aided detection tasks related to CXR analysis and compared to two reference normalization methods. In the first task, automatic lung segmentation, the average Jaccard overlap significantly increased from 0.72±0.30 and 0.87±0.11 for both reference methods to with normalization. The second experiment was aimed at segmentation of the clavicles. The reference methods had an average Jaccard index of 0.57±0.26 and 0.53±0.26; with normalization this significantly increased to . The third experiment was detection of tuberculosis related abnormalities in the lung fields. The average area under the Receiver Operating Curve increased significantly from 0.72±0.14 and 0.79±0.06 using the reference methods to with normalization. We conclude that the normalization can be successfully applied in chest radiography and makes supervised systems more generally applicable to data from different sources.

Characterization of two novel human small heat shock proteins: protein kinase-related HspB8 and testis-specific HspB9.

Using search profiles based on the conserved alpha-crystallin domain that is characteristic for small heat shock proteins (sHsps), we traced two new human sHsps. One of these, being the eighth known human sHsp and thus named HspB8, was recently described as a serine-threonine protein kinase (H11), but not identified as an sHsp (C.C. Smith, Y.X. Yu, M. Kulka, L. Aurelian, J. Biol. Chem. 275 (2000)). Northern blotting showed that HspB8/H11 is predominantly transcribed in skeletal muscle and heart, like most other sHsps. The other, named HspB9, is specifically expressed in testis, notably in the spermatogenic cells from late pachytene spermatocyte stage till elongate spermatid stage. While mammalian sHsps are generally highly conserved, mouse HspB9 shows 38% sequence difference with human HspB9, which may confirm its sex-related role.

Morphometric analysis of cisplatin-induced neurite outgrowth in N1E-115 neuroblastoma cells.

Cisplatin, a widely used cytostatic drug for the control of a variety of neoplastic tumors, unexpectedly induced neurite outgrowth in N1E-115 neuroblastoma cells and this phenomenon was studied further in detail with morphometric analysis. As expected, cisplatin dose-dependently reduced cell number. At the same time, however, cisplatin affected the morphology of the neuroblastoma cells that changed from small rounded cell bodies into large flat cell bodies with neurites. The neurite length/cell as a function of cisplatin concentration showed a bell-shaped curve. The maximal effect (1200% of control) on neurite length/cell was observed at 1 microgram/ml cisplatin. In conclusion, cisplatin induced cellular differentiation in N1E-115 neuroblastoma cells at and just above threshold doses for cytostatic activity.

Alpha-sialyl cholesterol increases laminin in Schwann cell cultures and attenuates cytostatic drug-induced reduction of laminin.

Schwann cells play an important role in peripheral nerve regeneration. Here, we report the effect of alpha-sialyl cholesterol (alpha-SC), a derivative of the sialic acid-containing natural gangliosides, and the cytostatic agents, cisplatin, taxol and vincristine on the laminin production in Schwann cell cultures isolated from rat sciatic nerves. Laminin, one of several extracellular matrix components produced by Schwann cells, is known to potentiate axonal outgrowth. Laminin content was increased by alpha-SC, starting at 7.0 micrograms/ml with a maximal effect at 22.4 micrograms/ml (30%, P < 0.001). The three cytostatic drugs, dose-dependently reduced laminin content in Schwann cell cultures: (1) cisplatin at a threshold dose of 2 micrograms/ml (-26.4%, P < 0.001); (2) taxol, starting at a dose of 1 ng/ml (-8.0%, P < 0.05); and (3) vincristine, starting at 0.5 ng/ml (-5.9%, P < 0.05). Cultured Schwann cells were incubated with cytostatic drugs in combination with increasing amounts of alpha-SC and it was found that, depending on the cytostatic drug concentration used, alpha-SC could reduce or completely prevent the cytostatic drug-induced reduction of laminin in Schwann cell cultures. Co-treatment with alpha-SC also reduced part of the morphological changes caused by the cytostatic drugs. alpha-SC did not counteract the anti-proliferative effect of the cytostatic drugs on K-562 human erythroleukemia cells. In conclusion, alpha-SC increased laminin content in Schwann cell cultures and protected Schwann cell cultures against the decrease of laminin by cytostatic drugs without interfering with the anti-proliferative potential, suggesting that alpha-SC may have clinical use in protecting cancer patients against the neurotoxic effects of cytostatic drugs.