Browsing by Author "Thienemann, Friedrich"

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    Open Access
    A semi-automatic technique to quantify complex tuberculous lung lesions on 18F-fluorodeoxyglucose positron emission tomography/computerised tomography images
    (Springer Berlin Heidelberg, 2018-06-25) Malherbe, Stephanus T; Dupont, Patrick; Kant, Ilse; Ahlers, Petri; Kriel, Magdalena; Loxton, André G; Chen, Ray Y; Via, Laura E; Thienemann, Friedrich; Wilkinson, Robert J; Barry, Clifton E; Griffith-Richards, Stephanie; Ellman, Annare; Ronacher, Katharina; Winter, Jill; Walzl, Gerhard; Warwick, James M
    Background There is a growing interest in the use of 18F-FDG PET-CT to monitor tuberculosis (TB) treatment response. However, TB causes complex and widespread pathology, which is challenging to segment and quantify in a reproducible manner. To address this, we developed a technique to standardise uptake (Z-score), segment and quantify tuberculous lung lesions on PET and CT concurrently, in order to track changes over time. We used open source tools and created a MATLAB script. The technique was optimised on a training set of five pulmonary tuberculosis (PTB) cases after standard TB therapy and 15 control patients with lesion-free lungs. Results We compared the proposed method to a fixed threshold (SUV > 1) and manual segmentation by two readers and piloted the technique successfully on scans of five control patients and five PTB cases (four cured and one failed treatment case), at diagnosis and after 1 and 6 months of treatment. There was a better correlation between the Z-score-based segmentation and manual segmentation than SUV > 1 and manual segmentation in terms of overall spatial overlap (measured in Dice similarity coefficient) and specificity (1 minus false positive volume fraction). However, SUV > 1 segmentation appeared more sensitive. Both the Z-score and SUV > 1 showed very low variability when measuring change over time. In addition, total glycolytic activity, calculated using segmentation by Z-score and lesion-to-background ratio, correlated well with traditional total glycolytic activity calculations. The technique quantified various PET and CT parameters, including the total glycolytic activity index, metabolic lesion volume, lesion volumes at different CT densities and combined PET and CT parameters. The quantified metrics showed a marked decrease in the cured cases, with changes already apparent at month one, but remained largely unchanged in the failed treatment case. Conclusions Our technique is promising to segment and quantify the lung scans of pulmonary tuberculosis patients in a semi-automatic manner, appropriate for measuring treatment response. Further validation is required in larger cohorts.
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    Open Access
    Cardio-thoracic ratio is stable, reproducible and has potential as a screening tool for HIV-1 related cardiac disorders in resource poor settings
    (Public Library of Science, 2016) Esmail, Hanif; Oni, Tolu; Thienemann, Friedrich; Omar-Davies, Nashreen; Wilkinson, Robert J; Ntsekhe, Mpiko
    BACKGROUND: Cardiovascular disorders are common in HIV-1 infected persons in Africa and presentation is often insidious. Development of screening algorithms for cardiovascular disorders appropriate to a resource-constrained setting could facilitate timely referral. Cardiothoracic ratio (CTR) on chest radiograph (CXR) has been suggested as a potential screening tool but little is known about its reproducibility and stability. Our primary aim was to evaluate the stability and the inter-observer variability of CTR in HIV-1 infected outpatients. We further evaluated the prevalence of cardiomegaly (CTR≥0.5) and its relationship with other risk factors in this population. METHODOLOGY: HIV-1 infected participants were identified during screening for a tuberculosis vaccine trial in Khayelitsha, South Africa between August 2011 and April 2012. Participants had a digital posterior-anterior CXR performed as well as history, examination and baseline observations. CXRs were viewed using OsiriX software and CTR calculated using digital callipers. RESULTS: 450 HIV-1-infected adults were evaluated, median age 34 years (IQR 30-40) with a CD4 count 566/mm 3 (IQR 443-724), 70% on antiretroviral therapy (ART). The prevalence of cardiomegaly was 12.7% (95% C.I. 9.6%-15.8%). CTR was calculated by a 2 nd reader for 113 participants, measurements were highly correlated r = 0.95 (95% C.I. 0.93-0.97) and agreement of cardiomegaly substantial κ = 0.78 (95% C.I 0.61-0.95). CXR were repeated in 51 participants at 4-12 weeks, CTR measurements between the 2 time points were highly correlated r = 0.77 (95% C.I 0.68-0.88) and agreement of cardiomegaly excellent κ = 0.92 (95% C.I. 0.77-1). Participants with cardiomegaly had a higher median BMI (31.3; IQR 27.4-37.4) versus 26.9; IQR 23.2-32.4); p<0.0001) and median systolic blood pressure (130; IQR 121-141 versus 125; IQR 117-135; p = 0.01). CONCLUSION: CTR is a robust measurement, stable over time with substantial inter-observer agreement. A prospective study evaluating utility of CXR to identify cardiovascular disorder in this population is warranted.
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    QuantiFERON conversion following tuberculin administration is common in HIV infection and relates to baseline response
    (BioMed Central, 2016-10-07) Esmail, Hanif; Thienemann, Friedrich; Oni, Tolu; Goliath, Rene; Wilkinson, Katalin A; Wilkinson, Robert J
    Background: HIV-1 infection impairs tuberculosis (TB) specific immune responses affecting the diagnosis of latent TB. We aimed to (1) determine the proportion of HIV-1-infected adults with a negative QuantiFERON®-TB Gold in-tube (QFT-GIT) and Tuberculin skin testing (TST) that convert to QFT-GIT positive following TST, and (2) evaluate the relationship between conversion and baseline QFT-GIT results. Methods: HIV-1 infected adults being screened for a TB vaccine study in South Africa underwent QFT-GIT followed by TST. As per protocol, QFT-GIT was repeated if randomization was delayed allowing for evaluation of TST boosting in a proportion of participants. Results: Of the 22 HIV-1 infected, TST and QFT-GIT negative adults (median CD4 477/mm3 IQR 439–621) who had QFT-GIT repeated after median 62 days (IQR 49–70), 40.9 % (95 % CI 18.6–63.2 %) converted. Converters had a significantly greater increase in the background subtracted TB antigen response (TBAg-Nil – all units IU/mL) following TST, 0.82 (IQR 0.39–1.28) vs 0.03 (IQR −0.05–0.06), p = 0.0001. Those who converted also had a significantly higher baseline TBAg-Nil 0.21(IQR 0.17–0.26) vs 0.02(IQR 0.01–0.07), p = 0.002. Converters did not differ with regard to CD4 count or ART status. ROC analysis showed a baseline cut off of 0.15 correctly classified 86.4 % of converters with 88.9 % sensitivity. Conclusions: Our findings support the possibility that there are 2 distinct groups in an HIV-1 infected population with negative QFT-GIT and TST; a true negative group and a group showing evidence of a weak Mtb specific immune response that boosts significantly following TST resulting in conversion of the test result that may represent false negatives. Further evaluation of whether a lower cut off may improve sensitivity of QFT-GIT in this population is warranted.