CAD for TB:
proven
Artificial Intelligence
Artificial intelligence is increasingly applied to medical image analysis and for chest radiography such as Computer Aided Detection (CAD). Specifically for tuberculosis (TB), CAD4TB was the first algorithm that is validated in clinical and technical operational research studies. CAD4TB as a rapid TB triage tool takes ~10 seconds to quantify lung field abnormalities, and can be used in individuals from 4 years of age. The CAD design allows for rapid key population screening also in remote settings without internet access and without trained human readers.
Computer-aided detection (CAD) is being recommended by WHO for the first time as an alternative to human interpretation of digital chest X-ray (CXR) for screening and triage for TB. CAD4TB quantifies lung field abnormalities suggestive of active TB, assigning a score between 0 and 100 and produces an CXR abnormality heatmap. CAD4TB requires screening programmes to select a triaging threshold score above which participants receive sputum testing. Ultra-portable X-ray systems (PDX) powered with CAD allowed also key populations living in remote areas without internet, to access high quality TB screening services.
ISR-WHO World TB Day Symposium 2021:
- Computer-aided-detection (CAD) for automated interpretation of chest X-ray is now recommended as an alternative to human interpretation for TB screening and triage for all adults aged 15 years and older.
- CAD can resolve numerous difficulties in human interpretation of CXR. These include the lack or scarcity of trained health personnel to interpret radiographic images for TB screening and substantial intra- and inter-reader variation in correct detection of abnormalities associated with TB.
- CAD could thus allow significant scale-up of TB screening and increase access to CXR screening.
- Evaluations indicated that CAD software programmes are accurate and their performance compares well with human interpretation of CXR for detection of pulmonary TB disease.
The probability of the presence of abnormalities consistent with TB serves to select individuals that benefit most from further testing with Xpert® MTB/RIF. Computer Aided Detection for TB (CAD4TB) developed by Dutch Thirona / Radboud University incorporating AI, now outperforms trained human readers (such as clinicians) to detect and quantify the probability of the presence of abnormalities consistent with TB [1]. According to Stop TB Partnership CAD4TB is the most rigorously validated AI software and its 2021 version 7 further increased its performance especially on specificity. Partial financing for R&D was obtained from the Dutch Ministry of Economic Affairs & Innovations with support from CheckTB!
CAD4TB can be operated offline on a laptop on site or in the cloud and is implemented in programmatic settings. CAD4TB has shown encouraging findings for the diagnostic accuracy in several sub-Saharan Africa countries, and recently in Bangladesh [2]. Also other suppliers of computer assisted reading software for chest radiographs are now available, but these can be considered to be in the earlier phase of operational, technical and clinical evidence build-up. CAD4TB was under evaluation by WHO as part of a systematic review of available evidence and now part of the updated TB screening guidelines. The development of the CAD4TB continues and may in the future also be used to detect abnormalities suggestive of silicosis, pneumonia, emphysema and lung cancer.
At the recent UNION Conferences CAD4TB sensitivity and specificity scores on data sets from Bangladesh, Cameroon (Stop TB Partnership/TB REACH), Nambia (TB prevalence survey), Zambia (TB prevalence survey), Philippines (WHO), Tanzania (USAID), South Africa (Aurum / DCS inmate screening) and Zambia (TB prevalence survey) were presented, confirming the potential of CAD4TB as a rapid triage before Xpert® MTB/RIF.
Texture and shape system abnormality detection and scoring provide the CAD abnormality score 0 – 100.
CAD design
CAD4TB was developed to automatically detect tuberculosis-related abnormalities in posterior anterior chest X-rays. This computer-aided detection software takes a single chest X-ray as its input, in the form of a DICOM image, and produces several outputs: a quality assessment of the input image, a heat map highlighting possible abnormal areas, and a score between 0 and 100 indicating the likelihood of the X-ray being abnormal and the subject on the X-ray being affected by tuberculosis.
Image credit: Delft Imaging.
The CAD system follows the general machine learning approach of supervised learning. In supervised learning the system learns from a set of examples, called the training data. The training data consists of a number of labelled images of which the TB status is known. For the CAD4TB system there are two classes and the labels are normal and presumptive for TB. A number of features is extracted from these images and combined to form a feature vector for each image. These feature vectors are used to train a TB classifier. This TB classifier incorporating state-of-the-art pattern recognition techniques can then be used to classify images of which the label is not known.
Computer Aided Diagnosis will enable automated accurate pre-screening on site by the digital X-ray system allowing radiologists or pulmonologists to focus more on analyzing the images that may be TB. In addition, CAD4TB can contribute to fewer "over-reading" by radiographers or clinical officers. CAD in combination with molecular tests such as Xpert® allows for rapid active case finding, which is particular useful in key populations such as PLWH, diabetics, mine workers and inmates at lower costs compared to Xpert® for all.
Summary of CAR for CXR and TB Evidence.
Current System
The objective was to achieve a CAD system with a sensitivity of at least 90% and a specificity of 80%. CAD4TB 5 (2017, CE certified) on a large dataset from the Philippines achieved 94% sensitivity and 84% specificity with Xpert MTB/RIF as reference. CAD4TB 7 (2021 CE certified) offers enhanced specificity (less false positives) and includes modules for registration, symptom screening with easy to modify questionnaires, X-ray imaging including the CAD4TB results and the possibility to seamlessly integrate test data from Cepheid GeneXpert systems.
CAD improves TB screening and supports active case finding by:
- A high percentage of presumptive TB patients is identified automatically wherever the digital X-ray
is used
- Supporting radiographers and/or clinical officers with first image reading
- Reducing number of human image interpretations and prevent under or over-reading
- Providing a powerful offline tool in prevalence studies
- Offering an effective quality assessment tool for health workers and NTP
- Reducing case finding costs by saving > 60% on Xpert MTB/RIF cartridges
- Ultra-portable X-rays (PDX) with CAD provide access to rapid and accurate screening in remote settings
- A limited number of complex Chest images may require further human radiological expertise
While developed for TB, this system supports patient-centric and integrated services with the detection of other lung diseases as well as cases of cardiomegaly. It is thus expected to contribute to a broader healthcare strengthening and cross-disease impact in areas where this is most needed. That is why CAD4TB 8 not only automatically generates a heatmap and TB abnormality score (0-100), but also a general lung abnormality score (0-100) and Cardio thoracic ratio. This functionality will support the diagnostic value of chest radiographs in TB screening for more people-centred services and multi-disease impact.
More than 70 countries use CAD4TB in their TB programs. In the graph below the role of CAD in these programs is illustrated [3]. IRD in Pakistan - one of the early adopters of CAD4TB with Global Fund support - plans to screen more than 5 million people using CAD4TB as a rapid triage in support of the Zero TB initiative.
CAD is specifically of value for rapid and cost-effective systematic screening for active TB. Certain people have a higher risk of either being infected with TB bacteria or becoming sick with TB disease once infected. Guidelines highlight these groups to provide specific considerations for systematically screening and testing these groups such as people living with HIV, close contacts, health care workers, migrants, PDL and people with medical co-morbidities such as diabetes.
Futhermore, the CAD4TB box also allows for teleradiology and telemedicine services by using the internet. In any setting with internet access it will take less than 30 seconds for the compacted digital image taken at a remote district hospital to become visible for expert interpretation in a provincial hospital or in the capital.
Teleradiology on CAD4TB Platform
Results of a CAD user survey performed by CheckTB! in 2015 indicating the various ways this AI software is used
Namibia, Philippines, Southern Africa, UK and Tanzania
More recent studies with digital chest images from Namibia, Southern Africa, London Find & Treat, Zambia and Tanzanian TB prevalence surveys, confirm that CAD is already as accurate as the trained expert human reader. As presented at the 2018 UNION Conference by Namibia, CAD4TB accuracy allows the trained human reader to be replaced by this AI algorithm in future surveys.
WHO in Philippines
A study was performed on CAD4TB performance in the Philippines to automatically interpret digital chest images made for migrant TB screening programs. This research is a collaboration between Radboud University Medical Center and WHO Philippines with initial liaison by KNCV Tuberculosis Foundation and CheckTB!.
12,256 CXRs from Palawan province of the Philippines [4]; CAD4TB version 4 achieved 90.0% sensitivity at 80.0% specificity*. The results with CAD4TB version 5 with (see below) its further increased accuracy, both sensitivity and specificity to augment to 94 and 84% respectively, was published in December 2018.
*46th Union World Conference on Lung Health, 2015; Rick H.H.M. Philipsen et al Computerized Chest Radiography Screening to Detect Tuberculosis in the Philippines, 2015.
CAD4TB AI continuously being improved
As shown below the (Area under the ROC curve) AUC of CAD4TB has significantly increased since the initial CAD version was released in 2013.
The (Receiver Operating Characteristic) ROC [5] below provide information on the pooled sensitivity and specificity scores of in total 4 consecutive CAD4TB versions again with reference radiological (expert human reader) and bacteriological (culture). As can be noted the performance in terms of sensitivity and specificity improves per each new version of the software. Users can select the preferred trade-off between sensitivity and specificity through setting the CAD abnormality score threshold. This also depends on the diagnostic algorithm and the available budget for e.g. Xpert® cartridges.
Conclusions
From the various studies (please refer to CAD Publications section on this site) it can be concluded, that CAD4TB performs similar or better than the human readers in classifying radiographs as being normal or abnormal, suggestive of TB. The performance of the CAD system is expected to further improve with more training of the system. The current version 6 (October 2018) performs equal to expert/radiologist level for classifying abnormal chest images suggestive of TB. CAD as a rapid triage before Xpert® has the potential to cost-effectively scale up systematic screening in key populations in support of the End TB Strategy. This supports the Stop TB Partnership Paradigm shift as also in low resource settings people at risk of TB can with AI support obtain access to high standards of TB care that are available for decades in Western Europe and North America.